Principles and Practice of Mechanic (

Principles
and Practice
of Mechanical
Ventilation
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Professor of Medicine and Anesthesiology
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CONTENTS
CONTR1ll lfi'ORS xi 8. Intermittent Mandatory Ven tilation 201

PREFACE xix Catherine S. H. Sassoon
9. Pressure-Support Ventilation 221
Laurent Brocltard n11d Frn11~ois Lellouche
PART I
10. Pressure-Controlled and Inverse-Ratio
HISTORICAL BACKGROUND 1 Ventilation 251
1. Historical Perspective on the Development of Mllrce/o B.P. Amnto a11d john f. Mnriui
Mechanical Ventilation 1 11. Positive End-Expiratory Pressure 273
Gene L. Co/ice Paolo Navalesi and Saltmtore Maurizio Maggiore
PART II PARTV
PHYSICAL BASIS OF MECHANICAL ALTERNATIVE METHODS OF
VENTILATION 37 VENTILATOR SUPPORT 327
2. Classification of Mechanical Ventilators 37 12. Airway Pressure-Release Ventilation 327
Robert L. Chntbum Christian Putense11 and Herma11n Wrigge
3. Basic Principles of Ventilator Machinery 53 13. Proportional-Assist Ventilation 335

Robert M. Kacmarek and Daniel Chipman Magdy Younes
4. Equipment Required for Home 14. Closed-Loop Ventilation 365

Mechanical Ventilation 97 jasou H.T. Bates
Robert M. Kncnwrek and Atul Malhotra 15. Permissive Hypercapnia 373
John G. Lnffey and Brian P. Kavanagh
PART lii 16. Feedback Enhancements on Ventilator
INDICATIONS 129 Breaths 393
Neil Macintyre tmd Richard D. Branson
5. Indications for Mechanical Ventilation 129
Franco Laghi aud Martiu f. Tobin
PART VI
PART IV NONINVASIVE METHODS OF

VEN TILATOR SUPPORT 403
CONVENTIONAL METHODS OF
VENTILATORY SUPPORT 163 17. Negative-Pressure Ventilation 403
Antonio Corrado and Massimo Goriui
6. Setting the Ventilator 163
Steve Holets and Rolf D. Hubmayr 18. Noninvasive Respiratory AIDS:
Rocking Bed, Pneumobelt, and
7. Assist-Control Ventilation 183 Glossopharyngeal Breathing 421
jardi Mancebo Nicholas S. Hiii
..
Vll
V lll CONTENTS
19. Noninvasive Positive-Pressure Ventilation 433 33. Chronic Ventilator Facilities 691
Nicholas S. Hill Stefatw Nava and Michele Vitacca
34. Nonin vasive Ventilation on a General Ward
705
PARTVll Mark Elliott
UNCONVENTIONAL METHODS OF
VENTILATOR SUPPORT 473
PART IX
20. High-Frequency Ventilation 473
Aliso11 B. Froese PHYSIOLOGIC EFFECTS OF
MECHANICAL VENTILATION 715
21. Extracorporeal Membrane Oxygenation and
Extracorporeal Life Support 493 35. Effects of Mechanical Ventilation on Control of
Robert Bartlett and Theodor Ko/obow Breathing 715
Dimitris Georgopoulos
22. Extracorporeal Carbon Dioxide Removal 501
Antonio Presenti, Luciano GnHinoni and Michela Bambino 36. Effect of Mechanical Ventilation on Heart-Lung
Interactions 729
23. Liquid Ventilation 513 Michael R. Pinsky
R11pa Seetharnmaiah, Stefano Tredici and Ronald B. Hirschi
37. Effect of Mechanical Ventilation on
24. Transtracheal Gas Insufflation 525
Gas Exchange 759
L/uis Blanch and Avi Nahum
Robert Rodnguez-Roisou and Antoni Ferrer
PARTVlll
PART X
VENTILATORSUPPORTINSPEC~C
ARTIFICIAL AIRWAYS AND
SEITINGS 543 MANAGEMENT 779
25. Mechanical Ventilation in the Neonatal and 38. Airway Management 779
Pediatric Setting 543 Steveu Deem aud Michael J. Bishop
Peter C. Rimensberger a11d Juerg Hammer
39 Complications of Translaryngeal Intubation 801
26. Independent Lung Ventilation 573 Jolm L. Sta uffer
David V. Tuxen
40 Care of the Mechanically-Ventilated Patient
27. Mechanical Ventilation During Resuscitation 595 with a Tracheostomy 847
Achim von Goedecke and Volket Wenzel Jvltn E. Heffner and Bonnie Mnrtin-Harris
28. Transport of the Ventilator-Supported
Patient 609
Riclmrd D. Branson and Jay A. fohmmigman
29. Mechanical Ventilation in the Acute Respiratory COMPLICATIONS IN
Distress Syndrome 625 VENTILATOR-SUPPORTED PATIENTS
Jolm J. Marini 877
30. Mechanical Ventilation for Sever e 41 Complications Associated with Mechanical
Asthma 649 Ventilation 877
James W. Leatltennan Scott K. Epstein
31. Mechanical Ventilation in Chronic Obstructive 42 Ventilator-Induced Lung Injury 903
Pulmonary Disease 663 Didier Dreyfllss, Jea11-Damien Ricard, a11d Georges Saumo11
Sonia Khirnni, Guido Polese, Lorenzo Appendini, and
Andrea Rossi 43 Ventilator-Induced Diaphragm Dysfunction 931
Theodoros Vassilakopoulos
32. Mechanical Ventilation in Neuromuscular
Disease 679 44 Barotrauma and Bronchopleural Fistula 943
Ahmet Baydur David f. Piersol!
.
CONTENTS ZX
45 Oxygen Toxicity 965 57 Sleep in th e Ventilated Patien t 1173

Robert F. Lodnto Patrick). Hanley
46 Pneumonia in the Ventilator-Dependent 58 Weaning from Mech anical Ventilation 1185
Patient 991 Mnrti11 f. Tobin and Amal ]ubra11
fen/! Chastre a11d fenn-Yves Fagan
59 Extubation 1221
47 Sinus Infections in the Ventilated Martin f. Tobi11 and Franco Laghi
Patient 1019
jean-jacques Rouby and Qin Lu
PART XIV
ADJUNCTIVE THERAPY 1239

i!J>ART XII
60 Sur factant 1239
EVALUATION AND MONITORING OF fames F. Lewis
VENTILATOR-SUPPORTED PATIENTS 61 Inhaled Nitric Oxide 1251
1033 Klaus Lewnndowski
48 Imaging of the Mechanically Ventilated Patient 62 Diaphragmatic Pacing 1263

1033 Antho11y F. DiMarco
Lawrence R. Goodma11
63 Bronchodilator Therapy 1277
49 Monitoring During Mechanical Ventilation 1051 Rajiv Dhn11d
Amal Jubrnl! a11d Martin J. Tobin
64 Inhaled Antibiotic Therapy 1311
)eall-jacques Rouby,Jva11 Goldstein, nud Qin Lu
65 Fluid Management in the Ventilated Patient 1323
PART XIU
Andrew D. Bemsten
MANAGEMENT OF THE VENTILATOR-
SUPPORTED PATIENT 1081
PART XV
50 Prone Positioning in Acute Respiratory
Failure 1081 ETHICS AND ECONOMICS 1333
Lucimw Gattillolli, Fmnco VnlenZA, Paolo Pelosi and Daniele 66 The Ethics of Withholding and Withdrawi11g
Mascheroni Mechanical Ventilation 1333
51 Pain Control, Sedation, and Neuromuscular Elie Azoulny
Blockade 1093 67 Interpreting Clinical Trials of Mechanical
fohn P. Kress and Jesse B. Hall
Ventilation: The Importance of Routine
52 Humidification 1109 Care 1347
]ean-Damim Ricard Katherine f. Denus, Peter C. Milmeci, Xizho11g Cui, Steven
M . Banks, Charles Natai!SOII, and Peter Q. Eichacker
53 Fightin g the Ventilator 1121
Martin f. Tobin, Chal'les G. Alex, n11d Patrick J. Fnhey 68 Economics of Ventilator Care 1355
Shmmon S. Carson
54 Psychological Problems in the Ventilated
Patient 1137 69 Purchasing a Ventilator 1365
Ubnldo Mnrtin and Gernrd J. Criner fames B. Fink
55 Addressing Respiratory Discomfort in the 70 Long-Term Outcomes After Mechanical

Ventilated Patient 1153 Ventilation 1371
Robert B. Banzett and Robert Brown Catheri11e Lee Hough awl J. Randall Curtis
56 Ventilator-Supported Speech 1163

jemmette D. Hoit, Robert B. Banzett, and Robert Brown I NDEX 1383
CONTRIBUTORS
Charles G. Alex, MD Robert Bartlett, MD, FACS

Professor of Medicine, Division of Pulmonary and Critical Professor, General and Thoracic Surgery, The University of
Care Medicine, Loyola University of Chicago, Stritch School Michigan Health System, Ann Arbor, Michigan
of Medicine and Edward Hines Jr. Veterans Chapter 21: Extrncorporeal Membrane Oxyge11ation and
Administration Hospital, Hines, fllinois E::lirncorpornl Life Support
Chapter 53: Fighti11g the Ventilator
Jason H.T. Bates, PhD, DSc

Marcelo B.P. Amato, MD, PhD Research Professor, Vermont Lung Center, University of
Laboratory of Medical Investigation (LJM-09) and Vermont College of Medicine Burlington, Vermont
Respiratory ICU-HospitaJ das Clinicas
Grapter 14: Closed-Loop Ve11tilation
Pulmonary Division-University of Sao Paulo
Medical Sd1ool, Sao Paulo, SP, Brazil
Chapter 10: Pressure-Controlled and l11verse-Rntio VeHtilation Ahmet Baydur, MD, FACP, FCCP
Professor of Clinical Medicine, Division of Pulmonary and
Critical Care Medicine, Department of Medicine, Keck
Sd1ool of Medicine, University of Southern California,
Lorenzo Appendini, MD Los Angeles, California
Fondazione Salvatore Maugeri, IRCCS, Scientific Ins tih1te of Otapter 32: Mecltn.11ical Ve11tilation i11
Veruno, Pulmonary Division, Veruno (NO), Italy Neuromuswlar Disease
Otapter 31: Meclumical Ventilation in Chronic Obstructive
Pulmonary Disense
Andrew D. Bersten, MB, BS, MD, FJFICM
Professor, Department of Critical Care Medicine,
Elie Azoulay, MD, PhD Flinders Medical Centre and Sd1ool of Medicine,
Service de Reanimation Medicale, Hopital Flinders University, Adelaide, South Australia
Saint-Louis et Universite Paris 7 Ozapter 65: Fluid Mtmngemeut in the Ve11tilated Patient
Chapter 66: The Ethics of Withholdi11g and Withdrawing
Mechanical Ventilation
MirnaelJ. Bishop, MD
Professor of Anesthesiology and Medicine (Adjunct,
Pulmonary and Critical Care), Veterans Affairs Puget Sound
Steven M. Banks, PhD Health Care System, University of Washington, Seattle,
Mathematical Statistician, Critical Care Medicine Washington
Department, Clinical Center, National lnstirutes of 01apter 38: Airway Ma11agement
Health, Bethesda, Maryland
Chapter 67: Interpreting Clinical Trials of Mechanical Ventilation:
The Importance of Routine Care Lluis Blanrn, MD, PhD
Critical Care Center, Hospital de Sabadell, Corporaci6 Pare
Tauli, lnstihlt Universitari Fundaci6 Pare Tauli Universitat
Robert B. Banzett, PhD Aut6noma de Barcelona Sabadell, Spain
Associate Professor, Physiology Program, Department of Owpter 24: Trnnstrnchenl Gas lllsllfflation
Environmental Health, Harvard Sd1ool of Public Health &
Beth Israel Deaconess Medical Center, Harvard Medical
School, Boston, Massachusetts Mich ela Bombino, MD
01apter 55: Addressi11g Respiratory Discomfort in Staff, Department of Perioperative Medicine and Intensive
the Ventilated Patient Care, A.O. Ospedale S. Gerardo, Monza, Italy
01apter 56: Ventilator-Supported Speech Otapter 22: Extracorporeal Carbon Dioxide Removal
Xl
Copyright© 2006 by McGraw-Hill, Inc. Click here for terms of use.
..
Xll CONTRIBUTORS
Richard D. Branson, MS, RRT Gerard J. Criner, MD

Associate Professor of Surgery, University of Cincinnati Professor of Medicine and Director, Pulmonary and Critical
Medical Center, Cincinnati, Ohio Care Medicine, Temple University School of Medicine and
Chapter 16: Feedback Enlumcements 011 Ventilator Breaths Temple Lung Center, Philadelphia, Pennsylvania
Chapter 28: Transport of the Veutilator Supported Patient Chapter 54: Psychological Problems in the Ve11tilated Patient
Laurent Brochard, MD Xizhong Cui, MD, PhD

Reanimation Medicale, Assistance Publique-Hopitaux de Senior Research Specialist, Critical Care Medicine
Paris, Hopi tal Henri Mondor, Universite Paris 12, and Department, Clinical Center, National Institutes
INSERM U 615, Creteil, France of Health, Bethesda, Maryland
Chapter 9: Pressure Support Ventilation Chapter 67: l11terpreting Clinical Trials of Mechanical Ventilation:
The Importance of Routi11e Care
Robert Brown, MD
Director, Respiratory Acute Care Unit; Director, Pulmonary J. Randall Curtis, MD, MPH
Function Laboratory; Associate Professor of Medicine, Professor of Medicine, Division of Pulmonary and Critical
Pulmonary and Critical Care Medicine Unit, Department of Care Medicine, and Director, Harborview /University of
Medicine, Massachusetts General Hospital, Harvard Washington End-of-life Care Research Program, University
Medical School, Boston, MA. of Washington, Harborview Medical Center, Seattle,
Chapter 55: Addressiug Respiratory Discomfort in the Ventilated Washington
Patient Chapter 70: Long-Term Outcomes After Mechanical Ventilation
Chapter 56: Ventilator-Supported Speech
Katherine J. Deans, MD
Shannon S. Carson, MD Research Fellow, Critical Care Medicine Department,
Assistant Professor, Division of Pulmonary and Critical Care Clinical Center, National Institutes of Health, Bethesda,
Medicine, University of North Carolina School of Medicine, Maryland; Department of Surgery, Massachusetts General
Chapel Hill, North Carolina Hospital, Boston, Massachusetts
Chapter 68: Economics of Ve~~tilatvr Care Chapter 67: Interpreti11g C/inicnl Trials of Mecha11ical Ve11tilntio11:
The Importa11ce ofRoutine Care
Jean Chastre, MD
Service de Reanimation Medicale, Institut de Cardiologie, Steven Deem, MD
Groupe Hospitalier Pitie, Paris, France Associate Professor of Anesthesiology and Medicine
Chapter 46: P11eumonia in the Ventilntor-Dependent Patient (Adjunct, Pulmonary and Critical Care), University of
Washington, Harborview Medical Center, Seattle,
Washington
Robert L. Chatburn, BS, RRT-NPS, FAARC Chapter 38: Airway Management
Director, Respiratory Care Department, University
Hospitals of Cleveland; Associate Professor, Department of
Pediatrics, Case Western Reserve University, Rajiv Dhand, MD, FCCP
Oeveland, Ohio Professor of Medicine and Director, Division of Pulmonary,
Chapter 2: Classification of Mechanical Ventilators Critical Care, and Environmental Medicine, Department of
Internal Medicine, University of Missouri- Columbia; Staff
Physician, Harry S. Tntman VA Hospital_ Columbia,
Daniel W. Chipman, BS, RRT Missouri
Assistant Director, Department of Respiratory Care, Chapter 63: Bronchodilator Thernpy
Massachusetts General Hospital, Boston, Massachusetts
Chapter 3: Basic Principles of Ventilntor Machinery
Anthony F. DiMarco, MD
Professor of Medicine, Physiology and Biophysics, Case
Gene L. Colice, MD Western Reserve University, Cleveland, Ohio; Director,
Professor of Medicine, The George Washington University Deparhnent of Respiratory Therapy and Chief, Department
School of Medicine; Director, Pulmonary, Critical Care and of Medicine, University Hospitals Health System, Geauga
Respiratory Services, Washington Hospital Center, Regional Hospital
Washington, DC Chnpter 62: Diaphragmatic Pacing
Chapter 1: Historical Perspective 011 the Development of
Mechanical Ventilatio11
Didier Dreyfuss, MD
Professor of Critical Care Medicine, Faculte Denis Diderot,
Antonio Corrado, MD Paris; Chairman of Critical Care Department, Hopital
Unita di Terapia Intensiva Respiratoria-Fisiopatologia Louis-Mourier, Colombes, (Assistance Publique- Hopitaux
Toracica, Azienda Ospedaliera-Universitaria Careggi, de Paris); and Institut National de Ia Sante et de Ia Recherche
Firenze, ltaly Medicale, Faculte Denis Diderot, Universite Paris VTI, France
Chapter 17: Negative Pressure Ventilation Chapter 42: Vmtilator-Induced Lwzg Injury
CONTRIBUTORS Xlll
Peter Q. Eichack er, MD D imitris Georgopoulos, MD, PhD

Senior Investigator, Head Critical Care Section, Critical Care Professor of Medicine and Director of Intensive Care
Medicine Department, Clinical Center, National Institutes of Medicine Department, University Hospital of Heraklion,
Health, Bethesda, MD University of Crete, Heraklion, Crete, Greece
Chapter 67: l11terpreti11g Clinical Trials of Mechanical Ventilation: 01apter 35: Effects of Mechanical Ventilation on
The Importance of Routine Care Control of Breathi11g
Mark Elliott, MD, FRCP Achim von Goedecke, MD

Depar tment of Respiratory Medicine, St James's University Associate Professor of Anesthesiology and Critical Care
Hospital, Beckett Street, Leeds, England Medicine, Department of Anesthesiology and Critical
Chapter 34: Non Invasive Ventilation 011 a General Ward Care Medicine, lnnsbruck Medical University,
Innsbruck, Austria
Owpter 27: Mechanical Vwtilation During Resuscitatio11
Scott K. Epstein, MD
Vice Chair, Department of Medicine, Carita s-
Ivan Goldstein, MD, PhD
St. Elizabeth's Medical Center; Professor of Medicine,
Reanimation Chirugicale Polyvalente Pierre Viars, Hopi tal
Department of Medicine, Tufts University School of
Piti€!-Salpetriere, Assistance Publique Hopitaux de Paris,
Medicine Boston, Massachusetts
Universite Pierre et Marie Curie, Paris, France
Otapter 41: C01nplicntions Associafet'i with
Owpter 64: lnhaled Antibiotic Therapy
Mecluw icnl Ventilation
Lawrence R. Goodman, MD
Jean-Yves Fagon, MD, PhD Professor, Diagnostic Radiology & Pulmonary Medicine,
Service de Reanimation Medicale, Hopital Europeen Medical College of Wisconsin, Milwaukee, Wisconsin
Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Ompter 48: Imaging of the Mechmzically Ve11tilnted Patie11t
Universite Rene Descartes-Paris 5, Paris, France
Ozapter 46: Pneumonia in the Ventilator-Dependent Patient
Massimo Gorini, MD
Unita di Terapia Intensiva Respiratoria-Fisiopatologia
Patrick J. Fahey, MD, FACP Toracica, Azienda Ospedaliera-Universitaria Careggi,
The John W. Clarke Professor and Chairman, Department of Firenze, Italy
Medicine, Loyola University Medical Center, Maywood Chapter 17: Negative Pressure Ve11tilation
Ozapter 53: Fighti11g the Ventilator
Jesse B. Hall, MD
Antoni Ferrer, MD Professor of Medicine, Section Chief Pulmonary and Critical
Servei de Pneumologia, Hospital de Sa badell, Corporacio Care Medicine, Department of Medicine, Section of
Pare Tauli, lnstitut Universitari Fundacio Pare Tauli, Pulmonary and Critical Care University of Chicago,
Universitat Autonoma de Barcelona, Sabadell, Spain Chicago, Illinois
Chapter 37: Effect of Mechanical Ventilation Ol'z Gas Exchange Chapter 51: Pain Control, Sedatiou, 1111d
Neuromuscular Blockade
James B. Fink, MS, RRT, FAARC

Juerg Hammer, MD
Fellow, Resp iratory Science, Nektar Therapeutics, Mountai11
Professor of Pediatrics, Head, Division of Intensive Care and
View, California
Pulmonology, University Children's Hospital Basel, Basel,
Ozapter 69: Purchasing a Ventilator Switzerland
Chapter 25: Mecfumical Ventilation i11 the Neonatal a11d
Alison B. Froese, MD, FRCPC Pediatric Setti11g
Professor of Anesthesiology, Physiology and Pediatrics,
Queen's University; Staff Anesthesiologist, Deparhnent of Patrick J. Hanly, MD, MRCPI, FRCP C, ABSM
Anesthesiology, Kingston General Hospital, Kingston, Professor of Medicine, University of Calgary, Alberta,
On tario, Canada Canada; Director, Lung Association Sleep Centre, Foothills
Chapter 20: High Frequency Ventilation Medical Centre, Calgary, Alberta, Canada
Chapter 57: Sleep i11 the Ve~~tilated Patient
Luciano Gattinoni, MD, FRCP
Professor of Anesthesia and Intensive Care, University of John E. Heffner, MD
Milan, Is tituto d i Anestesia e Rianimazione, Fondazione Professor of Medicine and Executive Medical Director,
IRCCS, Ospedale Maggiore Policlinico, Mangiagalli e Medical University of South Carolina, Charleston,
Regina Elena, Milano, Italy South Carolina
Ozapter 22: Extracorporeal Carbon Dioxide Removal Chapter 40: Care of the Mechanically-Ventilated Patie11t
Chapter 50: Pro11e Positio11i11g i11 Acute Respiraton; Failure with a Tracheostomy
.
X l V CONTRIBUTORS
Nicholas S. Hill, MD Brian P. Kavanagh, MB BSc MRCP(I) FRCP(C)

Chief, Division of Pulmonary, Critical Care and Sleep Dr. Geoffrey Barker Chair in Critical Care Medicine
Medicine, Tufts-New England Medical Center; Professor of Professor of Anesthesia, Medicine & Physiology, University
Medicine, Tufts University School of Medicine, Boston, of Toronto Staff Physician & Director of Research,
Massachusetts Department of Critical Care Medicin e,
Chapter 18: Noninvasive Respiratory Aids: Rocking Bed, Hospital for Sick Children, Toronto, Canada
Pneumobelt, and Glossopharyngeal Breathing Chapter 15: Permissive Hypercapnia
Chapter 19: Noninvasive Positive-Pressure Ventilation
Ronald B. Hirschi, MD Sonia Khirani

Professor of Surgery and Section Head, Department of Recip ient of a European Respiratory Society Fellowsh ip
Pediatric Surgery, C.S. Mott Children's H ospital and (Number 174), U.S.C. Pneumologia, A.O. Ospedali Riu11iti,
The University of Michigan Health System, Bergamo, Italy
Alm Arbor, Michigan Chapter 31: Mecha11ical Ve11tilation itt Chronic Obstructive
Owpter 23: Liquid Ven tilation Pulmonary Disease
Jeannette D. Hoit, PhD, CCC-SLP Theodor Kolobow, MD

Professor, Department of Speech, Language, and Hearing Chief, Section on Pulmonary and Cardiac Assist Devices,
Sciences, University of Arizona, Tucson, AZ Pulmon ary and Critical Care Medicine Branch, National
Chapter 56: Ventilator-Supported Speech Heart, Lung and Blood Ins titu te, Nationa l Institu tes of
Health, Bethesda, Mar yland
Steven R. Holets, RRT Chapter 21: Extmcorporeal Membrane Oxygenation mzd
Anesthesia Clinical Research Unit, Department of Extrncorpornl Life Support
A nesthesiology, Division of Intensive Care and Respiratory
Care, Mayo Clinic College of Medicine, Rochester,
Minnesota John P. Kress, MD
Chapter 6: Setti11g the Ven.tilator Assistant Professor of Medicine, Departmen t of Medicine,
Section of Pulmonary and Critical Care, University of
Chicago, Chicago, Illinois
Catherine Lee Hough, MD, MSc
Assistant Professor of Medicine, Division of Pu lmonary and
Chapter 51 : Pain Co11trol, Sedation, a11d
Neuromuswlar Blocknde
Critical Care Medicine, Department of Medicine, University
of Washington, Harborview Medical Cen ter, Seattle,
Washington
John G. Laffey, MD, BSc, MA
Chapter 70: Long-Term Outcomes After Mechanical Ventilation Consultant and Oinical Lechtrer, Department of Anesthesia
and Intensive Care, Galway University Hospitals and
Rolf D. Hubmayr, MD National University of Ireland,
Professor of Medicine and Physiology, Mayo Clinic College Galway, Ireland
of Medicine, Rochester, Minn esota Chapter 15: Permissive Hypercapnia
Chapter 6: Setting the Ventilator
Jay A. Johannigman, MD, Col USAFR Franco Lagbi, MD

Associate Pr ofessor of Surgery, Director Division of Trauma Associate Professor of Medicine, Division of Pu lmonary and
and Critical Care, University of Cincinnati Medical Cen ter, Critical Care Med icine, Loyola University of Cnicago Stritch
Oncinnati, Ohio School of Medicine and Edward H ines Jr. Veterans
Chapter 28: Trn11sport of the Ve11tilator Supported Patient Administration Hospital, Hines, Illinois
Clznpter 5: Indications for Mechn11ical Ventilation
Chapter 59: £xtubntio11
Amal Jubran, MD
Professor of Medicine, Division of Pulmonary and Critical
Care Medicine, Loyola University of Chicago, Stritch School James W. Leatherman, MD
of Medicine; Section Chief, Edward Hines Jr. Veterans Associate Professor of Medicine, Pulmonary and Critical
Administration Hospital, Hines, Illinois Care Medicin e, University of Minnesota, Hennep in County
Chapter 49: Monitori11g Duri11g Mechmzical Velltilatioll Medical Center, Minneapolis, Minnesota
Chapter 58: Weaning from Mecfta11ical Veutilation C1wpter 30: Mecha11ical Ventilation for Severe Asthma
Robert M. Kacmarek, PhD, RRT

Professor, Department of Anesthesia, Harvard Medical Fran~ois Lellou che, MD
School; Director, Respiratory Care Services, Massachusetts Reanimation Medicale, Assistance Publique-Hopitaux de
General Hospital, Boston, Massachusetts Paris, Hopital Henri Mondor, Universite Paris 12,
Chapter 3: Basic Principles of Ve11tilotor Mnchi11ery Creteil, France
Chapter 4: Equipment Required for Home Mechanical Ventiltltion Chapter 9: Pressure Support Ventilation
CONTRIBUTORS XV
Klaus Lewandowski, Prof. Dr. med. Ubaldo Martin, MD

Direktor der Klinik fur Anasthesiologie, lntensivmedizin Assistant Professor of Medicine, Division of Pulmonary and
tmd Schmerztherapie, Elisabeth-Krankenhaus Essen, Critical Care Medicine, Temple University School of
Akademisches Lehrkrankenhaus der UniversiUit Medicine, Temple Lung Center, Temple University Hospital,
Dillsburg-Essen, Germany Philadelphia, Pennsylvania
Otapter 61: Inhaled Nitric Oxide Chapter 54: Psychological Problems irt the
Ventilated Patient
James F. Lewis, MD, FRCPC
Professor of Medicine/ Physiology /Pharmacology, Bonnie Martin-Harris, PhD, CCC-SLP
St. Joseph's Health Centre University of Western Ontario, Associate Professor, Otolaryngology-Head and Neck
London, Ontario Canada Surgery and College of Health Professions, College of
Otapter 60: Surfnctant Dental Medicine; Director, MUSC Evelyn Trammell Institute
for Voice and Swallowing, Medical University of South
Carolina, Charleston; Consultan t, Evelyn Trammell Voice &
Robert F. Lodato, MD, PhD
Swallowing Center, Saint Joseph's Hospital of Atlanta,
Associate Professor of Medicine, Division of Pulmonary and
Atlanta, Georgia
Critical Care Medicine, University of Texas Health Science
Chapter 40: Care of the Mechanically-Ventilated Patient
Center at Houston, Houston, Texas
with n Tracheostomy
Chapter 45: Oxygen ToxicihJ
Qin Lu, MD, PhD Daniele Mascheroni, MD

Ospedale Policlinico, Servizio di Anesthesia e Rianimazione,
Reanimation Chirurgkale Polyvalente, Researd 1
Milano, Italy
Coordinator, Hopital Pi tie- Salpetriere, Faculte de Medecine
Chapter 50: Pr011e Positioni11g in Acute Respiratory Failure
Pierre et Marie Curie, Paris, France
Chapter 47: Sinus lnfectiolls in the Ventilated Patient
Chapter 64: Inhaled Antibiotic Therapy Peter C. Minneci, MD
Research Fellow, Critical Care Medicine Department,
Clinical Center, National h1stitutes of Health, Bethesda,
Neil Macintyre, MD
Maryland; Department of Surgery, Massachusetts
Professor of Medicine, Division of Pulmonary an d Critical
General Hospital, Boston, Massachusetts
Care Medicine, and Medical Director of Respiratory Care
Chapter 67: Interpreting Clinical Trials of Mecluwical Ventilatio11:
Service, Duke University Medical Center, Durham,
The importance of Routine Care
North Carolina
Chapter 16: Feecfback Enhancements on Ventilator Brentlzs
A vi Nahum, MD, PhD
Section Head, Department of Pulmonary and Critical Care
Salvatore Maurizi o Maggiore, MD, PhD
Medicine, Regions Hospital, St Paul, Minnesota; Associate
Department of Anesthesiology and Intensive Care, Agostino
Professor of Medicine, University of Minnesota.
Gemelli University Hospital Universita Cattolica del Sacro
Chapter 24: Transtracheal Gas llzsuffllltion
Cuore, Rome, Italy
01apter 11: Positive End-Expi1'11tory Pressure
Charles Natanson, MD
Senior Investigator, Critical Care Medicine Department,
Atul Malhotra, MD
Clinical Center, National Institutes of Health,
Staff, Department of Pathology, Massachusetts Genera]
Bethesda, Maryland
Hospital, Boston, Massachusetts
Chapter 67: Interpreting Clinical Trials of Mechrmical Ventilntio11:
Otnpter 4: Equipment Required for Home Mechanical Ventilation
The Importance of Routine Care
Jordi Mancebo, MD
Stefano Nava, MD
Un it Director, Servei de Medicina Intensiva, Hospita l de
Sant Pau, Barcelona, Spain Associate Professor of Medicine, Respiratory Intensive Care Unit, Fondazione S. Maugeri,
Universitat Autonoma de Barcelona, lstituto Scientifico di Pavia, Pavia, Italy
Barcelona, Spain Chapter 33: Chronic Ventilator Facilities
Owpter 7: Assist-Omtrol Ve~ttilatiOir
Paolo Navalesi, MD
Respiratory Intensive Care Unit,
John J. Marini, MD Fondazione S. Maugeri-IRCCS, Pavia, Italy
Professor of Medicine, University of Minnesota,
Chapter 11: Positive End-Expirntory Pressure
Minneapolis/ St. Paul; Director of Physiological and
Translational Research, Regions Hospital,
St. Paul, Minnesota Paolo Pelosi, MD
Owpter 10: Pressure-Controlled and Inverse-Ratio Ve11tilatio1! Ospedale Policlinico, Servizio di Anesthesia e Rianimazione,
Owpter 29: Mechanical Ventiln.tio11 irz the Acute Respiraton; Milano, Italy
Distress Syudrome Chapter 50: Prone Positioning in Acute Respiratory Failure
.
XVZ CONTRIBUTORS
Antonio Pesenti, MD An drea Rossi, MD

Professor of Anesthesia and Intensive Care, University of Director U.S.C. Pneumologia, A.O. Ospedali Riuniti,
Milan-Bicoccaj Director, Department of Perioperative Bergamo, Italia
Medicine and Intensive Care, A.O. Ospedale S. Gerardo, Chapter 31 : Mec1umical Ventilation;, Chronic Obstructive
Monza, Italy Pulmonary Disease
Chapter 22: Extracorpoteal Carbon Dioxide Removal
Jean-Jacques Rouby, MD, PhD
Professor of Anesthesiology and Critical Care Medicine,
David J. Pierson, MD
Director, Reanimation Chirurgicale Polyvalente, H6pital
Medical Director, Respiratory Care, Harborview Medical
Pitie-Salpetriere, Faculte de Medecine Pierre et Marie Curie,
Center; Professor of Medicine, Division of Pulmonary and
Paris, France
Critical Care Medicine, University of Washinh>ton,
Chapter 47: Sinus Infections in the Ventilated Patient
Seattle, Washington. Cluzpter 64: lnhnled Antibiotic Therapy
Chapter 44: Barotrauma and Bronchopleural Fistula
Catherine S.H. Sassoon, MD

Michael R. Pins ky, MD, CM, Or he, FCCP, FCCM Professor of Medicine, Pulmonary and Critical Care Section,
Professor of Critical Care Medicine, Bioengineering and University of California, Irvine and
Anesthesiology, University of Pittsburgh, Veterans Affairs Long Beach Healthcare System,
Pittsburgh, Pennsylvania Long Beach, California
Chapter 36: Effed of Mechanical Ventilation on Chapter 8: Intermittent Mandatory Ventilation
Heart-Lung I11teractions
Georges Saumon, MD
Institut National de Ia Sante et de Ia Recherche Medicale,
Guido Polese1 MD Faculte Xavier Bichat, Paris, France
U.S.C. Pneurnologia, A.O. Ospedali Riuniti, Bergamo, Italy Cllilpter 42: Ventilator-Induced Lung Injury
Chapter 31: Mechanical Ventilati011 in Chronic Obstmctive
Pulmonary Disease
Rupa Seetharamaiah, MD
Research Fellow, Section of Pediatric Surgery, C.S. Mott
Christian Putensen , MD Children's Hospital and The University of Michigan Health
Professor of Intensive Care Me.d icine, Division of Intensive System, Ann Arbor, Michigan
Care Medicine, Department of Anesthesiology and Chapter 23: Liq11id Ventilati011
Intensive Care Medicine, University of Bonn,
Bonn, Germany
John L. Stauffer, MD
Chapter 12: Airway Pressure Release Ventilation
Clinical Professor of Medicine, Division of Pulmonary,
Allergy, and Critical Care Medicine, The Pennsylvania State
University College of Medicine, The Milton S. Hershey
Jean-Damien Ricard, MD, PhD Medical Center, Hershey, Petmsylvania; Senior Director,
Associate Professor of Intensive Care Medicine, Denis Respiratory Medicine Development Center,
Diderot Medical School, Paris VII University, Paris and GlaxoSmithKline, Research Triangle Park, North Carolina
Service de Reanimation Medicale, Hopital Louis-Mourier, Chapter 39: Complications ofTrnnslanj11geal lntubation
Assistance Publique- Hopitaux de Paris, Colombes, France.
Chnpter 42: Ventilntor-bzdaced Lung Injury
Chapter 52: Humidification Martin J. Tobin, MD
Professor of Medicine and Anesthesiology; Director,
Division of Pulmonary and Critical Care Medicine, Loyola
Peter C. Rimen sberger, MD University of Chicago Stritch School of Medicine and
Associate Professor of Intensive Care Medicine, Pediatric Edward Hines, Jr., Veterans Administration Hospital;
and Neonatal Intensive Care, Children's Hospital, Attending Physician, RML Specialty Hospital,
University Hospitals of Geneva, Geneva, Switzerland Maywood, illinois
Chnpter 25: Meclu:mical Ventilati011 in the Neouatal and Petliatric Chapter 5: Indications for Mechanical Ventilation
Setting Chapter 49: Monitoring During Mechanical Ventilation.
Chapter 53: Fighting the Ventilatot
Chapter 58: Wea11ing fi'Om Mechanical Ventilation
Robert Rodriguez-Raison, MD, FRCPE Chapter 59: Extubntion
Professor of Medicine, Chair, Servei d e Pneumologia,
Hospital Clinic, Jnstitut d1nvestigacions Biomecliques Stefano Tredici, MD
August Pi i Sunyer (IDIDAPS), Departament de Medidna, Research Fellow, Department of General Surgery,
Universitat de Barcelona, Barcelona, Spain C.S. Mott Children's Hospital and The University of
Chapter 37: Effed of Mechanical Ventilation on Michigan Health System, Ann Arbor, Michigan
Gas Exchange Chapter 23: Liquid Ventila.tion
CONTRIBUTORS XVll
David V. Tuxen, MB, BS, FRACP, D ip OHM, MD, Michele Vitacca, MD

FJFICM Pulmonary Rehabilitation and Weaning Center, Fondazione
Assoc Professor, Senior lntensivist, Department of Intensive S. Maugeri IRCCS, Gussago/
Care Unit and Hyperbaric Medicine, The Alfred, Prahran, Lumeaane (85) Italy
Victoria, Australia Ozapter 33: Chronic Ventilator Facilities
Ompter 26: independent Luug Ventilation
Volker Wenzel, MD
Associate Professor of Anesthesiology and Critical Care
Franco Valenza, MD Medicine; Head, Experimental Anesthesiology, Department
Assistant Professor, Universita degli Studi di Milano, of Anesthesiology and Critical Care Medicine, lnnsbruck
Department of Anesthesia and Intensive Care, Ospedale Medical University, hmsbruck, Austria
Maggiore Policlinico, Mangiagalli e Regina Elena, Ompter 27: Mechanicnl Ventilation Duri11g Resuscitation
Servizio di Anestesia e Rianimazione, Milano, Italy
Ompter 50: Prone Positio11i11g in Acute Respiratory Hermann Wrigge, MD
Failure Associate Professor of Anesthesiology, Department of
Anesthesiology and Intensive Care Medicine, University of
Bonn, Bonn, Germany
Theodoros Vassilakopoulos, MD Grapier 12: AirWfly Pressure Release Ven tilation
Assistant Professor, Department of Pu lmonary and Critical
Care Medicine, National and Kapodistrian University of Magdy Younes, MD
Athens Medical School, Athens, Greece Departments of Medicine, St. Michael's Hospital and the
Chapter 43: Ventilntor-TIIrluced Diaphragm University of Toronto, Toronto, Ontario, Canada
Dysfunction 01npter 13: Proportio11nl Assist Ventilation
PREFACE
The second edition of a textbook is typically a cosmetic job. ventilation. I hope that future developments vvill be stimu-
A snip here. A hiCk there. And correction of major howlers. lated by the new edition, through its shining a spotlight on
New editions usually arrive within three or four years of hidden recesses of ignorance and areas of controversy.
their p redecessor. This short interval decreases the incentive In the Internet age, readers have questioned the useful-
of contributing authors to make substantial changes to their ness of textbooks. Today's physicians can access the latest
chapters. As such, content changes much less than might research across a wide spectrum of journals. By design, how-
be expected. Twelve years have passed before bringing out ever, the information is fragmented, and little effort is made
a new edition of Principles a11d Prnctice of Mechanirol Venti- to fit new research into the mosaic of existing knowledge.
latioll. Thus, this volume is more representative of a fourth A state-of-the-art review article can provide comprehensive
than of a second edition. Rather than confess to laziness, I discussion of a subject. The authors of such an article, how-
would like readers to believe that I did not wish to burden ever, ca1mot achieve substantial depth unless they focus on
them with the usual second and third editions. a narrow area. A detailed discussion of all the nuances of
The goal of the book is u nchanged: to provide a com- positive end-expiratory pressure requires much more space
prehensive and contemporary discussion of mechanical than a journal editor wou ld be wil lin g to allow. Thus, physi-
ventilation based on the application of knowledge gain ed cians wishing to gain expertise across a broad fie ld are left
through research. By providing a single resource where clin- with many gaps-especially of subjects that journal editors
icians can find answers to all their questions about mechan- deem unfashionable. For trainees struggling to acquire ex-
ical ventilation, I hope the contained information will im- pertise in a field, new understanding necessarily depends
prove the care of ventilated-supported patients. on the epistemic ideals they set for themselves, the path they
The content of the book, however, is drastically changed. choose for gaining knowledge. One vital epistemic ideal is
The new edition contains twenty-four completely new chap- coherence: that beliefs within a field not only make sense
ters. Subjects include dyspnea in the ventilated patient, individually but they also hang together in a coherent pat-
diaphragmatic pacing, inhaled antibiotic therapy, liquid tern. From the Middle Ages onwards, Summa accounts that
ventilation, inhaled nitric oxide, ven tilator-induced di- collate, synthesize and integrate all known information in a
aphragmatic damage, and speech and sleep in the venti- field have been sought after by scholars and professionals.
lated patient. Other new chapters cover additional exciting For this task, the textbook has no competitor.
developmen ts since the early 1990s. Integrated accounts of Book chapters can vary enormously in organization,
ventilator strategies in major disease states, such as the acute presentation, and readability. To minimize such variation,
respiratory distress syndrome, asthma and chronic obstruc- authors of the new edition of Principles mrd Practice of
tive pulmonary disease, are presented in new chapters. To- Mechanicnl Ventilatio11 were given detailed guidance on the
day, mechanical ventilation is used increasingly outside the structure of their chapter and also the expected content of
intensive care unit; several new chapters distill the expel'" every other chapter. This p lanned structure should make
tise that has been garnered at these locations. For seventeen it easier for readers to contrast tl1e advantages and dis-
of previously included chapters, new authors provide com- advantages of various ventilator techniques. To enhance
pletely fresh accoun ts. To make way for all this new material, clarity and readability and to aclueve a relatively uni-
several chapters (in the previous edition) have been deleted. form style throughout the book, I personally copy-edited
All in all, the content bears Little resemblance to that of the each manuscript. Some chapters underwent several revisions
first edition, with the exception of the historical perspective after their first submission.
chapter. The dread of every textbook editor is the delay between
Editing this book has been a tremendous educational ex- arrival of the first and last chapter. A year or more may
perience. It is fascinating to see how mechanical ventilation elapse, making chapters of punctual contributors appear
has changed over the past twelve years. When engaged in dated by the time a book is published. Every effort was made
day-to-day practice of a discipline, we underestimate how to avoid this problem, and chapters arrived within four
much it changes from year to year. Leafing through the months of their due date. (A couple of authors who could not
two editions of this book makes it clear that few areas of meet an extension of the deadline were dropped.) McGraw-
medicine have undergone so much change as mechanical Hill placed the book on a rapid production track. As such,
.
xzx
Copyright © 2006 by McGraw-Hill, Inc. Click here for terms of use.
XX PREFACE
the book achieves a freshness attained by few medical physicians who seek the most authoritative writing on a
journals. subject must turn to articles and texts published by non-
A multi-authored text can only be as good as its authors. intensivists.
For each chapter, I selected the scientists and clinicians at the This book would not have been possible without the
forefront of research in that area. Such authors are attw1ed help of several people, and to them 1 am extremely grate·
to evolving developments in a field, thus guarding against ful. First are the more than one hundred authors, whose
early obsolescence of covered material. A striking feahtre knowledge, commitment and wisdom form the core of the
is the geographical diversity of the authors, reflecting the book. I am grateful to jane LaMarre, Lynne! Hodge, and
international base of advances in this field. Karen Janata for invaluable assistance at several stages
The corpu.o; of knowledge required for the practice of a of the project. 1 thank Patrick J Fahey, MD, Chairman of
medical subspecialty is generated by researchers who typ- Medicine at Loyola and Brian Schmitt, MD Chairman of
ically devote their professional life to that field. Virtually Medici11e at Hines for their support of scholarly activ-
all patients admitted to an intensive care w1it can be clas- ity. The faculty and fellows in the Division of Pulmonary
sified under one or two headings: admission for the de- and Critical Care Medicine at Loyola-Hines provided stim-
livery of mechanical ventilation or for detailed monitoring ulation and insight. Penelope Linskey, Christie Naglieri,
of vital organ fwlction. Thus, the unique corpus of knowl- and Karen Edmonson at McGraw-Hill guided the book
edge required for expert practice of intensive care medicine through its production. Finally, 1 thank my family for their
is provided by Pri11ciples and Practice of Mechanical Venti- forbearance.
lation and its companion text, Principles and Practice of Inten-
sive Care Monitoring. Outside these two areas, intensive care Kilken11y, 2006
Principles
and Practice
of Mechanical
Ventilation
PART I and breathed into his nostrils the breath of life and man
became a living being" (Genesis 2:7); "when thou takest
away their breath, they die and return to their dust" (Psalms
HISTORICAL 104:29). Understanding why breathing is essential to life,
that is, the physiologic role of ventilation, however, was
BACKGROUND not intuitively apparent. It has taken millennia and a cir·
cuitous route encompassing advances in widely disparate
fields before humankind has developed clear insights into
1!1 the purpose of ventilation.
Chapter 1 The history of understanding ventilation is intimately
intertwined with the history of anatomy, chemistry, and
HISTORICAL physiology; exploration under wa ter and in the air; a nd
of course, modern medicine. Anatomists from the early
PERSPECTIVE ON THE Greek physician-scholars to Malpighi described the struc-
tural connections of the lungs to the heart a nd vasculature
DEVELOPMENT OF and developed the earliest insights into the functional re-
lationships of these organs. They emphasized the role of
MECHANICAL the lungs in bringing air into the body and probably ex-
pelling waste products but showed little understanding of
VENTILATION how air was used by the body. Chemists d efined the con-
GENE L. COUCE
stituents of air and explained the metabolic p rocesses by
which the cells used oxygen and produced carbon diox-
ide. Physiologists complemented these studies by explor-
ing the relationships between levels of oxygen and carbon
dioxide in the blood and ventilation. Explorers tested the
true limits of physiology. Travel in the air and underwa-
ter exposed humans to extremes in ventilatory demands
ANATOMISTS: OF THE HEART AND LUNGS and prompted the development of mechanical adjuncts to
Early Greeks ventilation. Following the various historical threads pro-
Renaissa nce Physicians vided by the anatomists, chemists, physiologists, and ex-
CHEMISTS AND PHYSIOLOGISTS: plorers will provide a useful perspective on the tapestry of
OF THE AIR AND BLOOD a technique modern physicians accept casually: mechanical
Understanding Gases ventilation.
Metabolism
Blood Gases a nd Ventilation
EXPLORERS AND WORKING MEN:
OF SUBMARINES AND BALLOONS Anatomists: Of the Heart and Lungs
Exploration Under Water
EARLY GREEKS
Exploration in the Air
MECHANICAL VENTILATION: TI1e Chinese and Egyptian civilizations apparently devel-
OF RESUSCITATION AND ANESTHESIA oped practical and reliable medical treatments millennia be-
Vivisection fore the birth of Christ but left little evidence of an interest
Resuscitating the Apparently Drowned in either anatomy or physiology. During the Greco-Roman
Negative-Pressure Ventilators period, study in many aspects of biology flourished. Be-
Positive-Pressure Ventilation ginning with Anaxirnenes around 550 sc and ending w ith
In the Operating Room Galen about AD 160, the Greeks showed gn~at interest in
CONCLUSION the structure and function of the human body. Early Greek
physicians endorsed Empedocles' view that all matter was
Breathing is both fundamentally obvious and essential to composed of four essential elements: earth, air, fire, and wa-
We. From ancient times, humankind has attributed to air ter. Each of these elements had primary qualities of heat
and the inhalation of air unique and almost mystical proper· and cold, moisture and dryness.1 Empedocles applied tllis
ties. Chinese philosophers as far back as 2000 nc described global philosophic view to the human body by stating that
lien cJz'i as the process of transmitting the inspired breath "innate heat," or the soul, was d istributed from the heart via
into the "soul s ubstance." Anaximenes of Miltus, a Greek the blood to various parts of the body.
physician born around 570 sc, stated that pneuma, or breath, This concept of the heart as a source and distributor of
was the essence of all things and recognized it as essential an innate heat played an important role in how these early
to We. He noted that "as our soul, being air, sustains us, physicians viewed the relationship among the lungs, heart,
so pneuma and air pervade the whole world." Biblical ref- and blood. The Hippocratic corpus, for instance, stated that
erences similarly emphasize the importance of breathing: the purpose of respiration was to cool the heart. Air was
"then the Lord God formed man of dust from the ground thought to be pumped by the atria from the lungs to the right
1
2 PART I HISTORICAL BACKGROUND
ventricle via the pulmonary artery and to the left ventricle parently, however, he did not understand fue true circular
through the pulmonary vein. 2 Aristotle performed vivisec- nature of blood flow. Galen also failed in two critical ways to
tions and dissections on hundreds of species but did little appreciate tl1e true interaction of the heart and lungs. First,
to clarify how the heart and lungs cooperated. He believed he believed, as did Aristotle and other earlier Greeks, that
that blood was an indispensable part of animals but that the left ventricle is the source of the innate heat that vital-
blood was found only in veins. Arteries, in contrast, con- izes the animal. Respiration in animals exists for the sake
tained only air. This conclusion probably was based on his of the heart, which requires the substance of air to cool it.
met11ods of sacrificing animals. The animals were starved, Expansion of the lung caused the lightest substance, that is,
to better define their vessels, and fuen ti1ey were strangled. the outside air, to rush in and fill the bronchi. Galen pro-
During fue strangulation, blood probably pooled in the right vided no insight, though, into how air, or pueumn, might be
side of the heart and venous circulation, leaving the left side drawn out from the bronchi and lungs into the heart. Sec-
of the heart and arteries empty. 2 Aristotle described a three- ond, he did not clearly describe blood flow from the right
chamber heart connected witi1 passages leading in the di- ventricle through the lungs and into the left ventricle. In-
rection of ti1e lung, but these connections were minute and deed, his w ritings left the serious misconception that blood
indiscemible. 3 Presumably, the lungs cooled the blood and was somehow transported directly from the right to the left
somehow supplied it witi1 air. 4 ventricle through the mterventricular septum. 1•5' 6
Erasistratus (born around 300 Be) took significant steps
forward from Aristotle's views. He believed that air taken
RENAISSANCE PHYSICIANS
in by the lungs was transferred via the pulmonary artery
to the left ventricle. Within the left ventricle, air was trans- Galen's influence was pervasive for hundreds of year s, in
formed into pneuma zotikon, or the "vital spirit," and was large part because the Romans did little to encourage ex-
distributed through air-filled arteries to various parts of the perimentation in anatomy, and feudal lords and barbarians
body. The pneuma zotikon carried to fue brain was secondar- disparaged all science during tl1e Dark Ages. Fortunately,
ily d 1anged to the pneuma psycltikon ("animal spirit"). This Byzantine and Arab scholars mamtained Galen's legacy and
animal spirit was transmitted to the muscles by the hollow provided a foundation for the rebirth of science during the
nerves. Apparently, Erasistratus understood fua t the right Renaissance.1' 6' 7 A renewed interest in anatomy was trig-
ventricle facilita ted venous return to fue heart by suction gered in the 1400s and 1500s by artists such as Leonardo da
during diastole and also that venous valves allowed only Vinci, who strove for an accurate and natural representation
one-way flow of blood. These concepts would become in- of the human form. For the first time in over a millennium,
strumental in leading to understanding the true nature of there was a surge of interest, primarily by Italian physicians,
circulation.1 in dissection. Around 1550, Vesalius, ti1e foremost anatomist
As Greek civilization waned and the Roman Empire flour- of his time, corrected many inaccuracies in Galen's work
ished, medicine became more pragmatic, with one out- and even questioned Galen's concept of blood flow from
standing exception. The Greek physician Claudius Galen the right ventricle to the left ventricle. He specifically was
established a practice in Rome in AD 161 and soon be- skeptical about the flow of blood through the interventric-
came recognized as fue most influential physician in the ular pores Galen described. 1 • 6~ 8 Vesalius's ideas may have
world. Galen's insights, based on extensive vivisection and been the critical catalyst for subsequent work leading to a
physiologic studies, are well worth examining. He demon- true understanding of fue circulation.
strated that arteries contain blood by inserting a tube into Servetus, a fellow student of Vesalius in Paris, suggested
the femoral artery of a dog. 5' 6 Blood flow through the tube that the vital spirit is elaborated both by the force of heat
could be controlled by adjusting tens.ion on a ligature placed from the left ventricle and by a change in color of the blood
around the proximal portion of the artery. He described a to reddish yellow. This change in color " is generated in the
four-chamber heart witl1 auricles distinct from the right and lungs from a mixture of inspired air with elaborated subtle
left ventricles. Galen also believed ti1at fue "power of pul- blood which the right ventricle of the heart communicates to
sation has its origin in the heart itself" and that fue "power the left. However, this communication is made not through
[to contract and dilate] belongs by nature to the heart and the middle wall of the heart, as is commonly believed, but
is infused into the arteries from it."5.6 He described valves by a very ingenious arrangement: the subtle blood courses
in the heart in detail and, as did Erasistratus, recognized through the lungs from the pulmonary artery to pulmonary
their essential importance in preventing the backward dis- vein, where it changes color. During this passage the blood is
cl1arge of blood from the heart. He alluded several times mixed with inspired air and through expiration it is cleansed
to blood flowing, for example, from the body furough the of its sooty vapors. This mixture, suitably prepared for the
vena cava into the right ventricle and even made fue remark- production of the vital spirit, is drawn onward to the left
able statement that " in the entire body the arteries come to- ventricle of ti1e heart by diastole."6•9 Although Servetus'
gether with the veins and exchange air and blood through views proved ultin1ately to be correct, they were consid-
extremely fine invisible orifices."6 Furthermore, Galen be- ered heretical at the time, and he was subsequently burned
lieved that "fuliginous wastes" were somehow discharged at the stake, along with most copies of his book, in 1553.
from the blood through the lung.6 This appreciation that Fortunately, religious fervor did not dissuade Columbus,
the lungs served bofu to supply some property of air to the a dissectionist to Vesalius at Padua, from continuing the
body and to discharge a waste product from fue blood was line of reasoning advanced by Servetus. In 1559 he cited
the first true insight into the lung's role in ventilation. Ap- evidence supporting the view that blood travels to the ltmgs
CHAPTER 1 H ISTORICAL PERSPECTIVE ON THE DEVELOPMENT OF MECHANICAL VENTILATION 3
via the pulmonary artery a nd then, along with air, is taken the hvo vessels .... blood flowed away along [these] tortu-
to the left ventricle through the pulmonary vein. H e further ous vessels ... always contained within tubules." 1•6 Second,
advanced the concept of circulation by noting that the left Borelli, a mathematicia n in Pisa and a friend of Malpighi,
ventricle distributes blood to the bod y through the aorta, first suggested the concept of diffusion. Air dissolved in liq-
blood returns to the right ventricle in the vena cava, and uids could pass through membranes without the existence
venous valves in the heart allow only one-way flow. L, 6, 10 of pores. Air and blood finally had been linked in a plausible
These views clearly influenced William Harvey, who manner.I
studied ana tomy with Fabricius in Padua from 1600 to 1602.
Harvey set out to investiga te the " true movement, pulse,
action, use a nd usefulness of the heart and arteries."
He ques tioned why the left ventricle and right ventricle Chemists and Physiologists:
traditionally were felt to play such fundamentally different
roles. If the right ventricle existed simply to nourish the Of the Air and Blood
lungs, why was its structure so simila r to that of the left
UNDERSTANDING GASES
ventricle? Furthermore, when one directly observed the
beating heart in animals, it was dear that the ftmction of The anatomists had identified a n entirely new set of prob-
both right and left ventricles also was similar. In both cases, lems for chemists and physiologists to consider. The con-
when the ventricle contracted, it expelled blood, and when ce pt of blood circulation had been well developed. It was
it relaxed, it received blood. Cardiac systole coincided w ith accepted that the right ventricle pumped blood through
arterial pulsations. The motion of the auricles preceded the pulmonary artery to the lungs. In the lungs the blood
that of the ventricles. Indeed, the motions ar e consecutive took up some substance. This was evidenced by the change
with a rhythm about them, the auricles contracting and in color observed as blood passes through the pulmonary
forcing blood into the ventricles and the ventricles, in turn, circulation. It also was presumed that the blood released
contracting and forcing blood into the a rteries. "Since blood "ruliginous wastes" into the lung. The site of this exchange
is constantly sent from the right ventricle into the lungs was thought to be at the alveolar-capillary interface, and it
through the pulmonary artery and likewise constantly is probably occurred by the process of diffusion. What were
drawn the left ventricle from the lungs ... it cannot do the substances exchanged between blood and air in the
otherwise than flow through continuously. This flow mus t lung? What changed the color of blood and was essential for
occur by way of tiny pores and vascular openings through the production of the "inna te heat''? Wl1a t was the process
the lungs. Thus, the right ventricle may be said to be made by which "innate heat'' was produced, and where did this
for the sake of transmitting blood through the lungs, not combustion occur, in the left ventricle as supposed from the
for nourishing them."6;ll earliest Greek physician-philosophers or elsewhere? Where
Harvey described blood flow through the body as be- were the "fuligino us wastes" produced, and were they in
ing circular. This was easily understood if one just con- any way related to the production of "innate heat''? If the
sidered the quantity of blood pumped by the heart. If the blood was a carrier, pumped by the left ventricle to the body,
heart pumped 1 to 2 drachms of blood per beat and beat what was it carrying to the tissues and then again back to
1000 times per half-hour, it put out almos t 2000 drachms in the heart?
this short time. This was more blood than was contained Von Helmont provided a new approach to these problems
in the whole body. Clearly, the body could not produce by performing experiments with gases. In about 1620 he
amounts of blood fas t enough to supply these needs. Where added acid to limestone and potash and collected the "air"
else could all the blood go but around and around "like a liberated by the chemical reactio n. This "air" extinguished
stage army in an opera." If this theory were correct, Harvey a flame and seemed to be similar to the gas produced by
went on to say, then blood must be only a carrier of critical fermentation. This "air" also appeared to be the same gas
nutrients for the b ody. Presumably, the problem of the elim- as that found in the Grotto del Cane. This grotto was noto-
ination of waste vapors from the lungs also was explained rious for conta ining a ir that would kill dogs but spare their
by the idea of blood as the carrier.l.6, n taller masters.1 The gas, of course, was carbon dioxide, but
With Harvey's remarkable insights, the relationship be- von Helmont's studies were not appreciated for well over
tween the lungs and the heart and the role of blood a hundred years. What was appreciated, however, was that
were finally understood. Only two steps remained for the air was a complex substance. In the la te seventeenth cen-
anatomists to resolve. First, the nature of the tiny pores tury, Boyle described this new insight well. He considered
and vascular openings through the lungs had to be ex- the constitution of air, which he called "atmospherical air,"
plained. About 1650, Malpighi provided s uch an expla na- a confused aggregate of effluviums. For exan1ple, he recog-
tion through his work with early microscopes. He found nized that sulfur particles could impregnate the air. This was
that air passes via the trachea and bronchi into and out of apparent by the odor. Furthermore, there is some substance
microscopic saccules w ith no clear connection to the blood- in air that is necessary to keep a flame burning and an ani-
stream. He further described capillaries: " ... and such is mal alive. Place a flame in a bell jar, and the flame eventually
the wandering about of these vessels as they proceed on will go out. Place a n animal in such a chamber, and the an-
this side from the vein and on the other side from the artery, imal eventually will die. 1f another animal is placed in that
that the vessels no longer maintain a straight direction, but sam e cl1amber soon thereafter, it w ill die sudden!y. This con-
there appears a network made up of the articulations of cept was nicely supported by Mayow's simple experiments
around 1670. Enclosing a mouse in a bell jar resulted even-

tually in the mouse's death. If the bell jar was covered by
a moistened bladder, the bladder bulged inward when the
mouse died. Obviously, the animals needed something in
air for survival. Mayow called this the "nitro-aereal spirit,"
and when it was depleted, the animals died. 1• 12 It was well
recognized that air had at least four qualities: heat, cold,
dryness, and mois ture. Philosophers and chemists recog-
nized that air also had gravity, springiness, and the power
to refract light. Boyle's suspicions, however, that air had
other qualities primarily owing to its ingredients seemed
well founded.13 ·14
In a remarkable and probably entirely intuitive insight,
Mayow suggested that the ingredient essential for life, the
"nitro-aereal spirit," was taken up by the blood and formed
the basis of muscular contraction. Evidence supporting this
concept came indirectly. The concept of air pressure a ppar-
ently had just been apprecia ted by Galileo in the early 1600s.
Torricelli found in 1644 that a column of mercury 30 inches 1
high could be supported in a glass tube with its lower end
in a base of mercury. He postulated that the weight of air
supported this colum11 of mercury. Pascal realized that if
air did have weight, air pressure should vary w ith altitude.
This hypothesis was confirmed when the height of a col-
umn of mercury was measured simultaneously by Pascal's ~
:.:-t~'"" -
brother-in-law Perier in the Puy-de-Dome mountains and ·~·· ... c . . -=
at sea level in 1648.
The ability to study the effects of changes in air pressure ...-·.
J~.
-~ -
became possible when von Guericke invented the pneu-
matic machine, a device that reduced air pressure. 1•15 Robert .. .
·~
Boyle was stimulated by Harvey's work on circulation to ask

what part did air and respiration play. He saw the pneu-
matic pump as an ideal way to answer this question, and
he commissioned Robert Hooke and the instrument maker FI GU RE 1-1 A pneumatical engin e, or vacuum pump, devis ed by
Hooke in collabontion with Boyle around 1660. Th e jar (6)
Ralph Greatorex to d esign and build a closed vessel from
contains an animal in this illus tration. Pressure is lowexed in the
which air could be extracted using a pumping mechanism jar by raising the tigh tly fitting slide (5) with the crank (4). (Used,
to produce something approaching a vacuum (Fig. 1-1). with permissiou, from Graubard.6)
Hooke, being an impatient and demanding type, soon
dropped Greatorex from the endeavor and developed the
pump himself. H e also was the only one who could consis-
tently operate the tempermentaJ device. Boyle a nd Hooke working on a cure for kidney stones when he found that
used this pneuma tic engine to study animals under low- limestone was transformed into caustic lime and lost weight
pressure conditions. Appru·ently Hooke favored dramatic on being heated. The weight loss occurred because a gas was
experiments, and he often demonstrated in front of crowds liberated during the heating process. TI1e same results oc-
that small animals died after air was evacuated from the curred when the carbona tes of alkali metals were treated
cl1amber. Hooke actually built a human-sized chamber in with an acid such as hydrochloric add. He called the liber-
1671 and volunteered to enter it. Fortunately, the pump ef- ated gas "fixed air" and found that it would react with lime
fectively removed only about a quarter of the air, and H ooke water to form a w hite insoluble precipitate of chalk. This
survived .16 Boyle believed that the difficulty encountered in reaction became an invaluable marker for the presence of
breathing under these conditions was caused solely by the "fixed air," Black subsequen tly found that "fixed air" was
loss of elasticity in the air. He also went on to observe, how- produced by burning charcoal and fermenting beer. In a re-
ever, that a nimal blood bubbled when placed in a vacuum. markable experiment he showed that "fixed air" was given
This observation clearly showed that blood contained a gas off by respiration. In a Scottish church where a large con-
of some type."13•14 In 1727 Hales introduced the pneumatic gregation gathered for religious devotions, he allowed lime-
trough (Fig. 1-2). With this device he was able to distinguish water to drip over rags in the air ducts. After the service,
between free gas and gas no longer in its elastic state but which lasted about 10 hours, he found a precipitate of crys-
combined w ith a liquid.1 The basis for blood gas machines talline lime (CaC03 ) in the rags, proof that "fixed air" was
had been invented. produced during the services. Black recognized that "fixed
TI1e first constituent of air to be truly recognized was air" was the same gas described by von Helmont and would
carbon dioxide. Joseph Black (around 1754) probably was extinguish flame and life.l,4, 14
CHAPTER 1 HISTORICAL PERSPECTIVE ON THE DEVELOPMENT OF MECHANICAL VENTILATION 5
ing was nonphlogiston.1A Remarkably, both men described

their observations to Antoine Lavoisier, who would go on to
discredit the phlogiston theory. Lavoisier was a successful
businessman but enjoyed dabbling in science on an inter-
mittent basis. His research proved to have a profound in-
fluence on chemistry. H e repeated Priestley's experiments
and found that if mercuric oxide was heated in the pres-
ence of charcoal, Black's "fixed air'' would be produced.
Further work led Lavoisier to the conclusion that ordinary
air must have at least two separate components. One part
was respirable, combined with metals during heating, and
supported combustion. The other part was noruespirable.ln
1779 Lavoisier called the respirable component of air "oxy-
gen." He also concluded from his experiments that "fixed
air" was a combination of coal and the respirable portion of
air.lt was apparent to Lavoisier that oxygen, not phlogiston,
was the explanation for combustion. 1A· 17
METABO LISM
Political upheavals kept Lavoisier from his scientific work
for several years, but later in the 1780s he performed a
brilliant series of studies witl1 the French mathematician
Laplace on the use of oxygen by aninlals. Lavoisier knew
that oxygen was essential for combustion and necessary for
life. Furthermore, he was well aware of the Greek concept
of internal heat presumably produced by the left ventricle.
The obvious question was whether animals used oxygen
for some type of internal combustion. Would this internal
combustion be similar to that readily perceived by the burn-
ing of coal? To answer this question, tl1e two great scientists
built an ice calorimeter (Fig. 1-3). This device could do two
things. Because the melting of ice was a heat-consuming
process, the rate at which ice melted in the calorimeter
could be used as a quantitative measure o f heat produc-
tion within the calorimeter. In addition, the consumption
of oxygen could be measured. It then was a relatively sim-
FIGURE 1-2 In 1727, H ales developed the pneumatic trou gh,
ple task to put an animal inside the calorimeter and care-
shown on the bottom of this illus tration. This device enabled h im
to collect gases produced by heating. On the top is a closed-circuit fully measure heat production and oxygen consumption.
respiratory apparatus for inhaling the collected gases. (Used, witlt As Lavoisier suspected, the amount of heat generated by
pen11ission, from Perkins.1 ) the animal was similar to that produced by burning coal for
the quantity of oxygen consumed.1' 4
Despite Lavoisier's prodigious aclUevements in identify-
In the early 1770s, Priestley and Scheele, working inde- ing the respirable portion of atmospheric air and in defining
pendently of each o ther but using similar methods, both the cl1ernical processes involved in the production of "innate
produced and isolated "pure air." Priestley used a 12-inch heat," his political and business activities were caug ht up in
lens to heat mercuric oxide. The gas released in this process the vortex of the French Revolution. In May 1794 the Fa-
passed through the long neck of a flask and was isolated ther of Modern Chemistry was guillotined. 17 Fortunately,
over mercury. This gas allowed a flame to burn brighter Lavoisier's findings and opinions were distributed widely
and a mouse to live longer tl1an in ordinary air. 1•4•.15 Scheele and believed. More important, they stimulated intensive re-
also heated chemicals such as mercuric oxide and isolated search in two areas: metabolism and fue role of oxygen and
the gases produced. He collected the gases in ox or hog blad- carbon dioxide in ventilation.
ders. Like Priestley, Scheele found that the gas isolated made It was not clear from Lavoisier's work where in the body
a flame bum brighter. Neither Priestley nor Scheele under- interna l combustion actually too k place. The Greeks sus-
stood the real significance of their findings. They attempted pected that the left ventricle produced innate heat, and
to explain their findings by the phlogiston theory of Stahl. Lavoisier himself may have thought that internal combus-
Stahl felt tl1at all material contained variable amounts of a tion occurred in the Iungs. 4 Spallanzani redirected atten-
substance called phlogiston, which could transform itself into tion to the tissue level. H e took a variety of tissues from
fire on heating. The residual material, or ash, left after heat- freshly killed animals a nd fow1d that tl1ey took up oxygen
,..
.. ' I •
II
FIGURE 1-3 The ice calorimeter, desig,ed by Lavoisier

and Laplace, allowed these French scientists to measure
the oxygen consumed by an animal and the heat
produced by Ulat same animal. With careful
meas urements, the intemal combustion of animals was
foun d to be similar, in tenns of oxygen consump tion
and heat production, to open fires. (Usetl, w itll
permission, from Perkius.1 )
and released carbon dioxide. 1 Magnus, relying on improved "fuliginous wastes" were released from the lung. In sepa-
methods of analyzing the gas content of blood, found higher rate experiments, the British scientist Lower and the Irish
oxygen levels in arterial blood than in venous blood but scientist Boyle provided the first evidence that uptake of
higher carbon dioxide levels in venous blood than in arte- gases in the lungs was re lated to gas content in the blood.
rial blood. He believed that inhaled oxygen was absorbed In 1669 Lower placed a cork in the trachea of an animal and
into the blood, transported throughout the body, given off at found that arterial blood took on a venous appearance. Re-
the capillary level to the tissues, and there formed the basis moving the cork and ventilating the lungs with a bellows
for the formation of carbon dioxide.18 Many other scientists made the arterial blood bright red again. Lower felt that the
pursued this area of research and built elaborate devices blood must take in air during its course through the lungs
to study metabolism and respiration. In 1849 Regnault and and therefore owed its bright color entirely to an admixture
Reiset perfected a dosed-circuit metabolic chamber with de- of air. Moreover, after the air had in large measure left the
vices for circulating air, absorbing carbon dioxide, and peri- blood again in the viscera, the venous blood became dark
odically adding oxygen (Fig. 1-4). Pettenkofer built a closed- red. 20 A year later Boyle showed with his vacuum pump
circuit metabolic chamber large enough for a man and a bi- that blood contained gas. Following Lavoisier's studies, sci-
cycle ergometer (Fig. 1-5). 19 This device relied on a steam en tjsts knew that oxygen was the component of air essential
engine to pump air, gas meters to measure air volumes, and for life and that carbon dioxide was the "fuliginous waste."
barium hydroxide to collect carbon dioxide. Although these The next step, understanding how oxygen and carbon diox-
devices were intended to examine the relationship between ide were related to ventilation, required valid methods of
inhaled oxygen and exhaled carbon dioxide, they also could measuring the content of these gases in blood.
be viewed as among some of the earliest methods of con- In about 1797 Davey was the first actually to measure the
trolled ventilation. These efforts were essential in leading amount of oxygen and carbon dioxide extracted £rom blood
chemists to study cellular metabolism. by an air pump. 4 The significance of this finding was not
appreciated at the time. Magnus in 1837, however, success-
fully built a device for quantitative analysis of blood oxygen
and carbon dioxide content.'18 This was a mercurial blood
BLOOD GASES AND VENTILATION
pump. Blood was enclosed in a glass tube in continuity w ith
Lavoisier's work also provided the critical pieces of data nec- a vacuum pump. Carbon dioxide extracted by means of the
essary for an explosion of knowledge on the role of gases in vacuum was quantified by the cl1ange in weight of carbon
ventilation. From ancient times it was understood that some dioxide-absorbent caustic potash. Oxygen content was de-
element in air was necessary for life and, furthermore, that termined by detonating the gas in hydrogen.15 A limiting
CHAPTER 1 HISTORICAL PERSPECTIVE ON TI-lE DEVELOPMENT OF MECHANICAL VENTILATION 7
r· . II
.a~. . j -
\ T
..........,...
'
FIGURE 1-4 Regnault and Reiset

developed a closed-circuit
metabolic chamber in 1849 for
studying oxygen consumption an d
-
-
carbon dioxide production in
/ }
animals. (Used, with penuissiou,

•'
•
•• ~-
from Perkius."1)
factor in Magnus's work was the assumption that the quan- achieved during the latter ha lf of the nineteenth century. Be-
tityof oxygen and carbon dioxide in blood simply depended sides his extensive experiments with animals in either high-
on absorption. Hence the variables determining gas content or low-pressure chambers, Bert also examined the effect of
in blood were presumed to be the absorption coefficients ventilation on blood gas levels. Using a bellows to artifi-
and partial pressures of the gases. In the 1860s, working in cially ventilate animals through a tracheostomy, he found
concert, Meyer and Fernet showed tha t the gas content of that increasing ventilation would increase oxygen content in
blood was determined by more than just simple physical blood and decrease the carbon dioxide content. Decreasing
properties. Meyer found that the oxygen content of blood ventilation had the opposite effect.15 Dohman, in Pfluger's
remained relatively stable despite large fluctuations in its laboratory, showed that both carbon dioxide excess and lack
partial pressure. 21 Fernet showed that blood absorbed more of oxygen would stin1ulate ventilation. 23 Miescher-Rusch
oxygen than did saline solution a t a given partial pressure. 15 demonstrated in 1885 that carbon dioxide excess was the
Paul Bert was trained originally in law but later turned to more potent stimulus for ventilation.1 Haldane and Priest-
medicine and studied under Claude Bernard in Paris in the ley, building on this work, made great strides in analyzing
1860s. He became interested in altitude physiology through the chemical control of ventilation. They developed a de-
a close friendship with Jourdanet, a wealthy patron who vice for sampling end-tidal, or a lveolar exhaled, gas (Fig.
had developed mountain sickness during a trip to Mexico. 1-6). Even small changes in alveolar carbon dioxide fraction
Jourdanet was willing to support many of Bert's experi- greatly increased minute ventilation, but hypoxia did not
ments financially; thro ugh this work, Bert made a series of increase minute ventilation until the alveolar oxygen frac-
extremely important contributions to this field. For instance, tion fell to 12-13%.24
he felt that it was intuitively obvious tha t oxygen consump- Early measurements of arterial oxygen and carbon diox-
tion could not be strictly dependent on the physical prop- ide tensions led to widely divergent results.ln Ludwig's lab-
erties of oxygen dissolving under pressure in the blood. As oratory the arterial partial p ressure of oxygen was thought
an example, he posed the problem of a bird in flight chang- to be about 20 mmHg. The partial pressure of carbon diox-
ing a ltitude abruptly. Oxygen consumption could be main- ide reportedly was much higher than currently believed.
tained w ith tl1e sudden changes in pressure only if chemi- These results could not entirely support the concept of pas-
cal reactions contributed to the oxygen-carrying capacity of sive gas movement between lung blood and tissues based
blood. 15 In 1878 Bert went on to describe the first air curvi- on p ressure gradients. Ludwig and others began to sus-
linear oxygen dissociation curves relating oxygen content pect that an active secretory process was involved in gas
of the blood to its pressure. Hoppe-Seyler was instrumental transport. 4 This hypothesis was suggested in part by the
in attributing the oxygen-carrying capacity of the blood to French biologist Biot, who observed that some deep-water
hemoglobin. 22 fish had extremely large swim bladders. Of immense inter-
Remarkable insights into the relationship among venti- est was the fact tl1a t the composition of the gas in those swim
lation and blood oxygen and carbon d ioxide contents were bladders seemed to be different than that of atmospheric
FIGURE 1-6 This relatively simple device enabled Haldan e and

Priestley to collect end-tidal expired air, which they felt
approximated alveolar air. The subject exhaled through the
mouthpiece at the right. At the end of expiration, the s topcock on
the accessory collecting bag was opened, and a small aliquot of air
was trapped in this device. (Used, with permission, from Bes t et al:
A P/,ysiological basis of 111edica.l practice. Baltimore: Williams &
Wilkins, 1939: 509.)
lung did not rely on active processes for transporting oxy-

gen and carbon dioxide; passive diffusion was a sufficient
explanation. 26
Although Pfluger's findings were fairly convincing at the
time, Bohr resurrected this controversyP He found greater
variability in blood and air carbon dioxide and oxygen ten-
sions than previously reported by Pfluger and suspected
that tmder some circumstances secretion of gases might oc-
cur. h1 response to this suspicion, Krogh, a student of Bohr's,
developed an improved blood gas-m ea suring techniqu e re-
lying on the microaero tonometer (Fig. 1-7). With his wife,
B Krogh convincingly showed that alveolar air oxygen ten-
sion was higher than blood oxygen tension and vice versa
for carbon dioxid e tensions, even when the composition of
inspired air was varied.28 Douglas and Haldane confirmed
Krog h's findings but wondered w hether they were appli-
cable only to people at rest. Perhaps during the stress of
either exercise or hig h-altitude exposure, passive diffusion
might no t be sufficient. Indeed, the ability to secrete oxy-
gen might explain the tolerance to hig h altitude developed
by repeated or chronic exposures. Possibly carbon diox-
ide excretion might occur with increased carbon dioxide
levels. 26 In a classic series of experiments, Marie Krogh
showed that d iffusion increased with exercise secondary to
the concomitant increase in cardiac output. 29 Barcroft put
to rest the diffusion-versus-secretion controversy w ith his
c
"glass chamber" experiment. For 6 days he remained in a
FIGURE 1-5 A. This huge device, constructed by Pettenk offer, closed chamber subjected to hypoxia similar to that found
was large enough for a person. B. The actual chamber. The gas
on Pike's Peak. Oxygen saturation of radial artery blood was
meters used to measure gas volumes are shown next to the
ch amber. The steam engine and gasometers for circulating air are always less than that of blood exposed to simultaneously
labeled A. C. A close-up view of the gas-absorbing device obtained alveolar gas, even during exercise. These were ex-
adjacent to the gas meter in B. With this device Pettenkoffer and pected findings for gas transport based simply on passive
Voit studied the effect of diet on the respiratory quotient. (Usetl, diffusion. 30
with permissiou,from Perkins.1) With this body of work, the chemists and ph ysiologists
had provided the fundan1ental knowledge necessary for
the development of mechanical ventilation. Oxygen was
air. Biot concluded that gas was actively secreted into these the component of atmospheric gas understood to be essen-
bladders. 4• 15•24, 25 Pfluger and his coworkers d eveloped the tial for life. Carbon dioxide was the " fuliginous waste" ga s
aero tonometer, a far more accurate d evice for measuring gas released from the lungs. The exchange of oxygen and car-
tensions than that used by Ludwig. When they obstructed a bon dioxide between air and blood was d etermined b y the
bronchus, they found no difference in the gas composition of tensions of these gases and simple passive diffusion. Blood
air distal to the bronchial obstruction and that of pulmonary was a carrier of these two gases, as Har vey first suggested.
venous blood draining the area. They concluded that the Oxygen was carried in two ways, both dissolved in plasma
The concept of blood acid-base activity was just beginning

to be examined in the early 1900s. By the 1930s, a practi-
cal electrode became available for determining anaerobic
blood pH,33 but pH was not thought to be useful clini-
cally until the 1950s. In 1952, during the polio epidemic in
Copenhagen, Ibsen suggested that hypoventilation, hyper-
m~rcury
A capnia, and respiratory acidosis caused the high mortal-
" sea.J
ity rate in polio patients with respiratory paralysis. Clini-
cians disagreed because a high level of 'bicarbonate" in the
blood of these patients indicated an alkalosis of uncertain
origin. By measuring pH, Ibsen was proved correct, and
clinicians soon became acutely aware of the importance of
determining both carbon dioxide levels and pH. 4 Numer-
c ous workers looked carefully at such factors as base ex-
cess, duration of hypercapnia, and renal buffering activity
before Siggaard-Anderson published a pH/log Pco2 acid-
base d1art in 1971.34 This chart proved to be an invalu-
able basis for evaluating acute and chronic respiratory and
metabolic acid-base disturbances. The development of prac-
tical blood gas machines suitable for use in clinical medicine
did not occur until electrodes became available for measur-
ing oxygen and carbon dioxide tensions in liquid solutions.
Stow built the first electrode capable of measuring blood
Pco2 . As the basis for this device, he used a glass pH elec-
trode with a coaxial central calomel electrode opening at its
I tip. A unique adaptation, however, was the use of a rub-
ber finger cot to wrap the electrode. This w rap trapped a
film of distilled water over the electrode. The finger cot
then acted as a semipermeable membrane to separate the
FI GURE 1-7 Krogh 's microaeroton ometer. A. An enlarged vi ew of measuring electrode from the sample.35 Clark used a simi-
the lower part of B. Through the bottom of the n arrow tube (1) in lar idea in the development of an oxygen measuring device.
A, blood is introduced. The blood leaves the upper end of th e Platinum electrodes were used as the measuring device, and
narrow tube (1) in a fine jet and p lays on the air bubble (2). Once
polyethylene served as the semipermeable membrane. 36 By
equilibrium is reached between the air bubble and blood, th e air
bubb le is drawn by th e screw plunger (4) into the graduated
1973, Radiometer was able to commercially produce the first
capillary tube s hown in B. The volume of the air bubble is automated blood gas analyzer, the ABL, capable of measur-
measured b efore and after treatment with KOH to absorb C0 2 ing Po2, Pco2, an d pH in blood.4
and p otassium pyrogallate to absorb 0 2 • The changes in volume
of the bubble reflect blood C0 2 and 02 content. C. A model of A
designed for direct connection to a blood vessel. (Used, w ith
pennission, from Best et al: Pl1ysiological basis of medical practice. Explorers and Working Men:
Baltimore: Williams & WilkitiS, 1939: 521.) Of Submarines and Balloons
Travel in the deep sea and flight have intrigued humankind
and chemically combined with hemoglobin. Blood carried for centuries. Achieving these goals has followed a typical
oxygen to the tissues, where oxygen was used in cellular pattern. First, individual explorers tested the limits of hu-
metabolism, that is, the production of the body's "innate man endurance. As mechanical devices were developed to
heat." Carbon dioxide was the waste product of this re- extend those limits, the deep sea and the air became acces-
action. Oxygen and carbon dioxide tensions in the blood sible to commercial and military exploration. These forces
were related to ventilation in two critical ways. Increas- further intensified the need for safe and efficient underwater
ing ventilation would secondarily increase oxygen tensions and high-altitude travel. Unfortunately, the development of
and decrease carbon dioxide levels. Decreasing ventilation vehicles to carry humans aloft and under water proceeded
would have the opposite effect. Because blood levels of oxy- faster than the appreciation of the physiologic risks. Calami-
gen and carbon dioxide could be measured, physiologists tous events ensued, with serious injury and death often a
now had a means of assessing the adequacy of ventilation. consequence. Only a clear understanding of the ventilatory
Decreased oxygen tensions a nd increased carbon dioxide problems associated with flight and deep-sea travel has en-
tensions played a critical role in the chemical control of abled human beings to reach outer space and the depths
ventilation. of the ocean floor. Appreciation of the requirements for
Of course, much work remained. How carbon dioxide med1anical ventilation in submarines and planes has pro-
was carried by the blood was not entirely understood un- vided valuable insights into methods of providing mechan-
til experiments were performed by Bohr31 and Haldane.32 ical ventilation in disease.
1Q PART I HISTORICAL BACKGROUND
EXPLORATION UNDER WATER Techniques used to make diving bells practical also were
applied to divers. Naked divers have been described since
Diving bells undoubtedly were derived from ancient hu-
mans' inverting a clay pot over their heads and breath- the begirmings of recorded history. Xerxes used them to
ing the trapped air while w1der water. These devices were recover sunken treasure.39 Sponge divers in the Mediter-
ranean in the 1860s could stay submerged for 2 to 4 minutes
used in ~arious forms by Alexander the Great at the siege
and reach depths of 45 to 55 m.40 Amas, female Japanese
of Tyre m 332 ac, the Romans in numerous naval bat-
divers using only goggles and a weight to facilita te rapid
tles, and pirates in the Black Sea. 37·38 In the 1500s Stur-
•
mtus constructed a heavy bell that, even though full of

I
desc~nt, made up to 60 to 90 dives a day to similar depths. 41
a_ir, sank of its own weight. When the bell was posi- Desptte the remarkable adaptations of breath-holding mea-
sures developed by these naked divers,42 t11e commercial
tioned at the bottom of fairly shallow bodies of water,
workers were able to enter and work w ithin the pro- and military use of naked divers was limited. In AD 77, Pliny
tected area. Unfortunately, these bells had to be raised described divers breathing tllrough tubes while submerged
and engaged in warfare. More sophisticated diving suits
periodically to the surface to refresh the air. Although the
were described by Leonardo da Vinci in 1500 and Renatus
nature of the foul a ir was not w1derstood, an important prin-
in 1511. These suits also relied on tubes connected to the
ciple of underwater work, the absolute need for adequate
ventilation, was appreciated.15 surface for ventilation. Although these breatl1ing tubes pro-
longed tmderwate.r activities, they did not enable divers to
. Halley ?evised the first modern version of the diving bell
m 1690 (Ftg. 1-8). To drive out the air accunmlated in the bell r~a0 even mo~erate de~ths. 15 Borelli described a complete
a~d "mad e foul" by tl1e workers' respiration, small barrels of
dtvt!'g. dres~ ~tth tubes m the helmet for recirculating and
ru.r were let down periodically from the surface and opened purifym g atr m 1680. Whether this actually was useful is
unclear (Fig. 1-9).37
within the bell. Old air was re leased through the top of
Klingert described the first modern diving suit in 1797.37
the bell by a valve. In 1691, Papin developed a technique
It consisted of a large helme t connected by twin breathing
for constantly injecting fresh air from the surface directly
into the bell by m eans of a strong leather bellows. In 1788, pipes to an air reservoir tllat was large enough to have an
Smeaton replaced the bellows witl1 a pump for supplying associated platfonn . The diver stood on the pla tform and
fresh air to the submerged belJ.15,37,38 inhaled from the air reservoir through an intake pipe on
the top of the reservoir and exhaled through a tube con-
nected to the bottom of the reservoir. Siebe made substantial
FIGURE 1-8 Halley' s version of the divin g bell. Small barrels of
fresh air were lowered periodically to the bell, and the worker
inside the bell released the aiL "Foul air" often was released by FIGURE 1-9 A fancih1l diving suit designed by Borelli in 1680.
way of a valve at the top of the bell. Workers could exit the bell (Used, w itll permission, from Hiff.38)
for sh ort p eriods. (Used, 1vitl1penn issior~, from H i /1.38)
F
CHAPTER 1 HISTORICAL PERSPECTIVE ON THE DEVELOPMENT OF MECHANICAL VENT1LATION 11
A - B
FIGURE 1-10 A. The metal hclmet devised by Siebe is still used today. B. The complete diving suit produced by Siebe, Gorman, and
Company in the nineteenth century included the metal helmet, a diving dress sealed at the wrists and ankles, and weighted shoes. (Usetl,
witl1 perm.issiou, from Hill.38)
revisions in this diving suit and constmcted the first com- sorbents. Construction of this appliance was so precise that
mercially viable diving dress. The diver wore a metal helmet Fleuss used it not only to stay underwater for hours but also
riveted to a flexible waterproof jacket. This jacket extended to enter chambers containing only noxious gases. The Fleuss
to the diver's waist but was not sealed. Air under pressure appliance was adapted rapidly and successfully to mine res-
was pumped from the surface into the diver's helmet and cue work, w here explosions and toxic gases previously had
escaped through the lower end of the jacket. ln 1837, Siebe prevented such efforts. 43
modified this diving dress by extending the jacket to cover As Siebe, Gorman, and Company successfully marketed
the whole body. The suit was watertight at the wrists and diving suits, commercial divers began to dive deeper and
ankles. Air tmder pressure entered the suit through a one- longer. Unfortw1ately, complications developed for two
way valve at the back of the helmet and was released from separate reasons. Decompression illness was recognized
the suit by an adjus table valve at the side of the helmet. first. In 1830, Lo rd Cochrane took out a patent in England
Variations of this diving suit are still in use (Fig. 1-1 0).37 for "an apparatus for compressing atmospheric air within
Siebe, Gorman, and Company became the world- the interior capacity of subterraneous excavations [to] .. .
recognized leaders in producing diving suits in the nine- counteract the tendency of superincumbent water to flow
teenth century. Modifications of Siebe's original design were by gravitation into such excavations . .. and which appa-
encouraged by thls company. In 1866, Denayouze incorpo- ratus at the same time is adapted to allowing workmen to
rated a metal air reservoir on the back of the diver's suit. carry out their ordinary operations of excavating, sinking,
Air was pumped directly into the reservoir, and escape of and mining."38 In 1841, Triger described the first practically
air from the suit was adjusted by the diver.15 In 1878, Siebe, applied caisson for penetrating the quicksands of the Loire
Gorman, and Company produced the first practical self- River (Fig. 1-11). 44 This caisson, or hollow iron tube, was
contained diving dress. The suit had a copper chamber con- sllilk to a depth of 20 m. The air within the caisson was
taining potash for absorbing carbon dioxide and a cylinder compressed by a pump at the surface. The high air pressure
of oxygen under pressure. 37 Fleuss cleverly revised this div- within the caisson was sufficient to keep water out of the
ing suit in 1879 with the help of Davis, managing director tube and allow workers to excavate the bottom. Once the
of Siebe, Gorman, and Company. The Fleuss appliance in- excavation reached the prescribed depth, the caisson was
cluded an oro nasal mask with an inlet and an exhaust valve. filled with cement, providing a firm foundation. During the
The inlet valve allowed inspiration from a metal chamber excavation process, workers entered and exited the cais-
containing oxygen under pressure. Expiration through the son through an airlock. During this work, Triger described
exhaust valve was directed into metal cl1ambers underlying the firs t cases of "caisson disease," or decompression ill-
a breastplate. These chambers contained carbon dioxid e ab- ness, in workers after they had left the pressurized caisson.
diving in 1906. Haldane understood that minute ventilation

varied directly with alveolar carbon dioxide levels. It ap-
peared reasonable that the same minute ventilation needed
to maintain an appropriate PAco 2 at sea level would be
needed to maintain a similar PAco2 under water. What was
not appreciated initially was that as the diver descended
and pressure increased, pump ventilation at the surface
necessarily also would have to increase to maintain minute
ventilation. Haldane realized that at 2 atm, or 33ft under
water, pump ventilation would have to double to ensure ap-
propriate ventila tion. This does not take into account mus-
cular effort, which would further increase ventilatory de-
mands. Unfortunately, early divers did not appreciate the
need to adjust ventilation to the diving suit. Furthermore,
air pumps often leaked or were maintained inadequately.
Haldane demonstrated the relationship between divers'
symptoms and hypercapnia by collecting exhaled gas from
divers at various deptl1s. The fraction of carbon dioxide
in the divers' helmets ranged from 0.0018 to 0.10 atm.26•38
The investigations of Bert and Haldane finally clarified the
na ture of "foul air" in diving bells and suits and the role
of adequate ventilation in protecting underwater workers
from hypercapnia. Besides his work w ith divers, Haldane
also demonstrated that the "black damp" found in mines ac-
tua~ was a dangerous! y toxic blend of 10% C02 and 1.45%
0 2 . He developed a self-contained rescue apparatus for
use in mine accidents that apparently was more successful
than the Fleuss appliance. 46
FIGURE 1-11 The caisson is a complex device enabling workers Diving boats were fancifully described by Mru·senius in
to function in dry conditions under shallow bodies of water or in 1638 and others. Only tl1e boat designed by Debrell in 1648
other potentially flooded circumstances. A tube composed of appeared plausible because "besides the mechanical con-
concentric rings opens at the bottom to a widened chamber, where trivances of his boat, he had a chemical liquor, the fumes
workers can be seen. At the top of the tube is a blowing chamber of which, when the vessel containing it was ullStopped,
for maintaining air pressure and dry conditions within the tube. would speedily restore to the air, fouled by the respiration,
Workers enter at the top through an air lock and gain access to the such a portion of vital spirits as would make it again fit
working area via a ladder through the middle of the tube. (Used, for that office." Although the liquor was never identified, it
witlr permission, from Hi11.38 )
tmdoubtedly was an alkali for absorbing carbon dioxide. 38
More s uccessful submarine boats were built in the nine-
teenth century. Fulton demonstrated sucl1 a vessel in the
As this new tedmology was applied increasingly in shaft Seine. Payerne built a submarine for underwater excava-
and tunnel work (e.g., the Douchy mines in France in 1846; tion in 1844. Since 1850, the modern submarine has been
bridges across the Midway and Tamar rivers in England in developed primarily for military actions a t sea.
1851 and 1855, respectively; and the Brooklyn Bridge, con- As naval warfare became more sophisticated, submarines
structed between 1870 and 1873), caisson disease was recog- were seen as an invaluable asset for preying on shipping.
nized more frequently. Bert was especially instrumental in They also could be viewed as an intriguing physiologic ex-
pointing out the dangers of high pressure.15 Denayouze su- periment in simultaneously ventilating many subjects. Ven-
pervised many commercial divers and probably was among tilation under these conditions became more complex be-
the first to recognize that decompression caused illness in cause it involved not only oxygen and carbon dioxide lev-
these divers.l 5 In the early 1900s, Haldane developed safe els but also heat, humidity, and body odors. Early work
and acceptable teclmiques for staged decompression based in submarines documented substantial increases in temper-
on physiologic principles.38 ature, humidity, and carbon dioxide levels.47 Mechanical
Haldane also played a critical role in examining how well devices for absorption of carbon dioxide ru1d air renewal
Siebe's closed diving suit supplied the ventilation needs of were developed quickly, 48 and by 1928, Du Bois felt that
divers. This work may have been prompted by Bert's stud- submarines could remain submerged safely for up to 96
ies with animals placed in high-pressure chambers. Bert hours. 49 With the available carbon dioxide absorbents, such
found that death invariably occurred when inspired carbon as caustic soda, caustic potash, and soda lime, carbon diox-
dioxide levels reached a certain threshold. Carbon dioxide ide levels could be kept within rela tively safe levels of less
absorbents placed in the high-pressure chamber prevented than 3%. Supplemental oxygen could be carried by the sub-
deaths. 15 Haldane's studies in this area were encouraged by marine and used to maintain a preferred fractional inspired
a British Admiralty committee studying the risks of deep oxygen concentration (Fro 2 ) of above 17%.39,50- 52
EXPLORATION IN THE AIR high altitude in Mexico City. Compared w ith sea-level val-
In 1782, the Montgolfier brothers astounded the world by ues, respirations were deeper and more frequent, and the
constructing a linen balloon about 18 m in diameter, filling quantity of air expired in 1 minute was somewhat increased.
it with hot air, and letting it rise about 2000 m into the air. He felt that "this is logical since the air of altitudes contains
Soon after, a larger balloon was constntcted and carried a in a given volume less oxygen at a lower barometric pres-
sheep, a cock, and a duck to a great height above the palace sure ... [and therefore] a greater quantity of this air must
square at Versailles. After a series of experiments with teth- be absorbed to compensate for the difference."15 Although
ered balloons, two Frenchmen, de Rozier and the Marquis these conclusions might seem reasonable now, physiologists
d'Arlandes, had the honor of being the first humans to fly of the time also considered decreased air elasticity, wind
in a Montgolfier balloon on November 21, 1783.53 Within a currents, exhalations from hannh.tl plants, expansion of in-
few years, Jeffreys and Blanchard had crossed the English testinal gas, and lack of support irt blood vessels as other
Channel in a balloon, and Charles had reached the aston- possible explanations for the breathing problems experi-
islung height of 13,000 ft in a hydrogen-filled balloon. As enced a t high altitude. Bert, the father of aviation medicine,
with diving, however, the machines tha t carried them aloft was instrumental in cla rifying the interrelationship among
brought human passengers past the limits of their physio- barometric pressure, oxygen tension, and symptoms. He
logic endurance. By 1804, balloonists were reaching heights perfonned a series of experiments on animals exposed to
of over 20,000 ft but were greatly affected. Glaisher and low-pressure conditions in chambers (Fig. 1-12). Carbonic
Coxwell reached possibly 29,000 ft in a memorable flight acid levels increased withirt the chamber, but carbon dioxide
in 1862 and suffered temporary paralysis and loss of con- absorbents did not prevent death. Supplying supplemen-
sciousness. Only heroic efforts by Coxwell enabled them to tal oxygen to the animals, however, protected them from
survive. 4,26,54 dying under simulated high-altitude conditions (Fig. 1-13).
The French physiologis t Bert was greatly intrigued by the More important, he recognized a critical physiologic con-
risks of high-altitude flight. He was very much aware of the cept. Death occurred as a result of the interaction of both
symptoms described by climbers at high altitude. Acoste's the fraction of inspired oxygen and barometric pressure.
description in 1573 of vomiting, disequilibrium, fatigue, and When a multiple of these two variables- that is, the par·
distressing grief as he traversed the Escaleras (Stairs) de tial pressure of oxygen- reached a critical threshold, death
Pariacaca, between Cuzco and Lima, Peru(" one of the high- ensued. t5,39
est places in the universe"), was widely known in Europe. 55 Croce-Spinelli, Sivel, and Tissandier were adventurous
In 1804, von Humboldt attributed the symptoms he felt at French balloonists eager to reach the record height of 8000 m.
high altitude to a lack of oxygen. Surprisingly, however, he At Bert's urging, they experimented with tl1e use of oxy-
found that the fraction of inspired oxygen in high-altitude gen tanks in preliminary balloon flights and even in Bert's
air was similar to that found in sea-level air. H e actually sug- decompression chamber. ln 1875, they began their historic
gested that respiratory air might be used to prevent m oun- attempt to set an altitude record supplied with oxygen cylin-
tam sickness.56 Longet expanded on this idea in 1857 by ders (Fig. 1-14). Unfortunately, at 24,600 ft they released too
suggesting tllat the blood of high-altitude dwellers should much ballast, and their balloon ascended so rapidly that
have a lower oxygen content than that of sea-level natives. In they were stricken unconscious before they could use the
a rema rkable series of observations d uring tl1e 1860s, Coin- oxygen. When the balloon eventually returned to earth, only
det described respiratory patterns of French people livirtg a t Tissandier ren1a ined alive. 4' 54 This traged y shook France.
FIGURE l-12 A typical device

used by Bert to study animals
under low-pressure con ditions.
(Used, witlr permissiorr, from
Bert.15 )
14 PART I HJSTORICAL BACKGROUND
~-=.:::::-, ·. The idea that two men had died in the air was especially
a' disquieting. 53 Unfortunately, the reasons for the deaths of
Croce-Spinelli and Sivel were not clearly attributed to hy-
poxia. Von Schrotter, an Austrian physiologist, believed
Bert's position regarding oxygen deficit as the lethal threat
and encouraged Berson to attempt further high-altitude bal-
loon flights. He originally devised a system for supplying
oxygen from a steel cylinder with tubing leading to the bal-
loonists. Later, von Schrotter conceived the idea of a face
mask to supply oxygen more easily and a lso began to use
liquid oxygen. With these devices, Berson reached 36,000 ft
in 1901.4•54
The Wright brothers' historic flight at Kitty Hawk in
1903 substantially changed the nature of flight. The military
value of airplanes soon was appreciated and applied dur-
ing World War I. The Germans were especially interested in
increasing the altitude limits for their pilots. They applied
the concepts advocated by von Schrotter and provided liq-
uid oxygen supplies for high-altitude bombing flights. In-
FIGURE 1-13 A bird placed in a low-pressure bell jar can terest in airplane flights for commercial and military uses
supplement the enclosed atmospheric air with oxygen inspired was especially high following Lindbergh's solo flight across
from th e bag labeled 0. Suppl emental oxygen prolonged survival the Atlantic in 1927. Much work was done on valves and
in these exp eriments. (Used, with permission, from Bert.15)
oxygen gas regulators in the hope of further improving al-
titude tolerance. A series of high-altitude airplane flights
using simple face masks and supplemental oxygen culmi-
na ted in Donati's reaching an altitude of 47,358 ft in 1934.
This was dearly the limit for human endurance using this
FIGURE 1-14 The adventurous French ball.oonis ts Croce-Spinelli, tech.nology.4,54
Sivel, an d 'Iissandier begin their attempt at a record ascent. The
Somewhat before Donati's record, a breakthrough in
balloonist at the right can be seen inhaling from an oxygen tank.
Unfortunately, the supplemental oxygen did not prevent tragic
flight was achieved by Piccard, who enclosed an aeronaut
results from a too rapid ascent. (Used, tvith permission, from in a spherical metal chamber sealed with an ambient baro-
Ann strong: Principles and practice of aviation medicine. metric pressure equivalent to that of sea level. The aero-
Baltimore: Williams & Wilkins, 1939: 4.) naut easily exceeded what soon would be Donati's record
and reached 55,000 ft. This work recapitulated the in1por·
tant physiologic concept, gained from Bert's earlier experi-
mental work in high-altitude chambers, that oxygen avail-
ability is a function of both fractional inspired oxygen and
barometric pressure. Piccard's work stimulated two sepa-
rate investigators to adapt pressurized diving suits for high-
altitude flying. In 1933, Post devised a rubberized, hermet-
ically sealed silk suit. In the same year, Ridge worked with
Siebe, Gorman, and Company to modify a self-contained
diving dress for flight. This suit provided oxygen under
pressure and an air circulator with a soda lime canister for
carbon dioxide removal. These suits proved quite success-
ful, and soon pilots were exceeding heights of 50,000 ft.
Parallel work with sealed gondolas attached to huge bal-
loons led to ascents over 70,000 ft. In 1938, Lockheed pro-
duced the XC-35, which was the first successful airplane
with a pressurized cabin {Fig. 1-15). 4•54 These advances
were applied quickly to mWtary avia tion in World War II.
The German Air Ministry was particularly interested in
developing oxygen regulators and valves and positive-
pressure face masks for facilitating high-altitude flying. 57
Work throughout World War II had defined certain lim-
its for technological support of high-altitude flight. Pilots
could reach up to 10,000 to 12,000 ft safely without oxygen
supplements. Above this limit, oxygen-enriched air was es-
sentiaL With flights going above 25,000 ft, oxygen supple-
mentation alone usually was not sufficient, and some type of
CHAPTER 1 J-llSTORICAL PERSPECTIVE ON THE DEVELOPMENT OF MECHANICAL VENTILATION 15
question of how air could be drawn into the heart. Unfortu-

nately for Galen, this was a question that could not be solved
before the development of the microscope and the concept
of diffusion. Also unfortunate for Galen was his failure to
appreciate how ventilating the lungs could help him in his
vivisection work. Galen opera ted on many living animals,
but his studies on the function of the heart were limited by
the risk of pneumothorax. Opening the thoracic cavity al-
most certainly resulted in death of the anima1.1,6 It was over
a thousand years later that Vesalius realized that ventilation
could protect animals from pneumothorax.62,63 The beating
heart would almost stop when Vesalius opened the chest
t~~ .· ... cavity, and the lungs would collapse but could be restarted
~.J by inflating the lungs through a reed tied into the trachea.
FIGURE 1-15 Lockheed p roduced the XC-35 in 1938. This was the It is unclear whether Vesalius learned this procedure from
first plane to have a pressurized cabin. (Used, witll permissiou, others or developed the idea directly £rom Galen's work.
Armstroug: Priuciples a11tl practice of a"viatiou mediciue. A fascinating coincidence is that Paracelsus, a contempo-
Baltimore: Williams & Wilkins, 1939: 337.) rary of Vesalius, is reported to have used a similar tech-
nique around 1530 in attempting to resuscitate a human. Did
Paracelsus adapt Vesalius's research efforts, or vice versa? 63
pressurized system-cabin, suit, or mask-was needed. It is also unclear whether Vesalius himself tried artificial
Pressurization as an adjunct, however, reached its limit ventilation during the dissection of a Spanish nobleman.
of usefulness at about 80,000 ft. At this altitude, air com- Legend has it that when the nobleman's heart began to beat
pressors became too leaky and inefficient to maintain ade-
once more, Vesalius's medical associates were so outraged
quate pressurization. A completely sealed cabin was essen-
that they reported him to the religious authorities. Vesal-
tial to protect passengers adequately from the rarefied atmo- ius only avoided being burned at the stake by embarking
sphere outside. AI1 altitude of 80,000 ft thus became a func- on a pil~image to the Holy Land, but he died during the
tional definition of space because at this height complete
voyage.
control of the atmosphere in the plane (i.e., the supply of It is probably reasonable to assume that Vesalius's tech-
oxygen, a means of removing carbon dioxide, and adequate nique for ventilation during open-chest procedures re-
control of temperature and humidity)was required.ss,s9 Ad-
mained well known in Padua. Presumably, Harvey, during
vances in submarine ventilatory physiology were adapted
his studies in Padua, became familiar with this technique
easily to the space program. In 1947, the American Air
because he mentions artificial ventilation in his work later
Force began the XI program, which culminated in the pro- in England. 63 Other English scientists soon after began to
duction in 1952 of the X15 aircraft. This plane reached a mention artificial ventilation in their own studies.65 In 1664,
top speed of 4159 mi/ h at an altitude of 314,750 ft. More Hooke dramatically described dissecting a dog, placing a
important, the technology developed for this plane was a
pipe into the windpipe of the animal, and using a pair of
prelude to manned satellite programs. The United States bellows to ventilate the dog (and keep the heart beating)
Mercury and the Russian Vostok programs both relied on
for well over an hour. 63 Lower, an associate of Hooke, later
rockets to boost small, one-person capsules into space or· showed that artificial respiration kept the color of blood red
bit. The Mercury capsule had a pure oxygen atmosphere during dissection. 63
at a reduced cabin pressure. In addition, the pilot wore
a pressurized suit with an independent, closed oxygen
supply. In April 1961, Gagarin was the first person to be
launched into space. Shepard followed soon after, in May R ESUSCITATING TH E APPARENTLY DROWNED
1961, and reached an altitude of 116 miles. More sophisti-
Artificial respiration with a bellows and tracheal tube re-
cated space flight-in the Gemini, Apollo, and space station
mained popular for vivisection work but was applied to
programs-was based on similar ventilation systems and humans only after a curious turn of events. Attempts to
principles.60 resuscitate apparently dead people were first recorded in
the mid-eighteenth century. The origins of this movement
are not entirely clear. Indeed, there were strong reasons for
Mechanical Ventilation: people to fear the dead. The risk of contagious disease was
well known-memories of the plague were still fresh-and
Of Resuscitation and Anesthesia religious beliefs dissuaded many from believing in the wis-
dom of resuscitation. Despite these disincentives, sporadic
VIVISECTION
attempts were made at organized resuscitation. In 1740, the
Galen is the first to have described ventilating an animal: Academie des Sciences in Paris issued an avis strongly ad-
"If you take a dead animal and blow air through its larynx vising mouth- to-mouth respiration for resuscitating the ap-
[through a reed], you will fill its bronchi and watch its hmgs parently drowned. 63 In 1744, Tossach may have been the
attain the greatest distention."61 He was fascinated by the first to use this technique successfully in saving a life.66
Fothergill soon after provided an excellent description of did Fine in 1800. These carmulas could be placed through
the mouth-to-mouth resuscitation technique, including the the nose, mouth, or trachea.
use of bellows if the "blast of a ma n's mouth" were not Many other physicians were encouraged to develop inge-
sufficient. 63·64•67•68 In 1760, Buchan went on to advise creat- nious devices as resuscitation a ids by the Royal Humane So-
ing " an opening in the windpipe" when air cannot be forced ciety (Fig. l -17). This society held competitions and offered
into the chest through the mouth or nose.69 Societal pres- prizes and medals for the best work in this area. 63·64,67•72 As
sures led to widespread dissemination of knowledge about an alternative to trad1eal intubation, Chaussier constructed
resuscitation techniques. In response to citizens' concerns a simple bag and fa ce mask for artificial ventila tion in 1780
about the large number of lives lost in canals, a group of in- (Fig. 1-18). He felt that this device would protect the res-
fluentiallaymen in Amsterdam formed the Society for the cuer from t11e deleterious effects of exhaled air. Chaussier
Rescue of Drowned Persons (Maatschnppy tot Reddi11g von devised accessory tubing for the face mask to allow the use
Dreykhingen) in 1767.63•64•67 The express purpose of this so- of supplemental oxygen. 73 Kite, Curry, and Chaussier a lso
ciety was to publicize the need for and the techniques of developed d evices to assist the operator in cannulating the
resuscitation. Similar societies soon were formed in other trachea through the mouth.n74
maritime cities, such as Venice and Milan in 1768, Paris in As these techniques for resuscitation were gaining
1771, London in 1774, and Philadelphia in 1780. w idespread acceptance, concerns were being raised about
The Dutch method emphasized five steps: keeping the pa- the effectiveness of bellows ventilation. Leroy confirmed
tient warm, artificial respiration through the mouth, fumi- these doubts in a dramatic series of studies in 1827 and
gation with tobacco smoke through the rectum (Fig. 1-16), 1828. By subjecting an animal to overzealous bellows in-
stimulants placed orally or rectally, and bleeding. Cogan, flation, he caused fatal pneumothorax.75•76 Although only
an English physician w ith a Dutch w ife, trans lated a pam- later would it be realized that the pressures reached in
pillet describing the Dutch method into English. Hawes, an this demonstration were unlikely to be acllieved in clini-
apothecary, read the pamphlet and led a concerted effort to cal practice,63 the French Academy quickly condemned the
introduce this technique into England. In encouraging this technique. Despite adapta tions of bellows to limit the ven-
work, Hawes' activities led directly to the formation of the tilatory volumes,77 the Royal Humane Society also a ban-
Royal Humane Society in 1774.67 Through this society, many doned the use of tracheal intubation and bellows ventilation
physicians were encouraged to develop techniques for re- for resuscitation.63 Consequently, positive-pressure ventila-
suscitating the apparently drowned . In 1776, Hunter advo- tion was banned from medical practice early in its infancy,
cated the use of a double bellows for artificial ventilation. not to be routinely relied on for patient care w1til well into
The first stroke blew fresh air into the lw1g, and the second the twentieth century.
stroke sucked out stale air. He had perfected this technique
during physiologic s tudies with dogs. Almost certainly this
NEGATIVE- PRESSURE VENTILATORS
physiologic work was influenced by the earlier studies of
Hooke and Lower. Hunter also advised the use of Priestley's As an alternative to positive-pressure ventilation, physi-
pure air (oxygen) for resuscitation, but it is unclear whether cians began to develop machines for negative-pressure ven-
tins advice was ever followedM·67•70 Also in 1776, Cullen tilation. The first tank respirator was produced by Dalziel,
suggested relying on tracheal intuba tion and bellows ven- of Scotland, in 1832. It was a n airtight box in which the p a-
tilation for reviving the apparently dead.71 In 1791, Curry tient sat enclosed up to the neck. Negative pressure was
developed an intralaryngeal cannula for this purpose, as created by bellows placed within the box but operated from
the outside by a piston rod and one-way valve.'8•79 Jones, of
Kentucky, patented the first tank respirator in America in
FIGURE 1-16 An attempt at resuscitating an apparently drowned 1864. The design appears similar to that of Dalziel's appara-
person using the modified Dutch method. One resuscitator is tus (Fig. 1-19).78•80 Although Jones used this device to treat
assisting respiration b y massaging the chest. The fumigator is asthma and bronclutis, he also claimed cures for paralysis,
instilling tobacco smoke through the rectum. (Used, w itll neuralgia, rheumatism, seminal weakness, and d yspepsia.80
permisiou, from Morclt.64) Von Hauke designed a series of cuirass and tank respirators
in the 1870s that were intended specifically to treat patients
with respiratory diseases, but he showed little insight into
the physiologic basis for how this type of respirator might be
of benefit in lung d isease. Woillez presented his version of a
tank respirator to the French Academy of Medicine in 1876
(Fig. 1-20) . It was basically a hollow cylinder of metal w ith
a rigid lower end a nd an upper end enclosing a neck made
of a rubber diaphragm seal. Air was evacuated from the
cylinder by a bellows. Woillez understood the physiologic
basis of ventilation and incorporated a bar placed on the pa-
tient's sternum to measure tidal excursions and adequacy
of ventilation. Unfortunately, this device seemed to have
been used only for resuscitating the apparently drowned
and with little success.78,81
CHAPTER 1 HISTORICAL PERSPECTIVE ON THE DEVELOPMENT O F MECHANICAL VENTILATION 17
l
1"-··ov
1
l
1
e.
A B
c D
FIGURE 1-17 A. Examples of some of the devices included in the RoyaJ Humane Society's compendium of resu scitation techniques in
1806. Figures 1, 2, and 3 are bellows of different sizes. Figure 6 is a brass b ox for holding a stimulating substance. Various connecting tubes
and n ozzles are also enclosed. (Used, with permission, from Muslzin et al: The principles and pra.ctice of thoracic anestl1esia. Oxford, England:
Blackwell Scientific Publications, 1953:32.) B. A two-bladed intubating spatula was developed to hold the m outh open and allow passage
of the tracheal tube through the larynx. (Used, with pennission, from Muslzin et at: T11e principles and p·r actice of t horacic anesthesia. Oxfo rd,
England: Blackwelt Scientific Publications, 1953:36.) C. The Royal Huma ne Society approved this typ e of box of intubation equipment
with a bellows ventilator for distribution in 1806. (Used, with permission, from McClettan: Anaesthesia 36:308, 1981.) D. T he bellows is
shown connected to the otolaryngeal cannula and ready for u se. (Used w ith permission. McClellan: Anaesthesia 36:308, 1981.)
1 -z
FIGURE 1-20 The spirophore produced by Woillez in 1876 had a
FIGURE 1-18 Chaussicr developed this face mask and bag for rod placed on the patient's s ternum to indicate the adequacy of
artificial ventilation in 1780. (Used, tvitlt permission, from Musfliu tidal excmsions. (Used, tvit/J permission, fro m Emerson: Evolution
et al: Tile principles and practice of tlzoraci.c anesthesia. O.tford, of iron lungs. ]H Emerson Co., 1978: fig. 2.)
England: Blackwell Scientific Publications, 1953:39.)
an abdominal cuirass shell.84 An important advantage of

Many other ingenious devices were invented for these devices was the access they allowed to the patient for
negative-pressure ventilation over the next 50 years. Breuil- nursing care. This consideration prompted Lord, of Worces-
lard, of Paris, patented a tank respirator operated by a steam ter, to build a respirator room (Fig. 1-23). Huge pistons in
boiJer? 8-80 Bell devised a vacuum jacket for newborns with the ceiling created the pressure cl1anges but required heavy
neonatal respiratory distress. It is unlikely that this was ever equipment_78,80 Severy in 1916 and Schwake in 1926 built
used clinically, but a resuscitation box developed by Braun negative-pressure ventilators that required the patient to
reportedly was quite useful for children with respiratory stand (Fig. 1-24). Although they incorporated ingenious me-
distress (Fig. 1-21).78•80•82 Eisenmenger designed several res- chanical elements, their practicality for severely ill patients
pirators that, like Bell's, did not cover the entire body. His was limited.80
first prototype extended from the upper part of the ster- The first negative-pressure ventilator to be used suc-
num to the pubis (Fig. 1-22A). A more sophisticated device cessfully in clinical practice on a widespread basis was
covered the chest and only a portion of the abdomen (Fig. 1- the Drinker-Shaw "iron lung" developed in 1928 (Fig. 1-
228). These devices allowed positive-pressure compression 25).80·84- 86 With this device, the body was enclosed entirely
of the chest to assist exhalation and negative-pressure suc-
tion to facilitate inhalation.78•80•83 A later device, called the
Eisenme11ger biomotor, was patented in 1927 and had only FIGURE 1-21 In Egon Bra\m's resuscitation box, children were
seated in a plaster mold with their noses an d mouths p rotruding
through a rubber diaphragm. The operator b lew through the tube
FIGURE l-19 The body-enclosing tank respirator constructed by on the right first, comp ressing the chest. Then suction was
Jones in 1864. The large syringe was used to create negative applied to the tube expanding the chest. (Used, wit/1 permission,
p ress me. (Used, witlz pennission, from Emerson: Evolution of iron from Emerso11: Evolution of iron lungs. Cambridge, MA: JH
luugs. Cambridge, MA: JH Emerson Co., 1978: fig. 1.) Emerson Co., 1978: fig. 4.)
CHAPTER 1 HISTORICAL PERSPECTNE ON THE DEVELOPMENT OF MECHANICAL VENTILATION 19
FIGURE 1-22 A. Eisenmenger's earlier version of his

cuirass shell. (Used, witl1 pennission, from Emerson:
Ev olution of iroulungs. Cambritlge, MA: JH Emerson
Co., 1978: fig. 5.) B. The more sophisticated version
described in 1904. A foot bellows allows positive and
nega tive pressure to assist expiration and inspiration,
respectively. This device is quite similar to ch est shells
still in use today. (Used, with permissi011, from
B Eisenmenger: Ln11cet, ii:515, 1904.)
within a cylindrical sheet-metal tank sealed at the lower end. POSITIVE-PRESSURE VENTILATION
The patient's head protruded out the upper end through
a close-fitting rubber collar. Pressure within the chamber IN THE PHYSIOLOGY LABORATORY
could be either increased or decreased by air blowers. This Followmg the admonitions agamst bellows ventilation, the
design is remarkably similar to the spirophore first built use of positive-pressure ventilation was disavowed by clin-
by Woillez in 1876. Unfortunately, it suffered from several icians but flourished in the physiology laboratory. Through-
of the same disadvantages, being cumbersome and iJ1con- out the middle to late 1800s, physiologists were becoming
venient for patient care. Despite these limitations, this iron more sophisticated in their investigative techniques and
lung saved many lives during polio epidemics. When the were relymg mcreasmgly on positive-pressure ventilation
Consolidated Gas Company of New York paid for large m animal experiments. Hering and Breuer used this tech-
numbers of these machines to be built, their use spread nique to examine how alterations m lung volume influenced
quickly worldwide. 80 A severe poliomyelitis epidemic in the vagi in 1868.87 Bert, in his studies on blood oxygen and
1931 prompted Emerson to build a simplified and improved carbon dioxide content, wrote of giving animals sufficient
tank respirator (Fig. 1-26). Because of its low cost, ease of op- curare to induce total paralysis and of providing artificial
eration, and technologic improvements, the Emerson tank ventilation through a tracheostomy tube in 1878. A bel-
respirator became the mainstay u1 treatmg patients with lows with a graduated handle for controllillg tidal volume
respiratory paralysis from polio80 until remtroduction of proved to be quite effective u1 these experiments (Fig. 1-
positive-pressure ventilation in the 1950s. 27).15 Pfliiger-26 and Head 88 described complex experiments
in which cuffed tubes were used to ventilate isolated por-

tions of the lung. Bowditch wrote of a simple but reliable
volume-cycled ventilator used for animal studies as a stan-
dard piece of laboratory equipment at Harvard in 1879
(Fig. 1-28).89
I N THE OPERATING ROOM

The reintroduction of positive-pressure ventilation into clin-
ical medicine occurred in two distinctly different stages. The
initial s tage began around the turn of the twentieth cen-
tury and involved the use of this technique in the operating
room. Only after positive-pressure ventilation had become a
well-established technique during surgery was it applied to
nonopera tive patients, beginning in the 1950s. There was a
clear and pressing need for positive-pressure ventilation to
facilitate thoracic surgery. From the time of Galen, it was
appreciated that opening the thorax invariably caused fatal
pneumothorax. Vesalius had shown that positive-pressure
ventilation could keep an animal's lungs inflated and the
- animal alive during these operations, but this lesson seems
•
to have been forgotten. Consequently, lung surgery in the
-·
.:
'
1-- ' I
nineteenth century was limited to rare cases of draining
J~. lung abscesses and bronchiectatic or tuberculous cavities.
. Although pneumonectomy had been performed success-
• - ..
fullyinanimals by 1881,90•91 between 1880and 1920 the mor-
COL
I
tality rate for thoracic surgery remained high, and these pro-
cedures were performed infrequently.90' 92 By 1896, Quenu
and Longuet realized that to have success in thoracic opera-
tions, one had "to maintain a difference in pressure between
FIGURE 1-23 A negative-pressure respirator room, patented by
the intra-alveolar air and the surrounding air." The surgeon
Lord in 1908, provided optimal access to the patient for the could cl1oose either to '1ower the extra thoracic pressure, the
musing staff. (Used, with permission, from Eml!"rson: £vol11tiou of intrapulmonary tension remaining the same, making it nec-
iron lungs. Cambridge, 1\llA: JH Emers011 Co ., 1978: fig. 8.) essary ... to operate in a relative vacuum, or to increase the
intrabronchial pressure.'193 Over the ensuing 10 to 15 years,
ingenious methods were devised to achieve both these ven-
tilatory end points.
FIGURE 1-24 Severy's negative-pressure venti lator obliged the Tracheal Intubation
p atient to stand but had a remarkable set of eletromagnetic Intuitively, the obvious way to increase intra bronchial pres-
controls and p ulleys for adjusting pressure changes within the sure would be to follow Vesalius's example by placing a
box. (Used, w-itJt pennission, from Eml!"rson: Evolution of iron tube in the trachea and inflating the lungs w ith a bellows.
lungs. Cambridge, MA: JH Eml!"TSOn Co., 1978: fig. 9.)
Positive-pressure ventilation had been well s tandardized in
the physiology laboratory. Although techniques to caru1U-
late the trachea had been developed in the late eighteenth
century, translaryngeal intubation still was viewed skepti-
cally by many physicians until the early 1900s.94 Physicians
only became reassured about the usefulness of translaryn-
geal intubation through work on controlling the airway.
The most compelling reason for airway control always had
been upper-airway obstruction. Tracheostomy historically
was a well-known meU1od of gaining access to the airway
in such situations. Indirect references to this technique can
be found in sucl1 ancient texts as the Rig Veda, written be-
tween 2000 and 1000 sc, and Eber's Papyrus, from about
1550 sc. Alexander the Great reputedly performed a tra-
cheostomy with his sword in 400 sc on a soldier who was
choking on a bone.95 According to Frost96 a nd McClelland,97
Asclepiades of Bithynia was the first surgeon to perform
CH APTER 1 HISTO RICAL P ERSPECTIVE ON THE DEVELO PMENT O F MECHANICAL VENTILATION 21
FIGURE 1-25 The Drinker-Shaw iron lung developed

in 1928 had a sliding bed and a close-fitting rubber
collar for sealing the patien t's neck. The patient's
head protruded from the device at the right and rested
on a flat support. (Used, w itl1 permission, from
Emers on: Ev olution of iron Lungs. Cambridge, MA: fH
Emerson Co., 1978: fig. 13.)
tracheostomy routinely, around 100 Be . The Roman Antyl- Chaussier's tubes to be useful in managing neonatal r espi-
los also was noted for his skill in this procedure in AD 340.96 ratory distress. He devised and successfully used modifi-
Although few surgeons were reported to have performed cations of Chaussier's tubes fo r this purpose. 73 Apparently,
this procedure d uring the Dark Ages, Brasavola reintro- Bouchut unsuccessfully a ttempted translaryngeal intuba-
duced the technique to the medical community in 1546. In tion to relieve diphtheritic croup in 1848.73 Later, MacEwen
1833, Trousseau clearly demonstrated the lifesaving value of of Glasgow in 188098 and O'Dwyer of New York in 1887
101
tracheostomy for managing upper-airway obs truction with 99 - would be recognized as the first physicians to use
his report on 200 of these operations for diphtheria.96· 97 translaryngeal intubation successfully for managing upper-
With the development of techniques and devices to can- airway obstruction.
nulate the trachea through either the nose or the mouth
(translaryngeal intuba tion) in the late eighteen th century, Tracheal Anesthesia
physicians had a practical alternative to tracl1eostomy for As clinicians began to appreciate the value of trans laryngeal
managing upper-airway obstruction. Depaul, w ho suc- in tubation for managing upper-airway obs truction, anes-
ceeded Cha ussier at the maternity hospital in Paris, believed thetists slowly began to grasp how useful this technique
might be for adminis tering anesthesia in the o perating
room. Ether anesthesia had first been used during an oper·
FIGURE 1-26 The Emerson tank respirator build in 1931 used a
bellows device to change pressure (hand pumps also were
ation by Mo rton in 1846.102 Snow recognized the potential
available in case of electricity failure), was Jess cumbersome and value of such anesthesia a11d developed various ways of
expensive than the Drinker-Shaw iron lung, and was easily administering inhalational agents. One novel m ethod he
opened and closed for nursing care. (Used, w ith p ermission, from described in 1858 was to give rabbits chloroform vapor
Emerson: Evo lution of iroulungs. Cambridge, MA: fH Emersou Co., thro ugh a tracheos tomy tube. 103 Trendelenberg apparently
1978: Jig. 15.) adapted this method for use in pa tients d uring operations
on the mouth and larynx. A practical problem limiting
these operations at the time was aspiration of blood into
the lungs du ring the procedure. Trendelenberg solved
this problem by devising a cuffed tracheostomy tube for
sealing the airway in 1869 (Fig. 1-29).73, 104 Witl1 this cuffed
, .HA _;:a. tube in place, inhalational a nesthesia could only be given
. ..
WI FIGURE 1-27 A bellows with graduated handle for controlling
tidal volume was u sed by Bert to ventilate paralyzed animals in
1878. (Used, w itli permission, fro m Bert.1 ; )
...
D .j ljt "
EMERSON
FIGURE 1-28 The volume-cycled ventilator us ed in the Harvard

Physiology Department in 1870s. Air from a bellows or tromp
enters A and passes to the animal through B. The respiratory rate
is determined by adjus ting the dri ving band on cone C. The
amount of air entering the animal is determined by screw clamp
D, which p ermits air to escape. (Used, witlr pennission, from
Bowditch: T Plrysiol 2:202, 1879-1880.)
practically through the tube itself. MacEwen's original work ·.. .. ~
on translaryngeal intubation for upper-airway obstruction ;.;·=~·:, '~,:,f: ::'~ ~

r.t · ••
included one case in which successful anesthesia given
through the tube a llowed surgical removal of a pharyngeal FIGURE 1-30 The Fell-O'Dwyer apparatus with modifications
tumor.98 Maydl of Prague and Eisenmenger of Vienna both by Matas for delivering anaesth esia. (Used, witlr permission, from
described cases of upper-airway surgery in 1893 using Matas: JAMA 34:1468-73, 1900.)
endotracheal anes thesia.104
Matas is recognized as playing a pivotal role in introduc-
ing positive-pressure ventilation into the operating room,
but he clearly credited others with inspiring him. Tuffier ministered readily through the apparatus, the Fell-O'Dwyer
and Hallion in 1896 described the efficacy of artificial ven- ventilator would be well suited for managing intrathoracic
tilation of the lungs through a translaryngeal tube in pre- surgery. Matas modified tllis ventilator successfully and in-
venting lung collapse during surgery in animals. 105 Doyen dicated that the new machine indeed was effective (Fig. 1-
improved their techniques. 106 At about the same time, Fell 30).106, 108
devised a bellows for positive-pressure ventilation of pa- The interest in translaryngeal intubation for administer·
tients with respiratory paralysis from opiate overdose. '~ 07 ing anesthesia and facilitating positive-pressure ventilation
This bellows could be connected to either a face mask or a was stuttering at first. Kuhn apparently used this technique
tracheotomy tube. O'Dwyer modified Fell's device so that regularly and with great success. He experimented exten-
it could be a ttached to a translaryngeal tube, and soon sively with both the size and position of the tracheal tube,
the Fell-O'Dwyer apparatus for mechanical ventilation was even using separate tubes for inhalation and exhalation.109
marketed. Matas realized that if anesthesia could be ad- In 1909, Meltzer and Auer presented a modified approach
to this technique.lnstead of using a tracheal tube that nearly
approximated the diameter of the trachea and allowing the
FIGURE 1-29 Trendelenberg first used this type of tracheostomy patients to inhale a nd exhale through that same tube, these
tube with inflatable cuff to prevent asphation during operations physiologists used a narrow-bore tube. Air was blown into
on the mouth and larynx in 1780. (Used, w itlr permission, from
Lomholt: Acta Anaestlresio/ Scarrd 11:312, 1967.)
the lung through the tube and allowed to escape from the
lung between the external wall of the tube and the trachea.
This technique was referred to as endotracheal in.suffiation . '~~ 0
Ellsberg was the first to use endotracl1ea l insuffla tion on
a patient,m but others criticized the technique. Meyer dis-
paragingly called Meltzer's insufflation method the ''blow-
pipe apparatus." Meyer cited numerous concerns (i.e., risks
of aspiration through the tube; incomplete control of air-
way pressure, especially when closing the ches t; unreliable
administration of anesthesia; and difficulties placing the
CHAPTER 1 HISTO RICAL PERSPECTIVE ON THE DEVELOPMENT O F MECHANICAL VENTILATION 23
face masks and helmets to supply positive-pressure venti-
la tion (Fig. 1-34).116- 1 18
Seve ral factors favored the endotracheal insufflation
method for bo th a nesthesia and lung inflation during tho-
racic operations. T he differential-pressure chambers were
either large and cumbersome or small and confining, and
all were expensive. A d evice for endotracheal insufflation,
which was portable and easy to use, was built in 1910 by
Elsberg for less than $100, 119 although more complex d e-
vices also were built (Fig. 1-35). The positive-pressure cab-
inets limited access to the patient's head during the proce-
dure .Positive-pressure masks were not reliable in mainta in-
ing lung inflation. Techniques and devices for facilitating
translaryn~eal intubation w ere being d eveloped quickly.
Dorrance,Lo for example, d escribed a simple endotracheal
tube made of flexible rubber with an inflatable cuff at its dis-
tal end. Janeway developed the firs t modem laryn goscope,
an invaluable aid for translaryngeal intubation. 64 Jackso n
was instntmental in providing clea r guidelines for per-
forming translaryngeal intubation.121 With these develop-
ments, endotracheal insufflation became firmly established ,
and new devices for anesthesia an d ventilation b y insuf-
FIGURE 1-31 The differential-pressure cabinet, developed by flation were d eveloped q uickly.122•123 Man y o ther devices
Sauerbruch, had the s urgeon placed inside a small chamber. for positive-pressure ventila tion, including the "pulmotor"
Suction was applied to this chamber. With the animal' s (in this portable resuscitator, were d evised in ti1e early 1900s.64
case) or patient's head outside the chamber, the intrabronchial
pressure remained at effective sea level. This d ifferential pressure Translaryngeal In tubation
maintained lung inflation when the thorax was open. (Used, witl1.
By World War T, endo tracheal intubation had become an
pemtission, f rom Morch. 64 )
invaluable method, especially for extensive plastic facial re-
constructions. However, a nesthetists began to express dis-
tracheal tube correctly) and concluded tha t end otracl1eal satisfaction with the insufflation technique for an esthesia
insufflation was not suitable for thoracic surgery.94 and ventilation. Insufflation did not protect from aspira-
tion, especially during upper-airway operations. In these
Differential Pressure procedures, pharyng eal packing to prevent aspira tion re-
Meyer ad vocated the use of a differential-pressure appa- quired placement o f two tubes, one for insufflation and the
ratus for open-chest procedures. Around 1904, Sauerbruch other for exhalation. Placem ent of two tubes was technically
d evised a working model of a cabinet tha t generated neg- difficult. Anesthetists would much prefer to use a cuffed
ative pressure around the lung. Sauerbrucl1 built a small tracheal tube, which, of course, was not feasible with insuf-
airtight operating room with the pa tient's body and the sur- fla tion. Anesthetists were find ing tha t nitrous oxide was a
geon inside. The patient's head extended out of the room. better a nesthetic agent tha n chlo roform or ether, but it was
By applying suction to this room, differential pressure was very expensive to administer by insufflation. Periodic d efla-
created across the pleural surface, atmospheric pressure tions o f the lung usually were r equired , with insufflation to
within ti1e bronchial tree, and negative pressure outside ensure adequate carbon dioxide removal. As a consequence
the lung (Fig. 1-31).64 Meyer built a much la rger version of of these problems with insufflation, Magill and Rowbo tham
a negative-pressure apparatus. The entire operating room returned to Matas's old " inhalation" method. They used a
was subjected to suction, and a small chamber was built tracheal tube large enoug h to allow both inhalation and
within the operating room to enclose the patient's head and exhalation. A balloon cuff could be attached to the outer
the anesthetist. This cl1a mber either could be kept at at- dis tal end of the tube to prevent aspiration. 104•124• 125 Row-
mospheric pressure or could subjected to positive pressure botham also was instrumental in popularizing nasotracheal
(Fig. 1-32).112 intuba tion.126 A number of cleverly d esig ned machines
Surgeons also had ti1e op tion of using d evices tha t em- were produced before World War II that could be used to
ployed positive pressure without intuba tion to inflate the administer anesthesia and artificial ventilation via positive-
lungs. Brauer g enerally is credited as devising the first pressure rhy thmic "insufflation" (ventilation) through these
positive-pressure cabinet in 1904. This appara tus appar- large-diameter tubes.64.'127•128 By 1934, Guedel and Treweek
ently was large enough for the patient's head to fit inside . d escribed apneic anesthesia, or purposely giving enoug h
Positive pressu re in the cabinet would be transmitted to the anesthesia to cause complete respiratory paralysis. Arti-
lungs during the patient's respiratory efforts.64•113- ns Mod - ficial respiration by rhythmic bag ventilation ad equately
ifications of the positive-pressure cabinet were put forth supported the patient during apnea. This technique pro-
by Murphy, 113 Green,1 14 and Green and Janeway (Fig. 1- vided the "quiet" field necessary for abdominal and tho racic
33).115 As an alternative to cabinets, other surgeons used surgery. 129
A.
FIGURE 1-32 A larger version of the differential-pressure cabinet

w as constructed by Meyer. A The large chamber, shown from an
outside view on the left, has s uction applied to it. Inside this
chamber, the patient is placed on a table with the patient's head
inserted into a smaller chamber. Within this smaller chamber (B),
kept at positive pressure, resides the anesthetist. (Used, witfr
B p ennissiatr, fro m Meyer: JAMA 77:1984,1909.)
CHAPTER 1 1-IISTORICAL PERSPECTIVE ON THE DEVELOPMENT OF MECHANICAL VENTILATION 25
PtJrhnn ...
' •I II n '"'Ilk.•
ti•u
I'
" .~,_\. ' u ¥!
A 6
FIGURE 1-33 Green and Janeway proposed this positive-pressure chamber in 1910. The patient's head is inserted into the chamber (A).
The anesthetist's arms also can reach into the chamber (B). (Used, with penni.ssion, from Green: Amt Surg 52:58-66, 1910.)
FIGURE 1-34 A positive-press ure mask us ed by Bunnell in 19U.

(Used, w itl1permission, from Bunnell: JAMA 58:836, 1912.) Further favoring the use of translaryngea1 intubation was
recognition of retained pulmonary secretions as a cause of
postoperative morbidity and mortality. As pointed out by
Jackson in 1911, "when tracheal and bronchial secretions are
in excess of the amount required properly to moisten the in-
spired air, they becom e a menace to life unless rem oved." 130
Postoperative atelectasis, attributed to retention of thick
bronchial secretions and inhibition of coughing, was first
FIGURE 1-35 A sophis ti cated and complex ventilator built by

Janeway in 19U. (Used, witlt permiss itm,from Janeway: Ann Surg
56:328-30, 1912.)
s-,r ( " _ _.,

• II'< VJ..1"'" ~lf'~_,.
described in 1928.131 Bronchoscopy and intratracheal sue-

honing were the earliest techniques advised for rem oving
secretions,1 30•132·"133 but it became apparent that easy access
to the tracheobronchial tree for repeated suctioning might
be necessar y in difficult cases. Tracheostomy was recom-
mended as early as 1932 specifically for this problem in
polio patients 134•135 and later for patients with a variety of
surgical problems.136- 139 Physicians soon realized that sue-
honing through a large tube placed translaryngeaUy might
be just as effective as through a tracheotomy tube. In the
1940s, case reports began to appear describing the success-
ful and prolonged use of translaryngeal intubation for tra-
cheobronchial toilet.140 - 142 Modification of tracheal tubes
to include "Murphy eyes" at the tips probably has reduced
the likelihood that these tubes would become occluded by
mucus.143
FOR THE NONOPERATIVE PATIENT

The second stage of the reintroduction of positive-pressure
ventilation into clinical practice involved nonoperative pa-
tients and occurred dramatically in the 1950s. There had
been isolated reports of physicians' using positive-pressure
ventilation for purely mechanical problems before this time.
Bert describes a positive-pressure chamber built by Jour-
danet in the 1870s (Fig. 1-36) and used for a variety of
mechanical problems.'5 Williams wrote of treating pul-
monary disease with a pneumatic differentiation chamber in
1885. The patients were placed w ithin a cabinet, and the air
in this cabinet was exhausted by suction. Simultaneously,
"antiseptic air charged with remedial agents" was adminis-
tered to the patient's mouth. The reduced pressure around
the thorax and atmospheric pressure applied to the lungs
were thought to dilate the lungs beneficially. Remarkable
improvements were described for a w ide variety of lung
disorders with this device.144 Fell used a bellows ventila- FIGURE 1-36 Jourdanet used this positive-pressure chamber to
tor to manage respiratory depression secondary to opiate treat patients with a wide variety of disorders in the 1870s. (Used,
overdose in the la te 1880s. 107 A remarkable series of stud- with permissiOII,from Bert. 15 )
ies described the use of positive-pressure respira tion fo r
the treatment of pulmona ry edema.145- 147 The emphasis of freelance anesthetist Bjorn Ibsen for consultative ad vice. Af-
these s tudies was not to assist respiration- forced respi- ter review ing the medical records and autopsy results, Ibsen
ratio n by intubation was felt to be unjustifiable 145- but to made two startling conclusions. First, he felt that in the fatal
use positive pressure to counterbalance the backward pres- cases there was not sufficient atelectasis within the lungs
sure on the pulmonary capillaries. 147 The widespread use to make adequate ventilation impossible. Second, he sug-
of positive-pressure ven tilation did not begin, however, un- gested that the increased blood levels of total C02 did not
til its value was demonstrated dramatically during a polio reflect metabolic alkalosis, as was generally believed, but
epidemic in Copenhagen in 1952. rather acute respiratory acidosis. Ibsen's observations about
respiratory acidosis were derived directly from work he had
Paralytic Polio perfom1ed measuring exhaled carbon dioxide levels in the
A series of polio epidemics had swept across Europe and operating theater. Ibsen, as the anesthetis t, had noted that
the United States in the 1930s and 1940s. Respiratory paraly- exhaled carbon dioxide levels fluctuated during the course
sis secondary to poliomyelitis was an infrequent but feared of surgery a nd could be compensated by more vigorous bag
complication. Even with the best management techniques ventilation. Most important, when exhaled carbon dioxide
us ing iron lungs and cuirass ventilators (Fig. 1-37), the mor· levels increased, the patients in the operating theater had
tality rate for polio-induced respiratory paralysis probably developed clammy skin and high blood pressure, similar
was about 85 percent. 64 In the late summer of 1952, an epi- signs to those found in the paralytic polio patients just be-
demic struck Copenhagen. Of the first 31 patients admit- fore death. Based on these observations, Ibsen suggested
ted to Blegdamshospital, Copenhagen's hospital for com- inadequa te ventilation as tl1e cause of death and advised
municable diseases, during this epidemic with respiratory tracheostomy to allow the operative techniques of positive-
paralysis, 27 died within 3 days. Out of desperation, HerU"y pressure ventilation. Lassen was not convinced; the iron
Lassen, the chief physician and epidemiologist, called the lung and cuirass respira tors had reliably provided adequate
CHAPTER 1 HISTORICAL P ERSPECTIVE ON THE DEVELOPMENT OF MECHANICAL VENTILATION 27
B.
A.
FIGURE 1-38 A prototype intermittent positive-pressure
breathing device used by Motley in 1948. (Used, with pennissiou,
Motley eta/: JAMA 137:3n, 1948.)
respirator attachment for the sta ndard tank respirator d ur-

ing the 1948 Los Angeles poliomyelitis epidemic (Fig, 1-39).
This device was installed easily and supplied intermittent
positive-pressure breaths in synchrony with the tank res pi-
FIGURE 1-37 Young patients with respiratory paralysis from
rator's ins piratory negative-pressure phase. 156
polio being treated in an "iron lung." (Use(f, w ith penuissiou, from Lassen eventually agreed to a trial of Ibsen's theory. The
Hansel Mietll, Time Life Pictures, Getty Images, 1938.) thirty-second patient with respir atory paralysis admitted
to Blegdamshospital was the poignant case of a 12-year-old
girl. When her condition deteriorated, Ibsen asked a surgeon
ventilation in the past. Lassen argued that it was unlikely to perform a tracheos tomy, and a cuffed tracheal tube was in-
that positive-pressure ventilation would save paralytic po- troduced. During the procedure, the girl becam e comatose.
lio patients if the underlying disease process actually in- Ibsen initially was unable to ventilate her effectively. He
cluded extensive brain-stem involvement. 148 assumed that re tained secretions were the problem, and he
As a counterargument, Ibsen cited recent experience from suctioned her. Her condition deteriorated further, and many
the United Sta tes with a positive-pressure valve capable of physicians observing the trial began to leave, assuming that
providing mechanical positive-pressure ventilation to po- the outcome would be fa tal. In this despera te situa tion, Ibsen
lio patients. These valves were d eveloped as a result of in- decided to paralyze the girl. She collapsed immediately, and
tense interest by the U.S. Air Force during World War II Ibsen finally was able to ventilate her adequately. H er con-
in using positive pressure to increase altitude tolerance in dition improved immediately.148 Eventually, arterial blood-
pilots.149.'!50 The unique attribute of these valves, such as the gas levels confirmed Ibsen's suspicions about respiratory
pneumatic balance respirator (PBR) and the Bennett clinical acidosis as the cause of death in the previous patients, and
research model, was their ability to convert a continuous positive-pressure ventilation proved successful in substan-
positive pressure into intermittent positive pressure. It was tially red ucing the mortality rates from paralytic polio. The
believed to be importa nt that positive pressure only assist only drawback was the equipment available (Fig. 1-40) .
inspira tion, allowing expira tion to be passive. Intermittent Only bag ventilation was possible. During the remainder
positive-pressure breathing w as applied in the late 1940s to of the epidemic, it is estimated that 1500 medical and dental
a variety of medical problems and found to be effective in students worked arotmd the clock providinS bag ventila-
providing artificial ventilation to an apneic person151 - 153; in tion by hand to help support these patients.1 •158
managing acute pulmonary edema, acute asthma, and post- The Copenl1agen experie nce provided the impetus for a
operative patients with poor respiratory excursion'~ 52 ; pos- revolution in the medical care of patients w ith respiratory
sibly in improving oxygenation in various lung diseases154 ; failure. First, it confirmed the value of positive-pressure
and in administering medications by nebulization1ss (Fig. ventilation and demonstrated the need for practical me-
1-38). The Bennett valve was adapted as a positive-pressure chanical ventilators. Second, by encouraging the grouping
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FIGURE 1-39 A schematic of the Bennett

posi tive-p ressure valve used via a
tracheos tomy tube in a patient in an iron
lung. (Used, w ith penuissiou, from Bower
et al: A1111 West Med Surg 4:567, 1950.)
of acutely ill patients in certain sections of the hospita l and able, application of this technique to other medical prob-
the organization of intensive care for these patients, it led the lems was slow. Again, the Scand inavians took the lead
way for the later development of intensive-care units. 157,158 in applying positive-pressure ventilation to other condi-
Third, Ibsen realized that provisions had to be made for tions characterized by inadequate ventilation. Extens ive
resuscitating acutely ill patients in small outlying towns work in pulmonary emphysema and chronic bronchitis had
and transporting them to specialized centers.159 Accord- confirmed that in severe cases ventilatory failure was ac-
ingly, mobile teams were formed with expertise in perform- companied by high carbon dioxide levels and low oxy-
ing translaryngeal intubation and tracheotomy. After intu- gen levels. Suer,lemental oxygen alone seemed to worsen
bation and stabilization, patients could be transferred sec- the situation.1 Sporadic reports described the use of me-
ondarily. This was obviously the precursor of our present chanical ventilation for treating this problem. Usually used
emergency medical system. were body respirators, 160- 164 but occasionally either inter-
mittent positive-pressure breathing via a pneumatic balance
Other Diseases with Inadequate Ventilation respirator161 or hand ventilation163•164 was used transiently.
Although the results using positive-pressure ventilation By 1961, Munck had collected a total of 42 case reports de-
for the respiratory paralytic form of polio were remark- scribing some form of mechanical ventilation for exacer-
bations of chronic obstructive pulmonary disease (COPD)
with successful outcomes in 31 .165 Munck's group was the
FIGURE 1-40 This hand ventilator was used in the Copenhagen first to rely strictly on positive-pressure ventilation through
p olio epidemic of 1952 by hundreds of "ventilators"(i.e., medical a tracheotomy tube to treat patients w ith COPD in acute
students, technicians, volunteers, and others) to save many lives. respiratory crises. Their methods emphasized reliance on
(Used, with permissiot1, from Lassen: Laucet i:38, 1953.) monitoring arterial blood oxygen, carbon dioxide, and p H
levels. The average duration of treatment in their series was
24 days. They emphasized that mechanical ventilation pro-
vides a fair chance of "tiding patients with diffuse chronic
I
I
- HUMIDIFIER lung disease over a n episode of life-threatening respiratory
I
fa ilure-and of obtaining a reasonable recovery," provided
Ozj 112 \
there is some historical evidence of pulmonary reserve.165
REDUCTION
'I Many other groups throughout the 1960s and early
VALVE 1970s found that positive-pressure ventilation through ei-
SODA LIME
ther a translaryngeal tube or tracheos tomy was an effective
method of managing acute exacerbations of COPD. 166-"~ 75
Conservative treatment, including the use of controlled lev-
els of supplemental oxygen, antibiotics, bronchodilators,
and respiratory stimulants, was useful for treating some
patients with acute ventilatory failure complicating chronic
lung disease,176; 177 but it soon became dearly recognized
CHAPTER 1 HISTORICAL PERSPECTIVE ON THE DEVELOPMENT O F MECHANICAL VENTILATION 29
that in severe cases with either coma or deteriorating arterial TABLE 1-1 Mechanical Ventilation
blood-gas values, endotracheal intubation and mechanical
Year of
ventilation provided the most appropriate a ltemative.178 Introduction Bra nd
The Scandinavians also adapted these techniques to other
medical problems. As early as 1951, Nilsson recognized 1948 Bennett TV-2P
the value of translaryngeal intubation for controlling the 1950 Engstrom 150
airway in patients with barbiturate poisoning.179 He later 1954 Drager Poliom at
emphasized that artificial respiration via a m echanical ven- 1954 Thompson Portable Respira tor
tilator is essential when barbiturate poisoning causes apnea 1955 Morch " Piston"
or res piratory insufficiency.180 Avoiding the potentially 1955 Bird Mark?
1955 Emerson High-Freque ncy Ventila tor
stigmatizing tracheotomy scar a lso was an important con-
1958 Emerson Assistor /Controller
sideration in patients prone to depression. Bjork pio- 1963 Air-Shields 1000
neered the use of pos itive-pressure respirator treatment 1963 Puritru1 Bennett PR-2
in postoperative thoracic surgery patients. Initially, he 1964 Emerson " Post-Op" 3-PV
was conservative in his approach and postponed tra- 1964 Boums L5-104-150
cheotomy until the patient was in severe respiratory failure. 1967 Puritan Bennett MA-l
By the late 1950s, however, he was performing elective 1968 Ohio/ Monaghan 560
tracheotomy after pulmonary resections and cardiovas- 1968 Drager Spiromat
cular surgery and providing " prophylactic'' positive- 1968 Loos Co. Amsterdam
pressure ventilation to prevent atelectasis and to minimize 1968 Engstrom 300
"heavy respiratory work." He believed that any patient 1970 Veriflo CV 2000
1970 Hamilton Standard PAD 1
with a small cardiopulmonary reserve, who could be- 1972 Monaghan 225, 225-SIMV
come exhausted rapidly following major s urgery, would 1972 Bird-Baby Bird
benefit from this a pproach.181 - 184 As these principles were 1972 Bird-IMV Bird
established in thoracic surgery, the Scandinavians also be- 1972 Siemens Servo 900/9008
gan to apply them to patients with crush injury of the chest, 1973 C hemtron Gill 1
pulmonary edema, renal failure, tetanus, pneumonia, peri- 1974 Emerson TMV
tonitis, and so on. The best results were obtained when res- 1974 SearleVVA
pirator treatment was initiated early in the acute illness and 1974 Ohio550
not when chances for recovery were nil.185 1975 Boums Bear 1
1976 Forreger 210
1978 Purita n Bennett MA-TI.2-2
Modem Respirators 1980 Engstrom Erica
Providing mechanical ventilation on a widespread basis 1982 Siem ens Servo 900C
could only be achieved with reliable respirators, and again, 1983 Biomed IC-5
it was the Scandinavians who led the w ay in developing 1984 Purita n Bennett 7200
these machines. Morch built the first clinically proven vol- 1984 Sechrist Adult 2200B
wne ventilator during World War ll in Denmark for use in 1985 Bear Medical Bear 5
the operating room. Because of the war, pistons and cylin- 1985 OhmedaCPU
ders for this ventila tor were made from discarded sewer 1986 Hamilton Vcolar
pipes.64 As a direct result of the 1952 polio epidemic in 1986 Bird 6400ST
1986 Infrasonics Infant Star
Denmark, Bang constructed a mechanical respirator. Man-
1988 Bear3
ual ventilation of patients with respiratory paralysis was 1988 llrunilton Amadeus
possible in Copenhagen because of the availability of med- 1988 Siemens E
ical students. In Skive, where Bang practiced, medical stu- 1988 Bird 8400ST
dents were not available, and Bang's respirator was a 1989 Bunnell Life P ulse
practical necessity. Fortunately, it w orked.186•187 The Eng- 1989 PPG (Drager)IRISA
strom respirator, built for the same reasons, proved to be 1989 Bird VIP
hugely successful for managing poliomyelitis patients.188 1989 lnfrasonics Adult Star
This volume-cycled respirator a lso was used by Bjork in 1991 Siem ens Servo 300
his outstanding work in postoperative respira tory care. By 1993 Bear 1000
1954, a number of modern automatic respirators had been souRCE: Adapted, with pennissiol\ from, Masferrer eta!: History of the respi-
developed in Europe. 189 Morch was instrumental in bring- ratory care professioll. In: Respiratory Care. Philadclphia: Uppincott, 1991:12.
ing the concept of pos itive-pressure ventilation across the
Atlantic to America. 64.'190 The incorporation of this tech-
nique into standard medical practice apparently was slower practical ventilators have been introduced for everyday use
in the United Sta tes than in Scandinavia. 64 Tank respira- (Table 1-1 ). This was p aralleled by a significant increase
tors still were used routinely in the United States until the in the number of patients receiving mechanical ventilation
1960s,191, l 92 although the benefits of endotracheal intuba- in American hospitals throughout the 1960s. Pontoppidan
tion and positive-pressure ventilation were slowly being found a fivefold increase in artificial respiration cases at the
appreciated. 191• 193 Since the 1950s, an enormous number of Massachusetts General Hospital between 1960 and 1968.·194
Intesive Care treatment was beneficial unfortunately led to its indiscrim-

Incorporating pos itive-pressure ventilation into the stan- inant use. It was not appreciated that supplemental oxygen
dard clinical practice of medical patients was not easy. Many given to a patient with COPD who had an acute ventila-
practical problems had to be overcome. Organizing the tory crisis with hypercapnia could result in paradoxic hy-
"intensive care" that patients with ventilatory failure re- poventilationand worsened respiratory acidosis. Campbell
quired was a substantial logistical problem. The Danes had played a leading role in recognizing this problem and de-
answered this problem by congregating respiratory patients vising a device, the venturi mask, for administering oxygen
in special units. In the United States and elsewhere in the in a controlled fashion with a reduced risk of carbon dioxide
world, intensive-care w1its similarly were developed. By the retention. 218 - 220
middle to late 1960s, widespread experience had been ac- Just as oxygen use generally was believed to be beneficial
cumulated with intensive-care units specifically designed for treating respiratory disorders, the use of oxygen was
for managing patients requiring sophisticated respiratory incorporated routinely into many early mechanical ventila-
care and mechanical ventilation} 95- 199 By the 1970s, sev- tors. This approach was justified in some cases because oxy-
eral centers reported impressive reductions in mortality rate gen requirements to achieve adequate arterial oxygenation
through reliance on the intensive-care-unit approach. 200-202 often were surprisingly high. 221 Mean inspired oxygen lev-
At present, intensive-care units are accepted as a standard els in the early respirators, however, could not be regulated
and essential part of any modem acute-care hospital. accurately. Substantial and occasionally dangerous varia-
tions in inspired oxygen levels were found when ventilators
Adequacy of Ventilation were compared directly. 222 - 224 Nash and coworkers pointed
Assessing the adequacy of positive-pressure ventilation was out the potential gravity of this problem when they linked,
critically important. Until arterial blood-gas machines be- for the first time in humans, diffuse alveolar damage (or the
came available commercially, physicians had to rely on la- respirator lung syndrome) with the prolonged use of ventila-
borious and exacting methods of measuring blood oxygen tors delivering a high inspired oxygen concentration.225
and carbon dioxide levels. Astrup and others emphasized As an interesting aside to the issue of inspired oxygen
that measuring Pao2 , Paco2 , and pH should be the ultimate variability among various ventilators, Frumin and cowork-
goal for determining how well the respirator actually was ers found that insertion of an expiratory resistance increased
ventilating the patient.203•204 By 1957 it was realized that arterial oxygen levels in anesthetized, paralyzed, artificially
intermittent positive-pressure breathing was not always ventilated humans.226 Manipulation of airway pressure by
effective in reducing hypercapnia in emphysema. In fact, immersion of the exhalation limb from a tracheotomy tube 1
the more severe the obstructive lung disease, the less to 4 em under water had been shown previously to improve
effective pressure-cycled respirators seemed to be in pro- ventilation in patients with multiple rib fractures. 227 These
ducing hyperventilation. 205 Conversely, pressure-cycled simple measures for increasing airway pressure, termed
respirators easily could overventilate a patient and convert variously the positive expiratory pressure plntenu,228 continuous
a dangerous acidosis into an equally dangerous alkalosis. 206 positive ainvay pressure,229,230 and later, positive end-expiratory
The issue of pulmonary encephalopathy secondary to hy- pressure, were to prove enormously successful in improving
percapnia was of serious concern to physicians,2w as was the oxygenation in patients with both adult and infant respira-
realization that mechanical ventilation could be followed by tory distress syndromes.
paradoxical central nervous system acidosis.208•209
Adequacy of ventilation also was determined by oxy- Quality Control of Ventilators
genation. Supplemental oxygen had been used to treat nu- The variability in oxygen concentrations found among var-
merous medical ailments since Priestley and Scheele had ious respirators reflected a more serious underlying prob-
identified "pure air" in the 1770s. By the beginning of the lem. As the need for ventilators, gas cylinders, connectors,
n.ventieth century, the physiologic benefits of oxygen ther- oxygen-delivery masks, and myriad other types of respi-
apy were better understood, and physicians became more ratory equipment increased, the number of manufactur-
interested in using oxygen specifically to treat respiratory ers producing this equipment proliferated. Quality control
disorders. The intravenous injection of oxygen was advo- among manufacturers varied. More important, manufactur-
cated by Tunnicliffe and Stebbing in 191621 0 but a ttracted ers tended to produce equipment of various size specifica-
little interest from others. Haldane devised an apparatus for tions, often making integration of breathing circuits impos-
supplying controlled amounts of oxygen 211 that was used sible. Anesthesiologists were particularly concerned with
on soldiers exposed to suffocating gases during World War I. these problems because of the difficulties they had encoun-
Building on the observation that patients with pneumonia tered in establishing universal color codes for anesthetic gas
had low blood oxygen levels, Meakins used the Haldane cylinders during World War ll. For example, carbon diox-
apparatus to treat hypoxic patients with pneumonia. 212 ide cylinders in Britain were painted green, but U.S. oxygen
Stadie constructed a11d used an oxygen chamber for treat- cylinders also were painted green. Inevitably, when U.S. and
ing pneumonia in 1922.213•214 Barach described the intro- British anesthesiologists worked together, cylinders were
duction of other methods of oxygen administration, includ- filled with the wrong gas, and deaths occurred. 231 - 233
ing the oxygen tent, nasal catheter, and mouth funnel in The American Society for Anesthetists (ASA) performed
1926. 215 Physicians believed that oxygen was useful in re- a critically important service by organizing a Committee
ducing the mortality rate in pneumonia but did not un- on Standardization of Anesthetic and Resuscitating Equip-
derstand why it was effective. 216•217 The belief that oxygen ment, charged with forging a consensus on manufacturing
standards for this type of equipment. In 1955, the com- Weaning
mittee met with representatives of anesthesia equip- An intriguing problem developed as the use of pos itive-
ment manufacturers and the American Standards Associ- pressure ventilation became more widespread. Once pa-
ation (later the American National Standards Institute, or tients were placed on a mechanical ventilator, how were
ANSI). Following this meeting, the ASA approved finan- they to be "weaned" eventually from such respiratory sup-
cial support for the American National Standards Com- port? This question actually had two components: How
mittee Z79 on Anesthesia and Respiratory Equipment to could the physician determine when a patient was ready
operate under the umbrella of ANSI. Members of this to be weaned? What methods could be used to facilitate
committee included representatives of various medical spe- the weaning process? Numerous criteria have been advo-
cialties and principal manufacturers of anesthesia and res- cated as reasonable indicators that patients are weaning
piratory equipment. candidates, but none has yet proved infallible.194,235- 237 Sim-
Committee Z79 tried to obtain consensus on equipment ilarly, numerous techniques have been proposed as useful
production both within the United States a nd internation- modalities for maximizing the chances for a successful
ally. Initially, it worked closely with the British Standards weaning process. Modifications of ventilator technology
Committee SGC 15. In 1967, the International Standards in the 1970s led to the proposal of such methods as inter-
Organization (ISO) convened its own technical committee mittent mandatory ventilation (IMV) 238•239 and mandatory
in this field, for which the British Standards Committee minute volume240 as alternatives to the standard T-piece
acted as secretariat. Committee Z79 was extraordinarily ef- method of weaning.241 - 243 Although many physicians ex-
fective in developing standards for a wide range of respira- pressed strong preferences for one weaning modality over
tory equipment. Under the Medical Device Amendments of another,244 it has never been shown clearly that modalities
1976, the Food and Drug Administration (FDA) was charged such as IMV hasten the weaning process. 245•246 Whether
with regulatory respons ibility for the safety and efficacy more recently introduced teclmological advances in ven-
of medical devices. The FDA had a significant impact on tilator techniques, such as pressure-support and pressure-
refining the standards established by Committee Z79. In control ventilation, will improve clinicians' ability to wean
1983, the relationship between ANSI and Committee Z79 patients is still unclear.
was terminated for financial and liability reasons. At that
time, the ASA agreed to transfer this committee's sponsor-
ship to the American Society for Testing Materials (ASTM).
The committee's name was then changed to F29. American Conclusion
medicine indeed has been quite fortunate in having ongo-
ing committees to gain consensus effectively and voluntarily In this historical review of the development of mechani-
on manufacturing and performance standards for ventila- cal ventilation, a rich and complex weave of discoveries in
tors (ASTM F1100-90, for standard specifications for ventila- many different scientific and technical areas has brought
tors intended for use in critical care), tracheal tubes (ASTM us to the early 1990s, a time during which physicians have
F1242-89, standard specifications for cuffed and uncuffed been trained to rely routinely on mechanical ventilation for
tracheal tubes), and many other standard pieces of respira- managing all manner of acute, serious illnesses. It is r emark-
tory equipment. 233 able that only 40 years ago, cadres of medical and dental
Numerous other problems were encountered with the students were needed to manually ventilate polio patients
regular and prolonged use of positive-pressure ventila- with respiratory paralysis, and at the tum of the century,
tion. There was serious concern about accidental discon- a foot-operated bellows for mechanical ventilation was a
nections from the ventilator. Appropriate safegu ards and remarkable innovation. In the late eighteenth century, the
alarm systems were incorporated g radually into respirator concept of using a bellows and translaryngeal tube for resus-
systems to reassure the nursing s taff, respiratory therapists, citating the apparently drowned was just being introduced,
and physicians that such disconnections would be recog- and in the sixteentl1 century, Vesalius was forced to make a
nized promptly. Adequate humidification of tl1e ventilator pilgrimage to the Holy Land to atone for tl1e sin of restarting
air supply had to be ensured.190 The risks of nosocomial a Spanish nobleman's heart by inflating his lungs. The debt
pneumonia were not understood initially. Vigilant attention we owe to the many pioneers who have contributed to the
to sterilization of respiratory equipment, proper suctioning advances in the field of mechanical ventilation is humbling,
technique, and minimization of s tagnant water in tubing just as the hope for future unforeseeable developmen ts in
and humidification sources was advised to reduce the risk this field is enthralling.
of "ventilator lung."196 There was considerable debate for
decades over whether translaryngeal intubation was pre-
ferred over tracheotomy for patients requiring prolonged
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34 PART I HISfORICAL BACKGROUND
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CHAJYI'ER 1 HISTORICAL PERSPECTIVE ON THE DEVELOPMENT OF MECHANICAL VENTILATION 35
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PART II muscles in performing the work of breathing. Therefore, to
understand mecllanical ventilators in general, we must first
understand their basic functions : (1) power input, (2) power
PHYSICAL BASIS OF transmission o r conversion, (3) control scheme, and (4) out-
put. This simple format can be expanded to add as much
MECHANICAL detail as desired (Table 2-1).
A discussion of input power sources and power conver-
VENTILATION sion/ transmission is beyond the scope of this chapter, and
these topics have been treated elsewhere?.S I will, however,
explore in detail control schemes and ventilator output be-
cause these directly affect patient management.
Chapter 2
CLASSIFICATION OF Control Scheme
MECHANICAL
MODELS OF PATIENT-VENTILATOR INTERACTION
VENTILATORS To understand how a machine can be controlled to re-
ROBERT L. CII/\TBURN place or supplement the natural function of breathing, we
need to first understand something about the mechanics of
breathing itself. The study of mechanics deals with forces,
displacements, and the rate of change of displacement.
In physiology, force is measured as pressure (pressure =
force/ area), displacement as volume (volume= area x dis-
placement), and the relevant rate of change as flow (average
CONTROL SCH EM E
Models of Patient-Ventilator Interaction flow = 6volume/ 6time; instantaneous flow (\!) = dv/ dt,
Control Variables the derivative of volume with respect to time). SpedficaUy,
Phase Variables we are interested in the pressure necessary to cause a flow of
OUTPUT WAVEFORMS gas to enter the airway and increase the volume of the lungs.
Idealized Pressure, Volume, and Row Waveforms The study of respiratory mechanics is essentially the
Effects of the Patient Circuit search for simple but useful models of respiratory system
MODES OF VENTILATION mechanical behavior. Figure 2-1 illustrates the process by
Breathing Pattern which the respiratory system is represented first by a graph-
Control Type ical model, and then by a mathematical model based on the
Control Strategy graphical model. Pressure, volume, and flow are measur-
VENTILATOR ALARM SYSTEMS able variables in the mathematical model that change w ith
THE FUTURE time over the course of one inspiration and expiration. The
SUMMARY AND CONCLUSION relation among them is described by the equntion of motion.
for the respirntory sysfem. 9 The derivation of this equation
sterns from a force-ba lance equation that is an expression of
A good ventilator classification scheme describes how ven- Newton's third law of motion (for every action, there is an
tilators work in general terms, but with enough detail so equal and opposite reaction):
that one particular model can be distinguished from others.
It facilitates description by focusing on key attributes in a
(1)
logical and consistent manner. A clear description allows
us to quickly assess new facts in relation to our previous
knowledge. Learning the operation of a new ventilator or where PrR is the transrespiratory pressure (i.e., pressure at
describing it to others then becomes much easier. Under- the ain.vay opening minus pressure at the body surface), PE
standing how the ventilator operates, we can then anticipate is the pressure secondary to elastic recoil (elastic load), and
appropriate ventilator management strategies for particular PR is the pressure secondary to flow resistance (resistive
clinical situations. The classification system described in this load).
chapter is based o n previously published work. 1- 7 Transrespiratory pressure can have two components, one
A ventilator is simply a machine, a system of related ele- secondary to the ventilator (Pvent) and one secondary to the
ments designed to alter, transmit, and direct energy in a pre- respirato ry muscles (Pmusc). Elastic recoil pressure is the
determined manner to perform useful work. We put energy product of elastance (E = 6pressure/ 6volume) and vol-
into the ventilator in the form of electricity (energy= volts x ume. Resistive pressure is the product of resistance (R =
amps x time) or compressed gas (energy = pressure x vol- A pressure/ M low) and flow. Thus Eq. (1) can be expanded
ume). That energy is transmitted or transformed (by the to yield the following equation for inspiration:
ventilator's drive mechanism) in a predetermined manner
(by the control circuit) to augment or replace the patient's P vent + Pmusc = EV + RV (2)
37
38 PART II PHYSICAL BASIS OF MECHANICAL VENTILATION
TABLE 2-1 Outline of Ventilator Classification System

flow
I. Input
A. Pneum atic
IV. Output
A. Pressure waveforms I T
transairway
B. Electric 1. Rectangular pressure
I. AC 2. Exponential
2. DC (battery)
II. Power conversion and
transmission
A. External compressor
3. Sinusoidal
4. Oscillating
B. Volume waveforms
1. Ascending ramp
t
transthoracic
pressure
transrespiratory
pressure
B. Internal compressor 2. Sinusoidal

C. Output control valves
m. Control scheme
C. Flow waveforms
1. Rectangular
l
A. Control circuit 2. Ascending ramp FIGURE 2-1 The respiratory system is often modeled as a single
1. Mechanical 3. Descending ramp flow resis tance (representing the endotrach eal tube and the
2. Pnewnatic 4. Sinusoidal airways) connected to an elastic chamber (representing the lungs
3. Fluidic V. Alarms and chest wall). Flow through the airways is generated by
4. Electric A. Input power alarms transairway pressur e (pressure at the airway opening minus
5. Electronic 1. Loss of electric power pressure in the lungs). Expansion of the elastic chamber is
B. Control variables 2. Loss of pneumatic power generated by trans thoracic pressure (pressure in the lungs minus
1. Pressure B. Control circuit alarms pressure on the body surface). Transrespiratory pressure (pressure
2. Volume 1. General systems failure at the airway opening minus pressure on the body surface) is the
3. Flow 2. Incompatible ventila tor sum of these two press ures and is the total pressure required to
4. Time settings generate inspiration. The " airway-pressure" gauge on a
C. Phase variables 3. Warnings (e.g., inverse p ositive-pressure ventilator displays transrespiratory pressure.
'1. Trigger l:E ratio)
2. Limit C. Output ala rms (high/low
3. Cycle conditions) spontaneous breathing (i.e., vent pressure = 0). Between
4. Baseline 1. Pressure
those two extremes, an infinite number of combinations of
D. Conditional variables 2. Volume
E. Modes of ventilation 3. Flow
muscle pressure (i.e., patient effort) and ventila tor pressure
1. Breathing pattern 4. Time are possible under the general heading of "partial ventila-
2. Control type a. Frequency tor support." The equation of motion also gives the bas is for
3. Specific control b. Inspiratory time defining an assisted breath as one for which ventilator pres-
strategy c. Expiratory time sure rises above baseline during inspiration or falls below
5. Inspired gas baseline during expiration.
a. Temperature
b. Fro2
CONTROL VARIABLES
The combined ventilator and muscle pressure causes vol- In the equation of motion, the mathema tical form of any
ume and flow to be delivered to the patient. (Of course, of the three variables (i.e., pressure, volume, or flow as
muscle pressure may subtract rather than add to ventilato r functions of time) can be predetermined, making it the in-
pressure in the case of patient-ventilator dyssynchrony, in dependent variable and making the other two the depen-
which case both volume and flow delivery are reduced.) dent variables. We now have a theoretical basis for classi-
Pressure, volume, and flow are functions of time and are fying ventilators as pressure, volume, or flow controllers.
called variables. They are all measured relative to their val- Thus, during pressure-controlled ventilation, pressure is
ues at end expiration. Elastance and resistance are assumed the independent variable and may take the fonn of, say,
a step function (i.e., a rectangular pressure waveform). The
to remain constant and are called parameters.
For passive expiration, both ventilator and muscle pres- shapes of the volume and flow waveforms then will de-
sure are absent, so Eq. (2) becomes pend on the shape of the pressure wavefom1 as well as
the parameters of resistance and compliance. On the other
hand, during volume-controlled ventilation, we can spec-
-RV= EV (3) ify the shape of the volume waveform making flow- and
pressure-dependent variables. The same reasoning applies
The negative sign on the left side of the equation indicates to a flow controller. Very crude ventilators, such as the
flow in the expiratory direction. This equation also shows early jet ventilators, controlled only the duration of inspi-
that passive expiratory flow is generated by the energy ration and expiration, making them what we could call
stored in the elastic compartment (i.e., lungs and chest wall) "time controllers."
during inspiration. It follows from the preceding discussion that any con-
Equation (2) shows that if the patient's respira tory mus- ceivable ventilator can control only one variable at a tin1e:
cles are not functionin~ muscle pressure is zero, and the pressure, volume, or flow. Therefore, pressure, volume, and
ventilator must generate all the pressure for inspiration. flow ar e referred to in this context as control variables. I will
On the other hand, a ventilator is not needed for normal discuss later in the section on modes of ventilation exactly
CHAPTER 2 CLASSIFICATION OF MECHANICAL VENTILATORS 39
how ventilator control systems work. We will see that it is set frequency independent of the patient's spontaneous ef-
possible for a ventilator to switch quickly from one control forts. Pressure is the trigger variable when the ventilator
variable to another, not only from breath to breath but even senses a drop in baseline pressure caused by the patient's
during a single inspiration. inspiratory effort and begins a breath independent of the set
frequency. Flow or volume are the trigger variables when
the ventilator senses the patient's inspiratory effort in the
PHASE VARIABLES
form of either flow of volume into the lungs.
Because breathing is a periodic event, the ventilator must be Flow triggering has been shown to reduce the work the
able to control a number of variables during the respiratory patient must perform to start inspiration. 12 This is so be-
cycle (i.e., the time from the beginning of one breath to the cause work is proportional to the volume the patient in-
beginning of the next). Mapelson10 proposed that this time spires times the change in baseline pressure necessary to
span be divided into four phases: the change from expira- trigger. Pressure triggering requires some pressure change
tion to inspiration, inspiration, the change from inspiration and hence an irreducible amount of work to trigger. With
to expiration, and expiration. This convention is useful for flow or volume triggering, however, baseline pressure need
examining how a ventilator starts, sustains, and stops an not cha nge, and theoretically, the patient need do no work
inspiration and what it does between inspirations. A par- on the ventilator to trigger.
ticular variable is measured a11d used to start, sustain, and The patient effort required to trigger inspiration is deter-
end each phase. In this context, pressure, volume, flow, and mined by the ventilator's smsitivity setting. Some ventilators
time are referred to as phase variables.'ll The criteria for de- indicate sensitivity qualitatively ("min" or " max"). Alterna-
termining phase variables are shown in Fig. 2-2. tively, a ventilator may specify a trigger threshold qtJantita-
tively (e.g., 5 cmH20 below baseline). Once the trigger vari-
TRIGGER VARIABLE able signals the start of inspiration, there is always a short
All ventilators measure one or more variables associated delay before flow to the patient starts. This delay is called
with the equation of motion (i.e., pressure, volume, flow, the response time and is secondary to the signal-processing
or time). Inspiration is started when one of these variables time and the mechanical inertia of the drive mechanisms.
reaches a preset value. Thus the variable of inte.rest is con- It is important for the ventilator to have a short response
sidered an initiating, or trigger, variable. Ttme is a trigger time to maintain optimal synchrony with patient ins piratory
variable when the ventilator starts a breath according to a effort.
FIGURE 2-2 Criteria for determining the phase variables during a ventilator-assisted breath.
Inspiration Is Inspiration is Inspiration is Inspiration is

Pressure Triggered Volume Triggered Flow Triggered Time Triggered
i i
-
.....
t
yes
I
Does inspiration
start because a preset - no
yes
I
Does inspiration
IJo start because a preset -no
yes
I
Does inspiration
... start because a preset -no IJo
l
Inspiration starts
because a preset time
pressure is detected? volume is detected? flow is detected? interval has elapsed.
Inspiration is Inspiration is Inspiration is

Pressure Limited Volume Limited Flow Limited
t
yes
t
yes
t
yes
I I I
. Does peak pressure
reach a preset value
before inspiration ends?
- no ...
Does peak volume reach
a preset value before - no ...
Does peak flow reach a
preset value before - no IJo
No variables are
limited during
inspiration ends? inspiration ends? Inspiration.
·-as-c:
41 Inspiration Is Inspiration Is Inspiration is Inspiration is
(/)
.0 Pressure Cycled Volume Cycled Flow Cycled Time Cycled
0
t i t
..
yes
I
Does expiration s tart
because a preset - n o
yes
I
Does expiration start
... because a preset -no
yes
I
Does expiration start
... because a preset -no
r
Expiration starts
IJo because a preset
- pressure Is met? volume is met? flow is met? time is met.
A B c flow stops and expiratory flow begins. If expiration does

0 ! no t begin immediately after inspira tory flow stops, then an
iii :J
:=: en inspiratory hold has been set, and the ventilator is, by defi-
i!
>C.. nition, time cycled (see Fig. 2-3). Note that the volume that
~--~----~--~------~~--~--------- passes through the ventilator's output control valve is never
exactly equal to the volume delivered to the patient because
..
E
of the volume compressed in the patient circuit. Some ven-
tilators use a sensor a t theY-connector (such as the Drager
g"' Evita 4 with the neonatal circuit) for more accurate tidal vol-
ume measurement. Others measure volmne at some point
inside the ventilator, and the opera tor must know whether
the ventilator compensates for compressed gas in its tidal
volume readout.
When a ventilator is set to flow cycle, it delivers flow un-
til a preset level is met. Flow then s tops, and expiration be-
gins. The mos t frequent application of flow cycling is in the
FIGURE 2-3 This figure illustrates the distinction between the pressure-support mode. In this mode, the control variable is
terms limit and cycle. A. Inspiration is pressure-limited and pressure, and the ventilator provides the flow necessary to
time-cycled. B. Flow is limited, but volume is not, and inspiration
meet the inspiratory pressure limit. In doing so, flow starts
is volume-cycled. C.Both volume and Bow are limited, and
inspiration is time-cycled. (Reproduced, with permissio11, from
out a t a relatively high value and decays exponentially (as-
CIU1tb11m Frmdamcutals ofMecltau-ical Veutilatiou.)6 smning that the patient's respiratory muscles are inactive).
Once flow has decreased to a relatively low value (such as
25% of peak flow, typically preset by the manufacturer),
inspiration is cycled off. Manufactures often set the cycle
UMIT VARIABLE threshold slightly above zero flow to prevent inspiratory
Here, limit means restricting the magnitude of a variable times from getting so long that patient synchrony is de-
during inspiration. A limit variable is one that can reach and graded. On some ventilators, the flow-cycle threshold may
maintain a preset level before inspiration ends (i.e., it does be adjusted by the operator to improve patient synchrony.
not end inspiration). Pressure, flow, or volume can be limit Time cycling means that expiratory flow starts because a
var iables and actually all can be active for a single breath preset inspiratory time interval has elapsed.
(e.g., using the Pmax feature on a Drager ventilator). Note
that time cannot be a limit variable because lin·titing inspi-
BASELINE VARIABLE
ratory time would cause inspiration to end, violating the
The baseline variable is the parameter controlled during ex-
preceding definition.
piration. Although pressure, volume, or flow could serve as
Clinicians often confuse limit variables with cycle vari-
ables. To cycle means " to end inspiration." A cycle variable the baseline variable, pressure control is the most practical
always ends inspiration. A limit variable does not termi- and is implemented by all modern ventilators. Baseline or
nate inspiration; it only sets an upper bound for pressure, expiratory pressure is always meas ured and set relative to
atmospheric pressure. Thus, when we want baseline pres-
volume, or flow (see Fig. 2-3). The confusion over limit and
sure to equal atmospheric pressure, we set it to zero. When
cycle variables is caused, in part, by the nomenclature used
we want baseline pressure to exceed atmospheric pressure,
by many ventilator manufacturers . They often use the term
we set a positive value, called positive eud-expiraton; pressure
limit to describe what happens when a pressure or time
(PEEP).
alarm threshold is met (i.e., inspiration is tem1inated, and an
alarm is activated). To be consistent with accepted nomen-
clature, it is best to refer to these alarm thresholds as backup
cycli11g mechanisms rather than limits. Output Waveforms
C YCLE VARIABLE Just as the s tudy of cardiology involves the use of electro-
The inspiratory phase always ends when some variable cardiograms and blood pressure waveforms, the s tudy of
reaches a preset value. The variable that is measured and med1anical ventilation requires an understanding of out-
used to end inspiration is called the cycle variable. The cy- put waveforms. The wavefomlS of interest are, of course,
cle variable can be pressure, volume, flow, or time. Manual the pressure, volume, and flow waveforms.
cycling is a lso available on some ventilators.
When a ventilator is set to pressure cycle, it delivers flow
IDEALIZED PRESSURE, VOLUME,
until a preset pressure is reached, a t which time inspiratory
AND FLOW WAVEFORMS
flow stops and expiratory flow begins . The most common
application of pressure cycling is for alam1 settings. Output waveforms are conveniently graphed in groups of
When a ventilator is set to volume cycle, it d eliver s flow three. The horizontal axis of all three graphs is the same
tmtil a preset volume has passed through the control valve. and has the wlits of time. The vertical axes are in tmits of
By definition, as soon as the set volume is met, inspiratory pressure, volume, and flow. For the purpose of identifying
A B c D E
Q)
E
j
expiration
FIGU RE 2-4 Idealized ven tilator output waveforms. A. Pressure-controlled inspiration with a rectangular pressure waveform. Note that
this is identical to How-controUed inspiration with an exponential-decay How waveform. B. Flow-con trolled i n.~piration with a
rectangu lar fl ow waveform. Note th at this is identical to volume-controlled inspiration with an ascending-ramp volume waveform.
C. Flow-controlled inspiration with an ascending-ramp flow waveform. D. Flow-controlled inspiration with a descending-ramp flow
waveform. E. Flow-controlled inspiration with a sinu soidal flow waveform. The short dashed lines represent mean inspiratory pressure,
and the long dashed lines represent mean pressure for the complete respiratory cycle (i.e., mean ainvay pressure). Note that mean
inspiratory p ressure is the same as the pressure limit in A. These waveforms were created as follows: (1) defining the control waveform
using a mathematical equation (e.g., an ascending-ramp ftow waveform is specified as flow = constan t x time), (2) specifying the tidal
volume for How- and volume-control waveforms, (3) specifying the resistance and compliance, (4) substituting the preceding information
into the eq uation of motion for the respiratory system, and (5) using a computer to solve the equation for the unknown variables and
plotting the results against time. (Reproduced, witlt permission, from Chatb11ru.)
characteristic waveform shapes, the specific baseline values EFFECTS OF THE PATIENT CIRCUIT
are irrelevant. What is important is the relative magnitudes The pressure, volume, and flow the patient actually receives
of each of the variables and how the value of one affects or are never precisely the same as what the clinician sets on the
is affected by the value of the others. ventilator. Sometimes these differences are caused by instru-
Typical waveforms available on modern ventilators are il- ment inaccuracies or calibration error. More commonly, the
lustrated in Fig. 2-4. These waveforms are idealized. That is, patient delivery circuit contributes to discrepancies between
they are precisely defined by mathematical equations and the desired and actual patient values. This is so because the
are meant to characterize the operation of the ventilator's patient circuit has its own compliance and resistance. Thus
control system. As such, they do not show the minor devia- the pressure measured inside a ventilator upstream of the
tions, or "noise," often seen in waveforms recorded d uring patient always will be higher than the pressure at the airway
actual ventilator use. This noise can be caused by a variety of opening because of patient circuit resistance.ln addition, the
extraneous factors such as vibration and flow turbulence. Of volume and flow coming out of the ventilator's exhalation
course, scaling of the horizontal and vertical axes can affect manifold will exceed those delivered to the patient because
the appearance of actual waveforms considerably. Finally, of the compliance of the patient circuit.
the waveforms in Fig. 2-4 do not show the effects of the Exactly how tl1e mechanical properties of the patient cir-
resis tance and compliance of the patient circuit. cuit affect ventilator performance depends on whether they
No ventilator is an ideal pressure, volume, or flow con- are connected in series or in parallel with the patient. It turns
troller, and ventilators are designed to only approximate out that the resistance of the patient circuit is connected in
a particular waveform. Idealized waveforms as shown in series while the compliance is modeled as a parallel con-
Fig. 2-4 are nevertheless helpful because they are u sed com- nection. To ttnderstand this, we first make the simplifying
monly in o ther fields (e.g., electrical engineering), which assumption that we can examine tl1e patient circuit's resis-
makes it possible to use mathematical procedures and ter- tance separate from its compliance. It is intuitively obvious
minology that have already been established. For example, that the same flow of gas that comes from the ventilator trav-
a standard mathematical equation is used to describe the els through the circuit tubing as through the patient's ainvay
most common ventilator waveforms for each control vari- opening. We also can see that the pressure drop across the
able. Tl1is known equation may be substituted into the equa- patient circuit will be different from that across the respi-
tion of motion, which is th en solved to get the equations for ratory system because they have different resistances. By
the other two variables. Once the equations for pressure, a definition we borrow from electronics, when two circuit
volume, and flow are known, they are easily graphed. This components share the same flow but have different pres-
is the procedure used to generate the graphs in Fig. 2-4. sure drops, they are connected in series. This means tl1at
42 PART IT PHYSICAL BASIS OF MECHANICAL VENTILATION
the patient circuit resistance, however small, adds to the to- compliance. Substituting zero for Cpe, we get
tal resistive load seen by the ventilator. Tims, in a volume-
controlled breath, the peak inspiratory pressure is higher, vscl
and in a pressure-controlled breath, the tidal volume and V delivered =
1
+
peak flow are lower. In practice, the effect of patient circuit (5)
resis tance is usually ignored because it is so much lower Y set Vset
than the resistance of the respira tory system. = Vset
1 + 0 1
Now consider the patient circuit compliance: As the ven-
tilator delivers the breath to the patient, pressure at the air- which shows that there is no effect on the delivered tidal
way opening rises relative to atmospheric pressure, which volume. Suppose now that Cpe is as large as CRS (i.e.,
is the driving force for flow into the lungs. The patient circuit Cpe = CRS). Now we have
is connected between the ventilator and the airway, so the
pressure it experiences across its walls is the same as that Vdehvered = ___V..,t
..::.;__ _ Yset Yset
(6)
experienced by the respiratory system (remember, we are 1 + (Cpc/ CRS) 1 +1 2
ignoring its resistance now, so we can ignore any pressure
drop between the ventilator outlet and the airway open- in which case, half the volume from the ventilator goes to
ing). The volume change of the patient circuit tubing will the patient, and the other half is compressed in the patient
be different from that of the respiratory system because the circuit.
compliance of the circuit is different. Because the patient cir- The effect of the patient circuit is more troublesome
cuit and the respiratory system fill with different volumes during volume-controlled modes than during pressure-
during the same inspiratory time, the flows they experience controlled modes. This is so because during volume control,
are different (remember that flow = volume+ time). Again the ventilator meters out a specific volume of gas, and un-
borrowing a definition from electronics, if two circuit com- less it measures flow at the airway opening, it has no way
ponents share the same pressure drop but different flows, of knowing how much goes to the patient and how much
they are connected in parallel. Because they are in parallel, goes to the patient circuit. ln contrast, during pressure-
the two compliances are additive, so the total compliance is controlled modes, the ventilator simply meters out a set
greater than either component. pressure change no matter where the gas goes. Because the
Patient circuit compliance sometimes can be greater than respiratory system and the patient circuit compliance are
respira tory system compliance and thus can have a large in parallel, they both experience the same driving pressure
effect on ventilation. It must be accounted for either auto- (peak ins piratory pressure minus end-expiratory pressure),
matically by the ventilator or manually by increasing the so tidal volume delivery is affected very little. The only effect
tidal volume. For example, when ventilating neonates, pa- might be that the patient circuit compliance may tend to in-
tient circuit compliance can be as much as three times that crease the pressure rise time, which would tend to decrease
of the respiratory system, even with small-bore tubing and peak flow and tidal volume slightly.
a small-volume humidifier. Thus, when trying to deliver a Another area where patient circuit compliance causes
preset tidal volume during volume-controlled ventilation, trouble is in the determination of auto-PEEP. There are
as little as 25% of the set volume will be delivered to the pa- several methods for determining auto-PEEP. One method
tient, with 75% compressed in the patient circuit. The com- to determine auto-PEEP during mechanical ventilation is
pliance of the patient circuit can be determined by occluding to create an expiratory hold manually (i.e., delay the next
the tubing at the patient Y, delivering a small volume un- inspiration) until static conditions prevail throughout the
der flow control (using zero PEEP), and noting the resulting lungs (i.e., no flow anywhere in the lungs). The pressure
pressure. Using a short inspiratory hold will make it easier at this time (total PEEP) minus the applied PEEP is an es-
to read the pressure. Then compliance is calculated as before timation of global auto-PEEP. Note that auto-PEEP may
by dividing the volume by the pressure. Once the patient vary throughout the lungs depending on the distribution
circuit compliance is known, the set tidal volume can be of lung disease and may not reflect pressure behind col-
corrected using the following equation: lapsed areas in patients with severe flow limitation. Auto-
PEEP (PEEPA) is an index of the gas trapped in the sys-
tem at end expiration secondary to an insufficient expiratory
V delivered = 1 + (Cpe /CRS)
(4) time:
Ytrapped
Measured PEEP A = C (7)
where Vdehvered is the tidal volume delivered to the patient, total
Ysc~ is the tidal volume setting on the ventilator, Crc is the
patient circuit compliance, and CRS is the respiratory sys- where PEEP A is auto-PEEP, Y rrapped is the volume of gas
tem compliance. We can get a more intuitive understanding trapped in the patient and the patient circuit at end expira-
of this equation if we put in some values. Suppose, for ex- tion (above that associated with applied PEEP), and Ctotal
ample, that we use the perfect patient circuit that has zero is the total compliance of the respiratory system and the
patient circuit. The problem is that we want auto-PEEP to
• The effective compliance of the patient ci rcuit is a combination of reflect the gas trapped in the patient, not in the circuit. If
the tubing compliance and th~ compressibility of tl1c gas inside it. we know the compliances of the patient circuit and the
respiratory system, we can correct the measured auto-PEEP automatically adjust the pressure limit from breath to breath
as follows: in an attempt to achieve a preset tidal volume target. To
accommodate these situations in which both pressure and
CRS+Crc volume signals are used to control the size of the breath, we
True PEEP A = CRS x measured PEEP A (8)
invoke the intuitively satisfying term dual contro/. 2
The breath sequence is the pattern of mandatory or sponta-
where true PEEP A is the auto-PEEP in the lungs, measured neous breaths that the mode delivers. A breath is a positive
PEEPA is the auto-PEEP in the lungs and patient circuit, CRS airway flow (inspiration) relative to baseline, and it is paired
is the respiratory system compliance, and Crc is the patient with a negative airway flow (expiration), both associa ted
circuit compliance. If the ventilator displays auto-PEEP on with ventila tion of the lungs. This definition excludes flow
its monitor, check the ventilator's opera ting's manual to see changes associated with hiccups or cardiogenic oscillations.
whether or not the auto-PEEP calculation is corrected for A spontaneous breath, in the context of mechanical ventila-
patient circuit compliance. The larger Crc is relative to CRS, tion, is a breath for which the patient determines both the
the larger \·V iii be the error. Again, the error will be most timing and the size. That is, the patient both triggers and cy-
noticeable in pediatric and neonatal patients. cles the breath. On some ventilators, the patient may make a
short spontaneous effort d uring a longer mandatory breath,
Modes of Ventilation as in the case of airway pressure-release ventilation. It is im-
portant to make a dis tinction between spontaneous breaths
The objectives of mechanical ventilation are to ensure that and assisted breaths. An assisted breath is one for which the
the patient receives the minute volume of appropriate gases ventilator does some work on the patient, as indicated by
required to satisfy physiologic needs while not damaging an increase in airway pressure (i.e., Pven1) above baseline
the lungs, impairing circula tory function, or increasing pa- during inspira tion or below baseline during expiration. For
tient discomfort. The manner in which a ventilator achieves example, in the pressure-support mode, each breath is assis ted
these objectives is referred to as a mode of ventilation. Specif- because airway pressures rises to the pressure-support setting
ically, a mode can be identified and /or classified by speci- above PEEP (i.e., Pvent > 0). Each breath is also spontaneous
fying the because the patient both triggers and cycles the breath. The
patient may cycle the breath in the pressure-support m ode by
1. Breathing pattern in terms of the primary breath control actively exhaling, but even if the patient is passive at end
variable and the breath sequence inspiration, his or her resistance and compliance determine
2. Control type used to manipulate the primary control vari- the cycle point and thus the size of the breath for a given
able during inspiration pressure-suppol't setting. In contrast, for a patient on continu-
3. Control strategy, including phase variables and opera- ous positive airway pressure (CPAP), each brea th is sponta-
tional logic used to generate the breathing pattern neous but unassisted. Breaths are spontaneous because the
patient determines the timing and size of the breaths with-
out any interference by the ventilator. Breaths during CPAP
BREATHING PATTERN
are not assisted because airway pressure is controlled by
Tl1e simplest way to identify a mode is in terms of the inspi- the ventilator to be as constant as possible (i.e., Pvent = 0).
ratory control variable and the breath sequence. I have al- Understanding the difference between assisted and unas-
ready mentioned that pressure, volume, or flow can be consisted spontaneous breaths is very important clinically. For
trolled during inspiration. When d iscussing modes rather example, when making measurements of tidal volume and
than specific ventilator design characteristics, it is more con- respiratory ra te for calculation of the rapid-shallow breath-
venient simply to refer to inspiration as being pressure- ing index, the breaths must be spontaneous and unassisted. If
controlled or volume-controlled. We can justify ignoring they are assisted (e.g., w ith pressure support), an error of
flow control because when the ventilator controls volume 25-50% may be introduced. A mandatory breath is any breath
directly (i.e., using a volume-feedback signal), flow is con- that does not meet the criteria of a spontaneous breath. That
trolled indirectly, and vice versa (i.e., mathematically, vol- is, the machine triggers and/ or cycles the breath. It is pos-
ume is the integral of flow, and flow is the derivative of sible to superimpose a short mandatory breath on top of a
volume). longer spontaneous breath, as in the case of high-frequency
There are clinical advantages and disadvantages to vol- oscillatory ventilation.
ume and pressure control. To keep w ithin tl1e scope of this Having defined spontaneous and mandatory breaths,
chapter, we can just say tl1at volume control results in a there are three possible breath sequences, designated as
more stable minute ventilation (and hence more stable blood follows:
gases) than pressure control if lung mechanics are unstable.
On the other hand, pressure control allows better synchro- • Co11tinuous mandntory ventilation (CMV). All breaths are
nization with the patient because inspiratory flow is not mandatory unless the ventilator permits spontaneous
limited to a preset value. While the ventilator must control breaths during mandatory breaths; spontaneous breaths
only one variable at a time during inspiration, it is pos- are not permitted between mandatory breaths. The newer
sible to begin a breath in pressure control and (if certain ventilators with the "active" exhalation valves actually
criteria are met) switch to volume control or vice versa. In will allow a patient to inhale and exhale spontaneously
addition, it is possible to pressure-control inspiration but to during the mandatory inspiratory time as opposed to
older devices that only let a patient inl1ale. This may be disturbances in the system. Figure 2-SA is a diagram of an
easier to appreciate if you consider an old-fashioned infant open-loop system. Shown are three subsystems connected
ventilator, wherein the mandatory breaths were essen- in series: a controller, an effector, and a plant.
tially a transitory high CPAP level, and infants breathed The plant is the subsystem being controlled. Its output is
quite freely during both set inspiratory and expiratory the controlled, or output, variable. The effector is the mech-
times. This is how the "new" airway pressure-release ven- anism that drives the plant to respond in a given way.
tilation modes work on ventilators su ch as the Draeger Its output is the variable that is manipulated to control
Evita 4. the behavior of the controlled system. We w ill refer to it
• Continuous spontaneous ventilation (CSV) . All breaths are as the manipulated variable (we have called it the control
spontaneous. variable in relation to mechanical ventilators). The effec-
• Intermittent mandnton; ventilation (IMV). Spontaneous tor, typically, is the prime mover or the device that drives
breaths are permitted between mandatory breaths. When or powers the controlled system. In a ventilator, the effec-
the mandatory breath is triggered by the patient, it is com- tor might be a piston pump or an electronic flow-control
monly referred to as SIJnchronized IMV (SIMV). Because valve.
the trigger variable can be specified in the description of The control circuit or controller contains the logic used to
phase variables, however, I will use JMV instead of SIMV interpret or translate the input signal into a signal to which
to designate genera l breath sequences. the effector responds. Figure 2-SB shows the controller and
effector together within tl1e ventilator. One of the few ex-
CMV originally meant that every breath was mandatory. amples of open-loop control of mechanical ventilation is
The recent development of the "active exhalation valve," the type of jet ventilator used experimentally in the early
however, made it possible for the patient to breathe spon- 1980s.14,15 The operator could set a driving pressure, and the
taneously during a m andatory pressure-controlled breath controller would turn a valve on and off at a set frequency
on some ventilators. In fact, it was always possible for the and inspiration-expiration (I:E) ratio. Gas was metered to
patient to breath spontaneously during pressure-controlled the patient, but the actual pressure and volume delivered
mandatory breaths on infant ventilators. The key distinction. were dependent on the moment-to-moment changes in the
between CMV and IMV is that with CMV, the ventilator at- patient's respiratory system impedance.
tempts to deliver a mandatory breath even; time the patient makes Thus an open-loop control system cannot correct for
an inspiratory effort (unless a mandatory breath is already in disturbances in the conditions a ffecting the controlled
progress). This means that during CMV, if the operator de- plant. It goes on its merry way oblivious of its s ur-
creases the ventilator rate, the level of ventilator support is roundings. Disturbances are influences on the system that
unaffected so long as the patient continues making inspi- make the output unpredictable. During mechanical ven-
ratory efforts. With IMV, the rate setting directly affects the tilation, the major disturbances are changes in the pa-
number of mandatory breaths and hence the level of venti- tient's respiratory drive, respiratory system mechanics, and
lator support. Thus CMV is normally used as a method of leaks.
full ventilator support, whereas iMV is usually viewed as a
method of partia l ventilator support.
Given the three ways to control inspiration (i.e., pressure, CLOSED-LOOP CONTROL
volume, or dual) and the three breath sequences (i.e., CMV, All modern ventilators use closed-loop control to ma in-
IMV, o r CSV), there are eight possible breathing patterns tain consistent pressure and flow waveforms in the face of
(Table 2-2). changing environmental conditions. Closed-loop control is
accomplished by using the output as a feedback signal that
is compared w ith the operator-set input. The difference be-
CONTROL TYPE13 tween the two is used to drive the system toward the desired
OPEN-LOOP CONTROL output. For example, pressure-controlled modes use airway
The simplest type of control is called open loop. Its advantage pressure as the feedback signal to control gas flow from the
is low cost. Its weakness is that it is unable to cope with ventila tor. Manufacturers typically do not use flow at the
airway opening as a feedback signal because they do not
trust the flow sensors available for that purpose. Instead,
TABLE 2-2 The Breathin g Patterns they would rather measure flow inside the ventilator near
the main flow-control valve.
Breath-Control
Closed-loop control (also called feedback control) uses a
Va riable Breath Sequence Abbreviation
sensor to measure the output of the effector. This signal
Volume Continuous ma ndatory ventilation VC-CMV is passed to a comparator (represented by the circles in
Intermittent mandatory ventilation VC-!MV Fig. 2-6) that essentially applies a simple equation : error=
Pressure Conti.nuous mandatory ventilation PC-CMV input - output. lf the e.rror in the effector output is large
Intermittent mandatory ventilation PC-IMV enough, an error signal is sent to the controller. The con-
Continuous spontaneous ventilation PC-CSV troller then adjusts the effector so that its output is closer to
Dual Continuous mandatory ventilation DC-CMV the desired input (i.e., the error is smaller). The advantage
Intermittent mandatory ventilation DC-IMV
of closed-loop control is that the output is adjusted con-
Continuous spontaneous ventilation DC-CSV
tinuously and automatically so that disturbances are not a
A
-input + Controller .. Effector

manipulated ..
variable
Plant 1-output _ .
-input ... Ventilator

Controller Effector
gas
flow
..
~
Patient I--output ~
FIGURE 2-5 Sch ematic diagram s of open-loop
control systems: (A) basic control circuit; (B)
c open-loop control circuit diagram for a
drive
pressure
~ Ventilator aas
flow
Patient
airway
pressure
..
r
ventilator; (C) examp le of open-loop control of
a jet ven tilator. (Reproduced, with penuissiou,
from Clmtbum: Respir Care 49:507- 15, 2004.)
problem. Of course, the higher complexity of the system THE HIERARCHY OF VENTILATOR
makes it more expensive to build and maintain. CONTROL SYSTEMS
Note that a feedback signal may be electrical (e.g., from The basic concept of dosed-loop control has evolved into
an electronic pressure transducer) or mechanical (e.g., pres- at least seven different ventilator control sys tems (setpoint,
sure regulators and CPAP valves). In mechanical devices, auto-setpoint, servo, adaptive, optimal, knowledge-based,
a spring provides the input setting, and the position of the and neural-net control). These control types are the foun-
diaphragm (a measure of the gas pressure) is the feedback dation that makes possible several dozen apparently differ-
signal. When the force caused by the pressure exceeds the ent modes of ventilation. Once we understand how these
spring load, the diaphragm deflects and vents gas to the control types work, many of the apparent differences are
atmosphere to relieve the pressure. seen to be s imilarities. We then avoid a lot of the confusion
•
disturbances FIGURE 2-6 Schematic diagrams of closed-loop
Ventilator control of mech anical ventilators: (A) pressure
error gas control; (8) flow con trol; (C) the flow signal is
- input Controller Effector Plant r -output___.
A + '.l"' signal flow integrated to provid e a signal for volume
- control; (D) flow/volume control using a
calibrated gas-control val ve instead of an actual
feedback signal
flow sensor. (Reproduced, with permissiou, from
(pressure)
Chntbum: Respir Care 49:507- 15, 2004.)
•
disturbances
Ventilator
-input ... error ...

+ '.l"' signal
Controller Effector
gas
flow
.. Plant 1---output___.
B
-
feedback signal
(flow)
•
disturbances
Ventilator
- input
error
+ -, ,.., signal Controller Effector
gas .. Plant 1---output ___.
c flow
-
feedback signals
.__,volume~flow1 -
•
disturbances
Ventilator
-input
...
+ .
error _..
'.l"' signal Controller Effector
gas
flow
.. Plant 1---
D
- feedback signal I
(valve position)
46 PART II PHYSICAL BASIS O F MECHANICAL VENTILATION
disturbances
set point .. ~
Operator
pressure
volume
.. Ventilator .. Patient .
p
flow
I flow or volume -
FIGURE 2-7 Setpoint control. (Reproduced, witll
penuission,from Clzatbum: R espir Care 49:507- 15,
p ressure - 2004.)
surrounding ventilator marketing hype and begin to appre- load imposed by disease while the patient's own muscles
ciate the true clinical capabilities of different ventilators. ha ndle a normal load secondary to natural resistance and
compliance of the respira tory system (Fig. 2-8). Recall from
Setpoint Control Eqs. (1) and (2) that the "load" experienced by the ventila-
All ventilators use at least setpoint control (Fig. 2-7). In set- tor or the pa tient has an elastic component (elastance times
point control, the output is constrained to ma tch a con- volume) and a resistive component (resistance times flow).
stant input (i.e., a set maximum pressure or flow value).
This allows the typical ventilator to genera te pressure- or Adaptive Control
flow-controlled inspiration. The operator sets either a fixed Adaptive control means automatic adjustm ent of one set-
pressure or flow limit, and the ventilator then maintains a point to maintain a different operator-selected setpoint
consistent pressure or flow waveform output. (Recall that (Fig. 2-9). One of the first examples of a mode using adaptive
the term limit means that a control variable reaches a pre- control was pressure-regulated volume control on the Siemens
set maximum value before inspiration ends). This type of Servo ventilator. Adaptive control is an evolutionary step
control is similar to "cntise control" on an automobile. because it gives the ventilator the capability to determine a
setpoint level independent of the operator. While setpoint
Auto-Setpoint Control control occurs w ithin breaths, adaptive control introduces
Auto-setpoint control is a more advanced version of set- another feedback loop that occurs between breaths. The
point control. It gives the ventilator the decision of whether breath-by-breath feedback of exhaled volume, a long w ith
the breath will be pressure- or flow-controlled according to calculation of compliance, allows the ventilator to adapt to
the operator-set priorities. The breath may start out in pres- changes in the patient's lung m echanics (e.g., if compliance
sure control and automatically switch to flow, as in the Bird decreases, the pressure limit is increased). Despite ha ving
volume-assured pressure-control support (VAPS) mode,16 various nam es for the specific modes it allows, adaptive
or the reverse, as in the Drager Pmax mode. control to date has been in1plemented as a way for the ven-
tila tor to automatically adjust the pressure limit of a breath
Servo Control to meet an operator-set volume target over several breaths .
While setpoint control attempts to maintain a constant out- Notice that the operator's influence has subtly moved away,
put to match a constant input, servo control is designed to in a sense, from direct control of the breath.
track a moving input, much like power steering on an auto-
mobile. Servo control was developed during World War II to Optimal Control
aim ship's guns and radar equipment. Servo control makes Optimal control takes adaptive control a step further by
the proportiona l-assist mode possibleY In this m ode, the allo"ving the ventilator to determine its own setpoints
ventila tor's output follows and amplifies the patient's own (Fig. 2-10). Optimal control takes its name from the fact that a
flow pattern. The ventilator thus can support the abnormal mathematical model is used to find the best (e.g., minin1um)
Operator
setpoint
elastic load 1 Ventilator
.
disturbances
~ Patient ~~·
FIGURE 2-8 Servo control is the basis for the
proportional-assist mode. In this mode, the operator sets
targets for elastic and resistive unloading. The ventilator
then delivers airway pressu,re in proportion to the patient's
resistive load
own inspiratory volu me and flow . When the patient's
muscles have to contend with an abnormal load secondary to
c = pressure, volume and flow
disease, proportional assist allows the operator to set
amplification factors (Kt and K 2) on the feedback volume
Pmus =Loadnormal+ Load disease and fl ow signals. By amplifyin g volume and flow, the
ventilator generates a press ure that supports the abnormal
load, freeing the respiratory muscles to support only the
normal load caused by the natural elastance and resistance
of the respiratory system. (Reproduced, witll pcrmissiou, fro m
Clwtlmm: Rcspir Care 49: 507- 15, 2004.)
~nus + P vent =Loadnormal +Load disease

OiAPTER 2 CLASSIFICATION OF MECHANICAL VENTILATORS 47
Model
set oint Setpolnt Minimize
Operator t-~E~II>I
volume Adjustment
Wori<
exhaled volume
pressure
disturbances
Setpoint
, + Adjustment 14--- - - - - - - - - . ,
Ventilator ~
Patient
..
exhaled
I
l
now pressure volume flow C02
pressure-
lfreq~ency disturbances
FIGURE 2-9 Adaptive control. Notice that the operator has
stepped back from direct control of the within-breath parameters
of pressure and flow. Examp les of adaptive control are
pressure-regulated volume control (PRVC) on the Siemens ~
.. Ventilator r
•
Patient .....
ventilator and Auto flow on th e Drager Evita 4 ventiltaor.
(Reproduced, w i tfl permiss-ioll, f rom Cfln tburn: Respir Care 49:
I flow
507- 15, 2004.) pressure-
FIGURE 2-11 An experimental form of optimal control allows the
value of some performance function. For example, once the ventilator to estimate the patient's minute ventilation needs by
feedback of the exhaled carbon dioxide signal. This eliminates
operator enters the patient's ideal body weight, the ventila-
the need for the operator to set any of the major breath
tor selects the tidal volume a nd frequency that both meets parameters. Setpoints, however, for F102 and PEEP are stil l
the patient's minute volume need and minimizes the work required. (Reproduced, wit/1 permission, from. Chatburn: Respir
of breathing. The Hamilton Galileo is currently the only Care 49:507- 15, 2004.)
ventilator with this feature, and it allows the ventilator to
make all subsequent adjustments to tidal volume and fre-
quency based on continuous monitoring o f exhaled volume is still required fo r all the other parameters, such a PEEP,
and lung mecha nics. Again, the operator is moved another fractional inspired oxygen concentration (FI01 ), and alarm
step away from dir ect control of the breath. settings.
An experimental form of optin1al control gives the venti-
lator even mo re authority.18 Feedback of the exhaled carbon Knowledge-Bas ed Control
dioxide signal allows U1e ventilator to estimate the patient's Knowledge-based control is yet a further evolutionary step
minute ventilation needs (Fig. 2-11). Now the operator has because it gives the ventilator more knowledge than what
stepped completely out of the picture. Of course, we are may be contained in a simple, static, mathematical model.
only talking about eliminating the operator in the sense of In fact, knowledge-based control attemp ts to capttue the
establishing the level of ventilatory support. Operator input experience of any number of human experts and thus ex-
pand the scope of control to po tentially all paran1eters of the
ventilator mode. An experimental application of this type
FIGURE 2-10 Optimal control. A static mathematical model is of control has been described for automatic adjustment of
u sed to optimize some performance parameter, such as work of pressure support. 19 An even m ore sophisticated approach
breathing. The only commercially availab le form of optimal coupled a knowledge base with fuzzy logic (Fig. 2-12). 20
control is the adaptive-support ventilation (ASV) mode on the
In this case, the ventilator used both instantaneous mea-
Hamilton Galileo ventilator. (Reproduced, w·i tfl perm.iss ior1, from
Cl1ntbum: Respir Care 49:507- 15, 2004.) surements of physiologic values, such as respiratory rate
and oxygen saturation, and their rates of change. Fuzzy
Model logic21 was used as a way to integrate the m easurements
Minimize
Work with predefined ranges of values representing the patient
status. Once the patient's status was determined, appropri-
ate expert rules were selected from a lookup table and used
Operator 1---'se=< t -~ Setpolnt
t 7o"'-ln::.
to adjust the ventila tor. While this was a limited application,
patient Adjustment it p roved the concept.
weight
exhaled volume The most convincing proof of the concept was presented
by East et al. 22 They used a rule-based expert system for
•
pressure volume
ventilator management in a large, multicenter, prospective,
l frequency dlstur! nces randomized trial. While survival and length of stay were
, not different between human and computer management,
•
computer contro l resulted in a significant reduction in mul-
r
Ventilator Patient
tiorgan d ysfunction and a lower incidence and severity of
flow lung overdistension injury. The most important finding,
pressure - however, was that expert knowledge can be encoded and shared
Expert Fuzzy produce an overall unit activation. If this activation exceeds

Rules Logi a certain threshold, the w1it produces an output response.
Setpolnt Determine Determine Large numbers of neurons can be linked togetller in layers
Adjustment Action Status (Fig. 2-14). The nodes in the diagram represent the summa-
tion and transfer processes. Note that each node contains
information from all neurons. As the network learns, the
volume
pressure heart rate weights change, and thus the values at the nodes change,
respiratory rate affecting the final output.
disturl~tnces Mespiratory rate In summary, ventilator control schemes display a defi-
~
Sa02 nite hierarchy of evolutionary complexity. At the most basic
t.Sa02 level, control is focused on what happens within a breath.
.. Ventilator .
r Patient
I • We can call this tactical control, and there is a very direct
~ need for operator input of static setpoints. The next level up
I flow is what we can call strategic control. Here, setpoints are dy-
pressure - namic in that they may be adjusted automatically over time
by tile ventilator according to some model of desired perfor-
FIGURE 2-12 A knowledge-based control system for
automatically adjusting pressure support levels. (Reproduced,
mance. The operator is somewhat removed in that inputs are
witlr permission, from Chntbum: Respir Cnre 49:507-15, 2004.) entered at tile level of tile model and take effect over several
breaths instead of at the level of individual breath control.
Finally, the highest level so far is what might be consid-
successfully with institutions that had no input into the model. ered intelligent control. Here, the operator can be eliminated
Note that the expert system did not control the ventilato r altogether. Not only dynamic setpoints but also dynamic
directly but rather made suggestions for the human opera- models of desired performance are permitted. There is the
tor. In theory, of course, the operator could be eliminated. possibility of the system learning from experience so tl1at
the control actually spans between patients instead of just
Artificial Neural-Net Control between breaths (Fig. 2-15).
TI1e ultimate in ventilator control to date is tile artificial
neural network (Fig. 2-13).23 Again, this experimental sys-
tem did not control the ventilator directly but acted as a CONTROL STRATEGY
decision-support system. What is most interesting is that
the neural network was capable of learning, which offers signif- Finally, we can fully characterize a mode by adding the spe-
cific strategy it employs. This begins with the naming of
icant advantages over static matl1ematical models and even
the phase variables, followed by detailing the operational
expert rule-based systems.
logic and, if necessary, giving the parameter values used
Neural nets are essentially data-modeling tools used to
in the conditional statements. The specification of the breath-
capture and represent complex input-output relationships.
ing pattern that the mode cm1 produce, the type of control, and
A neural net learns by experience the same way a human
the specific strategtj it uses, for both ma11daton; and spontn11eous
brain does, by storing knowledge in the strengtlls of inter-
breaths, comprise a complete classification for any mode of venti-
node connections. As data-modeling tools, they have been
lation (Fig. 2-16). This system helps us to distinguish modes
used in many business and medical applications for botl1
that appear similar (i.e., look the same on graphics mon-
diagnosis and forecasting.24 A neural network, like an ani-
itors) and suggests what the operator must do to set the
mal brain, is made up of individual neurons. Signals (action
potentials) appear at the unit's inputs (synapses). The ef- controls. For example, pressure support (any ventilator) is
fect of each signal may be approximated by multiplying the PC-CSV, for which the opera tor sets the sensitivity and pres-
signal by some number or weight to indicate the strength sure linlit. In contrast, volume assist (Siemens 300) is DC-
CSV and looks similar to pressure support on the graphics
of the signal. The weighted signals then are summed to
monitor, but the opera tor must set a tidal volume in addition
to sensitivity and pressure limit.
FIGURE 2-13 Artificial neural network controi.(Reproduced, tvith
permiss ion, from Clrn.tbum: Respir Cnre 49:507- 15, 2004.)
inspiratory time Ventilator A larm Systems

Expert expiratory time
System ~
neural 14-- - - --p
r 'e ak inspiratory pressure - - - -., As witll other components of ventilation systems, ventila-
P EEP
network
FI0 2 tor alarms have increased in number and complexity. Fortu-
I nately, the classification system I have been describing can
suggestions be expanded to include alarms as well (see Table 2-1).
disturbances
Maclntyre25 has suggested that alarms also be cate-
Operator 1-----1~----~
gorized by the events that they are designed to detect.
Ventilator Patient f-r-...1---+ Level 1 events include life-threatening situations, such as
• 1....._ _ _____.
loss of input power or ventila tor malfunction (e.g., exces-
L - - - - - - - - -pressure sive or no flow of gas to tl1e patient). The alarms in this
Single Neuron
threshold
inputs weights summation output
function
~~~~~_o___r-
_____1~----_.~
Neural Network
FIGURE 2-14 Neural network structure. A single

neuron accepts inpu ts of any value and weigh ts
them to indicate the strength of the synapse. The
weighted signals are summed to produce an overall
unit activation. If this activation exceeds a certain
threshold, the unit produces an output response. A
first second network is made up of layers of individual
input output
hidden hidden neurons. (Reproduced, with p ermiss io11, from
layer layer
layer layer Cllatburn: Respir Care 49:507- 15, 2004.)
category should be mandatory (i.e., not subject to opera- dude such things as blender failure, high or low airway
tor choice), redundant (i.e., multiple sensors and circuits), pressure, autotriggering, and partial patient circuit occlu-
and noncanceling (i.e., alarm continues to be activated, sion. They also may include suspicious ventilator settings
even if the event is corrected, and must be reset man- such as an I:E ratio greater than 1:1. Alarms for level 2
ually). Level 2 events can lead to life-threatening situa- events may not be rednndant and may be self-canceling
tions if not corrected in a timely fashion. These events in- (i.e., alarm inactivated if event ceases to occur). Level 3
FIGURE 2-15 Summary of

Tactical Control (within breaths)
H H
control-system hierarchy.
Static set points (Reproduced, with pennissio·n, from
• set point Operator Ventilator Patient I C/ratbum: Respir Care 49:507- 15,
• auto set point 2004.)
• servo
Strategic Control (between breaths)

Dynamic set points Operator .. Model
Static models
• adaptive ~
• optimal Ventilator ~ Patient
Intelligent Control (between patients)

Dynamic set points
Model
Dynamic models
Ability to learn from experience
• knowledge based ~
• artificial neural networks Ventilator ~ Patient
50 PART II PHYSICAL BASIS OF MECHANICAL VEI\lTILATION
Ventil ator Name: Bear 1000 sta te-of-the-art computer control, and then we c01mect it
Manufacturer ' s Mode Name: SIMV/CPAP (PSV)
to the patient with a $1.98 piece of plastic tubing that is
Breathing Pattern: VC-LMV
Control Type: Setpoint subject to filling with condensate from a heated humidifier
Control Strategy: w hose design has not changed appreciably in 20 years. The
Phase Variables for Mandatory Breaths resistance and compliance of the delivery circuit make flow
Trigger: Pressure (sensitivity adj ustable from 0.2 to 5.0 em I hO)
time (rate adjustable from 0 to 120 cycles/minute) control and volume delivery more difficult (as discussed ear-
Limit: Flow ( 10 to 150 liters/minute) lier). It's like buying a Ferrari and putting wooden wheels
volume (whenever the inspiratory pause time is set >0) on it. In the future, water vapor should be trea ted like any
Cycle: Volume (tidal volwne adj ustable from 100 to 2.000 ml) other gas constituent (e.g., air, oxygen, or nitric oxide) and
time (whenever the inspiratory pause time is set >0)
pressure (when inspiratory pres.~ure violates alarm setting) metered from within the ventilator. The inspiratory part of
Baseli11e: PEEP/CPAP level adj ustable from 0 to 50 em H20 the patient circuit should be a sterile, insulated, permanent
part of the ventilator right up to the patient connection,
Ph ase Var iables for Spontaneous Breaths
Trigger: Pressure (sensitivity adj ustable from 0.2 to 5.0 em I hO) w hich can be a disposable tip for cleaning p urposes. The gas
Limit: Pressure (0 to 65 em H20 above baseline) should be delivered under high pressure as a jet to provide
Cycle: Flow (when inspiratory flow decays to 30% of peak flow); not only conventional pressure, volume, and flow wave-
time (when inspirat ion exceeds preset threshold)
Baseli11e: PEEP/CPAP level adjustable from 0 to 50 em H20
forms but also high-frequency ventilation. The jet also can
be used to provide a counterflow PEEP effect, eliminating
Operational Logic any need for a n exhalation-valve system. The disposable tip
If the patient triggers a breath after the start of a ventilatory period (the
could be d esigned to house disposable sensors and would
time equal to the reciprocal of the set ventilatory rate) then a mandatory
breath is delivered. If subsequent breathing efforts arc detected during ll1c be the only part of the circuit to be exposed to the patient's
same period. then spontaneous breaths are delivered. If a breathing effort exhaled gas. U ventilator manufacturers saw themselves as
is not detected during a given ventilatory period. then a mandatory breath providers of the entire system, instead of letting thirdparties
is time triggered at dte beginning of the next period and time triggered
mandatory breaths will continue at dte set rate until a breadting eflor1 is
deal in plastic connecting tubing, tl1en I think we would see
detected and dte sequence repeats. a huge evolutio nary step in ventilator performance, better
FIGURE 2-16 An example of how a ventilator mode can be
patient ou tcomes, and potential savings in labor costs for
completely specified. SJMV, synchronized intermittent providers.
mandatory ventilation; VC-IMY, volume-controlled intermittent Third, the most exciting a rea for development probably
mandatory ventilation; CPAP, continuous positive airway will be in the intelligence built into ventilator control cir-
pressure; PEEP, positive end-expiratory pressure. (Reproducecl, cuits of the future. The real challenge in closed-loop control
tvitlr pemrissio11, fro m Cllntbumet nl: Rl'spir Cnre 46:604-2.1, 2001.) of ventila tion is defining, measuring, a nd interpreting the
appropriate feedback signals. If we stop to consider all the
events are those that affect the patient-ventilator interface variables a human operator assesses, the problem looks
and may influence the level of support provided. Examples insum1ountable. Not only does a human consider a wid e
of such events a re changes in patient compliance and resis- range of individual physiologic variables, but there are
tance, changes in patient respiratory drive, and a uto-PEEP. the more abstract evaluations of such things as metabolic,
Alarm function at this level is similar to that of level 2 alarms. cardiovascular, and psychological states. Add to this the
L.evel4 events reflect the patient condition alone rather than various environmental factors that may affect opera tor
ventilator function . As such, these events usually are de- judgment, and we get a truly complex control problem
tected by s tand-alone monitors, such a s oximeters, cardiac (Fig. 2-17).
monitors, and blood gas analyzers. Some ventilators, how- I would like to speculate now about a response to
ever, are able to incorporate the readings of a capnograph this challenge. The ideal control strategy would have
in their displays and alarm systems. to start out with basic tactical control of the individ-
ual breath. Next, we add longer-term strategic control
that adapts to changing load cha racteristics. Mathematical
The Future models could provide the basic parameters of the mode,
whereas expert rules would place limits to ensure lung
There are three directions to go to improve ventilators in protection.
the future. First, just like computer games, ventilators need Next, we sample various physiologic parameters and use
to improve the operator interface constantly. Yet very little, fuzzy logic to establish the patient's immediate condition.
if any, research has been done to call attention to problems This information is passed on to a neural network, which
with current d isplays. We have come a long way from using would then select the best response to the patient's condi-
a crank to adjust the s troke of a ventilator's piston to set tidal tion.
volume. The operator interface must provide for three basic The neural network ideally would have access to a huge
functions: to a llow input of control and alarm parameters, to database comprised of both human expert rules and actual
monitor the ventilator's status, and to m onitor the ventilator- patient responses to var ious ventilator strategies. This ar-
patient interaction status. We have a long way to go before rangement would allow the ventilator not only to learn from
the user interface provides an id eal experience with these its interaction with the current patient but also to contribute
functions. to the database.
Second, the weak link in the patient-ventilator system Finally, the database and this ventilator could be net-
is the patient circuit. We buy a $30,000 ventilator with worked with other intelligent ventilators to multiply the
0 -IAPTER 2 CLASSIFICATION OF MECHANICAL VENTILATORS 51
.. Adjustment
Setpoint ...
I
pressure
volume
IIow
pressure resp rate
(PIP and PEEP) heart rate
Environment volume PeC02
I frequency Pa02
Fi02 Fi0 2
time
cost Sp02
triage priority PO.I
experience distur1 nces
0
r---'L-- l - -alarms
-- ..
-r
~
Operator - - - - - - Ventilator Patient
'----,......----'- - - - - - -- I
I
I
Ilow
I
pressure-
I
R GURE 2-17 The chalJenge of total com puter control
I
bronchospasm of m echanical ventilation. Solid arrow s depict signal s
1
- - - - - - - underlying disease ----- metabolic state
acid-base state
-----1 that h ave been u sed at l east experim ent all y. D otted
strength/endurance cardiovascular state arrow s represen t p ot en tial feedback signal s.
neural control psychological state (Reproduced, w ith permission, from Chntbum: Respir
autoPEEP drugs Cnre 49:507- 15, 2004.)
learning capacity exponentially (Fig. 2-18). Whatever the system. From this model we deduce that as far as an indi-
fu tu re brings, it seems clear that ventilators will have more vidual inspiration is concerned, any conceivable ventilator
intelligence built in to increase patient safety and decrease can be classified as either a pressure, volume, or flow con-
the time required to provide care. troller (and in rare cases, simply an inspiratory-expiratory
time controller). An individual breath is shaped by the
phase variables that determine how the breath is triggered
SummanJ and Conclusion (started), limi ted (sustained), and cycled (stopped). Ideal-
ized pressure, volume, and flow waveforms of individual
Mecl1anical ventilators have become so complex that a sys- breaths can be identified and named according to conven-
tem of classification is necessary to communicate in telli- tions in electrical engineering. Individ ual breaths can be
gently abou t them. The theoretical basis for this classifica- classified as being either mandatory or spontaneous, the
tion system is a mathematical model of patient-ventilator definitions of which are very specific and form the basis for
interaction known as the equation of motion for the respiratory characterizing modes.
FIGURE 2-18 A potential approach to th e

Human challenge of full y automated control of
Experts Optimization ... mechanical ventilati on . (Reproduced, w ith
Models pennissiou, fro m Clr ntburu: Respir Cnre
I .
strateg1c 49:507- 15, 2004.)
~
Competitive , control
Regi stry
Database
prior
experience
... Neural
Network
determine
best
intelligent
control
Expert
Rules
•
rules
•
,r ..
disturbances
D D
networked ventilators
r
Ventilator
flow
•
~
Patient
tactical control
pressure
Fuzzy
Logic
determine ...
patient
condition
A mode of ventilation can be characterized simply as a par- ll . Desautels DA. Ventila tor performance. m: Kirby RR, Smith
ticular pattern of mandatory and spontaneous breaths that RA, Desautels DA, editors. M echanical ventilation. New York:
are either volume-controlled, pressure-controlled, or have ChurdliU Livingstone, 1985: 120.
elements of both (dual-controlled). More detail (enough to 12. Sassoon CSH, Girion AE, Ely EA, Ligllt RW. Inspiratory work
distinguish any mode) can be added by describing the con- of breathing on flow-by and demand flow con tinuous positive
airway pressure. Crit Care Med 1989; 17:1108-14.
trol sd1eme, the phase variables, and the operational logic
13. Chatbum RL. Computer control of mechanical venti lation. Respir
used in the control circuit. Care 2004; 49:507- 15.
The trend in ventilator control schemes has been from ba- 14. Carlo WA, Cha tburn RL, Martin RJ, Lough MD, eta!. Decrease in
sic tactical control (within-breath control requiring operator airway pressure during high-frequency jet ventilation in infunts
input of static setpoints), to more advanced strategic con- w ith respiratory distress syndrome. J Pediatr 1984; 104:101-7.
trol (between-breath control of setpoints that are adjus ted 15. Branson RD, H urst JM, DeHaven CB. Use of high frequency jet
automatically by the ventilator with minimal operator in- ventilation d uring mechanical hyperventilation for control of el-
put), to the highest level of intelligent control (in which the evated intracranial pressure: A case report. Respir Care I 984;
operator theoretically may be eliminated altogether in favo r 29:1121-4.
of artificial intelligence systems capable of learning). 16. Amato MB, Barbas CS, Bonassa J, Saldiva PH, et at. Volume-
assured pressure support ventilation (YAPS): A new approach
for reducing muscle workload during acute respiratory failure.
Chest 1992; 102:1225-34.
17. Younes M. Proportional assist ventilation, a new approach to
References ventilator support: I. Theory. Am Rev Respir Dis 1992; 145:
114-20.
1. C hatbum RL. A new system for understanding mechanical ven- 18. Laubscher TP, Frutiger A, Fanconi S, Brunner JX. The au-
ti lators. Respir Care 1991 ; 36:1123-55. tomatic selection of ventilation parameters during the initial
2. C hatbum RL. C lassification of mechanical ventilators. Respir phase of mechanical ventilation. Intensive Care Med 1996; 22:
Care 1992; 37:1009- 25. 199- 207.
3. Chatbum RL, Volsko TA. Mechanical ventilators. In: Wilkins RL, 19. Dojat M, Harf A, Touchard D, et a!. Oinical evaluation of a
Stoller JK, Scanlan CL, editors. Egan's fundamentals of respira- computer-controlled pressure support mode. Am J Rcspir Crit
tory care. 8th ed . St. Louis: Mosby, 2003: 929-62. Care Med 2000; 161:1161-6.
4. C hatbum RL. Medlanical ventilators: Classification and princi- 20. Nemoto T, Hatzakis G, Thorp e CW, et a!. Automatic control of
ples o f operation. Ill: Hess DR, Madntyrc NR, Mishoe SC, et al, pressure support ventilation using fuzzy logic. Am J Respir Crit
editors Respiratory care: Principles and practice. Philadelphia: Care Med 1999; 160:550-6.
Saunders, 2002:757-809. 21. Bates jHT, Hatzakis GE, Olivenstein R. Fuzzy logic and mechani-
5. Chatbum RL, Primiano FP Jr. A new system for understanding cal ventilation. In: Iotti GA, ed. Respiratory Care Clinics of North
modes o.f medlanical ventilation. Respir Care 2001; 46:604-21. America 2001; 7(3):363-377.
6. C hatbum RL. Fundamentals of mechanical ventilation. Oeve- 22. East TO, Heerma1m LK, Bradshaw RL, et a!. Efficacy of com-
Jand Heights, OH: Mandu Press, 2003. puterized decision support for mechanical ventilation: RCl>'Uits of
7. Branson RD, Hess DR, Chatbum RL. Respiratory care equipment. a prospective multicenter randomized trial. Proc AMlA Symp
2nd ed. Philadelphia: Lippincott Williams & Wilkins, 1999. 1999; 251- 255.
8. Cairo JM, Pilbeam SP. Mosby's respiratory care equipment. 7th 23. Snowden S, Brownlee KG, Smye SW, Dear PR. An advisory sys-
ed. St. Louis: Mosby; 2004. tem for artificial ventila tion of the newborn utilizing a neural
9. Rodarte JR, Rehder K. Dynamics of respiration. Ill: Macklem PT, network. Med Inform (Lond) 1993; 18:367- 76.
Mead j, edi tors. Handbook of physiology. Section 3: The res- 24. Gottschalk A, Hyzer MC, Greet RT. A comparison of human and
piratory system. Volume. III: Mechanics of breathing. Part 1. machine-based predictions of successful weaning from mechan-
Bethesda, MD: American Physiological Society, 1986. ical ventilation. Med Decis Making 2000; 20:243-4.
10. Mushin WW, Rendeii-Baker L, Thompson PW, Mapelson WW. 25. Macintyre NR. Ventilator m onitors, d isplays, and alarms. In:
Automatic ventilation of the lungs. 3rd ed. Oxford, England: Macintyre NR, Branson RD, editors. Mechanical ventilation.
Blackwell Scientific, 1980: 62- 131 . Philadelphia: Saunders, 2001: 131-44.
Chapter 3 Electronic Valves
Microprocessor Control
BASIC PRINCIPLES ESTABLISHMENT OF PEEP/CPAP
Threshold Resistors
OF VENTILATOR Flow Resistors
Actual Valve Function
MACHINERY PEEP / CPAP in Microprocessor Systems
Interchangeable PEEP / CPAP Valves
ROBERT M . KACMAREK IMPOSED WO RK OF BREATHING
DANIEL CJ ITPMAN ALARMS
Hierarchy of Patient-Ventilator Alarms
"Smart" Alarms
MON ITORING
Pressure Monitoring
Flow Monitoring
THE USER INTERFACE Waveforms and Loops
PNEUMATIC SYSTEMS Derived Variables
Gas Source Effective Compliance
Pressure Reduction Resistance to Flow
Gas Blending Auto (Intrinsic) PEEP
Accumulator Trending of Da ta
Flow and Pressure Regula tion Digital Electronic Communications
Inspiratory-Flow Waveforms THE FUTURE
Sigh Volume
Nebulizer The newest generation of mechanical ventilators has ob-
VENTILATOR SAFETY ISSUES tained a level of sophistication unparalleled in previous gen-
MODES OF MECHAN ICAL VENTILATION erations (Fig. 3-1). Most of these units incorporate multiple
Controlled Mechanical Ventilation (CMV) microprocessors to control the flow of gas precisely, to allow
Assist-Control Ventila tion (ACV) for the provision of ventilator support by multiple modes,
Assisted Mecha nical Ventilation (AMV) and to allow for the monitoring and alarming of virtually ev-
Intermittent Mandatory Ventilation (IMV) ery aspect of the ventilator and patient-ventilator interface.
Synchronized Intermittent Mandatory Ventilation The ratio na le for the development of these highly sophis-
(SIMV) ticated units was to provide a safer, more flexible machine
Continuous Positive Airway Pressure (CPAP) that would ensur e a less stressful patient-ventilator inter-
Pressure-Controlled Inverse-Ratio Ventilation face, as well as a ventilator capable of meeting the need s of
(PCIRV) an increasingly varied group of critically ill patients. In ad-
Airway Pressure-Release Ventilation (APRV) dition, because of the microprocessor design, these ventila-
Bilevel Airway Pressure Ventilation (BILEVEL) tors can be upgraded and updated easily with new modes
Pressure-Support Ventilation (PSV) or monitoring systems without the need to purchase new
Proportional-Assist Ventilation (PAV) hardware.
BiPAP The primary purpose of this chapter is not to compare
Mandatory Minute Ventilation (MMV) and contrast individual mechanical ventilator brands (Fig.
Pressure-Regula ted Volume Control (PRVC) 3-2) but to provide a detailed discussion of the individual
Volume Support (VS) components and operational algorithms of the newest gen-
Volume-Assured Pressure Support (VAPS) eration of mechanical ventilators (Fig. 3-3). We will begin
Automatic Tube Compensation (ATC) with the user interface and then proceed with tracing gas
Adaptive-Support Ventilation (ASV) flow from its entrance into the ventilator to its exit via the
Noninvasive Ventilation (NTV) exhalation valve, as well as the various approaches used to
ADULTS, PEDlATRIC PATIENTS, AND NEONATES monitor and ala rm patient-ventilator functions, along with
PATIENT MAN AGEMENT ASSISTANCE the modes used to provide ventilator support. This chapter
ALGORITHMS provides a detailed description of the technical complexities
VENTILATOR TRIGGERI NG of gas delivery during ventilator support.
Site of Trigger
Pressure Triggering
Flow Triggering The User Interface
EXHALATION VALVES
Mus hroom / Diaphragm Valves TI1e user interface is the interaction between clinician
Scissors Va lves and ventila to r. In first-generation ventilators, this con-
Electro magnetic Valves sisted of electrical switches and mechanical adjustments
53
FIGURE 3-1 Maquet Servo I ventilator.
FIGURE 3-3 Viaysis Avea ventilator.

(e.g., Emerson). As the control of ventilators became more
electronic and less mechanical, the user interface evolved
into an array of rotary knobs that adjusted gas deliv- face is commonly a touch pad and/ or rotary encoder.
ery and associated alarms. With the current generation Most ventilators incorporate a layering of Windows-type
of microprocessor-controlled ventilators, the user inter- screens displaying the variables that can be adjusted
or monitored. Some incorporate touch-screen control of
FIGURE 3-2 Puritan-Bennett 840 ventilator. the various parameters. All, however, incorporate a two-
step proc-ess of changing a particular setting: first select-
ing the setting and then accepting it with an encorder.
The user interface not only allows the clinician to con-
trol ventilator settings but also displays information re-
lated to ventilator function and patient status. All the
current generation of intensive-care unit (ICU) ventilators
also have the capability of displaying waveforms of pres-
sure, flow, and volume, as well as pressure-volume and
flow-volume loops. Ideally, the user interface should be
simple to use, logical in format, and difficult to adjust
accidentally.
Unfortunately, there is no consistency among manufac-
turers in terms of the names and functions of ventilator con-
trols. This is particularly true regarding modes of ventilation
and has led to confusion and potentially dangerous situa-
tions, especially in hospitals where several ventilator brands
are used. Especially confusing are single controls on a ven-
tilator that have multiple functions that depend on the set-
tings of other controls on the ventilator. Most of the newest
generation of ventilators have eliminated this problem, al-
though some of the older units still in use do have these mul-
tiple variable controls. Because of the multiple interactions
that can occur between ventilator settings, adjustments of
mechanical ventilators should be restricted to persons w ith
specialized expertise in the technical aspects of mechanical
ventilation.
CHAPTER 3 BASIC PRfNC IPLES OF VENTI LA TOR MACHINERY 55
Pneumatic Systems when patients are being transported and pressurized gas is
being provided by cylinders.
The primary system that defines the operational capabilities
of every ventilator is the pneumatic system, which consists PRESSURE REDUCflON
of the mechanical components that physically control gas
delivery. All pneumatic systems begin with a gas source, Although gases typically enter the ventilator at SO lb/ in 2 ,
have a means of blending gas to establish s pecific oxygen the working pressure u sually is reduced immediately to 20
concentrations, and include a precision flow-control mecha- lb/ in2 or less. Ideally, the working pressure should be as
nism capable of regulating and manipulating delivered flow low as possible for safety purposes and to lessen wear on
and volume (Fig. 3-4). components. If the working pressure is too low, however,
flow and volume delivery are affected. Consider the case in
which the working pressure is 80 cmH 20 and the patient's
GAS SOURCE peak airway pressure is 40 emH 20. During inspiration, the
A pressurized gas source is needed to power the pneumatics pressure gradient decreases from 80 to 40 cmH2 0 , cau sing
of all ventilator gas-delivery systems. In critical-care appli- the flow to taper to 50°/c:. of the initial flow, resulting in de-
cations, this consists of air and oxygen delivered at 50 lb I in2 creased volume delivery for a fixed inspiratory time. Work-
from a bulk-gas-delivery system. Alternatively, the ventila- ing pressure u sually is preset, but it has been adjustable
tor can be powered by an internal compressor system, with in some oldel'-generation ventilators not currently manu-
oxygen added to provide the desired oxygen concentration. factured (e.g., Siemens Servo 900 series). In the Servo 900
In some ventilators, air nnd oxygen are needed only for gas series ventilators, marked alterations in peak inspiratory
delivery to the patient. In other ventilators, gas is also con- flow are observed as working (driving) pressure is altered.
sumed to power the control fw1ctions of the ventilator. This In other old ventilators (e.g., Bear 2), the inspiratory-flow
occurs mos t commonly in ventilators that are driven pneu- waveform was controlled by adjusting the driving pressure.
matically (i.e., require no electricity), such as portable trans- Fortunately, none of the current generation of ICU ventila-
port ventilators. In these ventilators, the gas flow required tors suffers from this deficiency.
and consumed by the unit is greater than the minute ven- Historically, ventilators have been described as single- or
tilation of the patient. Knowledge of this volume is critical double-circuit designs. With the s ingle-circuit design, the
gas that enters the pneumatic system is delivered to the
FIGURE 3-4 Primary pneumatic system for the Puritan-Bennett patient. In the double-circuit design, the gas that powers
840 ventila tor. Compressed gases enter at the far leJt of the the pneumatic system is separate from that delivered to the
" inspiratory module"(ceuter) below PSl an d PS2. The lower part patient (e.g., Enstrom 300, Puritan-Bennett MA-1). All new-
of the figure dep icts the fu nction of the optional air compressor generation ventilators are single-circuit design.
unit. The top of the figure indicates the expiratory module. (Used,
w itII permission, from Puritnu Beuuett 840 Veutiln tor System
Operators Guide 4-075609-00 Rev C (01/99), p. C1.) GAS BLENDING
All critical-care ventilators have some mechanism for mix-
ing air and oxygen to achieve oxygen delivery in the range of
21-100%. In first-generation volume ventilators, s uch as the
Emerson postoperative ventilator, oxygen flow was titra ted
into a reservoir from which the piston drew gas for deliv-
ery to the patient. All current-genera tion critical-care ven-
CJ tilators use eith er an internal or an external blender. These
HUI,f!Xflfll blenders use a precision metering device called a propor-
INSP"..AA'TOR'f
tioning valve. By altering the opening through which air and
'll'll.ll(~ oxygen are passed, different oxygen concentrations are de-
- - - - - - - - - - iE.G;- - - -~sriiATOft-y MOaut.t - - -
Ql I livered. These often work in such a matmer that when the
I
I oxygen port is opened, the air port is proportionally closed,
osl and vice versa. For these blenders to deliver an accurate
·~~~~ : oxygen concentration, the gas pressure entering the pro-
I portioning valve must be stable and equal. In some of the
newest-generation microprocessor ventilators (e.g., Puritan
Bennett 840, Respironics Espirit), air and oxygen are mixed
by use of proportional solenoid valves (as discussed later).
It is important that the ventilator does not allow backflow
of oxygen into the compressed-air delivery system and vice
versa. Most accomplish this by one-way check valves placed
in the individual gas-pressure-reduction mechanisms. This
is critical because most ins titutional compressed-gas sys-
tems are not maintained at the same exact pressure. If the
oxygen system isat49lb/in2 and the compressed-airsystem
TABLE 3-1 Characteristi cs of 100% Oxygen Suction Feature Available on Adu lt ICU Ventilators
Manual
Ventilator Activation Duration Termination Alarms
Puritan-Bennett 860 Touch key entry 2 minutes Yes Active

Drager Evita 4 Touch key entry Up to 3 minu tes Yes Active/inactive~>
Servo i Touch key entry 1 minute Yes Active
Viasys Avea0 Touchkey entry 2 minutes Yes Active
Hamilton Galilco Touchkey entry 2 minutes Yes Active
e-Vent Inspiration LS Touch.key entry 5 minutes Yes Active
Datex-Ohmed Touchkey entry 2 minutes Yes Active
Engstrom Carestation
•n, e increase in F1~ can be adjusted with the Avea.

• Alarms M e iMctive on ventilator disconnection.
at 51 lb/ in 2 , the accuracy of gas mixing would be altered ACCUMULATOR

without check valves.
ln some ventilators, gases are s tored in an accumulator be-
In some ventilators, the delivered oxygen concentration
fore delivery to the patient. With the Servo 900 series venti-
is not constant throughout inspiration. Although small fluc- lators, gas accumulates in a 0.9-liter bellows. The pressure
tuations (±1-2%) in delivered oxygen concentrations may in this bellows can be adjusted and serves as the working
not be important clinically, this can be problematic during (driving) pressure during i11spiration. Gas accumulates in
indirect calorimetry measurements. The delivered oxygen
a 1.1-liter reservoir in the Bird 6400ST, in an 8-liter reser-
concentration can be stabilized by adding a secondary ex-
voir in the Hamilton Veolar, and in a 3.4-liter reservoir in
ternal blender to ensure gas mixing before entering the
the Bear 1000. The accumulator acts as a mixing chamber
ventilator or using a precision gas mixture during these for blended gases, which increases the stability of the deliv-
measurements.1 ered oxygen concentrations. It also allows high peak flows
A control that is available on most ventilators is 100% oxy-
(> 200 liters/min), even when gas enters the ventilator at
gen suction. Activation of this control provides 100% oxy-
low flows (<80 liters/ min). None of the newest-generation
gen for a defined period of time (e.g., 2 minutes), primarily
ventilators, however, incorporate accumulators. They have
for hyperoxygenation immediately before and after endo-
been replaced with more efficient gas mixing and delivery
tracheal suctioning. 2 This feature also can be used for pro-
systems.
cedures other than suctioning that may be associated with
desaturation (e.g., line insertion and postural drainage). The
FLOW AND PRESSURE REGULATION
100% oxygen suction feature is available on most current-
generation ICU ventilators} and characteristics of some of A ventilator can be classified as a pressure, volume, flow, or
these ventilators are described in Table 3-1. time controller (Fig. 3-5).3 If the pressure waveform does not
In all ventilators, except the Siemens Servo 300, Maquet change with changes in patient resistance and compliance,
Servo-i, and Viaysis Avea, blending of only oxygen and then the ventilator is considered a pressure controller. If the
room air is possible. With these ventilators, a third gas may delivered volume is measured directly, then t11e ventilator
be blended with oxygen and air. The two gases commonly is considered a volume controller. If the delivered volume
added to these systems are helium and nitric oxide. is determined by a flow transducer, then the ventilator is
FIGURE 3-5 Criteria for determining the control variable during a ventilator-assisted inspiration. (Used, w ith penuissiou, from Clratburn:
Respir Care 37:1009- 25, 1992.)
Pressure Time Volume

Controller Controller Controller
no y as
does waveform change does waveform change is volume measured and

observation and - --+ when patient resi stance y es o _.. ·used for control of the
when patient resistance _n_
previous knowledge and complianca _.:....__+
and compliance change? volume waveform?
ch ange?
Flow
Controller
CHAPTER 3 BASIC PRINCIPLES OF VENTILATOR MACHINERY 57
Motor
FIGURE 3-7 A linearly accelerating rolling-seal piston pneumatic

system, as seen with the Bournes LS-104 ventilator (see text for
detai ls). (Used, witlr permission, from Saubom: Respir Care
38:72-109, 1993.)
used in the original proportional-assist ventila tor (Win-

nipeg ventilator)5•6 and is used currently on the Puritan
Bennett 700 series ventilators. Piston venti11tors normally
are volume controllers because the volume delivered is
determined by the displacement of the piston, and pres-
0 sure varies secondarily.
• Compressor-bellows. With this design (Fig. 3-8), the gas to
be delivered is contained in a bellows. Gas is moved
to the patient by pressurizing the chamber surround-
ing the bellows. This method is no longer used in
current-generation critical-care ventilators. Most anes-
FIGURE 3-6 A rotary, motor-driven piston pneum atic system as
thesia ventilators, however, use this design because it
used with th e Emerson postoperative and IMV venti lators (see separates the breathing gas from any possible mechan-
text for details). (Used, witll permission, fro m Saubom : Respir Care ical contamination and increases safety with flammable
38:72- 109, 1993.) gases. Compressor-bellows ventilators are volume con-
trollers because the volume delivered is measured
directly, as determined by the degree of bellows compres-
a flow controller. If both pressure and volume waveforms sion. The rate of compression of the bellows determines
change w ith changes in patient resistance and compliance, the rate of gas flow to the ~atient. A relatively low driv-
then the ventilator is considered a time controller. Most coming pressure (e.g., 1.8lb/in or 125 cmH 2 0) is controlled
mercially available mechanical ventilators are either pres-
sure, volume, or flow controllers. FIGURE 3-8 Compressor bellows or a bag within a chamber-type
A number of methods are and have been used histori- pneumatic system, as used with the Bennett MA-l and MA-2 an d
cally on commercially available ventilators to regulate in- Monaghan 225 ventilators (see text for details). (Used, wit/1
spiratory flow and manipulate the inspiratory flow pattern. permissiou, from Sa ubom : Resplr Care 38:72- 109, 1993.)
These include the use of a piston, a compressor-bellows, a
variable restriction, a stepper motor with a scissors valve,
a proportional solenoid, and a proportional manifold with
digital valves. 4
t
• Piston. With this design (Fig. 3-6), a piston draws gas into
a cylinder during its downstroke (or return stroke). On its
upstroke (or forward stroke), the piston moves gas out of
the cylinder to the patient. A motor turns a r otary wheel
at a cons tant speed. The speed of the motor can be ad-
justed to determine the respiratory rate and inspiratory-
expiratory time (l :E) ratio. Because the piston rod connects
to the outer edge of the rotary wheel, the movement of gas
into and out of the cylinder is not constant and approxi-
mates tha t of a sine wave. This design is still used in many
home-care ventilators (see Chap. 4) available throughout
world. It has serious limitations in critical-care ventilators,
however, because of the slow response of the motor and
crank-shaft assembly. These limitations can be overcome
by use of the Hillman piston and motor, in which the ro-
tating moto r is replaced with a linear motor (Fig. 3-7). By
using a linear motor and rolling-seal piston, grea ter flex-
ibility and responsiveness are achieved. This design was
58 PART II P I IYSICAL BASIS OF MECHANICAL VENTILATION
Variable Restriction reducing valve is a variable restriction that limits the max-
Peak Flow Control imum flow. This mechanis m is a flow controller, and tidal
volume is d etermined by a preset inspiratory time relative
to the flow setting.
• Stepper motor with a scissors valve. This device meters
flow by a stepper motor attached to a scissors valve
\. / that pinches a silicon tube (Fig. 3-10). The peak in-
spiratory flow is d etermined by the p ressure entering
FIGURE 3-9 A variable-restri ction Bow-controller pneumatic
the scissors valve (e.g., 120 cmH20). A stepper mo-
system as used with th e Sech rist infant ventilator (see text for tor controls the scissors valve to allow an increase or
details). d ecrease in flow of approximately 100/o increments or
d ecrements, respectively, as required to maintain the se-
by a variable-orifice peak-flow controller. The peak-flow lected tidal volume or airway p ressure.' If tidal vol-
control determines the fl ow at the initiation of inspiration. ume is d etermined by a fl ow transducer, this design is
Flow decelerates as airway pressure increases, however, a flow controller. If inspiratory pressure is controlled by a
because of the decreasing gradient between the driving pressure transducer, this d esign is considered a pressure
pressure and the downstream airway p ressure. con troller.
• Variable restriction. In this design (Fig. 3-9), the flow con- • Proportio11al sole11oid. With this des ig n, gas flow during in-
trol is a variable restrictio n that limits gas flow. In some spiration is controlled by either one or two proportional
neonatal ventilators, this is simply a Thorpe-tube flowme- solenoids (one for ai r and one for oxygen or a single
ter. In more sophis ticated applications of this design, the solenoid a fter gas blending) or flow-control valves. Tradi-
inspiratory waveform is varied by an adjustable pressure- tionally, a sole noid has operated in one of two positions,
reducing valve. When a decelerating waveform is se- on or off. Proportional soleno ids, however, open and close
lected, the working pressure is reduced (e.g., from 3-1.8 p roportio nally to control flow. In the case of the Puritan-
lb/ in2 ). This decreases the gradient between driving pres- Bennett 7200, each solenoid has 4095 stops in an operat-
sure and a irway pressure, with a resulting d ecrease in ing d istance of 762 /Lm. In some cases the flowmetering
gas flow. The peak-flow control distal to the pressure- o rifice of the p roportional solenoid is actuated directly
by an armature moving linearly in a magnetic field (Fig.
3-11 ). Alternative designs include the use of a stepper
FIGURE 3-10 A stepper motor wi th scissors-valve pneumatic
motor coupled directly to the flowmetering orifice or a
system from the Siemens Servo 900C ventilator (see text for
d etai ls). (Used, witlt permiss ion, from Siemens product literature.) s tepper motor-driven cam (Fig. 3-12). With each of these
FIGURE 3-11 An electromagneti c proportional-solenoid

pneumatic system as used with the Puritan-Bennett 7200, the
Hamilton Veolar and Amadeus, th e Drager Evita, and the
Siemens Servo 300 ventilators (see text for detai ls). (Used, wi tlr
per111issio111 jro111 Sturbom : Respir· Care 38:72- 109, 1993.)
1- -------~
Coil - -:
Proportional
Valve
On/Off Solenoid Valves
o:
' . -. .
Motor
Digital Valves
FIGURE 3·13 A proportional manifold wi th digital valve pneu-

matic system as u sed with the Infrasonics Infant Star ventilator
(see text for details). (Used, 111ith pennission, from Sanbom: Respir
Care 38:72- 109, 1.993.)
~-.-.~ Proportional
resolution ofO.S liter / min. With this design, flow accuracy
from each valve and reliability of the individual compo-
nents are important. U problems of reliability and accuracy
Valve can be solved, the digital valve design is attractive because
each valve can be considerably less sophisticated than a
FIGURE 3-12 A step motor- driven cam proportional-solenoid full-range proportional valve.4 This design can serve as
system as used with the Bear 5 and 1000 and the Bird 6400ST and either a flow controller or a pressure controller.
8400ST ventilators (sec text for details). (Used, w itlr permission,
from Sanborn: Respir Care 38:72- 109, 1993.)
INSPIRATORY-FLOW WAVEFORMS
For each control variable (pressure, volume, and flow), a
designs, the position of the solenoid determines peak flow limited number of waveforms can be developed. These can
and flow waveform. When proportional solenoids are be grouped into four categories: rectangular, exponential,
used for both air and oxygen, the delivered oxygen con- ramp, and sinusoidal (Fig. 3-14).3 With ventila tors that are
centration is also controlled. A proportional solenoid can pressure controllers, rectangular and exponential] y increas-
function as either a flow controller or a pressure controller. ing waveforms are available. For volume controllers, in-
• Proportional manifold with digital valves. This design uses creasing ramp and sinusoidal waveforms a re available. The
digital solenoid valves in which each valve is either open greatest number of waveforms are possible for flow con-
or dosed (Fig. 3-13). When open, each va Jve produces only trollers: rectangular, sinusoidal, ramp (ascending and de-
one calibrated flow. The number of discrete flow steps (in- scending), and exponential decay.
cluding zero) is 2", where n is the number of valves. For ex- With pressure and How controllers, the delivered wave-
ample, a nine-valve design with 0.5 literI min increments form is a function of both ventilator settings and res piratory
between valves yields a flow ra nge of0-255 liters/ n'lin at a system impedance (Fig. 3-15). 8 With increased impedance,
FIGURE 3-14 During inspiration, the ventilator is only able to control one of three variables (pressure, volume, or flow) during a given
breath. Possible waveforms associated with each control variable are illustrated. (Used, ·with permission, from Chat buru: Respir Care
36:1123-55, 1991.)
Control Variable
~ It :,
'
Preasure
'
Volume '
FJow :
.. . . . .·
:; .
Rectangular EJponential Ramp Sinusoidal Rectangular Sir..JsoidaJ Ra~ Exponential

(flH ) (aaoencing) (O.ec:.nding) (decay)
n_!l_ A _/ n _n_ Ah_k_

__
. . ... . ... . . - ... . .
' -......
......... ~- -
• Peak airway pressure is lower w ith d ecelerating flow pat-

Venri lator Respiratory l .oad Desired Acr ual terns and higher with accelerating flow patterns.
Type Pararnerers"' e ffccr Waveform Waveform • Gas dis tribution is improved with decelerating flow pat-
terns . The res ult of this improved gas distribution is a
Pressure- • c. • " large
n (1 decrease in pulmonary shunt and dead space.
Controller
• c. • " medium
n n • Mean airway pressure is further increased by use of an
end-in spiratory breath hold.
.. c. • " medium
n n
• c. • " small
n n A decelerating flow pattern can be produced using either a
pressure controller or a flow controller.23
Because variation in flow waveform is teclmically fea-
sible, the spectrum defined earlier has been included on
Flow-
(,Jnrroller • c .• 1'1 small
n n many ventilators despite no clearly established benefit of
one over the other. The only exception to this is the de-
• c. t " medium
n I I celerating and exponential-decay waveforms, whicl1 result
• c.• " medi um
n n in the lowest peak airway pressure. On current-generation
ICU ventilators, only three wavefom1s are available: rect-
• c.• " large
n r-t
angular, descending ramp, and exponential decay. Rectan-
gular a nd descending-ramp waveforms are available with
volume-targeted modes, and exponential-decay waveforms
~ t = high: .t = l~>v,.: C =cnrnpliunce: R :: rcsiswnce.
are available with pressure-targeted modes.
FIGURE 3-15 Idealized effects of increasing impedance on pres-
sure and flow controllers. (Used, with permission, from Clrntlmrn:
Respir Care 36:1123-55, 1991.) SIG H VOLUME
The sigh breath is a deliberate increase in tidal volume for
one or more breaths at regular intervals.24 Much debate
the d esired waveform may differ considerably from the ac-
over the use of sigh breaths has occurred over the last 40
tual delivered waveform. When an inspiratory waveform
years. 25 - 34 The lack of demonstrated benefit has resulted in
other than constant flow is chosen, the ventilator must ad-
none of the current-generation ICU ventilators providing
just either the peak flow or inspiratory time to maintain a
a sigh function . Two recent clinical studies,35 - 36 however,
constant d elivered tidal volume (Fig. 3-16).
have demonstrated improved oxygenation with the use of
The clinical usefulness of inspiratory waveform manipu-
periodic sighs over the short term. With the current concern
lations is somewhat unclear. 9 Over the past 40 years, there over ventilator-induced lung injury, though, it is doubtful
have been a number of studies that have evaluated inspira- that the sigh function will be reintroduced into the current
tory flow pattems and their effects on system ~ressures, gas generation of ICU ventilators. No d ata are available to de-
exchange, and other variables (Table 3-2). tO- The fo llow-
termine whether the application of peak alveolar pressures
ing conclusions9 can be drawn from these studies:
of 40 cmH2 0 and tidal volumes of 12 ml/kg of ideal body
weight once every minute or two over days will result in the
• Mean a irway pressure is higher \•Vith decelerating flow same level of injury that the application of these volumes
patterns and lower with accelerating flow pattems. and pressures cause when applied continuously.37
FIGURE 3-16 When the inspiratory waveform is changed

from a square to a decelerating waveform, either peak
~, decelerating; inspiratory flow or inspiratory time must b e inc.r eased to
; \ I(""' Inspiratory maintain constant delivery of tidal volume.
, \ tlme fixed
'\
'
i-:---'------,_.- square wave
'
'
.. .' \
\
,.. ...
\
\
\
decelerating;
'' \ / fixed peak flow
''
\
\
time
TABLE 3-2 Studies of Inspi ratory flow Patterns and Their Effect on Pressures an d Other Vari ables
Model and Flow Mean Airway Peak Airway Gas

Tnvestigator(s) Generator Pressure Pressure Distribution Pao2 Other
Lyager 10 Lung mod el; Poorest with

Engstrom, Bird ascending
Mark 8, Bennett
PR-2
11
Adams et al Canine model; Highest with sine,
experimental descending; lower
flow generator with ascending
square
Jansson and Computer Higher with Lower with
jonson 12 simulation descending; lower descending;
with ascending higher with
and square ascending and
square
Johansson and Human subjects; Highest with Lowest to highest:
Lofstrom 13 Servo 900 ascending descending,
square,
ascending
Baker et a1 14 Canine model; Highest to lowest: Most favorable Yo/Yr. C, PacD!,
experimental descending, with descending CO most
flow generator square, sine, favorable with
ascending d escendi ng
Damann 15 Human subjects; Highest with sine Sine better
Servo900B wave than s quare
Modell and Canine lung in jury; 10% increase in
Cheney16 Emerson 3PY Pao2 with
d esce11ding vs.
ascending and
sine wave
Baker et al 17• 18 Can ine pulmonary Highest to lowest Lowest Pac~ with
edema and descending, descending
emphysema; square
experimental
flow genera tor
Banner et aJ 19 Lung model of Lowest with Improved Lowest Paco2 with
uneven descending, with descending;
ventilation; highest with descending decrease in
Hamilton Veolar ascending Petco2 with
(4 wavefom'IS) descending and
increasing
inspiratory time
Branson and Human subjects; Highe~'twith Lowest to highest:
Hurst2° Hamilton Veolar descending and sine, square,
(4 waveforms) square descending,
ascending
Smith and Pigs with high Raw; Higher with o differ~nces in
VenuS21 Hamilton Veolar ascending than gas exchange or
(4 waveforms) with square, sine, hemodynamic
or d escending values
Rau and Lung mod el; Highest with full Lowest to highest:
Shelledy22 Hamilton Yeolar d escending ; descendil1g;
(7 waveforms) lowest with full modified sine,
baselin e and low ascending sine, pa rtial
compliance descending,
square, partial
ascending, and
fu II ascending
AB8REV1ATIONS: Yo VT, dead space-to-tidal volume ratio; C, compliance; CO, cardiac output; Paco2 , arterial carbon dioxide tensio n; Paez, arterial oxygen tension;
PetCO:!, e nd-tidal carbon dioxide tension; R,..,, airway resistance.
souRcE: Used, with permission, from Rau.9
62 PART IT PHYSICA L BASIS O F MECHANICAL VENTILATION
NEBULIZER valve should be present on the inspiratory limb of the

ventila tor. In the event of a pneumatic failure, this valve
Some ventilators are capable of powering a nebulizer. When
activated, part of the delivered tidal volume is diverted opens to allow the patient to breathe room air. Some
v~ntila tors, in the event of an electrica l or pneuma tic
through an a u_xilia~ line to power the nebulizer. Normally,
the nebulizer ts activated only during the inspira tory phase fa1lure, open both the inspiratory and expiratory valves
to allow continuous gas flow through the circuit from
without affecting the delivered Fr~ . Some ventila tors, how-
ever, do use either compressed air or 100% oxygen to power w hich the patient may breathe spontaneously. 39• 40 All
new~ge~era tion ventilators incorpora te an apnea backup
the nebulizer (thus affecting Fr0 , ) . This feature of mechan-
ventila tion system that activates if the ventilation rate falls
ical. ventilators has becom e le~ useful in recent years in
below a clinician-selected level. In most current-generation
vanous parts of the world for the d elivery of aerosolized
bronchodilators because of increased use of m etered-dose ventila tors, a high continuous gas flow is produced with
inhalers during mechanical ventilation. The increasing use disconnection in a n attempt to compensate for the leak.
This can result in aerosolization of tubing condensate into
of ~r~g~ not available as metered-dose inhalers, especially
the room, w hich is potentially hazardous to clin.icians at
anhbto hcs, has caused many manufacturers to rethink the
the bedside. When a patient is purposefully disconnected
addition of th e nebulizer feature. Som e manufactures (e.g.,
from the ventila tor, the Y-piece of the circuit should be
~~quet Se~vo-i) ~ave developed ultrasonic nebulizers spe-
capped. Other ventilators (e.g., Purita n-Bennett 840) are
oft ~ for thetr ventilators; these offer an increased capacity to
able to differentiate between a leak and disconnection and
de.liver a larg~ volume of aer osol in the therapeutic ran ge.
Wtth the ongomg d evelo pment of new nebulizers a nd con- will stop all gas delivery if an achtal d isconnection occurs.
tinued research on drug delivery by the aerosol route, we
expect this to be an area of continued develo pment in ven-
tilator design.3S
Modes of M echanical Ventilation
A word of caution about the use of aerosolized med-
The relationships between the various possible breath
ication is in order. Because many ventilators now incor-
types a nd inspira tory-phase variables are referred to as
pora te highly developed fl ow-measuring capabilities, the the modes of ventilation.4'1 , 42 Three phase variables de-
aerosolization of drugs within the ventilator circuit can
fine inspiration: the trigger va riable, the limit variable,
cause ma lfunction of the expiratory-flow transducer. Many and the cycle variable (Fig. 3-17).3.43 The trigger variable
manufacturers now recommend the .inclusion of a filter in begins inspiration and is dis cussed later in this chap-
the expiratory limb just before gas enters the exhalation ter. The limit variable is the pressure, flow, or volume
manifold . These filters, however, must be removed and d is-
targe t that cannot be exceeded during inspira tion. The
carded after treatment to avoid the buildup of inadvertent
cycle variable e nds inspiration. Five control variables de-
P?sitive en~-expira tory pressure (PEEP) because of clog-
scribe gas delivery: pressure control, volume control, flow
gmg of the filter w ith d rugs and water.
control, time co ntrol, and dual control (normally pres-
sure and volume). Fina lly, two general terms can be
applied to the actual breath type: mnndntonJ breath (in-
Ventilator Safety Issues spiration is triggered and/or cycled by the machine)
and spontaneous bret~th (inspiration is triggered and cy-
Because mechanical ventilators are life-support devices, cled by the patient). A classification of common ventila-
it is imperative that they respond in a safe manner if tor modes is summarized in Table 3-3. Some modes must
there is a pneuma tic o r electrical failure. An antiasphyxia stand alone, based on their function, whereas others can be
Mandatory FIGURE 3·17 Classifi catio n of control

Breath Spontaneous
Type Breath Breath and p hase varia bles fo r the two basic
breath typ es: mandatory a nd
spontaneo\tS. (Used, w ith permissiou,
from Brausou et n/. 43 )
I I I l I 1
Control Pressure Volume Flow n me Dual Pressure Dual
Variable Control CQntrol Control Control Control Control c ontrol
I I I I T I
Trigger Trigger Trigger Trigger Trigger Trigger Trlgge r
• rnactlino · machine · machine • mar.!Vle · machine •p;l!K/nt · pmicrc
• patient • patient • patient • patient • patient Limit Limit
Limit Limit Limit Cycle Limit • presstJre • presw re
Phase • pressure • volJme • VOlume) · pressure · pressure Cycle •llaw
Variables • volume • low • llow •vok1me •..oome • prossore Cycle
Cycle cycle Cycle •llow · now • flow
• PfeSSillll!
• pressure • pressure • pressure •lime Cycle •flow
• volUme • volume • votlme • pres.sure
• How • tow • flow ·vot.ome
· lime · t'me • time • llow
•time
TABLE 3-3 Expan d e d C lassificatio n o f M o d es of Ventilator Operatio n
MANDATORY BREATH SPONTANEOUSBREATri

Mode Conh·ol Trigger Limit Cycle Control Trigg~ Limit Cycle
CMV Press ure Tunc Pressure, Tune, pressure,

'
volume, or volume, volume or
flow or flow flow
PCV Press ure Tune Pressure Tune
V-ACV Pressure, Pressure, Pre&mre, lime, pressure,
volume, or volume, or volume, volume, or
flow flow or flow flow
P-ACV Pressure Pressure, Pressure lime
volume, or
flow
AMV Pressure, Press ure, Press ure, lim e, pressure,
vo lume, or volume, or volume, volume, or
flow flow or flow flow
VC-IMV Pressure, lime Pressure, lime, pressure, Pressure Pressure, Pressure Pressure
volume, or volume, volume, or volume,
flo w or flo w flow or flow
VC-STMV Pressure, Tune, pressure, Pressure, lime, pressure, Pressure Pressure, Pressure Pressure or
volume, or volume, or volume, volume, or volume, flow
flow flow or flow flo w or flow
CPAP Pressure Pressure, Pressure Pressure or
volume, flow
or flow
PC-IMV Pressure lime Pressure Tune Pressure Pressure, Pressure Pressure
volume,
or flow
PC-SIMV Pressure Tune, pressure, Pressure lime Pressure Pressure, Pressure Pressure
volume, or volume,
flow or flow
PCIRV Pressure lime Pressure Tune
APRV Pressure lime or Pressure lime Pressure Pressure, Pressure Pressure
pressure volume,
or flow
Bilevel Pressure Tune, pressure, Pressure lime Pressure Pressure, Pressure Pressure
or flow volume,
or flow
PSV Press ure Pressure, Pressure Flow
volume,
or flow
MMY Volume or lime Volume or lime, volume, Pressure Pressure, Pressure Pressure or
flow flow o r flow volume, volume
or flow
YAPS Pressure, Pressure, Pressure Pressure,
volume, volume, volume,
or flow or flow or flow
BiPAP Pressure Tunc Pressure lime Pressure Flow Pressure Flow
vs Pressure Pressure, Pressure Flow
volume,
or flow
ASV Pressure Tune, pressure, Pressure Tune Pressure Pressure, Pressure Flow
volume, or volume,
flow or flow
ATC Pressure, Pressure Flow
volume,
or flow
PAY Pressure, Pressure Flow
volume,
or flow
ABBREVIATIONS: CMV, volurn~ontroll~d mechanical ventilation; V-ACV, volume assist-control ventilation, P-ACV, pressure assist-control ventilation; AMY, assisted
mechanical ventilation; VC-IMV, volume-controlled intermittent mandatory ventilation; VC-SLMV, volum~ntrolled synchronized intermittent mandatory ven-
tilation; CPAP, continuous positive airway pressure; PCV, pressure-controlled ventilation; PC-LMV, pressure-<ontrolled IMV; PC-SLMV, pressure-controlled SIMV;
PCTRV, pressure-controlled. inverse-ratio ventilation; APRV airway pressure release ventilation; Bilevel, bilevel pressure ventilation; MMV, mandatory minute ven-
tilation; YAPS, volume-assured pressure support; BiPAP, bilevel positive airway pressure; VS volume support; ASV, adaptive-support ventilation; ATC, automatic
tube compensation; PAV, proportional assist ventila tion.
SOURCl!: Modified and used, with permission, from Chatbum.3
TABLE 3-4 Pressu re versus Volume Target ing M odes TABLE 3-5 New Modes of Ventilation T hat Vary Gas Delivery
wi thin a Breath or between Breath s
Pressure Volume
Within-Breath Variability Between-Breath Variability
Tidal volume Variable Preset
Peak airway pressure Preset Variable Proportional-assist Pressure-regulated volume
Peak alveolar pressure Preset Variable ventilation (PAV) control (PRVC)
Flow waveform Preset but variable Preset Automa tic tube Volume support (VS)
Peak flow Variable Preset compensation (ATC)
Inspiratory time Preset Preset Volume-assured pressure Adaptive-support
Sensitivity Preset Preset support (VAPS) ventilation (ASV)
FtDl Preset Preset
PEEP Preset Preset
I:E ratio Preset or variable Preset or variable Two modes of ventilation target proportional unloading
of patient effort (PAVor ATC). That is, the ventilation target
ABBREVIATIONS: F1~, fractional inspired oxygen concentration; PEEP, positive
end-expi ratory pressure; T:E ra tio, inspiratory time-to-<!xpiratory time ratio.
is the percentage of the tidal effort that is unloaded either to
minimize overall patient effort (PAV) or to maintain tracheal
pressure constant (ATC). As a result, both tidal volume and
airway pressure can vary considerably on a breath-to-breath
basis from near zero to excessive.
combined. 42- 45 Finally, most modes of ventilation associ- For these more sophisticated or so-called new modes of
ated with actual gas delivery to the patient can be grouped
ventilation, gas delivery can be adjusted either within each
by their primary gas-delivery target- pressure, volume, o r
breath or between breaths (Table 3-5). That is, pressure or
both-although two modes, proportional-assist ventilation
volume vary within a given breath based on patient demand
(PAV) and automa tic tube compensation (ATC), target nei-
or on the subsequent breath based on the current breath
ther pressure nor volume.
demand to establish a new target level. Modes of ventilation
Pressure-targeted modes all set a peak inspiratory pres-
available on select ventilators are listed in Table 3-6.
sure that is targeted during inspiration; that is, initial gas
flow is delivered rapidly to achieve the pressure target. Af-
ter the target is reached, flow usually decelerates in an expo- CONTROLLED MECHANICAL VENTILATION (CMV)
nentially decaying manner to maintain pressure at the target
until the inspiratory phase is complete. If the patient should With CMV, all breaths are totally controlled by the ven-
inspire more forcefully in the middle of the breath, flow ac- tilator, and patient triggering is not possible (Fig. 3-18).
celerates to maintain the target pressure. Because of this CMV is also called volume-co/ltro/led ve11tilation or pressure-
gas-delivery forma t, tidal volume is variable on a breath-to- controlled ventilation (Fig. 3-19). In some ventilators, the only
breath basis. Other aspects of gas delivery, however, are set difference between CMV and assist-control ventilation is
the same as with volume-targeted modes (Table 3-4). the sensitivity setting. In reality, assist-control or intermit-
With volume-targeted modes, the primary gas-delivery tent mandatory ventilation modes can provide controlled
target is tidal volume. Normally, all aspects of the inspi- med1anical ventilation if the patient is sedated and I or par-
ratory phase are selected by the clinician with volume- alyzed. With volume-targeted CMV, the clinician sets the
targeted modes. Specifically, tidal volume, flow waveform, rate, tidal volume (in some machines, a minute volume is
peak inspiratory flow, and inspiratory time are set. This con- set)_ flow waveform, peak inspiratory flow or inspiratory
trasts with pressure-targeted modes, where the pressure time, and I:E ratio. With pressure-targeted CMV, the clin-
limit and the inspiratory time are the only variables set. ician sets the rate, pressure level, inspiratory time, or I:E
With volume targeting, peak inspiratory pressure may vary ratio.
on a breath-to-breath basis.
With dual modes, the gas-delivery pattern can vary in ASSIST- CONTROL VENTILATION (ACV)
two ways. First, each breath can be delivered as a pressure-
targeted breath but with a tidal volume target. As a re- ACV may be either pressure- or volume-targeted. With
sult, to ensure the tidal volume target, pressure may need ACV, a minimal rate and tidal volume (or inspira tory pres-
to vary on a breath-to-breath basis. With this approach, sure) a re set by the clinician. The patient may trigger the
tidal volume on the current breath is compared with the ventilator at a more rapid rate, but the clinician-determined
target, and pressure level on the subsequent breath is ad- tidal volume (or inspiratory pressure) is delivered with each
justed if the tidal volume is off target. Second, gas can breath (Figs. 3-20 and 3-21). Assisted breaths may be either
be delivered as a volume-targeted breath with a set min- pressure- or flow-triggered (see discussion related to trig-
imum tidal volume and peak flow. On any breath, however, gering later in this chapter).
peak flow and, as a result, tidal volume can be exceeded if
the patient's ventilatory demand increases. This is accom-
ASSISTED MECHAN ICAL VENTILATION (AMV)
plished by allowing the patient access to a demand flow any
time d uring the breath. With this approacl1, the volume- With this mode of ventilation, all breaths are triggered by
targeted breath can be converted to a pressure-supported the patient (no set backup rate) (Fig. 3-22), and each breath
breath. is delivered at the ventilator's set tidal volume (or pressure).
CHAPTER3 BASIC PRINCIPLES OF VENTILATOR MACHINERY 65
TABLE 3-6 Modes of Ventilation Available on Selecte d M echanical Ventilators
C PAP C,ACV SIMV MMV APRV Bilevel PS Apnea Vent. PRVC vs ATC ASV YAPS
BearS + v v + +
Bird 6400ST + v v +
Bird 8400ST + v v + +
Hamilto n V~llar + V,P V, P + + +
Hamilton Amadeus + v v + +
lnfrasonic:s Adult Star + v v +
O hmeda Advent + V,P V, P + + +
Orager IRISA + V,P v, p + + +
Puritan-Bennett
7200a + V,P V, P + +
7200ae + V, P V, P + +
7200sp + V,P V, P + +
Siemens Servo 900E + v v +
Siemens Servo 900C + V,P V, P +
Maquet Servo i + V,P V, P + + + + +
Puritan-BcJmett 840 + V,P V, p + + + +
Hamilton Gallileo + V,P V,P + + +
Viasys Avea + V,P V, p + + + + +
Oragcr Evita 4 + V,P V,P + + + + + +
e-Vent Inspiration L.S + V,P V, P + + + -1- +
Datex-Ohmeda + V,P V,P -1- + + -1-
ABBREVlATJONS: V, volume; P, pressure; CPAP, continuous positive airway pressure; ACV, assist-«>ntrol Vt!ntilation; C, control; SIMV, synchronized intermittent
mandatory ventilation; MMV, mandatory rninute ventilation; APRV, ain..,ay pressure-release ventilation; Bilevel, bilevel airway pressure ventilation; apnea vent.
backup, apnea ventilation; PRVC, pressure-regulated volu rne control; VS, volume support; ATC, automatic tube compensation; ASV, adaptive-support ventilation;
VAPS, volume-assured pressure support.
FIGURE 3-18 Volume-con trolled ventilation (CMV), d ecelerating ramp flow.
80
~
40
E
n..
<:::.-
0
~ 4 6 10 12 14
u::
-40
-80
16
0N
::c 12
E
.,
~
-
"
"'"'
8
4
!£
D.
0
0 2 4 6 8 10 12 14
600
:[ 400
"'
E
.2
200
~
(seconds)
0
0 2 4 6 6 10 12 14
!20
80
'E
"-
40
;..
~
0
0 4 6 10 14
i:i: -40
~0
-120
24
9:
:r:
E 16
.!!.
I!?
""' 8
"'I!?
0.
0
0 2 4 B 8 10 12 14
Time (seconds)
0 2 4 6 B 10 12 14
FIGURE 3-19 Pressure-controlled ventil ation (CMV).
FIGURE 3-20 Volume assist-con trol ventilation (V-ACV), decelerating ramp flow .
80
-E
c.
40
'="' 0 + ++_rl Id I I I II I I I I I
3l:
0 4 8 10 12
u...
-40
-00
16
-£
0
12
E
0
~
Q) 8
~
::I
(/)
(/)
Q)
4
~
0..
0
0 2 4 6 8 10 12 14
600
=E 400
~
Ill
E
::1
0 200
>
Tim (seconds)
0
0 2 4 6 8 10 12 14
4 6 12 14
++-t-+++·• · f ... I JI l • +t+-•+ -t ~{ +f ! I I I I I I I1I I I I, I I I fI I ; I II I I I It I i I II t J I I I I I I II I I I II I I I I

2 4 6 B 10 12 14
Time (secoll
4 6 8 10 12 14
FIGURE 3-21 Pressure assist-control ventilation (P-ACV).
This can be achieved on some ventilators in which the ACM the patient is allowed to breathe spontaneously from ei-
ra te can be set to zero. This mode is normally referred to as ther a d emand valve or a continuous flow of gas (Figs. 3-23
pressure support (see later section). and 3-24). The first applications of IMV were achieved by
setting the ventilator in the control mode and incorporat-
ing a one-way valve into the inspiratory limb of the cir-
INTERMITTENT MANDATORY VENTILATION (IMV)
cuit to allow the patient to breathe spontaneously from
IMV may be pressure- or volume-targeted. With this mode, atmosphere or from a seconda~ry continuous-flow system
CMV breaths are delivered at a set rate and volume (or between mandatory breaths. 47, 48 These early systems
pressure).40 - 46 In between the machine-delivered breaths, essentially coupled a parallel gas-fl ow system with
FIGURE 3-22 Volume-assisted ventilation (VAV), decelerating ramp flow .
4 B 14
2 4 6 B 10 12 14
me (seconds)
2 4 6 B 10 12 14
BJ
40 ..
E Q.
= 0
J
~
2 8
lJ...
-40
-80
24
q:
I
E 16
~
"
!!!
~ 8
"'
!!! -----.../---
a.
4 6 8 10 12 14
0 2 6 8 10 12 14
FIGURE 3-23 Pressure-controlled intermittent mandatory ventilation (PC-IMV).
the inspiratory limb of the ventilator circuit via a one-way tion w ith the patient's inspiratory effort during fMV re-
valve in such a m anner that gas did not flow continuously sults in increased work of breathing and hemodynamic
through the circuit.49 - 5" Such systems aJlow accurate mea- compromise.52•53
surements of exhaled tidal volumes. They are associated
with a high inspiratory work of breathing, however, par- SYNCHRONIZED lNTERMITIENT MANDATORY
ticularly if PEEP is in use. 47 IMV is available on older·
VENTILATION (SIMV)
generation ventilators that are still in use but not manufac-
tured any longer. It has been replaced on newer-generation This mode of ventilation is similar to IMV and available
ventila tors by synchronized intermittent mandatory ven- with pressure (Fig. 3-25) and volume (Fig. 3-26) targeting,
tilation (SIMV) (see next section). The lack of coordina- except that the ventilator delivers the mandatory breaths in
FIGURE 3-24 Volume-controlled intermittent mandatory ventilation (VC-IMV), decelerating ramp flow .
2 6 8 10 12 14
Time ds)
2 4 6 8 10 12 14
8 14
8 10 12 14
Time (sec
8 10 12 14
FIGURE 3-25 Pressure-controlled synchronized intermittent mandatory ventilation (PC-SIMV).
synchrony with the patient's inspiratory efforts, and gas is tory rate. As a result, the mandatory rate may vary from its
supplied by a patient-triggered demand system d uring set rate depending on when triggering occurs in a series of
spontaneous breaths.54' 55 In essence, the unit functions in windows. If a patient's inspiratory effort is detected w hile
the assist-control mode only during "windows" of time es- the w indow is open, a synchronized breath is delivered. If
tablished by the manufacturer (Fig. 3-27). The time available no patient effort is detected at the time the window closes,
within each window for patient triggering varies among the ventilator delivers a mandatory breath. This avoids
manufacturers but is usu ally a function of the set respira- the stacking of ma ndatory breaths on top of spontaneous
FIGURE 3-26 Volume-controlled synchronized intermittent mandatory ventilation (VC-SIMV), decelerating ramp flow .
40
e
Q.
0
= 4 B 12 14
~
u: -40
-80
16
~
0
J:
E
"' 12
<J
~
8
e
"'
.,"'
fJ)
-
a.
4
0 •
D 2 4 6 8 10 12 14
600
i
01
400 ·
E
..2
200
~
0
. .... ..........0
" ..... .......... 4......... ..... ....... ....6.,,...........
' ' '" ' "" '"'" '
8...... ""... ................
10 ...... .... ... 12 14
CPAP is a specific mode on mechanical ventilators, whereas

PEEP is the elevation of baseline system pressure during
other positive-pressure modes of ventilation. Both establish
d>
~
;:J
A an elevated system baseline pressure by manipulating op-
"'"'
Q)
~
eration of the ventilator's exhalation valve (see the section
0. Exhalation Valves below for details), although the CPAP
mode can be used without an elevation of baseline pressure
~- as.slst (0 cmH20 CPAP).
window - - -
PRESSURE- CONTROLLED INVERSE- RATIO
time
VENTILATION (PCIRV)
FIGURE 3-27 Depiction of the SIMV assist window. In assisted
breaths (A), the ventilator senses the patient's inspiratory effort PCIRV is a variation of PCV il1 which inspiration is longer
and triggers the breath in synchrony with the patient's desires. In than expiration.60 - 68 PCIRV typically is initiated by select-
contras t, if patient effort is not sensed by the end of the assist time ing PCV and adjusting settings to provide the desired I:E
window (B), a controlled p ositive-pressure breath is delivered.
ratio or inspiratory time (Fig. 3-30). In some ventilators, the
breaths or machine inspiration or expiration being delivered I:E ratio is set and does not vary when the respiratory rate
out of phase with the patient's desired phase of ventilation. is changed (e.g., Servo 300). ln other ventilators, the inspi-
In addition, pressure support can be provided during spon- ratory time is set and does not vary when the rate setting
taneous breathing with either pressure- or volume-targeted is changed (e.g., Puritan-Bennett 840), whereas others al-
SIMV. low the user to select either inspiratory time or I:E ratio as
the constant when respiratory rate is changed (e.g., Puritan-
Bennett 7200).
CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP)
AIRWAY PRESSURE- RELEASE VENTILATION (APRV)
This is a spontaneous breathing mode (Fig. 3-28); no me-
chanical positive-pressure breaths are delivered. The only APRV is described as two levelsof CPAP (high and low) that
variables set by the clinician ar e the level of CPAP and the are applied for defined periods of time where spontaneous
sensitivity of the demand system. As noted in Fig. 3-29, dif- breathing is allowed a t both levels (Fig. 3-31).69- 73 Normally,
ferences do exist among ventilators with regard to patient inspiratory time is longer than expiratory time. The clinician
effort during CPAP,56 although the problems observed with sets the two levels of CPAP and the amount of time spent
earber systems and high levels of work of breathing im- at each level. APRV is similar to pressure-controlled SIMV,
posed have been eliminated .57,s8 In fact, the u se of CPAP pressure-controlled ventilation (PCV), or PCIRV. If the pa-
via a mechanical ventilator has been advocated in recent tient is not breathing spontaneously, PCIRV and PCV are
weaning guidebnes.59 CPAP often is confused with PEEP. indistinguishable from APRV. ln the initial application of
FIGURE 3-28 Continuous positive airway pressure (CPAP).
40
20
e <>.
= 0 H
~ 4 6 10 12
G:
-20
-40
10
6 B
"'
J:
E
.B. 6
e 4
.,"'"'
2
"'
ci:
0 ++-t-+++++++-1-++++1-+·H I , , t I I II I I I ' I I I f I l I I I I• I f I tI I I I II I f I I j • 1 I II I I I II t I I I I I I I I
0 2 4 6 B 10 12 14
200
160
"""
g
., 120
E
::> 80
0
> 40
0
0 2 4 6 8 10 12 14
sec
0 0 0 m CD
0(It
0 BEAR(f) •
BEAR (F) • DEAR(P) •
BEAR (P) EVITA (F)
F.VlTA (F) • GALILEO(F) •
GM.ILEO(F) • GALILEO(P) •
GALl l EO (P) • c
~
PB740(F)
P8740(F)
PB140(f)
PBI40(F)
P8840 (P)
POI40(P)
SJOO (F)
SJOO (F)
SJOO(P) SJOO (P}
T-BIRD (f) T-BIRO (f)
A B
I
N 0
0
HEAR If) • BEAR If)
BEAR (P) BEAR IP)
t VITA If) • EVITA If )
CIALILEO If) GA LIU:O lfl

•
GALILF.O (P) GALI LF.O trl
•
P8740 (f) PR740 If)
PBI 40 (f) PB840 (f)
P8140 (P) PB840 (P)
S300 (F) 5300(f)
SJOO (P) «;) 00 !Pl

T-BIRO (f) r-BIRD If >
c D
FIGURE 3·29 Ins piratory-phase variables evaluated during CPAP on a number of current-generation JCU ventilators: (A) inspiratory
trigger delay time IDT); (B) inspiratory trigger pressure IPTI; (C) triggering pressure-time p roduct (PTP,); (D) inspiratory pressure-time
product (PTPT>· Mean ± SO of al l inspiratory peak flows. F, flow triggering; P, pressure triggering; Bear, Bear 1000; Evita, D rager Evita;
Galileo, Hamilton Galileo; PB 740, Puritan-Bennett 740; 840, Puritan Bennett 840; S300, Maquet Servo 300; T· Bird, Viasys T-Bird. • P < 0.05
versus flow-triggered 5300. (Used, w itl1 pen11issiou, from Takeuchi et al: A11estl1esiology 96:162- n, 2002.)
80
~
40
'§'
a. 0
= 2 4 6 10 12 14
~ -40
i:i:
-00
-120
20
0,-, 16
I
E
(..) 12
~
"'5
(J)
8
(J)
!!1 4
0.
0
0 2 4 6 8 10 12 14
1000
= 800
.s 1).) 600
E
40
0 "'
>
Time (seconds)
0
0 2 4 6 8 10 12 14
FIGURE 3-30 Pressure-controlled in verse-ratio ventilation (PC-IRV).
APRV, it was assembled using a modified continuous-flow coordinated. As a result, breath s tacking is avoided . In ad-
CPAP system (Fig. 3-32). In essence, this system requires a dition, pressure support can be added to the spontaneous
high-flow gas delivery, a rapid-response solenoid valve, and breaths at either or both levels of CPAP (Fig. 3-33).
two independent PEEP valves. The solenoid valve switches
gas flow in the expiratory limb of the system from one PEEP
valve to the otherto achieve the two different levels o f CPAP. PRESSURE-SUPPORT VENTILATION (PSV)
APRV is now available commercially on n ew-generation
This is a pressure-targeted m ode where the patient's insp i-
mech anical ventilators (i.e., Drager Evita).
ratory effort is supported by the ventila tor at a preset level of
inspiratory pressure? 4 - 77 lnspiration is initiated by patient
effort and terminated primarily w hen inspiratory flow falls
BILEVEL ALRWAY PRESSURE
to a ventilator-specific level (Fig. 3-34). During PSV, the p a-
VENTILATION (BILEVEL) tient d etermines the respiratory rate, inspiratory time, a nd
Bilevel is a modification of APRV similar to the improve- tidal volume; the ventilator only controls the inspiratory
ment seen when SlMV was introduced to replace IMV. Dur- pressure level. PSV can be combined with SIMV (Figs. 3-35
ing bilevel ventilation, the patient's spontaneous breathing and 3-36) and applied to the spontan eous breaths during
efforts and the chan ge from on e CPAP level to the o ther are bilevel pressure ventilation (Fig. 3-37).
FIGURE 3-31 Airway p ressure-release ventilation (APRV).

CHAPTER 3 BASICPRINCIPLESOFVENTILATORMACHINERY 73
cific period of inspiratory time, exceeds the set level by a
specific pressure (e.g., +3 cmH2 0).79 In addition, if inspi-
ratory time exceeds a manufacturer's specific time period
(e.g., 3 seconds), inspiration will end (Table 3-7).79
Patient-ventilator dyssynchrony can occur during
pressure-support ventilation. The three primarily reasons
for dyssynchrony are an inappropriate pressure level, an
inappropriate initial flow delivery, and an inappropriate
cycling criterion (terminal flow).80 Pressure level can be
corrected easily by increasing or decreasing the pressure
setting. It should be remembered that setting too high
A a pressure level can force too large a tidal volume and
increase the likelihood of air trapping and auto-PEEP.81
Frequently, the correct pressure adjustment is a decrease in
pressure level to allow a tidal volume consistent with the
patient's desired tidal volume.
Dyssynduony at the onset and termination of a pressure-
support breath can be corrected by varying the rate of gas
delivery at the onset of inspiration or varying the percent
of the peak-flow decrease required to cycle the breath to
exhalation. The addition of rise time and inspiratory termi-
nation criteria as adjuncts to pressure-targeted breaths can
improve synchrony at these two points of the breath.
RISE TIME
B As illustrated in Fig. 3-38, the rise-time control on ventila-
FIGURE 3-32 Schematic presentation of APRV w ith an tors alters the slope of the rise in flow (to its peak level) at
inspiratory CPAP level set at 30 cmH20 and an expiratory CPAP the onset of a pressure-targeted breath.81 Rise time on mos t
level set at 10 cmH20. Flow is produced by a high-flow g enerator, ventilators is active during all pressure-targeted modes of
and a solenoid valve is used to move gas flow to one of the PEEP ventilation. A change in rise time from rapid to slow has
valves (+ 30 and + 10). A High CPAP period. B. Low CPAP period.
three potential effects during pressure support First, the
(Used, with permission, from Cane eta /: Chest 200:460-3, 1991.)
time to peak airway pressure (and flow) is increased. Sec-
ond, the actual peak flow obtained is decreased. Third, the
PSV is triggered only by the patient; when the pressure- inspiratory time rna y be increased to maintain the same tidal
support breath is triggered, the ventilator delivers sufficient volume. As shown in Figs. 3-38 and 3-39, too rapid a rise
flow to rapidly achieve the set pressure level. After the pres- time causes airway pressure to overshoot the peak level at
sure is established, flow must decrease rapidly to ensure that the onset of the breath . In this situation, the rise time should
the pressure does not exceed the set level. When the flow be slowed.82 As illus trated in Fig. 3-39, however, too slow
decreases to the target cycling level (normally 25% of peak a rise time also results in air hunger and a convex initial
flow), ventilator inspiration is terminated.78 The breath also airway pressure curve.82 In this situation, rise time should
may be terminated if pressure, after a manufacturer's spe- be increased.
FIGURE 3-33 Bilevel airway pressure ventilation (bilevel) with p ressure support at the low CPAP level.
~~~~~~HH~HHHH~~~~~ · I I I I I I I I il~ l ~·I I I II I I I I II I I II I I I I I II I II I •I

6 8 10 12 14
ro
~
40
E
Q.
= 0
~
0 6 B 14
u: -40
-80
16
0
l:.N 12
E
s. B
~
::>
"'"' 4
~
Q_
0
0 2 4 6 B 10 12 14
500
=
E.
400
300
"'
E
::3 200
~ 100
Time (seconds)
0
0 2 4 . ........ .. 6 . ~· ' . '. B. ~ .. ... ....10" 12 14
FIGURE 3-34 Pressure-support ventilation (PSV).
INSPIRATORY TERMINATION CRITERIA situation, the flow setting for terminating the inspiration (as
TI1is control is effective only in pressure support. It adjusts a percent of peak flow) is too low. The problem is corrected
the percent of peak flow terminating the pressure-support by increasing the latter setting until the spike in airway pres-
breath. If the airway press ure increases above the set level at sure at the end of the breath disappears. The opposite prob-
the end of a pressure-support breath, the patient is activat- lem a lso can occur, as illustrated in Fig. 3-41, where machine
ing the expiratory muscles to achieve exhalation before the inspiration ends before the patient is ready to exhale.85 In
ventilator is ready to permit exhalation (Fig. 3-40).83•84 In this this case, both air way pressure and flow tracing appear as
FIGURE 3-35 Volume-controlled synchronized intermittent mandatory ventilation (VC-SIMV) with pressure-support ventilation,
decelerating ramp flow.
00
~
AO
E
c.
<::;.
0
~ 6 6 12 14
u.
-AO
-00
16
'?:
J: 12
E
u
~
8
"'
:;
"' 4
a:"'"'
0
0 2 4 6 B 10 12 1-4
600
=E 400
~
"'E
.a0 200
>
(seconds)
0
.. .. . ..0. 2 4 6 6 10 12 14
0 2 4 8 1
FIGURE 3-36 Pressure-controlled synchronized intermittent mandatory ventilation (PC-SIMV) with pr essure-support ventilation.
if a secondary small breath is provided immediately after amplification of these variables. Thus
the end of the normal breath. The problem is corrected by
decreasing the flow setting for terminating inspiration (per-
cent of the peak flow) until the abnormality is eliminated.
where f.t and f2 are the amplification factors. In practical ap-
plication, £1 and f2 become volume (elastic) and flow (resis-
PROPORTIONAL- ASSIST VENTILATION (PAV)
tive) assist settings, respectively. Theoretically, this should
produce an ideal relationship between inspiratory effort and
This mode permits free flow of gas to the patient in response gas delivery from the ventilator. When adjusting the volwne
to patient-generated effort (Fig. 3-42).5' 6 The difference be- and flow amplification controls, the clinician is determining
tween pressure at the patient's proximal airway and pres- the level of unloading regardless of patient volume or flow
sure in the piston chamber of the device creates flow and vol- requirements. That is, if the ventilator is set to unload patient
ume signals that can be amplified by the device. The airway effort at the 50% level, all breaths are unloaded at this level
pressure produced by the device to support the patient's regardless of volume or inspiratory flow rate. This mode
inspiratory effort is determined by patient-generated inspi- is equivalent to PSV in a number of settings86 - 89 and can
ratory flow ('/) and volume (V) and clinician-determined support patients during exercise.
FIGURE 3-37 Bilevel pressure ventilation with press ure support applied to breaths at both the high and low CPAP levels.
~~f
...
~
E 40
= 0
~
0 2 4 12
lJ.. ·40
.81)
-120
40
0
r.""
E
3D
~
!':' 20
"'"' 10
!'"':'
Q.
0
0
TABLE 3-7 Mechanisms Cycling Pressure Support in All #1 PSsel <~5 # 7

Ventilators ON 5Q f- VT =830 VT •930 Vr- 620
I
E
s 25
.Mil'
• Primary cycling mechanism: a decrease in inspiratory flow to
a specific percentage of peak flow, usuaJJy 25%. This is adjustable •
~
on some ventilators. 0 r- '--- ..,. \..-. I
• s~onclary cycling mechanism: pressure exceeding target by a # 1 PSse1=20 #6 # 7

specific level (i.e., 3 cmH20) after inspira tory time has exceeded a 0.. 50 Vt •728
::r. Vr-910 Vr =900
manufacturer-specific period. E
• Tertiary cycling mechanism: inspiratory time exceeding a ~ 25
manufacturer-specific period, usually about 2-3 st'Conds. ~
10
,& f\, ,1 \:J\
0 5 10 0 5 10
Time (secJ
BiPAP FIGURE 3-39 Examples of airway pressure tracings in two

patients with different initial peak flows during pressure support
BiPAP is a manufacturer-established term (Respironics) (PS). Initial PS flows are expressed as one of seven discrete
defining the noninvasive applkation of positive-pressure settings ranging from maximal (1) to minimal (7). For these two
ventilation.90 This mode is designed specifically to pro- patients, maximal, optimal, and minimal initial PS flow settings
vide partial ventilator support. It is the same as PSV with are depicted. In the top p anels, the optimal initial PS flow setting
for this patient was the third fastest (3). Note that the attained
PEEP or PCV w ith PEEP.91 This mode is available on spe-
preSS\tre and tidal volume (VT) appeared high est and the
cific ventilators designed to provide noninvasive ventila- inspiratory time (T1) longest at the optimal initial PS flow setting.
tion. A pressure-controlling valve maintains pressure atone In the bottom panels, the optimal initial PS fl ow setting for this
of two levels, PEEP (the expiratory positive airway pres- patient was the second slowest (6). Again note that the attained
sure, EPAP) and pressure support (the ins piratory positive pressure and VT appeared highest and the T 1 longest at th e
airway pressure level, !PAP). These devices and this mode optimal injtiaJ PS flow setting. (Used, wit/1p ermissiou, from
have been used extensively to manage various pathophys- Mncl11tyre et at: Ches t 99:134-.S, 1991.)
iologies with positive pressure noninvasively (see Chap. 4
for details).91 - 96 FIGURE 3-40 Recordings of flow , airway pressure (Paw), and
transversus abdominis EMG in a criticaLly iU patient with COPD
MANDATORY MINUTE VENTILATION (MMV) receiving pressure support of 20 cmH20. The onset of expiratory
muscle activity (vertical dotted /iue) occu rred when mechanical
TI1is was the first mode of ventilation in which the ven- inflation was only partly compl eted. Note the spike in airway
tilator changed gas delivery based on patient response or pressure at the end of the breath coinciding with the activation of
the first mode considered to constitute computerized con- the transversus abdominis muscle. (Used, with permission, from
trol of ventilation. Patients were allowed to breathe spon- Parathasaratl1y et al: Am J Respir Crit Care M ed 158:1471- 8, 1998.)
taneously, but the ventilato r ensured a minimum level of 2
~ v
0 ~
FIGURE 3-38 Effect of changing inspiratory rise time in a patient - :::r
u.. ~
preferring a midrange flow . A. Flow is in excess of patient
demand, and a pressure spike is seen. B. As flow rate is
decreased, inspiratory time (Tr) lengthens, and the pressure spike
is absent. Machine output matches patient demand. C. When
flow rate is further reduced patient demand exceeds machine
flow rate, and T 1 falls. Deformation of the pressure waveform
during the rise to the set PSV level is also seen in C. (Used, with
permission, ft·om Campbell et al: Respir Care 38:526-37, 1993.)
105 l.. / mfn ·-"'c:

A ·-E ~
"'
!:!.
10
0 c
"C ::s
.&l i!':
I'd
64 L / mln "'::l -e"'
~
B
1.2 se-es· ... ..!!
"'
CIJ
> ~
"' ~ 10
c: uJ
._
I'd
c 0.9 S&e&
49 L / mln 1-
0 3 6
TIMe Time (sec)
Termination Criterion 5% clinician-determined ventilation. 97- 100 With MMV, the ven-
tilator monitors the patient's minute ventilation, and the
:1 ,...
1\. 1\. A 1\.
amount of ventilator support provided is adjusted automat-
L/a ..) . ....L • '.). >. L ': ~? ~- ~ ~.?"'"' u•
~7
. - -~
/
-~
/ ically to compensate for fluctuations in the level of sponta-
o.a
1 neous breathing. The assurance of a preset level of ventila-
tion can be achieved either by increasing the tidal volume
L u
......c _....... ~--
. .. .. f-·· .. -~-· - ~--
..--:-:-.: or by increasing the frequency of mandatory breath deliv-
-0 . 2 ery. That is, the ventilator is allowed to alter gas delivery
30
r- ,...... r- p based on feedback from the patient. Although many of the
r- h
e m r-
HeD ~ - - -- .. -- ,.. ... - ...... ......... 1-·-·· -.. - .... r .,. . . . . . .
--- .... ··-·· - A
w models used to achieve MMV were crude, they opened the
-10
eo door to more sophisticated approaches to closed-loop venti-
C:ln ""-.. ---- .. -.. ----- ----- -.- .. ---- ----.. .... --- ---- 1- •••• t::
p
s
lation. The major problem with MMV was that the ventilator
made adjustments based only on minute ventilation. In
other words, the ventilator did not distinguish between a
tidal volume of 0.6liter with a rate of 10 breaths per minute
TerminationCriterion 45% and a tidal volume of O.l Sliter and a rate of 40 breaths per
a minute. The Drager Evita 4 is the only current-generation
L/•
f\.
-__b: " ---- ··h: "'-h· .
u:
r ~
1/\
~
·h:.. u• ventilator that includes this mode.
1
o.a
P RESSUR E-REGULATED V O LUME C O N T R OL (PRVC)
L u
I"·· · -· --~ ~ - -
.E•••• .. . . . .... -~ . -· - -~
This mode is a form of closed-loop ventilation that has com-
-o.e
30
p bined the features of volume and pressure ventilation (Fig.
In n../1 "0 rl h
HaD . ....... - - ~ -- - .-::.. ---- .. .. ..... ... 1- ••• ... ..... - ------ ---- .. ---
A
w 3-43). In essence, the clinician sets a target tidal volume and
-10 maximum pressure level. The ventilator attempts to achieve
eo ~ / ..... £
/"
---- .. ----- ----- .. --- ----- -····

/ /
"
--------- -.. . . -.. --.
p the volume target using a pressure-control gas-delivery for-
E
s mat at the lowest possible airway pressure.101 When acti-
vated, the first delivered breath is a test breath at some min-
FIGURE 3-41 Flow (V), volume (V), airway pressure (Paw), an d imal pressure level (5-1 0 cmH20), which is used to calculate
esophageal pressure (Pes) curves with termination criterion (TC) patient compliance. The next few breaths may be delivered
5% and 45% during 10 cmH2 0 of pressure-support ventilation. at a pressme below the calculated pressure needed to de-
With TC 5%, inspiratory flow terminated simultaneously with liver the target tidal volume as a further test. After this,
the cessation of the patient's inspiratory effort estimated by Pes. the calculated pressure is applied. If the target volume is
In contrast, prematu re termination with double breathing exceeded, the pressure limit is decreased by 1- 3 cmH 20 on
occurred wi th TC 45%. Work of breathing also increased from each breath until the target tidal volume is reached. Sim-
0.42 ]/li ter with TC 5% to 0.64 ]/liter wi th TC 45%. (Used, with ilarly, if the volume is low, pressure is increased by 1-3
permission, from Tokiaka eta/: Anesth Analg 92:161-5, 2001.)
cmH20 on each breath until the target is met. Of concern
with this approach is the potential for an inappropriate
decrease in delivered airway pressure when the patient's
inspiratory demand is increased as a result of increased
?;
0
-
( ,)
Q)
f/)
FIGURE 3-42 Airway pressure
(Paw), volume, an d flow during
proportional-assist ventilation and
...J
LL.
w
-
.....
.6
during spontaneous breathing
(arrow). Note the variation in both
pressure and volume on a
breath-to-breath basis. (Used, with
--
~ .4 pennission, from Younes et a.l: Am
::> Rev Respir Dis 145:114-20, 1992.)
...J
0 .2
>
~
«< :I:
-
0
N
0
20
10
n. E
- (,) 0
Upper
Pressure
Llmil Resp Cyckl FIGURE 3-43 Pressure and
flow waveforms during
Exp.
pressure-reg\tlated volu me
Pressure con trol: (1) 5 em H2 0 test
breath; (2, 3) adjustment of
pressure target to ensu re
delivered tidal volume; (4, 5)
® ® Time p ressure target con stant; (6)
® pressure target decr eased

because tid al volume is higher
than the target (see tex t for
details). Used witll p ermision;
Product literature Maquet
Servo I Ventila tor, users
m an ual US version No.
66-00-261-E313E Solna,
Sweden 2004.)
stress (e.g., hypoxemia, increased temperature, pain, anx- VOLUME-ASSURED PRESSURE SUPPORT (VAPS)
iety). That is, ventilator support can be decreased inappro-
VAPS also combines the benefits of pressure and volume
priately in the presence of an increase in ventilatory demand
ventilation. 102•103 The clinician sets a pressure-support level,
if the increased d emand increases tidal volume. This mode
a peak flow, and a tidal volume. If patient demand is high
is currently available on numerous ventilators by different
relative to the peak flow and tidal volume settings, VAl'S
names (Table 3-8).
functions simila r to PSV but guarantees a minimum tidal
volume delivery (Fig. 3-45). 104 If patient demand is low,
however, gas is d elivered as a ty pical ACV breath. This
VOLUME SUPPORT (VS) approach to dosed-loop ventila tion was available on the
This mode of ventilation is simila r to PRVC. It combines Bird 8400 and Bear 1000 ventilators but is not available on
volume-targeted ventilation w ith pressure support in spon- any of the newest-generation ventilators.
taneously breathing patients (Fig. 3-44). Similar to PRVC, it
performs an initial tes t breath (low pressure) to calculate AUTOMATIC T UBE COMPENSATION (AT C)
compliance and then administers additional test breaths at
a higher pressure before going to the calculated pressure. 101 This mode of ventilation is similar to the flow assist of
The inspira tory pressure is controlled automatically be- PAV except that it is designed to mainta in tracheal pres-
tween PEEP and tl1e set upper pressure limit. The pa- sure at baseline (PEEP level) during both inspiration and
tient has control of the inspiratory phase as in pressure expiration . Data from Guttman et alws d emonstra ted that if
support, w hereas w ith PRVC, inspiratory time, I:E ratio, the resistance properties of the artificial airway were pro-
and rate are set. If a patient's rate drops below the apneic grammed into a ventila tor, the ventilator would be able to
alarm threshold during volume support, some ven tilators calculate tracheal pressure if flow could be measured con-
switch automatically to PRVC ventilation. Similar concerns tinuously (which is done by all ventilators) (Fig. 3-46). With
as with PRVC regarding patients with s trong ventilatory activation of this mode, the type and size of the airway must
drives and large tidal volume should be exercised. See Ta- be programmed into the ventilator, as well as the percent of
ble 3-8 for select ventilators in w hich this mode is avail- ATC to be a pplied (100% versus lower per centages) . In ad-
able. dition, some ventilators apply ATC only during inspiration
(i.e., Puritan-Bennett 840); others allow application during
both inspiration and expiration (i.e., Drager Evita). Expira-
TABLE 3-8 Terms Used by Various Manufacturers to Define tory ATC is of concern because it applies a negative airway
Pressure-Regulated Volume Control (PRVC) o.r Volume- pressure, rapidly dropping pressure in the lung and poten-
Support Mod es (VS) tially increasing the level of air trapping. ATC seems most
Ventilator PRVC vs useful in tl1e patient witl1 a strong ventilatory drive (Fig.
3-47)"06 . As with PAV, there is no control over any normal
Servo300 PRVC vs ventilatory variable. ATC only controls tracheal pressure.
Servo I PRVC vs Thus patients may assume a ra pid-sha llow or slow-large
Drager Evita Autoflow A" tidal volume pattern.
Viasys Vvea PRVC NA
e-Vent PRVC vs
Datex-Ohmeda Volume Guarantee A ADAPTIVE-SUPPORT VENTILATION (ASV)
Drager Badylog Volwne Guarantee Volume Guarantee
This form of computerized control of ventilation is available
"NA, not available. only on the H amilton ventilators, and it represents the most
CHAPTER3 BASICPRfNCIPLESOFVENTILATORMACHINERY 79
Upper
Pressure
Pr essure Lim'It ' " - min
t t
~-~Q-.(J!i20 n
em
c:,..., 5
re:Sen~r;
Trigg.
[ ]
Apnea ••••,
j :' ,~ ~
lime
Fiow CD ®® @) ® ® 0 ®
FIGURE 3-44 Pressure and flow waveforms during volume support: (1) test breath; (2-5) adjustment of pressure target to ensure delivered
tidal volume; (5, 6) pressure limit decreas ed to maintain tidal volume at target level; (7) period of apneic ventilation; (8) ventilator switch es
to pressure-regulated control mode. Used with permision: Product literature Maquet Servo I Ventilator, users manual US version No.
66-00-261-E313E Solna, Sweden 2004.
sophisticated form of computerized control of ventilation ment of the patient's dynamic compliance and expiratory
available. This mode is designed to establish a ventilatory time constant to determine the ideal ventilatory pattern. A
pattern that results in the least work of breathing based tidal volume versus rate curve for the minute volume se-
on the original data of Otis,'~ 07 w here work of breathing is lected is determined, as well as high and low limits on the
related to compliance and resistance. Tha t is, if compliance rate and tidal volume. In addition, a target zone of rate and
is decreased, a rapid-shallow pattern results in the least tidal volume is established (Fig. 3-48). If the patient moves
work of breathing. Conversely, if resistance is increased, outside the defined zone, specific adjustments of airway
a slow rate w ith a large tidal volume results in the least pressure and ra te are established to force the ventilatory
work of breathing. The patient's weight and the percent of pattern into the target zone (Fig. 3-49). As w ith many of
ideal tidal volume (25- 350%) to be delivered must be pro- these new modes, gas delivery is based on a pressure-target
grammed. The ventilator uses these data as well as measure- delivery pattern. Depending on the relationship between
a patient's actual rate and the ideal ventilatory rate, venti-
lation can change between assisted and controlled ventila-
FIGURE 3-45 The possible breath types during volume-assured
tion. ASV also can be active in SfMV. Currently, ASV is not
pressure sup port (VAPS). In breath A , the set tidal volume and available in the United States. It is called adaptive tidal vol-
delivered tidal volume arc equal. This is a pressure-support ume ventilation, where the ventilator provides the clinician
breath (patient triggered, pressure limited, and flow cycled). with the adjustments needed, but the clinician must make
Breath B represents a reduction in p atient effort. As flow
decelerates, the ventilator determines that delivered tidal volume
will be less than Ute m inimum set volume. At the shaded portion FIGURE 3-46 Volume-pressure diagram in a traclteally intubated
of the graph, the breath cltanges from a pressure- to a patient during spontaneous breathing with inspiratory pressure
volume-limited (constant-flow) breath. Breath C demonstrates a support (PEEP = 5 cmH20, pressure support = 5 cmH20 ). The
worsening of comp liance and the possibility of extending pressure drop across the endotraclteal tube (aPml is <Em
inspiratory time to ens ure the minintum tidal volume delivery. indicated during both inspiration and expiration by a broken
Breath D represents a pressure-support breath in whiclt the tidal arrow. The direction of the arrow points from airway pressure to
volume is greater than the set tidal volume. This kind of breath traclteal pressure. (Used, with permission, Gu.ttman et a/: Anes
allowed during VAPS may aid in reducing work of breathing and 79:503-1.3, 199.3.)
dyspnea. (Used, with perm.ission, from Brausou et al: Respir Clin
North Am 7:397-408, 2001.) V[mij
600
·'
I
--~
P.-.tsure ... /'
,'
L&Vel
I
I
I
'
I :
........
J tJPETT-e
300 ;(
I I ; ·
;
li
/ IJPETT-i :· ~f
...,.. •••••••• '!
I '
Peek I
Paw
I
·>
Flow
Selling
I
\
' ,' Ptrach,calcvtatecl

...· Ptrach.measuree
·. /
TIME • 0 4 8 • 12 16
A B c D P [cmHPJ
p ost-operative patient c ritically ill patient with COPD

--Paw
P [mbar] P [mbar]
20 IPS JOmbar 40 IPS 15mbar --F\rac:n
-- ---- PEEP
30
20
5 10
t[s} t (s)
o~--~--~--~------------~----
0 1 2 3
0
0 1 2 3
P (mbar] P (mbar)
15 ATC 40 ATC
30
- .. -- ..
t[s]
0 ~-----~--~----~------~~
0 1 :>
FIGURE 3-47 Airway pressure and tracheal p ressu re curves during pressure support (IPS) (top) an d au tomatic tube compensation (ATC)
(bottom) in a patien t after open-heart su rgery (/eft) and a critically ill p atient with chronic ob structive pulmonary disease COPD (rig ltt).
Note that alth ough the ventilator lowers Paw during expirati on to subatmosph eric p resS\ue (botto m left), controlling the expiratory valve
ensures that Ptrach is above or equal to PEEP. Th e p atient wi th acu te resp iratory insufficiency dur ing ATC generates an inspiratory gas
flow of greater than 2 liters/s (bottom rigllt), which accoun ts for part of the d eviation between P1rad 1 an d PEEP. (llsed, witll permission, fro m
Fabry et a/: Intens ive Care Mcd 23:545-52, 1997.)
FIGURE 3-48 Graphic depicting target ventilatory pattern during adaptive-su pport ventilation (15 breaths per min ute with a 535-ml tidal
volu me). In additi on, the respira tory rate versu s tidal volum e curve for the specific minute ven tilation chosen is illustrated. The do tted-
line box indicates the limits of rate an d tidal volume. (Used, w itl1 permission, fro m Campbell et al: Respir Cliu No rth Am 9:425-40, 2001.)
2.5 --
2.25
Safety Box Imposed by ASV rules base
2 ~--· ··-- ·
1.75 • a. 111• • • ilt:lll. fill* I - A. • •• •a 1111 •A.A..A...&JI.• A ill. 111• Ill: Ill a •111: 1111. *ill.**. Ill:. 8 •• I.~'•• 8 *I. A•••• a :t:. a . •
••
•• ..•••
Q)
E 1.5
\ •
·- ·- - ·-··-·--·· -·--··- ........-_... .....- ..--
:s
0 1.25
:
\ •
•
••
.••
-
>
ca
"C
1 ~ •
•
i= • •
••• / Target Breathing Pattern (14 x 535) •
0.75
0.5 -
•
:
••
• '~
.••••••••••••••••••••••••••••••
•
.. - .. - ~
• •• •••••••••••••••••• ••••••• ••••••••••••

••
..........
••
•••
•
- -- _ ----- ~-
0.25 - - - -- --
0 - -----,---· - -- . .... . ... - .- - -·- - - · · ,.....-.-.- · - --r - - · ~- - ·
.. .,
0 5 10 15 20 25 30 35 40 45
Frequency
CHAPTER3 BASICPRINCIPLESOFVENTILATORMACHINERY 81
Vrtn98$Ured Patient Management Assistance

I
I
Algorithms
I
I : II A number of companies have included slow-flow pressure-
l volume (P-V) curve algorithms that identify the upper and
V,...target..- - ----------· -------- lower inflection points. One company (Hamilton) also al-
lows construction of the d eflation limb of the P-V curve. The
IV Ill open-lung approach algorithm on the Maquet Servo i assists
the clinician in performing lung recntitment maneuvers and
the performance of a decremental PEEP trial. Volume and
pressure changes during these procedures are identified
'I' fmeasured carefully for the clinician. It is expected that such a lgorithms
f-target will be more widely available on ventilators as the ability
to define precise ventilator management improves in the
Quadr. P 1nop mand.rate future.
+
II
Ventilator Triggering
Ill +
The interaction of a patient with a ventilator occurs essen-
IV + +
tially under two settings: Theventilatordeliversa controlled
breath, regardless of the patient's desire; or delivery of ven-
tilator support can be coordinated with patient effort. Over
the last 25 years, increasing emphasis has been placed on
FIGURE 3-49 Algorithm u sed to dictate adaptive-support ensuring patient synchrony w ith the ventilator. If the ven-
ventilation response to changing patient effort and lung tilator is to function in synchrony with the patient, it must
mechanics in order to maintain the target breathing pattern. respond rapidly to patient inspiratory effort with out impos-
(Used, witlr permission, from Campbell eta/: Respir Cliu Nortlr Am ing considerable work or effort.
9:425-40, 2001.)
the adjustment himself or herself. Limited data are available SITE OF TRIGGER
defining the efficacy of this mode of ventilation.108, 109
With perfect patient-ventila tor interaction, the ventilator
NONINVASIVE VENTILATION (NIV) would trigger in synchrony with electrical impulses orig-
inating in the centra l nervous system. Work is currently
A numberofiCU ventilators designed essentially to provide being done experimentally to evaluate the feasibility of
invasive ventilation (via an artificial airway) also include neurally adjusted ventilatory assist (NAVA). 110•111 Ventilator
modes that make noninvasive ventilation via a facemask triggering from diaphragmatic electromyographic (EMG)
easier. The primary adjustment made automatically by the signals, however, is not currently available clinically. The
ventila tor is leak compensation. In addition, a number of greater the distance from the diaphragm that the ventilator
alarm functions (i.e., low tidal volume) are modified to re- senses patient inspiratory effort, the greater is the potential
duce the number of false-positive alarms. for dyssynchrony or an increase in patient effort necessary
to trigger tl1e ventilator.
Adults, Pediatric Patients, and Neonates The next logical site for ventilator triggering is the trachea.
Pressure changes in the trachea are more directly reflective
An increasing number of the newest-generation ICU ven- of intrapleural pressure changes than pressures measured
tilators are being designed for use across all age groups: in the ventilator circuit; triggering based on tracheal pres-
adults, pediatric patients, and neonates . That is, as a result sur e results in marked decreases in imposed work of breath-
of microprocessor design, ranges and delivery rates can be ing when compared with trig~ering from pressure changes
altered to accommodate specific-sized patients. The same within the ventilator circuit.1 2 - 114 The primary reason for
ventilator can be used one day on an adult and the next day these differences is tl1e resistance to gas flow caused by the
on a 500-g neonate simply by selecting the correct size range. endotracheal tube. 115- 117 The endotracheal tube is a nonlin-
With the increasing cost of ICU ventilators and the small ear resistor. Thus the decrease in work produced by venti-
pediatric and neonatal market, one can expect this trend to lator triggering via sensors located in the trachea versus in
continue. During the last 10 years, more than 10 adult or all- the ventilator circuit is magnified by a decrease in the size of
age-range ventilators have been introduced to the market the endotracheal tube and an increase in ventilator drive.'117
worldwide. Over the same period, no new neonatal venti- Banner et al, 112 using a lung model, clearly demonstrated
lator entered the market. the beneficial effects of ventilator triggering from the
SIZE8 mm ETT
P'E.AK INSPikATOitY •
FLOW IIA'n DEMAHD • 30 90
CU•i~l
CONVEHTIONAL I
,RESSUaE E
TRIOOEJUNG
0 1 .. . , . , . I, . , . J I ' ' '.~ ' ' ' 'I ' ' ' 'I ' ' •.I '' ' I - ."7.";",;-:,.:-:-.-...~--{' .. '
~ I .. .. I " " I
~ 10 ., 20 0 5 10 I~ 20 -5 0 10 15 lO 2.5
~-
1
FLOW- IV
TRIOOYINO E
o, .... ,.. . ,.. 10
' ' ' ' I ' ' ' ' I
IS 10
. ' .. I ..•• I
_, 0
0 • I ' t ..• t •
5
0
10
0 • • t •••• I
IS 10
0 ' I •
' 10 IJ
I
TRACHEAl
PRESSURE
l1t IOOEJtiNQ
o- .... , .... , .... ".' ' t•' ' ' I . ;--:-,--( .. .. I " .. I .
10 u 10 "
10 IS 10
PR£SSURE AT TRACHEAL END OF ENOOTRAClfEAL TUBE (r• HtO)

FIGURE 3-50 Pressure-volume (imposed w ork) loops during spontaneous inhalation (I) and exhalation (E) with continuou s positive
airway pressure (10 cmH2 0) via an 8-m m inte rnal-diameter endotracheal tube (EIT) at peak inspiratory flow rates of 30, 60, an d 90
liters/min during conventional pressure triggering, flow (flow-by) triggering, and trach eal triggering. The shaded area circum scribed
lvithin th e ins piratoty portion of the loops is the inspiratory imposed work of b reathing. Note that im p osed work increased with peak
inspira tory flow and always was least with tracheal triggering. (Used, with permiss ion, from Banner eta /: Crit Care Med 21:183-90, 1993.)
tracheal site. They compared imposed work of breathing Both magnitude of pressure change and delay in trigger
calculated from pressures measured within the trachea activation are important in relation to triggering. Magnitude
during conventional pressure triggering, flow triggering, is the amount of patient effort required and should be as
and triggering from pressure measured in the trachea. small as possible. Delay is the time between the initiation of
The effects of endotracheal tube sizes of 6, 7, 8, and 9 mm, patient effort and the beginning of flow from the ventilator
as well as flows of 30, 60, and 90 liters/min, were eval- and should be as short as possible. Trigger delay is also
uated. As expected, imposed work with all methods of related to the pneumatics and electronics of the ventilator
triggering increased with increased peak inspiratory flow system.
and narrower endotracheal tubes but always was lowest
with tracheal triggering (Fig. 3-50).
Although the trachea appears to be the optional site for the PRESSURE TRlGGERING
trigger signal in lung models, practical problems have pre- All ventilators in use today that trigger inspiration from
vented ventilator manufacturers from using this site. Tra- a pressure signal do so from a signal measured within
cheal pressure triggering or pressure monitoring is unlikely the ventilator circuit. The exact point of measurement may
to become an everyday clinical reality until a highly durable be the patient Y (proximal endotracheal tube) or inter-
and inexpensive means of measuring signals at this site is nal to the ventilator on either the inspiratory or expira-
developed. tory side of tl1e circuit. Measurement of airway pressure
Presently, a ll mechanical ventilators trigger from signals at the proximal airway differs from pressure measured in-
measured within the ventilator circuit. The particular point side the ventilator because of resistance to gas flow cre-
of measurement, however, as well as the precise signal, ated by the ventilator circuit, humidifier, and exhalation
varies. The trigger signal can be sensed at the proximal en- valve. 113
dotracheal tube, in the inspiratory limb, and in the expira- The primary technical concern with triggering from a
tory limb of the circuit, and the signal can be either pressure pressure signal at the circuit Y is water accumulation in
or flow (Table 3-9).118 The ventilator must be able to appro- the pressure-sensing line. This dampens the pressure signal
priately sense patient effort yet not trigger in response to and results in increased patient effort to trigger. Even if fil-
artifact (autocycling). ters and water traps are placed in the pressure-sensing line,
CHAPTER 3 BASIC PRJNCIPLES OF VENTILATOR MACHINERY 83
TABLE 3-9 Advantages an d D isadvantages of the Different Circuit Pressure-Sensi ng Sites
Advantages Disadvantages
A. Exhalation port; Well protected from Requires protection from moisture of exhaled
mechanical abuse. During mechanical gas. During spontaneous inspiration,
inhalation, accu rately reads pressure at the underestimates pressure genera ted at theY
Y. During inhalation, increases in inspiratory to trigger the ventilator. During exhalation,
or expiratory circuit resistance do not underestimates pressure at theY. During
compromise inspiratory flow output, except exhalation, increases in expiratory circuit
for many-fold increases. resistaJlCe compromise expiratory flow.
Hence system requires well-maintained
expiratory filter to ensw·e that expiratory
circuit resistance remains low.
B. Inhalation port Well protected from During mechanical inhala tion, overestimates
mechanical abuse. Does not require pressure at theY. During spontaneous
protection from moisture or additional inspiration, underestimates pressure
filters. During exhalation, accurately reads generated at the Y to trigger the ventilator.
pressure at the Y as long as the inspiratory During inhalation, increases in inspiratory
circuit remains patient. During inhalation, circuit resistance compromise inspiratory
increases in expiratory circuit resistance do flow output. For example, factors such as
not compromise inspiratory-flow output. selection of humidifier and type of patient
circuit yield varying patient inspiratory
efforts for fixed ventilator settings.
C. Patient Y: During inhalation and exhalation, Susceptible to mechanical abuse. Requires a
accurately reads both inspiratory and separate pressure-sensing tube, which is
expiratory pressures. Pressure readings prone to occlusion, blockage, and
reflect relative condition of inspiratory and disconnection, all of which prevent sensing
expiratory circuits. of pa tient effort.
souRcE: Modified, with permission, from Sassoon. 118
as they fill with water, patient effort is increased. Pressure piratory phase, with triggering occurring when the differ·
sensing internal to the ventilator, on either the inspiratory ence between flow entering and exiting the circuit equals
or expiratory side, is also affected by accumulation of wa- the trigger sensitivity. The other approach is the measure·
ter in the ventilator tubing. This either dampens the signal ment of flow at the airway by use of a pneumotad1ometer
or results in premature cycling. Stationary water that par- or hot-wire anemometer.
tially occludes the circuit increases patient effort to trigger. The major problem with the measurement of flow at the
If, however, the water is moving to and fro in the circuit be- airway and use of this signal for triggering is the accu-
cause of high system flow, subbaseline pressure can be de- mulation of water and debris on the flow-measuring de-
veloped, causing self-cycling. If the pressure signal is sensed vice. Flow-measuring devices kept at the airway must be
internally on the inspiratory side of the circuit, a bubble- changed o r cleaned frequently to ensure their optimal func-
through humidifier should not be used because the patient tion. A potential problem with all flow-triggering mecha-
is required to create a pressure gradient across the water to nisms is system leaks, which are recognized as patient effort.
trigger the ventilator. Another potential problem with flow and pressure trigger-
As described by Sassoon, 119 a number of factors affect the ing occurs when w1cuffed airways are used. With both flow
delay time during pressure triggering. These include errors and pressure triggering, the ventilator should be set at the
caused by the speed of the pressure signal, errors caused by most sensitive level that avoids self-triggering.
digital sampling of the transducer, errors in the pressure-
transducing circuit, discrepancies in the set and actual PEEP,
and circuit noise.
Exhalation Valves
Gas exiting the patient's airway normally travels past the
FLOW TIUGGERI NG
Y connector of the system through a length (about 60 in) of
Most ventilators now allow triggering from a flow sig- large-bore tubing (22-mm internal diameter), pasta filter (in
nal. Based on imposed work of breathing data, it appears some ventilators), through a flow sensor and a check valve
that flow trig§ering is slightly more efficient than pressure (in some ventilators), and then through the exhalation valve
triggering, 56' 1 0 although this does not appear to be a clinical itself. All these components of the expiratory system affect
concern if the pressure trigger is set appropriately. 120 the ability of the system to operate appropriately in accom-
Two tedmical approaches to flow triggering have plishing the following goals: (1) sealing the circuit during
emerged. In one, a bias flow is established during the ex- inspiration, (2) cycling to exhalation, (3) maintaining the
desired PEEP /CPAP level, and (4) minimizing the imposed lation valve is always higher than the pressure exerted on
work of breathing.4 the airway. Thus leaks through the exhalation valve are very
A number of different physical designs have been used uncommon.
in the expiratory valving mechanism. The most common In earlier ventilators, inflation and deflation of the balloon
of these have been the mushroom and diaphragm types were controlled simply by changes in system pressure. With
of valves. All disposable exhalation valves used on home current-generation ventilators, however, the pressure inflat-
care and transport ventilators, as well as some ICU ventila- ing or deflating the valve is under microprocessor control. In
tors, areeithermushroom or diaphragm valves. In addition, most mechanical ventila tors, a pressure transducer is placed
many of the newest ICU ventilators still use these valves. just before the exhalation valve to provide feedback via the
The newest-generation ventilators, however, frequently lo- microprocessor to the inspiratory flow control to maintain
cate the valve internal!y wiU1in a heated compartment, elim- sufficient flow to establish the set PEEP. If the PEEP level
inating the need for changing the valve between patients should fall, this feedback loop increases system flow. As
and enhancing microprocessor control of the valve. In ad- noted in Fig. 3-51, the expiratory gas flow route through
dition, scissors valves and electromagnetic and electronic many of these valves is rather tortuous, and as a result, ex-
valves are used as exhalation valves. piratory flow is retarded. That is, because of the resistance
to gas flow through the valving device and the expiratory
circuit, system pressure does not drop to baseline immedi-
MUSHROOM/DIAPHRAGM VALVES ately when the expiratory phase begins but requires time to
These two types of valves, although slightly different, return to baseline. 122- '1 25 With most of the newest ventilator
function physically in a very similar manner. A typical systems, it takes about 0.3-0.5 second for complete passive
mushroom-type exhalation valve is depicted in Fig. 3-51. decompression of the ventilator circuit.4 If expiratory gas
In most ventilators, gas is either diverted from the inspi- flow is high, or if the patient coughs, high system pressures
ratory limb internal to the ventilator or from a secondary may be developed.122•125
gas-control module to the exhalation valve to inflate the Diaphragm-type exhalation valves (Fig. 3-52) function
mushroom-shaped balloon and occlude the exhalation port in exactly the same manner as mushroom-type valves.126
during the inspiratory phase.121 Because these exhalation Gas from the inspiratory limb compresses the diaphragm
valve charging lines are internal to the ventilator and be- and closes the valve during inspiration. The valve opens
fore the system humidifier, the pressure affecting the exha- when the inspiratory phase ends and the recoil pressure of
the patient-ventilator system exceeds that of the valve. The
opening of both mushroom and diaphragm valves is also
FIGURE 3-51 Schematic representation of balloon-type
delayed by the time necessary for gas pressurizing the valve
exhal ation valves under varying conditions of pressure. A. to be evacuated.
Inspiration . B. Exhalation without PEEP. C. End of exhalation
with 10 em H20 of PEEP. D. Active exhalation with 10 cmHzO of
PEEP. Restriction to flow is greater with the application of PEEP
SCISSORS VALVES
th an if end-expiratory pressure is zero. (Used, -witll permissiou, The prototype for this expiratory valve is the Servo ven-
from Slrapiro et af.121) tilators (e.g., 900 and 300 series). As crudely illustrated
in Fig. 3-53, these valves function by compression and
·30
~
0 FIGURE 3-52 Diaphragm-type exhalation valve w ith 10 em H20
of PEEP. This valve is partially closed during the expiratory phase
A
.~
ii
~
B - because of the PEEP. As a result, resistance to gas Oow is
increased compared with zero end-expiratory pressure. (Used,
a I witll permissiou, from Kacmarek et al: Anestllesiol Clin Nortl1 Am
•-
;
5:757- 76, 1987.)
I )
•10 ·10
c - To
Alrno5Phete
:jl -+--tH~.J
'-
)
•10 ___ ._..., ____......,. ----
-r---"
,
SCRE W- CLAMP VALVE
(VARIABLE ORIFICE) SCREW CLA?*
/ RE SISTANCE (R)
FIGURE 3-53 Crude representation of a scissors-typ e
exhalationJPEEP valve. Because this valve is a variable-orifice
flow resistor, resistance to exhalation, as well as the level of
PEEP established, depends on the patient's expiratory flow
¢ EXHALED FLOW (\1) rate. The greater the gas flow, the greater is the retard of
exhalation and the greater is the PEEP. (Used, with permission,
from Ba.trner et al: Cll.est 90:212-7, 1986.)
relaxation of a silicone tube. Generally, the level of constric- pressure in the inspiratory limb began to drop, while the
tion is controlled by a stepper motor. recoil of the patient-ventilator system moved gas into the
expiratory limb of the circuit. The combined effect of these
ELECfROMAGNETIC VALVES two phenomena allowed the exhalation valve charging-line
pressure to decompress and the valve to open.
Figure 3-54 depicts the Hamilton exhalation valve, which Microprocessor control greatly enhances the efficiency of
operates by the electromagnetic positioning of a large- this process by being able to identify precisely when the
surface-area diaphragm by an actuating shaft. This type of inspiratory process ends and expiration begins. This is per-
exhalation valve requires microprocessor control. As a re- formed easily during all control or assisted breaths in which
sult, the resistance to gas flow across this valve is very low airway pressure is elevated and where a precise defini-
even when PEEP / CPAP is applied.127•128 tion of the end of inspiration can be made. Spontaneous
unassisted breathing (CPAP) or pressure support are more
ELECfRONIC VALVES challenging transitions for the microprocessor to control. In
these modes, exhalation becomes a patient-controlled, in-
These valves appear and operate in a manner similar to elec- stead of a ventilator-controlled, event. The microprocessor
tromagnetic valves (Fig. 3-55). Opening the closure of the
must identify an elevation of system pressure, a decrease in
valve generally is controlled by a stepper motor under mi-
inspiratory flow demand, or an increase in expiratory flow
croprocessor control. Thus, as with electromagnetic valves,
to establish the onset of expiration. In this setting, micro-
as long as the surface area across which exhalation occurs
processor control is essential.
is large, resistance to gas flow should be minimized.
With most microprocessor-controlled ventilators, there is
an intimate linking of the inspiratory and expiratory con-
MICRO PROCESSOR CONTROL trol systems to ensure that undesirable alterations in sys-
Early exhalation valves functioned in a simple pneumatic tem pressure, as during a patient cough, can be controlled.4
manner. When the mechanical inspiratory phase ended, As a result, the valving mechanism for inspiration and ex-
piration can be said to operate in harmony to maximize
the reproducibility of the inspiratory and expiratory events.
FIGURE 3-54 Hamilton ventilator el ectromagnetic exh alation That is, during the inspiratory phase, the exhalation valve
valve/PEEP device. The exhalation diaphragm is positioned is opening and closing to maximize conformance of the in-
electromagnetically by the actuating shaft. (Llsed, witl1 permission, spiratory phase with that programmed. The same process is
from Kacmarek et al: Auesthesiol Cliu North Am 5:757-76, 1987.)
FIGURE 3-55 The electromechanical exhalation valve of the Bird

8400ST. A. The electromechanical driver moves the p lunger,
seating the exh alation diaphragm. B. Gas entry into the valve.
C. Gas exiting the valve.
Metal
Plate -11:::=:=-----., r------~
Actuating
Shaft
c
Exhalation
DiophroQm
+
I
I
I Atmosphere
From
Expiratory
Limb
86 PART II PHYSICALBASISOFMECHANICAL VENTILATION
occurring during exhalation to better ensure that the expi- appropriately by the following equation:
ratory pressure baseline is maintained.
F . .
Expiratory pressure oc SA + R(Vexh + Vsys)
Establishment of PE EP/CPAP
Since the first description of the use of PEEP in the man- where SA is surface area, Vexh is patient-exhaled flow rate,
agement of the acute respiratory distress syndrome was and Vsys is system flow during exhalation. Based on the
published by Ashbaugh and Petty 129 in 1967, numerous evaluation of numerous PEEP devices, 122- 128 the preceding
approaches have been described for the application of relationship more closely predicts the PEEP / CPAP level es-
PEEP / CPAP to mechanically ventilated patients, as well as tablished by a threshold resistor than the simple F /SA rela-
spontaneously breathing patients.127- 130 In general, PEEP tionship.
devices have been classified historically as one of two types,
threshold resistors and orificial (or flow) resistors, based on
the mechanisms used to establish PEEP and their effects on PEEP/CPAP IN MICROPROCESSOR SYSTEMS
resistance to flow. 130
In all the newest-generation ventilators, PEEP /CPAP is es-
tablished via the exhalation valve. When baseline pressure is
THRESHOLD RESISTORS increased, however, the efficiency of exhalation-valve func-
The ideal PEEP valve is a pure threshold resistor, a de- tion decreases,127- 128 resulting in greater retardation of ex-
vice that exerts a predictable, quantifiable, and constant halation and a prolonged period between peak inspiratory
force at the expiratory limb outlet of the ventilator or CPAP pressure and return to baseline pressure. This inefficiency
system.130 The PEEP level established is proportional to the can be modified by referencing the pressure in the exhala-
force (F) applied over the specific surface area (SA): tion valve to atmosphere early in the expiratory phase and
then gradually referencing it back to the PEEP /CPAP level
F as expiration continues and system pressure approaches
p ()( - the baseline PEEP /CPAP leve1. 4 That is, the function of
SA
the exhalation valve is under active microprocessor con-
That is, a force exceeding the threshold pressure must be trol throughout the entire expiratory period. This active
developed for gas to flow through the device. Ideally, a control of exhalation is provided by one of two schemes
threshold resistor maintains a constant force on the system in all new-generation ventilators (Fig. 3-56): (1) adjustment
regardless of the gas flow through the device. In fact, PEEP of the pressure in the air chamber (active pneumatic con-
is independent of flow, and no flow is necessary to maintain trol) behind the diaphragm (or within the mushroom valve)
the PEEP leveL or (2) manipulation of the diaphragm by a proportional
linear solenoid linked either directly or indirectly to the
diaphragm. 4
FLOW RES ISTORS
The PEEP level established with a flow resistor depends
on the flow of gas (\T) through the system and the physical INTERCHANGEABLE PEEP/CPAP VALVES
cl1aracteristics of the device (resistance R) that affect gas In addition to the integrated PEEP systems via the exhala-
flow. That is, the PEEP level is governed by the law of flow tion valves of microprocessor ventilators, numerous dispos-
(Ohm's law): able/interchangeable PEEP /CPAP devices are available for
use on older-generation ICU ventilators, as well as home
P oc RV care, transport, and manual ventilators and free-standing
CPAP systems. Most of these devices are either spring-
where Pis the expiratory pressure established . For a given loaded (Fig. 3-57) or magnetic valves (Fig. 3-58). All these
R, PEEP increases with an increase in total flow through the devices function as combined threshold/flow resistors, ex-
valve. Because of the turbulent flow characteristics of the hibiting greater or lesser flow-resistant properties.131 As a
valve, however, this relationship is often not linear. result, expiratory pressure during CPAP can be expected to
increase 2-3 cmH2 0,131 and the time for return of peak inspi-
ratory pressure to baseline during mechanical ventilation is
ACTUAL VALVE FUNCTION
also lengthened. In addition, because of mass production of
From the preceding it is obvious that a PEEP valve function- these devices and their flow-resistant properties, indicated
ing as a threshold resistor is desirable, and one functioning and actual PEEP /CPAP levels established may differ by 3-
as a flow resistor is undesirable. Unfortunately, no PEEP 4 cmH20.131 Thus it is necessary to measure actual system
valve can be classified as a perfect threshold resistor. All PEEP level during the use of these devices. Finally, as a re-
threshold resistors possess flow-resistant properties. Ban- sult of the marked flow-resistant properties of these valves,
ner et al127 have argued that the pressure exerted during they impose not only additional expiratory but also addi-
exhalation by any threshold resistor is represented more tional inspiratory work of breathing.13 1
IINSETC Sprinc;~
r Adjustment
I I
-- t\
lI PEEP/CPAP --lAtm~:phere
Equivalent I
1 Pressure , FIGURE 3-57 S pring-loaded interchangeab le PEEP valve. As
INSERT A: Passive Control PEEP is increased by ad justment of the spring and d iaphr agm, the
INSERT B: Active Control area available for expiratory flow to pass decreases, increasing
the Bow-resistant properties of ilie valve. (Llsed, 1Vith penn issiou,
FIGURE 3-56 An illustration of a diaphragm-type expiratory from Kacmarek et nl: AJ'Jesthesiol Clin North Am 5:757- 76, 1987.)
valve. Diaphragm positioning generally follows one of three
strategies: (1) maintenance of a specified PEEP/CPAP-equivalent
pressure in the air chamber (passive pneumatic control), (2) number of events associated with either the ventilator it-
algorithmic modulation of the chamber pressure between the self, the patient-ventilator interface, or the patient. 140, I42,'I44
PEEP/CPAP-equivalent value and a lesser value, thereby The question that has not been answered dearly, however,
improving expiratory efficien cy when PEEP/CPAP is finite is this: Is it necessary to alarm all the events that can be
(active pneumatic control), an d (3) algorithmic posi ti oning of the monitored." A secondary and equally important question
diaphragm via an electrodyn amic motor (active direct control). If is: What should the alarm threshold be for a given event?
the electrodynam ic motor and the diaphragm are coup led directly Ventila tor alarms, as designed today, greatly contribute
(in contrast to physically uncoupled), all positions of the
to noise pollution in the ICU and, based on our obser-
diaphragm must be specified by the control algorith m. In t11e
uncoupled design, the force of exhalation opens the valve, but
vation of clinician activities, actually encourage practi-
closu re is controlled by the electrodynamic motor. (Llsed, witlr tioners to ignore them because of the high frequency of
permission, from Sauboru: Respir Care 37:1009-25, 1992.) false alarms.140, 143•144 Because manufacturers have tried to
Imposed Work of Breathing FIGURE 3-58 Mag netic PEEP valve. Ad justm ent of the distance
between the two magnets determin es ilie PEEP level establish ed.
(llsed, with permissio11, from Kncmarek ct a/: A uesthesiol Cliu
Whenever instrumentation is affixed to the airway, work North Am 5:757- 76, 1987,)
of breathing is imposed. Artificial ainvays are responsi-
ble in la.r ge part for most of the work imposed, 132. 133 but a
close second is the ventilator itself. Numerous authors have
documented the impact of ventilators on imposed work of
+I
I .--- ·· Valve
brea thing.134 - 138 Ventilator-imposed work his torically has
been most pronounced (and has had the greatest clinical
impact) during CPAP, where the patient is expected to per-
form all the effort required to ventilate. More recent data on
the newest generation of mechanical ventilators, however,
indicate that imposed work, when sensitivity is set properly,
is minimal and of limited clinical concem.56•124•1 39 MOQnetic --+-+-t Expira tory
Pote ._._ ...... Limb
Alarms
Today's ventilators, because of their microprocessor con- Adjust able - -1
Screw
trol, are capable of monitoring and alarming an indefinite
TABLE 3-10 Priorities for Mechanical Ventilator Alarms
Immediate
Response
Priority Life-Threatening Required Redundant Alarm Type
Level l Yes, immediately Yes YC!s Loud audjble and visual

Leve12 Yes, pntentially Yes No Softly audible and visual
Levcl 3 No No No Visual
SOURCJ!: Used, with pern,ission rrom American Association for R.spiratory Care.147
maximize the sensitivity of alarms (the percentage of true a scenario may cause the practitioner to disregard future
events that are detected), and because of the type of alarm al- high-pressure events. This is also true of many volume and
goritluns currently used, specificity (the percentage of false rate alarms because the time interval over which the mon-
events that are ignored) of these alarms is frequently low. 140 itored variable is integrated is so small with some venti-
This is especially true when evaluating the number of fa lse- lators (5-10 seconds) . That is, a change in tidal volume or
positive alarms in the area of patient or patient-ventilato r ra te outside the defined range for a single breath or over
interface variables.144 Even if the false-positive rate is low
(5%), however, but there are 20 alarms that all ftmction at TAB LE 3-11 Events and Monitoring Sites for Ventilator Alarms
this false-positive rate, there is a 64% probability tha t any
given alarm will be false-positive alarm. 126 Such a frequency Event Possible Monitoring Site
of false-positive alarms clearly prevents practitioners from
taking alarms seriously. Levell
Power failure (includ ing when Electrical control system
battery in use)
Absence of gas delivery (apnea) Circuit pressures, circui t
HIERARCHY OF PATIENT- VENTLLATOR ALARMS
flows, timing monitor,
A few groups, including the International Organization for C02 analysis
Standardization and the American Society for Testing and Loss of gas source Pneumatic control system
Materials,145•146 have defined limited specific standards fo r Excessive gas delivery Circuit pressures, circuit
flow, timing monitor
ventila tor alarm systems. The group that has most specif-
Exhalation value failure Circuit pressures, circuit
ically defined g uidelines for ventilator alarms, however, flows, timing monitor
is the American Association for Respiratory Care.147 This lime failure Circuit pressures, circuit
group has recommended classifying ventilator alarms in flows, timi ng monitor
three levels of priority, with Ievel l indicating an immediate Level2
life-threatening situation and level3 indicating no threat to Battery power loss (Mt in use) Electrical control system
life (Table 3-10). Also recommended was the need for an im- Circuit leak Circuit pressures, circui t
media te response to Ievell priority alarms and a distinction flows
between the a udio and visual response of the ventilator to Blender failure Fto2 sensor
each alann priority leveL Table 3-11 lists events that should Circuit partially occluded Circuit pressures, circuit
be monitored and the possible sites for monitoring of each flows
event at all three levels of priority. In general, it is recom- Heater/ humidifier failure Temperature probe in circui t
mended that a ll ventilators include alarms for all Ievell and Loss of/ or excessive PEEP Circuit pressures
level 2 events.147 Generally, level3 alarms, although useful Au tocycling Circuit pressures, circuit
flows
in certain settings, are not necessary.147 Other electrical or preventative Electrical and pneumatic
subsystem out of limits systems moni tor
without immediate overt gas
II SMART"ALARMS delivery effects
Alarm-activation algorithms used historically on most ven- Level 3
tilators for patient-ventilator interface events were rela- Change in central nervous Circuit pressures, circui t
tively simplistic in design.4 For example, when the high in- system drive flows, timing monitor
spiratory pressure was met by a single breath violation, an Change in impedances Circuit pressures, circui t
alarm was activated that must be r eset by the practitioner. flows, timing monitor
Intrinsic (au to) PEEP> Circuit pressures, circuit
Because the event may have occurred on only one breath
5cmH20 flow
as the patient changed position, however, when the prac-
titioner arrived at the bedside, the peak inspiratory pres- souRCE: Used, with pt>mussion, from American Association for Respiratory
sure had returned to the level before the incident. Such Care.147
CHAPTER 3 BASIC PRJNCIPLES OF VENTILATOR MACHINERY 89
a short time but rapidly corrected by itself resulted in a integrated silicon-wafer pressure transducers, which are in-
sustained alarm. Many of the newest generation of venti- expensive and have an accuracy that is a clinically accept-
lators, however, reset alarms if the event occurs only for able estimate of the actual value (±0.1 cmH2 0 ± 3% of read-
one breath or corrects itself in a short period of time. Other ing and can target ~ressure with an accuracy of ±2 cmH20
alarms, once activated but self-corrected, provide a visual ± 3% of reading). 49 The format used to display pressure
but not audio indication of the event. Much of the prob- varies considerably from ventilator to ventilator. Few ven-
lem with false-positive a larms is a result of the a lgorithms tilators still employ analog scales. Most ventilators convert
designed to activate the alarms. More and more empha- the pressure signal to a digital format and dis play it either
sis, however, currently is being placed on the develop- as a moving or expanding bar on a liquid-crystal display or,
ment of "smart" alarms, that is, alarms that use up/ down more commonly, as a digitally displayed value.
counting sequences, time delays, or other software filter-
ing mechanisms that reduce the frequency of false-positive
alarms.141, 148 FLOW MONITORING
In addition, designing the a larm audiovisual response in Monitoring flow is considerably more difficult than mon-
the form of a hierarchy, which increases in urgency as an itoring pressure. In general, flow is not measured directly
alarm condition continues, helps to decrease the frequency but rather is calculated from change in pressure or tempera-
of false-positive alarms. These types of "smart" alam1 sys- ture or the development vortices as gas flows past a partial
tems are being used more frequently on the newest genera- obstmction.'141 Flow then is converted to volume at body
tion of ventilators. temperature and pressure saturated. All these factors de-
crease the accuracy of the flow and volume measurements
displayed by even the newest of mechanical ventilators. 142
Monitoring The mos t common flow sensors used in current mechani-
cal ventilators are (1) pressure-gradient measuring devices
Today's ventilators are capable of alarming various pa-
tient and patient-ventilator interface variables as a result (i.e., pneumotachometers, variable orifices or venturis), (2)
vane-displacement devices, (3) thermal-cooling sensors, (4)
of their ability to monitor pressure and flow. Numerous
vortex-shedding sensors, and (5) ultrasonic sensors .141
techniques are used to monitor flow, and both flow and
Numerous variations of the s tandard pneumotachome-
pressure are monitored in various locations within the ven-
ter (Fig. 3-59) are used to measure flow during mecha ni-
tilator circuit. 141 ·149 Ideally, pressure should be measured
cal ventilation. The Servo 300 and i series ventilators use
within the lung.U 2·113 As discussed earlier, however, this
screened pneumotacl10meters placed proximal to the exha-
is rarely done for clinical purposes. As a result, pressure
latio n valve and distal to the inspiratory-flow valve. Ad-
is monitored either at the ventilator circuit Y or internal
vantages of these pneumotachometers are decreased dead
to the ventilator, on either the inspiratory or expiratory
space, better frequency response, and ease of disassembly
side. The major concern with measurement internal to the
for cleaning. 149- 151 Moisture, however, significantly alters
ventila tor is that airway pressure changes during sponta-
their accuracy. This is particularly true if aerosolized phar·
neous breathing are dampened.
macologic agents are allowed to contaminate the device. As
Flow can also be measured at the airway or internal to the
a result, it is advisable to place filters in the expiratory limb
ventilator. If meas urements are made internal to the venti-
lator, the volume meas ured m ay reflect not only volume during aerosol therapy.
delivered to the patient's lw1g but also volume compressed
in the ventilator tubing (compressible volume is generally
FIGURE 3-59 Schematic representation of Fleisch
2-3 ml/cmH20). Many of the new-generation ventilators pneu motachograph with a differential press ure transducer. (Used,
compensate for this volume.141,142 When flow-measuring wit/1 permissiou, jro111 Sulliv an et aT: Respi•· Ct1re 29:736-49, 1984.)
devices are located at the airnray, only gas entering or leav-
ing the patient is monitored. Capillary
The advent of microprocessor control has led to an in- Tubes
crease in the development of inexpensive sensors that can
be incorporated into ventilators. It is important to realize
Aor .
Flow +P \
that the accuracy of these sensors is considerably less than
that of laboratory-grade sensors. 141 That is, displayed pres-
sure measurements range between ±3% and ±5% of actual p ressure _
pressure, and displayed flow measurements range between Hoses
±6% and ± 10% of the actual flow.141
......
>
PRESSURE MONITORING Press ure - Co il
Transd uce r Ele c lric al
Historically, pressure during mechanical ventilation was '"'"' Si gnal
_{'-¥¥
measured and displayed by aneroid manometers . Today, To Amplifier
I
most microprocessor-based ventilators employ solid-s tate Diaphragm
90 PART n Pf fYSICAL BASIS OF MECHANICAL VENTILATION
Prossure Tubes Obstructing

strul
Aar
IIow
Atr
flo w
¢::::::> Orifice
Rec etver
Vorte x
M~ Pulses
Fi xed or Va riable
Orifice Or ific e
FIGURE 3-60 Schematic representation of an orifice
pneumotachograph. (Used, witlr permissiou, from Sullivan et al:
Respir Care 29:736-49, 1984.)
I Counler
I
FIGURE 3-62 Schematic representation of a vortex
Volume
signal
pneu motachograph. (Used, witlr pennission, from Sullivan eta/:

Respir Cnre 29:736-49, 1984.)
Another popular device used by both the Bird and Hamil-
ton ventilators is the orifice pneumotachometer (Fig. 3-60).
TI1is device was designed to circumvent the moisture prob-
lems seen with both the Fleisch and screen pneumotachome- the old MA-1 ventilator. The accuracy of the volume dis-
ters. Generally, the orifice is large enough to allow the free played varies considerably from that actually measu red at
passage of water, and the device itsell is coated with a water- the ventilator circuit Y, 141 •149•157• 158 and the discrepancy in-
resistant substance. This device is produced in two designs: creases with increased tidal volume. Ventilators that actu-
one with a large orifice, creating turbulent flow and requir- ally measure fl ow at the circuitY (Hamilton ventilators) dis-
ing a linearizing electronic circuit, and the other using an play the most accur ate tidal volume. 158 A major reason for
elastic flap in the middle of the orifice, which produces me- thls difference is compressible volume. Many of the newer-
chanical lineari2ation of flow. 152. 153 generatio n ventilators, however, attempt to correct for com-
A hot-wire pneumotachometer (or anemo meter) (Fig pressible volume.
3-61) is used in the Puritan-Bennett 7200 and 840 ventila-
tors. This type of pneumotachometer consists of a heated
platinum wire positioned in the middle of a tube.154.l55 As
WAVEFO RMS AN D LOOPS
gases pass through the tube, the wire rapidly loses heat.
Cooling is offset by a n electronic circuit that adds additional All current-generation ICU ventilators display waveforms
current to maintain a cons tant temperature. The gas flow of a irway pressure, flow, and volume. These wave-
rate is proportional to the added current. forms have been invaluable in monitoring overall patient-
The old Bea r ventilators use a vortex-shedding pneuma- ventilator interaction, 159 the setting of various modes of
tachometer. As illustrated in Fig. 3-62, a partial obstruction ventilation,160 and the management of patients with spe-
(strut) is placed in the center of the device, causing turbu- cific conditions,161 - 165 as well as the identification of
lence and the formation of vortices as gas flows through the auto-PEEP. 165 In addition, many ventilators also display
pneumotachometer. The level of turbulence is detected by pressure-volume and flow-volume loops. Information re-
an ultrasonic beam located downstream from the strut. The garding patient effort, patient-ventilator synchrony, auto-
degree of turbulence is proportional to the flow rate.'56 PEEP, response to bronchodilators, and work performed by
With all the newest-generation ventilators, volume is de- the ventilator can be gained from the analysis of waveforms
termined by integrating flow over time. None of these units and loops, even if they a re measured internal to the ventila-
meas ures volume displacement directly, as was done with tor. Specific information regarding waveforms and loops is
available elsewhere in thls book (See Chapters 49 and 53),
as well as in other publications. 159 - 167
FIGURE 3-61 Schematic representation of a hot-wire
p neumotachograph. (Used, w itlr pennission, from Sullivau eta/:
R espir Care 29:736-49, 1984.)
D ERI VED VARIAB LES
Atr Heated wire On e-way Because the newest-generation ventilators are micropro-
flow \ valve
cessor controlled a nd monitor airway pressure and flow
C>~=====,c=~~~~ throughout both the inspiratory and expiratory phases, nu-
merous variables related to pulmonary mechanics can be
Tap11red tube l J derived. Of major concern with many of these mechanics
packages is that the formula used to calculate a particula r
variable may not be the most accurate formula. In addi-
Hell-loss
detection
circull ry
-1
.
; inearizer ]~---
_
Flow
si gnal
tion, few data evalua ting the accuracy of these packages are
available.'168•169
EFFECTIVE COMPLIANCE related to mechanical ventilation, and to the cardiac moni-

tors for display of variables and annunciation of alarms. 175
As has been pointed out by Marini170 and others, 152• 168, 171 the
measurement of compliance in passively ventilated patients That is, the exact time and specific changes made can be dis-
requires that total PEEP (auto-PEEP plus applied PEEP) and played, as also can all alarm conditions and events leading
ventilator tubing compliance be considered when effective to the condition.
static compliance (Ces) is determined: Airway pressure, flow, and volume waveforms also can
be displayed on separate computers or on the cardiac bed-
side monitor. This transfer of online data to systems capa-
VT - (Pplat - PEEPlOT)(compressiblevolumefactor) ble of manipulating and filtering the data and subsequently
Ces= ~--~~------~~--~~---------------
Pplat - PEEPlOT packaging them with other data associated with the pa-
tient's physiologic status opens the door for an integrated
where Pplat is the plateau (end-inspiratory hold) pressure, approach to the monitoring of the whole patient-ventilator
PEEPlOT is total PEEP, and the compressible volume factor system. 176 Ventilator data also can be transferred by the in-
is the volume compressed in the ventilator circuit per cen- stitution's Ethernet system to remote locations for assess-
timeter of water pressure. The algorithms used by specific ment or be interfaced directly with nurse call systems. It is
manufactures should be evaluated carefully to ensure they anticipated that highly sophisticated interactions of ventila-
confonn to this equation. tors and other monitors will be available in the near future.
RESISTANCE T O FLOW
The Future
Concerns regarding the calculation of either inspiratory or
expiratory resistance also exist. Of all the variables calcu- Today's generation of ICU mechanical ventilators is much
lated by ventilators, however, the estimate of inspiratory more sophisticated than those manufactured in the 1980s or
resistance is probably the most accurate. This calculation 1990s. This trend toward increasing sophistication, greater
requires gas to be delivered in a square-waveflow pattern. versatility, and enhanced capability is expected to continue.
Only peak airway pressure, plateau pressure, and inspira- From an engineering perspective, essentially anything is
tory flow are required for the calculation. Expirator y re- feasible. The factors limiting ventilator development today
sistance also requires the determination of total PEEP for are time and money, not engineering capability.
accurate calculation. We still believe that there are areas of ventilator perfor-
mance where significant improvement is needed and would
expect that the mechanical ventilators of the future will in-
AUTO (INTRINSIC) PEEP
corporate the following and more: (1) Alarms on all patient
Since the original description of auto-PEEP by Pepe and patient-ventilator interface variables should be "smart,"
and Marini,172 its importance in the management of pa- that is, capable by more appropriate activation a lgorithms
tients requiring ventilatory assistance has been increasingly of greatly reducing the number of false-positive alanns;
obvious.173•174 As discussed elsewhere in this book, auto- (2) monitoring, not the addition of more monitored vari-
PEEP usually is identified by the establishment of an end- ables but a better organization of trended data, should re-
expiratory hold during passive ventilation. This approach sult in a list of the potential problems identified; and (3)
provides an estimate of the mean level of auto-PEEP. Cur- more carefully designed approaches to closed-loop ven-
rently, all new-generation ventilators allow for the measure- tilation should become standard features of mechanical
ment of auto-PEEP provided that a static end-expiratory ventilators. With the introduction of more accurate and
pause can be established. continuous monitors, closed-loop ventilation a lgorithms
based on multiple patient physiologic variables should be
possible.
TRENDIN G OF D ATA
Most new-generation ventilators provide some trending of
data. This includes monitored patient/ventilator data as
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~hapter 4 Pneumobelt
Rocking Bed
EQUIPMENT REQUIRED Critical Analysis of Pneumobelt and Rocking Bed
FOR HOME Long-term home mechanical ventilation has been used

worldwide for over 70 years to manage chronic ventilatory
MECHANICAL failure. 1' 2 In the United States, long-term mechanical ven-
tilation via the iron lung was first used with polio victims,
VENTILATION although negative-pressure ventilators in Europe trace their
history to the mid-nineteenth century.3,4 In 1952, the use of
ROBERT M. KACMAREK intermittent positive-pressure ventilation via tracheostomy
ATUL MALHOTRA was introduced,5 whereas the use of mouthpiece intermit-
tent positive-pressure ventilation began in the late 1950s.6
All the various approaches to ventilator support have been
used successfully for long-term maintenance of patients
with respiratory failure secondary to either neuromuscular
and primary pulmonary diseases?- 10
INVASIVE POSITTVE-PRESSURE VENTILATORS Over the past 25 years, the number of patients receiving
Nelcor Puritan-Bennett LP-10 home mechanical ventilator assistance in the form of con-
Nellcor Puritan-Bennett LP-6 plus tinuous positive airway pressure (CPAP) and ventilation
Puritan-Bennett Achieva provided both invasively and noninvasively has increased
Lifecare PLV-1 00 markedly.H-ls As a result, there has been a resurgence of
Lifecare PLV-1 02 interest in the use of all approaches to chronic ventilator
Respironics PLV Continuum support. These include invasive and noninvasive positive-
Pulmonetic Systems LTV and negative-pressure techniques and the use of CPAP to
Versamed iVent2o1 manage sleep apnea. The concept of long-term mechanical
Newport HTSO ventilation has been approached from two distinct clinical
NONINVASIVE POSITIVE-PRESSURE VENTILATORS perspectives: mandatory, for use during true life support,
Respironics Bilevel Ventilators and elective, for managing chronic ventilatory failure and
Resmed Bilevel Ventilators sleep apnea.6 ,19, 20 In most patients requiring ventilator sup-
Puritan-Bennett Bilevel Ventilators port on a mandatory basis, invasive approaches have been
COMMON FEATURES OF ALL most common. Many patients in this category, however,
POSITIVE-PRESSURE VENTILATORS are being maintained with noninvasive methods.2I,22 In pa-
Delivery of Increased FI~ tients with slowly progressive chronic ventilatory failure
SIMV /IMV and work of Breathing who can sustain spontaneO\.lS breathing for lengthy peri-
Humidification ods, noninvasive methods are the primary approach.8 This
Application of PEEP is especially true for patients with chronic neuromuscular
Pediatric Ventilation or neurologic diseases.17, l8
The Ideal Home Positive-Pressure Ventilator If one were to gather every possible positive-pressure
CLINICAL APPLICATION OF ventilator produced for home use over the last 40 years,
POSITIVE-PRESSURE VENTILATORS dozens of units would be listed.23 - 26 Most of the older
Elective Positive-Pressure Ventilation units, however, have fallen into disuse, and many are not
Elective Ventilation via Tracheostomy presently manufactured. Only units currently marketed and
Invasive Nonelective Ventilator Support those no longer manufactured but still with large numbers
Noninvasive Nonelective Ventilator Support in use are presented herein. Detailed discussions of each of
FACIAL APPLIANCES FOR NONINVASIVE these units are presented as well as critical analyses. Follow-
PO SITIVE-PRESSURE VENTILATION (NPPV) ing the individual unit discussions, topics applicable to all
Oral-Nasal Masks positive-pressure home-care ventilators are discussed. We
Nasal Masks begin with a description of all volume-targeted ventilators,
Adams Circuit followed by the pressure-targeted or bilevel-pressure units.
Mouthpieces
Total Face Mask
Head Hood Invasive Positive-Pressure Ventilators
NON-POSITTVE-PRESSURE APPROACHES
TO VENTILATOR SUPPORT All the ventilators discussed in this section are designed for
Negative-Pressure Generators use via an artificial airway. That is, all include monitoring
Critical Analysis of Negative-Pressure Generators and alarms required when providing a patient with venti-
Negative-Pressure Chambers lator support 24 hours per day. In addition, each of these
Critical Analysis of Negative-Pressure Chambers ventilators includes an internal battery that will maintain
97
98 PART ll PHYSICAL BASIS OF MECHANICAL VENTILATION
FIGURE 4-1 The Puritan-Bennett LP-10

Ventilator.
ventilation for at least 1 hour. These ventilators may be used ing assisted ventilation is sensed via the proximal pres-
for noninvasive ventilator support. They are not designed sure tap. The one-way gas inlet valve (located a t C in Fig.
for this purpose, however, and do not do as good a job as the 4-2) is not included in ti1e LP-10 gas-flow path. The oxygen-
bilevel-pressure ventilators specifically designed for nonin- accumulating apparatus used on the LP-10 is depicted in
vasive ventilation. Fig. 4-3. To the gas inlet port on the back of the machine,
a 30 x 22 mm adapter is used to attach a large-bore con-
necting tube ti1at a ffixes to a specifically d esigned T piece
NELCOR PURJTAN-BENNEIT LP-10
attached to the unit's accessory side rail on the right side
The LP-1027 (Fig. 4-1) is a compact (93/3 in high x 14lf2 panel of the unit. This T piece is configured with an 0 2 tap
in wide x 13% in in diameter), lightweight (weighs and a reservoir bag. A detailed discussion of 02 delivery is
34 lb) microprocessor-based ventilator. The internal gas- provided later in ti1is chapter.
flow pathway in this unit is similar to that of the aiJ early-
generation positive-pressure home-car e ventilators (Fig.
4-2). Gas enters the unit from a tmosphere or via a reservoir- CLASSIFICATION
bag assembly attached to the gas inlet port on the back panel The LP-10 is a microprocessor-controlled, electrically pow-
of ti1e machine. From here, via a one-way valve (see Fig. ered, rotary-piston-driven pos itive-pressure home-care
4-2A), gas enters the piston chamber; gas exits the piston ventilator. As a result of ilie piston-driving mechanism,
chamber at a second one-way valve (see Fig. 4-28), from the unit is classified as a non-cons tant-flow generator iliat
which it p roceeds into the inspiratory circuit. Within the in- produces a sigmoidal pressure pattern (Fig. 4-4). Inspi-
ternal inspira tory circuit, a gas tap supplying flow to the ration is triggered by either time or pressure based on
exhalation valve is configured . Additionally, a manufac- the patient's inspiratory efforts, and expiration is cycled
turer-set nonadjus table pressure pop-off valve is located in- based on either volume or pressure: volume cycled un-
ternally on the inspiratory limb. A proximal pressure tap der normal operating conditions and pressure cycled if
leads from the patient's airways to the ventilator front panel the pressure-limited mode is chosen or if ti1e unit's high-
and on to the microprocessor. The system's pressure gauge pressure alarm/limit is reacl1ed. Assist-control ventila-
attaches to this line. The high-pressure limit is identified by tion (ACV), synchronized intermittent manda tory ventila-
the microprocessor that, when reached, alarms and termi- tion (SIMV), and pressure-limited ventilation modes can
na tes the inspiratory phase. be programmed. In addition, apnea ventilation is avail-
Parameters set on the control panel are relayed to the able. No inspiratory sigh or expiratory maneuvers are
piston motor via ilie microprocessor. Patient effort dur- included.
CHAPTER 4 EQUIPMENT REQUIRED FOR HOME MECHANICAL VENTILATION 99
,-
1
I
EXHALATION
A VALVE
TO PATIENT
FIGURE 4-2 Diagram showing generalized
gas-flow routes through a typical home-care
PISTON ventilator. A. One-way check valve allows gas entry
CHAMBER into the piston chamber during the piston
backstroke. B. One-way check valve prevents
BUBBLE-THROUGH HUMIDIFIER subatmospheric p ressure from developing in the
ventilator circuit during the backs troke of the
piston. C. One-way ch eck valve (antisuffocation
valve) allows patient to inspire spontaneously
during closure of B when p iston backstroke is in
progress. Some gas may enter system at the
MOTOR exhalation valve during spontaneous breathing.
I Arrows depict gas flow possible during
I
I I spontaneous inspiration. (Used, with ptmuission,
L---- --- -- --- - --- _.J from Kacm.arek et al: Respir Care 35:405-14, 1990.)
MODES spontaneously, drawing gas from the piston chamber or

ACV, SIMV, and pressure cycle and pressure limit are the through the exhalation valve. As with other piston venti-
modes available with the LP-10. In the ACV mode, the op- lators, the LP-10 does not have a demand system, nor is it
erator sets a control breath rate, the tidal volume, the inspi- normally configured w ith a continuous-flow system. If the
ratory time, and breathing-effort control (patient-triggered patient fai ls to create sufficient inspiratory force to be sensed
sens itivity). If the breath rate is set at 6 breaths per minute by the ventilator for a 20-second period, the tmit goes into
or less and the patient becomes apneic, the apnea alarms backup ventilation at a rate of 10 breaths per minute, deliv-
sounds. ering the preset tidal volume. If the SIMV breath rate is set at
During SIMV, the operator also must set breath rate, tidal 6 breaths per minute or greater, the apnea alarm wiU sound,
volume, inspiratory time, and breathing effort. Betw een but the machine will not revert to backup ventila tion.
SIMV positive-pressure breaths, the patient may breathe The pressure-cycle m ode functions exactly the same as
the ACV mode, except that inspiration is terminated when
the set high pressure is reached. This m ode does not result in
FIGURE 4-3 Schematic of the oxygen accumulator used on the LP
series ven tilators. See text for discussion . (Used, with pennission,
from Puritau-Bennett.l')
FIGURE 4-4 A. Sine-wave flow pattern established by older
O XYGE N IN LET home-care ven tilators during volume-Limited ventilation.
B. Corresponding sigmoidal pressure curve establislted during
insp irati on. (Used, w ith permi$siou, from Kacmarek et al: J Neuro
Rehab 6:103- 12, 1992.)
Inspiration Expiration Inspiration
A
~
0 0 - ---------- ----------- ---·-·· -----··· ··· ·- · ...... ..
~
INLET FILTER
~ 8
::::>
(/) 0 - ----------- ------ -------
~
[ TIME
a pressure plateau. Thus the inspiratory time setting in con- battery is charged automatically unless the unit is turned
junction with the tidal volume detem1ines peak inspiratory off. It takes 2 to 3 hours to recharge a discharged internal
flow. As in all pressure-cycled approaches to ventila tion, ac- battery. The internal battery can operate the LP-10 for up to
tual tidal volume delivered depends on ventilator settings 1 hour, depending on the actual ventila tor setup. The unit
and the patient's airway resistance and compliance. When converts automatically from ac to de sources if required.
this mode is used, the high-pressure a larm is inactivated . The power-switchover alarm is activated when switd 1over
Thus any acute change in system compliance or airways occurs.
resistance may go unnoticed because no method of moni-
toring tidal volume or minute ventilation is available on this MISCELLANEOUS
mlit. The llllit has a remote alarm access port and a communi-
The LP-10 also has a pressure-limit control. That is, dur- cations port for an optional printer. If the communications
ing either SIMV or ACV, a large tidal volume can be set port is used, access to detailed monitoring data is avail-
in association with a specific pressure linlit. During inspira- able based on alarm activation (i.e., each alarm condition
tion, the ventilator delivers the complete tidal volume. Pres- is categorized, a description of the alarm condition is pro-
sure will not be a llowed, however, to exceed the pressure vided, and an indication of why the condition occurred is
limit (volume delivered after the limit has been read1ed is detailed).
dumped to the atmosphere). In addition, the high-pressure
alarm limit is not affected by the pressure-limit control. If the CRITICAL ANALYSIS
high-pressure alarm limit is reached, the ventilator alarms Minimal tidal volume is 100 ml, and possible changes are
and dumps additional volume to the atmosphere without only in 100-ml increments. This limits the unit's use in pedi-
altering inspiratory time. Table 4-1 lists the ranges for gas- atric settings. Addition ofthe pressure-limit control does off-
delivery variables. set the preceding concern in certain settings; because no vol-
ume monitoring is provided, however, extreme care must
ALARMS be exercised whenever the pressure-lin1it control is used.
TI1e number of specific alarm conditions identifiable with This includes proper setting of the high- and low-pressure
the LP-10 is 23. These conditions are categorized under five alarms. Another concern with the pressure-limit control is
major a larm conditions: high pressure, low pressure/ apnea, the absence of calibration. The chance of an inadvertent pa-
low power, power switchover, and setting error. Audio rameter change is decreased (except for the pressure-limit
and visual indicators are available for these five major control) by the design of the unit (the recession of the control
categories. No other information except these five indica- panel and its door). The design of the control panel is sim-
tors is available to the practitioner unless the optional ple and straightforward, improving user-friendliness. The
printer is set up and active during ventilation. When the communications port greatly enhances the monitoring of
printer is in use, a specific description of the alarm, along and appropriate response to alarm conditions.
with an indication of why the alarm occurred, is provided.
There are six individual alarm specifications in the cat-
egory low pressure/apnea: low pressure (system pressure NELLCOR PURJTAN-BENNETI LP-6 PLUS
below limit for two consecutive breaths), valley alarm (sys-
tem pressure does not drop below the pressure setting for The LP-6 Plus27 (Fig. 4-5) is exactly the same as the LP-10,
two consecutive breaths), exhale fail (system pressure is except that the pressure-limit control is not included .
above the low-pressure alarm setting at the beginning of a
breath), apnea (1 0 seconds or greater), sta ll (failure to com-
PURITAN- BENNETT ACHIEVA28
plete a breathing cycle in 14 seconds), and failure of system
leak self-test. The Achieva is very similar in design to the LP6 plus and
The power-failure alarm results from two distinct condi- LP-10 (Fig. 4-6). It weights 32 lb and is 10% in high, 131/4
tions: internal ba ttery voltage below 11.6 V and failure of the in deep, and 151!2 in wide. The overall gas-delivery pattern
battery cha rger. The power-switchover alarm is activated is essentially the same as that illustrated i11 Fig. 4-2. The
when the internal de battery is the primary power source piston, however, is accelerated linearly and controlled by a
and its voltage is low. Under the high-pressure alarm, three microprocessor; as a result, gas-delivery pattern in volume
situations are identified: System pressure is above set level, ventila tion is not a sine wave. In addition, pressure-support
system pressu re exceeds set level by 10 cmH20, and fail- ventilation (PSV) and pressure assist-control ventilation (P-
ure of overpressure-relief valve during self-test. With the ACV) ar e available. This unit also controls the pressure in
setting-error alarm, a total of 11 different user or machine the mushroom exhalation valve electronically, allowing the
operational errors are identified. See Table 4-2 for details on setting of up to 20 cmH2 0 of positive end-expiratory pres-
alarm systems. sure (PEEP). An internal 0 2 blender is included on the up-
graded Achieva PS02. When a 50 lb/in2 gas source is at-
POWER SOURCE tached to the external standard--diameter index safety sys-
The LP-1 0 can be operated by ac, external de, and internal tem (DISS) ~connector, up to 100% 0 2 can be delivered. A
de current. The unit always selects the highest power source flow sensor (internal to the ventilator) allows precise control
available, ac, then external de, and then internal de. When of the gas-delivery pa ttern during various modes of ventila-
the unit is connected to an electrical outlet, the internal de tion. A specific circuit is required to ensure proper operation
TABLE 4-1 Set ling Ranges for Volume-Targeted Home-Care Positive-Pressure Ventilation
1idal Volume, Rate, per Peak R ow Rate, Inspiratory Sensitlvily, Stgh Volume,
ModC> ml minute liters/ min Tune, S<'ronds cm~!IO ml Sigh Rate l:E Ratio PEEP
PB ACV,SIMV, 100-2200 1-.38 0.5-55 - 10 to +10

LP-10 pn.~re-l•m•ted.
Prcs6U<<>-Iimitcd,
plAteau
PB ACV,SIMV, 100-2200 1-38 0.5-55 - IOto +IO
LP-6Pius pr<'SSUr<>-limitcd
Ltf'oolre C,A,SIMV 50--3000 2-40 1()-120 - 6to+l
PLV-100
Lifccarc C,C +sign, 50-IBOO 2-40 10-120 -5 to +18 1.5 times set VT I every 100
I'LV-102 ACV,ACV+ breath~
sign,SIMV
I'D C, ACV both preS>. 50-2200 1-80 Up to 180 0.2-5.0 3-25 liters/min Up to 20 onHzO
~ Achieva ond Vol., SIMV or 1- 15 cml 110
0 voi, CI'AI', 1'5,
~
npnca
R""pironics I'LV C,ACV,SIMV 50-2500 1-80 3-120 0.2-5.0 - 4 to 18 cmHzO '1 50"1. ol set VT I every 100
Continuum prco~s . and Vol., breath.;
PS, ilpnca
Pulmont:tic C, i\CV, SIMV 50-2000 Up to 160 0.3-9.9 1 to 9 11tcrs/mln Up to 20 cmH20
LTV pre~ . and vo1., a nu - 3 cml lzO external
PS, CPAP, npn~n.
NPI'V
Versa Mcd C,ACV,SIMV 100-2000 1-50 Up totSO 0.3-3.0 1-20 1Hcrs/min1 I SO'~o ol ~ct VT I every 25 to 1 Up to 20 onHzO
iVcntau press. and Vol., -OS to - 20 every 150
PS, CPAP, npncil, cmlllO breath<>
NPPV
Newport C,ACV,SIMV 100-2200 t -99 6-100 0.1-3.0 -9.9 to 0 cmH 20 Up to 30 cmH1 0
HTSO p~ ,1nd vol.,
PS,CPAP
xon C. control. ACV, •!>'b~trol \'"tonhbtion, SIMV, $fN'htoni:t.«< i.nbmnittent mandatory \-entibtion~ A, ~t. I:E raho. lrbJ"r.Uwn/ opuaUon uti<). P££f', pc:ll!l>•liw end~xpitatory ptes.'iure; V1, tidal volume,
P8. Punt.t~t
TABLE 4-2 Alaml Systems of Volume·.Yargeted Home-Care Positive-Pressure Ventilations
High
lnspiralory Low Rev~rse
Pressure Inspiratory Inverse Low External Switch Minimum
Alnrm., Pressure, Low 1/E Ventilator Inspiratory Battery Microprocessor to Power Minute
c:ml-120 em H 20 Apnea Battery Ratio Malfunction Fl O\\' Connections F<tilure B.1ttery failure Oxygen Volume
PB LP-10 25-100 2- 50 Yes Yes Yes' Yes Yes' No Yes Yes Yes No No
PB LP·6 Plu• 25-100 2-50 Yes Yes Yes' Yes Yes' No Yes Yes Yes No No
Lifecare 5-95 2- 50' Yesb Ycsb Yes Yes Yc" Yes Yes Yes Yes No No
PLV·100
f-.> lifec:are 5-95 2- So< Yes• Yesb Yes Yes Yes Yes Yes Yes Yes Yes No
0 I'LV·102
N PBAchieva 2-80 '1- 59 Yes Yes Yes Yes No No Yes Yes Yes Yes No
Rcspiron.ics 10-80 3- 50 Yes Yes Yes Yes No Yes Yes Yes Yes No No
Pl..V
Continuum
PuJmonetic 5-'100 '1-60 Yes Yes Yes No No No Yes Yes Yes Yt.."S Yes
LTV
Ver$a M ed 3-80 1- 77 Ye.; Yes Yes No No Ye.; Yes Yes Yes Ye.; Yes
iVent201
Newport 4-99 3-98 Yes Yes No Yes No No Yes Yes Yes No Yes
HTSO
11 Ac:tu3Uyreferred to 3.S setting error; rontt·oJs are set outside m:~chine limit'S.
bt.ow ii\Spir(ltory pr~ure and "'P•'ea C~lomns are actually co•nbined.
t Have separate alarm (o r low inll."mal and low e)(lernal battery.
MODES
Both volwne and pressure assist-control modes are avail-
able. In these modes, the ventilator is set as in most other
ventilators. Trigger sensitivity is either via pressure or flow.
Flow sensitivity ranges between 3 and 25 liters/min, and
pressure sensitivity ranges between off and 1- 15 cmH10.
•••
PEEP up to 20 em H20 can be applied to all modes of venti-
,
•
•
.. lation, and CPAP to 20 em H20 also can b e set. During CPAP,
as well as during the spontaneous brea ths w ith SIMV, gas
delivery is based on patient demand up to 180 liters/ min.
Only volume-targeted SIMV is available, and PSV can be
used as an independent mode or in conjunction with SIMV.
Table 4-1 lists ranges for gas-delivery variables.
ALARMS
The Achieva incorporates low- and high-pressure alarms,
an apnea alarm, an equipment-failure alarm, a low-
• • power alarm, an 02 fail a larm, a setting-error alarm, a
microprocessor-error alarm, and a power-switchover indi-
ca tor. Alarms activate at different levels to indicate the sever-
ity of the alarm activated. Repeating bursts of five alarm
pulses occur when low pressure or apnea is identified, the
ventilator has d etected an equipment error, and the internal
FIGURE 4,-s The Puritan-Bennett LP-6 Plus Ventilator. battery is depleted. Repeated bursts of three pulses occur
when the internal battery is low (10 minutes of power re-
maining), high pressure has developed, or the 0 1 system
of the PEEP control and to ensure that a gas-collection head fails. A single beep repeated every 5 minutes indicates in-
is available to allow monitoring of exhaled gas. appropriate inspiratory-expiratory time (I:E) ratio, 45 min-
utes of d e power, or a minor equipment fault. Setting errors
are also identified by single beeps. Activation of the ap-
CLASSIFICATION nea alarm results in ventilation being provided at a rate of
The Achieva is an electrically powered, linear-piston- 10 breaths per minute. See Table 4-2 for details on alarm
driven, microprocessor-controlled ventilator. It incorpo- systems.
ra tes a single gas-flow system and produces multiple
gas-flow patterns. Inspiration is triggered by either time or
pressure, whereas exhalation may be cycled based on vol- POWER SOURCE
ume, time, or flow. As with all ventilators of this class, the Acl1ieva operates via
three distinct power sources: ac, external de, and internal de.
On change of power source, both visual and audio alarms
are activated. The intemal de battery lasts from 1 to 4 hours
FIGURE 4-6 The Puritan-Bennett Achieva Ventilator. depending on ventilator settings.
MISCELLANEOUS
During machine power-up, a complete unit diagnostic check
of all systems occurs. Activation and setting of variables are
menu-driven. The ventilator can be connected to a telephone
by its internal modem using a standard R11 phone connec-
tor; in addition, the ventilator contains an RS-232 port. A
remote-alarm connector and nurse-call connection are also
available.
CRITICAL ANALYSIS
The overall design of the ventilator interface is somewhat
busy and requires knowledge of computer-driven systems.
The design, however, prevents inadvertent changing of pa-
rameters. The ability of this ventilator to provide pressure-
targeted ventilation or demand flow has not been evaluated.
104 PART fl PHYSICAL BASIS OF MECHANICAL VENTILATION
..........
- ~
--
(
FIGURE 4-7 The Liiecare PLV-100

Ventilator.
LIFECARE PLV-10029 It is classified as a non-constant-flow generator. Inspira-

tion is triggered by either time (control mode) or pressure
The Lifecare PLV-100 (now owned by Respironics) weighs (ACV, SIMV), whereas exhalation is always cycled based on
28.2 lb and has the following overall physical dimensions: volume. System pressure, however, is limited by the high-
9 in high x 12.5 in wide x 12.25 in deep (Fig. 4-7). It is a airv.ray-pressure alarm. This level, once reached, dumps the
compact and highly portable microprocessor-based home- remaining gas in the piston chamber to the atmosphere but
care ventilator. It is not currently manufactured, although a does not alter inspiratory time.
large number of units are still in clinical use. The basic gas-
flow pattern for the PLV-100 is illustrated in Fig. 4-2, with
two major exceptions. First, no 02 accumulator is available MODES
for a ttachment to the unit's gas entry port (A). Second, the Control, ACV, and SIMV modes are available on the PLV-
one-way valve a t C, which allows gas inflow during spon- 100. In the control mode, the practitioner sets ventilator rate,
taneous breathing when the piston is in its backstroke, is not tidal volume, and inspiratory-flow rate. The unit determines
present. Essentially, gas enters the piston chamber at A and inspira tory time based on these settings and displays an I:E
is moved from the chamber into the internal gas-delivery ratio. In the control mode, the patient is unable to activate
system at 8. A pressure pop-off valve is also located i.nsid_e a positive-pressure breath but can breathe spontaneously
the piston chamber. From 8, gas proceeds past an 1nsp1- via the piston chamber or the exhalation valve. In the ACV
ratory pressure-limit valve, out of the ventilator, through mode, all settings are identical to the control mode, with
the inspiratory circuitry, and to the patient. The exhalation- the addition of sensitivity setting. Inspiratory time remains
valve line originates from the internal ventilator circuitry. A constant with each positive-pressure breath, but the I:E ra-
proximal airway-pressure line provides input to the micro- tio display indicates a varied ratio depending on the rate
processor (the system manometer is tapped off this line). Oz that the patient is assisting. In the SIMV mode, the machine
is administered via an adapter interfaced with the unit be- setup is identical to the ACV mode. Because of the patient's
tween the external circuitry and the unit itself. An increase spontaneous breathing efforts, however, the l:E ratio display
in delivered tidal volume, as well as Fro21 results. is inactivated. A 6-second window is available for patient
triggering of the SIMV mandatory breath; as a result of this
CLASSIFICATION large window, delivered positive-pressure rate may vary.
The PLV-100 home-care positive-pressure ventilator is The PLV-100 does not contain a demand system. Thus, un-
rotary-piston-driven via an electric motor and under the less the unit is configured with a continuous-flow system,
control of a microprocessor. It incorporates a single gas- the patient must draw air during spontaneous ventilation
flow system, and the rotary-piston design produces a sine- either from the piston chamber or via the exl1alation valve.
wave gas-flow pattern with a sigmoidal pressure curve. Table 4-1 lists ranges for gas-delivery variables.
CHAPTER 4 EQUIPMENT REQUIRED FOR HOME MECHANICAL VENTILATION 1OS
ALARMS to 60 minutes of power, depending on the actual ventilator
The PLV-100 incorporates 11 system alarms: low pres- settings. The higher the demand, the shorter is the time pe-
sure/apnea, high pressure, inverse I:E ratio, increase inspi- riod. The internal battery is charging whenever the unit is
ratory flow, low internal battery, low external battery, re- plugged into an ac outlet, regardless of activation.
verse external-battery connection, switch to battery, power
failure, microprocessor failure, and ventilator malfunction. MISCELLANEOUS
The low-pressure audio alam1 is activated if the set low During machine power-up, a complete unit diagnostics
airway pressure is not exceeded within a 15-second pe- check of all systems occurs. This lasts about 5 seconds, dur-
riod. A front-panel light-emitting diode (LED) flashes wit!"\ ing which LEDs are active and alarms sound. Digital read-
each breath as pressure passes the set level. In SIMV, the outs of tidal volume, rate, I:E ratio, and inspiratory-flow rate
low-pressure alarm also acts as an apnea alarm. The pa- are provided. In addition, a front-panel cover is available as
tient's spontaneous inspiratory efforts are sensed by the low- an accessory.
pressure mechanism, and the 15-second delay is reset. Thus,
if either the machine does not sense a spontaneous breath
or the positive-pressure level does not exceed the set mark CRITICAL ANALYSIS
within a 15-second period, the alarm is activated. The overall physical layout of the control panel is very busy,
The high-airway-pressure alarm (audio only) is activated making the machine appear intimidating and increasing
each time the patient's peak airway pressure exceeds the the difficulty in teaching its operation initially. The sensi-
alarm setting. When this occurs, tidal volume remaining in tivity and high-airway-pressure-limit control knobs are not
the piston chamber is dumped to the atmosphere while the calibrated, making them difficult to set. To determine the
piston continues its forward motion. As a result, inspiratory high-airway-pressure-limit setting, the patient must be re-
time remains unaltered. The alarm resets automatically after moved from the ventilator. It is possible to provide inverse-
each breatl1. ratio ventilation, an approach that is not indicated in the
The inverse I:E ratio alarm is a visual flashing alarm that home. The attachments for the exhalation-valve line and
is activated whenever the inspiratory time exceeds the ex- the proximal-airway-pressure line are of different sizes to
piratory time. No action on the part of the practitioner is avoid inadvertent misconnection.
indicated if an inverse I:E ratio is desired.
The increase-inspiratory-flow alarm is a visual alarm ac-
tivated if inspiratory flow is insufficient to meet other set UFECARE PLV-102
parameters. When activated, the inspiratory-flow display TI1e PLV-10230 (Fig. 4-8) is essentially an update ofthe PLV-
will flash '1ncrease Inspiratory Flow" while the inspiratory 100. This ventilator, as w ith the PLV 100, is not currently
flow is increased automatically. Inspiratory flow, however, manufactured, but a large number of these units are still in
will not increase to a level to prevent an inverse I:E ratio. clinical use. The internal gas-flow path is the same as with
The low-internal-battery alarm is both an audio and vi- the PLV-1 00 with the addition of an 02 proportioning valve
sual alarm, activated if the internal battery falls below 9.5 and a 50 lb/in2 gauge 02 attachment. A DISS 02 connector
V. The external-battery alarm functions in precisely the exists on the back of tl1e ventilator; from here, 02 enters a
same manner. If an attempt is made to reverse the external- proportional valve, from which it proceeds to a flow sen-
battery connection, an alarm sounds until the connection is sor and then into the internal inspiratory circuit, bypassing
corrected. the piston chamber, thus allowing a delivered F1~ of up
Whenever the power source switches from ac to either to 0.90. In ACV and control modes, F1~ is simply set on
external de or internal ac, a 3-second audible alarm sounds. the front panel. The accuracy of 0 2 delivery, however, de-
Additionally, if the power switch is in the" on" position and creases at low tidal volume settings less than 300 ml and
no power is applied to the tmit, an audible alarm is activated. high F1~ settings of greater than 0.40. During SIMV, the
If the microprocessor fails to pass its diagnostic self-test, manufacturer recommends using tl1e unit's 0 2 sensor. The
an audio alarm is activated, and the piston motor locks, sensor cable originates on the front of the machine and is
preventing uncontrolled function. In addition, if tl1e unit's interfaced between the humidifier a nd the ventilator at leas t
pressure transducer fails or the piston system fails to cycle 18 in proximal to any H valveorto the unit itself. The sensor
properly, a "fast beep" audible alarm is continuously acti- is necessary to ensure consistent Fr~ during spontaneous
vated if attempts are made to use the unit. See Table 4-2 for ventilation. If the sensor is not present during SIMV, room
a comparison of ventilator alarm ftmctions. air is inspired during spontaneous unassisted ventilation.
POWER SOURCE
As with all the ventilators in this class, the PLV-100 is oper- CLASSIFICATION
ational via three distinct power sources: ac, external de, and The PLV-1 02 is classified i11 the same manner as the PLV-1 00.
internal de. This unit always selects ac power if the power-
ing mechanism is available. If the unit must switch to either MODES
de source, a 3-second alarm is activated. When functioning In addition to the control, ACV, and SIMV modes, the PLV-
on a de source, the voltage level of the source can be eval- 102 incorporates control + sigh and ACV + sigh modes.
uated rapidly by the "Read Battery Volts" indicator on the During both these modes, the ventilator automatically de-
front panel. TI1e internal battery is capable of providing up livers a sigh breath at 150% of the set tidal volume once
FIGURE 4·8 The Lifecare PLV-102 Ventilator.
every 100 breaths. Table 4-1 lists the ranges for gas-delivery and inverse I:E ratio ventilation is also feasible, as in the
variables. PLV-100.
ALARMS 1
RESPIRONICS PLV CONTIN1JUM3
ThePLV-102incorporates the 11 ala rms included on thePLV-
100, with the addition of a n02 a larm that is activated if(1)0 2 The PLV Continuum is a highly versatile, compact (10 in
source pressure is less than 45 lb/in 2, (2) 0 2 source pressure wide x 12 in deep x 5.5 in high), lightweight (23 Ib), micro-
is greater than 55lb/ in2 , (3) the ventilator 0 2 valve is stuck processor-controlled portable home-care ventilator (Fig.
open, (4) the 0 2 sensor is defective, and (5) the ventilato r 4-9). This unit is turbine-d riven; as a result, gas deliv-
demand exceeds 0 2 valve capability (>90 liters/ min). In ery is highly programmable. ACV (pressure or volume),
addition, the PLV-102 elisplays alarm codes in the peak-flow SIMV (pressure or volume), PSV, CPAP, and apnea modes
cligital readout window. A decal with code definitions is are available. In addition, a sigh can be delivered during
attached to the machine. A 30-second alarm silence also has
been included . See Table 4-2 for a comparison of ventilator
alarm conditions. FIGURE 4-9 The Respironics PLV Continuum Ventilator: (1)
p ower on/off, (2) system p ower indicators, (3) alarm reset button,
(4) alarm s ilence button, (5) status indicators, (6) display control
POWER SOURCE buttons, (7) p atient pressu re port, (8) exhalation valve port, (9) gas
The power-source da ta are identical to those of the PLV-100. outlet port, and (10) display panel. (Used, with permissio11, from
Respirouics.31 )
MISCELLANEOUS
The PLV-102 has two options not available on the PLV-100: a 5
remote alarm and a printer hookup. In addition, a manual-
sigh button allows for sighs on user discretion.
CRITICAL ANALYSIS
The PLV-1 02 is even more complex than the PLV-100 and less
user-friendly. In addition, the 50 lb/in 2 Oz attachment and
F1~ delivery system make it even less practical for home
use. This add-on, however, makes the unit very attractive for
use in long-term-care facilities or hospitals. The sensitivity
and high-pressure-limit control knobs are not calibrated,
volume ACV. As with other ventilators in this class, it op- and modes, and an alarm screen provides control of alarm
erates from multiple power sources, including an internal settings. The final screen is a preference screen, directing
battery. Both flow and pressure are monitored during gas the clinician to other screens and functions. The ventilator
delivery; thus tidal volume is displayed. The ventilator can can download data via an RS-232 port or upload revisions
be operated with or without supplemental 0 2 entrained, of software via a PC connection port. A remote-alarm at-
although precise Oz delivery is not possible. tachment is also present. A proximal pressure line is used
to monitor pressure and enhance triggering to inspiration.
CLASSIFICATION
The PLV Continuum is an electrically powered, turbine- CRITICAL ANALYSIS
driven, microprocessor-controlled home-care ventilator. It is TI1is is a very versatile home-care ventilator, usable in pedi-
single-circuited, with inspiration activated by time or pres- atric to adult patients requiring any of the standard modes
sure, and expiration cycled based on time, volume, pressure, of ventilation. Its major drawback is the lack of PEEP. In-
or flow. advertent parameter change is almost impossible; the use
of the system requires knowledge and comfort with com-
MODES puter systems. The function of this ventilator has never been
The ACV and SIMV modes operate like any other demand- compared with that of other similar units.
flow ventilator. Both modes can be set as volume- or
pressure-targeted ventilation. In addition, PSV is available.
During PSV, pressure ACV, and pressure SIMV, rise time is PULMONETIC S YSTEMS LTV32 , 33
active. PSV is terminated by flow decreasing to 25% of peak
or by pressure increasing above the set level at the end of a TI1is is one of the most compact of all volume mechanical
breath by 5 cmH20 or 10% of the set pressure+ 2.5 cmH20. ventilators. It is 10 in wide, 12 in deep, and 3 in high, weight-
Both square and decelerating ramp flows are available during only 12.6 lb (Fig. 4-10). Because of its turbine design, it
ing volume breaths. Apnea ventilation at a rate of12 breaths is able to operate without an externa I gas source. Because of
per minute is also activated after a 20-second apnea period. its microprocessor control, it is able to provide a variety of
PEEP is not available. Table 4-1 lists ranges of gas-delivery both pressure and volume modes of ventilation. This venti-
variables. lator also incorporates leak compensation to coordinate pa-
tient triggering more effectively. Depending on the particu-
ALARMS lar model, precise Fio, delivery to 100% via a high-pressure
A total of 14 ventilator alarms and alerts and 7 patient alarms gas source is available. Despite its small size, an internal
and alerts are present. From the patient perspective, ap- battery is included. Patient triggering is primarily by flow
nea, high-inflation pressure (two consecutive breaths), ex-
cessive inspiratory time, low pressure, and system occlu-
FIGURE 4-10 The Pulmonetic System LTV-1000 Ventilator.
sion/ disconnect are alarmed. In addition, patient visual
:
alerts are activated if airway pressure is high for a sin- .
gle breath or if an inverse I:E ratio is established. Machine
alarms include alarm failure, barometer failure, depleted
external battery, depleted internal battery, external battery
connection, high gas temperature, indicator failure, low in-
ternal battery, primary alam1 failure, using default settings,
and ventilator inoperable. Ventilator alerts are activated vi-
sually if indicators fail, the external battery power is low,
and the ventilator is nmning on the internal battery. See
Table 4-2 for a comparison of ventilator alarm conditions.
POWER SOURCE
Operation is possible by ac, internal de, and external de
power. The internal battery lasts 15 minutes to 1 hour de-
pending on ventilator settings. When the internal battery
is running, a visual alert is provided, as well as when the
internal battery charge is low. The internal battery charges
whenever the unit is plugged into ac current.
MISCELLANEOUS
The ventilator is set using a series of four screens in a menu
format. A group of five control buttons on the front upper-
right side control screen and setting selection. Multiple en-
tries are required to make a setting chaJlge. With startup,
a self-check is performed, and the startup screen indicates
the last patient's settings. A settings screen controls settings
(1-9 liters/ min)-diverting flow from the fixed-bias flow POWER SOURCE
of 10 liters/min established during the expiratory phase. Ac, de internal, and external de power are available. The
A secondary pressure trigger is active when airway pres- internal battery lasts a maximum 1 hour and 37 minutes
sure falls to -3 cmH 2 0. The displayed leak measurement is depending on ventilator settings. When the internal battery
useful in setting the flow sensitivity. is operational, an alert is activated.
MISCELLANEOUS
CLASSIFICATION On activation, the ventilator performs a power-on self-test
The LTV ventilators are electrically powered, turbine-
that ventilates with the last set parameters. Mode selection is
driven, microprocessor-controlled home-care ventilators.
made by pressing the mode-select button twice, and the use
l11is unit is single-circuited, with inspiration triggered by
of pressure or volume ventilation is determined the press-
time, flow, or pressure and expiration initiated by time, pres- ing these controls twice. In addition, the user may set any of
sure, volume, or flow. the following extended-feature options by entering a sep-
arate field: alarm volume, low-pressure alarm, variable in-
MODES spiratory time termination, apnea interval, pressure-control
ACV and SIMV modes are available in both pressure and flow termination, NPPV mode, high-pressure alarm delay,
volume ventilation. In addition, PS and CPAP are avail- and variable flow termination. A manual-breath control is
able. During SIMV, PSV can be applied to the spontaneous also provided. A specific ventilator circuit is required with
breaths. Duri11g pressure ACV breaths, rise time can be ad- a proximal pressure-sensing line to monitor pressure and
justed. During PSV, the terminating flow can be adjusted improve triggering.
from 10-40% of peak flow. Pressure ACV breaths also can
be terminated by flow if des ired. That is, either flow or time CRITICAL ANALYSIS
can end the breath, whichever is met first. The same can oc- This is a very sophisticated home-care ventilator offering
cur in PSV by setting the variable time limit or if inspiratory many modes and adjuncts to modes. Its biggest limitation
time exceeds two breath periods. Apnea backup ventila- is the lack of electronic integration of the PEEP controL It
tion is present in all modes a t a rate equal to the set rate is also not a user-friendly ventilator. Actual setting of vari-
if the set rate is greater than 12 breaths per minute and at ables is confusing. It has a user-lockout feature, however,
a rate of 12 breaths per minute if the set rate is less than preventing inadvertent parameter adjustment.
12 breaths per minute. A noninvasive ventilation mode is
also included (NPPV). Activation of this mode can occur 34
only in conjunction with the other primary modes of ven- VERSAMED i VENT201
tilation. When activated, the NPPV LED is lit, and only the The iVent201 is a turbine-driven home-care/subacute-care
following alarms are active: high pressure, apnea, external ventilator incorporating most of the features of an intensive-
power lost_ internal battery low, ventilator inoperable, and care-unit (ICU) ventilator. It is the only ventilator of this class
default settings . Specifically, the low-minute-volume and that provides continuous waveforms of pressure, flow, and
low-peak-pressure a larms are inactive. PEEP is not an in- volume. The ventilator is portable and compact (13 in high
tegrated microprocessor-controlled function with this ven- x 9.5 in wide x 10.3 in deep), weighting only 22 lb (Fig.
tilator. PEEP is established by addition of a spring-loaded 4-11). With startup, the ventilator goes through a ventilator
PEEP valve on the expiratory limb. A specific ventilator cir- verification test to ensure proper function . In addition, an
cuit is required with this ventilator. Table 4-1 lists ranges for operational verification test requiring attachment of the cir-
gas-delivery variables. cuit to a test lung should be preformed with every circuit
change. In addition to multiple modes and monitoring and
ALARMS alarm functions, PEEP is an integrated aspect of the func-
A total of 12 alarms are included on the LTV: apnea, battery tion of this ventila tor. Ventilator triggering to inspiration
depleted, low battery, defaults settings activated, pressure- can be by either time, press ure, or flow, and cycling to ex-
sensing-line disconnect/ malfunction, high 0 2 pressure, halation can be based on time, volume, pressure, or flow.
high airway pressure, hardware faults, ventilator inoper- A high-pressure DISS 02 connection is available providing
ative, low minute ventilation, low 0 2 pressure, and low air- precise Fio,, or the unit may be run by entraining room air
way pressure. In addition, a number of patient variables and titrating 0 2 into the system gas inlet.
are monitored and displayed. In order to measure many
of these variables, the inspiratory-hold or expiratory-hold CLASSIFICATION
control must be activated periodically. The inspiratory hold, The iVent20'1 is an electrically powered, turbine-driven,
however, is only active in volume ventilation, and the expi- sil1gle-circuited microprocessor-controlled ventilator.
ratory hold requires passive exhalation. The specific moni-
tored variables are peak inspiratory pressure, mean airway MODES
pressure, PEEP, frequency, exhaled tidal volume, minute ACV and SIMV pressure- o r volume-targeted ventilation
ventilation, I:E ratio, calculated peak flow, plateau pressure, is available. In addition, PSV, CPAP, and bilevel venti-
quasi-static compliance, and auto-PEEP. See Table 4-2 for a lation are included. Sigh breaths during volume ventila-
comparison of ventilator alarm conditions. tion can be provided. Rise-time variability is available for
volume, flow-volume, and pressure-flow loops can be dis-

played. A lung mechanics package (compliance, resistance,
and m ean airway pressure) is also available. Trends of mon-
itored data also can be displayed. See Table 4-2 for a com-
parison of ventilator alarm conditions.
POWER SOURCE
The iVent201 can be operated on ac, de internal, or de ex-
terna l current. On switchover to internal de, indicators are
activated. The internal battery may last up to 2 hours de-
pending on ventilator settings.
MISCELLANEOUS
The ventilator operates via a rotating control knob requir-
ing a push to enter a charge and a series of touch pad keys
located on the ventilato r front panel . Data and options are
presented in a series of menus accessible by the rotator con-
troler. The ventilator has an RS-232 port, and an Spo2 probe
can be connected to the ventilator. A specific circuit is re-
quired with a proximal pressure-sensing line for monitoring
of pressure and to improve triggering.
CRITICAL ANALYSIS
The only major concern with this ventilator is that it may
be too much of a ventilator for use in the home. It clearly
FIGURE 4-U The VersaM ed iVent2o1 Ve ntilator. contains modes and monitoring capabilities more useful
in the ICU than in the home. It is very busy and somewhat
intimidating to the uneducated user. For home-car e use,
pressure-targeted breaths. Easy exhale is an adjus tment rec- the a irway pressure, flow, and volum e waveforms may be
ommended for use during bilevel. When activated, this fea- too much.
ture momentarily relieves the exhala tion-valve diaphragm
of pressure immedia tely at end inspiration. The ventila tor
also includes two unique mode adjuncts: adaptive peak flow NEWPORT HTS0 35
and adaptive time. Adaptive peak flow allows the ventila- This ventilator is also a very compact (10.24 in high x 10.63
tor to determine the inspiratory peak flow required to meet in wide x 7.87 in deep) and lightweight (15 lb), por table,
the set tidal volume w hile maintaining an I:E ratio of 1:2. rnicroprocessor~controlled home-care ventilator (Fig. 4-12).
Adaptive time allows the ventilator to d etermine the inspi- The unit is turbine-driven and has an attachment for the
ratory time (in pressure ventilation) to maintain a 1:2 I:E addition of low-flow {1-10 liters/min) 0 2 . At high minute
ratio. Bilevel is similar to airway pressure-release ventila- volumes, however, high Fiaz is not attainable. A specifically
tion (APRV), where the patient can breathe spontaneously designed circuit is required. A proximal-airway-pressure
at two levels of CPAP or during SIMV. I:E ratio in this line is included in the circuit for monitoring and triggering.
mode can be inverted. Table 4-1 lists ranges of gas-delivery A number of modes of ventilation are offered, and sensitiv-
variables. ity is via pressure triggering.
ALARMS CLASSIFICATION
This ventilator has 26 alarms arranged by priority: high, This is an electrically powered, turbine-driven, micro-
middle, and low level. High-priority alarms are apnea, bat- process or-controlled single-circuit ventilato r producing a
tery empty, excessive leak, high Fro_,, high minute volume, variety of gas-flow patterns. Inspiration is triggered by ei-
high airway pressure, low battery, low breath rate, low Fr0 2, ther time or pressure, and expiration is cycled based on
low minute volume, low 0 2 pressure, needs service, high in- either time, volume, flow, or pressure.
ternal ventilator temperature, patient disconnect, proximal-
pressure-sensor disconnect, tubing disconnect, and high MODES
PEEP. Middle-priority alarms are ac power disconnect, high The HT50 provides ACV and SIMV in both pressure and
breath rate, low airway pressure, needs calibration, low tidal volume ventilation. In addition, CPAP and PSV are avail-
volume, and volume limit reached in pressure ventilation. able. PSV may be added to the sponta neous breaths during
Inverse I:E ratio is a low -priority alarm. In addition, anum- SIMV, and PEEP can be applied with any mode. During
ber of pa tient variables are m onitored and displayed : ex- PSV, the breath is terminated when th e peak flow decreases
haled tidal volwne, rate, I:E ratio, inspiratory time, and peak to 25%, the peak pressure exceeds 3 cmH20 above the set
inspiratory pressure. Waveforms for pressure, volume, and level, or inspiration time equals 3 seconds. Backup venti-
flow are also displayed continually. In addition, pressure- lation is available in all modes a t a frequency of 1.5 times
or volume for up to 3.0 seconds with continued touchpad

depression. The panel is locked automatically 20 second af-
ter the last adjustment. The unlock-panel touch pad must be
depressed for at least 1.0 second to unlock the control panel.
An R$-232 port is also included.
·-- ... _
.. ....... •• ft ........
-·~-
CRITICAL ANALYSIS
This is the easiest to operate of all the newest ventilators
of this group. The control panel is very user-friendly, and
the automatic lockout feature makes undesired changes un-
likely. PEEP is an integrated fw1 ction of the ventilator, mak-
. " .. - . .'
' ,.. .. . ing the unit much more useful in a variety of clinical set-
tings. 0 2 delivery is the one concern. 0 2 must be titrated
into the external gas entrainment port, and the capability of
delivering high Fr01 is questionable. The unit's gas-delivery
functions have not been compared with those of other ven-
tilators in this class.
Noninvasive Positive-Pressure Ventilators

FIGURE 4-12 The Newport HTSO Ventil ator:.
This group of positive-pressure ventilators only provides
pressure ventilation, either pressure ACV or PSV, and gen-
erally, they are designed exclusively for noninvasive use.
the frequency setting with a minimum of 15 breaths per The primary reason for avoidance of invasive application
minute during ACV and SIMV. During CPAP and PSV, the is the inability to provide a high FI0 2, inadequate monitor-
mode changes to pressure control at a rate of 15 breaths per ing of patients status, and inadequate alarms. These units
minute, peak pressure 15 cmH2 0, and inspiratory time of have a distinct advantage over ventilators designed for in-
1.0 second. Table 4-1 lists ranges for gas-delivery variables. vasive use because they compensate for leaks. 23,24,36,37 In
addition, they are highly responsive to patient inspiratory
ALARMS effort, responding at least as well as ICU ventilators.24,36,37
A total of 16 alam1s are included on the HT50: high and Each of these ventilators includes some or all of the follow-
low airway pressure, high and low baseline (PEEP) pres- ing modes: control, ACV, PSV, and CPAP. See Table 4-3 for
sure, high and low minute volume, circuit occlusion, device modes offered by specific ventilators.
occlusion, apnea, check proximal pressure line, set pres- In addition to the lack of monitoring and alarms, there
sure not reacl1ed (pressure control), low battery, empty bat- are two other major issues with these devices: delivery of
tery, power switchover, device alert, and device shut down. an increased F10 , and the "potential" for C02 rebreathing.
The ventilator includes a message window where tidal vol- As with all ventilators, 0 2 can be titrated into the inspira-
ume, peak pressure, PEEP, frequency, mean airway pres- tory circuit. With these units (Fig. 4-13),38 0 2 can be titrated
sure, and minute volumes are displayed. In addition, an into the mask or the circuit at the attachment to the ven-
airway-pressure meter and battery charge indicator are lo- tilator. The actual FrCh delivered depends on a number of
cated on the front panel. factors. The first factor is the location of the expiratory port.
As noted in Fig. 4-13, the circuit is a single-limb circuit with-
POWER SOURCE out an exhalation valve. Exhalation occurs through a small
As with aH these ventilators, the HT50 can be operated by orifice either in the mask itself or in the circuit near the mask.
ac, internal de, and external de current. Power switchover A secondary isolation valve can be added to the circuit distal
is indicated on the front panel, as well as internal battery to the expiratory port. Thus the circuit is open. Ventilation
charge level. Low- and empty-battery alarms also are in- is accomplished because these units rapidly compensate for
cluded . The internal battery lasts up to 8 hours when fully leaks and have a high enough flow to maintain system pres-
charged depending on actual ventilator settings. See Table sure despite the leaks. The second factor that affects Fio, is
4-2 for a comparison of ventilator alarm functions. pressure settings: The higher the settings, the lower is the
Flo, because higher settings translate into greater flow com-
MISCELLANEOUS pared v.rith the fixed flow of 02 into the circuit. Schwartz
This ventilator is set by touchpad key entry of all parame- et al,38 using a lung model (see Fig. 4-13), recently demon-
ters. Individual touchpads for each variable are located on strated the large variability in F10z at 5 and 10 liters/min
the front panel. An optional humidifier is available, and its 0 2 flow into the circuit. At high ventilator settings with the
operation is monitored on the front paneL A manual infla- leak port in the mask and 0 2 titrated into the mask itself,
tion control is also on the front panel. Depression of the only 22-25% delivered 0 2 could be achieved at 0 2 flows
touchpad delivers a mechanical breath at the set press ure of 5 and 10 liters/ min. With the leak port in the circuit,
TABLE 4-3 Specifications of Bilevel Pressure Noninvasive Ventilators
Puritan Bennett Puritan Bennett

Respironics Respironics Rcspironics Rcspironks Rcspironics Rcspironics Res Med Res Med RcsMcd Knight Star Knight Star
B,PAPS{f B,PAP S{f·D 30 Vis-ion B, PAPPro2 B,PAP Plus Synchrony VPAP Ill VPAP Ill ST VPAP ST-A 335 330
Modes C,ACV, A C, AOJ, A C, ACV,A A A C, ACV,A A,CPAP C,ACV, A C,ACV, A C,ACV, A, ACV,
CPAP CPAP CPAP CPAP CPAP CPAP CPAP CPAP
Inspiratory pressure, 4-20 4-30 4-40 4-25 4-20 4-30 4- 25 4-25 3-30 J.-35 3-JO
em H20
Expiratory pressure, 4-20 4-30 4-40 4-25 4-20 4-20 4-25 4-25 J.-25 J.-20 3- 20
.....
..... em H20
..... Rate, per Min 4-30 4-30 4--40 4-30 ~ J.-30 J.-30 3- 30
Inspiratory time,% 10-90 '1 0-90
Maximum flow, 120 120 180 120 120 120 130 130 130 120 120
bites/ min
Inspiratory time, s 0.5-3.0 0.5-3.0 0.1--4.0 0.1--4.0
Oxygen concentration 21- 100%
l:E ratio 1:1to1:4 1:1 to 1:4
co,. tidal
\'Oiume
Purlan·Bennett 840
BIPAP
venfilet!Ot
FIGURE 4-13 Illustration of 0 2 addition to a bilevel
ventilator circuit in a lung model. (Used, with
pennission, from Schwartz et al: Respir Ca,re 49:270-5,
CO, tivatcd into bellows 1997.)
however, and 0 2 titrated into the mask at 10 liters/min controls flow, pressure level, and inspira tory and expira-
and low ventilator pressures, over 60% 0 2 could be deliv- tory cycling times via a microprocessor. Before gas leaves
ered. This point is important: It is impossible to predict o r the unit, it passes a flow transducer that provides feedback
measure delivered Fr0 , with most of these systems. As a via the microprocessor to the control solenoid valve.
result, very careful monitoring of patient response is re- The unit includes five separate controls: mode selector
quired whenever supplemental 0 2 is needed. Very high inspiratory positive airway pressure (IPAP) level; peak in-
flows of 0 2, up to 75liters/min, can be titrated into some spiratory pressure setting; and EPAP (PEEP) or CPAP level,
of these units, establishing greater than 90% 0 2 •39 These rate, and inspiratory time percent. Even when the EPAP
high 02 flows, however, increases PEEP above the set level control is set at minimum, a low level of CPAP / PEEP
and peak airway pressure by as much as 7 cmH20.39 As a
result, the addition of high-flow 0 2 into the circuit is not
recommended. FIGU RE 4-14 Volume of C0 2 inhaled from the ventilator tubing
As discussed earlier, the ventilator circuit is single-limbed at various IPAP and EPAP settings during Br PAP ventilatory
without a true exhalation valve. This, coupled with the assistance in normal subjects (top) and patients (bottom).
fact that these ventilators have low internal resistance, • p < 0.05 com pared with other devices at similar B1PAP settings.
increases the possibility of inadvertent C02 rebreathing. (Used, with permission, from Ferguson eta /; Am J Respir Crit Care
M ed 151:1126-35, 1995.)
As noted in Fig. 4-14, when PEEP or end-expiratory air-
way pressure (EPAP) is set at zero or at a low levet 24 • N ormar..
exhaled gas can move retrograde through the ventilator
20
circuit all the way back through the ventilator, causing
CD2 rebreathing. 40 The setting of PEEP, however, ensures 16
• •
*
flow from the ventilator toward the patient during exha- 12
lation, preventing CD2 rebreathing. C02 rebreathing also
can be prevented by the use of an isolation valve or a stan- a
dard exhalation valve. All newer bilevel ventilators main- 4
tain a minimum PEEP (2~ cmH20) even when PEEP is 0

turned off to minimize C02 rebreathing. The lower the
PEEP level, however, the greater is the likelihood of C02 IPAP 0 4 8 12 16 20 20 20 20 20 20
rebreathing. EPAP 0 0 0 0 0 0 4 a 12 16 20
The original bilevel ventilator is the Respironics B1PAP 16 Potionrs

S/T ventilator41 (Fig. 4-15). Although these units are no •
•
longer manufactured, many of them are still in general use. 12 •
The unit provides pressure-limited, time- or flow-cycled 8
ventilator assistance via a mask. The BrPAP S/T is operated *
by a turbine blower and is designed to provide a continu- 4
ous flow of gas. It is 73j4 in high, 9 in wide, and 12 3/16 in 0

in diameter and weighs 9.5 lb. Gas is drawn into the unit
from the filtered back panel and then passes through an IPAP 0 4 8 12 16 20 20 20 20 20 20
electromagnetically operated solenoid valve (Fig. 4-16) that EPAP 0 0 0 0 0 0 4 8 12 16 20
CHAPTER 4 EQUTI'MENT REQUIRED FOR HOME MECHANICAL VENTILATION 113
FIGURE 4-15 The Respitonics B,PAP Sfr Ventilator.
RESPIRONICS BILEVEL VENTILATORS

(2 cmH20) is maintained in the system. The B1PAP S/T
ventilator does not incorporate any alarms. The unit only S/T-030
operates via ac current. It does not have an internal battery, This ventilator is lightweight (17.6 lb) and relatively small
although it may be attached to an external de battery. All (7.75 in high x 9 in wide x 15.25 in deep). It offers the same
other ventilators in this class essentially operate in the same modes as the S/T. It also has an optional alarm package,
manner. Each has a flow-regulating valve (see Fig. 4-16) as with high and low pressure monitored. It appearance is es-
the basis of its operation. This valve allows for easy trig- sentially the same as the S/T (see Fig. 4-15). The system
gering, cycling, and leak compensation. The electric current used to track leaks is "auto-track sensitivity." The ventilator
in the coil, in combination with a magnetic field, produces incorporates a process known as "shape signal" to effec-
a force on the valve disk that mus t equal the force created tively trigger and cycle during spontaneous breathing (Fig.
by the air pressure in order to maintain a stable pressure 4-17}. The patient's inspiratory and expiratory flow is mon-
level. As changes from the preset pressure are sensed, the itored continuously. The shape sig11al appears as a shadow
electric current adjusts the disk automatically to increase image of the patient's actual flow, establishing a sensitiv-
or decrease the amount of air vented from the pressurized ity threshold for inspiration and expiration. When the pa-
valve chamber. tient's actual flow crosses the s hape signal, the unit changes
8iPAP EXHAUST FIGURE 4-16 Schematic of the B1PAP pressure-flow

VALVE DISC
):.
.•.:( . control valve. The electrical coil and magnet cyclically
apply a force to the valve disk that is equal to the IPAP and
EPAP settings. Excess pressure is vented to the room,
allowing for maintenance of stable pressures despite
changes in flow r ate. (Used, with permissior11 from
AIR TO --(···· • --(• • • • ·• ~ • Respirouics.41 )
AIR FROM
PATIENT 9iPAP UNIT
.,m:S!I!!I!~
COIL PRESSURE
CHAMBER
MAGNET
114 PART IT PHYSICAL BASIS OF MEO-IANICAL VENTILATION
! PAP
PRESSURE
P.PAP- - - '
Cycle to
Shape EPAP
Signal Crossover
Point
F•.diml\t"<l
FLOW Patient'· ' ,
'
F low '
'
'I
Trij!j!Cr t o
I PAP
Crossover
Point
FIGURE 4-17 Tracking th e patient's flow pattern with a shape
FIGURE 4-19 The Respironics BtPAP Pro 2 or BtPAP Plus
signal provides a sm sitive mechanism to trigger inspiration or to
Venti lators.
cycle to expiration in response to changing breathing pattents and
circuit leaks. (Used, witlt permission, from Respiro11ics.42 )
for pressure, flow, and volume are provided, and the venti-
pressure level. The control panel of the S/ T-D30 is the same lator displays monitored pressures, volumes, rate, and Flo, .
as the 5 / T, and no internal battery is included. As with all other venti]ators in this group, the Vision does
not include an internal battery.
VISION
This is the only bilevel pressure noninvasive ventilator de- B1PAP PRO 2 AND B1PAP PLUS
signed for use in the ICU43 (Fig. 4-18). Because of size These two ventilators appears exactly alike except that the
(16 in deep x 143/s in wide x 105/s in high), weight (34 lb), Pro 2 has the ability to accept a "Smart Card" for recording
and cost, it is unlikely thatitwould be used in the home. This of health-status data, and the Plus has a communications
ventilator has the same modes as the S/ T-D30 and the same connection port44 (Fig. 4-19). Tn addition, the Pro 2 allows
enhanced ability to trigger and cycle. In addition, it monitors the activation of the "Bi-Flex" option45 (Fig. 4-20). This
and alarms high and low pressure, the delay in establishing
low pressure, apnea, low minute ventilation, and high and
lo'"'' rate. The ventila tor can be a ttached to a high-pressure FIGURE 4-20 lllusttation of the function of the Bi-Fiex adjunct on
02 source and can provide 90% or greater FrO:! . Waveforms the Respitonics B1PAP Pro-2. Adjustment of Bi-Flex allows rapid
decompre-Ssion of the ventilator circuit, making exhalation easieL.
Three levels can be set. (Used, tvith permissiou, from Hess et al:
Chest 124.:2275, 2003.)
FIGURE 4·18 The Respironics Vision Ventil ator.
'$"....
14
12 I
r
........
10
I
I
0
.... 8
I
E
u
...... 6
....
G>
::l
Bll'lexo
In 4 Blflex 1
(II 8iflex 2
....
G>
Q. 2
Biflex3
0
0 1 2
time (s)
FIGURE 4-21 The Rcspironics Syn chrony Ventilator. FIGURE 4-22 The ResMed VPAP III or VPAP ill ST Ventilators.
control causes a rapid decrease in a irway pressure at the

start of exhalation that can be set at three levels and is
designed to make exhalation easier. Both these v~tila~ors
PSV or CPAP (Fig. 4-22). It allows rise-time control over
provide o nly PSV. In addition, each includes a nse-time
100-900 ms. A unique feature is T 1 control or control over
adjustment. Also, included is an automatic off/ on option.
minimal and maximal inspiratory time; that is, a minimal
This feature allows the u nit to turn off automatically when
inspiratory and maximal inspiratory time can be set (Fig.
the mask is disconnected and to turn automatically on when
4-23). This unit also evaluates mask fit by measuring the
the patient begins inhaling (three consecutive b~eaths).
extent o f the leak with the particular mask. A "Smart Start"
A ramp fu11ction slowly increases pressure as assiStance
opinion is available, starting and s.topping the machin~ as
is started to make it easier for the patient to accept the
the patient begins and ends b reathmg through the ventJia-
ventilator. A dual-time meter is provided to track the time
tor. An additio nal unique and useful feature is the d ata-
the unit is plugged in versus the time it is operational. In
management option. This feature allows the clinician to
addition, the unit provide alerts to the patient: system error
monitor and compare trends in leak volume, tidal volume,
and patient disconnect.
respiratory rate, minute volume, apneas, and hypopneas .
Data can be stored for up to 365 sessions of ventilator sup-
B1PAP SYNCHRONY
port. A 9-pin communica tions port and a 15-pin auxiliary
The Synchrony, similar to the Pro 2 or Plus, is a small (1~ in
port are included .
long x 7 in wide x 6 in high) and lightweight (6 lb) ventila-
tor. Unlike the Pro 2 a nd Plus, however, all modes are avail-
able: control, ACV, PSY, and CPAP. It also includes a ramp
to set pressure and a rise-time adjustment. This ventilator FIGURE 4-23 Res Med T1 control. With this option, minimal and
incorporates a large number of alarms: high priori~ (power maximal inspiratory tim es duri ng pressure support can be set.
failure, apnea, low pressure, high pressure, low mmute vol- (Used, witll pemrissiou, from ResMed.47 )
ume, patient disconnect, ventila tor inoperative, external d.c
battery failure), medium priority (low battery), and low pn-
ority (battery in use, call for service, and power failure). This
unit is designed to allow attachment to an external de power
source but has no internal battery. An integral modem is
IPAP
Min
Time
0
7jCONTROL
lPAP
rau
Time
included to allow for monitoring at a distance via the tele-
phone. An RS-232 communications port is also included.
An optional 0 2 supplement port is provided, which allows
automatic s hutoff and turn on when the ventilator is turned
off and on.
Patient
Flow
RESMED 8 1LEVEL VENTI LATORS
VPAPITI47
This is a sma ll (10.6 in long x 9.1 in wide x 5.6 in high)
and lightweight (5 !b) noninvasive ventilator that provide
FIGURE 4-25 Puritan -Benn ett Knight Star 335 Ventilator.
peak inspiratory flow, leak volume, respiratory rate, and I:E

FIGURE 4-24 The ResMed VPAP III ST-A Ven tilator. ratio are monitored and displayed. A unique aspect is the
ability to remove the control m odule after setting the ven-
tilator or using the m odule at a distance of up to 100ft to
VPAPIITST monitor patient response and adjunct settings.
This ventila tor looks and operates exactly the same as the
VPAP III except that it also includes the ability to deliver KNIGHT STAR 330
ACV and control mod e ventilation . This is the featured ventilator from Puritan-Bennett (Fig.
4-26). It is very small (3.75 in high x 8.25 in d eep x 5.62 in
VPAP Ill ST-A wide) and lightweight (2.7 lb), with features similar to the
This ventilator has aU the featu res of the VPAP III ST w ith 335. Assist, ACV, and CPAP modes are present, with both
the addition of a number of new fea tures 48 (Fig. 4-24). A delay in starting ventila tion and ramp of setting over time.
new leak management system referred to as "Vsync" has Rise time can be set during assist and ACV. A number of
been added. This ensures better a nd faster recognition of conditions are alarmed: ltigh pressure, low p ressure, system
system leaks and adjus tment of triggering and cycling lev- leak, ventilator malfunction, apnea, power loss, and pres-
els. Both triggering sensitivity and cycling sensitivity are sure above 40 cmH2 0. In addition, respiratory rate, pres-
now adjustable. An upgraded data-management system re- sure, tidal volume, leak, peak flow, and I:E ratio are moni-
ferred to as "Smart Data" is included . This system monitored and displayed. The ventilator can be powered by an
tors a number of patient parameters a nd allows for com- external battery or ac current and has an RS-232 port for
parison to trended data. Specifically, hours of use, mask remo te communications.
leak, tidal volume, r espiratory rate, minute volume, per-
cent spontaneous triggered breaths, percent spontaneous
cycled breaths, and pressures are monitored and displayed. Common Features of All
A series of adjustable and nonadjustable alarms is included .
Ad justable alarms include mask leak, low pressure, hig h
Positive-Pressure Ventilators
pressure, low minute volume, and non vented. Preset alarms
DELIVERY OF INCREASED Ft 0
include power fail, excessive pressure above set level, and 2
system fault/ failure. The ty pical home ventilator is not designed to provide a
precise, constant Fr~ . These machines have evolved in this
manner because many patients receiving home ventilation
PURITAN-BENNETT BILEVEL VENTILATORS
do not require a precise or high Fr~. Typically, an Fr ~ of
KNIGHT STAR 335 0.25-0.35 is needed, and a ± 0.05 variation in Fro, is usually
This ventilator is the largest and heaviest of the bilevel ven- clinically acceptable in these patients.
tilators designed for home use (Fig. 4-25). It provides assist, Of the ventilators presented, only the PLV-102, LTV,
ACV, and CPAP modes.49 During all mod es, pressure ap- iVentzm, and Vision are capable of setting and maintaining
plication can be delayed for a specific period of time after a relatively precise and hig h Fr0:,. Each of the other units in-
application of the mask, and pressure can be ramped up creases the Fro1 by attachment of an ~ accumulator to the
slowly therea fter in steps of 1-3 cmH 20 per minute. Both gas entry port (see Fig. 4-3) or titration of 0 2 into the inspira-
trigger sensitivity and cycling sensitivity can be adjusted . tory limb between the ventilator and humidifier (Fig. 4-27).
The madtine incor porates bas ic alarms: ventilator inopera- The exception to this may occur during noninvasive mask
tive, disconnect, and power failure.Tidal volume, estimated ventilation. In this setting, 0 2 may be delivered directly into
CHAPTER 4 EQUWMENT REQUIRED FOR HOME MECHANICAL VENTILATION 117
FIGURE 4-26 Puritan-Bennett Knight Star 330

Ventilator.
some masks that include pressure monitoring and 02 delivered in a manner similar to that of ICU ventilators. None
livery ports. With all noninvasive ventilators, however, it is of the older units still in use, however, incorporates a de-
difficult to approximate and impossible to measure Fio,, as mand valve. Thus, during the spontaneous breathing phase
discussed earlier. of SIMV with these older units, the patient must draw gas
Normally, 0 2 is bled into the accumulator while room from the piston chamber, from a piston chamber bypass
air is drawn into the accumulator during the backstroke of valve, or through the exhalation valve. As a result, even with
the piston. Although all manufacturers provide elaborate the use of an optimal humidifying system (e.g., a passover
formulas with which to calculate Fio, delivered in this way, humidifier), a large amount of work is imposed by the venti-
the formulas hold true only if the patient is ventilated in lator system. 26•51 This work increases as patient peak spon-
the volume-control mode. Variation in the ventilator rate, taneous inspiratory flow rate increases and with use of a
tidal volume, inspiratory flow rate, ~ flow, and level of bubble-through humidifier.
spontaneous breathing all affect the breath-by-breath F1o, Whenever SIMV is used on these older ventilators (e.g.,
delivered. LP-10, LP-6 Plus, PLV-100, PLV-102, or any other older ven-
tilators), the following are highly recommended: the use
of a passover humidifier and incorporation of a one-way
SIMV/IMV AND WORK OF BREATHING H-valve between the ventilator and the humidifier (Fig.
Most of the new volume-targeted home-care ventilators in- 4-28). This configuration significantly reduces inspiratory
corporate a demand system, which allows SIMV to be de- work imposed during the spontaneous phase of SIMV.26 If
an increased F10 , is required, a reservoir bag, with or with-
out a venturi to provide high flow (see Fig. 4-28), may be
FIGURE 4-27 Oxygen delivery elbow used on LP series used. The addition of a one-way H-valve, particularly if an
ventilators, although this type of adaptor may be u sed on any of increased F10z is desired, significantly complicates the ven-
the h ome ca.r e ventilators. Oxygen is titrated directly into the
tilator setup, limits portability, and wastes 02 if an elevated
inspiratory limb, bypassing the piston chamber. (Used, w ith
permission, from P11rita u-Bem1Ctt.27)
F1o, is needed. For this reason and because of increased
workload, use of snvrv on these older ventilators should be
avoided.
P ATI ENT CIRCUIT -

HUMIDIFICATION
In general, two basic humidification systems are avail-
able for home use: heated passover humidifiers and heat
and moisture exchangers (HMEs). HMEs, while not rec-
BACTERIA Fll TER~ ommended on a continuous basis, are very useful dur-
ing transport and periods of time away from home. Use
of these devices greatly simplifies the ventilator setup o n
a wheelchair or in a car. Once the patient returns home,
however, reattachm ent to a passover humidifier is recom-
mended. It should be remembered tl1at the respiratory re-
I
OXYGEN FITTING sistance of artificial noses increases over time and varies
PEEP should not be used in the SIMV mode on ventilators

without an integrated PEEP control. Appropriate setting
of the sensitivity may allow for triggering during positive-
pressure breaths, although work of breathing during spon-
taneous breaths is increased markedly. The pressure gradi-
1 ent required to inspire is increased by the amount of PEEP
applied. If indications for the use of PEEP arise, use of the
ACV mode w ith an appropriate sensitivity setting is rec-
ommended. All the pressure-targeted ventilators have an
integrated PEEP function.
PEDIATRIC VENTILATION
The ventilation of pediatric patients, whether they are
8 weeks or 8 months of age, is a challenge with the older
generation of home-care ventilators. The introduction of
the newer volume ventilators with pressure-targeted modes
TO 02 makes is easy to ventilate children in a manner similar to
FLOWMETER that used in the ICU. Pediatric ventilation can be accom-
plished easily with the LTV, iVent201 , and Newport HTSO
ventilators.
2
c
-
. . . . . . . . . . . . . . . . . . . . . 0 9 . . ..
~lfU~~~i~~~!~~~f
THE IDEAL H OME POSITIVE-PRESSURE
VENTILATOR
Whether there is such a thing as an idea l home mechan-
A ical ventilator is questionable. We will, however, present
our perspective o n such a tmit for use with adults. This
FIGURE 4-28 Diagram of one-way H-valve systems: (1) valve description is based on the assumption that adult home
open to atmosphere, (2) valve with 3-li ter reservoir bag attaclted to mechru1ical ventila tor pa tients are stable and not wean-
28% oxygen air-entrainment device powered by 4 liter/min able. The h-vo key words that describe such a unit are sim-
oxygen, (A) p assover humidifier, (B) one-way val ve, (C) reservoir, plicity and reliability. Because operation of such a unit is
(D) 28% oxygen air-entrainment valve. Arrows indicate gas flow primarily by non-health care workers, its design must be
during spontaneous inspiration. Setu p (1) is used if no straightforward and its operation user-friendly. It should
supplemental oxygen is requ ired. Setup (2) allows for the titration
only incorporate modes commonly used in the ICU. It
of oxygen into the system. (Used, with p ermission, from Kacmarek
should be alarmed with the following: high pressure, low
et a/: Respir Care 35:405-14, 1990.)
pressure/apnea, ventilator failure, power switchover, low
minute ventilation, and disconnect. In addition, a simple
from one unit to another. 52 To our knowledge, there are no method of increasing the Fr~ to 0.40 should be included.
published data to support the use of artificial noses as the In addition, PEEP should be an integrated function to
sole source of humidity for ventilated patients in the home. allow use without imposing work. Many of the newest
generation of volume home-care ventilators fulfill this
recommendation.
APPLICATION OF PEEP
Few volume-targeted ventilators available for home venti-
lation are designed for the application of PEEP. The excep-
tions a re the Achieva, iVent201 , and Newport HTSO. A PEEP Clinical Application of
device can be affixed easily to the ventila tor circuit of any Positive-Pressure Ventilators
unit, however, work of breathing is increased if ventilation
is patient triggered because none of these units automati- The choice of a specific mechanical ventilator and method
cally compensates for PEEP. With these UJ1its in PSV, ACV, of application depends on whether the application is elec-
or CPAP modes, sensitivity must be adjusted to decrease the tive or required because of chronic ventilatory failure and
pressure gradient necessary to trigger the unit; if 5 em H2 0 of whether the application is invasive (via tracheostomy) or
PEEP is applied, sensitivity must be set to about +4 cmH20 noninvasive. Based on design and overall features, all the
(1 cmH20 below baseline required to trigger inspiration). units discussed, except the pressure-targeted bilevel units,
Many patients at home do not maintain a tight seal at the ar e capable of providing ventilator support under all cir-
tracheostomy cufC however, which increases the likelihood cumstances. The pressure-targeted bilevel units, because
of self-cycling. Table 4-1lists th e limits of the sensitivity set- of their lack of alarms and their inability to monitor gas
tings of all units discussed. As noted, a significant variation delivery, should be used only for elective, noninvasive
in the range of sensitivities exists. applications.
ELECTIVE POSITIVE-PRESSURE VENTILATION TAB LE 4-4 Gu idelines fo r the Use of Elective NPP V
The type of patient who benefits from the elective, non- Primary ventilator Remote alarm
invasive application of positive-pressure ventilation is still Backup ventilator Battery
controversial (see Chapter 19). It is our opinion and that System humidifier Battery charger
of others53- 56 that elective support benefi ts any patient in Ventilator circuits Manual ventilator
whom the progression of ventilatory dysfunction has re- Oxygen source Compressor for aerosol medication
sulted in retained C02- d isturbed sleep, loss of energy, and Suction apparatus Small volume nebulizer' (or metered
an inability to perform functions of daily diving. This is par- dose inhaler)
Suction catheters
ticularly true if the process is irreversible and progressive.56
Spare tracheostomy tube Electric generator»
The goal of elective ventilator support is unloading of the
respiratory muscles for about6-12 hours per day. It is hoped •only neccs~ary if aerOS<.)I medication required.
that this rest allows muscles to recover from incipient fa- bOnly necessnry if greater than 16 hours a day ventilator support required or
tigue a nd resu Its in normalized sleep, increased energy, and locnted more than 4 hour~ from a hospital.
frequently, an improvement in baseline Pea, during spon-
taneous breathing.57- 60 To achieve these goals, care must be
taken that the application of positive pressure is comfort- INVAS IVE NONELECTIVE VENTILATO R SUPPORT
able, that it is capable of meeting the patient's ventilatory
demands, and that it is set to unload effort during sleep .54•56 As indicated earlier, only volume ventilators capable of
Bilevel positive-pressure ventilators are ideal for this pur- monitoring patient s tatus with appropriate alarms should
pose. A major problem with patient acceptance is the peri- be used during invasive ventilator support. The primary
odic blast of air through the nose (or nose and mouth) d uring controversy in this area is the mode of ventilation. Gener-
inspiration. Because pressure-targeted ventilators maintain ally, no a ttempt is made to wean adult home-care patients.
a continuous gas fl ow, it is our experience that the change The overriding goal is to maximize ventilator independence
from expiration to inspiration is not as dramatic with these for short periods of time, which is the same goal as with elec-
units and is better tolerated than with volume-targeted ven- tive ventilation. We believe that this can be accomplished
tilators. When setting bilevel pressure, the primary goal is best with the ACV mode of pressure or volume ventilation
patient comfort. The selection of both inspiratory pressure or PSV by maximizing respiratory muscle rest during pe-
and PEEP must be acceptable to the patient to ensure com- riods of ventilation to ensure maximum capability during
pliance. The PEEP level selected depends on the need to (1) periods of ventilator independence.
establish functional residual capacity, (2) overcome upper Many patients requiring home ventilator support require
airway obstruction, and (3) decrease the work of breath- a secondary backup ventilator. Generally, we recommend a
ing associated with the presence of air trapping and auto- backup ventilator if the patient requires 16 hours or more of
PEEP. We have found that in the vast majority of patients, ventilatory support per day or if he or she res ides more than
a PEEP of minimal (2 cmH 20) to about 6 cmH20 is suffi- 4 hours from a hospital. Additional equipment frequently
cient to accomplis h these goals. Higher levels usually result needed by these patients is lis ted in Table 4-4.
in overdistension and patient discomfort. The inspiratory
pressure level is set to ensure an adequate tidal volume NONINVASIVE NONELECTIVE
and reasonable respiratory ra te. With some bilevel pressure VENTILATOR SUPPORT
units it is impossible to determine tidal volttme delivery, and
o ther units have optional monitoring modules available that The provision of noninvasive positive-pressure ventilator
can estimate tida l volume. We normally base the inspiratory support to patients requiring home ventilation demands
pressure setting on patient comfort, chest expansion, use of careful monitoring of both tJ1e patient and the status of the
accessory muscles, cl1est auscultation, respiratory rate and equipment. Most clinicians prefer to provide ventilator sup-
pattern, and arterial blood-gas results. Most patients require port invasively in these settings. Otl1ers,61 - 64 however, have
a peak airway pressure of about 12-16 cmH2 0 or a ventila- demonstrated the effective use of both noninvasive positive-
tory pressure of 6-12 cmH 20 . pressure61·62 and non-positive-pressure techniques65•66 in
large numbers of patients requiring ventilator support. In
this setting, a mouthpiece and lip seal, a nasal mask, or an
ELECTIVE VENTILATION VIA TRACHEOSTOMY oral-nasal mask have been used to interface the patient with
the ventilator. The actual setup of tile ventilator is consistent
Provision of elective ventilation via a tracheostomy is rare. with that of elective, noninvasive ventilator support.
Nevertheless, there are individuals who require a tra-
cheostomy for upper airway disorders who also benefit
from elective support. in this setting, a volume ventilator
always should be selected because of its monitoring and Facial Appliances for Noninvasive
alarm capabilities in the face of a closed ventilatory system . Positive-Pressure Ventilation (NPPV)
The setup of the venti lator is the same as that described
for noninvasive ventilation, with the actual delivered tidal TI1e most d ifficu lt aspect of establishing NPPV is finding
volume generally in the (r10 ml/ kg range depending on a properly fitting facial appliance. Six different approaches
patient tolerance a nd comfort. are currently in use: (1) total face mask, (2) oral-nasal mask,
120 PART n PHYSICAL BASIS OF MECHANICAL VENTILATION
FIGURE 4-29 A ResMed. Oral-Nasal Mask.
FIGURE 4--30 A nasal mask.
(3) nasal mask, (4) Adams circuit, (5) head hood, and (6) NASAL MASKS
mouthpieces. All approaches s hould be considered with ev-
ery patient, although there are different problems with each The most popular approach to the application ofNPPV for
appliance. home use is the nasal mask. Numerous commercial nasal
masks are available that work well on most patients (Fig.
4-30). Most, similar to today's oral-nasal masks, have an
inner Hp of 1/.r 1h in that forms an open space between the
inner and outer walls of the mask. As a result, when positive
ORAL-NASAL MASKS pressure is applied, force is exerted between the inner and
For many practitioners,67- 69 an oral-nasal mask has been outer folds, creating a better seal. Because of this, only low
the appliance of choice for the delivery of NPPV in the to moderate pressure is needed to secure the mask. As with
emergency room and in the rcu, whereas othersS-1,59.61.66 the o ral-nasal mask, pressure must be applied equally at all
have used oral-nasal masks successfully in patients requir- points of connection to the headgear: at the bridge of the
ing long-term ventilatorsupport(Fig. 4-29). Many oral-nasal nose and at each side of the mask. If a properly fitting mask
masks are available curre ntly; we find that most work well, is chosen, and moderate but equal pressure is applied at
provided that a proper fit is achieved. The ideal face mask each connection, a very comfortable fit can be achieved.
for long-term ventilation (1) is made of dear plastic to allow Choosing the proper s ize mask is critical. As a general
visual assessment of secretions, (2) has a soft contour that rule, the smnller the mask, the better is the fit. There are
conforms to the anatomy of thepatient'sface, (3) is deformed many types and sizes of masks available, although we
easily from its factory shape as needed to fit the patient, and would estima te that nearly all patients are fitted with the
(4) has " memory" so that it maintains its deformed shape smaller s izes. TI1e ideal mask fits closely to the lateral con-
when it is removed. Tdeally, a number of different masks of tour of the nose, extending from just under the external
varying sizes should be available when attempting to fit a nares to two-thirds of the way up the bridge of the nose.
particular patient. Chinstraps are available to reduce mouth leak Although
Proper fit is the essential feature in mask selection. Leaks we frequently try them, they infrequently reduce mouth
at the bridge of the nose, causing air to blow into the patient's leak. If patients are actively opposing nasal NPPV, nothing
eyes, will result in NPPV failure because of patient intoler- eliminates mouth leak. ln many patients, the extent of the
ance. The mask should fit comfortably from just below the mouth leak decreases as tl1ey acclimate to ventilation. Also,
lower lip to about two-thirds of the way up the bridge of many patients who have a large leak while awake demon-
the nose. The exact fit is depends on the patient. Patient strate little or no leak while sleeping, or vice versa. Because
comfort is essential: The patient is always the final judge of peak pressures are usually 12-16 cmH2 0, during sleep the
proper fit. soft palate and the base of the tongue are elevated suffi-
The most comm on error in securing the mask is exerting ciently to prevent excessive leak in many patients.
excessive pressure. With PPV, low peak airway pressures
(generally 12-16 cmH20) usually are used. Because some
leak is expected, masks do not need to be secured so tightly ADAMS C IRCUIT
that pressure sores develop. Firm but even pressure dis- A variation on the application of nasal ventilation, the
tributed over the entire mask usually is sufficient to make a Adams circuit (Fig. 4-31) is available from several manu-
seal. Remember, if a patient cannot tolerate the facial pres- facturers. Individual "nasal pillows" fit into a manifold that
sure, the whole process may fail. Most mask have inner lips is attached over the top of the patient's head. Some patients
that seal tighter during inspirations. prefer this approach to the nasal mask. Others who are more
CHAPTER4 EQUIPMENTREQUIREDFORHOMEMECHANICAL VENTILATION 121
been applied 24 hours per day. 70 This requires more than
the use of a standard mouthpiece. Many mouthpieces with
inner flanges are available commercially (Fig. 4-32). Some
patients do best when a customized mouthpiece is made
from an impression of the patient's mouth. With a cus-
tomized mouthpiece, many patients are capable of comfort-
ably maintaining ventilation for indefinite periods. Mauy do
not experience significant nasal leaks during sleep, whereas
others also require nasal plugs or nose clips. With this ap-
proach, the gumline should be monitored for sores.
TOTAL FACE MASK

One company makes a full face mask (Fig. 4-33). This mask
fits over the whole face, including the eyes. Despite its size,
it is very comfortable. The primary concern with this mask is
dead space and thus a decreased ability to eliminate co2.71
This interface normally is used for the acute application of
NPPV; it is not used commonly in the home.
HEAD H OOD
Figure 4-34 illustrates the newest facial appliance for the
application of noninvasive positive pressure. The head
hood has been used successfully by a number of European
groups 18·72- 73 but is not currently available in the United.
States. Des pite its appearance, it is very comfortable. Again,
the biggest concern with the device is deadspace and C~
FIGURE 4-31 Adams circuit. (Courtesy of Puritnu-Beunett.) rebreathing.n ·74 It appears to be best suited for the appli-
cation of CPAP using a high-continuous-flow approach to
clear C02 continually from the hood. The head hood should
sensitive to pressure use both nasal masks and nasal pillows, be reserved for acute application of positive pressure in the
switching back and forth as irritation develops. Because of ICU.
differences in design, the points of pressure differ greatly
between the two approaches. Multiple sizes of pillows are
available, corresponding to the s ize of an individual's exter-
nal nares. Non-Positive-Pressure Approaches
to Ventilator Support
MOUTHPIECES
Three basic approaches are used to provide ventilator sup-
Many patients who use negative-pressure ventilation at port without the application of positive pressure to the
night use periodic positive-pressure ventilation during the airway: (1) negative-pressure ventilation, (2) pneumobelts,
day. In others, mouthpiece positive-pressure ventilation has and (3) rocking beds.
FIGURE 4-32 A mouthpiece for NPPV application.

122 PART D PHYSICAL BASIS OF MECHANICAL VENTILATION
..
1
)
FIGURE 4-35 Emerson Iron Lung.
wheel (the actual diameter of the wheel varies from one end
FIGURE 4-33 The Respironics Total Face Mask. (Used witll to the other) via a fan belt. The w heel is connected to a cam
permissiou.) by a transfer case that translates the motion of the wheel to
the cam. The cam is connected by a series of linkages and
arms to the movable leather/rubber diaphragm at the rear
NEGATIVE-PRESSURE GENERATORS of the iron lung. The level of negative pressure created is
There is only one commercially available negative-pressure controlled by the size of an adjustable leak. In the event of
generator in the United States. Iron lungs still exist in many a power failure, the machine may be cycled manually. The
centers and are used by some neuromuscular diseased pa- unit functions at a fixed I:E ratio of 1:1, with ra tes available
tients in the home. from about 10-30breaths per minute in the adult unit. Ado-
lescent and pediatric units are available that provide even
greater rates. Pressures up to -60 cmH20 are obtainable.
EMERSON IRON LUNG
A pressure manometer is affixed to the top of the unit for
TI1e oldest of all mechanical ventilators still available com- monitoring. A number of locking ports located on each side
mercially for use in the United States is the Emerson Iron of the unit allow access to the patient, and glass panels are
Lung75 (Fig. 4-35). Jack Emerson manufactured his first iron configured across the top of the unit. A seal at the patient's
lung in 1931.76 The unit consists of a large, relatively airtight neck is achieved with an adjustable plastic ring.
chamber in which the patient's body is placed. The patient's
head is exposed to the atmosphere, whereas on the opposite
end a fl exible diaphragm is attached by a series of arms and LIFECARE NEV-100
gears to an electric motor. The motor drives a var iable-sized The NEV-100 ventilator (Fig. 4-36) is the most technically
sophisticated of the negative-pressure ventilators currently
available.77 It is light (31 lb), compact (21 in high x 12 in
wide x 12 in diameter), and portable but is incapable of
FIGURE 4-34 Head hood currently availab le only in Europe.
being opera ted by battery. It is microprocessor-controlled
and turbine-driven. Five specific modes are available: con-
trol, control with sigh, ACV, ACV with sigh, and continuous
nega tive extra thoracic pressure (CNEP). In all but the CNEP
.••-··••
mode, a negative or positive base pressure (expiratory pres-
r -... -.'
-- .. sure) can be set. The front panel has three buttons lmanual
sigh, alarm silence (30 seconds), and panel lock/unlockL
• a computer screen menu display, and a single rotary pa-
rameter controller. All setting adjustments are made with
• • the rotary controller, which must be unlocked before use
-- (it locks automatically 30 seconds after last use).

Three different menus are available on the computer
screen. With the first menu, the following parameters
are displayed and can be set: mode, negative inspiratory
pressure (-5 to - 100 cmH 20), base pressure (-30 to +30
cmH20), rate (4-60 breaths per minute), inspiratory time
(0.5-5.0 s), I:E ratio (1:3 to 2:1), sigh pressure (-5 to -100
base pressure setting. If system pressure is below this level
for a 20~second period, audio and visual alarms are acti-
vated. Both are activated if excessive negative pressure or
base pressure develops or if the inspirato ry CNEP or base
pressure is out of range. Internal system failure, constant
pressure failure, missing parameter, and high or low inter-
nal temperature alarms are also present. A continuous audio
alarm sounds if a power failure occurs, and an information
message is displayed if an inverse ratio is set.
This w1it has a remote alarm and an hour clock and
is capable of being attached to a recorder for the display
of alarms and ventilation variables, as well as diagnostic
information.
CRITICAL ANALYSIS OF
NEGATIVE-PRESSURE GENERATORS
The iron lung is still the standard in the area of negative-
pressure ventilation, altho ugh it is no longer manufactured.
It is the most reliable and effective method of providing
negativ~pressure ventilation. The rapid development of
noninvasive positiv~pressure techniques since 1995 has all
but eliminated the use of negative pressure. As discussed
earlier, only one company in the United States currently
makes a negativ~pressure generator.
NEGATIVE-PRESSURE CHAMBERS
Negative pressure can be applied to the thorax using a full-
body chamber, chest cuirass, or Nu-Mo suit.
FULL-BODY CHAMBERS
The Portal-Lung (Fig. 4-37) is a full-body cl1amber without a
nega tiv~pressure generator. It is available from Respiron-
ics, is lightweight and easy to use, and can be driven by
FIGURE 4-36 Lifecare NEV-100 Negative-Pressure Ventilator. any negative-pressure generator. It is presently available in
child and adolescent sizes. Its majordrawbackis the require-
ment of an assistant to operate. The present model must be
cmH2 0), sigh multiple breaths (one, two, or three, sig h
frequency (1-20 per hour), and low-pressure a larm setting. secured from the outside.
The second menu indicates frequency of output to a
printer, units of pressure displayed (cmH20, kPa, mbar),
FIGURE 4-37 The Porta-Lung with the Respironics NEV-100.
and alarm history. In addition, screen brightness, date and
(Courtesy of Respironics.)
time, a larm volume, assist sensitivity (levels 1-10, no pres-
sure wlits indicated), alarm pitch, and remo te alarm status
all can be controlled and adjusted from this screen.
The final menu is for the setting of CNEP levels. Only
two variables are set in this menu: base pressure and low-
pressure alarm.
In the four ventilation modes, the clinician must set the
rate, negative inspiratory pressure, base pressure, inspira-
tory time, and I:E ratio. Sigh pressure, multiples and fre-
quency, and sensitivity are a lso set. Although I:E ratio can be
set, it depends on rate and inspiratory time a nd w ill default
to the ratio indicated by the combination of these variables.
Unlike older negativ~pressure ventilators, this unit is
highly alarmed. It incorporates 13 specific alarms, although
only one is set by the clinician: the low-pressure a larm. It
can be set from -1 cmH20 below to +1 cmH2 0 above the
124 PART D PHYSICAL BASIS OF MECHANICAL VENTILATION
FIGURE 4-38 Commercially available ch est cuirass.
CHEST CUIRASS
Figure 4-38 depicts a commercially available chest cuirass.
They are designed to be placed over the patient's thorax
and abdomen and are secured in place with wide straps. A
negative-pressure generator is attached a t the opening on
the top of the s hell. Each s hell is designed with a cushion
of 2- 3 in of air between the patient's maximum chest rise
and shell to ensure that the chest wall of the patient does
not come directly in contact with the top of the shell, w hich
would negate further thoracic expa nsion. Most pa tients find
the shell reasonably comfortable. The major problem w ith
commercial shells, however, is fit. ln many cases, towels
must be stuffed between the shell and the patient to ensure
a seal, or foam rubber must be added. Leaks normally occu r
at the neck and pelvis. For these reasons, it is best to have a
shell customized to the patient. Figure 4-39 shows a cast of a FIGURE 4-39 Cast of the thorax used to make a customized chest
patient's chest and abdomen from which a customized shell cuirass.
is designed. Customized shells are particularly important
in patients with thoracic deformities. To fit welt the shell
should extend from the clavicle to the pelvic arch and along simply prefer one chamber to another.ln general, the chest
the sides of the chest wall. Ideally, when attached, the shell cuirass is best tolerated, particularly if the patient is claus-
should not rest on the bed but should extend about halfway trophobic. A customized cuirass is preferable in most situa-
down the chest wall. Of all the negative-pressure chambers tions. The full-body chamber seems to work best with chil-
available, the chest cuirass is the easiest for patients to use dren a nd adolescents, although many adult polio victims
independent! y. and kyphoscoliosis patients s till use iron lungs or porta-
lungs. The Nu-Mo Suit is cumbersome for patients to use,
NU-MOSUIT and many become claustrophobic in them. All approaches
The Nu-Mo Suit is depicted in Fig. 4-40. This device is ac- should be considered and tried clinically before deciding on
tually a m odified poncho that is fit over a grid. The grid is one method in a given patient.
necessary to prevent the negative-pressure attachment from
being affixed directly to the thorax. It maintains a 2- 3-in P NEUMOBELT
cushion of air that can be decompressed during inspiration.
When applied, the Nu-Mo Suit is secured at the neck with The pneumobelt (Fig. 4-41) is actually an adjustable corset
a tie string and at the arms and hips with Velcro straps. It that contains an inflatable bladder. It functions by exerting
is available in tluee sizes. The primary problem w itll this a positive pressure on the abdomen, forcing tl1e abdomen
chamber is leakage. In fact, most patients compla in about cephalad and tlms assisting with exh alation3, 78 (Fig. 4-42).
being cold when using the Nu-Mo Suit because of room air Inspiration proceeds under the patient's own efforts. It is
drawn into it w hen negative pressure is generated. Leaks hoped, however, that witl1 proper application of the pneu-
are most prevalent at the hips and neck. mobelt, functional residual capacity is reduced slightly.
Thus, on release, elastic recoil leads to an increase in tidal
CRITICAL ANALYSIS OF
volume.
For proper function, an appropriately sized pneumobelt
NEGATIVE-PRESSURE CHAMBERS
should be selected and fitted tightly over the abdomen
Acceptance and acclimation to a negative-pressure cham- from tl1e xiphoid process to just about the pelvic arch.79
ber d epend primarily on patient preference. Many patients Fit is important to prevent paradoxical m ovement of the rib
air fl01ta ifl
inttltothorocic
prnua foil•
bloddtt inflottd blocSdef dtfklttd
u
FIGURE 4-42 lllustration of the function of the pneumobelt. The
pneumobelt functions by exerting pressure on the abdominal
contents by infJation of a rubber bladder, forcing the diaphragm
upward and assisting exhalation (/eft). When the bladder
deflates, gravity pulls the diaphragm back down, assisting
inhalation (right). (llsed, with penn iss ion, from ref. 79).
ROCKING BED
Operation of the rocking bed (Fig. 4-43) is based on the effect
FIGURE 4-40 The Respironics Nu-Mo Suit. (Comtesy of gravity has on the abdominal contents.3 That is, as the bed
Respirouics.) rocks, the abdominal contents assist the movement of the
diaphragm. When the bed tilts head down, exhalation is
assisted. When the head tilts up, inspiration is assisted.
cage during exhalation. Depending on the patient, between The rocking bed can move through a total arc of up to 60°:
30 and 50 cmH2 0 must be applied to the bladder, and pa- a maximum of30° head down and300 head up. Generally, a
tients ideally should be seated at a 75° angle. 78 As the angle 15° head-down with a 30" head-up tilt is sufficient for most
from supine decreases, the effectiveness of the belt also de- patients.3 In addition to the size of the arc, the rate can be
creases. The pneumobelt may be powered by any positive- adjusted from 8-34 tilts per minute, and a break at the knee
pressure generator. Although effective in some patients, this
device is used rarely today.
FIGURE 4-43 The Emerson Rocking Bed.
FIGURE 4-41 Pneumobelt with its internal inflatable bladder.
-· _,_ ..u... J_
JJ... l.l... J,...
~ ..W.. .LL ~
12 6 PART ll PHYSICAL BASIS OF MECHANICAL VENTILATION
can be established to prevent sliding. Some patients develop 14. Snider GL. Thirty years of mechanical ventilation: Changing im·
motion sickness with the rocking bed and r equire appro- plications. Arch h1tern Med 1983; 143:745-9.
pria te medication. 3 Although effective in some patients, this 15. Splaingard ML, Frates RC Jr, Harrison GM, et al. Home positive-
device is used rarely today. pressure ventilation: 1\vcnty years' experience. Chest 1983;
84:376-82.
16. Metha S, I !ill N. N oninvasive ventilation. Am J Rcspir Cri t Care
Med 2001; 163:540-77.
CRITICAL ANALYSIS OF PNEUMOBELT 17. Meduri G, Turner R, Abou-Shala N, et al. Noninvasive positive-
AND ROCKING BED pressure ventilation via face mask: First-line inte rve ntion in pa-
tients with acute hypercapnic and hy poxemic respiratory failure.
The pneumobelt and the rocking bed, both noninva- Chest 1996; 109:179- 93.
sive approaches to ventilatory support, have limited ap- 18. Antonelli M, Conti G, Pelosi P, e t al. New treatment of acu te hy-
plication but may be extremely beneficial in select pa- poxemic respiratory failure: Noninvasive pressure s upport ven-
tients. Neither functions well in pa tients with chronic lung tilation delivered by a helmet- A pilot controlled tria l. Crit Care
disease, although patients with primary pnewnomuscu- Med 2002; 30:602- 8.
lar/ neurologic disorders often benefit from their use. The 19. Pierson OJ, Kacmarek RM. Home ventilator care. In: Casaburi R,
pneumobelt is used primarily for daytime assistance in pa- Petty T, editors. Principles a nd practice of pulmonary re habilita-
tients requiring other forms of support during the night. tion, 2nd ed. Philadelphia: Saunde rs, 1993: 274-88.
The same is true with the rocking bed. Some patients, how- 20. G ilmartin ME. Long-term m echanical ventilation ou tside the hos-
ever, can tolerate the motion and sleep comfortably in the pital In: Pierson OJ, Kacm a re k RM, edi to rs. Fo unda tio ns of res·
piratory care. 'ew York: Churchill Livingstone, 1992: 1185- 205.
rocking bed. Because the pneumobelt requires a sitting po-
21. Bach JR, Alba AS. Non-invasive options for ventilatory support
sition, it is used rarely at night. It must be remembered that of tl1e tra uma tic high-level quadraplegic patient. Chest 1990;
both units function as controllers. Patients who are anxious 98:613-9.
and frequently change their respiratory rate rarely tolerate 22. Back JA, Alba AS. Management of chronic alveolar hypoventila·
either. tion by nasal ventilation. Chest 1990; 97:52- 7.
23. Kacmarek RM. Ho me mechanical ventilation equipment. m:
Branson RD, Hess DR, Chatburn RL, editors. Respira tory care
equipm ent, 2nd ed, Philadelphia: Lippincott, 1995.
24. Hess DR, Kaanarek RM. Noninvasive ventilation. In: Branson
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12. KJeopa KA, Sherman M, Neal B, eta!. Bipap improves s urv ival 37. Kaanarek RM. Characteristics of pressure-targeted ventilators
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CHAPTER 4 EQUIPMENT REQUIRED FOR HOME MECHANICAL VENTILATION 12 7
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40. Ferg uson G, Gilmartin M. C02 rcbrcathing during B1PAP vcn· Muscle Nerve 1987; 10:177-82.
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1126-35. tilation of patients with late-stage Duchemle muscular dystro·
41. B1PAP ventilatory s uppo rt system clinical manual for models S / T phy: Management in the ho me. Arch Phys Med Rehabil1979; 60:
and S/ T-D, form no 336051, Murrysville, PA, Respironics, 1989. 289-92.
42. Respironics B1PAP S/ T-D30, C linical manual, no. 556065, Mur- 63. Curren Fj, Colbert AP. Ventila tory management in Duchenne
rysville, PA, 1997. muscular dystrophy and post-polio m yelitis syndrome: Twelve
43. Respironics VISion, Clinical manual, no 1009071, Murryvillc, PA, years' experience. Arch Phys Med Rehabib 1989; 70:180-5.
1998. 64. Goldstein RS, Molotiu N, Skrastins R. Reversal of sleep-induced
44. Respironics B1PAP Pro 2 and B,PAP Plus, User manual, no hypoventilation in chronic respiratory failure by noctumal
1018989, Murrysville, PA, 2003. negative-pressure ventila tion in patients with restrictive venti-
45. Hess DR, Hardy WH. Labo ratory evaluation of Bi-Flex mode of lato ry impairment. Am Rev Respir Dis,1987; 135:1049-55.
the Respiro nics Pro bilevel system. Chest 2003; l24:227S. 65. Back JR, Alba AS. intermittent abdominal press ure ventilation in
46. Respironics Synclltony, User g uide. no 10031 21, Murrysville, PA, a regimen of noninvasive ventilatory support. Chest 1991; 99:630-
2000. 6.
47. ResMed VPAP m and Ill ST, Clinician manual, no 24808/3-04-04, 66. Back JR, Alba AS. No nin vasive options for ventilatory support of
Waterloo, Australia, 2004. the traumatic high -le vel quadriplegic patient. Chest 1990; 98:613-
48. ResMed VPAP lUST-A, Clinician man ual, no 24851 /1-04-07, Bella 9.
Vista, Australia, 2004. 67. Brochard L, lsabey D, Pique t J, et a!. Reversal of acute exacerba-
49. Puri tan-Bennett Knight Star 335 Ventilator, Clinical guide, no Y- tions of chronic obstru ctive lung disease by inspira tory assistance
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50. Puri tan-Bennett Knig ht Star 330 Ventilator, Clinician's manual, 68. Mcduri GU, Abou-Shala N, Fox RC, e t a!. Noninvasive face mask
no Y-500008-00, rev H, Pleasanton, CA, 2003. mecllanical ventilation in patients with acute hypercapnia. Chest
51. Robert P, Hirsch C, Barke rS, Kacmarek RM. Wo rk of breathing 1991; 100:445- 54.
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52. Ploysongsang Y, Branso n RD, Rashkin MC, Hurst JM. Effect of 70. Back JR, Alba A, Saporito LR. lntennitte nt positive-pressure ven-
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PART III ical ventilation for chronic respiratory failure or in pedi-
atric patients; these subjects are covered in Chapters 19, 25,
and 32.
INDICATIONS There is a paucity of research-and no clinical trials-
on the indications for mecl1anical ventilation. This situation
contrasts with the growing amount of research on the dis-
continuation of mechanical ventilation. Wltile it is tempting
Chapter 5 - - - - - - - - - - to apply indices used for predicting the outcome of weaning
trials as indices to identify patients who require mechanical
INDICATIONS FOR ventilation, such an approach has not been tested. It is also
probably unwise.
MECHANICAL Two factors account for the limited research on indica-
tions for mechanical ventilation. First, such patients are
VENTILATION extremely ill. Any intervention- such as careful collec-
tion of physiologic measurements- that delays institution
FRANCO LAGHJ
MARTI J. TOBIN
of ventilation might be viewed as unethical. Second, the
nosology of respiratory failure is unsatisfactory (see be-
low). In everyday practice, clinicians do not decide to
institute mechanical ventilation because a patient meets cer-
tain diagnostic criteria. Instead, clinicians typically decide
to institute ventilation based on their assessment of a pa-
tient's signs and symptoms. This decision is also grounded
OVERALL ASSESSMENT on a foundation of solid biomedical theory, specifically
Apnea principles of pulmonary pathophysiology. Accordingly,
Clinical Signs of Increased Work of Breathing we develop our discussion of ventilator indications along
Hypoxemic Respiratory Failure these two lines: physical examination and pathophysiologic
Hypercapnic Respiratory Failure principles.
Postoperative Respiratory Failure
Shock
Intubation Versus Mechanical Ventilation Overall Assessment
GOALS OF MECHANICAL VENTILATION
Reversal of Apnea Clinical presentations that cause a physician to institute me-
Reversal of Respiratory Distress chanical ventilation are protean. They range from patients
Reversal of Severe Hypoxemia presenting with frank apnea to patients with clinical signs
Reversal of Severe Hypercapnia of increased work of breathing w ith or without laboratory
Goals of Mechanical Ventilation in Postorerative evidence of impaired gas exchange.
Respiratory Failure and Tauma
Goals of Mechanical Ventilation in Shock
APNEA
DELIVERY OF MECHANICAL VENTILATION:
INVASIVE VERSUS N ONINVASIVE Apneic patients, such as tl1ose w ho have suffered catas-
MECHANICAL VENTILATION trophic central nervous system (CNS) damage, need im-
INDICATIONS FOR MECHANICAL VENTILATION mediate institution of mechanical ventilation. To advocate
AND NOSOLOGY controlled trials to determine the need for mechanical ven-
Indications: True verus Stated tilations in apneic patients is unethical.
Nosology
Disease Definition and Characteristics
CLINICAL SIGNS OF INCREASED
Definitions: Essentialist and Nominalist
WORK OF BREATHING
Diagnostic Process, Treatment, and Value Judgment
Factual Implications of Disease Terminology Asthma, chronic obstructive pulmonary disease (COPD),
CONTRAINDICATIONS TO MECHANICAL pneumonia, cardiogenic pulmonary edema, and acute res-
VENTILATION piratory dis tress syndrome (ARDS) are just a few of the
CO NCLUSION many conditions that cause an increase in work of breathing
and, with it, increased energy expenditure by the respira-
In this chapter we discuss the indications for mechan- tory muscles.
ical ventilation in adult patients. We focus on patients The energy expenditure of the respiratory muscles can
who are already in the intensive care unit (TCU) or who be quantified in terms of pressure-time product1-the time
are considered for transfer to the ICU, that is, patients integral of the difference between the esophageal pressure
with new onset of signs and symptoms over minutes or tracing and the estimated recoil pressure of the chest wall2•3
hours. We do not deal with the indications for mechan- (Fig. 5-1). The pressure-time product of patients in acute
129
130 PART lli INDICATIONS
()
Q)
0.8
:) 0.4
s:
.Q -0.0
u.
-0.4
5
--- -- ----- - CW recoil pressure
P•• upper bound
ON
0
-- ---- CW recoil pressure
I lower bound
E -5
() Lung recoil pressure
~
:::1
en -1 0
en
-
Q)
....
CL
PEEP,
-15
D Non-PEEP1 Elastance
k:J Resistance
-20
0.0 0.5 1.0 1.5 2.0 2.5

Time, seconds
FIGURE 5-1 Flow (inspiration upward) and press ure tracings during s pontaneous breathing. Recoil pressures of the chest wall (CW) and
lung are calculated from dynamic elastances of the chest wall and lung, respectively, and lung volume. Inspiratory pressure-time product
(PTP) is calculated using the integral of the difference between esophageal pressure (P,.) and CW recoil pressure from the onset of the
rapid decrease in P,. to the transition from ins piratory to expiratory flow (upper-bound PTP). The component of PTP caused by intrinsic
positive end-expiratory pressure (PEEP;) is computed using the integral of the differen ce between the upper-bound PTP and CW recoil
pressure from the onset of rapid decrease in P, 5 to the transition from inspiratory to expiratory flow (lower-bound PTP). The component of
PTP caused by non-PEEP; elastance is computed u sing the integral of the differen ce between lung recoil pressure and lowe r-bound CW
recoil pressure from the onset of ins piratory flow to the moment of transition from inspiratory to expiratory flow. The resistive fraction of
PTP is computed u sing the integral of the d ifference between PtS and lung recoil pressure. The vertical interrupted lines represent points
for zero flow. (Used, with pemrissiou, from fubrau et nl: Pathophysiologic basis of acute respirnton; distress in patients w ho fail n trial of
weauiug from m.eclranical veut i/ntiou. Am T Respir Crit Care Med 155:906-15, 1997.)
respira to ry failure is abou t four times4-6 the normal value muscle recruitment, expiratory muscle recruitment, tracheal
(100 cmH20 · s/min), and it can be increased sixfold in tug, intercostal recession, tachypnea, tachycardia, hyperten-
individual patients. 4•5 The inspiratory pressure-time prod- sion or hypotension, d iaphoresis, and changes in mental
uct can be pa rtitioned into resistive, elastic, and intrinsic status.
positive end-expiratory pressure (PEEP) components5 (see
Fig. 5-1). Patients in respiratory distress typically have a 30- FACIAL SIGNS OF RESPIRATORY DISTRESS
50% greater inspiratory resistance,5 100% greater dynamic Many intensivists often decide to institute mechanical ven-
elastance,5 and 100-200% greater intrinsic PEEp4,S than do tilation based on a patient's facial appearance.8 Gils ton has
similar patients w ho are not in acu te respiratory failure. provided an insightful description of many signs that go
Inspiratory effort is almost equally divided in offsetting in- unstated in reviews on mechanical ventilation.8 Take, for
trinsic PEEP, elastic recoil, and inspiratory resistance.5 The example, the mouth. At an early stage of respiratory dis-
increase in respiratory effort means that the respiratory tress, the mouth opens slightly and to a variable extent d ur·
muscles account for a much larger fraction of the body's ing inhalation (Fig. 5-2). At a later stage, the mouth opens
oxygen (0 2 ) consumption. In healthy subjects, this fraction throughout the respira tory cycle. Patients m ay switch to
is only 1- 3% of total 0 2 consumption. In patients with acute mouth breath ing perhaps to decrease r espiratory work8•9
hypoxemic respir atory failure and shock who are undergo- and physiologic dead-space ventilation.8 An open mouth is
ing cardiopulmonary resuscitation, the respiratory muscles sometimes seen in patients with a tracheostomy (Fig. 5-3)
account for about 20% of total 0 2 consumption? and in patients receiving ventilator support.8 The tongue
Increased work by the respiratory muscles causes respira- may be seen to jerk in unison with inspiratory efforts.8
tory distress. Clinical manifestations of respira tory distress Some distressed patients also exhibit pursed-lip breath-
include nasal flaring, retraction of the eyelids, accessory ing during exhalation. 8 In stable ambulatory patients w ith
CHAPTER S INDICATIONS FOR MECHANICAL VENTILATION 131
FIGURE 5-2 Mouth opening during respiratory dis tress. (Left) A patient developed respiratory distress precipitated by right-middle- and
right-lower-lobe atelectasis 1 week after mi tral valve replacement. The patient is moderately dyspneic, especially on talking; the mouth is
slightly open; the stemomas toids arc prominent; and tltere is some retraction of tlte eyelids. Sh e is anxious . (Right) Twenty-four hours later
the patient is complaining of severe dyspnea. The mouth is now more open, and contraction of the sterno mastoids is such that the head is
raised off the pillow. The patient is drowsy, and lid retraction has decreased. Also visible is thrombosis of the left extern al jugular vein.
Despite a Pao2 of 60 mmHg, the patient was intubated and mechanically ventilated (not shown). (Used, witlr permission, from Gils tou:
Anestlresia 31:385-97, 1976.)
COPD, pursed-lip breathing is associated w ith a n increase resulting in better tissue oxygenation.10 Pursed-lip breath-
in tidal volume and a decrease in respira tory rate. 10 Pursed- ing is thought to improve gas exchange by preventing air-
lip breathing can improve the arterial tensions of both car- way collapse. As a result, gas trapping is decreased, result-
bon dioxide (Paco2 ) and oxygen (Pao 2 ), w hereas oxygen ing in an increase in tidal volume. 10
uptake (V 02 ) remains unchanged.10 The latter finding sug- A few patients in respiratory distress moan during exha-
gests that pursed-lip breathing may allow a decrease in lation. Such m oans have been compared with the grunt-
cardiac output without changing tissue oxygenation.10 Al- ing tha t is typical of neonates with the respiratory dis-
ternatively, if cardiac output does not decrease, pursed-lip tress syndrome.8 Grunting results from glottic closure and
brea thing may increase mixed venous oxygen saturation, expiratory muscle recmitment during early exhalation. 11
FIGURE 5-3 Alterations in the configuration of the mouth in a patient with a tracheostomy. (Left) The patient is sleeping while
respiration is full y supported by mechanical ventilation. The mouth is closed. (Center) Eight mi nutes after b eing disconnected from the
ventilator, the patient has developed dyspnea with n asal flaring, restlessn ess, and anxiety. The mouth is open. (Right) Eleven days later,
the patient has recovered and is breathing comfortab ly withou t ventilator assistan ce. Her mouth is open but conveys a smile. (Used, witlr
p ennissiou, f r·om Gilstou: Anesthesia 31:385-97, 1976.)
FI GURE 5-4 D rooping of the eyelids accompanying de teriorati on of m ental status during an episode of respirato ry distress. (Left) A
patie nt developed respiratory dis tress 3 days after aortic- and mitral-valve r eplacement. The p atie nt is drowsy and m oderately d yspneic.
The mouth is op en, and s h e is moan ing during e.x halation. The eyelids are drooping . H er hemodynam ic status w as mai ntained
satisfactorily with medical th erapy. (Center) D espite respiratory distress, the patient is able to drink. (Right) After 2 days of medical
th erapy, w hich did no t include m echanical ventil atio n, dyspnea has resolved, an d th e patient is alert, cheerfu l, and talkative. H er
exp ression is relaxed. (Used, with permissicm, from Gilston: Anesthesia 31:385-97, 1976.)
It is associated with a rise in transpulmonary press ure and Mentation can be evaluated by inspection of the face
oxygenation.n If grunting is prevented by tracheal intuba- and by simple questioning. With early respiratory distress,
tion, oxygenation deteriorates_'~~ Use of continuous positive nearly all patients are anxious, and their eyelids are re-
airway pressure (CPAP) improves oxygenation and elim- tracted. As d istress increases, the level of consciousness of-
inates grunting.12 The improvement in oxygenation may ten d ecreases, and the lids tend to fall (Fig. 5-4). Instead
result from grunting acting as a natural form of PEEP that of remaining alert to their surroundings, patients gaze va-
recruits collapsed alveoli and partially overcomes inequal- cantly ahead. 8 If respiratory failure is left untreated, apa-
ities in gas distribution caused by differing time constants. thy leads to drowsiness and then coma. These changes in
Of course, grunting also can arise with disease outside the mentation arise because of the underlying cause of respira-
thorax, su ch as with an acute abdome.n.'13 tory failure (decreased cardiac output in cases of shock, im-
Nasal flaring, another facial sign of respiratory dis- paired neurologic function in sepsis), acute hypercapnia,22
tress, is caused by contraction of the alae nasi, the dila- or to a lesser extent, hypoxemia.22' 23 In a classic description,
tor muscle of the external nares. 9 In adults, nasal flaring Campbell noted that most (nonhypotensive) patients with
reduces nasal resistance by about 40-50% and total an exacerbation of COPD have preserved consciousness on
airwayresistance by about 10-30%.9 Factors regulating alae arrival to the emergency room despite Pao.. being as low as
nasi activity include chemical stimuli that cause hyper- 20-40 mmHg. 23 While extremely useful in overall patient
pnea (hypoxia and hypercapnia), 9•14• 15 inspiratory resis- assessment, facial signs of respiratory distress do not nec-
tive loading,15 and local stimuli (negative intraluminal essarily translate into an automatic decision to intubate a
nasal pressure). 14 The proportion of patients in r espi- patient (see Fig. 5-4).
ratory distress who present with nasal fla ring is un-
known, as is the level of interobserver agreement in de-
tecting flaring. Ventilator support reduces or eliminates ACCESSORY AND EXPIRATORY
alae nasi activity.16• 17 MUSCLE RECRUITMENT
Diaphoresis, often best detected on the forehead, 8 accom- Increased respiratory loads in healthy subjects24' 25 and in
panies respiratory distress in some patients. Among 49 pa- ambulatory patients with COPD26 are met with a propor-
tients admitted to the emergency ward for acute bronchial tionately greater use of the rib-cage muscles than of the
asthma, Brenner et al18 found that 9 patients had pro- diaphragm. 24- 26 As the load increases, tl1e expiratory mus-
fuse sweating. This subgroup displayed greater abnormal- cles are recruited.24•25•27 In addition to increased activity
ities in peak expiratory flow rate and Paco.,. In patients of rib-cage and abdominal muscles, the respiratory cen-
with respiratory distress, diaphoresis may result from inters may increase activity of the accessory muscles, es-
creased work of breathing,19 sympathetic stirnulation,19- 20 pecially the stemomastoids. 28, 29 The sternomastoids have
and hypercapnia-associated cutaneous vasodilation.19, 21 In been shown to be activated in patients with respiratory
contrast, diaphoresis in patients with heart failure often is compromise28 and in healthy subjects breathing with a high
associated with h ypoperfusion of the skin, vasoconstriction, level of inspiratory effort. The threshold for sternomastoid
and cold extremities.'19 activation, however, is lower in patients.29 In patients with
CHAPTER 5 INDICATIONS FOR MECHANICAL VENTILATION 133
respiratory distress,4·30 sternomastoid recruihnent can be •

phasic (during inhalation) or tonic. 27 Some patients hold +60%
• .
+30%
their head off the pillow to enhance sternomastoid action8
700
(see Fig. 5-2).
E
TACHYPNEA, PARADOX, TRACHEAL TUG,
INTERCOSTAL RECESSIONS
Changes in respiratory ra te are one of the most useful signs
-
~
t;
-
500
..
•
.
.. . . .
.
Q) • •• -30%
in evaluating the need for mechanical ventilation. Tachyp- ·~
..0
;::, •••
nea is a near-universal sign accompanying respiratory dis-
tress.
Obtaining reliable meas urements of respiratory rate
and interpreting the values are not straightforward. First
-
en
Q)
E
;::,
300
•
,•..
bedside assessment often is inaccurate. In one study, 40%
of nurses' estimations of respiratory frequencies deviated
~ ..
iU
by more than 20% from the true value. 31 Agreement as to ..._ .. ..
"'0 n: 14
••
100
the presence of tachypnea among physicians, expressed r : ·0 324
as a K value (K of 0 indicates that agreement is no better p : ns
than chance; K of 1 indicates complete agreement), was
only 0.25.32 Second, the within-day (within an individual) 100 300 500
coefficient of variation in respiratory rate among young Tidal Volume (Objective). ml
healthy adults is 21 ± 12%; in old healthy adults, it is
29 ± 11%.33 Thus accurate quantification of respiratory FIGURE 5·5 Subjective estimates by 14 observers of tidal volume
rate requires counting more breaths than contained in the in one critically ill patient breathing spontaneously compared
with objective m easurements at that time. The diamonds signify
usual 15-second sample. 33•34 Third, the day-to-day coeffi-
attending physicians, triangles signify fellows, squares signify
cient of variation of respiratory rate is 7 ± 2% in healthy respiratory therapists, and circles signify critical·care nurses. The
individuals,33 the value in patients with pulmonary dis- correlation between subjective estimates and objective
eases is unknown. Fourth, the typical respiratory rate in meas urements was not significant. (Used, wit/1 permissiou, from
patients with different clisease states varies from one s tate Semmes et al: Subjective aud objective measuremeut of tidal
to the next34 (Table 5-l); a rate that is judged high in a volume i11 critically ill patieuts. Cllest 87:577- 9, 1985.).
previously healthy subject may arouse no concern in a
patient with restrictive disease. The upper limit of normal
(mean + two standard deviations) in health is 22 breaths respectively, and respiratory problems accounted for more
per minute. 34 The equivalent value for stable patients than half the readmissions. Of 18 patients who where dis-
with COPD is 30 breaths per minute and for patients w ith charged from the ICU with a respiratory rate of more than
restrictive lung disease 44 breaths per minute. 34 30 breaths per minute, 12 required readmission. In a study
Despite limita tions in its measurement, tad1ypnea is an of patients who had experienced a cardiopulmonary arrest,
important clinical sign. In a retrospective case-controlled 53% had d ocumented deterioration in respiratory ftmction
study of patients discharged from an ICU, the only contin- in the 8 hours preceding the arrest.36 Of interes t, res piratory
uous variables that predicted readmission to the ICU were rate was elevated in most patients [mean 29 ± 1 (standard
higher respiratory rate (24 versus 21 breaths per minute) error) breaths per minute], whereas other routine laboratory
and lower hematocrit.35 Readmitted patients had a mud1 tests show ed no consistent abnormalities. That detection of
higher mortality than the control patients, 42% and 7%, tachypnea did not lead to a change in patient management
(in an effort to prevent the arrest) led the authors to surmise
TABLE 5-1 Respiratory Rates in H ealth and Disease that physicians do not fully appreciate its clinical impor-
tance.
Number of Mean Mean Shallow respiration (when meas ured with ins trumenta-
Condition Subjects (breaths/ min) so + 250 tion) is common in patients with acute respiratory distress. 37
Healthy nonsmoker 65 16.6 2.8 22.2
Judging tidal volume as shallow based on physical exami-
Healthy smoker 22 18.3 3.0 24.3 nation is very wueliable38•39 (Fig. 5-S). Clinical skill in this
Asthma 17 16.6 3.4 23.4 task is not improved by years of experience.39
COPD, eucapn.ia 16 20.4 4.1 28.6 Pa tients in distress commonly display abnorma l chest-
COPD, hypercapnia 12 23.3 3.3 29.9 wall movements.40, 41 Abnormal movements can be sepa-
Restrictive lung 14 27.9 7.9 43.7 rated into three categories. One, asynchrony, consists of a
d isease difference in the rate of motion of the rib cage and abdomen.
Pulmonary 7 25.1 6.4 37.9 Two, paradox, consists of one compartment moving in the
hypertension opposite direction to tidal volume. The third abnormality is
Chronic anxiety 13 18.3 2.8 23.9
greater than normal breath-to-brea th variation in the rela-
SO, standard deviation. tive contribution of the rib cage and abdomen to tidal vol-
souRcE: Data from Tobin et al: 0 1est 84:286-94,1983. ume; this pattern, termed respiratory altemans, represents
recruitment a nd derecruitment of the accessory intercostal coefficient; the explicit, measurable components may be the
muscles and the diaphragm. In the past it was thought that least relevant. Another problem with research on physi-
these three abnormalities of motion represented respiratory cal signs is test-referral bias. For example, the studies of
muscle fatigue. 42 It is now known that they represent signs Godfrey et al 50 and Spiteri et a1 32 were confined to patients
of increased load and occur in the absence of fatigue. 43 These with respiratory diseases; a more appropriate design also
abnormalities are seen not only in patients with r~iratory would have included healthy subjects and patients w ith
dis tress44 but also in some ambulatory patients34• or dur- diseases not affecting the lungs. These flaws in the method-
ing sleep (sleep apnea syndrome) .~ ology of such studies markedly overestimate the diagnostic
Increased tidal swings in intrathoracic pressure are ax- power of physical examination.
iomatic to increases in the work of breathing. The greater
downward movement of the diaphragm tends to pull down CARDIOVASCULAR SIGNS OF
the trachea (just as a sexton ringing a bell) with each RESPIRATORY DISTRESS
inspiration,46 producing a sign termed tracheal t ug. Tracheal Respiratory distress frequently is associated with tachycar-
tug correlates closely with severity of airway obstruction.47 dia and hypertension. Tachycardia and hypertension likely
The intercostal spaces normally bulge inward during in- are caused by incr eased sympathetic dischar ge. 5·1 In some
ha la tion and outward during exhalation.13 Inspiratory re- patients, such as those with sepsis, cardiac impairment, or
traction of the intercos tal space-serving as a window into severe hypoxemia, respiratory distress is associated with
the pleural space-is increased in patients with respira- hypotens ion and not hypertension.
to ry disease. The suprasternal fossa also moves inward in Pulsus paradoxus is defined as an inspiratory fall in the
direct proportion to swings in pleural pressure.48A 9 Focal systolic pressure of greater than 10 mmHg. 13 Pulsus para-
exaggerated retraction of the intercostal space can occu r doxus is very common in patients with an exacerbation of
with a flail chest. Focal expiratory bulging may be seen on asthma but also in patients with COPD, shock, and pericar-
the side of a tension pneumothorax or over the area of a dia] tamponade 13•18 (see Chapter 36).
flail chest. 13 As with other physical signs, studies often re-
veal poor agreement among physicians.32' 50 For example, NONUNIFORM PRESENTATION
Godfrey et al50 found agreement among 11 relatively ex- Patients with impending respiratory fa ilure do not have a
perienced chest physicians in identifying tracheal tug to uniform presentation. The spectrum ranges from a patient
be midw ay between chance and maximum possible agree- complaining of dyspnea to a patient with impending respi-
ment. Spiteri et a132 found poor agreem ent among experi- ra tory arrest. Several factors are r esponsible. Patients differ
en ced physicians for detecting reduced chest m ovements (K in the balance between workofbreathingand thecapacityof
= 0.38) and cricosternal distance (K = 0.28)32 (Fig. 5-6); they the respiratory muscles to genera te pressure. They a lso dif-
did not address tracheal tug or inspiratory retractions. fer in the central processing of neura l a fferents. For instance,
The interpreta tion of data generated by studies that quan- patients with a history of near-fa tal as thma have a blunted
tify physical signs is hazardous. The entity that researchers perception of d yspnea,52 reduced sensitivity to added inspi-
are quantifying can be very different from th e skill involved ratory resistive loads,53 and a reduced chemosensitivity to
in the p hysician's actions. Physical examination is an ar t- hypoxia.52 In addition, hypoxia,and possibly hypercapnia,
learned through a pprenticeshlp, not out of a book. Thus we can impair sensations of respira tory load.54
should bear in mind Braque's caution abou t art apprecia-
tion: "The only thing that matters in art can't be explained." IMPENDING RESPIRATORY FAILURE
Likewise, the essence of physical examina tion is its tacit A commo nly listed indication for mechanical ventilation is
development of impending respiratory failure.55 But im-
pend ing respiratory failure has no clear definition. Some
FIGURE 5-6 Cricosternal dis tance. The physician notes the
clinicians use the term to mean development of severe
distance in finger breaths b etween the lower border of the tachypnea, diaphoresis, and use of accessory muscles of
cricoid cartilage and the suprasternal notch. The n ormal distance respira tion. Others use it to mean agonal breathing.
is three or four finger breaths. A decrease in this distance is a In some circums ta nces, physicia ns do not institute me-
sign of h yperinflation. (Used, with permission, from Flenley : chanical ventilation until they obtain results of diagnostic
Coucise medical te.:rtbooks: Respiratory mediciue. Londou: Ba.illiere testing, such as chest rad iographs, electrocardiograms, or
Tindall, 45, 1981.) arterial blood-gas analyses. Even in this situatio n, clinicians
commo nly d o not cl1ange their mind when the test results
-Ster-no-ma~toid . / Thyroid cartilage
.4_f\ . <.(J/J Cricoid cartilage

TAB LE 5-2 Common Caus es of Hypoxemi c Respiratory Fail ur e
.,) I \ ,. ., Pneumonia
Cardiogenic p ulmonary edema
-J \ ~ d\~ Acute resp iratory d istress syndrome
Aspiration pneumonia
Multiple trauma
Suprasternal lmmunocompromised host with pulmonary infiltrates
Pulmonary em bolism
notch
Yes No
Is PaC0 2 increased?
Hypoventilation Is A-aD02 increased?
Yes No
!
Is A-aD0 2 increased?
Is low Pa02 correctable with 0 2 ? J. Inspired PP2
No Yes 1. High altitude
r-0 ~
2.,!. PI0 2
Hypoventilallon Hypoventilation plus

alone another mechanism Shunt v,;a mismatch
1. J. Respiratory Drive 1. Alveolar collapse 1 . Airways disease
2 . Neuromuscular disease (atelectasis) (asthma, COPD)
2 . lntraalveolar filling 2. Interstitial lung disease
(pneumonia, 3. Alveolar disease
pulmonary edema) 4. Pulmonary vascular disease
3. lntracardiac shunt
4. Vascular shunt within lungs
FIGURE 5-7 The diagnostic approach to a patient with hypoxemia or hypercapnia. The alveolar-arterial 02 gradient (A-aDo2 ) is usually
less than 10 mmHg for subjects 30 years of age and younger and is increased by ~3 mmHg per decade after age 30. V AIQ,
ventilation-perfusion ratio; COPD, chronic obstructive pulmonary disease. Not included are conditions where a decrease in mixed venous
0 2 content in the presence of increased A-aD 0 2 contributes to hypoxemia. (Modified, witll permission, from Weinberger et al: ltz: Kasper et
al, edi-tors. Harrison's principles ofinternalmedicine. New York: McGraw-Hill, 1498-1505, 2005. )
are different from those expected. In most circumstances, a from either ventilation-perfusion (VA/Q) abnormalities or
patient's clinical presentation is so dramatic that mechanical excessive right-to-left shunt. (Diffusion impa irment, a third
ventilation is instituted without performing arterial blood- cause of increased A-aDo,, plays only a marginal role in the
gas analysis. If arterial blood-gas results a re not available development of hypoxemia.) Patients with hypoxemic res-
before connecting a patient to a ventila tor, they are almost piratory failure and a normal A-aDo 2 typically have alveolar
invariably available shortly after. Arterial blood-gas analy- hypoventila tion or inadequate inspiratory partial pressure
sis is helpful in choosing the type of support best suited to a of 0 2 . Hypoxemia results from a low inspired Po 2 or when
patient's needs. Analysis also serves to classify patients into the fractional concentration of inspired 0 2 (Flo,) is less than
two broad groups: hypoxemic respiratory failure (Table 5-2) 0.21, such as at high altitude or when Oz is consumed from
and hypercapnic respiratory failure; some patients display ambient gas secondary to a fire. A low Fro, also can arise
features of both.56 during anesthesia if a low-02 gas mixture is admi11istered
inadvertently. Hypoxemic respiratory failure also can be
caused by the combination of a decreased mixed venous
HYPOXEMIC RESPIRATORY FAILURE 0 2 content and impaired gas exchange, such as in patients
PATI-10PHYSIOLOGY with heart failure and concurrent V AIQ derangements or
The pathophysiologic mechanisms responsible for hypox- increased shunt.
emia can be grouped into two broad categories d epending
on whether there is (or is not) an increased alveolar-arterial Right-To-Left Shunt
~gradient (A-aDo2 )* (Fig. 5-7). An increased A-aD~ results A right-to-left shunt is present when venous blood re-
turning from the tissues passes to the systemic arterial
• A-aDoz is calculated as PAo 2 - Pa~, where Pao 2 (alveolar 02 at 37"C), and R is respira tory exchange ratio of the wh ole lung. The
tension) can be estimated according to the simplified alveolar gas respiratory exchange ratio (R) = C02 production/ 0 2 consumption
equation: (Vc~ / Vo2 ) is nonnally about 0.8. fn steady sta te, R is determined
b y the relati ve p roportions of free fatty acids, protein, and carbohy-
drate consumed by the tissues. In this equation it is assumed that
alveolar Pea, and Paco, are the same (usually they nearly are). In
where Fro2 is fractional concentration of inspired 0 2 (about0.21 when healthy young subjects (:::;30 years old) brea thing air at sea level,
breathing room air), Ps is barometric pressure (a bout 760 mmHg at A-aDo2 is usually less than lOnun Hg, but it increases to as much as
sea level), PH2o is water vapor pressure (usually taken as 47 mmHg 28 mmHg in some healthy 60-yea.r-old subjects.
136 PART III INDICATIONS
circulation without coming into contact with gas-containing ically produces more severe hypoxemia than does V AIQ
alveoli. A sm all degree of shunting (about 2-3% of cardiac inequality.
output) is caused by the bronchial veins entering the pul-
monary veins and the thebesian veins of the myocardium, Ventilation-Perfusion Inequality
which empty directly into the left-ventricular cavity.57 Optimal uptake of 0 2 depends on proper matching of ven-
Shunting also may occur through abnormal intracardiac tilation and perfusion within the lung. The lung consists of
or intrapulmonary a na tomic pathways: a trial or ventricu- about 300 million alveoli,59 each with its own share of venti-
lar septal defects, pa tent ductus ateriosus, and pulmonary lation and perfusion. In semi recumbent young healthy sub-
arteriovenous fistulas. Shunt is the major mechanism of ab-
jects breathing room air, the range (or dispersion) of VA/Q
normal gas exchange in patients with pulmonary edema, ratios is quite small: More than 95% of both ventilation and
ARDS, pneumonia, a nd a telectasis. In all the latter instances,
perfusion is limited between V AIQ ratios of 0.3 and 2.1.60
the shunt results from the perfusion of alveoli that are un-
ventila ted because they are filled with fluid or collapsed. TI1e dispersion increases with age. 60 With pulmonary dis-
A characteristics feature of a shunt is the failure of Pa 02 to ease, the range of VA/Q ra tios widens,61 varying from 0
increase to the expected level when a patient brea thes 100% (perfused but unventilated, i.e., shunt) to infinity (ventilated
02 (Fig. 5-8). This occurs because the shunted blood does not by unperfused, i.e., alveolar dead space). In other words,
make con tact with ventilated alveoli and thus is not exposed VAIQ inequality does not refer to alterations in the ratio of
to the higher PAOz . The addition of well-oxygenated blood total ventila tion to total perfusion, which constitute global
of nonshunted areas to the poorly oxygenated blood from hyper- or hypoventilation. (One lung could receive all ven-
the shunted areas is not sufficient to increase the Pao, . tilation and the other all perfus ion for an overall VAI Q ratio
Although the shunted blood is rich inC~, a patient w ith ofl.0).62 VA/0 inequality refers to regional mismatching of
an increased shunt typically does not have a raised Pac0: ventila tion to perfusion. V AIO inequality, no matter what
because any elevation of Pac0: causes chemoreceptor stim- its mechanism, inte rferes with overall efficiency of the lung
ulation and an increase in ventilation. Thus P CO: in the non- for exchanging all gases, including 02, C02, CO, and anes-
shunted blood is lowered such that Paco2 returns to normal. thetic gases.58
In patients with a large shunt (cyanotic congenital heart dis- VAIQ misma tch is the most common cause of hypox-
ease), PacO: may be low because the low Pa0 , stimulates res- emia. Most diseases affecting either the airways or lung
piratory drive and minute ventilation (VE).~8 A shunt typ- parend1yma are distributed unevenly. Thus they variably
affect ventilation and perfusion. Some lung regions may
have good perfusion and poor ventilation, whereas other
FIGURE 5-8 Relationship between arterial P0 2 (Pao2 ) and
regions may have poor ventilation but good perfusion.
increases in inhaled 0 2 concentrations for di fferent levels of When VAIQ inequality consists mainly of low VAIQ ar-
shunt. When the shunt fraction is 30'Yo or more of cardjac output, eas secondary to inadequate ventilation (e.g., COPD when
Pao2 increases little despite marked increases in inspired Oz severe bronchitis predominates) or increased perfusion of
concentration. The plot is a simplification that ignores factors normally ventila ted units (e.g., diversion of blood flow fol-
such as carwac output an d 0 2 uptake, which influence the lowing pulmonary embolism), the effects on gas exchange
location of the lines. (Used, witlr permissiou, from West:
are more marked for P0 2 than for Pc0 2.63 In the low V,\/Q
Pulmouary patlropltysiologtj: Tite esstmtials, 6th ed. Pltiladelpltia:
units, alveolar 0 2 is taken up by the perfusing blood at a
Lippiucott Williams & Wilkins, 163, 2003.)
high enough rate a nd is refreshed by ventilation at a slow
5 00~--~--~----~--rr---.
enough rate to maintajn an abnormally low PA0:. 64 There-
sult is a shuntlike mixing of poorly oxygenated blood from
the low VAIQ units with well-oxygena ted blood from the
400 high VAIQ units. The well-oxygenated blood ca1mot fully
compensate for the poorly oxygenated blood for the same
0> reason that supplemental 0 2 does not correct the hypoxemia
I of right-to-left shunt.
E 300
E When VAIQ inequality consists mainly of high VA/Q
C\1
areas, such as decreased perfusion of a compartment (se-
0 vere emphysema w here many capillaries are destroyed), de-
ct1
200
a... creases in Pa0: can be accompanied by rises in Paco2 because
high VA/Qunits are inefficientateliminatingC02.58,63 Units
such as these constitute part of alveolar (and physiologic)
100 dead space.58•62
Compensatory mechanisms tend to minimize the effects
of these abnormal VAIQ ratios. The low PAQ2 associated
100 with a low V AIQ ratio causes pulmonary vasoconstriction.
0 20 40 60 80
TI1e low PAcOz associated with a high V AIQ ratio causes
hypocapnic bronchoconstriction65 (e.g., pulmonary em-
Inhaled 0 2 Concentration, % bolism). These responses, however, only achieve partial
CHAPTER 5 INDICATIONS FOR MECHANICAL VENTILATION 13 7
compensation. As VAIQ inequality increases in the pres- The different responses of Pao2 and Pac02 to an increase
ence of a constant Vo, and Vc~, there is an immediate and in the level of ventilation is caused by the different shapes of
marked fall in Pa02 and a s lower increase in Paco.. TI1e in- the oxyhemoglobin a nd C~ dissociation curves (Fig. 5-10).
crease in Paco. and, to a lesser extent, the fall in Pao2 stim- TI1e oxyhemoglobin dissociation curve is flat in the normal
ulates the chemoreceptors and lead to an increase in VE· In range. Thus only units with moderately low V AIQ ratios
patients without a significant reduction in ventilatory ca- benefit appreciably from the increased ventilation. Lung
pacity, the increase in ventilation is sufficient to bring Paco1 units that are positioned on the upper portion of the dissoci-
back to normal, although it has only a small effect on the ation curve (high VAIQ ratio) develop little increase in the
fall in Pao. (Fig. 5-9). Thus most patients with VAI Q in- 0 2 concentration of their effluent blood. The net result is that
equalities have a low Pa~ but normal Pac0 / 6 Ventilation with increasing VE, the mixed Pa~ rises only modestly, and
in excess of normal alveolar requirement is termed wasted some hypoxemia always remains.58 By contrast, the C02
ventilation.58 All normocapnic patients with COPD have in- dissociation curve is almost linear in the physiologic range.
creased ventilation of their alveoli, as do most hypercapnic Thus an increase in VE raises C02 output of lung units with
patients.58 both high and low VA / Q ratios.58 TI1e different shapes of the
two dissociations curves are the main reason that patients
with parenchymal lung disease have greater hypoxemia rel-
FIGURE 5-9 Effect of increasing overall ventilation on Pao2 and ative to hypercapnia. One final compensatory adjustment is
Paco2 (lung model) as a fun ction of different degrees of VA/Q
possible: increase in cardiac output. 63 Adrenergic stimula-
mismatching, represented in terms of dispersion or standard
deviations (SO) of the lognormal distribution of ventilation and
tion by arterial hypoxemia can raise cardiac output by 50%
perfusion. (D ispersion of 0.30-0.05 = normal VA/Q mismatch; 1.0 or more; this improves arterial blood gases by raising mixed
= moderate VA/Q mismatch; 2.0 = severe VA/Q mismatch.) venous 02 and by lowering mixed venous co2.63
Increases in overall ventilation have a powerful effect on Pao 2 Administration of s upplemental 0 2 in patients with
and Paco1 when VAIQ dispersion is small. Abnormal VAIQ VAIQ inequality will cause arterial hypoxemia to reverse
dispersion does not cause an increase in Paco 2 as long as patients impressively because PA0 2 of even poorly ventilated units
are able to increase minute ventilation sifficiently. Pa02 also increasessufficiently to achieve saturation (Fig. 5-11). Unless
increase with increases in overall ventilation, although when F~ot is 1.0, it is impossible to determine the relative contri-
VA/Q dispersions are (very) altered, normal Pao1 cannot be
reached very easily, and further effects on ventilation have little
bution of right-to-left shunt versus VAIQ inequality to an
effect on Pa 02 • In the patients who cannot maintain a high rate of increase in A-aD0 2. 57 After breathing 100% 0 2 for a sufficient
ventilation owing to the increased work of breathing and in those time, only units that are totally or almost totally unventi-
whose respiratory drive increases only slightly when Paco1 is lated (shunt, true shunt, or anatomic shu nt) will contribute
high, hypercapnia can ensue. (Used, witl1 pel"missiou, from West: to hypoxemia.57
Am R ev Respir Dis ll6:919-43,1977.)
100 PHYSIOLOGIC EFFECTS OF HYPOXIA

~!I o---o Po.
Although the physiologic effects of hypoxia are graded, the
90 1 0.5
• - • Pc02 damaging effects are sudden .67 A remarkable degree of ar-
terial hypoxemia is required to cause tissue hypoxia. 23 In
clinical practice, Campbel123 observed that the lowest Pao.
0>
I 80 compatible with life is 20 mmHg [equivalent to an arterial 0 2
E 1.0 saturation (Sa0 2) of 30-40%]. Evidence of end-organ dam-
E 70 age is difficult to demonstrate in patients with a Pa02 above
(\1 40 mmHg (equivalent to an Sao, of about 70%). 23 Obviously,
0 the duration of hypoxemia and the s tate of circulation (02
60
()
ca
a.. 50
..,.___ ,_5 _ ' .......
...........
_ ___,_ 2 . 5
C"
delivery) play major roles in determining the minimum Pa~
that does not cause end-organ damage or deatl1.
The threshold Pao, commonly used to diagnose hypox-
""0 emic respiratory failure is 60 mmHg, which corresponds
c
ca 40 to an Sao1 of 90% (hypoxic hypoxia). Pao 2 values below
0(\1- 60 mmHg fall on the steep portion of the oxyhemoglobin
30 dissociation curve, and decreases below that value are as-
ca
a.. socia ted with precipitous falls in Sa02 (see Fig. 5-10). Al-
though physiologically reasonable, for self-evident ethical
20 reasons, the 60 mmHg (Pao,) threshold cannot be validated
experimentally.
10 The main concern with hypoxemia is impaired tissue
oxygenation, especially of the heart and brain. TI1e factors
0 determining 0 2 supply to the tissues include hemoglobin
2 4 6 8 10 12 14 16 (Hb) concentration, Sa02, the affinity of Hb for 0 2 (Pso),
cardiac output, regional 0 2 consumption-to-perfusion re-
Overall Venti lation, liters/min lationships, and the diffusion of 0 2 from the capillary to
0~
100 80
c
E
0
0 80 0
·.;::
!!!
~
:::. 60
-::J
<0 60 E
-- o xygenated
blood
-8
cQ) 40
CIJ
c
:0 40 T : 37'C c
0
0> pH = 7.40
20
0
E 20 0()
Q)
J:
0 0
20 40 60 80 100 20 40 60 80 100
P02 , mmHg PC02 , mmHg
FIGURE 5-10 (Left) Normal oxyhemoglobin dissociation curve. The curve has a sigmoid shape because when one subunit of the normal
tetrarneric form of normal adult hemoglobin becomes oxygenated, it induces a configuration (or structural) arrangement change in the
whole complex. As a result, the three other subuni ts gain a greater affinity for oxygen until four molecules of 0 2 are combined with
hemoglobin. (Right) The C02 dissociation curve for oxygenated and reduced blood. The relationship is steeper and mor e linear than the
oxyhemoglobin dissociation curve. Oxygenation of blood cau ses th e curve to shift in a rightward direction (Hald ane effect). Thus, for a
given C02 content, oxygenated blood has a higher Pco2 tl1an reduced b lood; this factor is one of the reasons for an i.n crcase in Pco2 when
b reathing supplemental 0 2.
intracellular sites. The amount of 0 2 delivered to the tissues to the respiratory centers (inspiratory neurons of the dorsal
is calcula ted as respira tory group and ventral respiratory group 73 ), caus ing
an increase in the VE.68, 69•74•75 Hyperpnea, in turn, activates
0 2 delivery= Ca0 2 x cardiac output pulmonary afferents, thereby buffering the sympathetic re-
sponse to hypoxemia.76
The ventila tory response to progressive hypoxia is
curvilinear 68 and increases in the presence of concur-
where arterial 0 2 content (Cao,) is calculated as rent hypercapnia 71 (Fig. 5-12). It decreases with age,77
Chronic hypoxia may induce a reduced ventilatory re-
sponse to hypoxia in patients with COPD,71 although the
role of airway narrowing in producing this effect cannot be
excluded.71
Even with a satisfactory Pa 0 2, tissue hypoxia may arise be- The ventilatory response to hypoxemia is attenuated or
cause of decreased Caaz (e.g., decreased Hb concentration or abolished in patients who have undergone surgical excision
decreased Hb function, such as in carbon monoxide poison- of the carotid bodies. 69• 70• 75•78 The increase in ventilation
ing or anemic hypoxia), decreased 0 2 delivery (e.g., cardio- inresponse to hypoxemia probably contributes to coronary
genic shock or stagnant hypoxia), and decreased capacity vasodilation.79 Stimulation of the carotid bodies with nico-
of the tissues to use 0 2 (e.g., sepsis, cyanide intoxication, o r tine under nom1oxic conditions causes an increase in venti-
histotoxic hypoxia). Otherwise stated, tissue hypoxia can be lation and coronary vasodilation. 79 Coronary vasodilation
present despite adequate Pa02, or it can be absent despite does not occur if the increase in ventilation is prevented by
an abnormally low Pa0 2 .55 general anesthesia. 79
Respiratory Responses
Peripheral chemoreceptors (carotid and aortic bodies) Car diovascular Responses
detectchanges in arterial 0 2 . Within seconds after the onset Hypoxic stimulation of chemoreceptors triggers reflex
of hypoxia, they initiate reflexes thatare important for main- adrenergic vasoconstriction in muscle a nd coronary vasodi-
taining homeostasis. 6S-70 The aortic bodies play a minor role lation but does not elicit a r eflex response in the cerebral
in modulating spontaneous respiratory activity, a lthough vessels.70•76•79•80 Hypoxia also causes local vasodilation 68•76
they have a discernible effect when their gain is increased through mechanisms that include local production of ni-
by hypercapnia. 71 tric oxide, activation of adenosine- and ATP-sensitive
Although hypoxia augments sensory discharge of both channels, and other metabolites.81 The net effects are in-
carotidand aortic bodies, it has been proposed that aortic creases in heart rate, cardiac output (resulting from the
chemoreceptors sense 02 delivery, whereas carotid bod- positive chronotropic effect of hypoxemia, not increased
ies sense P0z .n These notions are based on the finding stroke volume82 ), pulmonary artery resistance,83 and cere-
that carboxyhemoglobinemiacauses marked stimulation of bral and coronary blood fl ow70•76•i7,?9,SO,Sl,S4, 8S Hypoxemia
aortic bodies, whereas it has no effect on the carotid body fails to increase systemic blood pressure82•85 or increases
sensory activity.n it very modestly (<10 mmHg rise in systolic a nd diastolic
Hypoxia augments sensory discharge from the periph- pressures 74•84 ) . The increase in blood pressure, but not in
eral chemoreceptors, which, in turn, send neural impulses heart rate, is absent in patients in whom the carotid bodies
Inhaled 0 2 Fraction
0 02 04 06 08 I0
~-T--~~~-r--~~---r--~~--,
20
E
0 22
0 .
T"" c:
:::::::, .Q PaC02 , mmHg
21 ca '
E += 50
_.
c
- 20 J >
c:
Q)
10
40
Q)
_. 30
c
0 19
()
I I I
C\J 0 I
18
0 0 40 80 120 160
~ Pa02 , mmHg
co
FIGURE 5·12 The curvilinear relationship between ventilation
a. and Pao 2 at various levels of Paco2 • When Paco2 is 40 mmHg,
co 16 ventilation increases precipitously as Pao2 falls below 60 mmHg.
() When Paco2 is elevated, ventilation increases abrupUy at a higher
I
""0 Pao 2 • When Paco2 is lower, the ventilatory response to hypoxia is
15
c less steep. (Used, w itlr pennission, from Grippi et al: ln: Fislrma11,
w editor. Fislnnan's pulmonary diseases a11d disorders, 3rd cd.
New York: McGraw-Hill, Chap. 36, 563, 1998.)
0 tOO 200 300 400 ~00 600 700
carotid bodies by hypoxia and increased cardiac vagal ac-

Inhaled P02 , mmHg tivity induced by apnea? 6' 80 [The increased vagal activity
(induced by apnea) can be so intense as to induce bradycar-
FIGURE 5·11 The effect of alterations in inhaled partial pressure
dia in the absence of coexisting hypoxemia; this res ponse
of 0 2 on 02 content of end-capillary blood of a lung unit. Each
line depicts a different ventilation-perfusion ratio (VAIQ). With has been d escribed in patients with spinal cord injury w ithin
mild to moderate degrees of VA/Q inequality (VA/Q down to 0.1), seconds of discontinuation from a ventilator.91 ] Simultane-
end-capillary 0 2 content increases as inspired 0 2 is increased. ously with the increase in cardiac vagal activity, diminution
With severe VA/Q inequality (VA/Q below 0.1), the increase in of lung inflation causes marked potentiation of the sym-
end-capillary 0 2 content with an increase in inspired 0 2 is much pathetic vasoconstrictor response to hypoxemia (secondary
slower; only when inspired Po2 is more than 40D-500 mmHg does to the lack of inhibitory influence of the pulmonary stretch
end-capillary 02 content of the lung unit reach values equivalent receptors).80•92 (This combination of sympathetic vasocon-
to those seen w ith mild to moderate degrees of V A/Q inequality. striction and vagal bradycardia constitutes part of the div-
(Used, with permission, from. West: Am Rev Respir Dis 116:919-43, ing reflex.80 )
1977.) Severe hypoxemia is not tolerated by the CNS because
it has a high rate of 0 2 consumption and lacks a lternative
energy reser ves. 93 Therefore, severe hypoxemia causes cer e-
are inactivated?0• 74 Persistent tachycardic res ponse to hy· bral depressio n.69•84 Patients with cerebral hypoxia develop
poxemia in patients with bilateral carotid body ablation bradycardia, hypotension,88 and hypoventilation, 84 which
likely is mediated by the effect of hypoxemia on the aor- further worsens hypoxia and induces a potentially lethal
tic bodies.68 viscous cycle.
Tachycardia caused by hypoxemia is mediated by mul-
tiple factors, including CN5-mediated sympathetic dis·
CLINICAL PRESENTATION OF HYPOXEMIA
charge, effect ofPo 2 on the cardiac pacemaker, a nd concomi·
tant hyperpnea?4 These mecl1anisms presumably override Cyanosis
the cardioinhibitory signals (bradycardic effect) from the Physicians commonly view cyanosis as the hallmark of
carotid body.74 The importance of hyperpnea in overriding hypoxemia.68 Cyanosis is recognized as a blueness of the
the bradycardic effect is supported by the observation tha t capillary blood visible through the mucous membranes or
hypoxemia combined with cessation of lung inflatio n (sleep skin, where capillaries are numerous and close together and
apnea,86 breath holding,87 or neuromuscular blockade dur· the tissues over them are thin and tra nsparent, such as the
ing intubation88) or diminution of lung inflation (such as lips (central cyanosis) and nail beds. 68
when hyperpnea is prevented by controlled ventilation89·90 ) Central cyanosis is believed to depend on the presence of
is more a pt to produce bradycardia than tachycardia.68,86 at least 5 g / dl of deoxygenated hemoglobin in the blood of
Bradycardia results from the concurrent activation of the the capillaries94 and of the subpapillary venous plexus.95
140 PART Ill INDICATIONS
With mild anemia (hemoglobin of 10 g/dl), hypoxemia TAB LE 5-3 Neu rologic Signs and Symptoms of Hypoxia
should be severe enough (02 saturation SO%, capillary
P~, mmHg Signs and Symptoms of Hypoxia
P~ about 24 mmHg) to produce cyanosis.64 Conversely,
with polycythemia (hemoglobin 20 g/dl), cyanosis should 35-50 Loss of critical judgment, confusion, delirium
be present when hypoxemia is only moderate (~ satu- (resembling alcohol intoxication), tremors,
ration 75%, capillary P~ 40 mmHg).64 The dictum that asterixis
cyanosis requires 5 g/dl of reduced hemoglobin is difficult 25- 35 Somenolencc, obtundation, myoclonic jerks, seizures
to substantiate.96•97 Cyanosis depends not only on variables 20- 25 Loss of consciousness
such as thickness and opacity of the skin and perfusion <20 Death
status but also on the vis ual skills of the observer.95•97 In
72 patients who had Sa~ values ranging between less than
75% and 100%, agreement among three observers was only
In the absence of defects of cerebral blood flow,
69% when ins pecting the tongue, 61% when inspecting the Pa~ below 40 mmHg is required to produce prominent
lips, and 53% when inspecting the nail bed.95 In that study,95 symptoms22· 100• 1o1 (Table 5-3). Confus ion and delirium (re-
cyanosis of the tongue and lips was recorded in 40-45% of sembling alcohol intoxication) appear at Pao2 values of
patients with normal Sa~ values. Rather than a blue or pink 35-50 mmHg. 62 Tremors and asterixis (flapping tremor
color, pallor is seen with both a nemia and shock. Thus se-
elicited by dorsiflexing the wrists with the arms out-
vere or fatal tissue hypoxia may occur without cyanosis.68
stretched and caused by a momentary interruption of nor·
The skin and arterial blood may be normal in color or even
mal continuous action potentials to both flexor and exten-
bright red in two other types of tissu e hypoxia: cyanide
sor muscles) are infrequent even w hen the Pa~ is less than
poisoning, where the tissues a re unable to use blood 0 2 de- 40 mmHg.22,23 Somnolence and obtundation occur at Pa~
spite its abundance, and carbon monoxide poisoning, where values of 25-35 mmHg. Some patients develop myoclonic
blood contains a bright-red pigment, carboxyhemoglobin,68 jerks (bursts of excitation to resting muscles) and seizures.22
that decreases the oxygen-carrying capacity of the blood
At about 25 mmHg, consciousness is lost,62 and death often
and shifts the oxyhemoglobin dissociation curve to the left.
ensues.
Both these changes-together with inhibition of the mito-
When considering the neurologic manifestations of hy-
chondrial respiratory chain at the cytochrome C by carbon
poxemia, Pa~ is only a small part of a complex situation. A
monoxide98- limit the uptake and use of 0 2 by peripheral decrease in Pa~ may be well tolerated if ~ delivery is main-
tissues. tained by the combination of increased cardiac output and
systemic vasoconstriction. 102 These compensatory mecha-
nisms, however, can be overwhelmed by anemia or car-
Cardiopulmonary Manifestations
bon monoxide poisoning, which decrease oxygen-carrying
Acute hypoxemia increases respiratory frequency, tidal vol-
capacity (anemic hypoxia), or by atherosclerosis or other
ume, and VEin almost all subjects. 68 Increases in VEl how- causes of vascular occlus ion (ischemic hypoxia) in which
ever, are an unreliable guide because the interindividual
the increased cardiac output does not suffice to prevent
response to hypoxemia is considerable.97 Thestandard devi-
tissue damage.
ation for the within-subject variabilityin day-to-day hypoxic
ventilatory response is about 22%.99 The respiratory re-
sponse to mild or modera te hypoxemia may be barely mea-
surable or absent.b8·92 An increase in heart rate is equally of HYPER CAP NIC RESPIRATORY FAI LURE
limited value because many other factors, such as fever, low PATHOPHYSIOLOGY
blood pressure, pain, apprehension, and drugs, can cause Hypercapnic respiratory failure is a state in which venti-
it to rise. 68 Moreover, under specific circumstances (see lation is insufficient to maintain a normal Pa~ for the
above), hypoxemia causes bradycardia rather than tachy- level of metabolic activity (measured by C02 production,
cardia. Hypoxemia tends to increase systolic blood pres- Vc~). Common causes include COPD, severe asthma, con-
sure in some subjects; the wide variations in response14 ditions where respiratory drive is decreased (e.g., neo-
renders arterial pressure of little value in the diagnosis of plasm and infections of the CNS, medications, and drugs),
hypoxemia. 68 neuromuscular-skeletal diseases (e.g., myasthenia gravis,
Guillain-Barre syndrome, a nd trauma), and upper airway
obstruction.
Neurologic Ma nifes tations Under steady-state conditions, the relationship between
The metabolic needs of the brain largely depend on oxida- Pac~, alveolar ventilation (VA), and Vc~ is given by the
tion of glucose to C02 and water.93 The brain cannot store equation
~.It survives only form inutesafterthesupply is reduced to
critica1levels. 93 In acute anoxia, consciousness is lost within
15 seconds. The electroencephalogram slows with a Pao2 of
less than 35 mmHg or with blood flow of less than 40% of
norma1.93 Loss of the electroencephalogram tracing occurs The constant K is us ually stated as 0.863; it converts mea-
when cerebral P~ reaches 20 rnmHg or following 20 sec- surements of Vc~ from s tandard conditions to body-
onds of complete anoxia. 93 temperature conditions. The term VA represents the portion
of VE that reaches the terminal gas-exchange u11its and is
calcula ted as , ~ecreasing Pa02
20 I /
I I
c I /
·e I /
where Vo equals dead-space ventilation. A reduction in VA :J I /
may result from an inadequate VE or an increase in V0 (re- c I /
I /
sulting from an increase in true V0 or a functional increase ....
.Q
I /
..!.!! 10 I I
in V0 secondary to lung regions with high VAIQ relation- +::
cQ) I /
ships).
> 1/
1/
The mechanisms responsible for hypercapnia can be
1/
grouped into two categories depending on whether there is
(or is not) an increased A-aDo, (see Fig. 5-7). In pure alveolar
hypoventilation (e.g., neuromuscular diseases, drug over-
doses, and CNS pathologies), A-aDo, is usually normal (tm- 42 46
less lung abnom1alities are present). In disorders associated
PaC02 , mmHg
with VA/0 inequality (e.g., COPD and ARDS), A-aDo, is in-
creased. FIGURE 5-13 Ventilatory respons e to progressive h yp erca pnia.
Paco, in excess of90 mmHg is unlikely in patients breath- Ventilation increases linearly with increase in Paco1 • Decreases in
ing room air because the concomitant degree of hypoxia is Pao2 produce more s teep ventilatory response to p rogressive
hypercapnia. (Used, wWr pennission, from. Grippi et al: In:
incompatible with survival. 23 Such Paco, values can occur Fishman, editor. Fislmrau's pulmonary diseases aud disorders,
if a patient is breathing 0 2 -enriched air. 103 3rrl ell. New York: McGraw-Hill, Clrap. 36, 561, 1998.)
PHYSIOLOGIC EFFECTS OF HYPERCAPNIA

Hypercapnia elicits autonomic and ventilatory responses Cardiovascular Respon ses
primarily through central chemoreceptors located in the Hypercar,nia causes greater increases in sympathetic
rostral ventrolateral medulla?0 These respond to changes activity9 ,·,os,m (Fig. 5-14) and (usually) greater increases in
in hydrogen ion concentration.70 Hypercapnia, probably systemic blood pressure (about 30 mmHg rise in systolic
via a reduction in pH, also stimulates peripheral arterial pressure and about 25 mmHg rise in diastolic pressure110)
chemoreceptors located in the carotid bodies, aortic bod- than does hypoxerrtia. 85•105 Acting via barore.flexes, this
ies, and abdomen. 104·105 Only 15-30% of the ventilatory greater hypertensive response may be partly responsible
response to hyperca~nia resttlts from peripheral chemore- for the more limited rise in heart rate during hypercapnia
ceptor stimulation. 1 ·107 Not surprisingly, the Paco1 of pa- than during hypoxemia. 85·105 The tachycardic (and hyper-
tients with bilateral resection of the carotid bodies is higher pneic) response to hypercapnia is blunted in the elderly. 77
[by 4.6 ± 1.3 (standard deviation) mmHgJ than in healthy Apnea increases the sympathetic nerve activity elicited by
subjects. 78 hypercapnia. 105 This increase, howeve~ is less than the in-
crease during hypoxemia 105 (see Fig. 5-14).
Respiratory Responses Combined hypoxia and hypercapnia have a synergis-
Hypercapnia causes an increase in VE; stimulation peaks tic effect on sympathetic nerve activity105 (see Fig. 5-14)
with an inhaled C~ of 10%.108 In contrast to the curvilin- and hyperpnea (see Fig. 5-13). This potentiation may arise
ear response to progressive hypoxemia (see Fig. 5-12), the because hypercapnia sensitizes the response of peripheral
hypercapnic ventilatory response is linear. 68 (Fig. 5-13). The chemoreceptor afferents to hypoxia.105 Another possibility
ventilatory response to C~ increases when concurrent hy- is that both peripheral and central chemoreceptors synapse
poxemia is present109 and decreases with age.77 on common nuclei in the brain stem.1os
Hypercapnia and hypoxia induce different patterns of Hypercapnia not only has a sympathetic vasoconstrictor
neuromuscular activation as VE rises- even when the res- effect (secondary to chemoreceptor activation) but also has
piratory components of tidal breathing (tidal volume and a direct vasodilator effect on systemic arterioles21,68; dilata-
inspiratory and expiratory tin1es) are similar. 73 First, hyper~ tion of conjuntival and superficial facial vessels may be
capnia is a more potent stimulus for expiratory muscle re- noted. The first action, however, is predominant in con-
cruitment than is hypoxemia-one-third of subjects do not scious persons, and blood pressure and heart rate increase.
recruit their expiratory muscles during hypoxemia. 73 Sec- If the vasomotor center cannot respond (e.g., secondary to
ond, activation of the diaphratm is greater during hypox- brain damage, severe ischemia or hypoxia, or deep anesthe-
emia that during hypercapnia. (The lack of expiratory re- sia) or is disconnected from peripheral parts of the sympa-
cntitment during hypoxemia may increase end-expiratory thetic nervous system (e.g., secondary to spinal cord dam-
lung volume, which increases 02 reserves.73) age or blocking drug or spinal anesthesia), direct vasodila-
The interindividual variation in respiratory r"€sponse to tion becomes the sole or dominant effect, and blood pressure
hypercapnia is large. In 31 healthy subjects inhaling 10.4% falls. 21,68,112
C02 in 0 2 , average maximum VErose to 76liters/ min, w ith Hypercapnia increases cerebral blood flow.m Cere-
a range of 40-130 liters/min.110 brovascular reactivity to C02 depends on age (i.e., there
Breathing Apnea isfactorily with Paco values of greater than 100 mmHg. 68
Therefore, there is no single threshold of Paco1 above w hich
Room Air mechanical ventilation is mandatory.
Car d iopulmonary Manifestations

Most signs and symptoms of acute hypercapnic respiratory
failure, including hyperpnea, dyspnea, tachycardia and hy-
pertension, and diaphoresis, are similar to those of hypox-
emia. Some consider it a waste of effort to try to separate
which manifestations are rela ted to hypoxemia and which
to hypercapnia.117
Neurologic Manifestations
The major clinical features of hypercapnia are those affect-
ing the CNS. One difference between acute hypoxemic and
acute hypercapnic respiratory failure is the greater inci-
dence of neurologic manifestations with the latter. Acute
hypercapnia can cause fine tremors (of the outstretched
5 Se<:
hands, head, o r legs), asterixis, myoclonic jerks, sustained
myoclonus, and seizures.22. 108 It also can cause cognitive
FIGURE 5-14 Direct intraneural record ings of sympathetic n erve
disorders, hostility, irritability, paranoid behavior, somno-
activity in during exposure to room air, isocapnic hypoxia (10%
02, 90% N2, and titrated C02), hyperoxic hypercapn ia (7% C02,
lence, stupor, and coma. 22 In a study of 32 episodes of
93% 0 2 ), and hypoxic hypercapnia (10% 0 2, 7% C02 , an d 83% N 2 ) acute respir atory failure, Kilburn22 reported that the sever-
d uring spontaneous breathing (left) and durin g en d-expiratory ity of cognitive disorders, asterixis, and somnolence and
apnea (riglrt). Sympathetic activity is a fu nction of both b urst the presence of stupor and coma were closely related to the
frequ ency and burst amplitude. Three points can be made. First, severity of respiratory acidosis- and not to the severity of
sympath etic activity during breathing increased more d uring hypoxemia.
h ypercapnia (7o/o C0 2 ) than during hypoxia (10% 0 2 ). Secon d, Some patients with severe hypercapnia have papilledema
apnea caused greater enhancement of sympathetic nerve activity and elevated cerebrospinal fluid pressure probably because
during hypoxia (10% 0 2 ) than during hypercapnia (7% C0 2 ). of the increase in blood volume within the near-rigid cra-
Thir d, hypoxia and hyp ercapnia had a synergistic effect on
sympath etic nerve activity. (Used, witlr permission, from Somers
nial cavity.68' 84' 113 Under conditions of prolonged hypercap-
et al: J Appl Plrysiol 67:2101- 6, 1989.) nia (several ho urs), cortical blood flow may return toward
baseline over timeH8 The la tter is probably mediated by a
buildup of brain extracellular bicarbonate and an increase
in pH.l'ts
is reduced cerebral perfusion reserve in the elderly)114 Some patients w ith combined hypoxemic and hypercap-
and state (i.e., there is a 70% reduction in cerebrovas-
nic respiratory failure become more comatose when treated
cular r eactivity to C02 during non-rapid eye move-
with 0 2 (C02 narcosis). The mechanisms responsible for
ment sleep).81 Hypercapnic cerebrovascular reactivity a lso
0 2 -induced hypercapnia are complex and probably include
is reduced in patients with preexisting cerebrovascula r
reduction in ventilation, increased wasted ventilation (alve-
diseases. 115 olar dead space). 119 and the Haldane effect (Pac~ increases
because of net release of C02 from erythrocytes when Sa~
Neurologic Responses is increased)120 (see Fig. 5-10).
Hypercapnia decreases cerebral metabolic rate for glucose
and interferes w ith cerebral energy production. 116 The cere-
bral metabolic rate for 0 2 is maintained, or slightly in- POSTOPERATIVE RESPIRATORY FAILURE
creased, provided that Paco1 is less than 90-100 mmHg.11 6 Postoperative respiratory failure can be defined as the need for
For higher values of Paco,, cerebral metabolic rate for 0 2 intubation and mechanical ventilation in the 4S hours after
decreases.116 Hypercapnia has a dual effect on neuron ex- surgery. 121 Among more than 180,000 patients undergoing
citability: stimulatory at low concentrations and inhibitory major noncardiac surgery, postoperative respiratory failure
at high concentrations. 68 In humans, very high concentra- occurred in 3%.121 This exceeds t11e incidence of myocardial
tions (30%) can produce surgical a nesthesia, which can be infarction after surgery (0.4-0.7%).'121 , 122 Among 1055 pa-
associated with seizures.6S,l03,l08 tients, most of whom under went lower abdominal/ inguinal
hernia repair or orthopedic limb surgery, 0.1% required in-
CLINICAL PRESENTATION OF HYPERCAPNIA tubation within 7 days of sur gery. 123
The clinical manifestations of hypercapnia resuJt from a PuJmo nary complications are estimated to account for
complex interaction of several factors, including severity nearly 25% of deaths within 6 days of surgery.124 This fig-
of hypercapnia, comorbidities, and t11e speed at which the ure may be an w1derestimate; m<my patients with respira-
increase in C02 has occurred. For example, pa tients receiv- tory failure can be kept alive by ventilator support, only
ing chronic 0 2 therapy have been reported to function sat- to die from nonrespiratory complications (e.g., sepsis and
TABLE 5-4 Causes of Postoperative Respi ratory Fai lure
Intrapulmonary causes
Atelectasis
Aspiration
Pneumonia
Acute respiratory distress sysdrome/acu te lung injury
Volume overload/congestive heart failure
Pulmonary embolism (thrombus, air, fat)
Bronchoconstriction (asthma /COPD)
Pneumothorax
Extrapu/11101111ry CIII/SI!S
Shock
Decreased respiratory drive
Phrenic nerve injury
Diaphragmatic dysfunction
Upper airway obstruction
Obstructive sleep apnea
FIGURE 5-15 Three-dimensional reconstruction of atelectasis (in

multiorgan failure).125 Among patients who undergo major dependent lung regions) and the ch est wall in an anesthetized
non cardiac surgery, mo rtality is 27-42% for those with post- and paralyzed p atient before the start of surgery. The chest wall
operative respiratory failure versus 1-6% for those without has a gray appearance; the anterior part is directed upward, and
postoperative respiratory failure.m, 126 Respiratory failure the dorsal border is directed downward. The dorsal ridge
is the most important determinant of postoperative mortal- indicates the spine. The caudal region of the ches t wall is closest
ity in 40-100% of thoracic surgery patients. 127 to the viewer, who is looking into the thorax from the position of
A common cause of postoperative respiratory failure the diaphragm. The black regions correspond to the atelectasis.
is the development of atelectasis. 125• 127·" 2~ Atelectasis is The size of the atelectasis decreases toward the apex, and its
the most frequent pulmonary complication after gen- surface is coarse. (Used, with penuission, from Hedeustiema: Cli11
Pllysiol Funct Imaging 23:123-9, 2003.)
eral surgery (particularly thoracic and upper abdominal
surgery)125 (Table S-4). Atelectasis occurs in about 90% of
patients during anesthesia. 129 During uneventful anesthe- periodic deep breaths. Lack of intermittent deep breaths
sia, before any surgery is begun, 15-20% of the lung base favors alveolar collapse by precluding alveolar recruitment
is collapsed130 (Fig. 5-15). With thoracic surgery and car- and decreasing active forms of alveolar surfactant. 139 Fifth,
diopulmonary bypass, more than 50% of the lung can be narcotics 138 and pain122 also suppress cough and interfere
collapsed several hours after surgery. 131 After abdominal with the ability to clear secretions. 140 In a prospective study
surgery, atelectasis can persist for several days.132 of 361 patients undergoing elective lung surgery (includ-
One mechanism for the development of atelectasis dur· ing pnewnonectomy, lobectom y, wedge and segmental re-
ing general anesthesia is decreased respira tory muscle to ne, section, and bullectomy), Bonde et al140 reported that com-
which is accompanied by a cephalad d isplacing of the plications related to retention of secretions (i.e., a telecta-
diaphragm, 20% reduction in functional res idual capac- sis, pneumonia, and respiratory failure) occurred in 30% of
ity (60% reduction in obesity), and compression of lung patients. On multivariate analysis, being a current smoker,
tissu e. 125• 133 Two other purported mechanisms are impaired having ischemic heart disease, and the absence of regional
function of surfactant and resorption of gas behind occluded analgesia or failure of regional analgesia (thoracic epidural
airways (particula rly with high Fro 2). 130 or extrapleural intercostal nerve infusion block) increased
Persistent or new atelectasis after anesthes ia can be the risk of secretion retention. 140 Of 12 in-hospital deaths, 10
caused by several mechanisms. First, patients undergoing were considered complications of secretion retention. Sixth,
abdominal or thoracic surgery experience a marked re- risk of a telectasis is increased with routine use of nasogastric
duction in vital capacity and a smaller but clinically im- tubes. 123• 141, " 42 Seventh, preexisting pulmonary disease'~ 43
portant decrease in functiona l residual capacity. 133 These and current smoking144-associated w ith increased post-
cha11ges are ascribed to postopera tive pain a nd diaphrag- operative secretions140- increase the risk of atelectasis. The
matic dysfunction.133•134 Abnormal abdominal mechanics end result of atelectasis can be hypoxemic respiratory fail-
reduce end-expira tory lung volume below (the increased) ure, hypercapnic respiratory fa ilure, or both and pneumonia
closing volume, leadinr to absorption of gas from poorly and sepsis.128•145
ventilated lung units.12 Second, the weakened diaphragm Preoperative assessment is useful in identifying pa-
no longer acts as a rigid wall between the thoracic and ab- tients at increased risk after thoracic and nonthoracic
dominal space. 134 The positive abdominal pressure trans- surgery.m· 123• 146 In a prospective study of 272 patients un-
mitted to the thoracic cavity increases pleural pressure dergoing nonthoracic surgery, McAlister et al146 identified
and causes compression atelectasis-particularly in the three independent risk factors for postoper ative complica-
dependent thorax. 130•135 Titi.rd, mucociliary clearance is tions: age of 65 years or more, smoking of 40 pack-years or
impaired. 136, l37 Fourth, narcotics138 and pain122 s uppress more, and maximum laryngeal height of 4 em or less.
In a subsequent study of 1055 patients undergoing non- contro1.165 Recovery to spontaneous respiration and extu-
thoracic surgery, these investigators reported four indepen- bation is shorter w ith rapid tracheal extubation strategies
d ent risk factors for postoperative complications: age of than w ith conventional strategies-median time of about
65 years or more, positive cough test (recurrent coughing 4 and 7 hours, respectively.149• 150 About 20-30% of pa-
after asking a patient to cough once), perioperative nasogas- tients, however, do not tolerate (or are not candidates for)
tric tube, and duration of anesthesia of 2.5 hours or more.123 rapid tracheal extubation strategies because of postoper-
In a prospective study of more than 180,000 patients under- ative complications (e.g., bleeding, myocardial ischemia,
going major nonca rdiac surgery, Arozullah et al121 reported myocardial infarction, refractory hypoxemia, or neurologic
that type of surgery, albumin and blood urea nitrogen levels, complications).149,150 Early extubation may improve cardiac
functional sta tus, COPD, and age could be used to generate output166 and renal perfusion159·167 and reduce cardiopul-
an index to identify patients at risk for postoperative res- monary morbidity168 and decrease hospital stay without ad-
piratory failure. Solid data on the usefulness of respiratory verse ou tcome. 162. 163
physiotherapy, including incentive spirometry and nonin- In addition to early extubation (extubation achieved
vasive ventilation to prevent pulmonary complications, after in less than 6 hours after surgeryl 62), immediate extu-
cardiac or upper abdominal surgery are lacking.147·148 bation in the operating room has been reported after
coronary bypass grafting with or without valve replace-
CARDIAC SURGERY ment,158·164•169·170 single-lung transplantation,l7 1 and two-
Cardiac surgery requires prolonged anesthesia and often stage esophagectomy.172 Recently, coronary bypass graft-
hypothermia. 149·150 Patients also often require therapy for ing with high thoracic epidural a nesthesia in the awake
hypotension or hypertension, as well as fluid resuscitation and spontaneously breathing patient has been achieved
(including blood transfusions). 149•150 Cardiac surgery can successfully.U3-175 This latter strategy remains highly
temporarily increase respiratory load.151- 153 At the end of controversia1.176
coronary bypass surgery, lung compliance is less and lung
resistance greater after chest closure than before surgery..151 SHOCK
An increase in lung water after cardiopulmonary bypass,
especially if the lungs remain collapsed during surgery, con- DEFINITION AND CLASSIFICATION
tributes to the worsening mechanics. In eigh t patients under- Shock can be defined as a "state in which a profound and
going valvula r surgery, compliances of the chest wall and widespread reduction of effective tissue perfusion leads to
lung were less at 4 hours after surgery that before surgery.152 reversible, and, if p rolonged, irreversible cellular injury."177
By 7 hours, chest-wall compliance was back to baseline, and Based on hemodynamic profile, shock is classified into four
lung compliance was higher than before surgery. 152 The in- categories: cardiogenic, hypovolemic, extracardiac obstruc-
vestigators speculated that the initial d ecrease in lung com- tive, and distributive177 (Fig. 5-16).
pliance is caused by interstitial fluid secondary to increased PHYSIOLOGIC EFFECTS OF SHOCK
vascular permeability. 152 The subsequent increase in lung All forms of shock exhibit common cellula r metabolic pro-
compliance may result from mobilization of fluid that had cesses that typically lead to cell injury, organ failure, and
accumulated before surgery (as a consequence of valvular eventually, death. 177· 178 These processes are caused by mul-
disease) and as a result of extracorporeal circulation (in- tiple interrelated factors, including cellular iscl1emia, cir-
creased permeability). Severe restrictive pulmonary defect culating or local inflammatory mediators, and free-radical
is the rule,154·155 and venous admixture (or sum of true shunt injury.177,178
and VAIQ mismatch) is increased.155 At the end of surgery,
Respiratory Responses
many patients are transferred to the ICU while fully ven-
Shock elicits at least three respiratory responses: in-
tilated. Patients then are given the time to rewarm, to me-
crease in dead-space ventilation, respiratory muscle dys-
tabolize the medications received during anesthesia, and to
function, and pulmonary inflammation. The increase
receive therapy for any hemodynamic derangements that
in dead-space ventilation is an early accompaniment
are present.
of shock. 179- 181 Jt r esults from a faU in pulmonary
From the 1960s to 1990s, prolonged controlled mechan-
ical ventilation was the standard of care following car- perfusion.'177* VE increases to achieve normocapnia.181·182
VE also may further increase through ot11er meclla-
diac surgery.156-158 This strategy was justified by the use
rlisms. First, baroreflex d eactivation (secondary to hy-
of high-dose narcotic anesthesia and concerns about my-
ocardial ischemia in the early postoperative period.158-160 potension) amplifies the ventilatory response to stimula-
Since the early 1990s, under pressure of cost contain- tion of the peripheral chemoreceptors.183 Second, direct
ment and improved resource u tilization,161 early extubation stimulation of the aortic chemoreceptors occurs as a re-
sult of decreased 0 2 delivery? 2 (This point, though dearly
strategies have been implemented successfully in uncom-
plicated cardiac surgery cases. 149•150,162 Early extubation
is achieved by modifying intraoperative anesthetic tech- •Terminology of dead space is confusil,g. Anatomic dead space is made
up of the conducting ain.,ays (nose, mouth, pharynx, larynx, trachea,
niques (e.g., usually a decrease in total opioid administra-
bronchi, and bronchioles). Alveolar dead space is made up of alveoli
tion, use of ultra-short-acting opiates, and use of inhaled that receive some or no blood flow, which does not match ventilation
techniques150,J63,164 ), minimizing sedation during the post- (units with very high VAIQ ra tio). Physiologic dead space is the sum of
operative ICU stay, 150 and improving postoperative pain anatomic dead space and alveolar dead space.
Extracardiac Obstructive Cardiogenic Hypovolemic Distributive
(myocardial Infarction) (hemorrhage) (septic)
I
! diastonc filling
\
i ventricular aftertoad
1
myocardial damage
1
! preload
1
myocardial depression
(tension pneumothorax or
pericardia! tamponade)
(massive pulmonary
embolus)
1 1 {.J. systolic and
diastolic function)
1
.J. diastolic function 1
! systolic function
J. systolic and diastolic
furlCtion
J. CO
(i SVR)
~I ---------------------1------------=~===-.J.SVR
(i CO)
4
J. MAP
1
Shock
maldlstribution
of flow
1
MODS
FIGURE 5-16 The hemodynamic profiles of fou.r categories of shock. With cxtracardiac obstructive, cardiogenic, and hypovolemic sh ock,
hypotension is caused primarily b y a decrease in cardiac output (CO), and systemic vascular resistance (SVR) increases secondarily. With
distributive shock, hypotension is caused primarily by a decrease in systemic vascular resistance with a secondary increase in cardiac
output. In 10% or fewer of patients with distributive shock, cardiac output is decreased. The dominant pathologic pathways are indicated
by heavier lines. MAP, mean arterial pressure; MODS, multiple organ dysfunction syndrome. (Used, with pemrission, from Kumar eta/: ln:
Parrillo eta/, editors. Critical ca re medicine: Principles of diagnosis amf management in tire adult. St. Louis.: Mosby, 372-420, 2001.)
demonstrated in the cat,72 remains controversial in for respiratory muscle dysh.mction in sepsis are also acti-
humans.71) Third, cerebral hypoperfusion causes intracellu- vated in cardiogenic and hemorrhagic shock. 204-209
lar hypercapnia and acidosis68 and, in turn, induces further Laboratory animals with cardiogenic210 and septic
hyperventilation unless the neurons are depressed (e.g., by shock 193,2n die of respiratory failure. Death is not caused
hypoxia, lack of substrates, or excessive accumulation of by pulmonary disease per se but by an inability of the res-
metabolic products).68 Fourth, increased respiratory drive piratory muscles to maintain adequate ventilation. In dogs
occurs as a result of peripheral stimulation of pulmonary J with cardiogenic shock, institution of mechanical ventila-
receptors. 177 Fifth, increased respiratory drive results from tion decreases the metabolic needs and thus the blood flow
vestibular activation during orthostasis (vestibulorespira- to the respiratory muscles (from 21-3% of the total cardiac
tory reflex).184 Sixth, VE increases to compensate for lactic output) .212 A nonrandomized study by Kontoyannis et al213
acidosis 185 resulting in part from the ovenvorked and un- in 28 patients with cardiogenic shock provides support for
derperfused respiratory muscles. 181• 186• 187 The increase in the view that hemodynamic instability is an indication for
VE accompanying these responses may enhance venous re- mechanical ventilation. Compared with nonventilated pa-
turn (through the respira tory pump) and vasoconstriction tients, ventilated patients were weaned from an intra-aortic
(through reduced Paco,), helping the cardiovascular system balloon pump more often, and their survival was greater. 213
to cope with hypovolemia.188 The failure to reverse shock and treat the underly-
Respiratory muscle dysfunction is one result of the as- ing cause promptly predisposes to ARDS (see Chapter
sociated cellular dysfunction and injury.134•189 Many mecll- 29). ARDS causes hypoxemia because of VA I Q mismatch
anisms contribute to this dysfunction in septic shock, in- and shunt. Pulmonary vascular resistance increases during
cluding failure of neuromuscular transmission (because shock, including septic shock (in which peripheral vascular
of elevated of muscle membrane ~o tential and failure of resistance is usually decreased).2'~ 4
excitation-contraction coupling 19~1 3 ), the cytotoxic effect of
nitric oxide and its metabolites,189•194•195 free radicals,196-198 Cardiovascular Responses
ubiquitin-proteasome proteolys is,193•1 99--202 and possibly, a Hypovolemic, distributive and extracardiac obstructive
decrease in nicotinic acetylcholine receptors. 203 Local dys- shock result in decreased diastolic filling. Low-pressure
regulation of the circulation and of the Krebs cycle alc;o may stretch receptors located in right atrium and pulmonary
contribute. 193 Many pathways purported to be responsible artery consequently signal the medullary vasomotor
centers, triggering sympathetic discharge.177, 215 1-ligh- sociated with increased mortality219 Altered consciousness
pressure baroreceptors in the aortic arch contribute (neg- by itself may be an indication for intubation.
ative feedback to the tonic discharge of the medullary vaso-
constrictor centers) to the vasomotor response of shock as
INTUBATION VERSUS MEC HANICAL VENTILATION
long as the mean arterial pressure is no lower than 80- 90
mmHg. 216 When mean pressure is less than 80- 90 mmHg, In some instances, patients require endotracheal intubation
the aortic baroreceptor response is eliminated (barorecep- to maintain airway patency because of upper airway ob-
tor deactivation). 177•21 6 Likewise, the carotid baroreceptors struction, an inability to protect the airway from aspiration,
contribute (negative feedback) to the vasomotor response or to manage secretions. Not all intubated patients neces-
as long as the mean pressure is no lower than 60 mml-Ig. 216 sarily require ventilator support.
When mean pressure is less than 60 nunHg, the carotid
baroreceptor response is eliminated.216 When mean pres- UPPER AIRWAY OBSTRUCTION
sure is less than 50-60 rom Hg, the peripheral chemorecep- Upper airway obstruction is one of the most urgent and
tors (sensitive to Pao 2 , Pac~, and pH) dominate.177 The most potentially lethal medical emergencies. Complete airway
powerful stimulus to sympathetic tone during severe shock, obstruction lasting for as little as 4-6 minutes can cause ir-
however, is the ischemic response of the CNS. 216 When mean reversible brain damage. 220 The upper airway, whiclt en-
pressure falls below 50-60 mmHg_ the medullary chemore- compasses the passage between the nares and carina,221 can
ceptors become active. 216 Maximal sympathetic stimulation be obstructed for functional or anatomic reasons. Among
is induced by these receptors when mean pressure is 15- 20 the first are vocal cord paralysis and laryngospasm. 221 - 223
mmHg, resulting in maximal cardiovascular stimulation.216 Among the second are trauma, burn, infections, foreign bod-
The Cushing response to increased intracranial pressure is ies, and tumors. 220·221 Functional and anatomic obstruction
an example of this reflex operating in a different setting. 177 can occur postoperatively in patients with redundant pha-
Increased sympathetic outflow from the CNS is aimed at ryngeal soft tissue (sleep apnea) and loss of muscle tone
supporting 0 2 delivery to vital organs. Other compensatory related to postanesthetic state.221-223
responses include releases of adrenocorticotropic hormone, The first warning of airway obstruction in an unconscious
antidiuretic hormone, and aldosterone, which contribute to patient may be failure of a jaw-thrust maneuver to o~en the
sodium retention and maintenance of cardiovascular cate- airway or an inability to ventilate with a bag valve. 220 In a
cholamine responsiveness. 177· 178•2t7 conscious patient, respiratory dis tress, s tridor, altered voice
(aphonia or dysphonia), s noring, dysphagia, odynophagia,
CLINICAL PRESENTATION OF SHOCK prominence of neck veins, and neck and facial swelling all
may indicate impending airway obstruction.220·221 Patients
Cardiopulmonary Manifestations may bring their hands to their neck, a sign of choking. 221
Patients in shock or in the process of developing it Other signs include suprasternal and intercostal indraw-
may report dyspnea. Patients are usually tachypneic and ing and reduced or absent air movement on auscultation.
tachycardic; they have primary respiratory alkalosis or a Wheezing may be present (or absent). Thoracoabdominal
metabolic acidosis with some degree of respiratory com- paradox may be prominent. Sympathetic discharge is high.
pensation. Tachypnea, combined with low tidal volume, Patients are diaphoretic, tachycardic, and hypertensive. As
worsens dead-space ventilation. The skin of patients il1 sep- asphyxia progresses, bradycardia, hypotension, and death
tic shock is initially warm and dry. It is typically cold and ensue. 221
clammy when cardiac output is low (see Fig. 5-16). Shock is Upper airway obs truction can be complicated by pul-
usually not an all-or-none phenomenon that occurs abruptly mona~ edema 221 ,222 - incidence of 11 % in one adult
after injury or infection. Instead, homeostatic compensatory series' 4-or pulmonary hemorrhage.223 Increased ve-
mechanisms are engaged.177•178 Early in the course, subtle nous return (more negative intrathoracic pressure and
signs of hemodynamic stress include tachycardia and de- catecholamine-induced venoconstriction) contributes to
creased urine output. During early shock, assessment based pulmonary edema, but it cannot be the sole mechanism225;
on vital signs, central venous pressure, and urinary output as intrathoracic pressure becomes more negative, venous
may fail to detect global tissue hypoxia. 218 If the precipitat- return to the right ventricle becomes flow-limited.226 Other
ing insult is too great or progresses quickly, compensatory factors contributing to pulmonary edema include decreased
mechanisms fail, and overt shock follows. 177 left-ventricular preload (leftward shift of interventricular
septum), increased Ieft-ventriet1lar afterload (increased neg-
Neurologic Manifestations ative intrathoracic pressure and catecholamine-induced el-
Compensatory mechanisms tend to protect the CNS from evation of systemic vascular resistance), pulmonary vaso-
the ill effects of decreased cerebral perfusion. In the absence constriction (hypoxemia and acidosis), an~ossibly, stress
of cerebrovascular compromise, ischemic injury is unusual failure of the alveolar-capillary membrane ·227 (Fig. 5-17).
if mean arterial pressure is 50-60 mmHg or higher. 177 Be- Whether pulmonary edema develops during (or after) re-
fore ischemic injury, consciousness may become altered, de- lief of upper airway obstruction may depend on whether the
pending on perfusion deficit. Contributory factors include obstruction is fixed or variable. 222 Fixed upper airway ob-
electrolyte disturbances, hypoxemia, and hypercapnia. 177 struction results in vigorous inspiratory efforts (Mueller ma-
Sepsis-related encephalopathy can occur at higher arterial neuver) followed by vigorous expiratory efforts (Valsalva
pressures (secondary to inflarnmatory mediators); it is as- maneuver). 222•224 Exhalation against an obstructed airway
Acute airway obstruction cheotomy, endoscopy, intubation over a fiberoptic brond10-
I scope, and medications (e.g., epinephrine, norepinephrine,
antihistamines, steroids, and antibiotics).221 In general,
tPa 02 Negative ITP phannacotherapy ca1mot reverse med1anical obstruction.
+PaC02 Use of helium-0 2 mixtures should not engender a false
/l""
+LV afterload +systemic Pulm onary
sense of security. 221
The nature of respiratory noises helps to localize
venous capillary
+cardiac
l return disruption
lesions.220 Stridor is an inspiratory sound typically caused
by a lesion above the thoracic inlet (us ually glottic or supra-
glottic). Wheezing is generated below this level. 220 Snoring,
output
a feature of obstructive sleep apnea, can be life-threatening.
A patient with an obstructed airway should not be sedated
Pulmonary tmtil the rurway has been secured; minimal sedation may
vasoconstriction
precipitate acute respiratory failure.
l
+ Pulmonary +Pulmonary
Cricothyrotomy and tracheotomy can be performed at the
bedside or in the operating room. If time permits and the pa-
tient is conscious and moving sufficient air to speak, it may
c ap illary pressure blood volume
be best to transport the patient to the operating room.220 Al-
+Capill a r y though percutaneous tracheotomy is gaining in popularity,
permeability
it is best performed in an already intubated patient and not
as an emergency procedure.220
~..-_..Pulmona ry edema .-----.....J
FIGURE 5-17 Mechanisms responsible for the development of
INABILITY TO PROTECT THE AIRWAY
pulmonary edema formation during acute airway obstruction.
ITP, intrathoracic pressure; LV, left ventricle. (Used, witil FROM ASPIRATION
permissiou, from Miro eta/: lu: Tobi11, editor. Priuciples mrd Patients with severe bulbar weakness or decreased con-
practice of mecilanica/ ve11tilatio11. New York: McGraw-Hill, 664, sciousness may be unable to protect the airway agains t
1994.) aspiration.228-229 The lack of a gag reflex or cough on suction-
ing suggests impaired protective reflexes. 230 If the cervical
spine is stable, the head should be flexed while checking for
raises intrathoracic and alveolar pressures. The positive
airway obstruction. Inability to maintain a patent airway is
expiratory pressure decreases pulmonary vascular filling
an indication for elective intubation.230
and opposes the hydrostatic forces that favor transuda-
Patients who require an oral airway or special appliances
tion of fluid into the alveoli during inhalation. 224 With
may require prophylactic intubation; such patients are un-
a sudden relief of obstruction, positive expiratory pres-
stable and canasphyxiateor vomit and aspiratesuddenly. 230
sure is lost; consequently, there is a massive transudation
Ideally, patients with depressed consciousness should be as-
of fluid from the pulmonary interstitium into the alve-
sessed while asleep, a time during which they are at greatest
oli (pulmonary edema) over minutes to hours. In contrast
risk of obstruction. 230
to fixed obstruction, variable extrathoracic upper airway
Severe head injury is a condition requiring intubation
obstruction hinders inl1alation. Exhalation usually is un-
for airway protection. In the past, controlled hyperventi-
affected. In this situation, the hydrostatic forces, which
lation (Paco, of 25-35 mmHg) was delivered in these pa-
favor transudation of fluid into the alveoli during inhala-
tients with the goal of reducing intracranial pressure. Such
tion, are unopposed, leading to edema before relief of the
a strategy, however, has proven harmfuJ231 and is no longer
obstruction. 222
recommended. 232 It is unknown whether the use of short
Upper airway obstruction may worsen suddenly because
periods of hyperventilation to suddenly lower intracranial
resistance varies with the fourth power of the radius. A
pressure are harmful or not.55
slight change in airway anatomy rna y increase resistive load
dramatically. 221 For example, manipulation of the upper
airway by an inexperienced clinician may induce edema,
which can increase airway resistance markedly and induce SECRETIONS
asphyxia. Occasionally, endotracheal intubation or tracheostomy may
An initial assessment is undertaken to detemline severity be required to manage large amount of secretions or to re-
of airway compromise. If compromise is judged severe, the move secretions in severely debilitated patients who them-
airway should be secured immediately. If ventilation is ad- selves cannot clear them.5S: 140
equate, more detailed assessment is wise.220 Arterial blood Many patients with the preceding conditions are capa-
gases are not particularly helpful because they are not spe- ble of maintaining adequate gas exchange following endo-
cific to airway patency. 220 They may show little change until tracheal intubation. Yet most intensivists still connect such
a patient is in extremis.220 patients to a ventilator. This decision commonly is taken
Steps to relieve airway obstruction include use of pharyn- independently of any consideration about the work of
geal airways, endotrad1eal intubation, cricothyrotomy, tra- breathing imposed by an endotracheal tube. 233
148 PART nr INDICATIONS
Goals of Mechanical Ventilation breathing, unloading by the ventilator may appreciably re-
duce Yo, and Yco,7·51 These reductions, in turn, may im-
The fundamental goal of mechanical ventilation is to keep a prove concurrent hypoxemia and hypercapnia.
patient alive and free from iatrogenic complications so that
the catastrophic precipitating event(s) may resolve. Atten-
REVERSAL OF SEVERE HYPOXEMIA
tion should be directed to the primary disorder.
Mechanical ventilation is commonly commenced with 100%
REVERSAL OF APNEA ~.The response helps to define the underlying pathophys-
iology and thus aids in differential diagnosis and therapy
The goal of mechanical ventilation in the apneic patient is (see Figs. S-8 and 5-11 ). For example, if 100% 0 2 fails to
to restore ventilation. increase Pao, in a patient with an exacerbation of COPD,
the underlying problem is not pure V AIQ mismatch (as
REVERS AL OF RESPIRATO RY DISTRESS is typical with acute bronchitis); instead, the patient has
For obvious ethical reasons, no human studies have ad- coexisting shunt. Common causes of shunt include pneu-
dressed the natural course of acute respiratory failure in monia, congestive heart failure, lobar a telectasis, and pul-
the presence of increased work of breathing or, for that mat- monary embolism. (For a discussion of 0 2 toxicity, see
ter, with any other type of res piratory failure. Animal data Chapter 45.)
indicate tha t increased loads can cause respiratory mus-
cle damage/34•235 C02 retention,236 and as a terminal event SHUNT
respiratory muscle fatigue. 236 Increased load may be re- Patients with increased shunt commonly exhibit consider-
sponsible for respiratory muscle damage in patients with able improvement in oxygenation with application of PEEP.
COPJY37 and in~a tien ts dying while supported by mechan- The improvement results from a decrease in shunt249 sec-
ical ventilation. In sepsis, increased respiratory efforts are ondary to recruitment of previously atelectatic areas and
particularly damaging to the respiratory muscles. 239 redistribution of extravascular lung water from alveoli to
Despite intense research, the role of contractile fatigue peribronchial and perivascular spaces. 250 If cardiac output
in the development of respiratory failure in patients is decreases (with PEEP), this can contribute to the decrease
unknown.134 Diaphragmatic contractility has been quan- in shunt. 249,251
tified objectively (phrenic nerve s timulation) in only one PEEP causes an increase in dead space through sev-
study where patients developed acute respiratory distress eral mechanisms. First, an increase in lung volume ex-
(during weaning from mechanical ventilation). 4 No change erts radial traction on the airways, increasing their vol-
in diaphragmatic contractility was documented.4 It is not ume with a consequent increase in anatomic dead space.
known if the la tter observation applies to patients in respi- Second, increased airway pressure tends to divert blood
ratory d istress who have yet to undergo mechanical venti- flow from ventilated lung units by compressing capillar-
lation. ies. The consequent development of areas of high VA/0.
It seems self-evident that connecting a patient to a ven- ratio (or even unperfused areas) produces an increase in
tilator a nd providing ventilator assistance should unload alveolar dearf space. Such dead space is especially common
the respiratory muscles a nd, possibly, reduce muscle stress. in the uppermost lung units, where pulmonary artery pres-
To date, however, we do not know the desirable level sure is relatively low because of the hydrostatic effect. 252,253
of unloading (and for how long) for a s pecific patient. If the capillary pressure fal ls below airway pressure, the
Insufficient unloading can be dangerous to the respira- capillaries may coll;.gse completely and the lung units
tory muscles,237•238•240 as can excessive unloading24 1-246 (see become unperfused (Fig. 5-18). Two factors encour-
Chapter 43). age collapse: very high airway pressure and low venous
Although most patients in acute respiratory failure have return.
increased work of breathing, this may not be the sole Dantzker et a1 249 showed that increasing levels of PEEP
problem. Most patie nts also have abnormal gas exchange, can induce two distinct patterns of VAI Q distribution. Some
impaired muscle.ur;rfusion, and sepsis-induced muscle patients experienced no change in the pattern of VA/0.
dysfunction. 5•247•2 In patients with increased work of relationships (Fig. 5-19). Other patients experienced
I ••
I • ,. #
\
\
...,;. ljJ.A \
I FIGURE 5-18 Effect of an el evated airway
press ure on the s tructure of p ulmonary
I capiiJaries. (Left) Normal appearance. <Rigl1t)
An increase in alveolar pressure above
, capillary pressure produces capillary
coUapsc. (Used, witll permission, from Glazier
• et al: I Appl Pll ysiol 26:65-76, 1969.)
36%
1-2 i 44% ! 1.2
.5 Shunt t
E
..._ Dead 16 em PEEP SO%
ai!S .... space
--
(J)
Q)
0 ;!::: 0 .8 0.8
c
0
:;::;
--;::• Ocm PEEP e 14%
FIGURE 5·19 Effect of PEEP on shunt and
dead space in a patient with ARDS. A
.5!1 progressive increase in PEEP from 0 to 16
:;::; 0 0.4
cQ) u:: 0.4 cmH2 0 caused a decrease in shunt from
> "0
0
44 to 14% of the cardiac output and an
0 increase in dead space from 36 to 50% of the
co 0.0 tidal volume. The shape of the distribution of
0.0
0.00.01 1.0 100 0 .00.01 1.0 100 ventilation and perfusion did not change.
(Used, witli permission, fro m Dat1tzker et al:
Ventilation-Perfusion Ratio Am Rev Respir Dis 120:1039-52, 1979.)
broadening of the ventilation dispersion-increases of ar- VENTILATION-PERFUSION INEQUALITY

eas with high V AIQ ratios and alveolar dead space (Fig. Theoretically, patients with hypoxemia secondary to VAIQ
5-20). The improvement in gas excl1ange with PEEP is even mismatch can be managed by increasing Fro 2 without me-
greater when pressors are used to prevent the expected de- chanical ventilation (see Fig. 5-11). In reality, such patients
crease in cardiac output during PEEP.254 always have increased ventilatory requirements (see Fig. 5-
In some patients, PEEP causes no improvement or even 9), which may demand ventilator support. Many patients
a decrease in Pa~. This effect is the result of increased with V AIQ inequality requiring mecl1anical ventilation are
dead-space ventilation, diversion of blood flow from hyperinflated (e.g., COPD or status asthmaticus). Hyperin-
well-ventilated to unventilated regions, and decreased fla tion decreases the efficiency of the respiratory muscles
cardiac outrut (especially if circulating blood volume is in generating pressure, which contributes to the respiratory
depleted). 25- Lack of improvement in oxygenation with distress. 134
PEEP also may result from a patent foramen ovale because In a study of seven patients with exacerbations of COPD,
PEEP can increases the right-to-left shunt. 255 mechanical ventilation improved V AI Q mismatch by redis-
Because PEEP can decrease cardiac output, 249•256 its net tributing blood flow away from low VA/Q areas.263 Disper-
effect should be judged in terms of 0 2 delivery. Mixed ve- sion of the distribution of ventilation also improved. Dead
nous P~ has been used as a surrogate for 0 2 delivery.218•256 space or ventilation of high VAI Q units did not change.263
Other potential hazards of PEEP include reduced splaclmic Patients with increased VAIQ mismatch associated w ith
and renal blood flow, barotrauma, and ventilator-induced COPD or ARDS may benefit from careful application of
lung injury (see Chapter 11). PEEP (see Chapter 11). Use of PEEP in patients with s ta-
In addition to mechanical ventilation, patients with tus asthmaticus is fraught with danger (see Chapter 30).
hypoxemic respiratory failure may require other thera-
pies, such as antibiotics (pneumonia), diuretics, and in-
otropic s upport (heart failure). Ancillary strategies to re-
REVERSAL OF SEVERE HYPERCAPNIA
verse hypoxemia include exogenous surfactant,257 nitric
oxide supplementation,258 prone position,259·260 and anti- Severe hypercapnia depresses the CNS and decreases respi-
inflammatory agents. 261•262 These strategies can increase ratory motor output. 264 A viscous cycle can arise: H~ercap
oxygenation in patients with ARDS, but none has improved nia depresses drive leading to more hypercapnia. 2 •266 Hy-
patient outcome. percapnia can decrease diaphragmatic contracti)jty/67•268
0.9 Cl9
t
Sh~nl
1
O.od
1
24.0%. FIG URE 5·20 Effect of PEEP on shunt
c 29 .0'11. Spoc.
.E
..._
177'1(, and dead space in a patient with ARDS.
ai!S ....
(J) An increase in PEEP from 0 to U
'0"
Q)
.'!:::
06
lo.,L.~w·l 06
l12~ :w•l cmH2 0 produ ced a decrease in shunt
~
c
0
:;::;
--• (from 29 to 18%) and increase in dead
space (from 17.7 to 24.0%). Also
.5!1 0
:;::;
s: apparent is a widening of the
cQ) u... 0.3 Q3 dispersion in ventilation with the
> "0 development of units with very high
0
0 • VA/Q; these may have resulted from
18.0.,.
co diversion of blood flow or increased
ventilation of these areas of the lung.
0.0 0.01 0.1 1.0 10.0 100.0 o.o 0.01 01 1.0 10.0 100.0 (Used, witlr permissiou,,from Dantzker
et al: Am R ev Respir Dis 120:1039-52,
Ventilation-Perfusion Ratio 1979.)
although not cons istently.236•269 Acidosis may be more im- tion may be contributory factors. In this setting, the circu-
portant than hypercapnia in depressing respiratory muscle lation usually is restored promptly by stopping ventilation
contractility.270•271 for 30 seconds (or more) and then resuming less vigorous
The goal of mechanical ventilation in pa tients with hy- ventilation.
percapnic respiratory failure is to improve VA· Ventilator In the 1940s and 1950s it was reported that rapid C02
strategies need to be ta ilored to the specific setting. In hy- washout after hypercapnia could cause hypotension
percapnic patients with status asthmaticus or COPD, the (removal of cyclopropane anesthesia in humans) 28 L 282
pro longed respiratory time constant poses a significant chal- and life-threatening ventricular arrhythmias (dog
lenge. 1f the ventilator is set to deliver small tidal volumes experiments).283,2B4 Hyperkalemia appeared to be
at high respiratory frequencies, the prolonged time constant involved.283,284 More recent series in patients, how-
may interfere with lung empting, and hyperinflation may ever, have not substantiated the earlier studies.103' 285 For
ensue. Moreover, s mall tidal volumes may not achieve ade- example, Prys-Roberts et al 103•285 reported no electrocardio-
quate alveolar ventilation because physiologic dead space is graphic alterations when Pac 0 1 was reduced from about
increased. Larger tidal volumes may achieve adequate a lve- 80 to less than 20 mmHg over 5 minutes in anesthetized
olar ventilation but require longer expiratory times than do patients. Some practitioners suggest that supraventricular
smaller tidal volumes. A common strategy to ensure suf- and ventricular arrhytl1mias associated with alkalemia286
ficient time for exhalation is to increase inspiratory flow. may occur only in patients wiili ischemic heart disease.287
The increase in flow decreases ilie time of mechanical infla- Whether reductions in ionized magnesium could contribute
tion and, if respiratory rate remains constant, prolongs time to cardiac irritability remains undear.277
available for exhalation. An increase in inspiratory fl ow, Excessive ventilatio n, over time, causes bicarbonate wast-
however, is commonly associated with an increase in respi- ing by the kidney. In patients who retain C02 w hen clini-
ratory rate. 2n 273 Yet, despite the reduction in the respiratory cally stable, this renal wasting (of bicarbonate) will increase
cycle, the decrease in inspiratory time is accompanied by an ventila tory demands during weaning.
increase in time available for exhalation-and a decrease in
inspira to ry effort. 273
Neuromuscular disorders such as Guillain-Barre syn- GO ALS OF MECHAN ICAL VENTILATION
drome, myasthenia gravis, and spinal cord injury 134 can IN POSTORERATIVE RESPIRAT ORY FA ILU RE
cause hypercapnic respiratory fa ih.tre. These patients usu- AN DTAUMA
ally have normal lung mecl1anics, unlike patients w ith Patients developing postoperative hypoxemia usually are
COPD or asthma. The normal time constant allows for treated with supplemental Oz and chest physical therapy
greater flexibility in the setting of the ventilator. (including incentive spirometry).128• 155, 288-290 In about 10%
Overz.ealous ventilation can cause serious complications, of pa tients undergoing major elective abdominal surgery,
including life-ilireatening alkalosis, decreased cerebral per- however, supplemental 0 2 and chest physical therapy do
fusion, and cardiovascular instability. Patients previously not prevent respiratory failure.291 Squadrone et al291 re-
hypercapnic are especially vulnerable to these complica- cently tmdertook a randomized s tudy in more than 200
tions. When severe, alkalosis is occasionally associated w ith patients who had undergone m ajor elective abdominal
coronary artery spasm, 274 confusion, myoclonus, asterixis, surgery and who developed hypoxemia within 1 hour of
and seizures. 275 the opera tion. They compared the incidence of intubation
Respiratory alkalosis reduces ionized calcium. Fo r in patients receiving standard treatment (50% 0 2 and chest
each 0.1-unit rise in pH, ionized calcium falls by physical therapy) and patients who also received 7.5 em H20
0.05 mmol/liter. 276 These changes are too modest and CPAP (delivered noninvasively with a helmet) . Compared
incons istent277 to account for the increased central and pe- with the control group, patients receiving CPAP had lower
ripheral excitability associated with alkalosis. Paresiliesias, rates of intubation (1% versus 10%) and complications
carpal-pedal spasm, and tetany, seen in acute hyperventi- (e.g., pneumonia, infection, and sepsis). The CPAP group
lation, are caused by the direct effects of respiratory alka- spent fewer days in the ICU. Exclusio n criteria included
losis on neurons.278 Other effects of alkalosis include in- history of COPD, asthma, sleep apnea, heart fa ilure, hy-
crease in hemoglobin affinity for ~ and, in the presence percapnia, and respira tory acidosis. Thus these results291
of increased shunt, a possible worsening of V AIQ rela- may not apply to patients at greatest risk of postoperative
tionship (secondary to a decrease in hypoxic pulmonary atelectasis.
vasoconstriction). 279 Precipitous decrease in Pac~ reduces Bonde et al145 undertook a prospective, randomized
blood flow to the CNS,280 which may contribute to con- study in 102 patients undergoing elective lung surgery w ho
fusion and loss of consciousness in patients with hyper- were considered at high risk for retention of secretions.140
ventilation.275 Minitracheotomy (4-mm percutaneous cricothyroidotomy
The most common hemodynamic instability associated device) was performed at the conclusion of surgery in
with overzealous ventilator management of ilie hypercap- one gr oup. Sputum retention was 30% irt a convention-
nic patient (prolonged time constant) is hypotension. Hy- ally treated group and 2% in the rninitracheotomy group
potension often results from an increase in intrins ic PEEP (p < 0.005).145 Atelectasis was less common in the mini-
after intubation-although a decrease in sympathetic tone tracheostomy group. Incidences of pneumonia, respiratory
caused by the decrease in Pac0 2 and administration of seda- failure, myocardial infarction, and death were not affected
by minitracheotomy.145 Sig nificant complications of mini- increase (from 20.5 to 34.3%). This study raises the possibil-
tracheostomy have been reported, h owever. 292•293 There- ity that introduction of a practice guideline may cause an
fore, its routine use, even in patients at risk of secre- increase in morbidity and mortality.309•310 A practice guide-
tion retention, needs to be considered on a case-by-case line could discourage physicians from the use of noninva-
basis. sive ventilation in subgroups of patients who are likely to
Some patients with multiple trauma present with a benefit from its use simply because benefit has not yet been
flail chest. Many such patients may have respiratory demonstrated in a randomized trial and thus has not been
failure secondary to underlying lung damage or other incorporated into the practice guideline. In an accompany-
pathophysiology and may require mechanical venti- ing editorial, Hill310 commented: "The concern is that by
lation. Flail chest on its own, however, is not an classifying a sizable category of patients as 'not meeting
indication for mechanical ventilation.294 In one. random- noninvasive positive pressure ventilation criteria,' the au-
ized study of patients w ith flail chest who were hypox- thors could have unintentionally encouraged endotracheal
emic and in respiratory distress, noninvasive CPAP d e- intubatio n in this subg roup, possibly contributing to mor-
creased mortality and nosocomial infection as compared bidity and mortality."
with patients w ho underwent endotracheal intubation and Detailed discussion of noninvasive ventilation is pro-
ventilation.295 vided in Chapter 19, as well as in Chapters 9 and 31-34.
GOALS OF MECHANICAL VENTILATION IN SHOCK

In hemodynamically unstable patients, tissue perfusion, in- Indications for Mechanical Ventilation
cluding that of the CNS, is compromised.178•218 Two main and Nosology
goals are to establish an adequate airway and reduce Vo, .177
By resting the respiratory muscles and allowing for se- INDICATIONS: TRUE VERUS STATED
dation, mechanical ventilation can reduce V~· 296• 297 and
In publications on mechanical ventilation, listed indi-
decrease sympathetic tone. 51 These effects may improve
cations commonly include acute respiratory failure, ex-
tissue perfusion,212•298 which may explain why ventila-
acerbation of chronic respiratory failure (secondary to
tor support improves outcome in animals210 and patients
inJection, bronchocons triction, heart failure), coma, and
in shock. 213 It is important to achieve good patient-ventilator
neuromuscula r disease. Many patients, however, have
synchronization299•300; otherwise, work of breathing in-
these same conditions but do not require ventilator assis-
creases, which diverts blood to the respiratory muscles and
tance. Take COPD, one of the most common indications
away from other vuh1erable tissue beds.
for mechanical ventilation. At any point in time, much,
much less than l % of patients with COPD are receiv-
ing mechanical ventilation. This small subset is commonly
Delivery of Mechanical Ventilation: identified as those with acute respiratory failure. But the
definition of acute respiratory failure is vague and the
Invasive versus Noninvasive criteria loose. The usual defining criterion is a Pao, of
Mechanical Ventilation less than 60 mmHg (sometimes combined with a Paco,
of greater than 50 mmHg). It is patently absurd to sug-
Solid experimental data support the use of noninvasive ven- gest, h owever, that all patients with a Pao1 of 59 mmHg
tilation in patients with acute respiratory failure caused by (or lower) need ventilator assistance a11d that all patients
severe exacerbations of COPD (limited to patients deemed with a Pao, of 61 mrnHg (or higher) can be managed
not to require immediate intubation).301- 305 Noninvasive without it.
ventila tion is probably superior to invasive ventilation in As such, the usually stated indications for mechani-
patients with cardiogenic pulmonary edema complicated cal ventilation are elastic, lacking meaningful boundaries.
with hypercapnia306and in immunocompromised patients What, then, is the real reason to institute it? We believe that
with earl y hypoxemic respira tory failure.307•308 The role of the most honest description of a physician's judgment at
noninvasive ventilation in difficult-to-wean patients is dis- this juncture is "The patient looks like he (or she) needs to
cussed in Chapter 58. be placed on the ventilator." Tha t is, a physician institutes
Sinuff et al309 studied the use of a practice guideline for mechanical ventilation based on his or her gestalt of disease
noninvasive ventilation in patients admitted to hospital for severity as opposed to slotting a patient into a particular
an exacerbation of COPD or congestive heart failure. The diagnostic pigeonhole.
d evelopers of the guideline pointed out that data from ran- At first blush, this admission makes the undertaking of
domized trials do not support use of noninvasive ventilation mechanical ventilation appear less scientific than other ar-
in other disease states. Before introduction of the guideline, eas of medicine. Students of medicine are taught to make
65% of patients with diseases other than COPD or cardia- a diagnosis before initiating treatment. The usual teach-
genic pulmonary edema were managed without endotra- ing is tha t an accurate diag110sis w ill make the ap propriate
cl1eal intubation. After introduction of the guideline, 100% treatment relatively obvious. But this medical model is plau-
of these patients were intubated; mortality also tended to sible only for d iseases where the precise etiology is known
(such as a microbial agent). The medical model is also 4. Causation (etiology). When tl1e cause of a disease is dis-
more ideal than real. To understand the limitations of this covered, the disease generally is redefined in causal terms
model-and the apparent lack ofscience concerning ventila- (Legionnaire's disease). Scadding'l14 refers to another cat-
tor indications-the reader needs to grapple with nosology, egory, "clinical entity," that always needs an ad hoc ex-
the discipline that names and classifies diseases.* Just as planation; he says, " It often seems to be the refuge of one
Moliere's "Bourgeois Gentilhomme" was delighted to learn who has not succeeded in clarifying his or her thoughts,
that he had been speaking prose a ll his life ""~ thou t know- but is nevertheless determined to put them into words."
ing it, we were astonished to discover (while writing this
cl1apter) that we have been thinking nosologically every In general, the direction of scientific advance follows the
day unawares. preceding sequence, although many conditions are never
described in etiologic terms. The primary purpose of ap-
plying a name to a disorder is to provide a brief statement
NOSOLOGY of the medical understanding of its nature (from syndrome
The first atten1pt to introduce a systematic and consistent to etiologic mecl1anism) and to serve as a verbal device for
nomenclature for diagnostic terms was made in the mid- ease of communication. The American-European consen-
nineteenth century.3 n Diseases were no longer viewed in sus definition of ARDS,315 for example, has served as the
terms of a Galenic humoral disequilibrium. Instead, they basis of patient recruitment for most of the recent trials of
were regarded as discrete entities-real things. This on- mechanical ventilation in ARDS. Yet, as discussed in detail
tologie model grew out of the increasing use of autopsy, by Marini (see Chapter 29), this definition lacks scientific
which was seen to uncover the true reasons for the cor- rigor. Nevertheless, in everyday practice, the term ARDS
poreal changes induced by disease.312 Ideally, each disease helps a clinician to predict prognosis and prescribe treat-
category would be identified through elicitation of pathog- ment. Moreover, in emergency settings (such as the ICU),
nomonic signs on physical examination and the finding of problems are discussed and major decisions often are made
a defining lesion on autopsy. This thinking is conveyed without making any explicit diagnosis. Indeed, this is the
in the quip circulated by nineteenth-century physicians: If rule rather than the exception when instituting mechanical
you were s uffering from some mysterious illness, the best ventilation. An experienced critical-care physician can iden-
thing to do was go to Vienna (then the Mecca of medical tify a patient who will die if left untreated but who might
science)3 13 and be diagnosed by Skoda and autopsied by live if managed by mechanical ventilation-even tho ugh the
Rokitansky. phys ician is unable to identify the etiology of that patient's
illness. Nevertheless, in such situations where physicians
cannot put forward a defensible diagnosis, they still apply
DISEASE DEFINITION AND CHARACTERISTICS descriptors (at Scadding's level of "clinical entity"), such as
"the patient is tiring out," to justify their judgment that me-
How is disease defined? A disease is "the sum of abnormal chanical ventilation is indicated.
phenomena displayed by a group of patients in association
with a specified common characteristic (or set of charac-
teristics) by which these patients differ from the norm (of DEFINITIONS: ESSENTIALIST AND NOMINALIST
healthy people) in such a way as to place them at a biologi-
What are the factual implications of the naming of a dis-
cal disadvantage."314
ease? Diseases are defined in essentialist or nominalist
There are four main classes of characteristics by which
terms. An essentialist definition tries to describe the true
diseases can be defined:
essence of an entity: the essential quality (invariable and
fixed properties) that makes a given entity the type of
1. Syndrome. Historically, diseases are defined initially by thing it is- the "whatness" of an entity. (The study of the
way of a description of symptoms and signs; when these essence of things is called ontologt;.316 ) Essentialist ideas
constitute a recognizable pattem, they are referred to as about diseases are implicit in everyday speech.3 17 For ex-
a syndrome (e.g., ARDS). ample, a patient presents with a cough and mucoid spu-
2. Disorders of stntcture (morbid anatomy). When a specifi- tum. The doctor makes a diagnosis of cluonic bronclutis.
able disorder is found to be associated constantly with The patient then thinks that cluonic bronchitis is caus-
a morbid-anatomic change, it tends to be named in these ing his or her cough. Given that cluonic bronchitis is de-
terms (e.g., the switch from jaundice to hepatitis). fined as a productive cough, the patient's reasoning is
3. Disorders of function (pathophysiology). When a disorder is circular.
found to be associated constantly with a specific abnor- Such usage lays a linguistic trap: Many laypeople and
mality of function, the abnormality may be used to name some doctors think that the names of diseases refer to ac-
the disorder (e.g., hypothyroidism). tive agents that cause the illness. To talk of diseases as if
they existed as real entities is plausible (at first sight) only
..The late Guy Scadding has written more lucidly on nosology than in relation to diseases that are defined in etiologic terms.318
most; he made explicit the factual implications of medical usage of Even then we must not confuse an etiologic agent with the
disease names. This account borrows extensively from his writings. disease itself. The disease is the effect on the affected person;
diseases have no existence apart from patients. We treat pa- or she then undertakes careful palpation (for tactile vocal
tients, no t diseases. When we speak of treatment of a dis- fremitus), percu ssion (for dullness), and auscultation (for
ease, we are employing a n ellipsis for treatment of patients wh ispering pectoriloquy, egophony, and bronchial breath-
with that disease. 314 All this brings to mind Osler's admo- ing).
nition: " It is much more important to know w ha t sort of The clinical diagnostic criteria a re the d escriptive features
patient has the disease than to know what sort of disease that best discriminate between one disease and other dis-
the patient has.'1312 eases w ith which it might be confused. Tn the best-case sce-
A nominalist definition recognizes that the task of revealing nario, the clinical diagnostic criteria are made up largely
the essence of the definien.dum is impossible.319•3 20 Instead, of d efining characteris tics. None of the features is conclu-
it simply uses words to s tate the set of characteristics tha t sive, but together they produce a degree o f probability that
are used to identify a member of a class (make a diagnosis). justifies a diagnosis on which practical management may
Such a definition makes it possible to determine whether a be based.321 It is possible to sta te defining characteristics
particular example (clinical picture) falls into a category to in objective, demonstrable terms when a disease is defined
wh ich a nam e (a disease) is applied.321 A nominalist defi- etiologically or as a disorder of structure or function.314
nition avoids the essentialist fallacy of regarding d iseases The same is also possible for a disease defined syndromi-
as causes of illness; instead, it is simply naming a class of cally if the d escription of the syndrome includes objectively
entities or events. demonstrable elements . For example, as entry criteria for a
The nominalist-essentialist distinction becomes clearer if research study, respiratory distress might be defined (arbi-
we consid er the definition of acute respiratory failure. Karl trarily) as meeting three o f the following four elements; res-
Popper, who condemned essentialist definitions, observed pir atory rate g reater than 33 breaths per minute, Pa~ /Fr~
that a good d efinition in science should be read from right to ratio of less than 300, phasic sternomastoid contraction, and
left, n ot left to right. 322 Take the sentence,"Acute respiratory nasal flaring. That is, in the context of this study, res piratory
failure is the presence of a Pao2 of less tha n 60 mmHg, with dis tress can be d efined without making subjective value
or without a Pac~ of greater than 50 mml-Ig, together with judgments.
physical findings indicative of increased work of breathing." When making decisions about the treatment of an indi-
Reading from right to left, the sentence provides a " nomi- vidual patient, however, it is n ot possible to avoid subjec-
nalist" answer to the clinician's question, 'What shall we call tive value judgments (things being assessed on a scale of
the presence of a Pa 0 2 of less than 60 mmHg, with or with- goodness or badness). Ultimately, the decision of whether
out a Paco, of greater than 50 mmHg, together with physical to institute mechanical ventilation (or not) boils down to a
findings indicative of increased work of breathing?" rather value judgment by the patient's physicia n.ln som e instances
than providing an "essentialist" answer to the question, this decision will be preceded by a physician's making of a
'What is acute respiratory failure?" That is, the term acute diagnosis . In many cases, h owever, physicians institute me-
respiratory failure i.e; handy shorthand for the lon ger, more chanical ventilation without having formulated a precise
cumbersome description. Nothing more . The term acute diagnosis. Along the same lines, Gross324 has argued tha t it
respiraton; failure contains no information about medicine, is unlikely that management of asthma would be improved
and nothing is to be gained from analyzing it. were it possible to articulate a more widely accepted defi-
nition o f this d isease.
DIAGNOSTIC PROCESS, TREATMENT,

AND VALUE JUDGMENT FACTUAL IMPLICATIONS OF DISEASE
TERMINOLOGY
The process of making a diagnosis goes through two broad
steps. First, the physician undertakes an initial review of the Nosology is rarely discussed at medica l conferences. 311
clinical features, looking for a pattern that suggests one or Questions on terminology are regarded as recondite and
more disease. For exan1ple, a clinician notes eyelid retrac- pedantic, eliciting yawns from the audience. When a
tion, tracheal tug, sternomas toid contraction, tachypnea, speaker is asked to d efine the clinical entity about which he
and monosyllabic speech. H e or she concludes that the pa- or she is speaking, he or she may appear puzzled-feeling
tient is in acute respiratory distress (an "entity" rather than a that everyone surely knows what the term means. The audi-
disease). Second, the physician undertakes a directed search ence becomes restless, seeing the question as a philosophi-
for the d efining characteristics (pathogn om onic findings) of cal diversion that distracts from the hard scientific facts that
each of a number of suspected diseases. 323 Let us consider the speaker is trying to discuss. Yet it makes little sense for
a patient w ho exhibits all the above-listed features of acute a speaker to present detailed data analysis on a condition
respira tory distress. On learning that the patient had been that he or she catmot d efine. Likewise, readers should treat
extuba ted a half hour previously, the physician sus pects la- with a jatmdiced eye statistics in surveys that list precise
ryngeal edema and carefully listens for stridor. In a second diagnoses for which mechanical ventila tion was used. The
patient, a physician's initial assessment again may reveal the ghost of such unrealistic (and una ttainable) precision also
genera l features of acute respiratory distress. On learning hovers over lists of reasons for wh y patients were intubated
that this patient also has fever, chills, and rust-colored spu- in reports on controlled trials of noninvas ive ventilation ver-
tum, the physician suspects pneumonic consolidation. He sus conventional therapy.
The application of precise mathematical methods to bedside senses a great deal of worthwhile information-
vague and ill-defined concepts gives them a false air much more than can be expressed in words. In short, there
of respectability that cloaks ignorance and perpetuates is a very large tacit coefficient to clinical knowledge-
confusion.318 It is unfortunate that the more fundamental phys icians k11ow much more than they can communicate
the concept to which a word refers, the less careful we tend verbally.328 There is an enormous difference between the
to be about the use of a clear definition.325 assessment made by an experienced physician standing at
a bedside and the assessment the same physician makes on
hearing infom1ation (about the same patient) relayed over
Contraindications to Mechanical the telephone by a junior resident. An experienced and w ise
Ven tilation physician employs intuition rather tha n explicit rules in de-
ciding what is best for a particular patient in a particular
Complications associated with mechanical ventilation can setting. A physician who regards such intuition as unscien-
be lethal (see Chapters 41, 44, 46, and 47). Thus mechanical tific betrays a fundamental misunderstanding of the episte-
ventilation should be used only w hen it is clearly needed. mology of science.320
Intubation is not the first approach for most patients with Our failure to formulate a list of indications does not mean
an exacerbation of COPD; instead, noninvasive ventilation that we advocate a laissez-faire approach to instituting me-
is the first choice. The same sequence probably holds fo r chanical ventilation. Earlier we mentioned the absurdity
selected patients with congestive heart failure or in1muno- of saying that mechanical ventilation is a lways indicated
compromise. Mechanical ventilation should not be insti- for acute respiratory failure, defined as a Paaz of less than
tuted when a mentally competent patient or a surr ogate 60 mmHg. This does not mean that we consider Pao1 unim-
designated to make decisions on behalf of a noncompetent portant. A physician, on learning that a patient has a sus-
patient refuses it. If time permits, the patient and family tained Paaz of 40 mmHg, will take immediate steps to insti-
should be instructed about the likely impact of mechanical tute assisted ventilation. But it is not possible to pick a Paaz
ventilation on prognosis. For instance, hospital mortality of breakpoint (between of 40 and 60 mmHg) below which the
patients with idiopathic pulmonary fibrosis requiring me- benefits of mechanical ventilation decidedly outweigh its
chanical ventilation is 68%326 to 100%,327 and 92% of the hazards. It is futile to imagine that decision making about
survivors are dead w ithin 2 months of hospital discharge.326 instituting mechanical ventilation can be condensed into an
algorithm with numbers at each nodal point. In sum, an
algorithm cannot replace the presence of a physician well
Conclusion skilled in the art of clinical evaluation who has a deep un-
derstanding of pathophysiologic principles.
When we started to write this chapter, we expected to end
it by formulating a set of concrete recommendations as to
when mechanical ventilation should be instituted. Readers Acknowledgment
willingly wade their way through complex pathophysio-
logic concepts if they believe the material enhances their This work was supported by grants from the Veterans Ad-
understanding of a clinical topic. At the end, however, they ministration Research Service.
expect to see the complexity reduced to a set of concrete
recommendations, preferably conveyed as a list of entities
with numerical values attached. That final step is not pos-
sible with this d1apter. More than is the case for any other References
chapter in this book, it is not possible to articulate the in-
dications for mechanical ventilation in the form of a list of 1. Field S, Sanci S, Grassino A. Respiratory muscle oxygen con-
sumption estim ated by the djaphragm pressure-time index. J
items.
Appl Physiol 1984; 57:44-51.
TI1us, if it is not possible to formulate a list, then what? 2. Jubran A, Van de Graaff WB, Tobin MJ. Variability of patient-
When you, dear reader, are in severe respiratory distress and ventilator interaction with presst1re support ven tilation in pa-
a physician is standing at your bedside deciding whether tients with chronic obstructive pulmonary disease. Am] Respir
or not to ventilate (and possibly intubate) you, what type of Crit Care Med 1995; 152:129- 36.
physician are you hoping will make this decision? We can 3. Laghj F,Jubran A, Topcli A,ctal. Effectoflungvolume reduction
speak only for ourselves. The physician we want is a person surgery on diaphragmatic neuromcchanical coupling at 2 years.
deeply versed in pathophysiologic concepts, skilled in the Chest 2004; 125:2188-95.
art of physical examination, with extensive experience of 4. Laghi F, Cattapan SE, Jubran A, et al. Is weaning failure caused
cases similar to our own illness, and blessed with good clin- by low-frequency fatigue of the diaphragm? Am J Rcspir Crit
Care Med 2003; 167:120-7.
ical judgment. We expect that physician to base the decis ion
5. Jubran A, Tobin MJ. Pathophysiologic basis of acute respi-
(on which our life depends) on his or her c.linical gestalt.
ratory distress in patients who fail a trial of weaning from
And we recognize that the physician may not be able to ar- mechanical ventilation. Am J Respir Crit Care Med 1997;
ticulate the precise reasons behind this decision in the form 155:906-15.
of words. 6. Appendini L, Purro A, Gudjonsdottir M, et al. Physiologic re-
Why can't our ideal physician express these thoughts sponse of ventila tor-dependent patients with chronic obstruc-
in explicit terms? A wise physician standing at a patient's tive pulmonary disease to proportional assist ventilation and
INDICATIONS FOR MECHANICAL VENTILATION 155
continuous positive airway pressure. Am J Res pir Crit Care Med 29. Skarvan K Mikulenka V. The ven tilatory function of sternomas-
1999; 159:1510-7. toid a nd scalene muscles in patien ts with pulmonary emphy-
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J Respir Crit Care Mcd 1995; 151:210-4. pressu re (Po.t l and breathing pa ttern during pressure support
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humanity. New York: Norton, 1998. 325. Scadding JG. Meaning of diagnostic tem1s in broncho-
313. Tobin MJ. ATS centenary: Four-century prologue to a century of pulmonary disease. Br Med J 1963; 5370:1425-30.
progress. AmJ Respir Crit Care Med 2004; 169:891-3. 326. Saydain G, lslam A, Afessa B, et a!. Outcome of pa tients wi th id-
31 4. Scadding JG. Health and disease: What can medicine do for iopathic pulmonary fibrosis admitted to the intensive care unit.
philosophy? J Med Ethics 1988; 14:118-24. Am J Respir Crit Care Med 2002; 166:839-42.
315. Bernard GR, Artigas A, Brigham KL, et al. The American- 327. Fumeaux T, Rothmeier C, Jollict P. Outcome of mechan-
European Consensus Conference on ARDS: Definitions, mech- ical ven tilation for acute respiratory failure in patients
anisms, relevant outcomes, and clinical trial coordi nation. Am J with pulmonary fibrosis. Intensive Care Med 2001; 27:
Respir Crit Care Med 1994; 149:818-24. 1868-74.
316. Magee B. The story of philosophy. London: Dorling Kindcrsley, 328. Polanyi M. Personal kllowlcdgc: Towards a post-critical philos-
1998. ophy. Chicago: University of Chicago Press, 1958.
fJARTN complished easily by adjusting the minute volume to correct
hypercapnia and by treating hypoxemia with oxygen (0 2)
supplementation. Because the volume, frequency, and tim-
CONVENTIONAL ing of gas delivered to the lungs have important disease-
specific effects on cardiovascular and respiratory systems
METHODS OF functions, however, the physician must avoid simply man-
aging the blood-gas tensions of the ventilator-dependent
VENTILATORY SUPPORT patient. After a brief review of the capabilities of modem
ventilators, this chapter discusses the m echanical detenni-
nants of patient-ventilator interactions and defines thera-
peutic end points in common respiratory failure syndromes.
Chapter 6 TI1ese sections provide background for the major thrust of
the chapter, which is to detail the physiologic consequences
SETTING THE of positive-pressure ventilation and to develop recommen-
da lions for ventilator settings in various disease states based
VENTILATOR on this knowledge.
STEVE 1-IOLETS
ROLF D. HUBMAYR
Capabilities of Modern Ventilators
The incorporation of microprocessors into ventilator tech-
nology has made it possible to program ventilators to de-
liver gas with virtually any pressure or flow profile. Sig-
CAPABILITIES OF MODERN VENTILATORS nificant advances have been made in producing machines
Choice of h1spired-Gas Compos ition that are more responsive to changes in patient ventilatory
Machine's Sensing of Patient's Demand (Ventilator demands, and most full-service mechanical ventilators dis-
Triggering) play diagnostic information contained in airway pressure
Options for Defining the Machine's Mechanical (Paw), volume (V), and flow (\7) waveforms. Because of
Output these added capabilities, the practitioner is being cllallenged
THE MECHAN ICAL DETERMIN ANT S OF with a staggering array of des criptive acronyms for so-
PATIENT-VENTILATOR INTERACTIONS called new modes of ventilation. To avoid unnecessary con-
Inspiratory Mechanics fusion, it is useful not to focus on specific modes for the
Expiratory Mechanics moment but rather to consider three general aspects of ven-
Limitations of Linear Single-Compartment Models tilator management: (1) the choice of inspired-gas compo-
DEFINING THERAPEUTIC ENDPOINTS IN sition, (2) the means to ensure the machine's sensing of the
COMMON RESPIRATORY FAILURE SYN DROMES patient's demand, and (3) the definition of the machine's
ACUTE LUN G INJURY AND HYPOXIC RESPIRATORY mecl1anical outpu t.
FAILURE
Fractional h1spired Oxygen Concentration (Fio2 ) CHOICE OF INSPIRED-GAS COMPOSITION
Manipulating End-Expiratory Lung Volume
Choosing the Appropriate Tidal Volume Practically speaking, decisions regarding the composition
Respiratory Rate of inspired gas concem only the 02 concentration (see Hy-
Timing Variables poxic Respiratory Failure below). While there may be occa-
Minute Ventilation <Va> sions in which the care provider considers supplementing
OBSTRUCTIVE LUNG DISEASES the inspired gas with nitric oxide, the efficacy of nitric ox-
Minimizing Dynamic Hyperinflation ide therapy for most forms of hypoxic respiratory failure
Use of Continuous Positive Airway Pressure (CPAP) remains to be established. There has been growing inter-
Ventila tory Pump Failure and Chronic C02 Retention est in the biologic effects of hypercapnia on gas exchange,
APPROACHES TO COMMON POTENTIALLY vascular barrier properties, and innate in1munity.1- 9 Thera-
ADVERSE PATIENT-VENTILATOR INTERACTIONS peutic hypercapnia, tha t is, the deliberate supplementation
Respiratory Alkalosis of inspired gas with carbon dioxide (C02 ), however, cannot
Asynchrony Between the Patient's Effort and be recommended at this point in time. On extremely rare
Machine-Delivered Breaths occasions, it may be appropriate to use a helium-oxygen
mixture10•11 in an attempt to lower the flow resistance
TI1e choice of ventilator settings should be guided by clearly across a lesion in the distal trachea or ma in-stem bronchi,
defined therapeutic end points. In most instances, the pri- and there has been some interest in the use of helium in
mary goal of mechanical ventilation is to correct abnormali- as thma. Currently, these approaches must be considered
ties in arterial blood-gas tensions. In most patients, this is ac- experimental.
163
164 PART N CONVENTIONAL METHODS OF VENTILATORY SUPPORT
MACHINE'S SENSING OF PATIENT'S DEMAND weak or heavily sedated patients with severe hyperinfla-
(VENTILATOR TRIGGERING) tion and high intrinsic respiratory rates.16•17
Flow-triggering algorithms are alternatives or adjuncts
Ideally, a mechanical ventilator should adjust not only its to Paw-based triggering. During "flow triggering/' a base
rate but also its instantaneous mechanical output in re- flow of gas is being delivered to the patient during the ex-
sponse to changing patient demands. Conventional modes piratory as well as the inspiratory phases of the machine
of ventilation cannot do so but ratl1er execute a predefined cyde. 12 Unless the patient makes an inspiratory effort, gas
pressure or flow program after an effort has been sensed. bypasses the endotracheal tube and is discarded through
Controlled mechanical ventila tion refers to a mode dur- the expiratory machine port. In the absence of patient effort,
ing whid1 rate, tidal volume (VT), inspiratory-to-expiratory expiratory flow is equal to inspiratory base flow. In the pres-
tirning (I:E ratio), and inspiratory flow profile are deter- ence of an inspiratory effort, gas enters the patient's lungs
mined entirely by machine settings and can be altered and is thereby diverted from the expiratory machine port.
by neither the rate nor the amplitude of the patient's A discrepancy between inspiratory and expiratory base
effort. Occasionally, investigators refer to ventilation as flow is sensed, and the ventilator switches phase. Because
"controlled" when spontaneous respiratory muscle activity "flow triggering" alleviates the need to rarefy gas against
has been abolished by mechanical hyperventila tion or by an occluded demand valve, initially it was considered su-
pharmacological means (e.g., sedation and neuromuscular perior to pressure-based trigger algorithms. 12•18 Since many
blockade). new-generation ventilators have combined pressure and
Assist-control ventilation (ACV) gives the patient the op- flow sensing capabilities, these distinctions may no longer
tion of initiating additional machine breaths when the rate, apply.
set by the physician, is insufficient to meet the patient's rate
demand . ACV differs from intermittent mandatory ventila-
tion (IMV) in tha t all delivered breaths are either volume- o r OPTIONS FOR DEFINING THE MACHIN E'S
pressure-preset depending on the choice of primary mode. MECHANICAL OUTPUT
TI1e ACV feature has lured many physicians into the erro- The mode of mechanical ventilation often refers to the shape
neous assumption that the primary machine rate setting is of the inspiratory pressure or flow profile and determines
unimportant (see Hypoxic Respiratory Failure: Respiratory whether a patient can augment Vr or rate tluough his or her
Rate, below). own efforts.
Traditionally, madline algorithms for detecting patient
effort have keyed on tl1e airway pressure signa1.12 Because
the inspiratory port of ventilators is closed during machine VOLUME-PRESET MODE
expiration, any inspiratory effort that is initiated near relax- In conve11tional volume-preset m ode, each machine brea th
ation volume (Vrel) causes a fall in Paw. When Paw reaches a is delivered with the same predefined inspiratory flow-
predefined trigger threshold (usually set 1- 2 cmH2 0 below time profile. Because the area under a flow-time curve de-
the end-expiratory pressure setting), the machine switches fines volume, Vr remains fixed and is uninfluenced by
from expiration to inspiration. In the presence of dynamic the patient's effort. Volume-preset ventilation with constant
hyperinflatio n, the inspiratory muscles must generate con- (squarewave) or decelerating inspiratory flow is the most
siderably more pressure than the set airway trigger pressure widely used breath-delivery mode. Breath delivery w ith
befo re a machine breath is delivered.13 (seeObstructi ve Lung flows tl1a t decrease with increasing lung volume a re effec-
Diseases, below). tive in reducing peak Paw. It is not clear, however, whether
Particularly in older ventilator models a nd in less sophis- they protect the lw1gs from overdistension injury any more
ticated portable machines intended for home use, it used to than squarewave flow profiles.
be common to find delays of up to 0.5 second between the The mechanical output of a ventilator operating in ilie
onset of inspiratory muscle activity and machine response. volume-preset mode is uniquely defined by four settings:
In most ventilators used nowadays, such delays are less (1) the shape of the inspiratory flow profile, (2) Vr, (3) ma-
than 100 ms. 14 Sensing delays are common when the. Paw chine rate, and (4) a timing variable in the form of either the
is monitored in the machine rather than near the patient- I:E ratio, the duty cycle (T,/Tror), or the inspiratory time
ventilator interphase. In the former case, the ventilator tub- (T,). In some ventilators, timing is set indirectly through
ing acts as a capacitor, delaying the transmission of pressure the choice of peak or mean inspiratory flow (VT/T,).
from the intrathoracic airway to the pressure transducer. Figure 6-1 illustrates the relationships among these and
Additional delays can be attributed to d ynamic hyperinfla- other breathing-pattern parameters of significance.
tion a11d physical constraints on the opening and closing
of demands valves. Considering that mos t ventilator- PRESSURE-PRESET MODE
dependent patients ~enerate between 4 and 8 cmH20 During pressure-preset ventilation, the ventilator applies a
pressure in 100 ms,l2· 5 delays can cause significant effort predefined target pressure to the endotracheal tube during
expenditure and discomfort. More important, patients may inspiration. The resulting VT and inspiratory flow profile
terminate seemingly ineffective inspiratory efforts prema- varies with the impeda nce of ilie respiratory system and
turely only to initiate anotl1er effort of greater amplitude with tl1e strengtl1 and duration of the patient's inspiratory
shortly thereafter. TI1is leads to discrepancies between pa- efforts. Therefore, when the lungs or cl1est wall become stiff,
tient and machine rate. 16 Discrepancies are seen often in airway resistance increases, the patient's own inspiratory
CHAPTER 6 SETTING THE VENTILATOR 165
2 3 TABLE 6-1 List of Abbreviations
r Time constant
AC Assist-control mode
v
" ARDS
CMV
Adult respiratory distress syndrome
Controlled mechanical ventilation
0 /
VrjTE CPAP Continuous positive airway pressure
L Ers Elastance of the respiratory system
u Edi Electromyographic tracing of u,e diaphragm
M
F Force
E
fA Actual breathing rate
TE FEFzs- 75 Forced expiratory flow in the mid vital capacity
range
6 5
Trm F~ Fractional inspired oxygen concentration
fM Machine backup rate
T IME
J:E ratio Inspiratory-to-expiratory time ratio
IMV Intermittent mandatory ventilation
FIGURE 6-1 Idealized spirogram of a breath delivered during MMV Mandatory minute ventilation
volume-preset mechan ical ven tilation. Examples 1 through 6 Arterial C02 tension
PacD:l
indicate sp ecific changes in ventilator settings and illus trate the Arterial 02 tension
Pao2
consequences on flow and timing variable. (For abbreviations, Paw Airway pressure
see Table 6-1.) (1) Increasing mean inspiratory flow (VT!Tr) at a PCV Pressure-controlled ventilation
constant machine rate setting res ults in a reduced l:E ratio and PEEP Positive end-expiratory pressure
vice versa. Tr, TrffTOT• and mean expiratory flow (VT/TE) PEEPE Extrinsic positive end-expira tory pressure
decline. (2) Increasing VT at constant T1/TTOT or l:E s etting PEEPr Intrinsic positive end-expiratory pressure
increases mean inspiratory flow and requires an increase in mean Pel Elastic recoil pressure
expiratory flow. Remember that mean inspiratory flow equals PL Transpulmonary pressure
peak inspiratory flow when delivery modes with constant Pmus Inflation pressure exerted by inspi ratory muscles
squarewave flow profiles are used. (3) Increasing VT at a Pres Resistive pressure
constant mean inspiratory flow setting increases Tr, TJrrTOT• J:E Prs Recoil of respiratory system
ratio, and mean expiratory flow. (4) Decreas ing mean inspiratory PSV Pressure support ventilation
flow at a constant machine rate setting results in an increase in SIMV Synchronized intennittent mandatory ventilation
the I:E ratio and vice versa. T1, TJ/TTo T), and mean expiratory Te Expiratory time
flow rise. (5) Reducing the machine backup rate (fM) at a fixed Tt Inspiratory time
I:E ratio or T1rrTOT setting always prolongs T1 an d lowers m ean Duty cycle
Tt/TTOT
inspiratory flow. The timing effects of reducing fM at a fixed Total cycle time
TroT
inspiratory-flow setting cannot be predicted without knowledge TLC Total lung ca pacity
of the patient's actual trigger rate. (6) Increasing fM at a fixed I:E v Aow
ratio or TriTTOT setting always raises inspiratory flow. The V/ Q Ventilation-perfusion ratio
timing effects of increasing fM at a fixed inspiratory-flow setting
ca1mot be predicted without knowledge of the patient's actual
VcDJ. Volume of C02 produced in liters per minute
trigger rate.
Ve Minute ventilation
"·VEIVT
V(t}
Mean inspiratory flow
Instantaneous lung volume
Dead-space-to-tid al-volu me ratio
efforts decline, or T1 decreases, VT decreases. An increase in Vee Volume of lungs at end expiration
respiratory system impedance can lead to a dangerous fall Vrel Relaxation volume
in minute ventilation (VE), hypoxemia, and C02 retention, Vr/ TE Mean expiratory flow
but in contrast to volume-preset modes, it does not predis- Vr/T1 Mean inspiratory flow
VT Tidal volume
pose the patient to an increased risk of barotrauma. On the
Vtrapped Volume of gas remaining in the elastic element at
other hand, pressure-preset modes are no safeguard against the beginning of a new machine inflation
ventilator-induced lung injury because large fluctuations in Wei Elastic work
respiratory impedance or patient effort would result in large
VT fluctuations directly undermining the primary objective
of lung-protective mechanical ventilation (see discussion of
ventila tor management in hypoxic respiratory failure). as well as on the timing and magnitude of inspiratory
Pressure-support ventilation (PSV) and pressure- muscle pressure output. 14•19
controlled ventilation (PCV) are the most widely used PSV is a popular weaning mode for adults. Its popular-
forms of pressure-preset ventilation. In contrast to PCV, ity is based on the premise that weaning from mechanical
PSV requires the patient's effort before a machine breath is ventilation should be a gradual process and that the work
delivered. PSV therefore is not suitable for the management of unassisted breathing through an endotracheal tube is un-
of patients with central apneas. During PCV, the physician reasonably high and could lead to respira tory muscle fail-
sets the m achine rate, the T1, and thus the I:E ratio. In PSV, ure in susceptible patients. Actual measurements of pul-
phase switching is linked to inspiratory flow, which, in monary resistance and work of breathing before and after
tum, depends on the impedance of the respiratory system, extubation do not support this reasoning,20•21 and several
166 PART IV CONVENTIONAL METHODS OF VENTILATORY SUPPORT
large clinical trials have established equivalence between cute a predetermined pressure-time program as long as the
PSV and T-piece weaning (unassisted breathing from a bias- desired VT is reached. When the VT target is not reached,
flow circuit). 22 - 24 In the PSV mode, a target pressure is inspiration continues at a preselected inspiratory flow rate
applied to the endotracheal tube, which augments the in- (volume-limited) until the target volume is attained. Volume-
flation pressure exerted by the inspiratory muscles (Pmus) assured pressure support and pressure augme11tation are exam-
on the respiratory system. When inspiratory muscles cease ples of such modes.32 Breath-to-breath dual-control modes
to contract and Pmus falls, inspiratory flow (a ventilator- are pressure-limited and time- or flow -cycled. Ventila tor
sensed variable) declines, and the machine switcl1es to expi- output is derived from the pressure-volume relationship
ration. Early PSV modules were designed to generate pres- of the preceding breath and is adjusted within predefined
sure ramps (squarewave inflation pressure) a nd had rela- pressure limits to maintain the target Vr. Pressure-regulated
tively rigid flow-based, off-switch criteria. More recent ver- volume control (PRVC), volume co11trol+, auto-flow, adnptive
sions of PSV afford control over the rate of rise in inspira- pressure ventilatio11, volume support, and variable pressure sup-
tory pressure and the flow threshold at which ins piration is port are examples of breath-to-breath control modes. There
teminated .14, 19' 25 is no evidence that the use of dual-control modes improves
patient outcomes.33 Moreover, there is a conceptual problem
SYNCHRONIZED INTERMmENT MANDATORY insofar as less complex modes already safeguard against
VENTILATION (SIMV) hypoventila tion, whereas dual-control modes do little to
During SIMV, a specified number of usually volume-preset protect the patient from a potentially harmful increase in
breaths are delivered every minute. In addition, the pa- the re~ulated variable, that is, large V-r-mediated lung
tient is free to breathe spontaneously between machine injury. ,3S
breaths from a reservoir or to take breaths augmented w ith Neurally adjusted ventilatory assistance (NAVA) and
PSV. Some ventilators allow the operator to choose between proportional-assist verztilntion (PAV)36-38 are the most com-
volume- and press ure-preset mandatory breaths. Unless the plex and arguably the most promising closed-loop ventila-
patient fails to breathe sponta neously, maclUne breaths are tion modes. At the time of this writing, neither mode is avail-
delivered only after the ventilator has recognized the pa- able in the United States. During NAVA, the diaphragm's
tient's effort; that is, ventilator and respiratory muscle ac- electrical activity is recorded with an esophageal probe, and
tivities are "synchronized." Because nowadays all IMV cir- the signal. is conditioned and transposed into a positive air-
cuits are synchronized, the terms IMV and STMV are used way pressure output. NAVA is undergoing early clinical
interchangeably. Although SIMV remains a viable and pop- testing at this time and must be considered experimental.
ular mode of mechanical ventilation, compared with the PAV, on the other hand, is available commercia)] yin Canada
alternatives, PSV and T piece, it has dearly proven inferior and Europe, but it has not achieved mainstream status.36,3?
as a weaning modality.22•23.26.27 Moreover, the care provider During PAV, the ventilator derives its mechanical output
needs to be aware of certain pitfalls when using IMV. Even from continuously monitored Paw, V, and V information,
a small number of volume-preset IMV breaths per minute which, in tum, reflects Pmus. The operating principles of
may make the blood-gas tensions look acceptable in pa- PAV will be easier to understand after a review of patient-
tients who otherwise meet criteria for respiratory failure. ventilator interactions (see below).
One should suspect this in patients with small spontaneous
Vr (.53 ml/kg of body weight), in those w ith 30 or more
inspiratory efforts per minute regardless of whether they
trigger a machine breath, and when dyspnea and thora- The Mechanical Determinants of
coabdominal paradox indicate a heightened respiratory ef- Patient-Ventilator Interactions
fort. One reason that IMV remains popular is because it
silences apnea alarms by masking PSV-i.nduced respiratory INSPIRAT ORY MECHANICS
dysrythmias, which are common in sleeping and obtunded
patients.28-l9 It is useful to think of patient-ventilator interactions in terms
of a mecl1anical or electrical analog system consisting of a
DUAL-CONTROL AND ADVANCED resistive element (resistor) and an elastic element (capaci-
CLOSED-LOOP MODES tor) in series. The forcing function is defined by the pressure
Many new-generation mechanical ventilators feature or flow "program" that is executed by the mechanical ven-
modes w ith closed-loop feedback control of both press ure tilator.
and volume.J0,31 While a detailed description of the oper- In Fig. 6-2, a piston pump (the mechanical ventilator) is
ating principles of every new mode is beyond the scope attached to a rigid tube (the resistive element) and a balloon
of this chapter, it is important to understand the rationale (the elastic element). An in-series mechanical arrangement
behind dual-control modes and some of their general op- means that at any time t, the pressure that is applied to
erating characteristics. The idea behind dual-control modes the tube inlet Pi(t) (near the attachment to the ventilator) is
is the meeting of a ventilation target while maintaining low equal to the sum of two pressures, an elastic pressure Pel(t)
inflation pressures. To this end, ventilator output is adjusted and a resistive pressure Pres(t):
based on volume, flow, and pressure feedback. This may oc-
cur within each maclUne cycle or gradually from one cycle
to the next. Modes that adjust output within each cycle exe- Pi(t) = Pel(t) + Pres(t) (1 )
CHAPTER6 SETTINGTHEVENTILATOR 167
+ is dissipated during the acceleration of gas at the beginning

Insp. Pause
Inlet of the pump instroke can be ignored. Therefore, the respi-
Pressure
Pi
lPel
J
ratory analog of the equation of motion [Eqs. (1) and (2)]
considers only elastic and resistive pressures.
Consider the Pi-time profile of a tube-balloon system w ith
resistance of 10 cmH20 x liter/sand an elastance of 10
Flow Exp . cmH20 when the piston pump is p rogrammed to deliver
In sp . ..___ _...J a volume of 0.5 liter with a constant (squarewave) flow of
0.5 liter Is. Because flow and R remain constant throughout
T1 T~ inflation, Pres is constant at 5 cmH2 0 and accounts for the
- -- -- Time-- - - - - initial step change in inlet pressure at the beginning of in-
FIGURE 6-2 Components of inlet pressure. The model of the flation. As gas enters the balloon, Pi increases further and
respiratory system at right consists of a resistive clement (straight reaches a value of 10 crnH20 at end inflation. At that in-
tube) and an elastic elem ent (balloon) connected to a ventilator stant, the tube is occluded (end-inflation hold), causing Pi
(piston). During inflation of the model with constant flow (lower to d rop by an amount equal to Pres (as flow retums to 0).
pauel), there is a stepwise increase inlet pressure (Pi) that equals The end-inflation h old pressure is equal to Pel at that vol-
the loss of pressure across the resistive element (Pres) (upper ume. Its value of 5 cmH2 0 is equal to tl1e product of piston
pauel). Thereafter, Pi increases linearly and reflects the
stroke volume (0.5liter) and elastance (10 cmH20/ liter), as
mechanical properties of the elastic element (Pell). Pi is the sum
of Pres and Pcl. At end inspiration, when flow has ceased (Insp .
follows from Eqs. (1) and (2). Subtracting Pres from Pi(t)
Pause), Pi decreases by an amoun t equal to Pres; Pi equals Pel yields the Pel per time course during inflation. Pel increases
during Insp. Pause. T l• inspiratory time; T £, exp.i ratory time. linearly with time and volume. Its rate of rise (dPel/dt) par-
(Used, with permissiou, from Huvmayr et al: Crit Care Med allels that of Pi and is determined byE and the flow setting
18:103-13, 1990.) of the piston41 :
The tube outlet pressure at the junction with the balloon

is equal to the pressure inside the balloon, that is, Pel. Pres is
EX v= (dpfdV) X (dVfdt) = dPfdt (4)
the difference in pressure between the tube inlet and the tube
outlet. Assuming linear~system behavior, the inlet pres~;ure While changes in inspiratory flow result in proportional
time profile can be computed for any piston stroke volume changes in dPeJ/ dt, flow has no effect on peak Pel, pro-
vided that stroke volume and thus peak lung volume are
(Vstroke) and flow (\!) setting, provided the resistive prop-
held constant. This is in contrast to peak Pi, which reflects
erties of the tube (R) and the elastic properties of the balloon
flow-dependent changes in Pres, as well as change in Pel,
(E) are known:
at end inflation. The relevance of this important property
of linear single-compartment systems will become appar-
Pi(t) = EV(t) + RV(t) (2)
ent later when the relationships between ventilator settings
and barotrauma (balloon yield stress) are discussed (see Hy-
The elastance (E) is a measure of balloon stiffness and is poxic Respiratory Failure, below).
equal to the ratio of Pel and Vstroke (assuming 0 volume and
pressure at the beginning of balloon inflation). Therefore,
Pel(t) in Eq. (1) can be replaced with EV(t) in Eq. (2). Because EXPIRATORY MECHANICS
Ohm's law states that the tube resistance (R) is equal to the
In med1anically ventilated subjects, expiration is usually a
ratio of Pres and V, Pres(t) in Eq. (1) can be replaced with passive process that is driven by the elastic recoil (Pel) of
the product RV(t) in Eq. (2). the respiratory system. Assuming linear pressur~volume
Equations (1) and (2) are based on the equation of and pressur~flow relationships, the instantaneous expira-
motion,39 which describes the force (F) that must be applied tory flow [Vexp(t)] is given by
to a mass (M) in order to move it a certain distance (d) at a
rate dd/dt against a spring (elastic) load:
Vexp(t) = Pel(t)/ R (5)
F(t) = kd(t) + k ' (ddf df)(f) + k" [d(ddf dt)fdt](t) (3)

Because Pel(f) is a function of E and of the instantaneous
lung volume [V(t)], Eq. (5) can be rew ritten as
where k =stiffness of the spring (analogous to E)
k' = frictional resistance between mass and
supporting surface (analogous to R) Vexp(t) =Ex V(t)/R = V(t)/ R x C (6)
k" = inertance, which is proportional to mass
where C (the compliance of the respiratory system) is sim-
The first and second derivatives of d (analogous to val- ply the inverse of the elastance (E). The product o f Rand C
tune) represent the velocity (dd/dt, analogous to flow) and characterizes the time constant (r) of single-compartment
the acceleration [d(dd/dt)/dt] of the mass at timet, respec- linear systems . The time constant defines the time at which
tively. As long as the mass of the moving parts in the model approximately two-thirds of the volume above Vrel has
of Fig. 6-240 is small, any inertive-pressure component that emptied passively. From this it should be dear that patients
with increased respiratory system resistances and compli- ventilatory failure that require fundamentally different a p-
ances (e.g., patients with emphysema) a re prone to dynamic proaches to mechanical ventilation are the acute respiratory
hyperinflation even if one ignores nonlinear system behav- distress syndrome (ARDS) and chronic airflow obstruction.
ior, such as flow limitation, for the moment. The therapeutic goal in ARDS is to raise lung volume in
The volume of gas remaining in the elastic element at an attempt to reduce shunt by reexpanding collapsed and
the beginning of a new machine inflation (Vtrapped) can be flooded alveolar units. In contrast, the therapeutic goal in a
calculated as follows: patient with hypercapnic ventilatory failure from exacerba-
tion of airways obstruction is to reduce dynamic hyperin-
Vtrapped = VTf (eTE/r - 1) (7) fla tion a nd to protect the respiratory muscles from overuse.
In other words, the degree of dynamic hyperinflation is de-

termined by the choice of ventilator settings, specifically
mean expiratory flow (VT /VE) and the time constant of the Acute Lung Injury and Hypoxic
respira tory system, which reflects its mechanical constants Respiratory Failure
Rand C.42 These important concepts are expanded on under
Obstructive Lung Diseases, below. Acute lung injury (AU) is a syndrome associated with bi-
lateral pulmonary infiltrates and a gas-exchange impair-
ment severe enough to lower the arterial oxygen tension-to-
LIMITATIONS OF LINEAR
fractional inspired oxygen concentration ratio (Pao2 / FIOt)
SINGLE-COMPARTMENT MODELS
below 300.48.49 Heart failure and moderate to severe pre-
Before linear model principles are a pplied to the ventila- existing chronic lung disease must be absent. ALI and its
tor management of patients, one must be cognizant of the more severe form, ARDS, are often complications of sys-
model's limitations. The limitations fall into two general cat- temic illnesses such as sepsis.50 The impairment on pul-
egories: those related to nonlinear respiratory system char- monary gas exchange therefore is accompanied frequently
acteristics and those related to respiratory muscle activation by microcirculatory failure. The general management goal
during mechanical ventilation. Sources of nonlinear sys- in these disorders is to augment systemic oxygen delivery
tem behavior include inhomogeneities w ithin the numer- until the metabolic demands of the organism can be met.
ous bronchoalveolar compartments (particularly when the This goal requires an integrated approach between cardio-
lungs are diseased),43 respira tory system hysteresis from vascular and ventilator support. 51
recruitment of alveolar units and time-dependent surface Ventilator support is often difficult because exceedingly
tension phenomena,« and phenomena related to dynamic high ventilatory requirements challenge the performance
airway collapse and expiratory flow lirnitation. 45 Coactiva- capacity of mechanical ventilators; render patients at risk
tion of the respiratory muscles during mecl1anical ventila- for barotrauma, ventilator-induced lung injury, and cardio-
tion invalidates Eqs. (1) through (7) insofar as they alter vascular collapse; and often are accompanied by excessive
the impeda nce of the respiratory system a nd change the respira tory muscle activity ("fighting the ventilator"). All
driving pressure for expiratory flow. If one assumes that these conditions on occasion can necessitate heavy sedation
the respiratory muscles and the ventilator are arranged in and neuromuscular blockade.
series, then the monito ring of pressure, volume, and flow
at the airway opening offers the opportunity to define the
magnitude, ra te, and duration of respiratory muscle output FRACTIONAL INSPIRED OXYGEN
in mechanically ventila ted subjects.46,47 CO NCENTRATION (Fio 2 )
The two principal means by which the physician can in-
crease Pao, in ARDS ar e to raise the Flo 2 and to elevate
Defining Therapeutic Endpoints in the volume about w hich the lungs are being ventilated. The
Common Respiratory Failure Syndromes danger inherent in raising Flo, is oxygen toxicity,52 whereas
manipulating lung and / or VT may result in ventilator-
Numerous diseases of cardiopulmonary systems can cause induced lung injury53,s4 and/ or barotrauma .55 Presented
respiratory failure. From a ventilator management perspec- with the choice between two different kinds of adverse re-
tive, it is useful to group them into those that cause lung actions, physicians currently tend to be more fearful of me-
failure and those that cause ventila tory pump failure. chanical lung injury than of oxygen toxicity. Unfortunately,
The hallmark of lung failure is hypoxemia, which is usu- there are no clinical outcome studies that shed light on the
ally the result of severe ventilation-perfusion mism a tch. The interactions between these two iatrogenic insults. It is com-
hallmark of ventilatory pump failure is hypercapnia. Ven- mon practice to initiate ventilator support with an FIOt of
tilatory pump failure may be caused by disorders of the 1.0 and to ignore the potential for oxygen toxicity during the
central nervous system (CNS), periphera l nerves, or res- first few hours of ventilator management. While, generally
piratory muscles. It also may accompany diseases of the speaking, the relative and combined risks of oxygen toxi-
lungs, such as emphysema, once the ventilatory pump fails city and overdistension injury of the lungs remain poorly
to compensate for inefficiencies in pulmonary C02 elimi- defined, there are instances in which it seems wise to min-
nation. Two classic examples of hypoxic and hypercapnic imize Flo 2 , namely, in patients who have received dmgs
extrinsic positive end-expiratory pressure (PEEP), (2) by

raising lung volume dynamically through "intentional gas
trapping," (3) by increasing VT, and (4) by taking advan-
tage of the local distending forces generated by an actively
contracting diaphragm. Any one of these approaches may
be combined with so-called recruitment maneuvers, which
consist of sustained (up to 40 seconds) inflations of the lungs
to high volumes and pressures. 65 - 69 The preferred and time-
tested approach is the judicious use of extrinsic PEEP. All
the other means of raising ltmg volume are comparatively
untested, and in the case of Vr, manipulations can be out-
right harmful. 34 - 35- 70 While there is a strong physiologic
FIGURE 6-3 Computed tomographic (CT) scan of a patient with rationale to condition (i.e., "open") the lungs with recruit-
acute respiratory failure in the supine position. Note the p atchy, ment maneuvers before a PEEP adjustment, most experi-
nonuniform distribution of alveolar edema. (Used, wit11 mental and clinical data indicate that conditioning effects
permissiou, from Gattiuoui eta/: Am Rev Respir Dis .135:73()-6, are short-lived. 71 - 74 Because it is common for patients with
1987.) ALI to have an increased respiratory rate, a component of
dynamic hyperinflation often is present.75 Despite the short
time constant for lung emptying, the use of extrinsic PEEP
such as bleomycin or amiodarone, which make the lungs valves, which in older-generation ventilators represent re-
susceptible to reactive 0 2 species-mediated injury.56 sistive as well as threshold loads, and ventilator settings
that require large mean expiratory flows (VT /T Ei see Mean
Expiratory Flow: The Hidden Variable, below) contribute to
MANIPULATING END-EXPIRATORY LUNG VOLUME
dynamic hyperinflation.
l11e insults to the lungs of patients with hypoxic respiratory Although the experimental evidence in support of PEEP
failure are often patchy and result in flooding and closure therapy in injured lungs is overwhelming, its specific appli-
of dependent airspaces57•58 (Fig. 6-3). Paraspinal regions of cation to clinical practice remains controversiaJ.76-79 There
the lung appear most susceptible to atelectasis Oack of aer- is general agreement among experts that patients with in-
ation) because, in the supine posture, they normally empty jured lungs should be ventilated with PEEP settings greater
dose to their residual volume and they receive most of the than 5 em ~0. 80 There is no consensus, however, as to
pulmonary blood flow. 59·60 Therefore, insults to their capil- whether PEEP should be set arbitrarily to 10, 15, or 20 em
lary integrity are most likely to promote alveolar flooding, H20, whether it should be targeted to specific physiologic
closure of airspaces by liquid plugs, surfactant inactivation, endpoints, and if so, what those endpoints and their tar-
and gas-absorption atelectasis. 61 The accumulation of air- get thresholds should be. This uncertainty was only ampli-
way liquid and foam also generates interfacial forces that fied by a recent large randomized clinical trial that failed
are large enough to abrade the epithelial lining of small to show an outcome benefit for patients managed with a
airways during breathing, causing further injury.62,63 Ven- high-PEEP strategy (mean value 13 cmH20) as opposed
tilator management therefore mus t be directed toward pre- to a low-PEEP strategy (mean value 8 cmH2 0).81 While
venting the repeated opening and closing of unstable lung at least one prior clinical trial had demonstrated an im-
w1its, which means reestablishing aeration and ventilation pressive survival benefit in patients managed with high
of the flooded lung as much as possible64 (Fig. 6-4). PEEP,34 there were too many covariates, most notably the
There are several ways to achieve this objective: (1) by choice of Vr, to attribute benefit uniquely to the choice of
raising overall lung volume through the judicious use of PEEP.
100~------------------------------~~~---, FIGURE 6-4 Schematic representation of the

Overdistension Injury
therapeutic endpoints of ventilator manageme.nt in
ARDS. Raising peak lung volume toward TLC
80-i-- increases the risk of barotrauma. Keeping the
minimal volume near relaxation volume (Vrel)
~ raises the likelih ood of alveolar derecruitment at
I-
.,. 60 -+-- -1 \----..- -.... ·- end expiration and the need to apply large opening
UJ
;[
pressures in order to recruit collapsed and flooded
~··
:::>
..J lung regions during the subsequent b reath.
g 40
)
- -----~~~~ -------- V r ei
20
170 PART N CONVENTIONAL METHODS OF VENTILATORY SUPPORT
In light of this dilemma in 2005, it seems reasonable to tar- volume- and pressure-mediated increases in pulmonary
get the initial PEEP settings to a default value of 10 cmH2 0. artery pressure and right-ventricular afterload,101 and (4)
PEEP may be and probably should be increased further if increases in systemic oxygen consumption as a behav-
there is evidence of additional lung recruitment at higher ioral response to increased lung expansion and C02 re-
PEEP settings. Most physicians assess this by monitoring tention. The cardiovascular and metabolic confounders of
arterial Oz saturation during step changes in PEEP. A very the recruitment response may be deduced from pulse and
large step change amounts to a recruitment maneuver. Al- blood-pressure responses. Alternatively, lung recn1itrnent
ternative tools for assessing recruitment responses include ought to result in a d1ange in respiratory system mechan-
(1) measures of regional lung aeration with computed to- ics. The clinician, however, should be under no illusion
mography or electrical impedance imaging of the chest,8 2- 84 that such dumge will be large and easy to discern from
(2) measurement of the respiratory system pressure-volume peak and plateau pressure measurements.'102 This is so be-
relationships,85- 87 and (3) assessment of within-breath os- cause comparisons between states require careful attention
cillations in arterial Oz tension with indwelling arterial 0 2 to muscle relaxation and the matching of volume a nd time
sensors with fast response times. 88 Patients w ho are likely histories.103 Finally, because clinicians generally must rely
to recruit in response to PEEP and who may indeed benefit on pulse oximetry as opposed to online Po2 measurements,
from raising PEEP above 10cmH20 at the outset are patients they must consider the time delays secondary to circulation
with a reduced d1est-wall/abdominal compliance89- 91 and time and signal processing when assessing the recruitment
patients whose airway and alveolar edema can be redis- response.104
tributed easily.92 In critically ill patients, the most common
conditions associated with reduced chest-wall compliance
are obesity, ileus, and ascites.93,94 The ability to influence CHOOSING T H E APPROPRIATE TIDAL VOLUME
the distribution of edema within and between lung regions The choice of VT is arguably the most important decision
is greatest in the early stages of inflammation. In the later a care provider makes when initiating mechanical venti-
stages of ARDS, when the inflammatory exudate turns from lation. For many years, physicians have chosen ventilator
liquid to a gel, it becomes much harder to "open'' a dosed VT between 10 and 15 cm3 / kg of actual body weight. This
airspace. The likelihood of high PEEP causing recruitment recommendation can be traced back to the early days of
is even less once organizing pneumonia, alveolar remodel- positive-pressure ventilation, when this therapy was re-
ing, and fibrosis dominate the pathology.95 One attempt to served for patients with neuromuscular diseases, such as
identify groups of patients who are more or less likely tore- poliomyelitis. Patients with near-normal lungs feel more
spond to PEEP has been to classify their ins ults as indirect comfortable when they are ventilated with two to three
versus direct. 89 Indirect insults such as abdominal sepsis times normal VT. In patients with injured lungs, however,
are associated with a favorable PEEP response (possibly be- a VT of as little as 10 cm3 / kg of actual body weight can
cause their chest-wall compliance is low and their alveolar have devastating effects on lung structure, function, and ul-
exudate is liquid), whereas a direct insult, from a microbial timately, outcome.34,35,105
lung infection, for example, tends to be PEEP-resistant (air- To fully appreciate the importance of VT settings, it
way secretions tend to be viscous, and the alveolar exudate is useful to consider distinct physical lung-injury mech-
has the consistency of a gel). anisms: (1) regional overinflation, caused by the applica-
To the extent to which many clinicians rely on acute tion of a local stress or pressure that forces cells and tis-
changes in Pao, as surrogate endpoints of PEEP manage- sues to assume shapes and dimensions that exceed those
ment, certain caveats are in order. In critically ill patients experienced during even the most strenuous exercise,54'"06
with injured lungs, Pao2 is sensitive to changes in metabolic (2) so-called low-volume injury associated with the re-
rate and cardiac output.96 - 97 Because patients with injured peated opening and closure of uns table lung units,'62•63
lungs have V/Q mismatch as well as shunt, changes in (3) inactivation of surfactant, on account of large alveo-
mixed venous oxygen tension, which result from changes lar surface-area oscillations,107•108 and (4) interdependence
in metabolic rate and cardiac output, must influence ar- mechanisms that raise cell and tissue shear stress be-
terial Po, . Therefore, the P~ response to s tep changes in tween neighboring structures with differing mechanical
PEEP (and/or recruitment maneuvers) is determined by properties. 109
a net balance between positive and negative effects. Pos- The injured lung is particularly susceptible to physical
itive effects include (1) reductions in the number of lung damage because its inspiratory capacity is reduced and its
tmits with low V/Q and shunt as a result of their recruit- dorsal units tend to get obstructed with liquid plugs. 11 0 As
ment, (2) increases in cardiac output driven by the sym- a result, the greater the VT, the greater is the likelihood that
pathominletic effects of C02 retention (the latter invariably the lung will be damaged by both high- and low-volume
accompanies recruitment maneuvers), (3) a fall in oxygen injury mechanisms. One approach that requhes no judg-
uptake associated w ith respiratory acidosis.98,99 Negative ment whatsoever is simply to adopt in all patients with
effects include (1) increases in low V/ Q and shunt in pa- injured lungs the settings of the low-VT arm of the ARDS
tients who are PEEP-resistant and in whom the increased Network clinical trial/ 5 whicl1 established the efficacy of
alveolar pressure diverts blood away from normal lung to- lung-protective mecl1anical ventilation. Patients random-
ward diseased lung,100 (2) a fall in cardiac output result- ized to the low-VT arm received a VT of 6 cm3 / kg of pre-
ing from volume- and pressure-mediated decreases in ve- dicted body weight. If their end-inflation pause pressure ex-
nous return,68 (3) a fall in cardiac output resulting from ceeded 30 cmH 20 , then VT was reduced further to as little as
4 cm3 / kg of predicted body weight. In patients in whom 6 agementof the low-VT group. 114 Be this as it may, the debate
cm3 /kg of predicted body weight resulted in breath stack- produced some important questions: (1) Is the choice of Vr
ing, effectively doubling their VT, and in whom stacking also important in patients who are ventilated with what
could not be abolished with sedation, Vr was increased up generally are considered "safe" inflation pressures? (2) Are
to 8 cm3 / kg of predicted body weight. This approach was ventilator modes in which d iaphragmatic activity is pre-
associated with a 23% reduction in all-cause mortality com- served superior to the low-VT approach used in the ARDS
pared with a high-Vr strategy.35 Network trial? (3) Should one care about Vr restrictions in
One important lesson from the ARDS Network trial is patients with lung diseases other than AU?
the scaling of Vr to predicted or ideal as opposed to actual
body weight. To the extent to which the treatment objec- 1. Is the choice of Vr also important in patients who are ven-
tive of lung-protective mechanical ventilation is to mini- tilated with what generally are co11sidered "safe" illf/tltion
mize lung stretch, one would want to scale Vr to the vol- pressures? Inflating the lungs beyond TLC greatly in-
ume of reouitable lung.m Because determining recruitable creases the risk for barotrauma. Barotrauma is charac-
lung volume requires imaging or more sophisticated respi- terized by extra-alveolar air and is an entity distinct from
ratory mechanics measurement techniques, estimating the ventilator-induced lung injury. 53.55 The transpulmonary
size and volume of the ltmg before injury is the next best and alveolar pressures at TLC approximate 25 and
alternative. Epidemiologic studies have established height 35 cmH20, respectively. 115 During medtanical ventila-
and gender as opposed to actual body weight as the best tion, peak alveolar pressure can be approximated from
predictors of absolute lung volume, including total lung pressure at the airway opening after occluding the endo-
capacity (TLC). 112•113 The ARDS Network investigators pre- tracheal tube at end inflation (hold or plateau pressure).
dicted ideal body weight from an equation based on height Measurement of the transpulmonary pressure requires
and gender. A graphic comparison of the two predictive placement of an esophageal catheter and thus is inva-
equations (Fig. 6-5) shows that 1 cm3 /kg of predicted body sive. Furthermore, use of esophageal pressure tends to
weight corresponds to 1% predicted TLC. Therefore, the result in overestimation of mean lung surface pressure
recommendation to restrict VT of patients with injured in the supine position. 116
lungs to 6 cm3 /kg of predicted body weight amounts to There is an ongoing debate as to whether mechanical
restricting Vr during mechanical ventilation to no more ventilation with plateau pressures of less than 30 cmH2 0
than 6% of preinjury TLC. The right-hand side of the fig- is safe irrespective of the choice of Vr. None of the avail-
ure shows that there is no correlation between predicted able clinical and experimental studies is sufficiently con-
TLC and actual body weight in a population of patients vincing to base general management recommendations
who were ventilated at the Mayo Clinic in 2001. 105 Because on. In the absence of convincing data, one should exercise
both reasoning and clinical outcome data are compelling, extreme caution w hen departing from low-Vr guidelines
the practice of scaling Vr to actual body weight should be in patients with ALI. Indeed, circumstantial evidence
abandoned. 35•105 and reasoning favor strict adherence to low-VT guide-
The results of the ARDS Network trial genera ted a heated lines in patients with ALI because (a) spontaneous hyper-
debate as to whether outcome differences reflected the ob- ventilation, which by definition never exceeds TLC, has
solete management of the high-VT group or improved man- been implicated as a cause of surfactant dysfunction and
FIGURE 6-5 Predicted or ideal {left panel) and actual body weights (rigllt pa11el) of 332 mechanically ventilated patients have been plotted
against their predicted normal total lung capacity (%TIC). The predictive equations for ideal body weight and TLC are based o n height
and gender. Not surprisingly, then, the correlation between predicted body weight and predicted T LC is excellent. Also note, however, that
the correlation between actual body weight and p ercent TLC is extremely poor. The source data are from patients included in a report by
Gajic et al.1 05
20- • -· 2Q- - • •
... •
..
• .. -. .
. .•:, .. -
. • . .-.. .. ..
.- •I '·= ~
.,.. ·.
~
,.
.. ..... . .... - ....., . .. .. •
•0 • -
~ - ~:· · ...J ... ~.: ·~· ·
... .
• •J •.~ .•• - •
.
I- 1- ~ ~·
0~
..
•• 0~
:.,.,..••..-___
,.-. -c • , , .·......
"W-~"''
' .
·· :-···
' ~
·~-
. •
1Q- 10- . .
. .. ... .-·. . . ..,
-':.
~~
. .. • . .. ...... ' . \, . ...., .
• • I
'~
:
• ,; •' -
,. • •,oil•
.--.. ..
• •
.' ' I
' I ' I
' ' ' I I I I , I I o
I ' ' ' ' ' 20
I '
10 20 10
Vt mUkg predicted body weight Vt mUkg actual body weight
noncardiogenic pulmonary eden1a,117 (b) repeated infla- cause (1) neurohumoral feedback from lung edema and
tions of the respiratory system to pressures and volmnes inflammation induces rapid shallow breathing indepen-
below TLC but above the upper inflection point of the in- dent of chemoreceptive and mechanoreceptive effects on
flation P-V curve have been associated with ltmg injury,87 central pattern generation, (2) in the presence of a severe
and (c) a post-hoc analysis of ARDS Network data sug- gas-excha nge impairment, low rates and minute volumes
gested that patients in all plateau pressure quartiles de- would cause C02 retention, which, in turn, elicits its own
rived benefit from VT reductions (R. Brower, personal disease state-independent effects on respiratory rate and
communication). drive, and (3) discrepancies between actual (triggered) and
2. Are ventilator modes in which diaphragmatic activity is preset machine (backup) ra te promote breathing patterns with
served superior to the low-Vrapproach used in the ARDS Net- inverse inspiratory-to-expiratory timing ratios and double
work trial? Patient-assisted breathing modes, such as PSV, triggering. Inverse breathing-pattern ratios are not compat-
bilevel pressure ventilation, and airway pressure-release ible with normal phase-switching mechanisms in the pres-
ventilation (APRV), have been touted as modes of choice ence of respira tory distress. Conventional ventilator modes
in the management of patients with ALT. 118• 119 The evi- are not capable of varying Tr or inspiratory flow with the ac-
dence in support of this recommenda tion is not as strong tual machine rate. For example, at an fM setting of10breaths
as that in support of the low-Vr strategy employed in the per minute, the total cycle time (Tror) is 6 seconds. If the
ARDS Network trial. 35 The rationale for partial support I:E ratio is set at 1:2, or if Vr and flow have been set to 0.5
centers on the increased regional ventilation and reduced and 0.25 liter/s, respectively, then Tr is fixed at 2 seconds,
incidence of atelectasis in dorsal lung regions when di- and expiratory time (TE) will be 4 seconds. If the patient
aphragmatic activity is preserved. 120•121 Whether this ob- actually triggers at 20 breaths per minute, then TroT) de-
servation has bearing on patient survival, however, is cJjnes to 3 seconds. Tr remains fixed a t 2 seconds because it
currently unclear. It should be noted that, on general prin- is determined by the preset machine (backup) rate, the I:E
ciples, Vr-related effects on lung s tructure and function, ratio, or the inspira tory-flow setting. TE now must decrease
including injury mechanisms, are not specific to ventila- from 4 seconds to 1 second, and the actual I:E ra tio will
tor mode. increase from 1:2 to 2:1. At a rate of 30 breaths per minute
3. Should V r be restricted in. pa.tie11ts with respiratory failure (TTOT) =2 seconds), TE becomes O,and "fighting the ventila-
from conditions other tlum AU? To the extent to which tor" must result. For these reasons, the fM always should be
alveolar overdistension is a prevailing injury mecl1a- set close to the patient's actual rate. If the actual rate is so high
nism, lungs with relatively preserved inspiratory capac- that effective ventilation cannot be achieved, then the pa-
ity ought to be less suscep tible to deformation injury. tient needs additional sedation and possibly neuromuscular
Consistent w ith this reasoning, ventilator management blockade.
of patients undergoing major surgery had no apparent
effect on pulmonary immm1e responses. 122 On the other TIMI NG VARIABLES
hand, the postoperative use of continuous positive air-
way pressure (CPAP) was shown recently to reduce the I:E RATIO
need for reintubation in such patients.94 Moreover, a ret- The setting of timing variables in conjunction with Vr and
rospective cohort study of patients who were mechan- extrinsic PEEP d etermines the volume range over which
ically ventila ted for more than 48 hours and who did lungs are cycled during ventilation. A long T1, a high
not have ALI from the outset identified VT as a major Tr / Tror), and a low mean inspiratory flow all promote
risk factor for the subsequent development of noncar- ventilation with an inverse I:E ratio. Despite the consider-
diogenic pulmonary edema. 105 Because there is no com- able number of endorsements of inverse-ratio ventilation
pelling reason why any patient with normal or near- in ARDS, the beneficial effects of increasing I:E beyond 1:1
normal lungs would benefit from or need a VT of greater on pulmonary gas exchange tends to be marginal, provided
than 10 cm3 / kg of predicted body weight, VT settings that VT and end-expiratory volumes are held constant.m
above this threshold should be used with caution. All ventilators provide the option of maintaining lung vol-
ume at end inflation through the use of an inspiratory-hold
time or pause time that usually is expressed as a percent-
RESPIRATORY RATE age of the total cycle time (%TroT). For the purpose of
Having settled on a VT and a.n end-expiratory volume, ad- defining the I:E ratio, the pause time is considered part
justments in the machine backup rate (fM) should be made of the inspir a tory machine cycle. Long pause times favor
considering (1) the patient's actual rate demand, (2) the the recruitment of previously collapsed or flooded alve-
patient's anticipated ventilatory requirement, and (3) the oli and offer a means of shortening expiration indepen-
impact of the rate setting on breath timing (see Fig. 6- dent of rate and mean inspiratory flow (Y, ). Although alve-
1). Virtually all patients with hyp oxic respiratory failure olar recruitment is a desired therapeutic endpoint in the
are tachypneic and usually require fM settings of between treatment of patients with edematous lungs, one should
20 and 30 breaths per minute. Unless the patient has been at least consider that keeping the lungs expanded at high
paralyzed or has been so heavily sedated that spontaneous volumes (and pressures) for some time may damage rela-
inspiratory triggering efforts are not sensed, fM settings of tively normal units and may cause adverse hemodynamic
20 breaths per minute or lower are poorly tolerated be- effects.
INSPIRATORY FLOW and consequently of the arterial C02 tension <Paco2 ):
v,
Most ventilators require that mean and its profile be spec-
ified. Mean V1 is equal to the ratio of Vr and T1. Therefore, Yco2 x k
P ac~= . (8)
one cannot change flow without affecting at least one of the VE(l - Vo/ VT)
other timing variables (see Fig. 6-1). It is also important to
consider that changing the flow profile from a squarewave where Vco2 = volume of C02 produced in liters per
to a d ecelerating or sine-wave pattern prolongs T1 in ven- minute
tilators that require a peak-flow setting. This is so because Vo/Vr =dead-space-to-tidal-volume ratio, a
nonsquarewave profiles have a higher peak-to-mean flow variable with which the efficiency of
ratio; that is, it takes longer to deliver the p redefined Vr the lung as a c~ eliminator can be
than in squarewave flow delivery modes. Unless the pa- approximated
tient is struggling, mean V1 usually is set to no more than k = 0.863 and is a constant that scales V c~
1 liter /s during volume-preset ventilation. In patients in and VE to the same temperature and
whom lung recruitment and oxygenation are the primary humidity
therapeutic endpoints, setting flow (and rate) so that the
T1/Tror) approximates 0.5 U:E = 1) tends to achieve the If the main goal of mechanical ventilation were to nor-
goal Increasing flow always will raise peak airway pres- malize Paco2 , then VE would be the most important ma-
sure, but this need not be of concern if most of the added chine setting. Although a "normal" Pac~ is o ne of the ther-
pressure is dissipated across the endotracheal tube. On the apeutic endpoints of mechanical ventilation, at times, nor-
other hand, there is experimental evidence that the rate of mocapnia can be achieved only with high lung inflation
lung expansion is a Vr-independent risk factor for lung volumes and pressures. This is particularly true in patients
deformation injury. Although V1 is one of the factors that with AU because they are often hypermetabolic (high Vc~
determine the regional distribution of inspired gas,43 the and in addition suffer from V/Q mismatch (high Vo/Vr).
lung volume-independent effects of flow on pulmonary gas For these reasons, it is not unusual to encounter patients
exchange are too unpredictable to warrant general guide- with ALI whose VE requirements exceed 20 liters. In the
lines. Much more important is the realization that the com- past, concerns about acid-base status dominated the choice
bined effects of flow, volume, and time settings influence of ventilator settings. In recent years, however, the focus on
the functional residual capacity and the degree of dynamic mechanical lung injury has resulted in a reappraisal of ther-
hyperinflation. 42•124•125 apeutic priorities that now places the prevention of lung
injury above the goal to normalize C02 tensions and acid -
base status. The corresponding ventilation strategy has been
MEAN EXPIRATORY FLOW: THE HIDDEN VARIABLE termed permissive hypercapnia.126•127 Permissive hypercapnia
Mean expiratory flow is defined by the ratio of Vr and TE. means that the physician accepts a Paco2 outside tl1e ex-
TE = Tror)- TJ. Tror) = 60/f (per minute). Because the fM pected or "normal' range in order to minimize the potential
and the actual f may differ from each other in the assist- for ventilator-induced lung injury. Because such a ventila-
control mode, the assumed and the actual TroT also may tion strategy nms contrary to the limits set by the chemore-
differ. Recall from the discussion on rate and timing that T, is sponses of neural ven tilatory control mechanisms, permis-
defined by both the set fM and the set I:E ratio and thatT, re- sive hypercapnia usually requires heavy sedation and at
mains constant irrespective of the actual rate. In contrast, T E times paralysis of the patient.
is affected by the actual breathing rate (fA): TE = 60/fA-TJ. There is a great deal of interest in the consequences of
Therefore, the choice of volume and timing settings, to- hypercapnia on pulmonary vascular barrier function, sig-
gether with the patient's trigger rate, determine mean expi- naling mediated by reactive oxygen and nitrogen species,
ratory flow. Vr / TE is the principal ventilator setting-related innate immunity, and ultimately, patient survival. 1- 9 The
determinant of dynamic hyperinflation. A patient with ait'- science is fascinating, but it is not sufficiently advanced to
derive clinical management decisions. That said, most ex-
way obstruction and a maximal forced expiratory flow of
0.2liter /sin the mid- vital capacity range obviously cannot perts probably would agree that (1) there is no universal pH
accommodate a Vr /TE of 0.5 liter Is without an increase or Pco2 threshold that mandates a corrective action, (2) the
in end-expiratory lung volume (see Obstructive Lung Dis- use of bicarbonate buffers to correct respiratory acidemia
eases, below). is unproven, and (3) tracheal gas insufflation generally is
effective in reducing Paco2 by 10 mmHg or less. 128- 130
MINUTE V ENTILATrON (VE) Obstructive Lung Diseases

With the exception of some older-generation Siemens series In patients with obstructive lung diseases, there is a re-
ventilators, VE is not a variable that is set directly by the duced capacity for generating expiratory flow. When ob-
operator, but it is consequence of the Vr and rate settings. struction is severe enough to cause ventilatory failure, dy-
VE is an important determinant of the body's C02 stores namic airway collapse is virtually always present during the
expiratory phase of the ventilatory cycle.13' 131 This means

that the passive elastic recoil forces of the relaxed respira-
tory system are large enough to produce maximal expira- 1.0
tory flows in the tidal breathing range. Such patients are
prone to d ynamic hyperinflation, which may adversely af-
Q
fect circulation,132 may increase the risk of bar otrauma, 133 )( 0 .5
and can place the diaphragm and inspiratory muscles at ,.., w
a mecha nical disad vantage.134- 136 TI1e primary therapeutic
goal of mechanical ventilation in obstntctive lung disease
therefore is to minimize the thoracic volume about which
-U)
._,
::
0
0 · -··-· _______
'
.....+ t
Infl ation 1
Vrel
the lungs are ventilated. Additional goals vary with the u. ..----- .. -~-·
a. Inflatio n 2
context in which airflow obstruction is observed. Patients
c 0 .5
U)
with long-standing obstruction from emphysema or chronic Inflation ss

bronchitis (unless they are "fighting the ventila tor'') usu-
ally are easy to ventilate and simply may need respiratory 1.0
muscle rest and a resetting of the C~-response threshold to
more normal values. These secondar y therapeutic objectives 3 .0 2.0 1.0 0
are highly controversial. In contrast, patients with acute se-
vere asthma often "fight the ventilator" and therefore often Liters Ab ove Re laxation Volum e (Vr el >
require sedation, neuromuscular blockade, and ventilation FIGURE 6-6 Diagrammatic demonstration of how insufficient
wi th permissive hypercapnia.126,133 Such patients are prone expiratory flow pToduces dynamic hyperinflation. The b roken
to neuromuscular insults from glucocorticoids and para 1ytic horizontal arrow shows the first breath of lliter initiated from
agents and may require prolonged mechanical ventilation relaxation volume (Vrel) at a rate of 20 breaths per minute and a
for weakness long after lung mechanics normalize. 137 T1/TTOT) of0.33 (inflation 1). The solid curved line shows the
maximal expiratory flow that can be produced during passive
exhalation by the elastic recoil pressure of the system. In the 2
seconds available from expiration, the maximum mean
MINIMIZING DYNAMIC HYPERINFLATION expiratory flow of the first b reath ( V1 ) is only 0.25 liter/s.
Therefore, only 0.5 liter can be exhaled in the 2 seconds before the
The ventilator management of pa tients who are prone to next inhalation of lliter is initiated (inflation 2). According to the
dynamic hyperinflation is best understood after a review of flow-volume relationship, a maximal mean expiratory flow of 0.3
the expiratory mechanics of the relaxed respiratory system liter/s ( V1 ) can be achieved over this volume range. A steady state,
(see The Mechanical Determinants of Patient-Ventilator In- during which inspiratory and expiratory volumes are matched,
teractions, above). TI1e key determinants of end-expiratory will be reached only when the maximal mean expiratory flow
lung volume in a ventilated patient are the time constant ( Vssl equals 0.51..iter/s. (Used, witlz pen1tissio11, from Hubm a.yr et
of the respiratory system (R x C) and the Vy/TE that has al: Crit Care MtU/18:103-13, 1990.)
been imposed by the ventilator settings. 42 Figure 6-6 under-
scores these concepts, which are fundamental to formulat- any pressure generated by respiratory muscles.13,'138 In the
ing a m eaningful m an agement pla n. If it is assumed that a absence of muscle activity, the d egree of dynamic hyper-
mechanical inflation of 1 liter is initiated from Vrel at a rate inflation can be inferred from the end-expiratory air way
of 20 breaths per minute and an I:E ratio of 1:2, the patient occlusion pressure (PEEPr) and the elastance of the relaxed
has 2 seconds to exhale. In the example in Fig. 6-6, the max- respira tory system (Ers):
imal mean passive expira tory flow that can be achieved in
this volume range (between Vrel a nd Vrel + 1liter) is given
by the expiratory flow-volume curve. In this example, the Vee- Vrel = Ersj PEEP1 (9)
maximal mean flow is only 0.25liter/ s. Hence, in the 2 sec-
onds available for expira tion, the patient can exhale only where Vee is the volwne of the lungs at end expiration.
half the inspired volume CO .Sliter) before the next inflation In the presence of muscle activity from active expira-
is initiated by the machine. TI1e second breath therefore is tion or inspiratory triggering efforts, PEEP, is a meaning-
begun at a lung volume of Vrel + 0.5 liter. Maximal m ean less measurement. This limitation also applies to some ex-
expiratory flow over the new volume range (Vrel + O.Sliter tent to esophageal pressure-derived estimates of PEEP,. In
and Vrel + l.Sliters) is 0.3 liter/s. This flow is still insuffi- some ventilators, PEEP, can be estimated at the " press of a
cient for adequate lung emptying. A new stead y state will button"-by pressing an end -expiratory hold button and
be achieved only when the increase in lung volwne results waiting until airway opening pressure reaches a steady
in a maximal mean expiratory flow of 0.5 liter Is, which is value. In ventilators in which the timing of end-expiratory
equal to the obligatory mean expiratory flow imposed by occlusions is not automated, the measurement of PEEP1 is
the ventilator settings. considerably more difficult.
Dynamic hyperinflation is associated with an increase As illustrated in Fig. 6-6, ventilator adjustments designed
in alveolar pressure at end expiration . Tllis pressure, also to minimize dynamic hyperinflation should be geared to-
called ilttrinsic positive eud-expiratory pressure (PEEP,), is the ward lowering mean expira tory flow (Vy/TE). In a para-
pressure of the respiratory system at end expiration plus lyzed patient with asthma, Vy can be reduced to as little
as about 4 cm3 / kg of predicted body weight, whereas TE with end-stage obstructio n may have maximal expiratory
is prolonged through increases in mean inspiratory flow flows of 0.2 liter/s or less up to volumes nea r TLC.131 In
(1-1 .5 liters/s), adjustments in the I:E ratio (1:4-1:5), and the non paralyzed patient, hypercapnia sets limits to there-
reductions in fwt (~10 breaths per minute). As discussed ductions in VT; therefore, attempts must be made to reduce
earlier, such a strategy is likely to produce hypercapnia, the patient's respiratory rate. Sometimes the only way to
but even severe acidemia is usually well tolerated in para- minimize hyperinflation without having to resort to neu-
lyzed subjects. 139 High inspira tory-flow settings, which are romuscular blockade is through the judicious use of seda-
required to prolong T E, are bound to increase peak Paw and tives w ith the intent of reducing inspiratory efforts until
may raise concerns about barotrauma. It must be empha- they fail to initiate a machine breath (see Asynchrony be-
sized, however, that much of this added " resistive pressure" tween the Patient's Effort and Machine-Delivered Breaths,
is dissipated along the endotracheal tube and proximal air- below).
ways and that, on balance, increasing the rate of lung infla-
tion seems less damaging than ventilating asthmatic lungs
near TLC. Consistent with this hypothesis, the incidence of USE OF CONTINUOUS POSITIVE AIRWAY
barotrauma can be reduced significantly in patients w it11
PRESSURE (CPAP)
status asthmaticus when ventilator settings are chosen to
maintain peak lung volume wit11in 1.4liters ofVreL133,-140,l 41 In patients with hypoxic respiratory failure, CPAP is used
Permissive hypercapnia and neuromuscular blockade are to raise lung volume to recruit closed and flooded alveoli
rarely required in patients with ventilatory failure from ex- and to improve oxygenation. In contrast, the goal of CPAP
acerbations of chronic obstructive lung diseases. Neverthe- therapy in patients with obstmction is to minimize inspi-
less, many such patients have respiratory rates in the high ratory work.142 Potential mechanisms of action of CPAP in
teens and low twenties, making it difficult to prolong TE obstructed patients a re shown schematically in Fig. 6-7 A
beyond about 2 seconds. This makes it virtually impossi- The figure shows the pressure-volume relationships of the
ble to ventilate these patients near Vrel. Recall that patients relaxed respirato ry system and depicts the elastic work
FIGURE 6-7A. Effect of dynam ic hyperinflation of elastic inspiratory work. The solid curve shows the relationship b etween the volume
above Vrel and th e recoil of the respiratory system (Prs). Dynamic hyperinflation exists. Inspiration is now initiated from a volume ab ove
Vrel. The increase in lung volum e n ecessitates an increase in the elastic insp iratory work, which may be considered to have tw o
comp onen ts: work to halt exp ir atory flow (darker-shaded areal and work required to inflate the respiratory system (lighter-shaded area). B.
Effect of CPAP on respiratory work. The solid curve is th e p ressure-volum e curve of th e respiratory system. With CPAP, a n ew Vrel is
ach ieved . To con serve insp iratory elastic work, the patien t recruits expiratory muscles and exh ales below the new Vrel. The clas tic w ork
p erformed by th e expiratory mu scles is represented by the darker shad ed area. Relaxation of the expiratory muscles inflates the lu ngs back
to the new Vrel withou t inspiratory effort. Th e insp iratory muscles then increase lung volume further, performing elastic inspiratory work
(lighter-shaded area). Hence CPAP redu ced the work of the inspiratory muscles by letting th e expiratory muscles do part of the inspiratory
work. (Used witfr pem rissio11. From H ubnwyr et al: Crit Care Med 18:103- 13, 1990.)
<1> (])
E E
-
0
:::J
-0
:::1
> >
-
c t:
-
0
as
X
as
t
End - Inspiration
0
as
X
as
<1> <l>
a: a:
(]) <l>
> >
0 0 Tida l Volume
..0 End- E x piration ..0
<( <(
f/)
-
f/)
~
Q)
...J -
1-
<1>
...J I
I
PEEP CPAP Prs
Prs
1\ B
(Wei) needed to raise lung volume from end expiration to Proponents of such a ventilator strategy may argue that C0 2
end inspiration (shaded area) in the presence of dynamic has negative inotropic effects on respiratory musdes151 and
hyperinflation. We! has two components: (1) work required that experience with nocturnal ventilator assistance sug-
to halt expiratory flow by counterbalancing respiratory sys- gests that resetting C02 responsiveness is feasible in some
tem recoil at end expiration (W related to PEEPr) and (2) instances. 152 Opponents argue that maintenance of normo-
work expended during inflation of the lungs and thorax. capnia in thepresenceoflungdiseaserequiresahigh minute
In theory, the inspiratory work related to PEEP1 (darker volume, which could represent a fatiguing load on the res-
shaded area) can be provided externally with CPAP equal piratory muscles. As a general rule, at the time weaning is
to PEEP1. As CPAP approaches PEEPr, however, additional contemplated, sustainable C02 tensions should range be-
hyperinflation may occur.l'l3 To guard against CPAP- tween 40 and 50 mmHg. Patients who are being weaned
induced worsening of hyperinflation, the physician can with C~ tensions in the sixties tend not to do well and are
monitor peak or end-inflation hold pressure as an indicator severely limited.
of peak lung volume.
An alternative mechanism by which CPAP may reduce
inspiratory elastic work is shown in Fig. 6-7B. CPAP may
result in exhalation below the new Vrel through the recruit-
Approaches to Common Potentially
ment of expiratory musdes:138•144 Subsequent relaxation of Adverse Patient-Ventilator Interactions
the expiratory muscle inflates the lungs passively back to
the new Vrel. Inspiratory muscles are unloaded because the RESPIRATORY ALKA LOSIS
expiratory muscles do part of the inspiratory work. This is
depicted by the lighter-shaded area in Fig. 67 B. This mecha- In spontaneously breathing normal subjects, VE is closely
coupled to Paco2 and reflects both rate and Vr responses of
nism is of limited value in patients with severe obstruction,
the ventilatory control system. In mechanically ventilated
however, because low maximal flows prevent significant
subjects, Vr is often preset, thereby uncoupling ventilation
reductions in lung volume below Vrel.
from respiratory drive and confining the influence of neu-
ral control on the regulation of breathing to machine trigger
VENTILATORY PUMP FAILURE AND CHRONlC rate. Consequently, ventilated patients with high intrinsic
C0 2 RETENTIO N respiratory rates can have C02 tensions significantly below
normal. Because associated alkalemia may contribute to ar-
RESTING THE RESPIRATORY MUSCLES
rhythmias and cardiovascular instability,l 53 patients often
In the 1970s and 1980s, much emphasis was placed on res-
are sedated, and the ventilator settings are adjusted with
piratory muscle fatigue as a common cause of ventilatory
the goal of raising Paco 2 • In most instances of ventilator-
failure. 145 Experimental evidence, however, that this truly
induced hypocapnia, tachypnea is unrelated to hypoxemia
occurs in a clinical setting remains elusive. 146 Without ad-
or increased C0 2 drive per se. The causes of tad1ypnea may
dressing all the pros and cons of minimizing the patient's
be behavioral in origin, as with pain and anxiety syndromes,
contribution to inspiratory work, evidence is mounting that
or neurohumoral in origin, as with circulatory failure or in
mechanical ventilation inhibits respiratory motor output
conjunction with lung and airway inflammation. Because
primarily through mechanoreceptive pathways. Studies on
tachypnea and increased ventilatory drive rarely are caused
volunteers and patients have shown that depending on
by C02 itself, any means of reducing ventilator-delivered
state and ventilator settings, spontaneous respiratory mus-
volumes is effective in raising Paco2 •
cle activity can be abolished, reduced, or entrained to the
ventilator. 147- " 49 Two respiratory control aspects of patient-
ventila tor interactions deserve particular emphasis. First, ASYNCHRONY BETWEEN THE PATIENT'S EFFORT
volume-preset mechanical ventilation at settings that nor-
AN D MACHINE-DELIVERED BREATH S
malize blood gas tensions provides no safeguard against
excessive respiratory work. 46 This means that ventilating Asyncl1rony between vigorous spontaneous efforts and
patients in a volume-preset assist-control mode offers no machine-delivered breaths is often referred to as "fight-
universal g uara ntee for sufficient respiratory muscle rest. ing the ventilator." Because inspiratory efforts often are
Second, sleeping and obtunded patients are susceptible to followed by active expiration in patients with increased
PSV setting- induced central apneas. 28.29 This can lead to drive, discrepancies between machine and patient T, cause
problems if a clinician feels compelled to increase ventilator peak Paw to exceed the alarm (safety) limit (usually set to
support without a mandatory backup in order to reduce the 45 cmH2 0), resulting in premature termination of inspira-
work of breathing at night. If this is done through low IMV tory flow and insufficient ventilation. Although the initial
backup rates, then apneas may trigger ventilator alarms and management should be to raise the fM and increase inspi-
cause arousal and sleep fragmen tation. 150 ratory flow up to 1.5 liters/s, many patients with asyn-
chrony require sedation and, on rare occasions, neuromus-
RESETTING THE CHEMOSTAT cular blockade. It is of note that the mechanisms of action by
It remains controversial whether patients with chronic hy- which sedatives facilitate mecl1anical ventilation have not
percapnia and complicating acute ventilatory pump fail- been fully detailed. When "fighting the ventilator" reflects
ure should be" mechanically"hyperventilated to normoca p- pain and anxiety, their mode of action is easily understood.
nia in an attempt to restore normal chemoresponsiveness. Not all manifestations of respiratory distress, however, are
PSlll machine inflation after the cessation of inspiratory effort,
1 and the presence of airways obstntction, with its propen-
Flow sity for dynamic hyperinflation, all contribute to machine
(IJs)
·I i 1 trigger failure. Note that the reduction in PSV from 10-
5 cmH2 0 and the lower peak volume account for the re-
Volume.
0.8~ duced number of wasted inspiratory efforts. An awareness
(liters) of this problem is important because the physician other-
-<!.2 wise may attribute an increase in madune ra te following
JO reductions in PSV to impending failure or a fatiguing load
Airway
pressure response.
(crnii,.O) Because asynchrony between the patient and machine is
· 10 -----------------------------------
common, its diagnostic and prognostic significance remains
tmcertain. When asynchrony impairs ventilator assistance
or causes patient discomfort, treatment is required in the
fonn of sedation a nd adjustments in CPAP, rate, flow, or
l'SS trigger mode. When "wasted" ins piratory efforts are not
perceived as uncomfortable, however, it is not clear that
Flow
(Us) --------------.. -------- .. .. .. --- adjustments in ventilator settings are warranted. After all,
increases in machine rate to match the rate of patient ef-
-1 i forts may cause worsening dynamic hyperinflation and may
0.8 compromise circulation.
Volume
(liters) /
... L .. - - - - ------ .. -- .. - - - ---
-0.2
lO References
Airway
press~ ·
(cml{p) 1. Shibata K, Cregg N, Engclberts D, et al. Hypercapnic acidosis
-10
-------------- ------------------------ ------- may attenuate acute llmg injury by inhibition of endogenous
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CHAPTER 6 SETIING THE VENTILATOR 181
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Chapter 7 _ _ _ _ _ __ _ _ __ Basic Principles
ASSIST-CONTROL In ACV, mechanical breaths can be triggered by the ventila-
tor or the patient. With the former, triggering occurs w hen a
VENTILATION certain time has elapsed after the previous inspiration if the
patient fails to make a new inspiratory muscle effort (Fig.
JORDI MANCEBO
7-1). The frequency at which time triggering takes place is
determined by the backup rate set on the ventilator. When
patients trigger a mechanical breath, their spontaneous in-
spiratory effort is sensed by the machine, usually as a change
in airway pressure or airflow (Fig. 7-2). When such a change
crosses the trigger-sensitivity threshold, the ventilator de-
BASIC PRINOPLES livers the preset tidal volume. Most machines delivering
PHYSIOLOGIC EFFECTS ACV are flow controllers because they measure and con-
Inspiratory Muscle Effort trol flow and calculate volume by appropriate flow trans-
Inspiratory Flow Settings and Breathing Pattern ducers. Special valves, run by microprocessors or by ana-
Inverse Inspiratory-to-Expiratory Ratio log electronics, control flow delivery. Their performance is
Respiratory Muscles similar, although it has been claimed that using micropro-
Sleep cessors provides increased flexibility-4 because they are run
RATIONALE, ADVANTAGES, AND LIMITATIONS by software programs. Such valves open and close propor-
INDICATIONS AND CONTRAINDICATIONS tionally by different motor mechanisms: solenoids (a cur-
COMPARISON WITH OTHER MODES rent generates a magnetic field), motor-driven cams, or dig-
Pressure-Controlled Ventilation in Animal Studies ital on-off solenoid systems. In some ventilators, volume is
Pressure-Controlled Ventilation in Acute Respiratory measured directly by volumetric displacement via a built-
Failure Patients in linear motor and a rolling-seal piston. Apart from deliv-
Pressure-Controlled Ventilation and Inspiratory ering gas to the patient, the ventilators control exhalation
Muscle Effort with appropriate valves. Expiratory valves are closed dur-
Intermittent Mandatory Ventilation ing inspiration and open during exhalation. Importantly,
Pressure-Support Ventilation they should provide minimal airflow resistance, which de-
Biologically Variable Ventilation pends on their physical design, and maintain the desired
VARIATION IN DELIVERY AMONG levels of positive end-expiratory pressure (PEEP) through-
VENTILATOR BRANDS out exhalation. This can be achieved w ith microprocessor
ADJUSTMENTS AT THE BEDSIDE active control mechanisms, with inflatable diaphragms, or
TROUBLESHOOTING by pinching silicon tubes. 4
IMPORTANT UNKNOWNS AND THE FUTURE Mechanical breaths have precise mechanisms for being
SUMMARY AND CONCLUSIONS initiated (trigger variable), sustained (limit variable), and
stopped (cycle variable). These are known as phase variables.5
Volume assist-control ventilation (ACV) is a ventilator In ACV, the mechanical breaths are limited by volume
mode in which the machine always delivers the same tidal and/or flow and cycled by volume or time. The limit vari-
volume during every inspiration, whether initiated by the able is that which increases to a preset value before inspira-
ventilator or by the patient. This occurs regardless of the tion ends. The cycle variable is that used to declare the end of
mechanical load on the respiratory system and no mat- inspiration. The inspiratory flow-shape delivery is usually
ter how strenuous or feeble the inspiratory muscle effort. a square (constant) during ACV, although some ventilators
Although it is one of the oldest ventilator modes, cur- also permit sinusoidal and/ or ramp (ascending or descend-
rent data indicate that ACV is still the most frequently ing) gas flows.
used mode in intensive-care units (TCUs). 1 The main rea-
son for patients being admitted to an ICU is the need
for mechanical ventilahon,2 and the most common rea- Physiologic Effects
son to initiate mechanical ventilation is acute respiratory
failure.'1 Mechanical ventilation is a lifesaving supportive treatment
About 60% of intubated, ventilated patients receive ACV that improves gas exchange and decreases the mechanical
and continue mainly w ith this mode throughout the course workload of the respiratory muscles while buying time for
of mechanical ventilation, a t least within the first 4 weeks the patient to recover. The way mechanical ventilation is
of its initiation.3 This percentage is similar for patients ven- used is central to its short- and long-term effects. Ventila-
tilated for acute respiratory distress syndrome (ARDS) or tor settings are a major determinant of the physiologic and
for decompensated chronic obstructive pulmonary disease clinical effects of ACV. The physiologic effects of ACV on
(COPD). 3 An international survey revealed that ACV was gas exchange and cardiovascular function are dealt with in
the preferred mode for 62% of physicians. 1 Chapters 38 and 39.
183
184 PART IV CONVENTIONAL METHODS OF VENTILATION
FLOW
[Lis] 87
time (s]
-1
I I I
87
20 time Is]
Pes
(cmH,O]
Pga
(cmH,OJ
o~~-L-L-L~--L-L-~~-L-L~~--L-~~-L-L-L~~~L-~~-L-L-L~--L-L-~-
1 57 87
time (s]
_,
FIGURE 7-1 (From top to bottom) Tracings of airflow (flow), airway pressure (Paw), esophageal pressure (Pes), gastric pressure (Pga), and
tidal volume (volume). Each mark on the time axis denotes 1 second. These recordings were obtained in a passively ventilated patient
Each breath is time-triggered.
.FIGURE 7-2 (From. t op to b ottom) tracings of airflow (flow), airway pressure (Paw), esophageal pressure (Pes), gastric pressure (Pga), and
tidal volume (volume). Each mark on the time axis denotes 1 second. These recordings were obt.a ined during patient-triggered
assist-control ventilation (ACV). Every spontaneous inspiratory muscle effort is followed by a mechanically delivered breath. Note th e
delay between the beginning of inspiratory effort (Pes tracings) and the beginning of the mechanical breath (Paw tracings). The presence
of intrinsic PEEP and the demand-valve sensitivity setting account for this delay.
FLOW
11-/s) 83
time (s)
-1
20
Pga
(em H2 0]
0
63 83
ume (s]
VOLUME
(L] 83 83
time (s)
-1
CHAPTER 7 ASSIST-CONTROL VENTILATION 185
In every assisted mode, the ventilator responds to a pa- (1 second w ithout end-inspiratory pause), as well as differ-
tient's inspiratory effort. Both pressure- and flow-triggering ent inspiratory time settings (0.6 and 1 second), with the
systems of modem ventilators offer high performance, and same tidal volume (8 ml/kg). When inspiratory flow was
the differences are small in terms of added work of breath- reduced either by reducing tidal volume or by lengthening
ing. Flow triggering, however, seems slightly superior to inspiratory time, work of breathing was increased consis-
pressure triggering during pressure-support ventilation tently. The duration of diaphragmatic contraction was un-
(PSV) but not during ACV. Thjs is p robably true because of affected by the ventilator settings and always was shorter
the relatively small effort needed to open the demand valves than 1 second.n Thus it appears that the effects of high air-
in comparison with the total effort made during the whole flow settings on muscle unloading are mainly exerted at the
inspiration and because the fixed inspiratory flow during very begi1ming of inspiratory efforts.
ACV does not necessarily match the patient's demand. 6 Compared with spontaneous breathing, Leung et al12 re-
ported a fivefold reduction in inspiratory effort during ACV
adjusted to deliver a tidal volume oflO ml/kg and an inspi-
INSPIRATORY MUSCLE EFFORT
ratory flow of 60 liters/ min. Although such settings induced
Marini et af reported that decreases in trigger sensitivity a major decrease in the sensation of d yspnea, they also were
increased work of breathing. Although decreasing the in- accompanied by the highest number of inspiratory efforts
spiratory flow rate from 100 to 80 liters/min did not af- failing to trigger the machine. The patients, who mostly had
fect the effort to breathe at a moderate minute ventilation obstructive airway disease, were ventilated without PEEP.
(12 liters/min), it increased the work expenditure signifi-
cantly when the minute ventilation was doubled? When
INSPIRATORY FLOW SETTINGS AND
inspiratory flow was reduced to 40 liters/ min and thus did
BREATHING PATTERN
not match the subject's demand, the work of breathing in-
creased by 50%. Marini et al8 later analyzed the inspiratory A number of authors have shown that patients11 •13- l5 and
work at two inspiratory flow settings,60 and 100 liters/min, healthy individuals 16, 17 react to an increase in inspiratory
in 20 patients. Tidal volume was unchanged. Such airflow flow with an increase in respiratory rate when tidal volume
rates generally exceeded those measured during unassis ted is kept constant. In these circumstances, the imposed venti-
breathing. The patients' work per liter of venHlation at both lator inspiratory time shortens as flow increases. This leads
ACV inspiratory flow settings represented around 60% of to a decrease in neural inspiratory time. When tidal volume
the work dissipated during spontaneous breathing. In com- is increased by lengthening the duration of inspiratory flow,
parison with the nonsedated state, sedation a nd curariza- neural expiratory time increases, and respiratory rate tends
tion rud not modify the work to inflate the respiratory sys- to decrease. These cl1anges have opposite effects on res-
tem. Dead space was added in half the patients and led to piratory rate. The mecl1anisms explaining these responses
marked increases in muscle effort. Patients' work of breath- are complex and include the Hering-Breuer reflex (inhibits
ing did not correlate with minute ventilation, although it inspiration and prolongs expiration), reflexes mediated
was highly correlated with respiratory drive and muscle by vagal mechanoreceptors, and perhaps consciousness-
strength. A decrease in inspiratory flow to 40 liters/min (in mediated reflexes.18- 20 A study in nonintubated normal
five pa tients) led not only to an increase in effort but also subjects who were ventila ted with ACV21 also reported the
to premature expiratory efforts, encroaching on the ventila- greatest breathing discomfort when inspiratory flow rates
tor's inspiratory time. In total, these data demonstrated that were at the extremes of those tested: 25 and 93 liters/min.
inspiratory muscle effort persists throughout the inflation Discomfort was minimal when flow rates were set at 34 and
and that a substantial amount of muscle work is dissipated 63 liters/ min.
during ACV. Airflow-induced changes in breathing pattern carry im-
Ward et a19 analyzed the inspiratory muscle effort a t sev- portant clinical implications, especially in patients with dy-
eral inspiratory flow rates between 25 and 651iters/mjn and namic hyperinflation. Because inspira tory time is made up
two trigger-sensitivity settings, -2 and -5 cmH2 0. Tidal vol- of the time of flow delivery and inspiratory pause, Laghi et
ume was constant, and no PEEP was used. As expected, the al 14 hypothesized that a decrease in ventilator inflation time
less sensitive the trigger sensitivity, the more work the pa- would cause an increase in rate. In 10 noninvasively ven-
tients performed. As inspiratory flow rate increased, inspi- tilated stable patients with an obstructive airway disease,
ratory muscle effort decreased. During time-triggered ACV, the authors increased flow at constant tidal volume and
in particular at inspiratory flow rates of 45 liters/min or decreased the inspiratory pause, keeping inspiratory flow
lower, the muscles contracted after the onset of inspiratory and tidal volume constant. Decreasing inspiratory time by
flow. 9 The authors suggested that the s timulus for muscle increasing flow from 30-90 liters/ min increased both respi-
contraction, rather than arising from a generalized increase ratory rate and expiratory tin1e significantly. Intrinsic PEEP
in respiratory drive, arises within the breath in response to diminished significantly despite the increase in respiratory
an abnormal imposed flow pattern. Flick et a110 analyzed rate. When inspiratory time was decreased by shortening
the duration of the diaphragmatic contraction at different the inspiratory pause, both respiratory frequency and ex-
ACV settings by using electromyography. They found that piratory time increased significantly. Again, this decreased
the diaphragma tic activity persisted well after triggering. intrinsic PEEP significantly. Additionally, the higher inspi-
Cinella et al11 analyzed the effects of different tidal vol- ratory flow rates also decreased respiratory drive and inspi-
umes (12 and 8 ml/kg) with an unchanged inspiratory time ratory effort. These results s uggest that imposed ventilator
186 PARTIV CONVENTIONALMETHODSOFVENTILATION
inspira tory time duration d etermines the respiratory rate significant diaphragmatic myofibril damage had occurred.
and that the strategies that reduce ventilator inspiratory This investiga tion supports the notion that a decrease in
time, although accompanied by tachypnea, also prolong the diaphragmatic force-genera ting capacity depends on time
time for exhalation, thus decreasing intrinsic PEEP. and that muscle inactivity is associated with injury. Simi-
lar data have been reported by others studying the same
animal species.35 Yang et a136 reported structural remod-
INVERSE I NSPIRATORY-TO- EXPffiATO RY RATIO eling of the diaphragm in rats under passive ACV for
4 days. They also found a decreased diaphragm-to-body-
ACV has been used with inverse inspiratory-to-expiratory weight ratio and a decrease in the m aximal force gener-
(I:E) ratio (i.e., > 1:1 ). The rationale is that a lower inspi- ated by the diaphragm as compared with spontaneously
ratory flow may improve intrapulmonar y d istribution of breathing controls. Several investigators37 - 39 have begun to
gas (via a better mixing of gas or by improving the efficacy
elucidate the complex cellular and molecular mechanisms
of collateral ventilation), reduce dead space, improve the underlying passive ventilation-induced respiratory muscle
ventilation-to-perfusion relationships, and enhance alveo- damage.
lar recruitment.22' 23 Recent findings by Sassoon et al40 carry important clini-
In an experimental study of oleic acid- induced lung
cal implications. The authors found that ACV, as compared
injury/ 4 the short-term effects of ACV with PEEP were
with passive ACV, can attenua te markedly the decrease
compared with those of inverse-ratio ACV at the same to-
in diaphragmatic force induced by total inactivity in rab-
tal PEEP. The authors found no differen ces in lung me-
bits. Another investigation with clinical ramifications has
chanics, hemodynamics, gas exchange, or computed to- shown that passive ACV improves diaphragmaticforce pro-
mogra phic lung densities. In sheep with bronchoalveolar duction in rats challenged with intravascular endotoxin as
lavage-induced acute lung injury, Mang et al25 analyzed compared with equally challenged spontaneously breath-
the effects of ACV and PCV (both with PEEP) a t different ing anirnals.41
I:E ratios while maintaining the mean airway pressure con-
If passive ventilation is one extreme, the other is a fatigu-
stant. No differences were found in gas exchange or hemo-
ing loading. Both extremes are harmful to the respiratory
dynamics, most probably because mean airway pressure muscles. Normal subjects submitted to inspiratory resistive
did not change. loading up to a fatiguin g threshold s howed a decrease in
In a study that compared ACV with inverse-ratio ACV, no
diaphragmatic contractility lasting for at least 24 hours. 42
differences in gas exchan§e were reported in patients with Jiang et al43 showed diaphragmatic injury and inflamma-
acute respiratory failure. 6 Mercat et al27 compared ACV
tion at 3 days after a 90-minute p eriod of acute moderate
with and without inverse-ratio ACV (l:E ratio2:1 versus 1:2)
and high inspiratory resistive loading in rabbits. The same
at unchanged total PEEP, respira tory rate, and tidal volume
group44 subsequently reported a marked decrease in the
in patients with ARDS. No advantages in terms of arterial force production of the diaphragm at 3 days after high in-
oxygen tension (Pae:,) were seen . In the first hour of the spiratory resistive loading over the same time. Such stress
study, cardiac index, oxygen delivery, and Pace:, were lower also induces selective upregulation of a mm1ber of cytokines
with inverse-ratio ACV, but differences d isappeared over in the diaphragmatic fibers and eventually may lead to sys-
time. temic effects. 45•46
RESPlRATORY MUSCLES SLEEP

Mechanical ventilation per se can induce respiratory mus- Sleep is new area of investigation in patients admitted to
cle damage,28 - 30 and patients appear to exhibit diaphrag- an lCU. Studies using appropriate tools reveal tha t pa-
matic weakness after a period of mechanical ventilation.31 tieJ1ts have major sleep disturbances in terms of quantity
Le Bourdelles et al32 showed that anesthetized, passively and quality.47 The acuity of illness, the use of medica-
ventilated rats had lower diaphragmatic weight a nd a re- tions (such as sedatives or opioids), the caregivers' inter-
duction in their force-generating capacity in comparison ventions, and the environmental elements are contributing
with spontaneously breathing control animals. The force- factors. Gabor et a1 48 indicated that only 30% of sleep dis-
generating capacity was not reduced in peripheral mus- ruption in ventilated patients was attributable to elements
cles, and the authors suggested that this might be sec- of the ICU environment. A large proportion of sleep dis-
ondary to the prior his tory of muscle activation. Anzueto ruption was unexplained, and-quoting preliminary work
et al33 studied sedated, paralyzed baboons under ACV for by Parthasarathy et al- the authors suggested the mode of
11 days. Endurance time decreased over this period, and ventilation a nd patient-ventilator dyssynchrony as plausi-
transdiaphragmatic pressure diminished by 25%, suggest- ble explanations.48
ing that the duration of passive ACV is also a relevant Parthasarathy and Tobin49 sought to determine if sleep
factor. quality was influenced by the m ode of ventilation. They
Sassoon et al34 showed that 3 days of passive ventilation in hypothesized that sleep is more fragmented during PSV as
rabbits led to a progressive decrease in the force-generating compared to ACV because of the development of central
capacity of the diaphragm in comparison w ith control an- apneas. Eleven pa tients were ventilated with ACV at tidal
imals who received the same total amounts of sedatives volumes of 8 ml/kg, inspiratory flow rate 1 llter/s, and a
but were breathing spontaneously. They also showed that backup rate of four breaths below the total assisted ra te. PSV
was set to deliver the same tida l volume. Patients also re- Some settings are almost impossible to achieve with ACV.
ceived PSV with 100 ml of added dead space. During wake- For instance, the simultaneous adjustment of a moderate
fulness, respiratory rate was similar with the two modes. tidal volume at a high inspiratory flow rate will produce
During sleep, minute ventilation fell more during PSV than a short machine inspiratory time, which under certain cir-
with ACV. Sleep fragmentation, measured as the number of cumstances may not match the patient's neural inspiratory
arousals and awakenings, was significantly greater during time properly. In addition, the patient's varying ventilatory
PSV than during ACV (79 versus 54 events per hour) . Six needs and the d1ange in the mechanical properties of the
patients had apneas while receiving PSV a nd none while respiratory system over the course of ventilation imply that
receiving ACV. The percentage of patients who had conges- periods of underassist are likely to be interspersed with pe-
tive heart failure was significantly higher among patients riods of overassist. These problems, however, are common
exhibiting apneas than among patients free of apneas (83% to virtually all ventilator modes.
versus 20%). Minute ventilation during sleep was greater
in patients who did not develop apneas, suggesting that in-
creased drive protects against the development of apneas. Indications and Contraindications
The addition of dead space reduced the number of apneas
markedly: from 54 to 4 apneas per hour. Whether or not ACV is indicated when a life-threatening physiologic de-
similar results would be obtained with PSV titrated at lower rangement in gas exchange or cardiovascular dynamics has
levels of assist is unknown. not been corrected by other means. Clinical manifestations
of severely increased work ofbreathing or impending r espi-
ratory arrest are indications for instituting ACV.50 Although
Rationale, Advantages, and Limitations there appear to be no absolute contraindications to ACV,
some of its shortcomings may prompt physicians to use
The main reasons for using ACV are to unload the inspi- other modes.
ratory muscles and to improve gas excl1ange. ACV permits
complete respiratory muscle rest, which is usually the case
when patients do not trigger the machine, and a variable de-
gree of respiratory muscle work. ACV commonly adlieves Comparison with Other Modes
an improvement in gas exchange, and only a minority of
ventilated patients die because of refractory hypoxemia. The main difference between ACV and PCV is that with the
During passive ventilation with ACV at a constant in- latter the ventilator functions as a pressure controller, and
spiratory flow, fundamental variables related to respiratory it is a pressure-limited and time-cycled mode. The trigger
system mechanics, such as tidal volume, inspiratory flow, variable is identical to ACV. With the PCV mode, delivery
peak airway pressure, end-inspiratory plateau airway pres- of airflow and tidal volume cl1anges according to the me-
sure, and total PEEP (the sum of external PEEP and intrinsic chanical impedance of the respiratory system and patient
PEEP, if any), are measured easily (Fig. 7-3). These variables inspiratory muscle effort. This mechanism implies that ev-
allow calculation of resistance, compliance, and the time ery increase in trans pulmonary pressure is accompanied by
constant of the respiratory system. an increase in tidal volume.
If airway pressure tracings are obtained during passive
ACV as well as during patient-triggered ACV at the same PRESSURE- CONTRO LLED VENTILATION
settings, we can estimate a patient's work of breathing sim- IN ANIMAL STUDIES
ply by superimposing the two tracings (Fig. 7-4). When pa-
tients are triggering the breaths, the end-inspiratory plateau In rabbits with oleic add- induced lung injury, Ludwigs
pressure also can be influenced by the amount and du- et aJ 5'l compared ACV with PEEP and inverse-ratio PCV
ration of inspiratory muscle effort (Fig. 7-5). When me- at equal total PEEP and found that arterial oxygenation and
cllanical breaths are triggered by tl1e patient, the scoop- a radionuclide index of ltmg epithelial permeability both
ing on the airway pressure profile allows indirect evalu- worsened during inverse-ratio PCV. Recently, Maeda et al 52
ation of patient-ventilator interaction (Fig. 7-6). Such capa- compared ACV at I:E ratios of 1:4 and 1:1 with pressure-
bilities are unique to ACV. These capabilities represent a regulated volume control ventilation at an I:E ratio of 1:4 in
major advantage because they enable one to properly under- healthy animals. After 6 hours, the animals ventilated witll
stand respira tory system mechanics and patient-ventilator pressure-regulated volume control, which delivered a high
interactions. peak inspiratory flow, exhibited a greater decrease in Paa:
A major limitation of ACV is tl1at it imposes a number and respiratory system compliance and more macroscopic
of constraints on the variability of the patient's breathing and microscopic lung injury in comparison with animals
pattern: inspiratory flow, inspiratory time, and backup rate. undergoing tl1e other two modes.
Adjusting ACV settings may be more complex than with
pressure-lin1ited modes. One reason is that manufacturers
PRESSURE-CONTRO LLED VENT ILATION IN ACUTE
employ different algorithms for implem enting the delivery
RESPIRATORY FAILURE PATIENTS
of a tidal breath. The other reason is that during ACV it is dif-
ficult to pinpoint the inspiratory flow rate and tidal volume Numerous studies53- 61 have compared the effects of PCV
settings that are optimal for an individual patient (Fig. 7-7). and ACV. These are surnmarized in the Table 7-1. They are
FLOW
fl.lsJ
~r
I
rr
I I
r- ( r
I I I I I I
( I
I I
(~
!f l38
I
me {s)
-1
40
- J A A
I .J I I I 1 ..t I I 1 .I I I
8 38
·10
lime (s)
.,
FIGURE 7-3 (From top to bottom) Tracings of airflow (flow), airway pressure (Paw), and tidal volume (volume). Each mark on the time
axis den otes 1 second. Note that expiratory fl ow is interrup ted by the beginning of each breath, thus herald in g dyn amic hyperinflation. A
prolonged end-inspiratory occlusion (fourth breath from the left) enables measurement of the static recoil p ressure of the respiratory
system. A prolonged end-expiratory occlusion (sixth b reath from the left) illustrates the presence of intrinsic PEEP (3 cmH2 0 ). These
values, together with p eak airway pressure, inspiratory flow rate, and tidal volume, enable the calculation of resistance, compliance, and
respiratory system time constant in passively ventilated patients.
all s hort-term studies with a limited nwnber of patients. time of 1 second and no end-inspiratory pause. At high
Different adjustments were used. Taken together, no majo r tidal volumes, no di fferences were observed between the
differences in terms of gas exchange seem to emerge be- two modes in terms of breathing pattern or indexes of in-
tween ACV and PCV. spiratory muscle effort. When a tidal volume of 8 ml/ kg
A randomized monocenter trial performed with a small was used (and thus inspiratory flow decreased with ACV),
number of pa tients 62 showed an early trend toward respi- differences arose. Respiratory rate and occlusion pressure (a
ratory system compliance improvement during PCV com- measure of respiratory drive) tended to be higher with ACV,
pared with ACV. Differences in gas excha nge between the and indexes of inspiratory muscle effort showed a marked
two modes were minimal. In a randomized multicenter increase as compared with PCV.
study,63 PCV and ACV were compared. End-inspiratory In a second part of this study'~~ the authors compared the
plateau airway pressure was kept at a maximum of effects of ACV and assist PCV using a fixed tidal volume
35 cmH20 during both modes, and I:E ratio adjustment was (8 ml/kg) and two different settings for inspiratory time:
at the discretion of the physicians. This resulted in a sim- 1 second and 0.6 second with no pause. With the longer
ila r inverse I:E ratio in the two groups, about 2:1. Arterial inspiratory time, the differences were the same as stated
oxygenation did not differ between the m odes. ICU mortal- previously. When inspiratory time was reduced and thus
ity was 69% (29 of 42 patients) in the ACV group and 49% inspiratory flow increased during ACV, however, the dif-
(18 of 37 patients) in the PCV group; the difference was not ferences between the modes virtually vanished . The study
significant. A multivariate analysis did not find ventilato r sh owed that both modes unloaded the respiratory muscles
mode to be independently associated with increased mor- equally, provided that the inspiratory flow rate was set a p-
tality. Although difficult to interpret, this study cast doubts propriately during ACV. These data confirm the importance
on the usefulness of inverse-ratio ACV in patients with of maintaining an inspiratory flow rate high enough to un-
ARDS. load the respiratory muscles adequately and also point out
that moderate- to low-tidal-volume ventilation using high
flow ra tes results in a short inspiratory time, which may not
PRESSURE-CONTROLLED VENTILATION AND be optimal for some patients. Similar resuJts were obta ined
INSPIRATORY MUSCLE EFFORT
by Mcintyre et al64 comparing ACV w ith a pressure-limited
Cinella et al11 compared ACV and assist PCV and used two volume-guaranteed dual mode. These a uthors, however,
tidal volume settings (12 and 8 ml/ kg) with an inspiratory suggested that the pressure-limited breaths could reduce
CHAPTER7 ASSIST-CONTROL VENTILATION 189
an increased C02 production, presumably caused by an in-
FLOW crease in work of breathing.
[1 LIS) Marini et al67 compared ACV (100% IMV) with IMV to
provide 80%, 60%, 40%, 20%, and 0% of the ventilation ob-
served during ACV. Tidal volume and flow settings dur-
ing ACV were 10 ml/ kg and 1 liter/s, respectively, and
average respiratory rate was 23 breaths per minute. The
total breathing frequency and spontaneous tidal volume in-
creased as far as IMV assistance was decreased. Duration of
inspiratory effort during assisted breaths was similar across
the different IMV levels. At all levels of support, patients
perfom1ed a substantial effort during the machine-assisted
breaths that increased p rogressively as IMV assistance was
withdrawn. These data emphasize several points. Machine
assistance does not suppress patient effo.rt. There is a poor
adaptation to VE!lltilator assistance on a breath-by-breath ba-
sis, suggesting that the intensity of muscle effort is fixed
Pes before cycle initiation. Off-switching of inspiratory muscle
(10 cmH 2 0 L) contraction is independent of volume and flow ventilator
settings.
Leung et al 12 compared ACV, IMV (80%, 60%, 40%, and
20% levels of assist), pressure support (100%, 80%, 60%,
40%, and 20% levels of assist) and a combination of IMV
with a pressure support of 10 cmH2 0. No PEEP was used .
Average tidal volume and respiratory rateduringACV were
VOL 600 ml and 17 breaths per minute, respectively. The ob-
[1 L) served rate during ACV was considered equivalent to IMV
100%. Pressure support 100% (average 17 cmH 20) was the
level of assistance that resulted in U1e same tidal volume
as during ACV; this led to a respiratory rate of 16 breaths
per minute. Nontriggering atten1pts occurred with every
TIME [S] mode and were most numerous at the highest levels of as-
1 second
sistance. At 100% levels of assistance, the inspiratory ef-
FIGURE 7-4 (From top to bottom) Tracings of airllow (flow), fort and dyspnea sensation were similar among the modes,
airway pressure (Paw), esophageal pressure (P es), and tidal
and both increased progressively when assistance was de-
volume (volu me). Each mark on the time axis denotes 1 second.
creased. When the tota l inspiratory effort was partitioned
The tracings in each pan el were obtained from the same
individ ual at two d ifferent times. They were then superimposed. between its triggering and posttriggering components, the
Ventilator settings wer e identicaL The vertical line on the airflow, former was tmchanged despite varying levels of ventilator
airway pressure, and esophageal pressure tracings in dicates th e assistance. The posttriggering effort, however, was highly
end of ventilator's total inspiratory time. The dotted areas within correlated with the respiratory drive at the beginning of the
the airway p ressure and esophageal pressure tra cings are breath.
identical. The dotted areas denote the amoun t of inspiratory
muscle effort that the patient mad e du ring the assisted breath.
PRESSURE-SUPPORT VENTILATION
patient-ventilator flow dyssynduony, although total inspi-
Tokioka et al68 compared ACV witl1 pressure-support ven-
ratory effort was similar between the modes, and tidal vol-
tilation (PSV) set to achieve the same value of peak air-
ume was significantly higher with the pressure-limiting way pressure as during ACV. This resulted in PSV levels of
strategy. 27 cmH2 0 above a PEEP of 12 cmH20. With these settings,
tidal volume was significantly higher and machine respira-
tory rate significantly lower during pressure support. These
INTERMJTTENT MAND ATORY VENTILATION
data indicate that peak airway pressure during ACV is an
Early studies compared ACV with intermittent mandatory inappropriate surrogate variable to adjust pressure support
ventilation (IMV). In a study by Hudson et al, 65 the manda- to get similar levels of assistance. Tejeda et al 69 compared
tory rates were 50% and 25% of the ACV rate. In a study by ACV with PSV in patients with respiratory failure of as-
Groeger et al, 66 the mandatory rates were 50% of the ACV sorted etiologies. PSV was adjusted to deliver the same tidal
rate, and patients always remained normocapnic. Patients volume as with ACV, although it actually resulted in signif-
in the study of Hudson et al were markedly hypocapnic icantly higher tidal volumes. The authors fetmd a slightly
and alkalotic during ACV, and a slight increase in Pace, better Pa~ only in a subgroup of patients with restric-
was observed during IMV. This change was attributed to tive disorders. Surprisingly, the calculated shunt in these
FLOW
(Us) 15
time (sl
-2
20
0 ~--~--~--~--L-~~~--~--~--~--~--~---L---L---L---L--~
16
limo (s)
16
time (s]
·1
FIGURE 7-5 (From top to bottom) Tracings of airflow (flow), airway pressure (Paw), transdiaphragmatic pressure (Pes), gastric press ure
(Pga), and tidal volume (volume). Each mark on the time axis denotes 1 second. The time of inspiratory flow is shorter than the duration of
diaphragmatic contraction. This patient did not exhibit expi.r atory muscle recruitment, as indicated by the gastric pressure recording.
Inspiratory muscles relax at the end of the inspiratory pau se tim e, thus explainin g the "M"wave shape on the airway pressure recording.
patients (18-20%) was lower than in patients with COPD breathing pattern, and several indexes of inspiratory muscle
(26- 29%). A significantly higher dead-space-to-tidal- effort were similar between the modes.
volume ratio also was observed during PSV (24%) than ChiumelJo et af1 compared the effects of PSV at 5, 15,
during ACV (18%). These are extremely low values for and 25 cmH2 0 with assist PCV at the same levels of pres-
patients with respiratory failure. For these reasons, the sure and ins piratory time as during PSV and ACV. ACV was
overall clinical significance of these findings is difficult to delivered with a square and decelerating flow pattern, both
judge. matched for the same tidal volume and peak inspiratory
Kreit et afO analyz.ed work of breathing during ACV flow as during PSV. No differences among the modes were
and PSV in 11 patients. During ACV, tidal volume was 10- observed. TI1e authors also compared clinician-titrated PSV
12 ml/kg, and inspiratory flow 75-80 liters/min. PSV was (average 10 cmH2 0) with two ACV modes (square and de-
increased progressively to reach the same tidal volume as celerating flow), both a t two flow settings (high and low).
during ACV. This strategy resulted in an average pres- Tidal volume was always the same. The peak inspiratory
sure support of about 19 cmH20. The authors confirmed flow obtained during PSV (0.78 liter Is) was the high-flow
previous studies indicating that both work of breathing setting for both ACV types. When high-flow settings were
and respiratory rate vary inversely with the PSV level. used, no differences were observed. The low-flow setting,
With such adjustments, the patient's work of breathing about 0.64 liter/s, induced a significant increase in work
and minute ventilation were almost identical between the of breathing without differences in respiratory rate or gas
modes. exchange.
In a study not specifically designed to compare ACV with In a very selected population of patients w ith acute lung
PSV, Aslanian et al6 used the average tidal volume mea- injury, Cereda et aln studied the physiologic changes that
sured during clinician-titrated PSV for later adjustments appeared during the 48 hours after the transition from ACV
of ACV. PSV levels were set at a target respiratory rate of to PSV. Hemodynamics and oxygenation were similar. An
between 15 and 30 breaths per minute, which resulted in increase in minute ventilation and a lower Paco2 were ob-
an average pressure support of 16 cmH20 and an average served during PSV. Of 48 patients, 10 did not tolerate PSV.
tidal volume of 500 ml. Settings during ACV were tidal vol- TI1ese patients had a lower static compliance a nd a higher
ume 500 ml with an inspiratory flow rate at 50 liters/min. dead-space-to-tidal-volume ratio when compared with pa-
With such adjustments, respiratory rate, minute ventilation, tients who succeeded. These data suggest that PSV might
FLOW
(Us]
_,
40
o~~--~~~~--~-L--~~--~~--~~--~--~-L--~~--~~--~~-
20
lJ a
time (s)
5 25
time (s)
-10
VOLUME
Ill 25
time tsl
_,
FIGURE 7-6 (From top to bottom) Tracings of airflow (Bow), .Urway pressure (Paw), esoph ageal pressure (Pes), and tidal volume (volume).
Each mark on th e time axis den otes 1 second. The scooping on the airway pressure recording immediately after peak inspiratory flow
delivery is ap paren t on aJI these assisted breaths.
be an alternative to ACV in carefully selected patients with other. Other studies73•75- 77 reported benefits of variable ven-
acute ltmg injury. tilation over ACV in terms of arteria l oxygenation, lung me-
chanics, degree of lw1g edema, proinflammatory cytokine
production, or combinations of these. Variable ventilation
BIOLOGICALLY VARIABLE VENTILATION may induce a better d istribution of tidal volume- thereby
Tidal volume during ACV is, by design, delivered in a matching ventilation to perfusion-better recruitment, and
monotonous manner. To recreate the spontaneous variabil- increased surfactant production. Whether these putative
ity of physiologic rhythms, mechanical ventilation using benefits are attributable directly to the ventilator mode per
computer-generated biologic variability in respiratory rate se, the type of injury, the animal species, the ventilator set-
and tidal volume has been used. The goal of this approach is tings (degree of variability, PEEP levels), or the respiratory
to improve gas exchange and respiratory system mechanics system mechanical characteristics is unclear. The physio-
and minimize ventilator-induced lung injury. Data compar- logic effects of this new mode in patients with acute lung
ing ACV w ith ventilation achieved with randomly variable injury are unknown.
tidal volumes and respiratory rates have been obtained in
several experimental models of acute lung injury?3 - 77 Mod-
els include different animal species (e.g., rodents, pigs, and
Variation in Delivery among
dogs), different type of insults (e.g., chemical, mechanical, Ventilator Brands
and biological), and different ventilator settings (e.g., PEEP
or no PEEP). In these short-term experiments, variable ven- This section does not pretend to explain exhaustively the
tilation was matched to ACV in terms of minute ventilation. working principles of the dozens of different mechanical
The study by Nam e t al74 in a canine oleic acid- induced ventilators available on the market. It only explains some
lung-injury model showed no benefits of one mode over the major differences in the way ACV settings a re to be adjusted .
FlOW
[I.JsJ
-2
Paw
(cmH:20J
10
22
-20
1
VOLUME
Ill 22
time(sJ
·I
FIGURE 7-7 (From top t o bottom) Tracings of airflow (flow), airway pressure (Paw), esophageal pressure (Pes), and tidal volume (volume).
Each mark on th e time axis denotes 1 second. Note the marked breath-by-breath variabili ty in inspiratory muscle effort (esophageal
pressure swings) and airway pressure profile. Thei e is profound patient-venti lator dyssynchrony, and n\Jmerous in spiratory attempts fail
to trigger the venti lator. It is also remarkab le how difficult it can be to estimate the end-inspiratory plateau airway pressure in such
circumstan ces.
TABLE 7-1 Compar ison of ACV and PCV in Acute Respiratory Failure
Author, Year
(Reference) Modes Matching Measurements Main Findings
Abraham , 1990 ACV, PCV Same total PEEP Gas exchange, hemodynamics Gas exchange improved
(53) with PCV
M ufioz, 1993 ACV decelerated flow, Same intrinsic PEEP Gas exchange, mechanics Compliance higher wi th
(54) PCV, no PEEP PCV
Mcrcat, 1993 ACV, PCV, PCV-IR Same total PEEP Gas exchange, hemodynamics Pac~ , card iac index, and
(55) Ch delivery lower wi th
PCV-IR
Lessard, 1994 ACV, PCV, PCV-IR Same total PEEP Gas exchange, hemodynamics, Pao2 and systemic blood
(56) medmnics pressure lower and mean
airway p rcssme higher
with PCV-IR
Mancebo, 1994 ACV, PCV-IR Same tota l PEEP, Gas exchange, hemodynamics, Mean airway pressure
(57) respira tory rate, and mechanics higher with PCV-IR
tidal volume
Davis, 1996 ACV, ACV decelerated Same setting as ACV Gas exchange and Lower Pao 2 and mean
(58) flow, PCV; all with hemodynamics airway pressure with
PEEP ACV
Zavala, 1998 ACV no PEEP, ACV, ACV, ACV-JR, and Gas exchange and multip le Pac~ improved and shunt
(59) ACV-fR, PCV-IR PCV-IR; all with same inert-gas elimination decreased with ACV
PEEP technique Pac~ and dead space
decreased with PCV-lR
Prella, 2002 ACV, PCV Patients' needs Gas exchange and gas Better gas distribution at
(60) distribu tion by computed end expiration d uring
tomography PCV
Ed ibam, 2003 ACV, PCV, PCV-IR Same total PEEP, Gas exchange, hemodynamics, More overinflated u nits at
(61) respiratory rate, and mechanics, and gas end inspiration durin g
tida l volume d istribution by computed PCV-IR, suggesting
tomography h1rther stretch
ABBREVIATIONS: PCV, pressure-oontrolled ventilation; PCV-IR, inverse-ratio, pressure-controlled ventilation; ACV-IR, inverse-ratio, assist-<:ontrol ventilation.
The decision to stick with one style or another depends inspiratory pause time. Respiratory rate and tidal volume
solely on the manufacturer. The fundamental settings dur· are mandatory for all three.
ing ACV are respiratory rate, tidal volume, and inspiratory With the Siemens Servo 300,64 the required adjustments
flow rate. The backup respiratory rate determines the to- are tidal volume, respiratory rate, inspiratory time (from
tal breath duration, and both tidal volume and inspiratory 10-80% of total cycle duration), and inspiratory pause time
flow rate determine the duration of mechanical inflation (from 0-30% of total cycle duration). The maximal I:E ratio is
within a breath. The inspiratory pause, if used, appears im- 4:1. The Maquet Servoi ventilate~ allows a choice of inter-
mediately after the machine's flow delivery has ceased and nal configur ations, either tidal volume and respiratory rate
thus increases the inspiratory time. The expiratory time is or minute ventilation and respiratory rate. Each one of these
the only part of the breathing cycle that is allowed to vary is also internally configurable, either inspiratory time or I:E
when a patient triggers an ACV breath. For this reason, we ratio. The inspiratory pause time is adjustable from 0-30%
consider machines that require I:E ratio adjustment during of total cycle duration and is independent of the preselected
ACV to be totally counterintuitive. interna l configuration. This machine has a particular feature
The Puritan-Bennett 7200,78 740, 760,79 and 84080 venti- during ACV: If airway pressure drops more than 3 cmH 2 0
lators allow direct setting of respiratory rate, tidal volume, during the inspiratory time window, for instance, because
inspiratory flow rate, and inspiratory pause time. In my of a huge inspiratory muscle effort, the ventilator delivers
opinion, this is the most comprehensive approach because more flow. The machine does so in a similar way to PSV
the time for flow delivery depends on the tidal volume and and switches off when flow reaches the preset ACV flow
inspiratory flow rate. The I:E ratio thus is a consequence of value. This is obviously a hybrid ACV, and the clinical con-
those settings. sequences of the machine reacting to this change in airway
The Drager Evita 2 ventilatorS' allows direct settings for pressure are unknown. We can speculate what might hap-
respiratory rate, tidal volume, inspiratory flow rate, and I:E pen, however, when ventilating patients w ith ARDS. When
ratio. This kind of configuration mandates that the inspi- they are receiving ACV and make an inspiratory effort that
ratory pause time will vary depending on those settings. it is not well matcl1ed w ith the preset machine settings, the
With this particular ventilator, the airway pressure alam1 ventilator will deliver more flow and volume when faced
(Pmax) limits the peak airway pressure in a way that flow with an increase in muscle effort. Of course, this scenario
decelerates w hen the Pmax threshold is reached, and then (i.e., an increase in volume and transpulmonary pressure)
airway pressure flattens. Flow decelerates throughout the is extremely harmful for these patients. A similar extra flow
remaining total inspiratory time in an attempt to deliver the delivery occurs with the Servo 300. With this macl1ine, how-
preset tidal volume, but the common peak airway pressure ever, extra flow is delivered when the a irway pressure de-
alarm (which is configurated a utomatically at 10 cmH20 creases 2 cmH20 below the preset PEEP level.
above Pmax) does not sound. In these circumstances, the Finally, the Servo 300 and the Servoi have an adjustable
only high-priority alarm tha t alerts caregivers is the minute- inspirator y pressure rise time (from 0- 20% of the total cycle
ventilation alarm. This may occur when tidal volume is ex- duration). When set at 0%, the flow delivery is completely
tremely low. This kind of setting may be dangerous and can squared. At the 20% extreme setting, the peak flow arrives
lead to life-threatening situations, such as in the case of an at the very end of the inspiratory flow delivery time, and
endotracheal tube obstruction. because the volume is controlled, the peak flow increases.
In the Drager Evita 4 ventilator,82 the settings to be ad-
justed during ACV are similar to those of the Evita 2, with
the exception that instead of adjusting the I:E ratio, it is Adjustments at the Bedside
necessary to adjust the totaJ inspiratory time. There is no in-
dependent adjustment of inspiratory pause time. With the Settings to be adjusted in ACV are inspired oxygen concen-
Evita 4 machine, there are two airway pressure alarms. That tration (FI~), trigger sensitivity (to be set above the thresh-
which appears together with the other adjustable settings old of auto-triggering), backup rate, tidal volume, inspi-
in ACV, Pmax, limits airway pressure in the same way as ratory flow ra te (or inspiratory time), a nd end-inspiratory
with the Evita 2. There is another airway pressure alarm pause and external PEEP, if any. When ACV is instituted
that is to be adjusted in the main alarm settings screen, after tracheal intubation, patients usually are sedated and
and it appears in a different ventilator window. The lat- passively ventilated. Proper calculations of compliance and
ter is a true a larm in the sense that when the preset pres- airflow resistance may help in adjusting the ventilator's
sure threshold is reached, the alarm sounds, and the ma- backup breathing pattern. The time constant of the respira-
chine cycles off. In consequence, it is highly advisable to set tory system determines the rate of passive lung emptying.
the Pmax value (which limits pressure) above the level of The product of three time constants is the time needed to
the true airway pressure alarm so as to inhibit Pmax from passively exhale 95% of the inspired volume. 86, 87 If expira-
working. tory time is insufficient to allow for passive emptying, this
The Hamilton Galileo ventiJator83 is user-configurable in will generate hyperinflation.
three different ways. One is inspiratory flow rate and inspi- Mechanical ventilation in specific scenarios, for example,
ratory pause time. The second is I:E ratio and inspiratory patients with obstructive disease, ARDS, and neuromuscu-
pause time. The third allows adjustment of inspiratory time lar disorders, are dealt with in Chapters 31, 33, and 34. Some
as a percentage of the total cycle duration 60 divided by general principles, however, are worth recalling.
backup respiratory rate L60: backup rate]. Example: if rate The goals of mechanical ventilation, in particular dur-
is 15, the total cycle duration is 4(60/15 = 4 seconds), and ing ACV, have changed profoundly in the last decade.
Nowadays, moderate tidal volumes are customary, and nia and res piratory acidosis and require adequate sedation
achieving normocapnia is no longer required per se. This and even neuromuscular blockade in some patients. Cur-
is the case for virtually all mechanically ventilated patients . rent knowledge, however, indicates that this is probably the
One exception, however, is patients with brain injury and less dangerous approach in patients with asthma. 9 1 ~93,%,98
relatively normal lungs, in whom a tight Paco. control is Ventilator settings should be readjusted in accordance w ith
required to avoid undesirable episodes of brain ischemia or the time course of changes in gas exchange and respiratory
hyperemia. system mechanics.
In patients with COPD, Tuxen and Lane88 showed that Most patients with ARDS require m echanical ventilation
at constant minute ventilation, the lowest degree of dy- during their illness. In this setting, mechanical ventilation
namic hyperinflation was obtained when ventilation was is harmful when delivering high tidal volumes.99 -100 There
performed at a high inspiratory airflow and long expira- is general agreement that end-inspiratory plateau airway
tory time. 88 These data indicate that the quotient between pressure should be kept at values no higher than 30-35
tidal volume and expiratory time-mean expiratory flow- cmH 20. End-inspiratory plateau airway pressure, however,
is the principal ventilator setting influencing the degree of is a function of tidal volume, total PEEP level, and elastance
dynamic hyperinflation.87, 88 Connors et al 89 showed im- of both the ltmg and chest wall. Importantly, patients with
provements in gas exchange using high inspiratory airflows ARDS have small lungs with different mechanical character-
and suggested that they produced a more even distribu- istics of the lw1gs and chest wall,l 01,102 and recommending
tion of ventilation. At the present time, a physiologically a single combination of tidal volume and PEEP for all pa-
sound recommendation can be made when initiating ACV tients is not sound. Patients with more compliant lungs pos-
in these patients. A moderate Fro 2 , usually 0.4, suffices to sibly can receive somewhat higher tidal volumes than those
improve hypoxemia; an arterial oxygen saturation of about delivered to patients with poorly compliant lungs. As in
90% is acceptable. Initiate ventilation with a respiratory any other disease state, individual titration of tidal volume
rate of 12 breaths per minute, tidal volume of about 8 ml/ and PEEP according to underlying physiologic abnormal-
kg, and a constant inspiratory flow rate of between 60 ities and to the time course of the disease seems the most
and 90 liters/ min. These settings need to be readjusted, as reasonable. Besides, such an approach serves as a control
needed, once basic respiratory system mechanics and ar· for comparison purposes.
terial blood gases have been measured. In these patients, Once the precipitating cause of the acute respiratory fail-
the goal is to keep a balance between minimizing dynamic ure is partially or totally reversed, a patient's ability to tol-
hyperinflation and providing sufficient alveolar ventilation erate ACV discontinuation should be evaluated, at least on
to maintain arterial pH near the low-normal limit, not a a daily basis. This is best done carrying out a spontaneous
normal Paco,. When patients are receiving ACV and me- breathing trial using a T tube or low PSV levels for 30 to
chanical breaths are triggered by the patient, external PEEP 120 minutes . This simple approach is successful in the vast
cow1terbalances the elastic mechanical load induced by in- majority (~70%) of intubated ventilated patients, although
trinsic PEEP secondary to expiratory flow limitation and it may be particularly difficult when COPD is present 103- "I07
decreases the breathing workload markedly. 90 It is impor- and in patients in whom cardiovascular fw1ction is not well
tant to remember that external PEEP does not decrease the preserved .108-116
degree of dynamic hyperinflation either in passively venti-
lated patients or in patients with spontaneous inspiratory
efforts. During ACV, when a patient triggers a mechanical
Troubleshooting
breath, the expiratory time is no longer constant. Exhaled
Solving problems related to mechanical equipment requires
volume therefore might change on a cycle-to-cycle basis and
special skills and intuition. Some troubles are intrins ically
modify the degree of dynamic hyperinflation. This may alter
related to machines and their own working principles/
patient-ventilator synchrony and cause subsequent wasted
algorithms but can be minimized if manufacturers' recom-
inspira tory efforts, as is seen in patients with low inspira-
tory drive (i.e., sedated) and those with prolonged time con- mendations are followed . It should be unnecessary to em-
phasize tl1at thorough reading of the operator's manual is
stants.
mandatory. One study showed that hospital environment
Data9l- 97 indicate consistently that the ventilator strategy
(e.g., electric power supply) affects ventilator reliability.117
in acute asthma should favor moderate tidal volumes, high
Overall, and according to a retrospective survey/ 18 the fre-
inspiratory flow rates, and a long expiratory time. These
quency of ventilator malfunctions is very low, about 176 me-
settings avoid large end-inspiratory hmg volumes, thus de-
chanical failures and 106 operator-related errors from over
creasing the risks of barotrauma and hypotension. The main
2 million hours of ventilator running time. This author a lso
goal in asthma is to avoid these complications rather than to
reported that ventilator reliability improves in direct rela-
achieve normocapnia. A reasonable recommendation from
tionship to its utilization.117
physiologic and clinical viewpoints when initiating ACV is
to provide an inspiratory flow of 80 to 100 liters/ min and a
tidal volume of about 8 ml/ kg and to avoid end-inspiratory Important Unknowns and the Future
plateau airway pressures higher than 30 cmH 2 0 . The respi-
ratory rate should be adjusted to relatively low frequencies Mechanical ventilation is instituted mainly to improve gas
(about 10-12 cycles/min) so as to minimize hyperinflation. exchange and to decrease respiratory muscle workload . The
TI1ese settings are accompanied most often by hypercap- clinical response to this lifesaving treatment in terms of gas
FLOW
[Lis] 61
timo [s]
-1
FIGURE 7-8 (From top to bottom) Tracings of airflow (flow), airway pressure (Paw), esophageal pressure (Pes), and tidal volume (volume).
Each mark on the time axis denotes 1 second. As can be seen from the esophageal pressure recordings, this patient was markedly unloaded
and exhibited a feeble respiratory drive. As a result, multiple wasted inspiratory efforts are intersp ersed between the patient-triggered
breaths.
FIGURE 7-9 (From top to bottom) Tracings of airflow (flow), airway pressure (Paw), esophageal pressure (Pes), and tidal volume (volume).
Each mark on the time axis denotes 1 second. These recordings and those in Fig. 7-6 were obtained in the same patient. As seen easily on
the esophageal pressure tracing, there is a highly variable inspiratory muscle effort over time, thus inducing p ermanent scooping on the
airway pressure recording.
FLOW
(LJS) -40
time [s]
·1
40
Paw
[cmHzO)
2g~~J_~_L~~J_~_L~~J_~_L~~J_~_L~~J_~_L~~J_~_L~~J_~~-
Iime [s]
1 -40
time [s]
· 1(}
·1
196 PART N CONVENTIONAL METHODS OF VENTILATION
exchange is usually evaluated by means of intermittent ar- ticular patient is making and how much unloading is to be
terial blood gas measurements, continuous pulse oxime- provided is very difficult to ascertain on clinical grounds. An
try monitoring, and less often, monitoring end-tidal C02 . excessive respiratory muscle effort may induce muscle dys-
These measurements provide an objective way to titrate function, and this eventually could delay ventilator with-
therapy. Although gas exchange is the main function of the drawal.
lungs, the respiratory system also has a muscular pump Clinicians sometimes judge tolerance to ACV from the
that is central to its main purposes. The way we evalu- respiratory-rate readings, but this can be very misleading
ate the function of the respiratory muscles clinically dur- when spontaneous inspiratory efforts do not trigger me-
ing the course of ACV and patient-ventilator interactions is chanical breaths. During the course of ACV, it is also diffi-
rudimentary. cult to know how many efforts are triggered by the patient
When ACV is first initiated, the ventilator usually over- and how many are triggered by time. In addition, tolerance
comes the total breathing workload. How long the period to ACV depends on the settings. If selected inappropriately,
of respiratory muscle inactivity is to be maintained is un- these may lead the physician to erroneously interpret that
known. This is relevant because it may induce muscle at- the problem lies with the patient and perhaps administer a
rophy and eventually may jeopardize withdrawal from the sedative agent when, in reality, the patient is simply reacting
ventilator. When ACV is triggered by the patient, multiple against improper adjustment of the machine.
factors interplay between the patient and the ventilator. Al- When patients are receiving ACV, they are at risk of un-
though high levels of assistance decrease the sensation of dergoing periods of underassistance alternating with pe-
dyspnea, they a lso increase the likelihood of wasted inspi- riods of overassistance. This is so because of the varying
ra tory efforts (Fig. 7-8). The clinical relevance of such abnor- ventilatory demands (Fig. 7-9) and because the mechanical
mal patient-ventilator interactions has not been elucidated. characteristics of the respiratory system also change over
How ACV is adjusted, in particular concerning inspiratory time. The frequency of such phenomena and their clini-
flow rate and tidal volume settings, is a major determinant cal consequences are unknown. The effects of permanent
of its physiologic effects. Knowing how m uch effort a par- monotonous tidal volume delivery, as well as whether or
FIGU RE 7-10 (From top to bottom) Tracings of airflow (flow), airway pressure (Paw), esophageal p ressure (Pes), gastric pressure (Pga) and
tidal volume (volume). Each mark on the time axis denotes one s econd. These tracings were obtained in the same patient as in Figure 7-1.
The calculated compliance was 0.049 UcmH 20, airflow resistance w as 14.8 cmH20 /Us, and total PEEP was 6 cmH 20 . There ar e two
superimposed airway pressure tracings: the spontaneous tracing generated by the patient and the tracing calculated by applying the
equation of motion (Paw + Pmus = [tidal volume/compliance] + [airflow x resis tance] + total PEEP). Pmus denotes the pressure
developed by the inspiratory muscles. In this case, Pmus is zero because the patient was relaxed. As predicted, the two tracings are
virtually identical. The tracing obtained by applying the equation of motion is the one that shows the expiratory airway pressure trajectory
b elow the recorded waveform from the patient. This is explained by the fact tltat the equation of motion assumed identical compliance
and resistance during both inspiration and expiration.
1 -.
'
">--
! -
....
Fl OW
(Us) 78
time [s]
·1
30
Paw !-
! ~.
(c1nH 20J
0 •t=:
·
58 78
20 rime [s)
Pas
(CinHzOJ
-1
not sighs are to be used in this setting, also remain to be 4. Sanborn WG. Mjcroprocessor-based mechanical ventilation.
elucidated. Rcspir Care 1993; 38:72- 109.
The only way to interpret clinically whether the patient 5. Chatburn RL. Classificatio n of m echanical ventilators. In: To-
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New York; McGraw-Hilt, 1994:37- 64.
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6. Aslaniru1 P, El A trous S, Isabey D, et al. Effects of flow trigger·
ter can be monitored on the ventilator simply by applying
ing on breathing effort d uring partial ventilatory support. Am J
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way occlusion pressure is an important component of the 612-8.
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Chapter 8 Basic Principles
INTERMITTENT DESCRIPTION
IMV is a means of ventilator support in which a preset
MANDATORY number of positive-pressure (mandatory) breaths are de-
livered willie the patient breathes spontaneously between
VENTILATION the mandatory breaths. The mandatory breaths can be in
CATHERTNES. H . SASSOON the form of a preset volume (flow-limited, volume-cycled,
or time-cycled), pressure (pressure-limited, time-cycled),12
or a combination of pressure and volume (dual control)U
In principle, IMV is similar to controlled mechanical venti-
lation (CMV), in which the patient receives a predetermined
number of mandatory machine-triggered breaths indepen-
dent of spontaneous breathing effort. Likewise, SIMV is sim-
BASIC PRINCIPLES ilar to assist-control ventilation (ACV), in which mandatory
Description breaths are triggered by the patient. In contrast to CMV
System Design and ACV, however, in botll IMV and SIMV the patient is
PHYSIOLOGIC EFFECTS allowed to breathe spontaneously between the mandatory
Control of Breathing and Breathing Patterns br~aths. In addition, with IMV /SIMV, the clinician can vary
Work of Breathing and Inspiratory Effort the ventilator support level according to the set IMV rate.
RATIONALE, ADVANTAGES, AND At a high IMV rate, in which the patient's spontaneous ef-
LIMITATIONS fort is suppressed, IMV provides full ventilator support. At
INDICATIONS AND CONTRAINDICATIONS a zero IMV rate, it provides no support, and all breaths are
COMPARISON WITH OTHER MODES spontaneous. Between these extremes, IMV provides partial
IMV as a Primary Means of Ventilator Support ventilator support.
IMV as a Weaning Method
VARIATION IN DELIVERY AMONG
VENTILATOR BRANDS SYSTEM DESIGN
ADJUSTMENT AT THE BEDSIDE
AND TROUBLESHOOTING Three types of IMV sys tems are described: continuous-
IMPORTANT UNKNOWNS flow IMV and pressure-triggered and flow-triggered SIMV
THE FUTURE systems.
SUMMARY AND CONCLUSIONS
ACKNOWLEDGMENT CONTINUOUS-FLOW IMV
The originaliMV design uses a continuous-flow system.3
Intermittent mandatory ventilation (IMV) allows the pa- Two parallel circuits- one for the patient's spontaneous
tient to breathe spontaneously between machine-cycled or breaths and the other for the mechanical breaths-are con-
mandatory breaths. This concept originated in 1955 with nected through a sidearm and a one-way valve and share a
an unnamed ventilator designed by Engstrom.1•2 In the common oxygen and air source. The continuous-flow IMV
early 1970s, Kirby et al3.4 introduced IMV as a means of setup can be either an open or a closed system.14 The open
ventila tor support of infants with respiratory distress syn- system employs a reservoir tube that has a capacity of at
drome. In 1973, Downs et al5 were the first to propose IMV least 1.5 times the patient's tidal volume (VT) and is open to
as a method to facilitate discontinuation from mechanical the atmosphere (Fig. 8-1). For this reason, continuous posi-
ventilation in adults. Those investigators6•7 also pioneered tive airway pressure (CPAP) cannot be applied during the
IMV use as a primary means of ventilator support dur- spontaneous breathing cycles. To reduce ins piratory resis-
ing acute respiratory fai lure. Subsequently, breath-delivery tance, the side port of the spontaneous breathing circuit is
design has been modified. Mandatory breaths initially de- placed between the patient Y and the humidifier. The con-
livered regardless of respiratory timing are synchronized tinuous flow of fresh gas is humidified using a venturi neb-
with the patient's inspiratory effort.8•9 This mode of venti- ulizer. The reservoir tubing's considerable length and the
lation has been termed intennittent demand ventilation,8 in- inability to maintain a CPAP level make this open system
tennitte11t assisted ventilation ,9 and SIJ11Chronous intermittent cumbersome.
riU!ndntory ventilation (SIMV); the latter designation is now The closed system employs a reservoir bag (Fig. 8-2)
standard. Currently, SIMV is an established partial me- that minimizes airway pressure fluctuations because the
chanical ventilation mode in critically ill patients, both inspired gas flow rate may be limited by the maximum
adults10 and neonates. 11 This chapter will use t11e terms IMV flow generated by tl1e hospital's compressed air and oxy-
and SIMV interchangeably unless specifically indicated for gen source. In addition, constant positive airway pressure
clarification. can be maintained during both the mandatory [i.e., positive
201
202 PART N CONVENTIONAL METHODS OF VENTILATOR SUPPORT
Reservoir tube continuous-flow IMV should resemble breathing from the

<ll atmosphere.
::1
OOl Continuous-flow IMV has several disadvantages. First,
cQ)C::~
·- ::J the high flow rate of fresh gas results in gas wastage, al-
(tJ £ 0
..... C'O ...
Venturi c0 ~ ·-0 though it can be minimized by arplying a weighted or
Nebulizer one-way valve a..o high-compliance reservoir bag. 15• 1 Second, measurement
,..- en
of exhaled volume is inaccurate because the continuous
flow of fresh gas contaminates the exhaled gas within
the expiratory circuit, making monitoring of VT difficultP
Ventilator Third, IMV requires extra circuitry,18 with the risk of tub-
- Patient ing disconnection,19 incompetence,2° and incorrect assem-
bly of the one-way valve, as well as added cost. Fourth,
patient-ventilator asynchrony potentially can occur because
- Exhalation valve mandatory breaths are not delivered in concert with the
PEEP valve (one-way valve) patient's inspiratory effort (Fig. 8-3A). Whereas asynchrony
FIGURE 8-1 Continuous-flow intermittent mandatory
has no significant effect in adults}1 in neonates, asynchrony
ventilation setup with a reservoir tube. The sidearm of the associated with continuous-flow IMV resulted in large
spontaneous breathing circuit is connected through a one-way
valve to the inspiratory limb of the ventilator circuit. The sidearm
is placed between the humidifier and the patient Y. See text for
FIGURE 8-3 A. Continuous-flow intermittent mandatory
further explanation.
ventilation (IMV). Airway pressure (Paw) and flow tracings (V).
The d ashed line indicates the onset of inspiratory flow. Minimal
end-expiratory airway pressure (PEEP)) and spontaneous fluctuations of Paw are due to circuit resistance. Large
breaths (i.e., CPAP). During spontaneous breathing, the pa- fluctuations of Paw occur when inspiratory flow rates are
insufficient and a reservoir bag is not used. PEEP, positive
tient breathes from the reservoir bag via the one-way valve.
end-expiratory airway pressure. B. Pressure-triggered
When the ventilator cycles, the one-way valve closes, and synchronous intermittent mandatory ventilation (SIMV). A
a positive-pressure breath is delivered to the patient. Dur- p eriod of zero flow b efore the onset of flow (indicated by the
ing the mechanical breath, excess gas in the reservoir bag dashed line) can be detected on the flow tracing. Zero flow
is vented through a relief valve. Exhalation occurs through coincides with patient triggering to open the proportional valve.
the ventilator's exhalation circui t, whicl1 is supplied with a During the unassis ted breathing after flow onset, Paw continues
PEEP valve. to drop during inspiration because of inad equate flow delivery.
In a continuous-flow IMV system, the inspired gas flow C. Flow-triggered syn chronous intermittent mandatory
rate within the spontaneous breathing circuit must exceed ventilation (S IMV). Triggering phase is significantly shorter than
the patient's peak inspiratory flow ra te to minimize airway with pressure-triggered SJMV. During the unassisted breathing
following patient triggering, Paw is maintained at or slightly
pressure fluctuations and hence the patient's inspiratory
above the PEEP level, suggestin g adequate flow delivery during
work. When set appropriately, spontaneous breathing in inspiration.
A. Continuous-flow IMV
-:--:-~\.~~ArPEEP
FIGURE 8-2 Continuous-fl ow intermittent mandatory ventilation
setup with a reservoir bag. The si dearm for the sp ontaneous
Paw o .:!:...
- I
breathing circuit is connected through a one-way valve to the I
inspiratory limb of the ventilator circuit. The sidearm is placed I
proximal to the humidifier. Sec text for further exp lanation. v o i~ -v \..J\/,...r'l)l..-f,__o/
Relief valve
B . Pressure-triggered SIMV
Paw o .i..
-
--~-=:-d~/_~I"EEP I
I
I
v 0 i~ '-../\._/·'~-"'---'-'-ft__
C. Flow-triggered SIMV
Ventilator Paw o....:!:...

-
_-::-:r:_j_~:: -·-:::.- _v::--_1'::-:-:::.
I
1 PI:I:.P
I
I
V 0 insp
exp ,_)Jl____.'"\...1"'\. ~,-...__ ,//
J \...__../\.
- Exhalation valve
(one-way valve) Time
CHAPTER 8 INTERMITTENT MANDATORY VENTILATION 203
fluctua tions of Vr 22 and lower Pao~ 23 than with SIMV. The with pressure triggering may not be adequate during the
effect of IMV on Pao, was confirmed in a large random- spontaneous breaths.28 The feedback signal for flow deliv-
ized multicenter tria l. 24 Low Pao, was postulated to result ery is the gradient between a manufacturer-determined tar-
from active exhalation because muscle relaxant improves get pressure and circuit pressure. As the pressure gradient
oxygenation. 25, 26 increases, flow delivery increases. This pressure gradient
A technologically advanced continuous-flow IMV ma- can be enhanced by adding pressure support (PS) or sens-
chine is the flow-regulated lMV /CPAP machine described ing the circuit pressure at the distal end of the endotracheal
by Akashi et al. 27 Flow w ithin the circuit is polled, for ex- tube.35•36 From a practical standpoint, adding PS is prefer-
ample, every 20 minutes and used as a feedback signal able. Alternatively, flow delivery during the spontaneous
to increase tl1e basal flow to match tl1e patient's ventila- breaths maybe a ugmented by using changes in flow instead
tory demand during inspiration and subtract it during ex- of pressure as a feedback signal for adding and subtracting
halation. Flow-regulated CPAP eliminates airway fluctua- flow from the base flow during ins piration and exhalation,
tions and decreases imposed work during both inspiration respectively.27
and exhalation. Using a mechanical lung model with flow- Augmenting flow delivery during the mandatory breaths
regula ted CPAP of 5 cmH20 , the total imposed work was can be accomplished by setting the pressure-a ttack rate suf-
3.4 mJ/breath versus 43.5 mJ/ breatl1 with a continuous- ficiently high when pressure-limited mandatory breaths are
flow CPAP device and an added 20-liter reservoir employed.37·38 To maintain a constant Vr with pressure-
bag.27 limited mandatory breaths, both pressure- and volume-
limited breaths can be combined in the form of dual con-
trol within breaths39 or breath-to-breath ventilation (see
PRESSURE- AND FLOW-TRIGGERED SIMV Chapter 16).40 Several microprocessor-based ventilators are
SIMV is currently the standard for clinical use.10• 11 SIMV in- equipped with dual-control breath-to-breath ventilation
corporates a dema nd valve tl1at is triggered by the patient that can be applied in the SIMV mode.41 In essence, this
with each spontaneous breatl1 and delivers a mandatory form of mandatory breath is a pressure-limited, time-cycled
breath in concert with the patient's inspiratory effort. If the breath that uses Vr as feedback control for continuously ad-
patient ceases to trigger the ventilator, mandatory breaths justing the pressure limit to attain the set Vr. The volume
will be triggered by the machine and delivered according to signal used as feedback to the ventilator controller is the
the preset rate. The demand valve is triggered by either a fall volume exiting the ventilator and not the exhaled Vr. This
in pressure (pressure-triggered) or a change in flow (flow- step prevents runaway of airway pressure that could oc-
triggered). In pressure-triggered (or demand-flow) SIMV, a cur if a leak in the circuit caused inaccurate measurement
preset pressure sensitivity must be achieved before the ven- of exhaled volume. With dual-control manda tory breaths, a
tilator delivers fresh gas into the inspiratory circuit. 28,29 A "test breath" is delivered, and the dynamic compliance of
noticeable delay in opening the demand valve occurs be- the respiratory sys tem is calculated. The next three breaths
tween onset of inspiratory effort and flow delivery (see Fig. are delivered at a pressure limit of 75% of that necessary to
8-38). Flow·-triggered (or f1ow-by) SIMV uses a preset flow acl1ieve the desir ed Vr. The ensuing breaths wiU increase
sensitivity as the trigger mechanism.28•29 The terms pressure- or decrease the pressure limit a t less than 3 cmH20 per
triggered SIMV and f1ow-triggered SIMV are preferred over breath in an attempt to achieve a relatively smooth transitio n
demand-flow SlMV and flow-by SIMV, respectively, be- from the initia l Vr to the target volume. The pressure limit
cause with both demand-flow and flow-by SIMV systems, will fluctuate between 5 cmH20 above the PEEP level and
flow delivery is essentially "on demand." In addition, the 5 cmH2 0 below the upper pressure alarm setting. 41 As a
term flmv-bl; signifies continuous flow rather than flow safety feature, if the volume exiting the ventilator exceeds
sensitivity. 150% of the set Vr, then the ventilator exhalation valve
The pressure- and flow-triggering characteristics of the opens, ending the mechanical inspiration. Thus, with SIMV,
spontaneous breaths (CPAP) are an important component mos t microprocessor-based ventilators are able to apply PS
of the imposed work of an SIMV system (see Chapter 3).30,31 and dual-control breathing to the spontaneous and manda-
This situation arises because there is little adaptation to the tory breaths, respectively, to improve flow delivery and
mandatory breaths' ventilatory assistance unless the system maintain a set Vr during pressure-limited mandatory
is set at a st.tbstantial assistance leve1.32 Fortunately, most breaths. ln preterm infants, because changes in respira-
modern microprocessor-based ventila tors employ a remark- tory system mechanics occur frequently, the set Vr of the
ably responsive proportional solenoid valve such that the mandatory dual-control breaths not only provides a guar-
work imposed during the trigger phase (the interval from anteed volume when respiratory system complia nce de-
onset of patient effort to valve opening or flow deli very) is a creases but also prevents overinflation when compliance
small percentage of the total inspiratory work of breathing improves.42' 43
( < 10% with pressure-triggered SIMV). 33 Nevertheless, flow
triggering has become the preferred triggering method not
only for SlMV but also for various other ventilation m odes
because of its faster response time and therefore shorter Physiologic Effects
triggering phase compared with pressure triggering (see
Fig. 8-3C).34 In the posttrigger phase (the interval from on- The physiologic effects of IMV not listed i11 this section are
set of flow delivery to the end of inspiration), flow delivery discussed in comparison with other ventilation modes.
204 PART IV CONVENTIONAL METHODS OF VENTILATOR SUPPORT
CONTROL OF BREATHING AND

BREATHING PATTERNS
In early IMV development, it was thought that inspiratory EMGd
muscle activity is downregulated during the mandatory
breaths and that IMV therefore allows a combination of
unassisted breathing with respiratory muscle rest to pro-
mote weaning.5•44 By adjusting manda tory breath fre- EMGscm
quency, inspiratory effort could be modified until the pa- s
tient res umed complete control of spontaneous breathing.
A S A
[20
Several studies, however, disproved this hypothesis. 32•45-47 l 0
Imsand et al45 studied the neuromuscular output of patients
recovering from acute exacerba tion of chronic obstructive
.........
1 sec
pulmo nary disease (COPD) who were receiving pressure- +8
triggered SIMV. The mandatory-breath VT was set a t 10-
12 ml/ kg. Neuromuscular output was estimated from the 0
amplitude of the integrated diaphragmatic electrical activ-
ity (EMGd), measured using bipolar esophageal electrodes. -8
Sternocleidomastoid muscle electrical activity (EMGscm)
was recorded using surface electrod es. N euromuscular out- FIGU RE 8-5 Electrical activity of the diaphragm {EMGd) and
put, occlusion esophageal pressure (PeSo.1, another index sternodeidoma.stoid muscles (EMGscm) in a patient receiving
of neuromuscular output), and neural inspiratory time (T1) SIMV. Intens ity and duration of electrical activity in successive
assisted (A) and intervening spontaneous {S) breaths arc similar.
were measured at three ventilator support levels: > 60%, 50- The regul ar sp ikes in the EMGd tracing are the QRS complex of
20%, and 0% of total support. Total support was defined as the electr ocardiogram signal. Paw, airway pressure; Pes,
the support at whicl1 EMGd was suppressed completely. esophageal pressure. (Adapted, w itl1permissiou, from Imsaud
Only at the highest machine assistance rate did EMGd de- et al: Auestllesiology 80:13-22, 1994.)
crease significantly, whereas EMGscm did not (Fig. 8-4).
Moreover, across all levels of ventilator support, botl1 EMGd
decreasing machine assistance. Likewise, neural T1, defined
(Fig. 8-5) and PeSo 1 of the unassisted and machine breaths
as the interval from onset to peak EMGd, was equivalent
were similar. Pes0.1 , however, tended to increase witl1
for unassisted and m achine breaths.
In another stud y, Uchiyama et al46 applied continuous-
FIGURE 8-4 Peak inspiratory amplitude of integrated electrical flow IMV in anesthetized rabbits and measured EMGd with
activity of the diaphragm (EMGd) and sternoCleidomastoid implanted electrodes into the diaphragm. The IMV rate was
muscles (EMGscm) at three levels of machine assistance during set at 0,5, 10, 15, and 20 breaths per minute, at which EMGd
SIMV, expressed as a percentage of mean value of 0% of or was suppressed completely. EMGd was expressed as per-
minimal {4 breaths per minute) machine assistance. Values arc cent of EMGd at zero IMV rate per minute. Compared w itl1
mean ± SE. • P < 0.01 compared with 0% of mach ine assistance. spontaneous breatl1ing, EMGd decreased significantly only
t P < 0.05 compared with spontaneous cycles at 50-20% of at an IMV rate of 15 breaths per minute (75% of total sup-
assistance. Assist, machine-assisted breaths; spont, intervening port). In contrast with the study of Imsand et a1,45 at an IMV
spontaneous breaths. (Adapted, tvitlt permission, from Iursaml
rate of 10 and 15 breaths per minute, EMGd of tl1e manda-
et al: AuestllesiologJJ 80:13-22, 1994.)
tory breaths was absent. The difference in neuromuscular
CJ Assist output response during m andatory breaths in the study of
120 - Spent
Uchiyama et al46 may be related to tl1e effect of anesthesia
100 and the large VT applied (15 ml/ kg), causing vagally medi-
~ 80
.. •t
~
ated inspira tory inhibition.48 It appears that in anesthetized
~60 animals at ventilator support of 50% or greater, breath-by-
u
~ 40 breath adaptation to ventilator assistance occurred, but it
w 20 was not observed in consciot1s humans.
In unsedated preterm infants with acute respiratory
0
failure receiving flow-triggered SIMV, Beck et al47 mea-
120 sured EMGd and neural timing of mandatory breaths and
100 the unassis ted breaths immediately preceding and fol-
~80
~
lowing tl1e mandatory breaths using miniaturized elec-
5 60 trodes mounted on a feeding tube. The set SIMV rate
V)
C>40
ra nged from 5-25 breatl1s per minute. Both EMGd and
::!! neural T1 amplitude were simila r for the m andatory and
w 20 tmassisted breaths (Fig. 8-6). In contrast to improved
0
>60% 50-20% 0% triggering in adults, 45 during the mandatory breatl1s, a
Level of machine assistance subs tantial delay was observed from onset of EMGd to
(% total ventilation) flow delivery, an average of 95 ms (range 5-110 ms).
CHAPTER 8 INTERMITIENT MANDATORY VENTILATION 2OS
10
~
0 pre-mandatory spontaneous breath
l._N_tt_u_ra
_•_n _e_u_r_a_lr_e___...JI Neural timing
_._]____N
~ 9 [J mamJat01 y brt!ath
~ <> post-mandatory spontaneous breath Trigger Prolonged delivery
-
~
>- 8
·:;;
'-'
1'0
1'0
u
:s'-'
7
6
5
delar.f ~o~fa~ss~~~~-~
Ventilator Tl
------.
Ventilator TE Ventilator timing
.,_
100 ms
(I)
Qi 4
E • Asynchrony (53%}
0) 3
1'0 _ _ ____J 0 Synchrony (47%)
.....
.c.
a.
2
1'0 FIGURE 8-7 Inspiratory and expiratory asynchrony during
i5 1 mandatory breaths. Schematic representation of patient neural
0 timing (upper bar) and ventilator timing (middle bar) during
mandatory breaths. Upper bar shows the neural inspiratory time
0 200 400 600 800 1000 1200 1400 (T 1) (light-gray area) and neural expiratory time (TE) (w lrite area).
Time (msec) Middle bar shows periods of ventilator timing, including trigger
FIGURE 8-6 Diaphragmatic electrical activity (EMGd) time delay, ventilator T 1 (rlnrk-gray area), and ventilator T E· Bottom bar
profile for group mean data. No significant difference exists shows periods of infant-ventilator synchr·o ny (wltite area) and
between peak EMGd amplitude and neural timing on inspiration asynchrony (black nrea). (Adapted, witlr permission, from Beck
for the premandatory spontaneous breaths (solid /iue), mandatory et al: Pediatr Res 55: 747- 54, 2004.)
breaths (daslll!d liue), or after mandatory spontaneous breaths
(dotted line). Neural expiratory time was prolonged significantly
for the mandatory breaths (dashed litre). The plot does not In the presence of s table chemical input, Po. 1 and VTIT 1
represent the shape of the EMCd recruitment pattern but simply measured during spontaneous breathing varied inversely
represents three points: the onset of EMGd, peak of EMGd, and with IMV rate. Increases in VTIT1 with IMV rate reduction
onset of EMGd of subsequent breath. Values are mean ± SE. primarily were the result of progressive VT augmentation
(Adapted, with permission, from Becket al: Pediatr Res 55:747- 54, because inspiratory time (T1) and the d uty cycle (TtfTroT)
2004.) remained unchanged at all IMV support levels. This VT re-
sponse probably was related to changes in C02 production
Because most of the infants had bronchiolitis and likely that stimulated chemoreceptors. In acutely ill patients,32 the
were hyperinflated, the authors attributed the trigger effect of IMV on Po.1, measured during spontaneous breath-
delay or inspiratory asynchrony to neuroventilatory ing, is similar to that in stable patients.54 Using another in-
uncoupling (a delay from onset of diaphragmatic activation dex of neuromuscular output, dP I d t of esophageal pres-
to flow generation)49 rather than to the ventilator trigger- sure at the onset of ventilator triggering, Leung et al33 also
ing system. Neural expiratory time (TE) of the mandatory demonstrated an inverse relationship between dP I dt and
breath, defined as the interval from peak to EMGd onset of machine assistance level.
the subsequent breath, was prolonged. The relative increase As with neuromuscular output, IMV's effects on breath-
in neural T E during the mandatory breaths was related to ing patterns are determined by assistance level. Both VT and
the time the ventilator continued to inflate beyond the end unassisted breath frequency increase progressively with
of neural T1 (R2 = 0.66; P = 0.01). 1l1is extended time was a decreasing IMV rate.32,33, 45•55 Because VT of the unas-
consistent with a vagally mediated reflex when pulse infla- sisted breaths is relatively small compared with the manda-
tion was delivered into early expiration. 50-5 1 Both inspiratory breaths, dead-space-to-tidal-volume ratio inevitably
tory asynchrony and expiratory asynchrony were present increases. Consequently, spontaneous breathing frequency
during every mandatory breath and constituted, on aver- increases to maintain constant alveolar ventilation. Indeed,
age, 53% of the total breath duration (Fig. 8-7). Expiratory Pac(h remained constant at all machine assistance levels.55
asynchrony may result in increased peak ainvay pressure The sensation of dyspnea during SIMV depends on assis-
as the subject attempts to terminate inspiration by recruit- tance level when applied without pressure-support venti-
ing the expira tory muscles. 52 It also may result in increased lation (PSV) but was independent of assistance level when
work of breathing and discomfort and manifest as a patient 10 em H2 0 of PS was added to the unassisted breaths.33 Dur-
"fighting the ventilator,"53 potentially dictating sedation. ing low assistance levels, dyspnea probably is secondary to
Using airway occlusion pressure (Po.1) and mean inspira- increased inspiratory effort, whereas the high rate of non-
tory flow rate (VT/T1) as indices of neuromuscular output, triggering efforts may be responsible for tl1e dyspnea at
Weiss et al54 examined the effect of IMV on respiratory drive higher assistance levels. Knebel et al56 also demonstrated
in stable ventilator-dependent patients who received me- that during the weaning trial on SIMV, the sensation of d ys-
chanical ventilation for 12-24 hours each day. The TMV rate pnea and patient anxiety were independent of support level.
was initially set at 10 breaths per minute and reduced grad- In that study,56 a PEEP of 5 cmH20 was maintained, which
ually to 6, 3, 2, and 1 breath per minute, and each level was might have offset the increased inspiratory muscle work
maintained for 10 minu tes. The VT of the mandatory breaths with a decreasing IMV rate.57, 5S
was set at 8-12 mll kg. End tidal Pco, and arterial oxygen In summary, with IMV, the neuromuscular output of both
saturation did not change as the IMV rate was reduced. the mandatory and unassisted breaths is downregulated
only at high machine assistance levels ("'75-80% of total ma- PTP of inteiVening spontaneous breaths
chine assistance). 45•46 Breath-by-breath adaptation to ma-
chine assistance does not occur. The fact that EMGd was the PTP of mandaloly breaths
15-: IMV
same during assisted and preceding unassisted breathing ......
1/) •
. PTPtrigger
suggests that neuromuscular output during the mandatory 6 .
10-
.
N
breaths must be determined at least in part by factors oper- J:
ating during the previous breath. This could be accounted E :
~
for by the central neural feedback mechanism described by 5 5:
Eldridge (see below).59 Neuromuscular output increases in- IV <
!
versely with the set fMV rate. Whereas VT and frequency ~ 0_._-
increase when IMV rate decreases, neural inspiratory tim-
ing of the mandatory and unassisted breaths is of the same
dura tion across aU levels of machine assistance. eural ex-
e::J
Q.
15 IMV + PS 10 cmH20
Q)
pira tory timing of the ma ndatory breaths is prolonged sec- E
ondary to mechanical T1 encroaching into neural TE, caus- F 10
ing expiratory asynchrony. Respiratory timing asynchrony, !'
however, potentially can be abolished by using inspiratory ~
1/)
5
and expiratory neural trigfgering with a neurally adjusted !
Q.
ventilatory assist (NAVA). 9
60 80
Percent Support of Assist Control Ventilation
WORK O F BREATHING AND INSPIRATORY EFFORT
FIGURE 8·8 Pressure-ti me product (PTP) per breath d uring
n,e effect of IMV on inspiratory muscle work and inspira- synchronous intermittent mandatory ventilation (IMV) in the
tory effort is, as expected, determined by the level of ma- p resence and absence of pressure support (PS). The addition of
chine assistance, and the response is similar in aduJts32.33.45 10 cmH20 PS to the interven ing sp on taneous breaths decreased
and neonates. 55 A higher number of mandatory breaths the overall PTP per breath. PTP per breath, h owever, did not
differ between the mandatory and intervening spontaneous IMV
reduces total workload and instratory effort in patients
b reaths at each level of machine assistance, irrespective of
during acute respiratory failure3 or recovery. 33·60•61 Marini whether PS was present or absenl (Adapted, witlr pennission,
et al32 measured work of breathing (WOB) per liter of ven- from Lermg l't al: Am J Respir Crit Care Med 155:1940-8, 1997.)
tilation (joules per liter) and pressure-time product (PTP)
per breath (PTPb) during ACV and at SIMV support lev-
els of 80%, 60%, 40%, 20%, and 0% of the ACV rate. When strated that the triggering system had no effect on patient
the SIMV support level was less than 80% o f the ACV rate, mandatory-breath workload. In contrast, Giuliani et al 60
the patient's total workload was increased markedly com- found that patient mandatory-breath workload was signifi-
pared with that during ACV. Moreover, at all SIMV lev- cantly less with flow-triggered than with pressure-triggered
els, the patient expended a similar effort during both the SIMV irrespective of the mandatory-breath type (whether
manda tory and sp ontaneous breaths, as gauged by PTPb, SIMV was flow- or pressure-limited). Moreover, patient
which reflects the energy consumed by contracting respi- workload with combined flow-triggered and pressure-
ra tory muscles (patient effort). The patient does not vary limited mandatory brea ths was lower th an the other
effort on a breath-by-breath basis in response to machine combinations of triggering and mandatory-breath types
unloading, as confirmed by others on the basis of EMGd (flow-triggered flow limit and pressure-triggered flow and
recording.45•47 It appears that during SIMV the heightened pressure limit) .60 The decrease was so substantial that the
respiratory activity during the spontaneous breath is car- PTPb of the mandatory breath was s ignificantly less than
ried over to the subsequent mandatory breath in the man- that of the interven ing spontaneous breaths. It is not clear
ner of an "afterdischarge" or "memory" phenomenon.59 In as to why the data of Giuliani et al 60 differed from the data
fact, when 10 cmH20 of PS was applied during the inter- of others 32·33·45•47 who demonstrated the lack of breath-by-
vening spontaneous breaths, inspiratory muscle effort de- breath adaptation to machine unloading.
creased not only during the intervening breaths but also In summary, during acute respiratory failure or recovery,
during the mandatory breaths (Fig. 8-8).33 This afterdis- patient workload during SIMV remains substantial unless
charge phenomenon is central in origin and unrelated to the SIMV support is equivalent to or greater than 80% of
chemoreceptor or mechanoreceptor feedback or the state of the support during ACV.32•33 IMV often allows adequate
sleep/ wakefulness. 59·62 gas exchange at lower support levels63 (see below) but at
The patient workload during lMV is determined not only the expense of increased patient workload.32.33.45
by machine assistance level but also by the !MV system
employed.60•61 Patient workload o r inspiratory effort dur-
ing spontaneous breathing cycles with flow-triggered SIMV Rationale, Advantages, and Limitations
was significantly less than with a pressure-triggered SIMV
system, 60•61 p articularly at a relatively low SIMV rate.61 The IMV was developed as an alternative to CMV and ACV. The
effect, however, of the triggering system on patient manda- rationa le for developing IMV was based on the premise that
tory breath workload is conflicting. Sassoon et aJ6 1 demon- by maintaining s pontaneous breathing amid the mechanical
breaths, (1) machine breaths can be titrated to ad just alveolar has no autonomy to alter breathing pattern with CMV, the
ventilation, ther eby decreasing the incidence of respiratory patient will increase inspiratory effort, which is manifes ted
alkalemia,64 (2) distribution of inspired gas and ventilation- as "fighting the ventilator" when ventilatory demand rises.
perfusion to the lung base improve, and physiologic dead No studies, however, have compared the respective seda-
space decreases, 65 (3) mean airway pressure and pul- tive doses used during CMV and IMV.
monary vascular resistance decrease, allowing PEEP titra- 2. IMV prevents respiratory alkalosis. In a prospective study
tion and therefore more effective treatment of hypoxen1ia,66 comparing lMV and CMV in patients with acute respiratory
and (4) pleural pressure decreases, resulting in better failure, CMV resulted in a mean pH of 7.49 and a Paco, of
venous return and cardiac output.65 Unfortunately, subse- 32.3 mmHg, whereas IMV resulted in a mean pH of 7.44 and
quent clinical trials did not support some of the ra tionales a Paco. of 39.9 mmHg. 7 The CMV rate, however, was set to
(see below). suppress spontaneous respiratory effort, whereas, during
IMV's flexibility in providing a range of support levels IMV, the rate was adjus ted downward continuously as long
makes it advantageous for use as a primary means of venti- as pH remained greater than 7.30. Hence the result in favor
lator support67 and as a method for discontinuing mechan- of IMV is to be expected. When a normal pH is achieved at
ical ventilation.5 An inherent limitation of IMV is the fixed a low IMV rate, subsequent data suggested that it was at
rate of machine brea ths. When set at a very high rate, IMV the expense of increased work of breathing.32,60 Moreover,
functions as CMV and potentially may lead to diaphrag- some patients on m echanical ventilation who are allowed
matic muscle atrophy. 68 - 70 During weaning from mechan- to set their own Paco2 do not a lways choose a normal level
ical ventilation, the pace of decreasing the IMV rate po- (e.g., patients with brain injury). These patients will have
tentially can prolong weaning when it is inappropriately persistent respiratory alkalosis regardless of ventilation
slow. mode.63,so
3. IMV improves intrapulmo11ary gas distributio11. This
hypothesis is based on the premise that in the supine posi-
Indications and Contraindications tion, spontaneous breathing causes inspired gas to be dis-
tributed preferentially to dependent lung regions because
IMV has been used as a primary means of ventilator support the dependent diaphragm, which is displaced cephalad, op-
in postoperative pa tientsn and during acute respiratory erates a t an improved mechanical advantage.81 Conversely,
failure of various etiologies.6' 7'72 - 76 For treatment of acute during mechanical ventilation, ventilation is distributed
respiratory failure, North Americans apply SIMV, with and preferentially to nondependent lung regions because the
without PS, more frequently than ACV (40% versus 34%, diaphragm is not used, and the nondependent lung and
respectively). 10 The level of machine assistance must be tai- chest wall are more compliant.82 Therefore, IMV's com-
lored to the patient's ventilatory requirement. The optimal bination of spontaneous and mechanical breaths theoreti-
mandatory-breath settings are similar in principle to those cally should result in a better matching of ventilation and
for ACV.77 - 79 A low IMV setting is contraindicated when perfusion.83 A comparison s tudy evaluating IMV and CMV
the patient's ventilatory demand is high; likewise, the set- ventilation-perfusion distribution with the inert-gas elimi-
ting should not be left high after the patient's ventilatory nation technique84 was performed in stable patients recov-
requirement has decreased. A gradual decrease in the IMV ering from major abdominal aortic surgery. 85 During CMV,
rate is unwarranted when discontinuation from mechanical VT was set a t 14-16 ml/ kgwith a set rate of8-10breaths per
ventilation is imminent. minute. During SIMV, the rate was set at 50% of the CMV
rate (4-5 breaths per minute); a PS of S-8 cmH2 0 was added
to the intervening spontaneous breaths to overcome the
ventilator circuit and endotracheal tube resistance.86 Each
Comparison with Other Modes ventilator mode was maintained for 45 minutes. Compared
with CMV, physiologic dead space increased with SIMV
IMV AS A PRIMARY MEANS OF
(22.0% versus 26.8 %, respectively; p<O.OS) a11d was asso-
VENTILATOR SUPPORT
ciated with a significant increase in '-IE, resulting in a simi-
IMV ANDCMV lar Paco2 • The SrMV perfusion distributions remained unal-
Unlike IMV, CMV imposes a fixed breathing pattern. Hence, tered. This study, using the inert-gas elimination technique,
to some extent, a comparison favors IMV, which has been shows that IMV does not improve ventilation-perfusion
claimed to be superior to CMV for the follow ing reasons: distributions.
(1) it prevents the patient from "fighting the ventilator," 4. IMV lowers meau airway pressure, benefitiug cardiac out-
reducing the need for sedation a nd paralysis, (2) it pre- put and preveutin.g barotrauma. Since IMV intersperses spon-
vents respiratory alkalosis, (3) it improves intrapulmonary taneous breaths between mechanical breaths, mean air-
gas distribution, (4) it lowers mean airway pressure, ben- way pressure averaged over time is lower than with
efiting cardiac output and preventing barotrauma, (5) it CMV. The lower mean airway pressure results in main-
decreases oxygen consumption Naz), (6) it prevents mus- tenance of cardiac output. Several s tudies have shown a
cle a trophy and discoordination, and (7) it improves renal higher cardiac output with IMV than with CMV.75 •76•87 The
function. interactions between intra thoracic pressure associated with
1. IMV preveuts the patieut fl'OIIl ''fighting the ventilator," re- mechanical ventilation and cardiac performance, however,
ducing the need for sedation and paralysis. Because the patient are quite complex.88 Right- and left-ventricular interaction,
direct pressure on the heart, and changes in systemic and proposed to achieve respiratory muscle conditioning and
pulmonary venous return all play a role. The net effect of preserve respiratory muscle function. 5 The periodic hy-
this interaction depends on left-ventricular filling pressure perinflation also may reinforce coordinated breathing.5•93
and reserve. Mathru et al 89 compared the effect of CMV, During CMV, muscle atrophy70•94•95·96 and myofibrillar
IMV with 5 cmH2 0 PEEP (IMV- SPEEP), and IMV with 0 damage69·98•99 that account for ventilator-induced diaphrag-
cmH20 PEEP (TMV- OPEEP) in two groups of patients fol- matic dysfunction have been demonstrated in experimental
lowing aortocoronary bypass sttrgery. VT and ventilator animals. Conversely, maintaining diaphragmatic activation
rate were adjusted to achieve a PacCh of between 35 and with ACV attenuates expression of the gene responsible for
40 mmHg. One group had normal left-ventricular function. developi11g muscle atrophy: the muscle atrophy F-box (see
The second group had decreased left-ventricular reserve: Chapter 46).7° The extent to which respiratory muscle at-
left-ventricular diastolic pressure of greater than 16 mmHg rophy develops during prolonged CMV in humans is un-
and ejection fraction of less than 0.6. In the first group, known. With IMV, diaphragmatic electrical activity of both
IMV--OPEEP resulted in an increase in cardiac output of27% mandatory and spontaneous breaths persists. Tints it is pos-
compared with CMV. In the second group, however, IMV sible that IMV prevents respiratory muscle atrophy. This
resulted in a significant decrease in cardiac output (19%) hypothesis remains to be investigated.
compared with CMV. IMV-SPEEP affected cardiac output Respiratory muscle discoordination with IMV and CMV
similarly to CMV. These data indicate that when compared has not been compared. IMV's efficacy in counteracting res-
with CMV, IMV improves cardiac output in patients with piratory muscle discoordination was demonstrated by An-
normal left-ventricular function or hypovolemia, but it may dersen et al93 in a study of 28 patients during discontinua-
be harmful in patients with poor left-ventricular reserve. tion of mechanical ventilation. The mandatory breaths were
The frequency of barotrauma with IMV and CMV was increased gradually to 75% of the patient's V£. In contrast,
compared in a retrospective study of 292 postoperative and Gibbons et al100 failed to show similar results when IMV
nonsurgical patients who received mechanical ventilation was applied to six patients receiving prolonged mechani-
for 24 hours or more. 90 The ventilator VT was set at 12- cal ventilation. The lowest spontaneous breathing rate was
15 ml/kg. The IMV rate was set at 6 breaths per minute or 29 breaths per minute at the lowest IMV rate of 10 breaths
lower, provided that normocapnia was maintained. If hyper minute. Gas exchange was adequate. Five of the six pa-
percapnia developed, it was treated by increasing VT to 15 tients manifested breathing discoordination in the form of
ml/kg and, if necessary, by increasing the lMV rate to 8 either rib-cage or abdominal paradox. In the patients whose
breaths per minute. No sedation or muscle relaxants were diaphragmatic electrical activity was measured, an elec-
used. In the CMV group, the rate was set at 12 breaths tromyographic fatigue pattern also was observed. In this
per minute. Hypercapnia was corrected by increasing VT. study, IMV was insufficient to reduce respiratory muscle
TI1e patients were sedated and paralyzed . Compared with workload, as reflected by the relatively high spontaneous
the CMV group, patients receiving IMV had a significantly breathing rate. fMV's efficacy in counteracting respiratory
higher peak airway pressure (34 versus 51 cmH 20 , respec- muscle discoordination appears to depend primarily on the
tively) and PEEP /CPAP (15 versus 27 cmH 20, respectively). extent of respiratory muscle unloading.
Yet the barotrauma was 22% in the CMV group compared 7. IMV improves renal junctio11. Steinl1offet al101 studied the
with 7% in the lMV group. The authors speculated that effect of CMV and IMV on renal function in patients with
the less frequent barotrauma with IMV was related to the acute respiratory failure. With CMV, the ventilator rate was
smaller number of mechanical breaths with large VT. Mean set to suppress inspiratory efforts, which averaged 10-16
transpulmonary pressure, which may be responsible for the breaths per minute. IMV was set at 4-10 breaths per minute.
barotrauma, was not measured in either group. PEEP was maintained constant during both CMV and IMV.
5. IMV decreases oxyge11 consumption. Downs et af found With CMV, urinary flow and creatinine and osmolal clear-
that VCh was lower both during mechanical ventilation ance decreased, with a net effect of water retention, in com-
and 15 minutes after its discontinuation in patients ven- parison with IMV. Impaired renal function during CMV was
tilated with IMV versus CMV. TI1e authors speculated that attributed to the increased intrathoracic pressure, which
the higher V0 2 on CMV could be ascribed to respiratory caused stimulation of atrial stretch receptors and release of
alkalosis91•92 and abntpt withdrawal from mechanical ven- antidiuretic hormone. A more important factor may be that
tilation rather than reflecting metabolic work of breathing. increased intrathoracic pressure during CMV decreases ve-
In contrast, Wolff et al67 showed that C02 production (Vem) nous return, and the consequent decrease in cardiac output
tended to be lower with CMV than with IMV. Because produces a decrease in renal plasma flow. Hence the effects
the respiratory quotient was similar with both ventilation of CMV and IMV on renal function are related directly to
modes, it is reasonable to assume that Vo2 during CMV was their respective effects on cardiac function.
lower than that during IMV. In this study, Paco 2 was 39 and
44 mmHg on CMV and IMV, respectively, suggesting that IMV ANDACV
pH was within the normal range. This observation suggests Comparison of IMV with ACV is more appropriate than
that, in the absence of alkalemia, VCh is lower on CMV than comparison of IMV with CMV because both IMV and ACV
oniMV. provide partial ventilator support. Few studies have com-
6. IMV prevents muscle atrophy and discoordination. Main- pared IMV with ACV. As discussed below, these studies
taining spontaneous breathing activity during IMV has been primarily concern effects on cardiac output,.102• 103 V(h, 1o2-'104
CHAPTER 8 INTERMITIENT MANDATORY VENTILATION 209
and respiratory alkalosis. 63•102•105 (Since IMV's effects on although cardiac output was not measured directly
work of breathing were discussed extensively earlier, com- during either IMV or ACV. The conflicting data concerning
parison of IMV with ACV will be limited to its application the effects of ACV and IMV on cardiac output underscore
in the neonate. 106• 107) the complex interaction between intrathoracic pressure and
1. Effect 011 cardiac output. Groeger et a1 102 studied the cardiac function.
effect of SIMV and ACV in 40 patients with acute res- 2. Effect on o;o;gen consumption. In the above-mentioned
piratory failure of various etiologies other than COPD. study by Groeger et al,102 Yo1 was comparable for both
SIMV, at a set VT of 10-15 ml/kg, was the initial venti- pressure-triggered SIMV and ACV. When the patients were
lation mode in all patients, and the mandatory rate was grouped according to the ratio between VE achieved by
adjusted to the minimum required to maintain a nonnal the mandatory breaths and total VE, however, the mean
pH and Pac02 . When the combined mandatory and spon- V0 2 for patients with a ratio of less than 0.5 was signifi-
taneous breathing rates were g reater than 35 breaths per cantly higher during SIMV than during ACV (320 versus
minute, the IMV rate was increased to ensure patient com-
296 ml/min/m2 , respectively; p .:;:0.05). Conversely, in the
fort. The ventilator mode was then switched to ACV, and
study of Sternberg and Sebahjami,103 when the mandatory
VT, PEEP, inspiratory flow rate, and inspired oxygen frac-
breaths during SIMV were set at 75% of the ACV rate,
tion (Fro2 ) were held constant. After 30 minutes on SIMV
V~ was unaltered during SIMV despite total frequency
or ACV, hemodynamic variables were measured. At this
being higher with SIMV than with ACV (20 breaths per
point, mean IMV rate was 7 breaths per minute, with a total
minute versus 12 breaths per minute). In healthy subjects
ra te of 34 breaths per minute, whereas the ACV rate was
15 breaths per minute. Cardiac output, measured by ther- breathing via a mouthpiece on SIMV or ACV, V02 (mea-
modilution, was 6% higher with SIMV than with ACV. Like- sur ed with a metabolic cart) also was similar with the two
wise, studying 12 patients recovering from acute respiratory modes.104 With STMV, both the VT and mandatory-breath
failure of various etiologies, Sternberg and Sal1ebjami103 rate were equivalent to those of the ACV: 10 ml/ kg and
demonstrated that cardiac index was significantly higher 12 breaths per minute, respectively, with a total rate of
with SIMV than with ACV (3.6 versus 3.3 liters/min/m2 ). IS breaths per minute. Thesestudies102- 104 demonstrate that
(The investigators also compared SIMV with PSV, which compared with ACV, the degree of machine assistance dur-
will be discussed below.) The average VT with ACV was ing IMV determines V01 .
715 ml, whereas with SIMV it was 491 ml. The SIMV 3. Effect on respiraton; alkalosis. Three prospective
mandatory breaths were set at 75% of the ACV rate. Al- studies 63• 102• 105 comparing IMV and ACV showed a sig-
though the cardiac output witl1 SIMV was significantly nificantly lower pH and higher Paco, during IMV than
higher than with ACV, the changes fall within the variabil- during ACV (Table 8-1). Groeger et al102 suggested that
ity of the thermodilution technique. 108 Despite the limited the higher Paco2 during IMV was related to an increased
differences in cardiac output with IMV and ACV, IMV may dead-space-to-tidal-volume ratio (V 0 / VT), because Yeo,
be helpful in patients who demonstrate significant hemody- and VE were similar for both IMV and ACV. Conversely,
namic deterioration during ACV. In the original description Hudson et a163 showed that the higher Pac~ during IMV
of intrinsic PEEP (PEEP1),109 two patients w ith COPD came a t the expense of a high patient workload given
developed hemodynamic compromise secondary to sig- elevated C02 and an unchanged alveolar ventilation level.
nificant PEEP1 while receiving ACV. The institution of Regardless of the mechanisms of tl1e elevated Pac~ during
IMV and fluid repletion produced an improvement, IMV, all three groups of investigators concluded that the
TABLE 8-1 Effect of IMV versus ACV on pH and Paco,
RATE (BREATHS PER

pH Paco2 (mmHg) MINUTE)
Reference
No. lM\1 AC\1 IMV ACV lM\1 AC\1 II
63 7.41 ± 0.063 7.45 ±0.06 43.0 ± 6.3• 38.0±6.3 7.1 (33.6) 15.'1 40
102 7.48 ±0.05b 7.51 ± 0.04 29.7 ± 6.1 28.6 ±4.9 1/2 AC\1 ra te NA 26
105 7.42 ± o.o8• 7.45 ±0.04 40.7 ± 7.6• 37.9 ±6.7 4 (21) 15.0 18
PATIENTS WITH PREEXISTING RESPIRAlORY ALKALOSIS
63 7.49 ± 0.03 7.49 ± O.Q3 27.4 ± 6.3 29.1 ±4.7 17

105 7.46 ± 0.07" 7.49 ± 0.03 37.8 ± 7.4 35.7±6.7 12
"p< O.Ql.
bp< 0.05.
NOTE: Values are mean± SD; only mean rate is sho>~n. Number in parenthesis denotes total mandatory and spontaneous brea th
rates. Tidal volume was maintained the same for the marldatory breath with both lMV and ACV.
ABBREVIATIONS: IMV, in termittent mandatory ventilation; ACV, assist-control ventilation; NA, not available.
SOURCES: Adapted, with permission, from Hudson et al,63 Groeger et al, 102 and Culpepper et al."105
decrease in pH and increase in Pac~ were minimal and of one study of a small number of patients with acute res-
questionable clinical significance. Furthermore, in studies piratory failure,120 PSV application at levels of up to 30
where IMV was compared with ACV in a subgroup of cmH2 0 during SIMV (IMV rate of 6-10 breaths per minute)
patients with preexisting respiratory alkalosis, respiratory and PEEP of 3-13 cmH2 0 did not result in cardiovascu-
alkalosis pers isted during IMV (Table 8-1).63, 105 lar compromise. Comparison between IMV and PSV will
4. Effects on work of breathing in the neonate. Kapasi et be discussed pertainin~ to cardiac output, 103 ventila tion-
1
al ()7 undertook a comparison of the effects of pressure- perfusion distribution, 1 1 and unloading of patient effort.33
limited ACV, SIMV, a nd IMV on WOB and inspiratory 1. Effects 011 cardiac output. Hemod ynamics during SIMV
effort of clinically stable neonates with respiratory d is- and PSV were studied in critically ill patients by initially
tress syndrome. The mandatory breath rate with both applying ACV to the patients. 103 The VT of the mandatory
SIMV and IMV was set the same as that of the ACV breaths with SIMV then was set the same as that of ACV,
(range 14-25 breaths per minute). Average total respira- at a rate of 75% of the ACV ra te. With PSV, the inspiratory
tory rate was not significantly different among the modes pressure was set to produce a VT similar to that of ACV (av-
(IMV, 56.3 breaths per minute; SIMV, 58.3 breaths per erage pressure of21 cmH 2 0 ). Cardiac output (measured by
minute; ACV, 58.8 breaths p er minute). The WOB was thermodilution), oxygen transport, and Vo2 were the same
estimated using the esophageal pressure, calculated us- for both ventilation modes. As a primary means of ventila-
ing the Campbell diagram. no, 111 Both WOB and inspiratory support, both SIMV and PSV have comparable effects
tory effo rt were least with ACV and highest with IMV; on hemodynamics.
SIMV had values between ACV and IMV. Patient-ventilator 2. Effects 011 ventilation-perfusion. Valentine et al 12"1 stud-
asyncluony occurred only with IMV. Jarreau et al106 re- ied the effect of SIMV, PSV, and airway pressure-release
ported a similar result when comparing IMV, ACV with ventila tion (see below) on ventilation-perfusion d istribu-
inspira tory pressure set at 10-15 cmH2 0, and spontaneous tion in post-cardiac surgery patients who were ready to be
breathing on CPAP. WOB with IMV was similar to that weaned; this section will discuss only the comparison be-
w ith CPAP: 0.81 versus 0.90 J/liter. WOB fell significantly tween SIMV and PSV. SIMV was the initial ventilatory sup-
only during ACV to 0.48-0.47 J/ liter at inspira tory pres- port mode. The IMV rate was adjusted to maintain a pH of
sures of 10 and 15 cmH20 , respectively. Thus, in neona tes, greater than 7.35. With PSV, pressure was titrated to achieve
patient-triggered ACV provides better patient-ventilator a mean end-tidal Pc~ of 40 mmHg. Ventilation-perfusion
synchrony and unloading of workload than continuous- distribu tion was assessed using the inert-gas elimination
flow IMV does. techniq ue.84 The dispersion of ventilation-perfusion ratios,
In summary, the limited number of studies suggests min- calculated as the logarithmic sta ndard deviation of perfu-
imal differences between the effects of high levels of IMV sion (log SDQ) and ventilation (log SDV), was similar for
and ACV on cardiac output, V0 2' and respiratory alkalosis. SIMV and PSV. Right-to-left intrapulmonary shunt and fra c-
Because of lower mean airway and intrapleural pressures, tional dead-space ventilation did not differ significantly. Ta-
IMV should help to improve cardiovascular function in pable 8-2 shows the effects on arterial blood gases, respira-
tients who exhibit hemodynamic compromise during ACV. tory mechanics, and V~. Differences in arterial blood gases
In neonates, ACV is more effective in unloading the WOB were of questionable clinical significance. Peak airway pres-
and providing synchrony than IMV. sure was significantly higher w ith SIMV, but mean transpul-
monary pressure was comparable. As sole ventilator sup-
IMV AND PSV port, SIMV and PSV provide comparable and adequate gas
As with JMV, PSV provides the patient with some auton- exchange in postoperative patients who were ready to be
omy to alter breathing patterns in response to ventilatory weaned. No s tudy has yet compared the efficacy of IMV
demand. PSV is a form of ventilatory support in which the and PSV as a primary m eans of ventilator support during
patient's inspiratory effort is assisted by the ventilator up to acute respiratory failure.
a preset inspiratory pressure level and remains at that level 3. Effects 011 patie11t effort. Leung et al33 carried out a head-
until the ventilator cycle-off algorithm is activated. 11 2, 114 Un- to-head comparison of the efficacy of SIMV and PSV in un-
like IMV, in which the number of mandatory breaths is fixed, loading inspiratory effort a t various levels of assistance. The
PSV assists every breath, and the ventilator contribution to rate of cha nge in ins piratory effort w ith increasing assista nce
total workload is variable. Because the set inspiratory pres- levels, estimated as PTP per minute, did not differ between
sure is fixed with PSV, when patient ventilatory demand the two modes. Unloading efficacy, however, differed ac-
increases, inspiratory effort may exceed the ventilator con- cording to the level of assistance. From 0-60% of maximum,
tribution to total workload (see Chapter 9).n 5 PSV can be the decrease in PTP per minute was greater with PSV than
added to IMV to unload inspiratory muscle work during with SIMV. At higher assista nce level, the converse was ob-
the sponta neous breathing cycles. The addition of a small served (Fig. 8-9). Frequency decreased linearly v.rith increase
amount of PSV (5 em HzO) to pressure-triggered SIMV is ad- in PSV. With SIMV, frequency changed little until a high as-
equate to overcome the lack of flow delivery observed with sis tance level was provided (see Fig. 8-9).122 Thus, when a
some press ure-triggered SIMV systerns.31 Higher levels of high assistance level is needed, both SIMV and PSV provide
PSV not only help in overcoming the ventilator circuit and comparable assistance. At low to medimn assistance lev-
endotracheal tube resistance 116, 1l7 but also a ugment VT and els, however, a greater decrease in patient effort with PSV
unload the elastic work of the spontaneous breaths.11 8, l19 In makes it mo re useful clinically than SIMV. Leung et al33 a lso
TABLE 8-2 Gas Exchange, Mechanics, and Oxygen creases inspiratory muscle effort but also increases ineffec-
Consum ption during SIMV and PSV tive triggering. The impact of ineffective triggering on ven-
srMV PSV
tilator outcome remains unclear.
FI~ 0.44 ± 0.11 0.44 ± 0.11 IMV AND AIRWAY PRESSURE-RELEASE

pH 7.41 ± 0.02 7.36 ± 0.02° VENTILATION
Pac~, mmHg 33.0±2.0 39.0 ± 2.0" Airway pressure-release ventilation (APRV) consists essen-
Pa~,mmHg 102.0 ± 7.0 98.0 ± 8.0 tially of two CPAP levels with a transient decrease or "re-
Peak Paw, on H20 32.8 ± 1.3 19.4 ±2.13
Mean Paw, crnH20 9.6 ± 1.1 8.4 ± 1.0
lease" of airway pressure from a higher CPAP to a lower
Ppl,cmH20 3.8 ± 1.0 3.8 ± 1.1 CPAP for a set release time. Spontaneous breathing is al-
Ptp, cmH20 5.8 ± 0.6 4.6 ± 0.5 lowed to occur between airway pressure releases. '~~ 3· 123-'l 25
V£, liters/ min 9.4 ± 0.6 9.0± 0.5 The pressure gradient between the two CPAP levels and the
fS, breaths per min ute 3.4 ± 1.8 frequency of releases determine the level of ventilator sup-
fM, breaths per mi11ute 8.4 ± 0.4 15.8 ± 0.9" port (see Chapter 12). The original version of APRV used
VTS, liters 0.08 ± 0.07 a short release time, and in the absence of spontaneous
Vr M, liters 1.03 ± 0.03 0.58 ± 0.03° breathing, APRV resembled pressure-controlled inverse-
Vo2 , ml/ min 269 ± 13 268 ± 14 ratio ventilation."123 The modified version, in which the
•p < 0.05.
inspiration-to-expiration (I:E) ratio is adjustable, is termed
NOTE: Valut-s are mean ± SE; 11 =9. biphnsic intermitte11t positive airway pressure (BiPAP). 125 The
ABBREVIATIONS: SIMV, synchronous intermittent mandatory ventilation; PSV, primary indication for APRV is the provision of ventilation
pressure-support ventilation; Fr~, inspired oxygen fraction. Paw, airway pres- during an oxygenation crisis.123 Although the indications
su re; Ppl, pleu ral pressure; Ptp, transpulmonary pressure; V£, total tninute and operating principles of IMV and APRV differ signif-
ventilation; fS, frequency of spontaneous breaths during SIMV; fM, frequency
of ma ndatory breaths or pressure support assisted breaths; VrS, tidal volume
icantly, both modes allow the patient to breathe sponta-
of spontaneous breath d uring SIMV; VrM. tidal volume of mandatory breath neously between machine-cycled breaths. 123· 124 Compari-
or presssure-support assisted breath; Vo2 , oxygen COMumption. son of IMV with APRV will be discussed with regard to
souRcE: Adapted, with permission, from Valentine el al. 121 its efficacy as a primary means of ventilator support in ra-
tients with acute respiratory distress syndrome (ARDS) 12 in
assessed the patient's wasted efforts or nontriggered at- relation to gas excllange, 121•126 - 128 hemodynamics,126· 128·129
tempts during both SIMV and PSV. The number of non- breathing comfort,128·130 intubation duration, and sedative
triggered attempts is proportional to the assistance level use.126, J31
and highest at 100% of macl1ine assistance (29% with SIMV Recently, Varpula et al 126 undertook a randomized, con-
and 26% with PSV). The breaths preceding the non triggered trolled comparison of pressure-limited SIMV (with 10
attempts had a shorter total duration and expiratory time, cmH2 0 of PS added to the unassisted breaths) and APRV in
higher VT, and higher dynamic intrinsic PEEP (PEEP,) than patients with ARDS. The primary endpoint was the num-
did the breaths preceding triggered breaths. This obser- ber of ventilator-free days from the time of randomization
vation suggests that nontriggered attempts resulted from to day 28. The secondary endpoints were the effect on gas
an inspiratory effort that was insufficient to overcome the exchange, hemodynamics, and sedative use. PEEP was set
elevated recoil pressure associated with dynamic hyperin- slightly above the lower inflection point on the pressure-
flation. Thus, increasing the ventilator assistance level de- volume curve obtained during paralysis (or if not detected,
at 10 cmH20). The upper inflection point was never ex-
FIGURE 8-9 Changes in PTP per m inute (left pauel) and ceeded (or if not detected, the inspiratory pressure was
frequency (riglt t pauel) as intennittent ma.n datory ventilation set at less than 35 cmH20). The pressure-release frequ ency
(IMV) and pressure-support ventilation (PSV) were increas ed with APRV and the macltine assistance ra te with SIMV
progressively. PSV of 100% represents the level necessary to
were similar at 12 breaths per minute. The I:E ratio with
achieve a VT equivalent to that during ACV (10 mVkg); IMV 100%
APRV was set at 4:1; with SIMV, it was set at 1:2 and ad-
is the same ventilator rate and VT as during ACV. (Adnpted, witl1
penuission, from Letmg et nl: Am TRespir Crit Care Mcd 155:1940-8,
justed to 2:1. Ventilator-free days, gas exchange, hemody-
1997; aud Tobi11 et nl: Am TRcspir Crit Care Met1163:1059-63, 2001.) namics, and sedative dosage were comparable with the two
modes, although average inspiratory pressure was signifi-
400 35 cantly lower witl1. APRV than with SIMV (25.9 versus 28.6
c
oiMV
~
c cmH20). Moderate hypercapnia developed during the first
E
U! 300 ] • PSV
0.
J:
.a
~
25
study day in both groups but returned toward normal after
4 days. Previous studies of patients with lung injury 127• 128 or
E 200 u
1: after cardiac surgery 12.'-'129 demonstrated comparable effects
u
c
-
·e 1oo "' .,.
Cll
:I
e
IL \
of SIMV and APRV on gas exchange and hemodynamics. In
contrast to patients witl1 ARDS, application of short-term
~
1-
~
0
15 • APRV proved superior to SIMV in patients who underwent
coronary artery bypass surgery. Intubation duration was
0 20 40 60 80 100 0 20 4C 60 80 100 about 4 hours shorter with APRV than witl1 SIMV (mean
Ventilator Assistance, percent 10.1 versus 14.7 hours). Analgesic and sedative dosage also
was less with APRV than with SitvfV. Tlus study, however, pared the short-term effects of ASV versus SIMV plus PS on
was a nonrandomized, open clinical trial. patient-ventilator interaction in patients ready to be weaned
Breathing comfort during SIMV and APRV were eval- from mechanical ventilation. ASV achieved aVE similar to
uated in inexperienced healthy s ubjects breathing via a that of SIMV. Central neural drive, however, estimated as
mouthpiece and compared with PSV. SIMV was set at 8 P0 .1 , and sternocleidomastoid electrical activity, measured
breaths per minute, VT at 5 ml/ kg, and PEEP at 5 cmH20. with surface electrodes, were reduced markedly. Thus ASV
The low and high PEEP levels with APRV were set at 5 and provided comparable total VE but with a significantly de-
10 cmH20, the release rate was 8 breaths per minute, and creased inspiratory load than did SIMV plus PS.
the I:E ratio was 1:2. PSV was set at 10 cmi-12 0 with PEEP
of 5 cmH20. Breathing comfort was measured with a visual
analog scale (0-10 em). PSV achieved the greatest comfort, Pressure-Regul ated Volume-Controlled Ventilation
SIMV the worst, and APRV fell between PSV and SIMV Pressure-regulated volume-controlled ventilation (PRVCV)
(2.03, 5.38, and 4.12 em, respectively). Unfortunately, flow- is a dual-controt breatll-to-breath mode. PRVCV has botl1
limited SIMV was employed rather than pressure-limited the benefits of pressure-controlled ventilation, with a con-
SIMV (both APRV and PSV are pressure-limited ventilation stant VT, and automatic weaning from pressure limit as pa-
modes). tient compliance improves and / or patient effort increases
(see Chapter 16). Piotrowski et al139 undertook a random-
ized, controlled comparison ofPRVCV and continuous-flow
IMV AND PROPORTIONAL-ASSIST VENTILATION, IMV in neonates with respiratory distress syndrome. Thirty
ADAPTIVE-SUPPORT VENTILATION, AND neonates received IMV, and 27 received PRVCV; the average
PRESSURE-REGULATED VOLUME CONTROL peak inspiratory pressures were 18.6 and 16.2 cmH2 0, re-
Prop ortional-Assist Ventilation spectively. The ItvfV rate was selected by the clinician. With
Proportional-assist ventilation (PAV) is a mode in which PRVCV, the VT was set at5~ ml/ kg. The primary endpoint
the ventilator instantaneously generates pressure in propor- was duration of mechanical ventilation and incidence of
tion to the patient's effort (see Chapter 13).'132 The ventilator bronchopulmonary dysplasia. The secondary endpoint was
amplifies the patient's inspiratory effort witl1out any prese- complications from mechanical ventilation, consisting of air
lected target voltune or pressure. A randomized crossover leaks, intraventricular hemorrhage, and hemodynamic in-
comparison of continuous-flow IMV versus PAY was con- stability. PRVCV did not decrease duration of mechanical
ducted in 36 preterm infants. 133 The inspiratory pressure ventilation or incidence of bronchopulmonary dysplasia,
with IMV was set to deliver a VT of4 to 6 ml/kg. The TMV although it decreased the incidence of high-grade intraven-
rate was not reported. With PAV, the volume-assist gain tricular hemorrhage (11 % versus 35%). The benefit may have
was adjusted to decrease lung elastance to its normal value, occurred in part because PRVCV delivers a stable volume.
whereas the flow-assist gain was set at -20 cmH20 /liter Is. In newborn preterm infants, large fluctuations in intratllO-
Each mode was applied for 45 minutes. With PAY, peak and racic and arterial pressures cause variations in cerebral
mean airway pressures and transpulmonary pressure were blood flow velocity that is a risk factor for intraventricu-
significantly lower, frequency was higher, and VT was com- lar hemorrhage. 140 In a subgroup of neonates weighing less
parable to that with lMV, resulting in a higher VE. Paco1 , than 1000 g,duration of mechanical ventilation was reduced
however, remained the same as with TMV, and Pa ~ was and hypotension was less in the PRVCV group than in the
higher. There were no significant differences in the num- IMV group. Unfortunately, the number of neonates in the
ber of apneic or hypoxemic episodes. The lower transpul- subgroup was small (n =10). In tl1e preterm infants, PRVCV
monary pressure with PAY might help to prevent lung in- appears to decrease complications related to mechanical
jury during prolonged mechanical ventilation. The results ventilation. A patient-triggered, pressure-controlled venti-
in preterm infants were similar to those in an earlier short- lation without volume guarantee would have been a better
term trial in a few adult patients.134 comparison with to assess PRVCV's efficacy.
Adaptive-Support Ventilation
IMV AS A WEANING METHOD
Adaptive-support ventilation (ASV) is based on the work by
Otis et al135 and Mead et al,'136 who demonstrated that any IMV, PRESSURE SUPPORT, AND T PIECE
given level of alveolar ventilation has an optimal respiratory IMV was first used in adult patients as a means of discontin-
frequency that is least costly in terms of respiratory work: uing mecl1anical ventilation.5 This method was claimed to
the frequency at which the respiratory muscles develop the be more efficient, safer, and more readily accepted by the pa-
least average force or tension. 136 ASV is a tnode that can tient, and it avoided the necess ity of setting up aT-piece cir-
alternate between pressure control and pressure support, cuit. While preceding ventilator support may be with either
relying on closed-loop regulation of ventilator settings that the ACV or IMV, IMV is applied when the patient is ready
respond to changes in respiratory system mechanics and to be weaned. The number of mandatory breaths is reduced
spontaneous breathing efforts (see Chapter 16). ASV adjusts gradually (1-3 breaths) at 1- to 4-hour intervals, provided
inspiratory pressure, I:E ratio, and mandatory rate to main- that arterial pH remains greater than 7.307 or 7.35,141 re-
tain the target minute ventilation and respiratory rate within gardless of other physiologic measurements. An TMV rate
a frarne designed to avoid both rapid, shallow breathing of zero or close to zero is maintained for several hours, or
and excessive inflation volumes. 137 Tassaux et al138 com- as long as 24 hours, before extubating the patient.
CHAPTERS INTERMITIENTMANDATORYVENTILATION 213
With PSV as a weaning method, tl1e pressure level is set Once o r tw ice a day, the SIMV rate was decreased by 2
initially at a maximum, defined as the level that produces a to 4 breaths per minute if patients did not demonstrate
VT of 10-12 ml/ kg; then the PS level is reduced according signs of poor tolerance. When a patient demonstrated poor
to the patient's respiratory frequency."142 When the PS level tolerance, the SIMV rate was increased to its preceding
reaches 5 anH20 , extubation is considered. level. When a patient tolerated a SIMV rate of 4 breaths
With aT piece, once the pa tient meets predefined weaning per minute or less over 1 day, tracheal extubation was per-
criteria, he or she is placed on a T-piece circuit. 143 Progres- formed. The T-piece method consisted of a gradual length-
sively longer intervals of spontaneous breathing through ening of the periods of d isconnection from the ventilator.
a T piece are alternated with ACV. Extubation is consid- The initial T-piece trial was set shorter than the initial toler-
ered when the patient can sustain breathing through a T ance duration (mean duration of 38 minutes). The number
piece for 1-2 hours. The early claim for IMV's superiority of T-piece trials depended on the length of disconnection
over a T piece was not based on a controlled study, and and on nurse availability a nd varied from three to eight
subsequent retrospective 144 and prospective studies145, 146 trials per day. The T-piece periods were lengthened incre-
failed to demonstrate IMV's superiority. Studies compar- mentally twice a day. Between the T-piece trials, ACV was
ing IMV and PSV s howed either a significantly reduced applied. When the duration of a T-piece trial had reach ed
dura tion147 or a tendency for a shorter weaning time148 2 hours with adequate gas exchange, tracheal extubation
with PSV. As PSV grew in popularity, two prospective, ran- was performed . In the patients assigned to PSV, the ini-
domized, controlled multicenter trials 149• 150 simulta neously tial pressure was adjusted until the frequency ranged be-
compared the three w eaning modalities: SIMV, PSV, and T tween 20 and 30 breaths per minute. Twice a day, the pres-
piece. These trials laid to rest IMV's claim to superiority over sure was decreased by 2-4 cmH20 if the patient did not
T piece and PSV. show any signs of poor tolerance; if tolerance worsened,
Brochard et al149 studied 109 patients who met three of pressure was increased to its preceding level. When the
the four defined weaning criteria and had failed a 2-hour patient tolerated a PSV level of 8 cmH 20 or less through-
T-piece trial. Patients were randomized to SIMV (n = 43), out a 24-hour period, tracheal extubation was performed.
PSV (n = 31), and T piece (11 = 35). Weaning failure was During the 21-day trial, the probability of being weaned
defined as continued inability to be weaned after 21 days was twice as high with PSV than w ith SIMV or T piece.
on the same mode, the need for reintubation after 48 hours Weaning dura tion did not differ between SIMV and T piece
of extubation, or intercurrent events (e.g., cardiac ischemia but was significantly shorter with PSV than with the other
or nosocomial pneumonia) w ithin 72 hours in the selected two modalities (6 versus 9 days, respectively). The num-
mode. The initial SIMV ra te was set a t half the total fre- ber of weaning success patients was significantly larger
quency during ACV or CMV, keeping VT and flow rates with PSV (77%) than with SIMV (58%) or T piece (57%)
constant (mean initial SIMV rate of 9.5 breaths per minute) . (Table 8-3).
TABLE 8-3 Tr ials Comparing Three Weaning Methods: I ntermittent T Piece, Pressure-Support
Ventilation (PSV), and Synchronized Intermittent Mandatory Ventilation (SIMV)
SUCCESSFUL WEAN [n (%))
Trial T Piece PSV SIMV
Brochard ct al 149 20/35 (57) 24/31 (77) 25 / 43 (58)

Esteban ct ai150 27/33 (82) 23/37 (62) 20/ 29 (69)
RISK DIFFERENCE (%)"
T Piece vs. PSV T Piece vs. SIMV PSV vs. SIMV
Brochard et al 149 - 20 (- 42, 2) - 1 (- 23, 21) 19 (- 2, 40)

Esteban et al 150 14 (- 5, 32) 7 (- 13, 27) - 7 (- 20, 16)
TIME 10 EXTUBATION (DAYS)
TPiecc PSV SfMV
Brochard et a 1149 8.5 ± 8.3 5.7 ± 3.7 9.9 ± 8.2

Esteban et al 150 3 (2, 6) 4 (2, 12) 5 (3, 11)
"Risk differences express..>d as the difference in proportions of successfully weaned subjects between respective wean-
ing methods. Negative numbers imply lower success rates and positive numbers higher success rates. The 95% con-
fidence intervals follow risk differences in parentheses. Time to extubation is presented as either mean ± 50 10 or
median (first and third quartiles). 150
souRcES: Adapted, with permission, from Brochard et al, 149 Esteban et al, 150 and Butler et aJ 151 for the risk-difference
calculations.
In the study by Esteban et al,1 50 130 patients who met two pressure was ma intained at 3 on H 20 throughout the study.
of three weaning criteria and had failed a 2-hourT-piece trial Weaning failure was defined as either the failure to achieve
were random!y assigned to one of four me thods: SlMV (n = a reduction in ventilator support w ithin 48 hours or re-
29), PSV (11 = 37), intermittent T-piece trials (two or more per quirement for reintubation within 48 hours of extubation.
day) (n = 37), and a o nce-daily T-piece trial (n. = 31). The ini- Reintubation was indicated w hen respiratory acidosis de-
tial SIMV rate was set at half the frequency during ACV (av- veloped or frequent apneas or one major apnea occurred.
erage 10 breaths per minute). When the patient tolerated it, In the first trial, there were no significant differences in the
SIMV was reduced twice a day by 2 to 4 breaths per minute. success rate with ACV or SIMV (70% versus 75%) or the du-
Tracheal extubation was performed w hen the patient toler- ration of successful weaning (median 33 versus 30 hours).
ated an SIMV rate of 5 breaths per minute for 2 hours with- In the second trial, differences between the weaning su c-
out signs of distress. WiU1 the PSV, U1e initial pressure was cess rates were not significant, but the median weaning du-
adjusted to achieve a frequency of 25 breaths per minute o r ration was significantly shorter with ACV (24 hours) than
less (average pressure of 18 cmH2 0). According to patient with SlMV (50 hours) (P< 0.05). The results of the second
tolerance, pressure was reduced at least twice a day by 2 to 4 trial are comparable with those of the adult studies, 149~ 150
cmH 20 . When the patient tolera ted a PSV level of 5 em H20 demons trating SlMV's inferiority toT-piece or CPAP wean-
for 2 hours, tracheal extubation was performed. With inter- ing methods. A reduction in inspiratory pressure alone
mittent T-piece trials, the patient breathed thro ugh aT-piece is favored in weaning preterm infants from mechanical
circuit or a continuous-flow CPAP of 5 cmH2 0 or less a t least ventilation.
twice a day. Trial duration was increased gradually, and
when the patient tolerated a 2-hour trial, extubation was IMV AND MANDATORY MINUTE VOLUME AND ASV
perfom1ed . Between the T-piece trials, ACV was applied. Manda tory minute ventilation (MMV) allows the patient to
WiU1 the once-daily T-piece method, the patient breathed breathe spontaneou sly yet ensures that a preset minute ven-
through a T-piece circuit, after which ACV was resumed for tilation is maintained should the patient's spontaneous ven-
24 hours. Trial duration was increased gradually. When the tilation d ecline below the set level. 155 MMV was developed
patient tolerated a 2-hour trial, extubation was performed. to overcome certain ineffective features of 1MV.156 When
Weaning failure was defined as the need for reintubation the set mandatory IMV rate is less than required to achieve
within 48 hours after extubation or the inability to extubate ade<Juate ventilation, alveolar hypoventilation will ensue
the patient after 14 days. The median successful weaning w henever a patient's total minute ventilation falls below a
duration was 5 days for SIMV, 4 days for PSV, 3 days fo r critical level. This drawback of 1MV can be circumvented
intermittent T-piece trials, and 3 days for the once-daily T- with MMV, which actuates a feedback control so that the
piece trials. The rate of successful weaning for the once-daily ventilator provides pressurized brea ths of a fixed volume
T-piece method was three times faster than with SIMV (rate to achieve a preset tota l minute ventilation.
ratio 2.83) and two times faster than with PSV (rate ratio Weaning with lMV and MMV was s tudied prospectively
2.05) . The rate of success for intermittent or once-daily T- in 40 patients recovering from acute respiratory failure
piece trials did not differ significantly. The percentage of caused by parenchyma l lung injury and chronic airflow
patients weaned successfully was 69%,62%, 82%, and 71% obstruction.157 After meeting defined weaning criteria, the
for SlMV, PSV, intermittent T piece, and once-daily T piece, patients were randomized to 1MV (11 = 18) or MMV (11 = 22).
respectively. In the 1MV group, IMV rate was decreased by 2 breaths per
These two large randomized studies showed conflicting minute at 3- to 4-hour intervals during the daytime only
results. In the study of Brochard et al, 149 PSV was s uperior to until the IMV rate was equal to zero. Weaning was con-
T piece and SIMV. ln the study of Esteban et al, 150 T piece was sidered complete after 4 hours of breathing on CPAP. In
superior to PSV and SIMV. Despite the subtle differences in the MMV group, MMV was set at 75% of the total minute
methodology, both trialc; demonstrated that weaning time volume preceding the weaning trial; this was achieved by
was the longest with SIMV.151 Thus both T piece and PSV decreasing frequency while maintaining a VTof 12 ml/kg as
were superior to SIMV (see Table 8-3).152, 153 a refere nce value. Weaning was considered complete after 4
In weaning preterm infants, Dimitriou et al 154 compared hours of independent spontaneous breathing. Weaning fail-
pressure-limited SIMV with ACV in two separate random- ure was defined as an inability to complete the trial or the
ized, controlled trials. With both SIMV and ACV (n = 20 need for ventilator support for the same underlying disease.
each), inspira tory pressure was reduced in decrements of Successful weaning was comparable: 86% for IMV and 89%
2 cmH20 until a defined target pressure tailored to the infor MMV. The weaning trial was longer in the IMV group
fant's bod y weight was reached. With SIMV, in addition to (33 hours) tha n in the MMV group (4.75 hours).
decreasing pressure, the SlMV rate was reduced in decre- SIMV and ASV were compared as weaning modalities in
ments of 5 breaths per minute until a target rate of 20 breaths a prospective, randomized study in post-cardiac surgery
per minute was reached in the first trial. In the second trial, patients.158 With both ASV (11 = 18) and SIMV (n = 16),
the target was 5 breaths per rninu te. The frequency of decre- the patients underwent three ventilation phases. With ASV,
ments in pressure or SlMV rate was not reported. When in phase 1, the initial settings were the ideal body weight
the infants tolerated the target pressure (for ACV) or tar- (IBW), the desired minute volume at the default value of
get pressure and rate (for SlMV), ventilation was switched 100 ml/kg of IBW, and peak airway pressure of less than
to CPAP for 1 hour before extubation. The end-expiratory 25 cmH20. Adjustment of minute volume was dictated by
CHAPTERS INTERMITTENTMANDATORYVENTILATION 215
a Paco1 of less than 38 or g reater than 50 mmHg. Phase 1 Elvira flow wavefo rm tha t accounted for the short contrac-
ended when there were no controlled breaths for 20 min- tion time was more of a ramp than a sine wave. The in-
utes. Phase 2 was a continuation of phase 1; it ended when vestigators concluded that differences in subject responses
PS was decreased to 10 cmH2 0 (±2 cmH2 0) and maintained to different ventilators were related to flow or pressure
for 20 minutes. The patient then entered into phase 3, where waveforms and that different subjects may prefer different
PS was set manually at 5 cmHzO for 10 minutes. When the waveforms.
patient showed satisfactory tolerance, tracheal extubation
was performed. The initial settings for phase 1 in the SIMV
group consisted of a VT of 8 rnl/kg and an SIMV rate ad- Adjustment at the Bedside
justed to achieve a Paco, of between 38 and 50 mmHg. The
SIMV rate was then set at 12 breaths per minute. When and Troubleshooting
spontaneous breaths exceeded 6 breaths per minute for
20 minute, the patient was switched to PSV of 10 cmH2 0 SIMV settings consist of the trigger sensitivity, VT, flow,
(phase 2). The patient was reassessed 20 minutes later for and the IMV rate for the flow-limit volume-cycled manda-
further reduction of PSV or returned to SIMV. If the patient tory breaths. For pressure-limit time-cycled breaths, the
tolerated it, PSV was reduced to 5 cmH2 0 (phase 3), as in ventilator settings include the trigger sensitivity, inspira-
the ASV group. There was no difference in duration of tra- tory pressure, inspiratory time, pressure attack rate, and
cheal intubation, and all patients except for two (one in eacl1 IMV ra te. VT is also set if dual hybrid breath-to-breath vol-
group) were exhtbated within 6 hours. In the ASV group, ume guarantee is applied. With either flow- or pressure-
patients required fewer manipulations of ventilator settings limited mandatory breaths, pressure support, but not vol-
and endured fewer high inspiratory pressure alarms. This ume support, can be added to the spontaneous breaths to
study was performed in postopera tive patients who had re- overcome circuit and endotracheal tube resistance. Monitor-
ceived mechanical ventilation for less than 24 hours before ing of the patient and the ventilator output waveforms can-
weaning attempts. Because mecl1anicaJ ventilation duration not be overemphasized. 164 For example, palpable abdomi-
before weaning influenced the weaning success rate, 159 the nal contractions suggest expiratory muscle r ecruitment and
response of critically ill patients to the preceding weaning possible encroachment of mechanicaJ inspiratory time into
methods may be different. neural expiratory time. 52 Adjustment to reduce mechanicaJ
inspiratory time can be made by increasing flow rate (flow-
limited breaths) or reducing inspiratory time (pressure-
limited breaths). Despite the risk associated with tachypnea
Variation in Delivery among when m echanical inspiratory time is reduced, Laghi et al165
Ventilator Brands demonstrated an increase in exhalation time and decrease
in intrins ic PEEP, changes conducive to improved pa tient-
To my knowledge, in the SIMV mode, no study has yet ventilator interaction.
evaluated the response of various ventilators to patient
flow demand or vice versa. As part of a study evaJuat-
ing the response of muscle pressure generation to various Important Unknowns
wuoading conditions with assisted ventilation, Mecklen-
burgh and Mapleson160 evaluated the response of three IMV has stood the test of time since its clinical applica-
ventilators, Hamilton Veolar, Engstrom Elvira, and Puri- tion as a primary means of ventilator support in the early
tan Bennett 7200, in the SIMV mode in healthy subjects . 1970s. To date, advanced technology enables most ven-
VT was set at 1.5 times the spontaneous VT and the SIMV tilators to be equipped with closed-loop ventilation that
rate at 6 brea ths per minute. The flow waveform was set allows full ventilator support with gradual support reduc-
to "sine wave." Muscle pressure was caJculated using the tion. Unfortunately, few large randomized, controlled tri-
equation of mo tion from instantaneous airway pressure, als have yet compared the efficacy of d osed-loop ventila-
flow, and volume with the respiratory system's known re- tion with SIMV in terms of mechanical ventilation duration,
sistance and elastance.16 1 Amplitude of muscle pressure patient-ventilator interaction, sensation of dyspnea, and
generation was similar across the three ventilators. Con- ventilator-associated complications.
traction time for mechanical breaths was shortest with the Studies have shown that inspiratory muscle activity is
Engstrom Elvira at 1.03 seconds versus 1.38 seconds for of the same intens ity during machine assistance as during
the H amilton Veolar and 1.37 seconds for the Puritan Ben- the intervening spontaneous breaths45 and that SIMV pro-
nett. For unassisted breaths, contraction time again was longs weaning. 149•150 Given that the diaphragm is activated
shortest with the Engstrom Elvira (1.33 versus 158 seconds with eacl1 breath, it is possible that SIMV protects the res-
for the Hamilton Veolar and 1.70 seconds for the Puritan piratory muscles from disuse atrophy, which occurs with
Bennett). Because VT was set constant for all three venti- CMV.68 - 70 Alternatively, the increased workload at low lev-
lators, the short contraction time led to higher peak air- els of machine assistance actually may cause overload 162; 163
way pressures w ith the Engstrom Elvira (9.4 versus 3.9 and prolong mechanical ventilation duration or weaning
cmi-12 0 for tl1e Hamilton Veolar and 4.0 cmH20 for the time. Which of those two factors plays a role during a low
Puritan Bennett). Despite the set sine wave, the Engstrom assistance level of SIMV is unknown.
The Future 10. Esteban A, Anzueto A, Alia I, et a!. How is mechanical ven-
tilation employed in the intensive care unit? An international
utilization review. Am J Respir Crit Care Med 2000; 161:1450-8.
A ventilator that adapts instantaneously to patient venti-
11. Greenough A, Milner A, Dimitriou G. Synchronized mechan-
latory demand would be ideal. Because SIMV has simple ical ventila tion for respiratory support in newborn infants.
ventila tor settings and the options of combining it w ith Cochrane Database Syst Rev 2004 Oct 18; 4:CD000456.
pressure support a nd of guaranteeing volume with use of 12. American Association of Respiratory Care. Consensus state-
pressure-limited mandato ry breaths, SIMV will remain an ment on the essentials of mechanical ventilators-1992. Respir
important primary ventilator mode for critically ill patients. Care 1992; 37:1000-8.
If SIMV were to be replaced, clinical trials would be needed 13. Macintyre NR, Gropper C, Westfall T. Combining pressure-
that compa re SIMV with other modalities, similar to those limiting and volume-cycling features in a patient-interactive
perfom1ed during weaning. If SIMV continues to be used mechanical breath. Crit Care Med 1994; 22:353-7.
widely, its long-term effects on respiratory muscle function, 14. Graybar GB, Smith RA. Apparatus and techniques for intermit-
tent manda tory ventilation. tnt Anesthesiol Oin 1980; 18:53-80.
whether protective or damaging as a result of overload,
15. Hillman DR, Breakey J , Lam M, et al. Minimiz ing
should be investigated. the work of breathing with continuous positive airway
pressure and intermittent mandatory ventilation: An im-
proved continuous low-flow system. Crit Care Med 1987;
15:665-70.
Summary and Conclusions 16. Braschi A, Iotti G, Locatelli A, et al. A continuous flow inter-
mitte11t mandatory ventilation with continuous positive airway
Recent studies have provided a better understanding of pressure circuit with high-compliance reservoir bag. Cri t Care
patient-ventilator interaction with SIMV. For critically ill pa- Med 1987; 15:947- 50.
tients, SJMV remains one of the most widely used modes 17. Weled BJ, Winfrey D, Downs JB. Measuring exhaled volume
of ventilation, as does ACV. To date, no large random- with continuous positive airway pressure and intermittent
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~
Chapter 9 tion, and maintenance of spontaneous respiratory activity
appears to lessen this likelihood.12 Finally, partial support
PRESSURE-SUPPORT may facilitate the weaning of problematic patients. An ideal
mode of pa rtia l support should supply both full ventila-
VENTILATION tor support and optimal support during weaning, optimize
patient-ventilator synchronization, o ptimize patient com-
LAURENT BROCI-IA RD fort while reducing the need for sedation and the risk of
FRAN<;OIS LELLOUCI-IE
cardiovascular consequences, and if possible, facilitate or
reduce the duration of the weaning. PSV may meet these
requirements, at least in part, as discussed in this chapter.
PSV also has limitations, which are delineated. Improve-
ment in the delivery of PSV continues as a field of research.
Despite more than 20 years of use, PSV remains at times
DEFINITION AND PHASES confus ing to clinicians. First, although PSV is remarkably
Initiation of the Cycle effective in reducing patient effort and avoiding respiratory
Pressurization d istress, it sometimes deHvers s upport much in excess of pa-
Cycling of Expiration tient needs. Problem s may relate to excessive delivered vol-
Other Settings ume, duration of inspiration relative to neural inspiratory
DIFFERENCES AMONG MECHANICAL time (TJ), or both. Much research was undertaken in the late
VENTILATORS 1990s to understand and analyze the consequences of d eliv-
MAIN PHYS IOLOG IC EFFECTS ering excessive pressure. Many benefits of PSV, which pro-
Breathing Pattern vides greater freedom to the patient than traditional modes,
Gas Exchange and Distribution of Ventilation may have been obscured by improper use.
and Perfusion Second, ma ny clinicians often view PSV primarily as a
Work of Breathing and Respiratory Effort mode devoted to weaning. Weaning often has been poorly
Compensation for Work Caused by ETI defined and may not be considered until late in a patient's
and Demand Valve course. TI1us possible indications for the early use of PSV
Effect of Instrumental Dead Space have been disregarded by many clinicians. Some clinicians,
DEGREEOFPATI EN~VENTliATOR SYNCHRONY
worrying about the consequences of providing excessive
DURING PSV freedom to a patient, have combined PSV with synchro-
At Initiation of the Cycle nized intermittent mandatory ventilation (SIMV) with little
Pressurization Rate and Ins piratory Flow clinical justification. In 1998, an international survey on me-
Inspiratory Cycling off or Cycling to Expiration chanical ventilation was undertaken in 361 ICUs in 20 coun-
DIFFERENCES FROM OTHER MODES tries (publis hed in 2002). 3 On the first day, PSV was used
OF VENTILATION in fewer than 10% of all patients, the combination of SIMV
£ntermittent Positive-Pressure Breathing with PSV was used in almost 15%, and assist-control ven-
Assist-Control Ventilation tilation (ACV) was used in approximately 60%. This result
SIMV could be interpreted as fa ilure of PSV to gain wide accep-
PAV tance. The percentage of use was relatively low (and did
NAVA not vary much over subsequent days), and sole use of PSV
HEMODYNAMIC CONSEQUENCES OF PSV was substantially less than use of a combination of SIMV
ADJUSTM ENT OF PRESSURE LEVEL and PSV, for which little physio logic or clinical data exist.
AT TH E BEDSIDE Providing a detailed explanation for low PSV use, however,
CLOSED-LOOP DELIVERY OF PSV is beyo nd the scope of this chapter.
CLINICAL APPLJ CATIONS Third, in the sa me survey,3 a low level of PSV was used
Weaning to perform a once-daily weaning attempt in 28% of such
Noninvasive Ventilation attempts, a gradual reduction of PSV was used as the sole
Use of Noninvasive Ventilation with PSV for Weaning weaning method in 21% of attempts, and a gradual reduc-
CONCLUSION tion of SIMV and PSV was used in 22% of attempts. Overall,
PSV was used (one way or another) in 45% of weaning a t-
tempts, indicating tha t clinicians consider weaning the main
Pressure-support ventilation (PSV) is a mode of partial ven-
indica tion for PSV.
tilator support. Such modes are used widely in intensive-
care units (ICUs) for several reasons. First, most ventilated
patients (unless deeply sedated and paralyzed) have an in-
tact respiratory drive, a nd thus it is necessary to synchronize Definition and Phases
patient activity with that of the ventilator. Second, by allow-
ing the patient to breathe spontaneously, assisted modes PSV is a pressure-targeted (or pressure-limited) mode
may reduce the need for sedation. Third, d isuse atrophy of in w hich eacll brea th is triggered by the patient a nd
the respiratory muscles can result from controlled ventila- supported.4 - 9 PSV provides breath-by-breath support by
221
IN ITIATION OF THE CYCLE

Triggering of inspiration is initiated by patient effort and is
Paw detected by a pressure or flow sensor. Trigger sensitivity is
adjustable. This mechanism requires an active effort by the
patient, the intensity of which depends on the characteris-
tics of the valve. The opening time delay varies between
50 and 250 ms depending on the ventilator.10-'15 The most
v recent data indicate that most ventilators now respond in
less than 100 ms."~ 6- 18 Opening of the demand valve can be
triggered by a fall in pressure or a difference in the flow sig-
nal between inspiratory and expiratory flows (referred to
Ppl as J1ow-by). For the latter, a constant flow is delivered to the
circuit during the expiratory phase; inspiratory effort then
is detected as a small difference between inspiratory and ex-
piratory flows. Flow triggering avoids the need for a closed
demand valve. Aslanian et alr9 showed that the difference
between pressure-triggered and flow-triggered systems has
FIGURE 9-1 A pressure-su pported breath with tracings of airway become quite small on modern ventilators. The triggering
pressure (Paw), Bow (V), and pleu ral pressure (Ppl). Four phases
phase represents less than 10"/o of a patient's overall effort
of patient effort can be discerned . Phase 1 is still expiratory and
corresponds to an effort performed against in trinsic p ositive
to breathe. A flow-triggering system makes a statistically
end-expiratory pressure (PEEP); it occurs b efore the triggering significant difference but is of limited clinical importance.
system of the ven tilator can d etect an y signal that indicates the
onset o f p atient inspiratory effort. Phase 2 is th e time required to PRESSURIZATION
activate the triggering system of the ventilator (also called the
initiation phase). Phase 3 is the insufflation p hase, during which Once inspiration has been initiated, the ventilator delivers
the ventilator pressurizes the airway at th e level set by the a high inspiratory flow, which decreases rapidly through-
clin ician. This phase is terminated by the cycling-off criterion. out the rest of inspiration. A servo regulatory mecha nism
Patient inspiratory effort may temtinate before the end of this ensures that the proper flow reaches the appropriate preset
ph ase. Phase 4 is the expiratory ph ase. PSV level and keeps this pressure constant until expiration
occurs. Flow regulation varies among ventilators, thus de-
termining the pressure waveform. Usually, the servo valve
is controlled continuously during the breath such that the
means of a positive-pressure boost synchronized with delivered pressure closely approximates the target pressure
inspiratory effort: patient initiated and flow terminated set by the clinician. In general, the aperture of the propor-
(Fig. 9-1). During inspiration, airway pressure is raised to a tional servo valve is reduced progressively as the moni-
preset level: the pressure-support level. The speed of pres- tored pressure gets closer and closer to the target press w-e.
surization initially was fixed and system-specific. Most re- For this reason, the wave shape often constitutes a pressure
cent ventilators, however, offer the possibility of adjusting ramp rather than a true squarewave. The pressure level can
this pressurization rate. Throughout the inspiratory phase, be adjusted between 0 (spontaneous breathing through the
the ventilator works as a pressurized demand-flow system ventilator circuit) and a maximum of 30 or 60 cmH20 (even
at a predetermined pressure level. PSV is maintained until more with some ventilators). In clinical settings, pressure
the machine determines the end of expiration, supposedly levels above 30 cmH20 are rarely reported.
reflecting the end of patient demand. This is achieved by Pressure increases according to a rate that is system-spe-
means of an expiratory trigger mechanism based on de- cific; formerly, it was not adjustable. A high speed of pressur-
cay of inspiratory flow. When inspiratory flow falls below ization produces a square pressure wave; low acl1ievement
a threshold value, which may indicate indirectly that the of the preset PSV level attenuates this shape.4 Many venti-
inspiratory muscles have relaxed, the ventilator cycles to lators now allow adjustment of the rate of pressurization.
the expiratory phase. That is, it releases the PSV and opens The influence of this adjustment on the effectiveness of PSV
its expira tory port. The expiratory phase is free of assis- in reducing the work of breathing is discussed below.
tance; a level of positive end-expira tory pressure (PEEP)
lower than the inspiratory plateau pressure can be applied.
CYCLING OF EXPlRATION
PSV thus can be defined as a patient-initiated (pressure or
flow), pressure-targeted, flow-cycled mode of mechanical During PSV, cycling to exhalation is triggered primarily by
ventilation. a decrease in inspiratory flow from its peak to a system-
Three phases of PSV can be distinguished: (1) recogni- specific threshold value. This critical decrease in inspira-
tion of the beginning of inspiration, (2) pressurization, and tory flow is taken as indirect evidence that the inspira-
(3) recognition of the end of inspiration. These phases con- tory muscles have begun to relax. Expiration is triggered
stitute the working principles of PSV and can vary from when either an absolute level of flow (between 2 and
one ventilator to another (see Fig. 9-1). As discussed below, 6liters/ min) or a fixed percentage of peak inspiratory flow
these variations may induce differences in the effect of PSV (12% or 25%) is reached, depending on the ventilator model
for similar levels of pressurization. (Table 9-1). The threshold value for cycling, which can be
TABLE 9-1 Technical Characteristics of Pressure·Support Ventilation and Available ScHings on lntcnsive·Carc Ventilators
INSP[RA10RY TRIGGER CYCLING-OFF-CRITERION

Ventilator Manufacturer Flow (liters/min) Pressure Pressurization Flow Cycle l)ressurc Cycle TimcCycl~
PB7200 Puritan-Bcnnet/ Tyco 1-15 0.5-20 5 liters/min +1.5cml-h0 3s

l' B 740 Purita n-Bennct/ Tyco 1- 20 10 liters/ min or 25% PF +3cmH20 3.5s
PB760 Puritan-Bennet/ Tyco 1-20 5-100% Adjust. 1-45% PF +J onH20 3.5 s
PB 840 Puritan-Bennet/Tyco 1- 20 5-100% Adust. 1-80% PF + 1.5cmH20 3s
Evita 2 Drager 25% PF High-pressure limit
Evita 2dura Drager 0.3- 15 0-2 s 25% PF l·ligh-pressurc limit
Evita 4 Drager 0.3-15 0-2s 25% PF High-pressure limit 4s
Evita XL Drager 0.3- 15 0-2s 25% I'F High-pressure limit
Savina Drager 25% PF High-pressu_re limit
Servo900C Maquet 0-20 25% PF +3 cmH,o
Servo300 Maquet 0.6-2 0-20 5% PF + 20cml-120
Scrv<>-i Maquet 0.6-2 0-20 0-0.4s Adjust. 1- 80% PP !-Ugh-pressure limit
N
N SerV()oS Mi'lquct 0.6-2 0-20 0-{).4 s Adjust. 1- 80% PF High.. pressurc limit
w Veolar Hamilton 25% PF High-prc,;surc limit 3s
Galileo Hamilton 0.5- 15 0.5-'10 25-200 m$ Adust. 10-40"h PF 1-iigh.. prcssurc limit 3 :'i
Raphocl Hamilton
Bird 8400 ViMys HcaHhcare 1- 10 1- 20 25% PF Hig h ·pr~su r(' Limit 3s
T-Bird Viasys Healthcare 1-20 5-30% PF (submenu) High-pressure limit 3s
Vela \ r,asys Hcalthcarc 1..S Adjust. 5-30% PF High-pressure limit 0.3-3 s
Avea Viasys Healthcare 0.1-20 0. 1- 20 1- 9 Adjust. 5-45% PF High-pressure limit 0.15-5 s
Bear 1000 Viasys Healthcarc 25% PF Ss
B i p~p Vis-ion Respironics Automatic (auto--track) 0.05-0.4 s Automatic (auto-trak)
Esprit Respironics 0.5-20 0-20 0.1-0.9 s Adjust. 10-45% I'F
LTV1000 PuJmonetics 1-9 Adjust. 10-40% PF High-pr<'SSure limit
EliSt.~ Saimc Adjust. 10-40% PF or automatic
e500 Newport 1- 19 Adj\1St. 5-500/ll PF, variable Hig-h·pressure limit
HTSO Newport 0 to - 10 High-prcs•urc limit 0.1-3 s
lnfrasonics Sti'l.r lnfrasonics -0.5-20 4 liters/ min or Hl"k PF 3.5 s
Inspiration eVent 1-25 - 1- 20 Fast/m~ium/low Ad just. 1Q-80%
ABBREVlAnON: Adjust, ndjuSt<tbl~; Pf. pMk flow.

viewed as the sensitivity of the expiratory trigger, formerly and quality of regulation, and termination criteria used to
was no t adjustable. Adjustment now is offered to clinicians cycle from inspiration to expiration. Nonspecific features in-
on many ventilators. clude d1aracteristics o f the d emand valve and/ or triggering
Detection of a small degree of pressure (1- 3 cmH2 0) mechanis m and flow-impeding properties of the expiratory
above the fixed PSV level, consequent to sudden expiratory circuits, including PEEP devices. These differences also may
effort by the patient, also can be used (alone or in combi- vary with the type of ventilator, whether it is designed only
nation with the fl ow criteria) to stop inspiratory assistance. for delivery of noninvasive PSV or is a full intens ive-care
Finally, a tin1e limit for inspiration usually is included. This ventila tor. 17•18•26•27 The relative weight of each factor is diffi-
serves as a safety mechanism if a leak d evelops in the cir- cult to d etermine and may vary from one patient to another.
cuit and the two previous methods of termina ting inspira- This consideration should be kept in mind, however, when
tion become inoperative. Complications have been reported interpreting the results of clinical studies of PSV usin g vari-
in the absence o f this time-limit mechanism, whereby con- ous ventilators. One study compared three ventilators set at
stant insufflation (at the PSV level) creates a hig h level of 0 and 15 cmH20 of PSV in seven patients. 28 No significant
continuous positive airway pressure (CPAP).20 difference was observed in the work of breathing performed
at pressure support (PS) of 0 cmH2 0 , but major work differ-
ences were observed at PS of 15 crnH2 0. These data suggest
OTHER SETTINGS
that different characteristics of PSV delivery may have a ma-
Because no mandatory breath is present with PSV, a safety jor influence o n its efficacy (Fig. 9-2). Although mos t recent
feature often is available in case of apnea. This may be an ventilators have much better systems of regulation, provid-
automatic feature or a minimal frequency or minute venti- ing more homogeneous delivery of PSV, clinically relevant
lation to be set. The time delay for apnea may be adjustable. differences still exist.
This safety feature is not available on all ventilators. As with o ther assisted mod es, the triggering mecl1anism
PSV can be used in conjw1ction with SIMV. 2"~ -24 Two ap- is a key determinant of the efficacy of PSV. A poorly fwlc-
proaches have been used: addition of a fixed level of PSV tioning d emand valve has two consequences: It imposes
during spontaneous breathing to overcome endo tracheal an effort to open the valve, and it prolongs the time be-
tube (ETT) or circuit resis tance25 or use of a variable level of fore assistance is delivered. Assisted modes, including PSV,
PSV between the mandatory breaths . The second approach are devoted p rimarily to reducing or optimizing this effort.
introduces considerable complexity into ventilator manage- What happens before delivery of assistance may interfere
ment of pa tients. with efficacy of the mode. Demand valves function w ith
an w1alterable delay before delivering gas flow to the pa-
tient. For instance, if 200 ms is required be tween the be-
ginning of an inspiratory effort and opening of the valve,
Differences Among Mechanical nearly one-third of the d u ration of inspiratory effort in a
Ventilators tachyp neic patient may take place without any gas enter-
ing the lungs. If auto (or intrinsic) PEEP is present, another
During PSV, specific characteristics of the ventilator may 200 ms may be wasted (while the respiratory muscles work
interfere with patient respiratory activity. These differences against this positive alveolar pressure) before any inspira-
may be determined by the ma nufacturer's algorithm to d e- tory flow can start. In addition, if the speed of pressuriza-
liver pressure, such as speed of pressurization and/ or ini- tion of PSV is low, another 200 m s is required to reach the
tial peak-flow setting, ability to maintain a plateau press ure plateau pressure. Thus assistance will be delivered to the
v p/s) FIG URE 9-2 The influence of a ventilator and its

sp ecific algorithm on p atient effort. Three ventilators
~I~ were studied (EE = Erica Engstrom, Bromma, Swed en;
SC = Servo 900C, Siemens, Lund, Sweden; and CP U =
CPUl , Ohmeda, M aurepas, France) at 15 cmH2 0 of PSV.
Flow, airway pressure (Paw), an d esophageal pressure
(Pes) are presented. Note the different airway and flow
profiles and the impact on esophageal pressur e swing.
Paw (cm H~~ Work of b reathing was significantly less with SC (from
ref. 28). Although modem ven tilators tend to
~~1'-..J --.... homogen ize the d elivery of PSV, d ifferences still exis t
and illustrate the effects of varying the pressure ramp.
1S
EE sc CPU
CHAPTER 9 PRESSURE-SUPPORT VENTILATION 225
T=0.3sec
f;::)
en
...c.XI
>- FIGURE 9-3 The m ethod used to calculate the
"'
~
trigger characteristics and pressurization phase
·-
~
during PSV based on the airway pressure-time
curve. The total trigger phase is evaluated by the
time delay (TD) between the onset of simulated
effort and the time at whjch airway pressure
PEEP
becomes positive after experiencing a pressur e fall
LJPaw
Time (.6.Paw). The quality of pressurization is b est
quantified as the area measured at
0.3 second. (Modified, witlr permissio111 from
TD .R ichard eta/: In tens ive Care Med 28:1049-57, 2002.)
patient 600 ms after the beginning of inspiratory effort, were used. The net area of the inspiratory airway pressure-
which may correspond to the end of that patient's inspi- time tracing was calculated over the first 0.3, 0.5 and
ratory effort.29 1 second at three levels of PSV (5, 10, and 15 cmH 20) (see
Comparison of the triggering functions of various venti- Figs. 9-3 and 9-4). To assess the relative role of PSV de-
lators demonstrates that the most recent generation of venti- livery and triggering function, triggering sensitivity was
lators, using pressure-sensitive mechanisms, flow-sensitive assessed independently by measuring the time delay and
mechanis ms, or both, usually require less effort and open the pressure fall with different levels of inspiratory drive
faster than older-generation ventilators. This was studied (see Figs. 9-3, 9-5, and 9-6). All new -generation ventila-
extensively by Richard et al,16 who compared different gen- tors (released after 1993) achieved significantly better re-
erations of ventilators, including the new turbine ventila- sults than most previous-generation ventilators regarding
tors (Figs. 9-3 to 9-6). The ability of different ventilators to the pressure-time area at 0.3 second and triggering de-
pressurize the airway during PSV was investigated. The lay, indicating large improvements in terms of trigger-
investigators reasoned that during PSV, unloading efficacy ing and pressurization. Regarding PSV and trigger per-
depends on a ventilator's ability to meet inspiratory flow formances, new-generation ventilators outperformed mos t
demand. Different levels of simulated inspiratory demand previous-generation ventilators; this also was the case for
PS ~ 15 cm H,O
OLow BModerate • High
s
lilf/1
c: 4
.. s s
-
f !l jo II
0
3
I'll
I'll 2
!
~
1
~ ~
u
g
...I'll o=0
..
~ X ·1 .0
f/1
c:
- >- ,-
E
u
--.. ~ ~
~
8
..,
0
~ ..
~
0
"'(3 8......
0
!
•
8 -g
':Q :0 •'c: \,
0
;! 'iii ...
•
0•
- ..
M
•
x,., ••
E 'li
...
•
Cll sg
c: u X .~
•• ..
••
..
0
0 Ill 1:::! (/)
i i Ill iii z ;:)
""i
ILl
-
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w ~
a. X
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a. =
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cr:
FIGURE 9-4 Inspiratory area, measured as U1e integral of the airway pressure-time trace over the first 0.3 second of inspiration
(see Fig. 9-3), for a PSV level of 15 cmH20 according to the s imulated l evel of inspiratory demand Oow, moderate, and high). The number of
asterisks indicates ventilator gen eration (no asterisk, new; one asterisk, previous; two asterisks, piston and turbines), # indicates p < 0.05
versus aU new-generation ventilators, $ indicates p < 0.05 versus at least one of the new-generation ventilators. The foUowing ventilators
were tested: New-generation veutilators: Evita II, Evita II Dura, and Evita IV (Drager, Liibeck, Germany); Servo 300 (Siemens-Elema, Solna,
Sweden); PB 840 (Puritan-Bennet, Carlsbad, CA); Galileo (Hamilton, Rhaziins, Switzerland); Horus (Tal!ltla, Antony, Fran ce).
Previous-generation vtmtilators: 8400 ST (Bird, Palm Springs, CA), Servo 900C (Sil!ltlens-Elema, Solna, Sweden), PB 7200 (Puritan-Bennet,
Carlsbad, CA), Bear 1000 (Bear, Palm Springs, CA), Adult Star 200 (lnfrasonics, USA), Veolar (Hamilton, Rh iiziins, Switzerland). Pistou or
turbine-based ventilators: piston: PB 740 (Puritan-Bennett, Carlsbad, CA); turbine: T-Bird (B ird, Palm Springs, CA), BiPAP ST 30 and
Vision (Respirorucs, Murrysville Pittsburgh, PA), Helia (Saime, Savign y-le·TI!ltlple, France), O'Nyx (Pierre Medical, Verr~res-le-Buisson,
France and Puritan-Bennett, Carlsbad, CA), Q uantum (Healthdyne Technologies, Marietta, GA), Respicare (Dr ager, Lubeck, Germany),
Achieva (Puritan-Bennett, Carlsbad, CA). (Modified, tvitlr permission, from Richard et al: Intensive Care Med 28:1049-57, 2002.)
Cllow 8Moderate 8 Hlgh

PSV 5, 10, 15 cmH20
-
0
Q)
U)
450
400
.. # "'
~ .. s FIGURE 9-5 Total time delay for
triggering (m, expressed in ms; see Fig.
-~
E 350
300
9-3) according to the simulated level of
inspiratory demand (low, moderate, and
..>. 250 high). Values for measurements ob tained
at PSV levels of 5, 10 and 15 cmH20 have
,!g 200
,
Q) 150 been averaged. The number of asterisks
indicates ventilator generation (no
Q) 100
E asterisk, new; one asterisk, previous; two
50
i= asterisks, piston and tu rbines), # and $
0
indicates p < 0.05 versus all
..."';:, ~
C) . • . • ••I!! ~!!
• •• new-generation ven tilators, See legend to
"'0 ..,,..
, ·;;;-"' ...,0 0
ien 2
- ! .... ,-
.~ 0~ 8N
\. '
c.> \.
Q •c: ~
... 0• •K
e
-
~
B 0 ~ Fig. 9-4 for a list of ventilators being
>
w -w 0 0
:r c3 ...
..
1/)
....
0
en <»
en 5
0
'iii a;
M
1/)
>.
z il
c "'u Gi
:z:: :E
G)
tes ted. (lvfodified, w ith pe1·mission, from
'
0.
'E en :J > 0. 0 ~
..
B 0 1-
> 1/) "'
m a; 0. ct ~
§
a
fl)
Ql
1.)
< Richard eta/: Intensive Care Med
w 1/) a: 28:1049-57, 2002.)
some piston- and turbine-based ventila tors, including sev- tics. For instance, a change in the criterion for cycling be-
eral of those specially designed for noninvas ive ventilation tween inspiration a nd expiration will result in a different T1
(NIV) . and different VT and may result in more (or less) dynamic
Ventilators delivering PSV and PEEP (tenned bilevel ven- hyperinflation.
tilation) a nd designed for home ventilation have been eval- The addition of PSV modifies the sponta neous breath-
uated in stable, awake patients with chronic ventilatory ing pattern.31 - 36 Most pa tients d evelo p an increase in VT
failur e.30 Despite som e variability in the delivery of pres- and decrease in respira tory ra te w ith increasing levels of
sure, no difference was found in terms of comfort or im- PSV. N umerous au thors have shown an inverse rela tion-
provement in inspiratory muscle unloading. These differ- ship between the PSV level and respiratory rate and a posi-
ences, however, might ha ve grea ter impact in patients with tive relationship with VT. 31 - 34 This has clinical im plicalions.
acute respiratory failure. First, it suggests that breathing pa ttern adapts raf idly when
the respiratory muscles face a new workload.3 Second, it
implies that adjustment of the PSV level can be guided
by noting the breathing-pattern response. This information
Main Physiologic Effects may be obtained very q uickly: Changes in breathing pat-
tern in response to loading conditions usually occur w ithin
BREATHING PATTERN
1-2 minutes.37•38 Excessive levels of support, however,
During PSV, the patient maintains control over respira- lead to hyperinflation, respirator~ alkalosis, respiratory de-
tory ra te and has partial control of T1 and tidal volume pression, and periods of apnea. 9 High levels of support-
(VT). As such, PSV seems to allow the patient to breathe ind uced hyperinflation may result in inability to trigger
in a " physiologic'' and natura l way. This is only partially the ventilator (so-called ineffective triggering). This will re-
tme because there is a complex interaction between venti- sult in a substantial difference in the ventilator's displayed
lator support and patient control of breathing. This inter- respira tory ra te and the patient's true res piratory rate40
action depends on the pressure level and PSV cl1a racteris- (see below).
-:r..
0
14
PSV 5, 10, 15 cm~O
s s s s s
Cll ow I Moderate I High FIG URE 9-6 Pressure fall before PSV
delivery (APaw, expressed in cml-120 ; see
Fig. 9-1) according to the s imulated level of
--
E
u
,
12
10
inspiratory demand (low, moderate, and
high). Values for measurements obtained at
d'! PSV levels of 5, 10 and 15 cmH2 0 have been
~ 8
averaged . The number of asterisks indicates
-
=
"'....
Q)
::l
411
6
4
ventilator generation (no asterisk, new; one
asterisk, previous; two asterisks, piston and
turbines), $ indicates p < 0.05 versus all
411 2 new-generation ventilators. (Modified, w ith
e
Q. 0 pennission, from Richard et a.l: 111te11sive
-ill ,... • • • • • .. ...0... •b • •

Care Med 28:1049-57, 2002.)
-.. ,--
~ 8 • : •'K •• •
''E
CIJ 0
80 8'If 8N (/)... 8c.>
0 II)
tG)
v 2 Cl> ~
...... •.!! ~
w> ~
>
w
::>
=
"'0
~
co
en 0
0. :r c3 ... 'E co ,..
lXI
en
3 0
. i! .2
J!l iii
en >
> 0. 1-
~
- -
(/)
z
b
>. E
::>
c iui :r
a; .~
.t::.
u
.5 0
"' 0. ~ Ill
m a; ~ <
(/)
>
w ct Ql
1/)
a Cl>
a:
In patients with acute lung injury, factors other than res- excessive assistance with PSV may induce respiratory alka-
piratory muscle load influence respira tory drive. Pesenti losis not controlled by the patient's respiratory centers has
et a141 reported that variation in arteria l oxygen (02) satu- important consequences. Parthasarathy et al46 found that
ration between 85-90% and 100%, obtained by modifying during sleep PSV was associated with numerous episodes
fractional inspired oxygen concentration (FI02 ), had a sig- of apneas, desaturation, and microarousals leading to sleep
nificant effect on r espiratory drive in patients with acute fragmentation. 46 This could be prevented by adding dead
lung injury receiving PSV. space to the circuit. Although not tes ted in this stud y, it is
The influence of PSV on the duty cycle (fractional inspira- also possible that reductions in the level of PSV might pre-
tory time, Tr/TmT) is variable. It probably depends on differ- vent this problem.
ences in working principles of PSV among ventilators. It is, The distribution of ventila tion and perfusion during PSV
for instance, influenced by the setting of the pressure ramp has been assessed in several studies. 47- 52 Valentine e t al 47
on the ventilator. 42 A decreasing duty cycle with increasing compared SIMV, PSV, and airway pressure-release ventila-
PSV levels has been observed in several studies.32- 34 tion (APRV) in nine patients a few hours following cardiac
The influence of PSV on minute ventilation is variable, surgery. The major cha racteristics of ventilation-perfusion
producing an increase or no cl1ange.31 - 35 An increase in (VAIQ) distributions were sinlilar with all modes. 47 Dead
minute ventilation is observed frequently when PSV is com- space was lower d uring APRV than during either SIMV or
pared with tmassisted breathing through the ventilator cir- PSV. Gas exchange was assessed with the s ix-inert-gas tech-
cuit. More frequently, a n increase in PSV fails to mod- nique by Beydon et al 48 in a study comparing controlled
ify minute ventilation substantially, whereas it modifies mechanical ventilation, unassisted spontaneous breathing,
alveolar ventilation. Breathing pattern therefore may be and PSV of 10 cmH20. Using isotopic scanning, these au-
modified markedly without signifi cant change in minute thors evaluated regional distribution of VAIQ ratios. The
ventilation.31 - 36 Thus, monitoring minute ventilation is of study was conducted in eight patients with chronic obstruc-
little help when titrating the level of PSV. tive pulmonary disease (COPD) who were dependent on
mecl1anical ventilation. Ventilato r discontinuation was as-
sociated with ra pid, shallow breathing and an increase in
GAS EXCHANGE AND DISTRIBUTION perfusion to low VAIQ regions. Isotopic scans revealed a
OF VE NTILATION AND PERFUSION horizontal cranioca udal difference of VAI Q with all modes,
The primary goal of PSV is to support patient effort w hile and the lowest VAIQ ratios were found at the bases. Ab-
delivering a satisfactory gas mixture. PSV is not aimed pri- normalities in VAI Q distribution observed during sponta-
marily a t improving oxygenation. The effects of PSV on neous breathing also were present during 10 cmH2 0 ofPSV,
gas excl1ange a re explained primarily by increased alve- although to a smaller extent. Whether a higher level of PSV
olar ventilation resulting from changes in breathing pat- might have been more effective in correcting the maldistri-
tern. Indeed, despite a lack of change in minute ventilation, bution of VAIQ ratios is unknown.
an increase in VT produces a decrease in the ratio of dead Ferrer e t al50 assessed whether PSV could improve VAIQ
space to VT <Vo/VT). Thus alveolar ventilation often is in- imbalanced uring the transition between positive-pressure
creased. Other factors may influence arterial blood gases, ventilation and spontaneous breathing in seven intuba ted
such as changes in ~ consumption, modification of total patients with COPD during weaning.50 PSVavoided VA/Q
dead space, and alter ed distribution of ventilation. Dur- worsening during this transition. Hemodynamics, blood
ing the weaning of patients with hypercapnic respiratory gases, and VAIQ distributions were equivalent during PSV
failure, addition of PSV produced a correction of Paco., and ACV when the two modes provided similar levels of
and respiratory acidosis.31 In normal, nonintubated sub- assistance. Diaz et a! 49 studied the reasons for improvement
jects, PSV of 10 cmH20 produces significant decreases in in Po., and Pco., in 10 patients with acute hypercapnic exac-
Paco., .39 PSV can induce hy perventilation that is not cotul- erbations of COPD w ho were switched from sponta neous
teracted by respiratory motor ou tpu t.43 Slight hypocapnia breathing to PSV during NIV49 Improvement in blood gases
was observed in patients following abdominal surgery, 44 was mediated primarily by a higher alveolar ventilation and
whereas normocapnia was observed in other studies. There- not improvement in VAIO relationships. While 0 2 uptake
fore, a lthough PSV permits correction of hypercapnia re- tended to decrease, the respiratory exchange ratio increased,
sulting from rapid shallow breathing or helps patients w ith explaining a slight increase in arterial-to-alveolar 0 2 differ-
chronic C02 retention to choose their own target Paco2 , the ence secondary to increased clearance of body stores of C02
level of PSV requires fine adjustment to avoid respiratory during NIV. These results suggested that attaining an effi-
alkalosis. cient breathing pattern rather than high inspiratory pres-
Although breathing pattern, and especially respiratory sures should be the primary goal for improving arterial
frequency, is controlled in part by the patient, an interac- blood gases during NIV with PSV in this type of patient.
tion exists between the level of PSV and a lveolar ventila- The effect of PSV on oxygenation varies and depends
tion, Pacoz, and pH that is not fully controlled blsrespiratory on many factors, such as the induced changes in alveolar
center command. Macintyre and Leatherma n 5 showed in ventilation, 0 2 consumption, dead space, and mean airway
a lung model that a biphasic effect can occur with increas- pressure.31 - 34 Most investigators have not found significant
ing levels of PSV. Above a certain limit, passive (hyper-) changes in arterial oxygenation when PSV was compared
inflation will result with high levels of PSV. The fact that with other modalities (primarily spontaneous breathing or
SIMV) delivered at the same Fr02.In two studies, an increase inability to be weaned from the ventilator. PSV then was
in Pao2 was found when PSV was compared with ACV. delivered at 10, 15, and 20 crnH20. EMG signs disappeared
Each mode was used for 30 minutes in one study,33 and two at 10 cmH20 in four patients and at 20 cmthO in three oth-
patient groups with identical postoperative characteristics ers. At this" optimal" PSV level, activity of the sternocleido-
were compared in the other study.53 Compared with contin- mastoid muscles was minimized or no longer present. Al-
uous positive-pressure ventilation in surgical ICU patients, though work of b reathing returned to n ormal, respiratory
Zeravik et a1 54 searched for a pulmonary index to predict rate remained around 30 breaths per minute in some pa-
the effect of PSV on oxygenation in patients with moderate tients. These findings were later confirmed by another study
acute respiratory failure. These investigators adjusted PSV that also included EMG measurements and analysis of cen-
and PEEP to achieve a similar VT and mean airway pressure troid frequency as an index of impending high-frequency
with both modes. Patients with a low level of extravascular fatigue.55
lung water, estimated by bedside thermal dye dilution mea- The respiratory-rate values in the study by Brocl1ard
surements, had improved oxygenation with PSV, whereas et al emphasize the fact that trying to lower respiratory rate
those with an elevated extravascular lung water level de- below a point where a patient is no longer in respiratory dis-
teriorated when shifted from continuous positive-pressure tress, such as 20 breaths/min or lower arbitrary values, is
ventilation to PSV. It should be noted that the switch to PSV usually not necessary or useful. This has important clinical
was accompanied by a reduction in patient sedation, which implications. In postoperative patients without pre-existing
may have accounted for some of the observed effects. pulmonary disease, PSV 15 cmH20 was shown to take over
the major part of work of breathing, quantified as 02 cost of
breathing.S6 In patients with COPD, similar findings were
WORK OF BREATHING AND RESPIRATORY EFFORT demonstrated by Annat et a l.57 In their patients, 15 crnH20
A major goal of PSV is to assist respiratory muscle activity PSV decreased markedly both 0 2 cost of breathing and di-
in a way that improves the efficacy of patient effort and aphragmatic pressure-time index as compared with CPAP.
decreases workload. Many researchers have focused on this PSV acts w ith great efficiency in decreasing work of
point and have measured work of breathing or indexes of breathing. This decrease is more or less proportional to
patient effort during PSV. 7•9, 31 ·33·34 the level of PSV and is accompanied by changes in breath-
Maclntyre7 studied the effects of various levels of PSV in ing pattern easily measurable at the bedside, together
patients. The level of PSV was correlated positively with VT with changes in respiratory muscle recruitment. In the
and negatively with respiratory rate. Using a lung model, study of Brochard et al,31 when PSV was absent, large
he suggested that PSV alters the characteristics of work of swings in esophageal pressure were associated with a small
breathing: The change in the pressure-volume ratio of the VT, whereas with 20 cmH20 of PSV, small excursions in
work of each breath decreased progressively with increas- esophageal pressure were associated with a large VT, sug-
ing levels of PSV. gesting amplification of patient effort. There is an indi-
In eight intubated patients recovering from acute respi- vidual limit of pressure, however, above which work of
ratory failure, Brochard et al9 compared breathing charac- breathing is not decreased and the patient is overassisted.32
teristics during 10 cmH2 0 of PSV, spontaneous unassisted This is associated with dyssynchrony, episodes of apneas
breathing through a Siemens Servo 900C ventilator, and a and desaturation, and/ or occurrence of ineffective efforts
continuous-flow system without a demand valve. PSV pro- (see below).
duced significant increases in VT and Pao, and a decreased Different indexes have been used to assess respiratory
respiratory rate. Transdiaphragmatic p ressure swings (Pdi) muscle activity. Becket al58 compared crural diaphragmatic
and the pressure-time index of the diaphragm were signifi- electrical activity (EAdi) with Pdi during varying levels of
cantly lower during PSV than during the other two modal- PSV in intubated patients. Changes in PSV did not alter
ities. Electromyographic (EMG) activity of the diaphragm neuromechanical coupling of the diaphragm: EAdi and Pdi
decreased markedly in the two patients in whom it was decr eased proportionally with the addition of PSV. In con-
measured. trast, Fauroux et al59 found that diaphragmatic pressure-
Subsequently, Brochard et aJ31 compared several levels of tinle product, often used to quantify loading and u nload-
PSV (0, 10, 15, and 20 cmH20) in eight patients experiencing ing of the diaphragm, did not exhibit a linear relationship
weaning difficulties, four of whom had COPD. During unas- with the diaph ragmatic EMG d uring PSV. These authors
sisted breathing (PS of 0 cmH2 0), patients breathed with a suggested that flow measurements are necessary when as-
small VT and a high rate, a pattern associated with unsuc- sessing diaphragmatic unloading during PSV.
cessful weaning. This pattern was accompanied by a slight
decrease in Pa02 and a significant increase in Paco, com-
COMPENSATION FOR WORK CAUSED
pared with controlled ventilation. All patients exhibited in-
BY ETT AND DEMAND VALVE
tense activity of their sternocleidomastoid muscles. Work of
breathing and 02 cost of breath ing were elevated. From the PSV has been used to predict patient tolerance of unassisted
diaphragmatic EMG recordings, the ratio of h igh-frequency breathing and extubation.60 The idea is based on selecting
to low-frequency components (H/L), an index of excessive a level of PSV just sufficient to overcome the circuit resis-
workload that suggests impending high-frequency fatigue, tance. Thus spon taneous muscular activity should be simi-
was measured. During PS of 0 cmH2 0, seven of eight pa- lar to wha t a patient would perform in the absence of an ETT
tients exhibited EMG signs of impending high-frequency or circuit.61 Measurement of breathing pattern is of major
diaphragmatic fatigue, a finding consistent with their help in assessing work of breathing or ability to tolerate
extubation.62 Therefore, the pressure needed to obtain a Heat and moisture exchangers (HMEs) and heated hu-
"reasonable" breathing pattern can provide insight into a midifiers both constitute a resistive load,75 - 79 but HMEs
patient's ability to tolerate extubation. This approach raises also add instrumental d ead space because they are posi-
the question of what is a "reasonable" breathing pattern tioned between the Y piece and the ETT. The mechani-
and of individual values of minimal PSV level, as discussed cal characteristics of HMEs can modify breathing pattern,
earlier. effort to breathe, and gas exchange substantially during
It has long been understood that breathing through PSV.80
an EIT and d emand valve increases respiratory muscle These effects were assessed in six studies during PSV
work 10,t5,63,64 and that PSV can compensate for this in- and invasive ventila tion7S,st - ss and three studies during
creased demand. 61 •65•66 This is only partially true. Initially, NIV_79,86,87 The studies revealed consistent results. Adding
the level of PSV required to compensate for added in- dead s pace with the HME reproduced the well-known ef-
spiratory work (caused by EIT resistance and a demand fects of C02 on breathing pattern.88 Acute hypercapnia
valve) had been evaluated and calculated using a mechani- induced by adding dead space was compared in intu-
cal m odel. 65 The resistance offered by the ETI, however, was bated patients during PSV and proportional-assist venti-
not compared with the natural resista nce opposed by the lation (PAV). 89 Additional dead space produced signifi-
upper airway. 65 With a lung model, the PSV level needed to cantly greater increases of all indexes o f effort, respiratory
compensate for EIT resistance varied from approximately rate, minute ventilation, and Paco., than during PAV. Dur-
5-15 cmH2 0 for a mean inspiratory flow varying from ing NIV with PSV, Lellouche e t a l'9 found that indexes
0.5-1liter/s with an ETT size of 8 mm. of effort doubled with HMEs compared with heated hu-
Similar reasoning was employed in nine intubated sub- midifiers. In intubated patients during PSV, Pelosi et al 82
jects breathing with various levels of PSV who were discon- reported that work of breathing increased from 8.8 ± 9.4
nected from the ventilator and finally extuba ted.61 The level J/ min with a heated humidjfier to 14.5 ± 10.3 J/min w ith
of PSV that compensated for the extra work of breathing an HME. They suggested that increasing the level of PSV
through the ETT and ventilator circuit was calculated post by 5-10 cmH2 0 may be necessary to compensate for tl1e in-
hoc. It varied among patients. In patients with underlying creased work of breathing caused by HME dead space. In
lung disease, the PSV level that compensated for the addi- a study by Iotti et al, 78 the level of PSV was adjusted au-
tional work ranged from 8-14 cmH20 , whereas it averaged tomatically by a closed loop to maintain a constant P0 .1 .'8
5 cmH20 in patients free of lung disease. The authors con- In comparison with the heated humidifier, PSV was in-
cluded that PSV provided the physician with information creased by a mean of 3 and 5 cmH20 when additional
to predict a patient's tolerance of extubation. For instance, dead spaces of HMEs were 37 and 77 ml, respectively. 78
a patient with COPD who exhibits satisfactory clinical and Girault et a l84 observed equivalent work of breathing with
gas-exchange status during PSV of 8 cmH2 0 should toleran HME and PSV of 15 cmH20 versus a heated humidi-
ate extubation, provided there is no major problem with fier and PSV of 7 cmH2 0. These studies suggest that use of
hypoxemia or coughing. HMEs should be accompanied by an increase in PSV of 3-
Based on the work of Sassoon et al 67 •68 and others, it has 10 cmH2 0 depending on dead space of the HME. Cljnicians
been recommended that a PSV level of 5-10 cmH20 be pro- should be vigilant about the impact of humidification de-
vided when a patient is breathing through a d emand valve. vices, especially when PSV is used during weaning or with
It is important to stress, however, that res istance of the ETT NIV.
plays little or no role in this pressure requirement. Several During weaning, it may be necessary to avoid HMEs in
subsequent studies compared work of breathing before and patients sensitive to dead space, such as patients with severe
immediately after extubation.66, 69•70 These studies demon- COPD. 90 Alternatively, the level of PSV should be adjusted
strated that the work of breathing was similar or even higher according to the humidification device in use.84 Tf a wean-
after extubation than before extubation. This indicates that ing trial is performed, the level of PSV should be adjusted
there is no rationale for compensating for the ETT in itself. according to the humidification d evice (5-8 cmH20 with a
What needs to be compensated for, however, is the ventila- heated humidifier and 10-12 cmi-hO with an HME).lf such
tor circuit through which the patient is breathing, including adjustments are not made, the outcome of the trial may be
the triggering system. misinterpreted.
Despite wide variation among patients in physiologic Patients who present with clinical signs of poor toler-
studies, a simplified approach, based on the same principle, ance or persistent hypercapnia during NIV may benefit by
has been applied in several large clinical trials. These studies a change from an HME to a heated humidifier.
show that a low level ofPSV (7- 10 cmH20) is as efficient as
aT-piece trial in testing whether a pa tient can be separated
from the ventilator and eventually extubated.71 - 74 Despite
the lack of individual titration of PSV, this approached has Degree of Patient-Ventilator Synchrony
performed remarkably well, providing results comparable during PSV
to a T-piece approadl?t,n ,74
The fundamenta l principle of assisted ventilation is to de-
liver assistance on a breath-by-breath basis in synchrony
EFFECT OF INSTRUMENTAL DEAD SPACE
with patient effort. As discussed earlier, some patient-
Instrumental dead space is usually constituted by the flex- ventilator asynchrony often exists with most current as-
tube connector, theY piece, and the humidification system. sisted modes, which can be aggravated by inappropriate
settings, chiefly excessive support. Synchrony has been treatment. We describe the asynchronies encountered most
the subject of several investigations, often no t specific frequently during PSV, according to recent publications. 95
to PSV. 24•91 - 95 Patient-ventilator asynchrony has been de- Some forms of asynchrony, such as s imple d elays, are dif-
scribed during invasive ventilation 24•94•96- 98 and N IV.99,'1CXl ficult to detect at the bedside and are better recognized b y
Synchrony between the patient and ventilator can be de- a careful examination of esophageal pressure or diaphrag-
fined as the adequacy of matching of patient demand w ith maticEMG.
support p rovided by the ventilator in terms of synchroniza-
tion of time, volume, or flow. PSV often is viewed as offering
AT INITlATION OF THE CYCLE
good synchrony w ith patient activity because it is desig ned
to recognize the beginning and end (more or less) of each Triggering d elay, ineffective triggering, and auto-triggering
spontaneous effort and to adapt mean ins piratory flow rate are all related to lack of synchrony behveen onset of pa-
to patient demand. As d iscussed earlier, this is far from true tient effort and onset of inspiratory assistance (Figs. 9-7 and
in all cases. The incidence of asynchrony has been studied 9-8). Short and multiple cycles (Figs. 9-8, 9-9, and 9-1 0) occur
by Chao et al94 and Thille et al. 95 and may be related to problems with inspiratory triggering,
During PSV, several forms of asynchrony can be identi- setting of the pressurization rate, and cycling criteria.
fied b y inspecting the airway pressure and flow curves on
ventilators. It is often possible to rule out the problem by INSPIRATORY TRIGGER DELAY
modifying ventilator settings. Man y asynchronies are not Trigger delay can be related to the system (pressure versus
specific to PSV.24•95 Descriptions of these asynchronies may flow triggering). Work (or effort) in triggering the ventila-
help clinicians to understand their mechanisms and thus tm- tor has been evaluated by comparing p ressure- and flow-
d ertake remedial steps. A parallel can be mad e with cardiac triggering systems.'19•23•101 - 105 The effort to trigger is sig-
arrhythmias, where each type of arrhythmia has a specific nificantly reduced with flow-triggering systems compared
1 FIGURE 9-7 Ineffective efforts. The third an d

sixth inspiratory efforts b y the patient fail to
trigger th e ventilator. The efforts by the patient
(visible on the esophageal pressure tracing) arc not
0 .5 accompanied by ventilator insufflations. A sm all
~
an d transient in crease in flow during expiration
::i
~
and a decrease in airway p ressure are visible at th e
~
0 time of th e failure-to-trigger events.
ii:
0
-0.5
15
~
ll.
5
0+-~--------~----------~------~--~--~--~--~
0 .-----------.-----------. ,-----------.-----------,
-10
0 5 10 15 20
Time (s)
1.5
en 0.5
-
:::J
~
0
LL. 0
-0.5
-1
20
0 15
N
X
E
(J
- 10
~
Q.
12
10
0N 8
X 6
-E
(J
1 /)
Gl
Q.
4
2
RGURE 9-8 Auto-triggering. This form of
asynchrony can occur when the inspiratory trigger is
0 set too sensitive or in the presence of end-expiratory
-2 leak s. As on this tracing, a "short cycle'' is a frequent
result of an auto-triggered cycle. The "auto-triggered
0 1 2 3 4 5
cycle" is accompanied by the absence of an initial
Time (s) ainvay p ressure decay.
with pressure-triggering systems. The specific amount of mouth necessitates that the respiratory muscles first coun-
this effort, however, accounts for 10-30% of total work teract this gradient before any inspiratory flow can be gener·
of breathing, and U1e clinical impact of this amount is ated. This constitutes an inspiratory threshold load that in-
unclear. Ventilator performance is extremely variable. In- creases breathing effort.109• 113 - ~"~ 5 The magnitude of positive
spiratory trigger delay varies from 40-200 ms among pressure generated depends on VT and therefore set PSV
ventila tors16•19; it was as long as 400 ms with previous- and minute ventilation. Intrinsic PEEP must be overcome
generation ventilators.15 In ventilators designed for NIV, first before triggering the ventilator by decreasing airway
Stell et a1 18 recently found U1at inspiratory trigger delay fre- pressure (in the case of pressure triggering) or generating
quently was 120- 300 ms; exceptionally, it was up to 500 ms. inspiratory flow (in the case of flow triggering). 23 When pa-
Inspiratory effort to overcome intrinsic PEEP is often tient effort is feeble, it does not reverse expiratory flow or
higher than the effort to trigger the ventilator. 19 The same is decrease pressure sufficiently to trigger the ventilator. This
true for inspiratory delay. Applied external PEEP may de- produces a missed cycle. External PEEP may decrease the
crease work to trigger the ventilator during invasive venti- frequency of wasted efforts.92•94•111
lation and NIV.106- l 09 In a study where assistance was varied between 0% and
100%, Leung et al24 found that there was almost no inef-
INEFFECTIVE TRIGGERING (see Fig. 9-7) fective efforts below 60% of assistance, but they increased
During invasive ventilation with PSV, asynchrony most of- gradually when assistance was 60% to 100%. In a cohort
ten results from ineffective triggering, also called wasted of 62 intubated patients, Thille et al110 recently found that
efforts.24·9 1, 92•94·96,97,lto The frequency of this asynchrony ineffective triggering represented almost 90% of all asyn-
is influenced directly by U1e level of PSV and dynamic chronies during PSV. COPD was a risk factor for asyn-
hyperinflation.24•40,92, 98•111 •112 When a patient starts an in- chrony. Patients with ineffective triggering had a higher VT
spiratory effort, a pressure gradient between the alveoli and and higher PSV. This asynchrony has been described with
20
~ 15
0
r."
E
~ 10
~
5
FIGURE 9-9 Double cycles. Two ventil atory cycles

occur within a single patient inspiratory effort.
Three mechanisms can induce this asynchrony:
auto-triggering, high pressurization rate (present
here with initial oversh oot), and early cycling off
Tlme(s) (also present in this case).
different diseases but is observed mainly in patients with be detected as accurately on flow and airway tracings as on
expiratory flow limitation leading to intrinsic PEEP.24,94,97 esophageal pressure tracings. Different approaches can be
In the s tudy by Leung et al/4 cycles preceding wasted efforts used to avoid wasted efforts: check trigger sensitivity, in-
were characterized by a higher VT and a lower T1, which crease PEEP,92•94,.111 lower PSV,23·24 or decrease instrumental
lead to greater levels of hyperinflation. A delay between dead space.80- 83
patient termination and ventilator termination of a cycle There is no indication that ineffective efforts are more fre-
can aggravate the problem.116•117 Indeed, if the ventila tor quent with PSV than with ACV. 95 The clinical consequences
continues the insufflation when the patient has commenced are unknown. Thille et al95 found that a high incidence was
expiration, inspiratory volume will increase and expiratory associated significantly with prolonged ventilation. Because
time will decrease, leading to further hyperinflation. Beck these asynchronies can be avoided by optimized ventilator
et a1 58 found that the greater the level of pressure, the longer settings, their treatment and/ or prevention might shorten
was this delay. Therefore, one major reason for ineffective the time spent on the ventilator.
efforts is excessive assistance (PSV), which simultaneously
generates d ynamic hyperinflation and depresses respira- AUTO-TRIGGERING
tory drive, both because of high VT and prolongation of in- Au to-triggered cycles (see Fig. 9-8) represent a default of ad-
sufflation far beyond the end of patient inspiratory effort.95 equate inspiratory triggering; a cycle is falsely triggered by
Ineffective triggering can be detected from irregularities a signal not coming from a patient's inspiratory effort. These
on airway and flow tracings during the expiratory phase23 cycles can be caused by expiratory leaks around a mask dur-
(see Fig. 9-7). A respiratory rate lower than 20 breaths per ing NIV, leaks in the ventilator circuit, or motion of liquid
minute or increases in flow and a concomitant decrease in in the circuit.95 An expiratory leak can be misinterpreted by
airway pressure on the ventilator screen should rouse suspi- the ventilator as patient effort; an inspiratory cycle then is
cion. Giannouli et al40 found that ineffective triggering could delivered independently of patient control. Auto-triggered
1
0.5
-~
~
u:: 0
·0.5
10
0N
~ 5
&
10
5
~
0N
:J:
e 0
..
~
G>
n.
-5 FIGURE 9-10 Multiple cycles. Multiple cycles
are frequently associated witlt auto-triggered
cycles and frequent "short cycles." A high
-10 pressurization rate can favor tltis form of
asynchrony. In this C!Xample, boUt
0 3 6 9 12
au to-triggering and high pressw ization rate are
Time (s) present.
cycling is also caused by cardiac oscillations118 and when reducing the effort to trigger and ineffective efforts but
the setting trigger is excessively sensitive. also increasing the rate of auto-triggering. As with conven-
Auto-triggering can be difficult to detect on the ventilator tional pneumatic inspiratory triggers, a compromise must
tracing. A sudden increase or a persistently high respira- be found between triggering iliat is too sensitive (posing
tory rate suggests auto-triggering. The absence of airway a risk of auto-triggering) and triggering that is insensitive
pressure drop at the beginning of an inspiratory cycle is (wiili risk of ineffective efforts or increased effort).
also suggestive (see Fig. 9-8). In recent-generation ventila-
tors with very sensitive flow-triggering systems, however,
this initial decay in airway pressure is very small on trig- MULTIPLE CYCLES (see Figs. 9-9 and 9-10)
gered cycles and difficult to detect visually. Two or more ventilator insufflations may be delivered
In cases of auto-triggered cycles, a careful search for a within a single patient effort. Auto-triggering can be re-
leak must be undertaken. Second, sensitivity of the inspi- sponsible for multiple cycles (see Fig. 9-10). Ventilator char-
ratory trigger can be reduced both as a diagnostic test acteristics, such as duration of the refractory period, also
and as a remedy. The ris k of slightly increasing the work may influence this kind of asynchrony. A risk for double-
of breathing must be balanced against the advantage of triggering exists with a high inspiratory pressure ramp pro-
improving synchrony between the patient and ventilator. file secondary to a reduction in ventilatorT1 relative to neu-
New automatic inspiratory triggers have been assessed re- ral T1.120•121 Tokioka et al122 described double cycles during
cently. Priniakis et al119 found that inspiratory triggers based PSV in intubated patients when the cycling-off criteria were
on flow were more sensitive than conventional triggers, high (35% and 45% of maxin1al inspiratory flow).
Three mechan isms (auto-triggering, high pressurization during NlV and invasive ventilation. Several mechanisms
rate, <md early cycling-off) should be considered when this explain this asynchrony. Auto-triggering is frequently of
asynchrony is detected during PSV. short cycles.95 (see Fig. 9-8).
DELAYEO EXPIRATION (Fig. 9-11)

PRESSURIZATION RATE AND INSPIRATORY FLOW
This asynchrony is related to the difference between the
The speed of pressurization determines the initial pressure criterion for inspiration termination on the ventilator and
ramp profile and depends primarily on the initial peak-flow the end of patient neural T1 (see Figs. 9-11,9-12, and 9-14).
rate. This rate usually is system-specific and is adjustable on Parthasarathy et al116 quantified this delay in terms of phase
several ventilators. Altering this parameter can influence angle. When patient T1 ended before the end of ventilator in-
breathing pattern and work of breathing directly.123- m fla tion, phase angle was defined as negative. When patient
Flow dyssynchrony related to the rise time during PSV, effort ended after the end of ventilator inflation, phase an-
patient respiratory drive, and ventilator performance has gle was positive. In healthy subjects w ith simulated airflow
been described. 28•42•121• 126- 128 On new ventilators, rise time obstruction, a negative phase angle was very frequent w ith
can be set to obtain a high rate of pressurization, especially early activation of the expiratory muscles during ventilator
if there is high patient dernand .128 Selecti11g a low speed of insuffla tion.11 7 The higher the PSV level, the earlier was acti-
pressurization can cause excessive patient effort, especially vation of the expiratory muscles. Becket al58 compared cru-
when respiratory drive is high and mechanics are poor. Con- ral diaphragmatic electrical activity with Pdi during varying
versely, a very fast rise time may not be optimal127 and is levels of PSV in 13 intuba ted patients. With changing PSV,
poorly tolerated by patients.'129 A high speed of pressuriza- no change in neuromechanical coupling of the diaphragm
tion also may make it difficult for the ventilator to regulate occurred . From lowest to highest PSV, VT increased and
the pressure properly throughout inspiration according to respira tory rate decreased, but the inspiratory volume cal-
its servo-control mechanism, especially in patients w ith low culated d uring the period when the diaphragmatic EMG
compliance or high resistance. Differences in pressurization increased to its peak did not change. Ventilator assistance
capability a mong ventilators can be significant. 16' 28' 39 continued during the period of diaphragmatic deactivation,
Macintyre and Ho123 examined the ventilatory-pattern a phenomenon that was further exaggerated at higher PSV
response to seven different levels of delivered initial peak- levels.
flow rate. They defined the optimal flow setting as tha t giv- In seven intubated patients, Spahija et ai'132 recently
ing the highest airway pressure-volume product. Settings compared PSV with neurally adjusted ventilatory assist
above and below this optimal flow were associated w ith (NAVA), where ventilator support is driven by the di-
tachypnea, smaller VT, and a tendency for airway pressure aphragmatic EMG signal. Marked expiratory delays were
not to reacl1 the selected PSV level. Patients w ith the low- found with high levels of PSV (1055 ± 1010 ms). These im-
est compliance and highest respiratory drive needed the pressive delays may be specific to the ventilator used, the
highest initial flows. Work of breathing was not measured, Servo 300 (Maquet, Lund, Sweden), which has a low and
however, and it is not known if the optimal airway pressure- nonadjustable cycling-off criterion (5% of peak flow).
volume product corresponded to the lowest level of work. The ins piratory-termination criterion frequently is a fixed
By contrast, in two studies, Bonmarchand et al 42•121 showed percentage of peak inspiratory flow ra te (12%, 25%, or 30%).
that the longer the time taken to reach the pressure level set This criterion freq uently does not correspond accurately
on the ventilator, the greater was the work of breathing in with the end of patient inspiratory effort. The effect of this
patients with both obstructive and restrictive lung disease. setting is complex and differs between patients w ith ob-
Excessively high pressurization a lso can lead to an initial structive and restrictive lung diseases. The validity of this
overshoot, with possible early termination of the cycle re- criterion has been questioned.133 Several authors have stud-
lated to high pressure. Chiumello et al127 fow1d that the ied variations of this criterion on breathing pattem.123•134•135
highest rate of pressurization did not optimally decrease In 16 patients, Macintyre and Ho123 increased the PSV ter-
work of breathing; the relationship between the pressur- mination criterion from 25-50% of peak flow. r. was shorter
ization ra te and dyspnea or work of breathing exhibited a when the criterion was SO% with no change in delivered VT.
U-shaped pattern. During NJV, Priniakis et al129 showed In patients recovering from acute lung injury, Chiumello
that the highest pressurization rate increased the amount et aJ1 28 found that a low cycling-off criterion (5% of peak
of leaks, was poorly tolerated by patients with COPD, flow) was beneficial in terms of breathing pattern (reduc-
and could induce asynchrony such as double-triggering. tion of respiratory rate and increase in VT) compared w ith
It could increase respiratory rate, as described previously a threshold at 40%. Tokioka et al122 found an increase in
with ACV. 130•131 VT and a decrease in r espiratory rate when the cycling-
off criterion was decreased from 45-1%. Work of breath-
ing w as less w itl1 the low cycling-off criterion. All tl1ese ob-
INSPIRATORY CYCLING OFF OR CYCLING
servations argue for the use of a low termination criterion
TO EXPIRATION
in patients with acute lung injury. Conversely, in patients
SHORr CYCLES (see Figs. 9-8 and 9-9) with COPD, the best cycling-off criterion may be above
Pertusini et al100 recently defined a short cycle as one in 50%.136·137 When the cycling-off criterion is set low [5% w ith
which T1 (based on flow) was less than half the T1 dur- the Servo 300 (Maquet, Lund, Sweden) or Sliters/ntin w ith
ing spontaneous breathing. These asynchronies can occur the Puritan-Bennett 7200 (1'yco, Carlsbad, CA)], one can
1.5
1 \
0.5
~
:S
~
0
~
~
.9.
~
-0.5
-1
-1.5
15
~\
10
0 ..
::1:
E 5
u
~ \
~
<'II
11.
0
FIGURE 9-11 Inspiratory and expiratory

-5 delay. Tracings in an intubated patient with
severe COPD receiving PSV. An inspiratory
delay secondary to auto-PEEP and triggering
5 delay is evident. The distance between the
~\I'\
first and second vertical dotted lines reflects
the delay between onset of patient
' ins piratory effort and positive flow from the
0
:J:
.. 0
2 4 6
ventilator; this delay is caused by auto-PEEP.
The delay between the second and third
v
E vertical lines is caused by triggering delay
~
u
(flow triggering). In this patient, mechanical
~ -5 insufflation occurs almost entirely after the
patient has terminated inspiratory effort.
Conseq uently, onset of the ventilator's
expiratory phase is markedly delayed
-10
compared with the patient's n eur al
Time (s) expiration.
expect the following consequences: Insufflation will con- does not decrease (because of these leaks). Thus the flow
tinue beyond patient neural T1, patients will activate their threshold cannot be reached. The breath does not terminate
expiratory muscles, and expiratory time will be shorti all and therefore is prolonged until maximum T1 is reached
these factors increase dynamic hyperinfl.ation.116•138 Con- (which can be several seconds). The patient may "fight"
versely, the risk of wasted efforts during subsequent respi- against the ventilator and may even a ttempt additional in-
ratory cycles increases. 117 Some patients exhibit high levels spirations. The inspiration is artificially hung up, and the
of expiratory muscle activity during PSV116• 138•139 (Fig. 9-13) . patient a ttempts to expire while the expiratory valve re-
mains closed. Ineffective efforts can be observed in this con-
PROLONGED INSPIRATION DURING NJV (see Fig. 9-12) text either within the same ventilator cycle or in following
Mechanical inflation may be prolonged far beyond the end cycles.
of patient inspiration, until a limit of maximum T1 has been Pertusini et al100 recently found that prolonged inspira-
reached. This limit is sometimes adjustable. This type of tion was the most common asynchrony in patients receiving
asynchrony can occur during invasive ventilation. 20 but is NIV for acute respiratory failure; its frequency correla ted
mostly specific to leaks during NIV.99 It occurs because with the level of PSV and the amount of leak.
of the impossibility of reaching the cycling-off criterion. This asynchrony can be detected by inspecting tl1e pres-
Med1anical inflation usually ends when flow decr eases to sure and flow curves o.n the ventilator. The first step is
about25% of(or below) peak inspiratory flow (see above). In to reduce leaks because prolonged inspirations are related
the case of end-inspiratory leaks around a cuff or a mask or directly to end-inspiratory leaks. A decrease in total in-
in the circuit, the ventilator continues insufflation, and flow spiratory pressure, by decreasing PEEP or PSV, also can
2.5
1.5
~
::l
~
1
:it
0
ii:
0.5
-0.5
10
~
6
0
N
:I:
E 4 Ti max
&
:it
... ~
8?. 2
·2
5
FIGURE 9-12 Prolonged inspira tion
during noninvasive ventilation. This
form of asynchrony dw i.n g PSV results
from a failwe to recognize the flow
~
0 cycling-off criterion. With an
0
N end-inspiratory leak, as in this exam ple,
:I:
E the ventilator increases and/or s ustains
& flow to maintain the set airway
fl
Q. (]) pressure (here ab ove 2liters/s). This
·5
prevents recognition of the decelerating
flow threshold and cycling to
®
expiration. Insufflation is s topped on ly
when maximum inspiratory time
·10 (Timax) is reached. Ineffective
0 5 10 15 20 triggering secondary to hyperin flation
may follow th e prolonged inspiration,
Time (s) as in this examp le.
reduce the leaks. This asynchrony can be avoided by ad- EARLY CYCLING OFF (Fig. 9-15)
justing the cycling-off criterion (based on inspiratory-flow If the cycling-off criterion is reached too early, the ventila-
decay), which is adjustable in most new ventilators. 99 When tor s tops insufflation and opens the expira tory valve while
leaks are unavoidable, an increase in this threshold to 50% patient inspira tory effort continues. This produces an ini-
(or more) enables the ventilator to detect the flow threshold. tial drop in airway pressure and flow followed by an in-
An inappropriately hif:h cycling-off threshold can shorten crease, related to patient inspiration, resulting in a char-
T1 and decrease Vr . 128• 36 A simpler temunation criterion is acteristic contour 122 (see Fig. 9-15). This asynchrony is ob-
to set a T 1 limit, as done with pressure-controlled ventila- served during invasive ventilation and NTV. It occurs when
tion. Calderini et al99 set T 1 between 0.8 and 1.2 seconds . the cycling-off criterion is based on either flow decay or
TI1is produced better matching between the patient and the time. In patients recovering from acute lung injury,128 the
ventilator, reducing the work of breathing and improving best cycling-off criterion may be different from the usual
patient comfort. Assist-controlled pressure ventilation also default criterion (25% of peak inspiratory flow). Tokioka et
can be used to deliver pressure with a fixed T1• Large de- al122 found that the airway pressure shape varied depend-
lays also may result with the use of a helmet for NIV.'140 ing on whether the cycling-off criterion was set at 35% or
(Fig. 9-14). 45%.
CHAPTER 9 PRESSURE-SUPPORT VENTILATION 23 7
1.5
0.5
~
-'
~
0
~
u: -0.5
-1
-1.5
20
15
0
::E:"'
E
10
.2.
3:
~ 5
·5
20
15
10
0
0 2 4 6 8
Time (s)
FIGURE 9-13 Expiratory muscle activation. An expiratory increase in gastric pressure (bottom tracing) is caused by expiratory muscle
activation (at the end of patient inspiration). The appa.rent "overshoot" on the inspiratory airway pressure tracing (circle) indicates, in
reality, the abrupt end of patient inspiratory effort. Active expiration is present throughout all of expiration.
1
.,d. 0.5
.t=
s0 0
E
o3: -0.5
ii:
-1
(j) ®
2
-.,
c-
::J
~
1
G>
~
-
!
3: 0
0
u::
-1
10
0 +-------------+-----~--~----------~------~--~--------------------~
-1 0
Tlme (s)
FIGURE 9-14 Inspiratory and expiratory delays and low pressurization during PSV with a h elmet system. In th is healthy subject, an
inspiratory delay is evident between the first vmical dotted l ine (onset of inspiratory effort) and the second (thicker) vertical Jjne (onset of
ventilator assistance) (Interval 1). A low rate of pressurization is evident, typical when PSV is delivered via a h elmet system (Interval 2).
Expiratory delay corres ponds to the time between the third (end of inspiratory effort) and fourth vertical lines (end of insu fflation)
(Interval 3)
1.5
::;.......
~
0.5
;:
0 0
u::
-0.5
-1
20
15
0
£
E 10
(,)
.......
FIGURE 9-15 Early cycling off. The

ventilator ends insufflation (thick
vertical dotted liue) before the patient's
inspiratory effort ceases (secot~d
vertical line). The airway pressure
tracing then drops transiently below
the baseline end-expiratory pressure
level because patient effort is stiU
substantial after ventilator insufflation
has ceased. The two cycles with this
form of asynchrony are associated with
increased effort (dotted horizontal line)
and prolonged neural T 1• The duration
of Tt on the second cycle (T2 ) is longer
-5
------------- 1
I
I
- --- -------~I
I
I
-------------· than T 1 on the first cycle (T1 ), as
reflected with the greater distance
between the arrow heads. A larger T 1
Time (s) favors this form of asynchron y.
The setting of the cycling-off criterion can be difficult. Ya- sponded to patients with acute lung injury, who have low
mada and Du.137 designed a mathematical model to ana- resistances and low compliance (resulting in a short time
lyze the mechanisms of expiratory asynchrony during PSV. constant).
This model yields several insights.137 The ratio of flow a t Hotchkiss et al141 used linear and nonlinear ma themat-
the end of patient neural inspiration (neural T1) to peak ical models to investigate the dynamic behavior of PSV.
inspiratory fl ow during PSV is determined by the ratio Predicted behavior was confirmed w ith a test lung. In the
of respiratory time constant (r ) to neural T1 and by the setting of airflow obstruction, PSV was accompanied by
ratio of set PSV to m aximal inspiratory muscle pressure. marked variations in Vr and end-expiratory alveolar pres-
With selected respiratory mechanics, the ratio of flow a t sure, even when patient effort was unvarying. Unstable be-
the end of neural T1 to peak inspiratory flow ranged from havior was observed in the simplest plausible linear math-
1-85% and had anexcelJent linear correlation with r/neural ematical model, and it was an inherent consequence of the
T1• A single fixed setting of the flow-termination criterion underlying dynamics of this mode. Because of its complex-
leads to either synchronized or asynchronized termina- ity and the frequent changes in ventilatory pattern during
tion depending on patient mecl1anics. The highest values PSV,1 41 automatic adjustment of triggering based on mathe-
of the cycling-off criterion corresponded to obstructive matical models might be helpful.142 Du et al143•144 proposed
patients with high resistances and high compliances (rean automatic adjustment of the cycling-off criterion based
sulting in a high time constant). The lowest values corre- on the measured time constant in a patient.
Major asynchronies can be detected at the bedside if under patient regulation. During ACV, patient inspiratory
the ventilator screen d isplays airway pressure and flow effort influences ventilator work, but it does not modify flow
tracings. New ventilators permit clinicians to ad just ventila- or volume. Therefore, the use of volume-assisted ACV is
to r settings in order to reduce the frequency of asynchrony. essential when strict control of V1 is considered important,
Education, however, is needed to enable clinicians to recog- such as in patients with acute respiratory distress syndrome
nize and treat asynchronies. During invasive PSV, a major (ARDS) to avoid excessive dis tension.150• 15 1 Use of PSV in
goal is recognition of ineffective efforts. During noninvasive unstable patients w ith a high respiratory drive has the ma-
PSV, a n important issue is recognition of prolonged inspi- jor disadvantage of offering no control over VT. Conversely,
ratio ns caused by leaks. Both problems can be recognized PSV may adapt better to variation in patient demand.
easily. Adjustment of settings (m ost often a decrease in pres- Effects of PSV and ACV on breathing pattern, gas
sure level) avoids or minimizes the problem. Likely this will exchange, and indices of work or effort have been
improve the efficacy and comfort of PSV. compared. 44•53 Cinnella et a1152 compared breathing pat-
tern and respiratory muscle effort d uring ACV and assisted
pressure-control ventilation. Although the latter mode dif-
Differences from Other Modes fers from PSV in that T 1 is preset, this comparison enabled
study of the effects of a pressure-targeted mode. Pressure
of Ventilation was adjusted to achieve a similar VT as w ith ACV; T1 was the
same for both. With a high V1 (12 ml/kg), the modes did
Comparison of PSV with other modes helps to define the not differ for respiratory muscle effort. At a moderate VT
indications or contraindications of various modes of partial (8 ml / kg), work of breathing and pressure-time index were
ventilator support and the relative advantages of each. signifi cantly lower with assisted pressure-control ventila-
tion. The decelerating-flow pattern better matched patient
demand than did the constant-flow pattern. No difference
INTERMITTENT POSITIVE-PRESSURE BREATHING
was found between the modes, however, when T1 was short-
PSV has some similarities with intermittent positive- ened and thus inspiratory peak flow rates increased. There-
pressure breathing (IPPB), an assisted mode used widely in fore, with adequate settings, both modes could unload the
the 1960s for physiotherapy.145 - 148 With both IPPB and PSV, muscles adequately. Leung et al 24 also showed that high lev-
cycles are triggered by the patient and limited by pressure, els of assistance were equivalent with PSV, ACV, and SIMV.
and both can assist patients in acute respiratory failure (w ith Pressure-targeted breaths are more effective than volume-
or without endotracheal intubation). They differ in tha t PSV targeted breaths in reducing patient effort during SIMV.23
but not IPPB maintains a constant level of pressure during In specific circumstances, a switch from ACV to PSV may
inspira tion. The mecl1anisms tha t cycle between inspiration improve pa tient-ventilator synduony. Patients w ith mod-
and expiration are also different. The end of inspiration is erate acute respiratory failure can be ventilated easily w ith
flow-cycled with PSV and pressure-cycled with IPPB. In nor- PSV. Some authors report that patients with severe ARDS
mal, nonintubated subjects, work of breathing was lower also benefit from PSV.5 .41
with PSV than with IPPB. 149 This difference was exagger-
ated considerably in the presence of C02 stimulation, when
SIMV
minute ventilation reached about 25 liters/min. Significant
extra work was induced by IPPB devices compared with SIMV combines delivery of assisted breaths with spon-
PSV, as well as compared with unassisted breathing. Ex- taneous unassis ted breaths.153·154 SIMV differs from PSV,
piratory work also was greater and comfort poorer w ith where every breath is supported to the same extent. Marini
IPPB devices than with PSV. These differences in operational et al155 stttdied eight patients receiving SIMV delivered at
principles have been made possible by the introduction of variou s percentages of total ventilatory requirement. On a
reliable flow sensors within the ventilators. breath-to-breath basis, the effort performed by a patient was
almost equivalent for assisted and unassisted brea thing.
Total work performed by a patient depended on the per-
ASSIST- CONTROL VENTILATION
centage of mechanical assistance delivered. This did notre-
Both PSV and ACV provide full ventilator support; ACV sult from a different percentage of unloaded breaths, how-
is u sed far more frequently. 3 The modes differ in ways that ever, because patient effort remained constant from breath
explain their relative ad vantages or disadvantages. During to breath. These findings were confirmed by Imsand et a!'156
ACV, VT is guaranteed and independent of respiratory me- using diaphragmatic EMGs. Differences in patient effort be-
chanics; thus a minimal frequency and manda tory minute tween assisted and unassisted breaths during SIMV, how-
ventilation can be set. During PSV, by contrast, VT may ever, have been found when the mandatory breaths were
change with alterations in respiratory compliance or resis- delivered as pressure-targeted breaths (delivery of a con-
tance. stant pressure during a fixed Tt).23
For a ny inspiratory effort, addition of PSV augm ents the Mad ntyre7 compared SIMV (VT set at 1(}-15 ml/kg) and
pressure difference between the circuit a nd the alveoli, lead- PSV (set at 13-41 cmH2 0) in a crossover study of 15 patients
ing to a higher inspiratory flow rate and higher VT than dur- recovering from acute respiratory failure. Sense of comfort
ing spontaneous breathing. Whatever the PSV level, it in- was increased, and respiratory rate slower with PSV. There
creases inspiratory flow rate in a way that remains partially was no change in hemodynamic para1neters. In 21 patients
ventilated for at least 3 days, Knebel et al157 compared PAV.89 In intuba ted patients, Grasso et al169 compared the
similar levels of partial support provided by SIMV and response to a restrictive load (cl1est and abdominal biJld-
PSV in terms of breathing comfort, defined by subjec- ing). PAV achieved a higher VT, lower respiratory rate, and
tive ratings of dyspnea and anxiety. On a single day, el- lower pressure-time product of the diaphragm (in response
igible patients experienced, in random order, both SIMV to the load), resulting in bettercomfortwhencompared with
and PSV weaning protocols (sequential 20% reducti.o ns in PSV. Such adaptations to loads with PAV and PSV also were
support at timed intervals). Preweaning levels of dysp- found in healthy subjects 170·171 and with a lung model. m
nea and anxiety did not differ significantly between the With pneumatic triggering systems, a delay can occur be-
modes at any level of support. Surprisingly, comfort was tween the onset of patient effort and effective triggering, 173
not influenced by the level of support, making it difficult to mainly when auto-PEEP is present. 19•116 Giannouli et al40
draw specific conclusions about the comparison of the two found less ineffective triggering with PAV than with PSV in
modes. intubated patients. The authors reasoned that during PSV, in
Leung et al24 compared the effects of PSV and SIMV a t contrast to PAV, ventilator T 1would outlast neural T 1, espe-
varying levels of support in the same patients. They also cially in patients with a long time constant. Thus insufflation
studied the combination of SIMV and PSV. The level of as- continues while the patient has begun to exhale, resulting in
sistance varied from 0-100%, the latter being equivalent to hyperinflation and greater risk of ineffective efforts . Otl1er
full support with ACV. Patient effort was similar with SIMV studies also found less ineffective efforts with PAV than with
and PSV at high levels of assistance but was higher with PSV.174· '175 In intubated patients with severe COPD and high
SIMV than with PSV a t lower levels of assistance (2~0% intrinsic PEEP (6.8 ± 3.9 cmH20), no ineffective triggering
of maximal support). Although the difference in patients occurred with PAV, with or without CPAP176; comparison
was of smaller magnitude than in animal experiments, the with PSV was not performed.
results are consistent with comparisons of IMV and PSV in Many studies r-eveal a greater variability of VT
small animals. 158·159 The studies suggest that when reduc- with PAV tha11 with PSV171 •177- 180 and better patient
ing the level of ventilator support, unloading of the respira- comfort.89,l63,l64,l 71·178·181 - 184 PAValso provided better con-
tory muscles may occur earlier with SIMV than with PSV.160 trol of Pc 02 compared with other modes.185 One study in
Whether this could explain (or partly explain) the different stable patients with neuromuscular and chest-wall disease
clinical outcomes with the two modes during weaning is noted better unloading and comfort with PSV than with
unclear (see below). PAV.186
DRAWBACKS OF PAV COMPARED WITII PSV

PAV
In contrast to any other mode (including PSV), greater
PAV was developed several years after PSV_I 61 •162 Promis- knowledge of resistive and elastic characteristics of the res-
ing initial results and great physiologic interest have piratory system is necessary when setting PAV. It can be dif-
characterized this mode. PAV, however, has remained es- ficult to obtain simple and reliable measurements of these
sentially a physiologic tool, and results of the first clinical characteristics in awake patients triggering the ventilator.
comparisons with PSV have been disappointing. Most phys- The values also frequently vary. The setting of PAV thus
iologic comparisons of PAV and PSV favor PAV in terms is complex and constitutes an obstacle to its wide accep-
of breathing-pattern variability, patient-ventilator interac- tance. Porta et a1179 found tl1at the time needed to set PAV
tion, and comfort. In clinical trials, mainly during NN, was longer than for PSV. Methods to automatically and in-
these physiologic effects did not produce any outcome termittently determine respiratory resis tance and elastance
benefit.16~-1 67 were proposed recently. 187· 188 These methods could be in-
PAV is designed to deliver assistance in direct proportion corporated into a closed-loop adjustment of PAV. A major
to patient effort.161· 162·168 In comparison with PSV, PAV al- drawback of PAV is the occurrence of a specific asynchrony:
lows more physiologic ventilation, but ventilator settings runaway. 168 Runaway is rela ted mainly to an excess of vol-
are more complex. ume assistance.40•174·181
ADVANTAGES OF PAV COMPARED WITH PSV CLINICAL STUDIES

During invasive ventilation and NlV, PAV is consistently Two prospective, randomized, controlled studies with clini-
superior to PSV on physiologic endpoints. In response to cal endpoints have compared PAV and PSV.163•164 The stud-
variable loads (e.g., dead space and resistive or restrictive ies were conducted during NIV. The first s tudy enrolled 44
loads), PAV adapts the level of assistance to patient demand. patients: PAV (n = 21) and PSV (11 = 23). Despite significantly
Witl1 PSV, in contrast, the level of inspiratory pressure re- better comfort and less treatment refusal..,vith PAV, intuba-
mains constant whatever the load. In response to acute hy- tion and mortality rates were equivalent. Fernandes-Vivas
percapnia (addition of 100 mi of dead space), Ranieri et al 89 eta! 164 used similar methodology in 117 patients. Intubation
showed that PAV adapted more efficiently to ventilatory and mortality rates were equivalent despite better comfort
demand than did PSV. Levels of inspiratory pressure in- and less intolerance with PAV. Even when used during NIV,
creased during PAV with a relative increase in VT and no in the presence of leaks, few problems related to nmaway
change in respiratory rate, whereas a small increase in VT were reported. These early clinical trials of PAV are disap-
and a large increase in rate were observed with PSV. This pointing when contrasted with the promising physiologic
resulted in lower work of breathing and better comfort with studies. No clinical study has yet been conducted using the
new methods that allow automatic measurement of respi- this reflects adaptation to a decrease in C02 production or
ratory mechanics. 187•188 a deleterious effect could not be inferred from these data. 194
NAVA Adjustment of Pressure Level

NAVA is a promising but experimental mode of venti- at the Bedside
lation. It provides assistance in proportion to patient ef-
fort. It depends on continuous recording of diaphragmatic Precise guidelines for the bedside use of PSV are lacking;
electrical activity (EAdi), which is obtained via a nasa- the pressure level has been adjusted in various ways in
gastric catheter incorporating a multiple-array esophageal many studies.7•195·196 The maximal PSV level that results
electrode (nine electrodes spaced 10 mm a part). The onin a stable breathing pattern (without bradypnea or apnea)
set and end of assistance and the level of assistance are has been proposed? Assessment of accessory muscle activ-
driven directly by the EAdi signal.173 In theory, NAVA ity, especially the sternocleidomastoid, by inspection and
should provide better patient-ventilator synchrony than palpation was suggested for deciding optimal assistance. 31
pressure-targeted modes. Firs t results support this expec- In this study, less work also was associated w ith a decrease
tation. Unlike all other modes (including PAV), NAVA in r espiratory frequency (below 30-32 breaths per minute).
should not be influenced by intrinsic PEEP or by the pres- Respira tory frequency can be used as a simple indicator of
ence of leaks, as in the case of standard triggering sys- the adequacy of PSV31 ·60; less than 30 breaths per minute
tems. The initial report on NAVA revealed advantages com- has been recommended. 60 •138•197 As indirectly suggested
pared with PSV in terms of triggering and cycling off of by weaning trials, a target of low frequency (25 breaths
the ventilator. 173 NAVA and PSV have been compared in per minute or below) may prolong weaning duration. The
a rabbit model of acute lung injury.189 Diaphragmatic un- latter also may be explained by increased occurrence of
loading was much more efficient with NAVA than with asynchrony w hen a low frequency is displayed on the ven-
PSV, with a reduction of indexes of effort and the ab- tilator. In early studies, PSV was adjus ted to reach a pre-
sence of wasted efforts. In intuba ted pa tients, Spahija et determined VT (8-12 ml/kg). 8•35•54 A setting of 6-8 ml/ kg
al132 compared the trigger delay and cycling off of inspi- VT seems more advisable to avoid patient-ventilator dysyn-
ration with NAVA and PSV. Both modes were studied at chrony. One study suggested, however, that patients who
low and high levels of assistance. Inspiratory trigger de- could be weaned controlled their own VT and were only
lay was around 100 ms with NAVA and a round 200 ms mildly influenced by the PSV level.198
with PSV. Cycling-off delays were markedly different:
40 ms (whatever the level of assistance) with NAVA and
500-1000 ms with PSV Oow and high assistance). Of note,
the cycling-off criterion during PSV was set at 5% of peak Closed-Loop Delivery of PSV
inspira to ry flow (Servo 300), which can cause prolonged
expiratory delay, especially in patients with COPD and The potential for variation in delivered ventilation has led
a long time constant. 137•190 These first physiologic results many manufacturers to develop servo-controlled modali-
are encouraging. The same research group recently re- ties of PSV. In one ventilator, the PSV level was adjusted
ported an evaluation of a n original closed-loop system us- automatically to achieve a preset breathing frequency.'199
ing EAdi as a target to select the level of PSV: target-drive This approach had advantages over fixed PSV when abrupt
ventila tion.191 This system was evaluated in 11 healthy changes in respiratory demand occurred. More often, servo-
subjects before and during exercise and without venti- controlled modes have been proposed to adjus t the PSV
lator support. Without target-drive ventila tion, EAdi in- level to keep VT cons tant. Pressure can be varied from
creased, as did indexes of effort and end-tidal C02 dur- breath to breath using various algorithms. These options
ing exercise. With target-drive ventilation, the level of have been designed to provide a better ventilator response
pressure increased during exercise, maintaining the EAdi to changes in respiratory mechanics. 200·201 An increase in
constant. resistance or elastance during PSV normally leads to a drop
in VT if no compensation is made by the patient or the
ventilator.
These new modes, often called dunl-control modalities, use
Hemodynamic Consequences of PSV closed-loop feedback control systems that enable the venti-
lator to adapt output based on the difference between mea-
Unique hemodynamic consequences have not been de- sured ventilation and a predefined target. The modes go
scribed with PSV. 7•8•33•35•47•60•192·193 Despite a wide range of by different names. To overcome the theoretical limitations
pressures, most studies have found little or no deleterious of PSV, volume-support ventilation (VSV) was introduced
effects of PSV on cardiovascular function in patients after in the 1990s on the Siemens Servo 300 ventilator (Siemens
cardiac surgery or in patients with respiratory failure. The Elema, Solna, Sweden). VSV is a pressure-limited m ode
negativity of pleural pressure during PSV and the control that uses a target VT and minute ventilation for feedback
of airway pressure may reduce the risk. One study found control. The level of PSV is adjusted continuously to de-
that PSV during NIV may lead to a reduction in cardiac liver a preset VT. Two anecdotal reports with VSV202,203 and
output without a change in mixed venous P~ . 49 Whether one randomized, controlled trial204 have yielded variable
results. Other modes working on the same principle- ventilation in PSV mode. It does not include mathematical
volume-targeted pressure-regulated mode-have been de- equations of a physiologic model. Several types of eval-
veloped extensively by manufacturers without extensive uation have been performed: (1) to determine how well
clinical validation. Specifically, physiologic studies have not the system adapts the level of assistance to patient needs
assessed the efficacy of VSV in terms of adjustment to spon- (evaluation of the control level) 213, (2) to assess the extu-
taneous changes in mechanics. TI1e response of such m odes bation recommendation made by the system (evaluation
to changes in ventilatory demand can be troublesome, such of the strategic levelf3 and (3) to estima te the impact on
as those occurring w ith different states of wakefulness, nu- clinical outcomes. 214•21 5 This system has been shown tore-
trition, episodes of sepsis, pain, and so on. With a fixed level duce periods of excessive respiratory efforts and to predict
ofVSV, but not ofPSV, Jaberet al205 found that an increase in extubation time with good accuracy.73•213 It has been used
ventila tory demand resulted in a decrease in PSV provided safely during prolonged periods of mechanical ventilation
by the ventilator, the opposite of the desired response. Con- and has been shown recently to reduce the time spent on
ceivably, VSV may result in respiratory distress in clinical the ventilator.214·215
settings.
More complex knowledge-based systems have been de-
veloped with the aim of providing an automatically per-
formed, pa tient-adapted ventilator support that is super-
Clinical Applications
imposed on an automated weaning strategy.73•206- 209 Such
WEANING
systems have been implemented in computers that drive a
ventilator. These approaches using SIMV plus PSV or PSV The usua l weaning methods are once-daily trials of spon-
alone have been evaluated in patients. Sophisticated m odes taneous breathing, most often w ith a T piece, resulting in
have been developed through improvements in computer abrupt discontinuation of mechanical ventilation, SIMV,
science.210,l ll and PSV with a gradual reduction in the level of assistance.
When the physiologic and clinical knowledge needed to A low PSV level can be used to mimic spontaneous breath-
manage a well-defined clinical situation is acquired, it can ing trials; the la tter thus constitutes the final step in the
be embedded within a computer program that drives the approach of gradual reduction in PSV or as a substitute
ventilator using artificial intelligence techniques, such as for aT-piece trial. PSV also can been used in combination
production rules, fuzzy logic, or neural networks 212 These with SIMV, although very few data support the use of this
new techniques allow pla1ming and control. Control is a lo- combination.22- 24 In a 1998 international survey of the use
cal task that consists of determining what is the inu11ediate of mechanical ventilation,3 PSV was used one way or an-
next step. Pla1ming is a strategic task aimed at regulating other in 45% of weaning attempts. These data indicate that
the time course of the process. For control and planning, PSV is considered an important weaning teclmique.
numerous techniques have been developed in the fields of Studies comparing T-piece trials, SIMV, and PSV were
control theory and artificial intelligence, respectively. The rare before the mid-1990s. Studies had included a large per-
main difference between these two fields lies in the process centage of postoperative patients who exhibited no persis-
models used. Control and planning are two complemen- tent weaning problen1; no conclusions were drawn regard-
tary and essential tasks that must be combined to design ing the type of ventilator support to use. 216 PSV as a sole
multilevel controllers for automatically supervising com- mode of ventilation has been tested in two prospective, ran-
plex systems such as mechanical ventilators. Because the domized, controlled trials.195·196 These trials share common
driving process is based on complex physiologic models, it conclusions: (1) Patients who tolerated 2 hours of breath-
is important to avoid both oversimplification and excessive ing on a T piece were not enrolled and were considered
complexity.203 Strickland and H asson208•209 tried to develop easy to wean: 60--80% of patients who reached the wean-
a controller incorporating an active clinical strategy repre- ing phase were separated easily from the ventilator on first
sented by production rules using SIMV and PSV (IF condi- attempt; (2) weaning outcome in the remaining patients de-
tions, THEN actions). Their work did not lead to commercial pended heavily on the weaning strategy used; and (3) SIMV
development. l08, 2D9 was consistently the worst weaning method. The two trials,
The Smart Care® system is an embedded version of the however, differed regarding efficacy of PSV. PSV was found
initial NeoGanesh system. The NeoGanesh system drives superior to other methods in the study of Brochard et aJ195
the ventilator with PSV, keeping a patient within a zone but not in the subsequent shtdy of Esteban et al. 196
of "respiratory comfort," as defined by respiratory pa- Brocl1ard et al195 compared three methods of gradually
rameters, and superimposing an automated strategy for withdrawing mechanical ventilation. In one group, PSV
weaning.73•207·213 The designers of the knowledge-based was decreased gradually according to patient tolerance. In
NeoGanesh system intended to build a closed-loop system a second group, SIMV was adjusted to decrease the percent-
that (1) was efficient for auto matically controlling m echani· age of total ventilator support gradually. In a third group,
cal support and planning of the weaning process, (2) could T-piece trials of increasing duration were interspersed w ith
be evaluated with the goal of gradually improving its rea- ACV. At 21 days, a significantly higher percentage of pa-
soning and planning capabilities, and (3) could be subjected tients had been separated from the ventilator withPSV than
at the beds ide to performance meas urements at each step with the other two methods. TI1is was accompanied by a
of its opera tion. The NeoGanesh system is based on model- shorter duration of weaning with PSV. Es teban et aJ196 did
ing of the medical expertise required to perform mechanical not use the same criteria for adjusting the pressure level in an
individual patient. PSV was adjusted to achieve a respira- devices,86•234 in terfaces,140•235- 237 and patient-ventilator
tory rate lower than 25 breaths per minute. PSV was found asynchrony. 99•100
to be inferior to once-daily T-piece trials and multiple-daily
T-piece trials. This PSV approach seemed to lengthen the
weaning process compared with once-daily T-piece trials. USE O F NONINVASIVE VENTILATION
In the study of Brochard et al, 195 PSV was adjusted to ob- WITH PSV FOR WEA NING
tain a respiratory rate lower than 35 breaths per minute. In patients with acute exacerbations of COPD, prolonged
In that trial, PSV was superior to all other approaches, in-
mecl1anical ventilation is associated with complications. In
cluding SIMV and intermittent T-piece trials. In the study
this setting, Nava et a1223 suggested that dellberate extuba-
of Esteban et a1,1 96 the final test before extubation was a tion followed by a switch to NlV might improve weaning
T-piece trial, during which frequency of up to 35 breaths outcome. Using PSV for such a goal achieved greater wean-
per minute was tolerated. In the same study, the final step ing success and higher survival rate. A subsequent study
with PSV was a level of 5 cmH2 0, during which frequency did not entirely confirm these results; patients switclled to
above 25 breaths per minute was considered a sign of poor noninvasive PSV experienced a longer time of ventilator
clinical tolerance. Thus the use of PSV differed markedly in support.238 In patients with stable chronic respiratory dis-
the two s tudies and likely explains differences in efficacy. orders who were unable to sustain spontaneous breathing,
No study has compared the PSV approach in the trial of Vitacca et al239 found that invasive PSV, delivered while
Brochard et al'195 with the once-daily T-piece method in the patients were still intubated, and noninvasive PSV were
study of Esteban et al. 196 Another trial, however, found no equally effective in reducing respiratory muscle work and
difference between T-fiece trial and PSV in patients with improving arterial blood gases. In addition, noninvasive
weaning difficulties. 21
PSV was slightly better tolerated.
PSV and T piece have been compared as a final step before
extuba tion. Use of a low level of PSV has been found equiva-
lent or slightly superior to aT-piece trial in both adults and
infants. 71 •72•74 A low level of PSV was slightly superior to Conclusion
T piece in terms of short-term success after extubation? 1•74
At 48 hours, the success rate was not significantly different PSV is a mode of partial ventilator assistance that has proved
in the largest trial. 71 very efficient in reducing work of breathing and provid-
A comparable approach was used in tl1e NeoGanesh ing relatively good synchrony with patient effort. PSV pro-
dosed-loop sys tem that employs automatic adjustment of vides a good model to increase understanding of patient-
PSV.73. 213 Although different from standard clinical use of ventilator interaction. Its place has been assessed mainly
PSV, the results with a computer-driven system constitute a during weaning and NIV. It also can be used early in the
form of validation of PSV weaning in a system that applies course of ventilation, enabling the patient to be ventilated
it on a 24-hour-a-day basis. without the need for sedation and in preparation for wean-
ing. Tn the early phase, its use may be limited by lack of con-
trol over the volume delivered. One of its main drawbacks,
N ONINVASIVE VENTILATION
however, is the possibility of overassis ting patients, caus-
ing major dyssynchrony between a patient's rhythm and
NIV has been used in many patients with acute respira- that of the ventilator, inducing hyperventilation, episodes
tory failure since the early 1990s.96•140•218- 224 PSV is used of apneas, and sleep fragmentation, especially in patients
preferentially by several groups for NIV. Dellvered via with obstructive lung disease.
a face mask, PSV decreases respiratory muscle activity
markedly in patients w ith COPD in acute distress. During
exercise, which also constitutes a high ventilatory work-
load, noninvasive PSV improves performance in patients
with COPD.225
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t:.hapter 10 _ _ _ _ _ _ _ _ __ in the most severe cases4 and including pediatric patients.5
Many publications address the implications of PCV on the
PRESSURE-CONTROLLED cardiovascular system, work of breathing, regio nal mechan-
ics, and the risks of ventilator-induced lung injury, which
AND INVERSE-RATIO increase physicians' comfort in moving away from volume-
controlled ventilation.
VENTILATION In contrast to the growing acceptance of PCV, use of
inverse-ratio ventilation (IRV)- that is, the prolongation
MARCELO B. P. AMATO of inspiratory time to the point of inverting the conven-
JOHNJ. MARINT tional inspiratory-to-expiratory O:E) ratio-has declined
in the last decade. In 1971, Reynolds6 reported that ventila-
tion with an extended inspiratory time improved oxygena-
tion in neonates with hyaline membrane disease. A decade
later, several investigators embraced this idea, repeatedly
showing oxygenation benefits in adults with acute respira-
TYPES OF CONTROLLED VENTILATION AND tory distress syndrome (ARDS).7- 12 Most studies applied
SELECTION OF THE "CONTROLLED" PARAMETER IRV in conjunction with pressure-controlled breaths (PC-
SPECIFIC CH ARACTERISTICS OF IRV) to minimize the risk of overinflation. Initial enthusiasm
PRESSURE-CONTROLLED VENTILATION was followed by a period of skepticism, when investiga-
Input Parameters of PCV tors suggested that the benefits of IRV could be better as-
Mean Airway and Alveolar Pressures cribed to the generation of intrinsic positive end-expiratory
Output Variables of PCV pressure (intrinsic PEEP) or purely to increased mean alve-
PHYSIOLOGIC EFFECTS OF PCV olar pressures. 13- 16 In subsequent comparative studies in
Advantages of Controlling Airway Pressures patients with ARDS, when equivalent mean airway pres-
The controversy on Optimal Distribution of sures were applied by different approaches, IRV produced
Ventilation worse oxygenation than did ventilation with conventional
Assisted Versus Controlled (Time-Triggered) I:E ratios plus external positive end-expiratory pressure (ex-
Ventilation terna l PEEP). 17•18 Over the years, concerns were raised re-
VARIANTS OF PCV AND ACTIVATION peatedly about hemodynamic deteriora tion, elevated mean
OF EXHALATION VALVE airway pressures, 14 regional overinfla tion of lung units,19· 20
Assisted PCV and difficulty with clinical implementation of this complex
Activation of Exhalation Valve During PCV: mode in everyday care. 21 The final result was progressive
Airway Pressure-Release Ventilation discrediting and a change of focus: Instead of IRV, system-
Combined Modes atic application of external PEEP and recruiting maneuvers
INVERSE-RATIO VENTILATION started to receive closer attention. 22•23
Implementing Inverse-Ratio Ventilation The perspective we present in this chapter is not going to
Later Comparative Studies on IRV change this scenario. We believe that IRV should be viewed
Effects of Total PEEP and ¢Jaw on Oxygenation primarily as an experimental m ode with few clinical indica-
Intrinsic PEEP Versus Extrinsic PEEP tions . There are safer, more predictable, and more efficient
Other Effects of IRV ventilatory solutions to be implemented at the bedside. We
Drawbacks also believe that close examination of the rationale and ev-
CONCLUSION idence behind the apparently contradictory reports on PC-
IRV offers insights on the pathophysiology of injured lungs.
Therefore, besides describing our general approach to PCV
The use of pressure-controlled ventilation (PCV) has in- and its variants, we discuss the history and progressive ev-
creased dramatically in the las t 10 years. Behind this grow- idence gathered on IRV.
ing usage, there is an increased awareness of intensivists
about the phenomenon of ventilator-induced lung injury
and the associated risks of high inspiratory pressures. The
recent familiarity with the concept of permissive hypercap- Types of Controlled Ventilation and
nia contributed to this change in attitude, helping physi- Selection of the liControlled" Parameter
cians to relax about the old and stringent limits for ar-
terial blood gases.1- 3 Tidal volume or minute ventilation Ventilators currently available regulate either the pressure
requirements were left progressively as secondary goals. profile applied in the airways or the pattern of flow deliv-
Physicians learned that critically ill patients have a surpris- ery. Somewhat imprecisely, flow-controlled ventilation has
ingly good tolerance against elevated carbon dioxide (C02 ) been designated "volume-controlled" ventilation (VCV).
levels.1- 3 Recent surveys in intensive-care units (ICUs) We avoid this convention because the criterion by which
around the world have demonstrated that PCV is no longer the ventilator ceases to pressurize the airway (initiates
a pure experimental mode; it is now used in up to 25% of pa- defla tion) may be a specified value of delivered volume,
tients receiving prolonged mechanical ventilation, usually pressure, elapsed time, or flow. The parameter, however,
251
actively controlled by the ventilator during "volume- teed, although minute ventilation is a t risk w heneve1· lung
controlled" breaths is in reality inspiratory flow. Therefore, impedance changes.
the modes of ventilation currently used in medical practice Independent of selection of the controlled parameter,
should be classified as either pressure- or flow-controlled and inspiration can be triggered by elapsed time or by small
as time-, volume-, flmv-, or pressure-cycled. Pressure-support perturbations in pressure/flow in the airways (usually in-
ventilation (PSV) is an example of a pressure-controlled, dicative of patient effort). The former case defines a totally
flow-cycled mode, whereas PCV is an example of pressure- controlled breath, whereas the latter case defines an assisted
controlled, time-cycled mode. (i.e., patient-triggered) breath. In recent years, modern ven-
In flow-controlled modes, the waveform theoretically can tilators have incorporated algorithms providing pressure-
be of any des ired contour; in clinical practice, however, the controlled breaths triggered by either elapsed expiratory
flow waveforms usually are rectilinear (sq uare), linearly de- time, characterizing traditional PCV, or patient effort (as-
celerating, and sinus oidal. Setting tidal volume as the "off sisted pressure-controlled ventilation), analogous to the tra-
switch" criterion (volume-et;cled) means that the pressure ap- ditional flow-controlled assist-control ventilation (ACV).
plied to theairwayopeningcan rise to any value required by
the impedance to inflation that does not exceed the pressure-
limit alarm. Very high absolute (if not transmural) alveolar
pressures can develop during expulsive efforts o r bouts of
Specific Characteristics of
coughing. Pressure-Controlled Ventilation
Although once used extensively, pressure-cycled ventila-
tion is now considered obsolete for continuous support, and Many recently introduced ventilator modes can be consid-
its application in intermittent positive-pressure breathing ered as variants of pressure-controlled or pressure-preset ven-
(IPPB) has been restricted greatly. Currently, pressure cy- tilation. This includes traditional PCV,8, 27 pressure-support
cling serves primarily as a backup cycling-off criterion dur- ventilation,28, 29 biphasic continuous positive airway
ing flow-controlled, vol-ume-cycled ventilation (when airway pressure (BiPAP), and variants of airway pressure-release
pressures reach a preset alarm threshold). ventilation. 30,31 In some modes, spontaneous respiratory
In an a ttempt to improve safety or to decrease the need efforts continue. In others, none occur. These modes vary
for repeated adjustments at the bedside, flow- and pressure- both in their intended objectives and in their criteria for
controlled algorithms have been combined recently to form initiating and terminating the machine's inspiratory cycle.
new modes (such as " volume-assured pressure support" Yet aUcan be viewed as modes in which the machine applies
and "pressure-regulated volume control"), incorporating approximately square waves of pressure to the airway
the desirable characteristics of each category. 24~ 25 opening. In concept, any pressure profile can be regulated.
The equation of motion of the respiratory system confines In current practice, however, most pressure-controlled modes
the clinician to setting independently the inspiratory flow build pressure rapidly, toward a preset value, attempting
and tidal volume or just the applied pressure profile. Flow to maintain pressure nearly constant throughout the
and pressure cannot be selected independently at the same remainder of the higher-pressure phase. During exhalation,
time because their relationship is defined by the mechanical pressure is released abntptly, allowing passive deflation to
properties of the respiratory system. Because modern ven- occur unimpeded or agains t a set PEEP leveL By fixing the
tilators can provide online feedback information about out- level of applied pressure during inspiration, the physician
put variables (airway pressures during flow-controlled ven- imposes an upper limit to the machine's energy transferred
tilation or flow and tidal volume during pressure-controlled to lung tissue and to the machine component of ventilation
ventilation), either flow-controlled, volume-cycled ventila- that can be ad1ieved.
tion (VCV) or pressure-controlled, time-cycfed ventilation The specifics of the new pressure-controlled modes are
(PCV) can be used effectively and interchangeably during discussed in other chapters. The physical principles gov-
specific conditions. For instance, instead of using tl1e orig- erning pressure-controlled, fime-et;cled ventilation-which
inal pressure-control algorithms during IRV, some inves- serves as the prototype for this group-and its major "out-
tigators have proposed the equivalent use of IRV through come" variables, such as tidal volume, minute ventilation,
flow-controlled, volume-et;cled (VCV) breaths, 26 with care- and intrinsic PEEP, are addressed here. Some discussion of
ful m onitoring and frequent readjustments. Depending on the concepts of mean airway pressure (c/J.w) and mean alve-
particular combinations of compliance and resistance in the olar pressure (c/J A) also will be presented because these con-
respiratory system, the pressure profile generated in the air- cepts are essential tools for understanding the physiologic
ways can be similar in both modes. implications of all pressure-controlled modes.
The major differences between J1ow- versus pressure-
controlled breaths appear during prolonged use, after un-
INPUT PARAMETERS OF PCV
predictable changes in respiratory system characteristics. By
using the traditional flow-controlled, volume-et;cled mode, Apart from the external PEEP, the clinician sets only
minute ventilation is guaranteed safely over prolonged three parameters in PCV: the applied inspiratory pres-
periods of time, although airway pressures may rise sig- sure, backup or mandatory frequency, and fractional in-
nificantly when respiratory system impedance increases. spiratory time (duty cycle, TJITror). The mos t salient fea-
Conversely, during prolonged use of pressure-controlled, ture of PCV is that maximal airway and alveolar pressures
time-cycled ventilation, airway pressure limits are guaran- are restricted by the cap of preset pressure, whereas tidal
CHAPTER 10 PRESSURE-CONTROLLED AND INVERSE-RATIO VENTILATION 253
volume, flow, minute volume, and alveolar ventilation de-
pend on the impedance of the respiratory system in conjunc-
tion with the three input variables just described. Once the
impedance (i.e., the resistance and compliance characteris-
tics) of the respiratory system is known, the machine's con-
tributions to ventilation and alveolar pressure can be charac-
terized completely from knowledge of just those three input
parameters.
Machines vary in the rapidity (rise time or i11spiratory
slope) with which airway pressure builds toward the preset Time
maximum value. Faster rates of pressurization are needed
in certain situations when flow demands are high (dur-
ing assisted pressu.re-confrolled ventilation) or during low-
impedance conditions (in large patients) because of machine
limitations. A more gradual pressure buildup is appropri- ~
ate for quiet breathing and during high-impedance condi- &l

(/)
tions. Some newer machines allow the clinician to adjust rise d 0+---~-----+----~------~-------+
time to suit the situation at hand, whereas others adjust it 3::
0
automatically. u:
With most machines today, physicians set the pressure
increment above external PEEP to be applied during in-
spiration. This means that absolute inspiratory pressures
increase as external PEEP increases. With a few maclunes, FIGURE 10-1 Airway opening pressure (Paw), alveolar pressute
the physician has to set the absolute inspiratory pressure, (PA), and flow during pressure-controlled ventilation. Intrinsic
which is independent of external PEEP. PEEP presents a backpressure that opposes the applied pressure
(Pset) and reduces the effective ventilating pressure, which is
equal to Pset - total PEEP (total PEEP = intrinsic PEEP +
MEAN AffiWAY AND ALVEOLAR PRESSURES extrinsic PEEP). Areas A and B represent the pressure-time
When considering a plot of airway-opening pressure (Paw) product dissipated during ins piration and exhalation,
over time, mean airway pressure is the integral of Paw over respectively. These areas are proportional to m ean inspiratory and
time divided by the time span of the breath. Two input pa- expiratory resistances.
rameters that the clinician sets during PCV bear direct rela-
tionships to mean airway pressure (cf> 3 w): preset inspiratory
pressure and T.fTroT· Because of the square waveform of tances are similar. In this particular situation, mean airway
pressure during PCV, cf>aw can be expressed simply as pressures will reflect alveolar pressures consistently. Con-
versely, when expiratory resistance exceeds inspiratory re-
sistance, a frequent condition in chronic obstructive lung
¢aw = Pset x TrJT TOT + PEEPE x (1 - Tr/TroT) (1) disease, mean airway pressures can seriously underesti-
mate mean alveolar pressures, especially when minute ven-
where PEEPE is external PEEP. Therefore, variations in tilation is high. Under such conditions, variations in fre-
either set pressure (Pset) or TIITTOT influence ¢nw pre- quency do influence mean alveolar press1.1re, and physicians
dictably. Frequency variations leave ¢aw unaffected.32•33 Un- easily could overlook the hemodynamic consequences of a
der passive conditions, airway pressure represents the total ventilator setting.
pressure applied across the respiratory system. It can be Figure 10-1 illustrates some additional features related to
demonstrated mathematically that this applied pressure, alveolar and airway pressures during PCV. Alveolar pres-
when averaged over both phases of the respiratory cycle, sure (PA) can rise no higher than Pset, the pressure to which
is everywhere the same along the airway once phasic dif- it equilibrates at end inspiration when sufficient inspiratory
ferences are accounted for in nonelastic pressure losses.32. 33 time is provided (in Fig. 10-1 there is no equilibrium). Peak
TI1erefore, mean alveolar pressure (¢A) can be easily esti- PA falls rather than rises with increasing frequency. One a lso
mated from ¢aw once inspiratory and expiratory resistances can grasp from the figure that intrinsic PEEP increases w ith
are known: increasing frequency, reducing the effective ventilating pres-
sure (Pset - total PEEP) and consequently reducing tidal
volume. As frequency increases further, PA oscillations de-
(2) cline to the point that ¢A sets the upper bounding value for
intrinsic PEEP.
where RE and R1 are mean expiratory and mean inspiratory Under cond itions of passive inflation, mean airway pres-
resistances, respectively, and 'his the minute ventilation. sure reflects the average distending pressure of the respira-
Some practical conclusions can be drawn from this sim- tory system. Understandably, therefore, mean airway pres-
ple formulation. First, changing frequency alters mean alve- sure has been associated with two beneficial physiologic
olar pressure very little if inspiratory and expiratory resis- effects (ventilation and oxygenation) and three potentially
nox.i ous effects (hemodynamic compromise, fluid retention, plish ventilation (driving pressul'e). Therefore, incomplete
and barotrauma). These e ffects, however, are nonlinear, and lung emptying is also an important factor affecting the deliv-
there are exceptions. For instance, as discussed later, the ered tidal volume. To allow near-complete lung emptying,
relationship between tf>aw and oxygena tion is very depen- expiratory time should be longer than the three expiratory
dent on the extent of pressure-volume hysteresis of the lung, time constants. The aggravating factor is that expiratory re-
w hich is greatly affected by lung disease. The greater the sistance is usually higher than inspiratory resistance, im-
hysteresis, the greater is the dependency of oxygenation on plying that the expiratory time constants are longer. An ex-
PEEP and previous ltmg history (i.e., the maximum alveo- piratory time shorter than 1.5 seconds in an adult patient
lar pressure achieved in previous breaths), and the looser is should be considered a potential source of intrinsic PEEP,
the correlation between the current tf>aw and oxygenation. In reducing the potential for tidal volume delivery.
situations of negligible lung hysteresis, for instance, during
partial liquid ventilation, tl1e correlation between tf>aw and
oxygenation is straightforward.34 The complex relationship INTRINSIC PEEP
between tf>awand oxygenation will be further elaborated in Intrinsic PEEP (auto-PEEP) that results from dynamic hy-
the discussion of IRV below. perinflation is a complex fw1ction of the input parameters
Mean airway pressure is also a measurable correlate of ofPCV in conjunction with the impedance characteristics of
the backpressure for venous return. Raising 1> A during pas- the respiratory system. 35 The general principles affecting it
sive ventilation increases both lung and chest volumes by can be summarized as follows: (1) higher-frequency, longer
similar amounts. Lung expansion tends to increase right- T1/TroTratio and higher Pset tend to increase intrinsic PEEP,
ventricular afterload, which is already high in many patients (2) incr ements in T 1/TTOT cause a monotonic increase in in-
with acute respiratory failure. More important, the increase trinsic PEEP from external PEEP up to Pset, (3) pure incre-
in intrapleural pressure raises right-atrial pressure, often ments in frequency also cause an increase in intrins ic PEEP
impeding venous return. Rising backpressure can have clin- but with a saturation effect that limits intrinsic PEEP to half
ical consequences in patients with impaired systemic ve- (a pproxirnately) the range between external PEEP and Pset
nous tone and reduced tissue turgor (e.g., consequent to which arises because as frequency rises, inspiratory time
sedation/paralysis). Sodium and water retention also tends is curtailed, preventing equilibration between applied air-
to correlate with the magnitude o f tf>aw· Although the way and alveolar pressures, keeping maximum PA well be-
place of 1>A in the generation of barotrauma is not clear, a low Pset; (see Fig. 10-2), and (4) the higher the compliance
high level of ¢A may exacel'bate damage or accentuate gas and the higher the expiratory resistance, the higher is the
leakage through rents in the alveolar tissues, thereby bring- intrinsic PEEP for the same input parameters. Figure 10-2
ing barotrauma to clinical attention. illustrates some of these relationships.
OUTPUT VARIABLES OF PCV

As discussed earlier, the major" output" variables ofPCV are FIGURE 10-2 Effect of frequency on intrinsic PEEP generation
tidal volume, inspiratory flow, minute ventilation, intrinsic durin g PCV. Three impedance combinations with moderate
PEEP, and ¢A· airflow obstruction and varying respiratory system compliance
(expressed in ml/cmH20). A decrease in com pliance causes both a
TIDAL VOLUME reduction in intrinsic PEEP and alteration in the curvature of the
When maximal airway pressure is preset, the tidal vol- intrinsic PEEP/frequency relationship. Note that curves converge
ume actually delivered varies with several key variables: to an asymptote at 10 cmH20, which corresponds to
approximately half Pset. Simulated conditions: Pset = 20 cmH20
the pressure gradient existing between the airway open-
above PEEP; T 1rrTOr = 0.4; Re = 25 cmH 20 /literls. (Adapted, w itl1
ing and the alveolus at the onset of inflation, the resistance permissiou,from Marini et al: Am Rev Respir Dis 147:14-24, 199.~.)
to airflow, the compliance of the r espiratory system, and
the time available for inspiration. Theoretically, ins piratory 10.0 .......... ... ------ .. -~-·
time should be longer than the three time constants of the C= 100 ----·-- -·- ~--
respiratory system to allow near-complete (>95%) lung fill-
ing, thus maximizing delivered tidal volume. This scenario 0 8.0
would guarantee that alveolar pressures are in equilibrium "'
J:
E
with airway pressures at the end o f inspiration. In adult .£. 6.0 , /./ ...................-····-····"
patients with orotradteal intubation, equilibration usually
a..
UJ
. .......
UJ .' ''
requires 1.0-1.5 seconds of inspiration. In the presence of a..
4.0 ' ..~····,.··'
severe obstructive lung disease, this value can be as high as .2
Ul
.
'•
'' ../ C=20
/ ..·······
4-5 seconds . In order to improve synchron y during assisted
PCV, sometimes it is necessary to match the spon taneous
inspiratory time of the patient. In this case, inspiratory time
-c:
·c:
.£ 2.0
/
/
rarely should exceed 1.2 seconds, usually resulting in in- ,. ............-············

0.0 .---....---.-----.-------.,r---
complete lung filling but promoting comfort.
0 20 40 60 80 100
Any residual end-expiratory pressure (intrinsic PEEP) de-
tracts from the total pressure difference available to accom- FREQUENCY
From a practical standpoint, the ventilator itself becomes tribution of a ir /pressure among heterogeneous units and
less able to generate the nominal pressure waveform, es- collateral ventilation. The consequences of such a flow pro-
pecially when flow impedance is low. As tidal volume de- file are reflected mainly in the C02 eliminated per breath
clines, the wasted fraction of each breath (V 0 /Vr) irlcreases (Fig. 10-5). The longer the inspiratory time, the more effec-
owing to the predominance of the series ("anatomic") dead- tive is the clearance of C0 2 , although most of the benefit
space component. Under certain conditions, this increase in may be seen already when T, slightly exceeds the point of
dead space actually may cause Paco.: to rise rather than fall zero flow (see Fig. 10-5). This topic will be discussed further
with increasing frequency.36 In practical terms, there is an in the section about distribution of ventilation below.
important message for the bedside: For a given Pset and The effects of resistance and compliance on flow profile
TdTror, increments in frequency may cause a decrease iri are illustrated in Figs. 10-6 and 10-7. Because of the conse-
Paco, up to the point that tidal volume decreases more than quent increase iri time constant, increments in resistance
approximately 25%. Beyond this limit, even when minute tend to reduce peak flow, producing a less decelerating
ventilation increases with frequency, it is almost certain that (more squared) flow pattern and rendering tidal volume
further increments in frequency will be counterproductive very sensitive to reductions in inspiratory time. In contrast,
because of excessive amounts of dead space. decrements in compliance tend to accelerate flow decay. It is
Because the prirlciples just outlined are rooted in physics obvious, therefore, that restrictive patients tolerate a shorter
and mathen1atics, hypercapnia can be an unavoidable con- inspiratory time without marked consequences to their tidal
sequence of a pressure-targeted s trategy for managing acute volume.
lung injury.
INSPIRATORY FLOW
Decelerating inspiratory flow necessarily is observed dur-
Physiologic Effects of PCV
ing pressure-controlled breaths witl't rectilinear pressure ADVANTAGES O F CONTRO LLiNG
waveforms-provided that there is no patient effort. Un- AIRWAY PRESSURES
der such conditions, the theoretical maximum of flow as-
sociated with a squarewave of pressure (Pset) depends on One of the major features of PCV is that peak alveolar pres-
inspiratory resistance (R1) and end-expiratory alveolar pressure cannot rise any higher than Pset. In critical situations,
sure (PEEPror) and is achieved at irlflation onset: when one attempts to minimize ventilator-induced lung in-
jury, this aspect of PCV may be very convenient. Specifying
the maximum achievable alveolar pressure, however, does
P set - PEEPror not cap the upper limit for transalveolar pressure unless the
P ea k flow= R, (3)
patient's own breathirlg efforts also have been silenced. As
suggested by many studies, transalveolar pressure, rather
where PEEPror =(intrinsic PEEP+ external PEEP). In prac- than alveolar pressure, is the key determinant of ventilator-
tice, however, the abruptness of the rise to the nominal peak induced lung injury and barotrauma.38
value is a set characteristic of the particular ventila tor, which In the absence of patient efforts, keepirlg peak alveolar
may be modulated by the slope or i11spiratory rise-time ad- pressures within a sale range makes sense. Under these cir-
justment. Under conditions of quiet breathing, a precipitous cumstances, controlling airway pressure effectively controls
buildup to peak flow often is associated with some pressure maximal alveolar pressure. Obviously, the same peak alve-
overshoot, which rna y be annoying for monitoring purposes olar pressure always can be achieved by flow-controlled,
because of alarm triggering. Because most of this pressure volume-cycled ventilation, although more bedside adjust-
overshoot represents pressure dissipation as frictional work ments are necessary. The subtle difference here is that by
across the endotracheal tube, it does not cause elevation of selecting pressure as the controlling parameter, the physi-
peak alveolar pressure and probably is 110t associated with cian better defines the priority of his or her strategy (i.e., to
any harm. minimize peak alveolar pressure at the expense of minute
Conversely, under high flow demands (especially iri large ventilation and possible hypercapnia) and probably mini-
patients), a slow "attack rate" up to peak flow can cause mizes violations to the target during ongoing tidal ventila-
some pressure undershoot or a slow ramp of pressure at tion (see below).
the initial phase of the breath, forcing the patient to expend When thinking in peak a lveolar pressures as opposed
considerable effort or delayirlg filling of the lung. 37 Because to peak airway pressures, it is important to stress some
of limitations iri the hardware controlling system, the flow important aspects of PCV. When irlspiratory time is brief,
performance of most ventilators tends to be poor when Pset end-inspiratory airway and alveolar pressures fail to equi-
is less than 10 cmH2 0. Under such conditions, maximizing librate, so the maximal alveolar pressure is considerably
rise time or slightly increasing Pset can be very helpful. less than the set value. This is reflected by persistent end-
The decelerating-flow pattern fotmd in PCV usually im- inspiratory flow. For a given inspiratory time and peak air-
proves the distribution of ventilation and limits the end- way pressure, however, PCV is the waveform that applies
inspiratory gradient of regional pressures among units with the greatest cumulative pressure to the respiratory system.
heterogeneous time constants. When inspiratory time is Stretching forces applied to the alveolus are also maximally
long enough, inspiratory flow may decrease down to zero sustained. 39 Therefore, for the same peak airway pressure--
before exhalation, a phenomenon that further favors redis- and provided that irlspiratory time is long enough-PCV
~
0
:I:"'
-
E 30
u
Q>
~
::>
20 PCV 1:2
~ 40
eQ. ~ ~--e!!_~se 111
?E
~ 10
~
<( -E 30
0"' ~
, "' - ---- -- ----- ... -~
~VCV1:2
0
c:
30 VCV 1:2
PEEPr= 10
PCV1:2
PEEPr= 10 > "0
e
·a.
20
/,'
~
X I
_, 0
-
3:
.2
w 10
0
I
I
u..
-50
Time (s) Time (s) 0 100 200 300 400 500
Expired volume (ml )
0 1 2 3 0 2 3
~
0
:I:"'
-
E 30
u
Q) 40 PCV3:1
phase Ill
~·-
~
::> 20
.,"'
<I)
...--_-:_::-:_;:-::_..,.._~-- - - - --
,"
~
Q.
~ 10
?E 30
~
/~
.§.
~
PCV1:2 PCV3 :1
> 0"'
0
20
I PCV 1:2
30
PEEPr= 15 PEEPr = 15
.,
"0
~ 10
'E' ·a.
§ .n
-u::
~
0
0
0 100 200 300 400

-50 Expired volume (ml)
Time (s) Time (s)
0 2 3 0 1 2 3
FIGURE 10-5 Effects of inspiratory flow profile on C02 elimination per breath (C0 2 single-breath tests obta.i ned in a mainstream
capnograph}. (Top) The change from flow-co ntroUed, volmne-cycled ventilation (VCV) to PCV, whi le keeping the sa.me inspiratory time,
resulted in more efficient elimination of C02 per breath, reflected by the large area under the curve of C02 versus exhaled-volume
(especially in the first 200 ml-and consequently reflecting a lower dead s pace). Note that inspiratory flow deca yed to zero before
e xhalation and that phase 3 slope is alm ost flat during PCV, reflecting less heterogeneity among lung units. Arterial Pco1 w as th e same (38
mmHgl in both conditions, des pite the lower tidal volume during PCV. (Bottom) Changi ng PCV with I:E ratio = 1:2 to PCV 3:1 (wh en part
of external PEEP was replaced by intrinsic PEEP) resulted in a further increase in the area under the curve of C02 versus exhal ed volu.me.
The benefit, ho w ever, was m uch less evident than in the top pa nel.
generates a higher peak alveolar pressure than VCV (flow- PEEP, Pset, and Tt/Tror, one can easily predict the gener-
controlled, volume-cycled breaths delivered with a square- ated ¢Jaw (or¢A) and hence the hemodynamic consequences.
wave profile). Recent studies have demonstrated the relative safety of re-
The consequences of PCV on mean airway pressure (¢J.w) cruitment maneuvers using PCV for 1-2 minutes, which
were discussed earlier. It is an important parameter for achieved the same efficacy as sustained_gressure maneuvers
evaluating the hemodynamic consequences of PCV. Un- (CPAP) adjusted to equivalent Pset. 40 Because the motor
like in flow-controlled VCV, ¢Jaw relates linearly to Pset and of effective recruitment is the surpassing of threshold open-
Tr/TTOT (see Eq. 1). As its defining equation indicates, ¢Jaw ing pressures of terminal airspaces, 43 applied long enough
is unaffected by changes of respiratory system impedance to overcome the forces of viscosity and adhesion, 44 repeated
and frequency. Provided that changes in inspiratory and cyclic pressurizations with PCV provide an interesting al-
expiratory resistance are roughly balanced, mean alveolar ternative. Theoretically, the only requirement is to adjust
pressures follow mean airway pressures very consistently. Pset above the threshold opening pressures, set PEEP above
Consequently, the impact of setting selections on ¢Jaw and the closing pressures, and ensure that inspiratory time is
¢A can be predicted and controlled easily during PCV much long enough to favor slow, sequential stepwise recruitment
more than during VCV. of clumps of alveolar units.43 As suggested by Neumann
Such a straightforward relationship between ¢Jaw and the et a!,4·5 inspiratory times exceeding 0.6 second (ideally closer
input parameters of PCV may be convenient during short- to 4 seconds)-for instance, obtained during PCV with a
term procedures such as recruiting maneuvers. By adjusting frequency of 8-10 breaths per minute and an I:E ra tio of
1:1-would be enough to maximize the potential for recruit-

,- Paw
..---·· ...---- ~
ment at a certain Pset. The great appeal of such PCV ma-
•
•• ••• neuvers is their good hemodynamic tolerance: Because ¢aw
generated during a PCV maneuver is usually less than ¢aw
l'
generated during a CPAP maneuver (at equivalent Pset), the
l'
''. PA hemodynamic consequences are less pronounced. 40' 42 Pre-
Intrinsic-PEEP \ ;
............... . .... ~
ceding volume expansion with colloids further improves
hemodynamic tolerance of the maneuver.42
External-PEEP
Some investigators, such as Schreiter et al,46 have ap-
0~----------------~----------------+
Time plied PCV recruiting maneuvers over much shorter pe-
riods (~1 0 seconds) but reached higher ins piratory pres-
sures (50-80 cmH 2 0 ) and reported good success in patients
with severe chest trauma. Comparative data of the relative
efficacyI safety of such shorter, more intensive application of
recruiting pressures versus longer (1- 2 minutes) application
0Q) ofless intensive (45-60 cmi-I2 0) recntiting pressures 47 - 49 do
(/)
d 0 4----L-------+------4-------~----------. not exist currently.

3: As with any time-cycled mode of ventilation, PCV invites
0
u:: dyssynchrony when the patient breathes spontaneously.
The implications of slow rising-time settings was discussed
earlier. It is important to think about the other end of the
inflation period, however, when the a irway continues to be
FIGURE 10-6 'I)tpical tracings in an obstructed patient receiving pressurized to the nominal value until the set inspiratory
PCV. Note that the flow pattern resembles a sq uare waveform, time has elapsed . As with flow-controlled VCV, the patient
mimicking flow-controlled, volume-cycled ventilation. Intrinsic may attempt to cycle to expiration before the ventilator com-
PEEP is evident, and end-inspiratory alveolar pressures are much pletes its pressurization cycle. One could imagine, however,
lower than end-inspiratory airway pressures. that unlike the situation with flow-controlled ventilation,
patient effort never could force airway pressure higher than
the preset value during PCV. Unfortunately, this is not al-
ways true (see immediately below) because of hardware
limitations in some ventilators. Notwithstanding these lim-
itations, conflicts between the rhythms of the patient and
FIGURE 10-7 'I)tpical tracings observed in a restricted patient ventilator are manifested during PCV much more as cur-
receiving PCV. Note that inspiratory flow decelerates quickly, tailment of tidal volume rather than as buildup of excessive
achieving zero-flow conditions well before the end of inspiration system pressure.
(generating a small area A; compare with Fig. 10-6). There is no Another feature related to dyssynchrony is the fa ct that
intrinsic PEEP, and end-inspiratory alveolar pressures equilibrate
by fixing T1, as required with many commercial ventila-
with end-inspiratory airway pressures.
tors, one allows TJITTOT to vary with frequency whenever
the patient retains control of the cycling rhythm. As fre-
Pser Paw quency increases, TdTTOT lengthens, often provoking dy-
~
0
namic overinflation and generation of intrinsic PEEP. Even
I "' with ventilators in which the direct input is "duty cycle,"
E most of them calculate the inspiratory time based on the set
_..
0
l!! frequency rather than on measured frequency. Therefore, the

:;)
(/) resulting TJITTOT can be very different from tl1e originally
-
a..
(/)
Q)
0
set T1 I TTOT·
Time THE CONTROVERSY ON OPTIMAL

DISTRIBUTION OF VENTILATION
Several studies have attempted to demonstrate a defini-
tive advantage of PCV over VCV (squared flow pattern)
in terms of ventilation distribution, oxygenation, hemody-
namics, lung injury, and patient outcome. At first glance, re-
su Its seem inconclusive. By separating the studies according
to key ventilator parameters measured, however, some con-
sistency emerges. First, it is important to distinguish studies
that compare PCV-IRV from studies comparing PCV with
normal I:E ratio versus other modes. As discussed below, the
effects of IRV are con1plex and depend on intrinsic PEEP
generation. Under sucl1 conditions, the choice of the con- Very likely, consistent differences in ventilator-induced
troller (f/mv versus pressure) is just a minor issue inside a lung injury will never be linked to PCV as opposed
complex picture. Second, it is important to observe whether to VCV. Isolated short-term changes in the controller,
all the remaining variables (I:E ratio, tidal volume, intrinsic from flow to pressure control, probably can induce very
PEEP, total PEEP, frequency, and 0 2 fraction) were kept con- mild perturbations in the effective stress applied on the
stant during the comparison and whether they were consis- parenchyma. When compared with the potential for iatro-
tent. For example, studies displaying different plateau pres- genic damage associated with minor changes in plateau
sures or tidal volumes during PCV and VCV hardly can be pressures, total PEEP, or pleural pressures commonly found
considered to be perfectly matched if one is interested in the in clinical practice, the controller option may be insig-
effects on oxygenation50 or lung overdistension.51 nificant.
Keeping such boundaries in mind and first considering As discussed earlier, with adequate feedback it is usually
only the effects of a pure change in the controller from possible to obtain the same ventilator output with either a
squared flow control to squared pressure control (keeping ex- flow controller or a pressure controller under very specific and
actly the same I:E ratio, tidal volume, frequency, total PEEP, restrained conditions. Therefore, a flow-controlled breath
and plateau pressure), most studies have demonstrated with a decelerating-flow waveform can be generated eas-
that ily by modern ventilators, mimicking som e of the physi-
ologic effects of PCV55•68 Because it is practically impos-
sible, however, to match the degree of deceleration with
• The resulting decelerating flow during PCV decreases
peak airway pressures but increases ¢ 3 ...,.15,l6,l9,V,5l-55 the impedance characteristics of different patients (e.g., ob-
structed patients would require less accentuated decelera-
• Paco2 and Vo/VT decrease slightly (.6.Paco, "' 2-
tion), peak airway pressures frequently are higher during
4 mmHg), with modest clinical significance,15,27,52,53,55 in
such pressure-control " imitations." 68,69
accordance with the example shown in Fig. 10-5.
Considering the evidence presented, we again suggest
• Minor, if any, changes in dynamic (within the breath)
that the choice for PCV should be decided in terms of a
or static lung aeration (end-expiratory or end-inspiratory
bedside strategy and not based on subtle physiologic dif-
pause) are observed by computed tomography. 19·5l,54
ferences. Only in the context of a global strategy do such
• Minor changes are seen in Paa,,l 5·19·56 slightly favoring
PCV. 27,ss,s7,ss minor details make a difference. For instance, in a thin
patient who requires high PEEP to minimally oxygenate
• No hemodynamic impairment is seen on switching from
and who also has high dead space and requires plateau
VCV to PCV, provided that the increments in ¢aw are mod-
pressures greater than 40 cmH20 to avoid excessive hy-
erate (usually the case when using f:E < 1:1).
percapnia, a strategy prioritizing strict control of transpul-
• No differences are seen in barotrauma or patient
monary pressure makes sense. In this scenario, changing
outcome.58 Studies suggesting benefit of PCV had imbal-
from VCV to PCV might be appropriate because (1) plateau
anced randomization, 56 whereas a study suggesting ben-
pressures will not exceed the physician-adjusted Pset, (2)
efit of VCV was poorly controlled (including crossovers
considering the entire duration of mecl1anical ventilation,
and rescue procedures).59
the number of violations to the Pset target probably will
be lower, (3) any dec1·ease in dead space afforded by decel-
Taken together, the evidence suggests a clear physiologic erating flow may allow further reduction in tidal volumes
difference between the two modes of flow delivery, although and plateau pressures, (4) an eventual rise in respiratory rate
the clinical implications are modest. At the bedside, the most triggered by the patient will not be translated into increased
consistent effects are a reduction of peak inspiratory airway plateau pressures despite the possible generation of intrinsic
pressures, increase in ¢ aw, and small reduction in Paco2. PEEP, and (5) paralyzing agents and sedation thus may be
Because of the increment in ¢aw, Pao, tends to increase with reduced.
PCV, but this depends on PEEP and plateau pressure in the Such advantages, however, may be nullified quickly
particular case (see Fig. 10-9b). if spontaneous efforts are excessive. By decreasing pleu-
Some concerns are raised repeatedly about the potential ral pressures, diaphragmatic activity may cause transpul-
generation of greater shear forces at the beginning of in- monary pressures to be excessive despite rigid control of
spiration during decelerating-flow patterns. It is suggested maximum alveolar pressures (capped at Pset). Therefore,
that the squared flow waveform might distribute stress after evaluating the spontaneous tidal volume generated
more evenly throughout inspiration, theoretically decreas- by a patient (i.e., observing the extra tidal volume gen-
ing ventilator-induced lung injury. This hypothesis, how- erated during a synchronous effort), one should estimate
ever, appears groundless today. The isolated effects of high the extra driving pressure generated by muscle contraction
inspiratory flow rates on ventilator-induced lung injury62 -66 and reduce Pset accordingly. Not observing these princi-
have been investigated. Two studies suggested a deleteri- ples can make PCV more dangerous than VCV. In fact, dur-
ous effect,65•67 whereas other studies suggested a neutral or ing strong patient efforts, a flow controller avoids excessive
protective effect.63·&4,66 Because deleterious effects could be transpulmonary pressure more efficiently than a pressure
demonstrated only under extreme experimental conditions, controller simply because airway pressures more closely fol-
it is unlikely that the early peak flow achieved during PCV low changes in pleural pressure, being trans iently reduced
(rarely exceeding 1.5 liters/s because of resistance of the during patient effort (i.e., there is no extra " demand" flow
endotracheal tube) causes harm. to maintain airway pressure).
ASSISTED VERSUS CONTROLLED strategy is to use intermittent dosing, giving only as much
(TIME-TRIGGERED) VENTILATION as is needed to suppress excessive muscula r activity. The
periodic withdrawal of paralytics also enables sedation ad-
Most reasons to control ventilation can be classified as needs
equacy to be better determined. With either technique, to-
to regulate the ventilatory pattern, reduce agitation and
tal isolation of the muscle from neural impulses should be
the 0 2 cost of breathing, or prevent excursions of the in-
avoided. This is also true for sedative agents. Totally con-
jured chest wall. Perhaps the most common indication is to
trolled ventilation may lead to muscle atrophy with or with-
provide maximal ventilator support to a patient with such
out paralys is.80
marginal cardiorespiratory reserve that breathing efforts Recent evidence suggests that calm assisted ventilation,
compromise comfort, gas exchange, or cardiac function. Re-
with efforts jus t sufficient to trigger the ventilator, can avoid
ducing Oz consumption in a patient with critical coronary is-
excessive muscle wasting. 80 Because spontaneous efforts
chemia, for example, may prove lifesaving, especiany in the
also can improve lung aeration during pressure-controlled
setting of circulatory shock or acute pulmonary edema. Si-
breaths,83 probably secondary to increased diaphragmatic
lencing ventilatory effort also can improve arterial oxygena-
tone, it is tempting to conclude that some level of sponta-
tion and lung volume recruitment in agitated patients with
neous effort always should be promoted in patients receiv-
ARDS.7°- 72 Controlling minute volume to achieve hyper-
ing PCV. An anticipated drawback of such a s trategy is an
ventilation may be appropriate when reductions in cerebral
undesirable increase in I:E ratio when the patient respiratory
blood volume and intracranial pressure are urgent priori-
rate is mucl1 higher than the set respiratory rate. Another
ties, such as after closed-head injury. Controlling ventilation
problem is the generation of unpredictably high transpul-
greatly facilitates the monitoring of respiratory mecl1anics
monary pressures during strong and synchronous effort by
but in itself is seldom sufficient reason to undertake deep the patient. In both circumstances, however, deeper seda-
sedation or pharmacologic paralysis. tion or partial paralysis could control the situation easily.
Apart from reducing Oz consumption and preventing
By keeping the spontaneous respiratory ra te close to the set
spontaneous efforts from interfering with intended patterns
rate, one easily can avoid changes in the I:E ratio. Also, by
of conventional ventilation, establishing ventilatory control
keeping the exhaled tidal volume close to the tidal volume
facilitates the therapeutic application of "nonphysiologic"
generated during totally controlled breaths, one may ensure
breathing patterns. Interventions such as IRV,7,11 indepen-
that a patient's spontaneous effort does not cause significant
dent lung ventilation,73 continuous-flow ventilation,74 and
increments in inspiratory transpulmonary pressures.
permissive hypercapnia 1- 3•75 usually require silencing pa-
tient effort.
Sedation is virh.1ally always needed to establish venti-
latory control in the conscious patient \<vith moderate to Variants of PCV and Activation
high minute ventilation requiremen ts. Overriding the spon- of Exhalation Valve
taneous res piratory rate of the pa tient is always possible but
us ual! y results in intrinsic PEEP and wasted ventilation. Use As discussed earlier, the variants of traditional PCV8•27 in-
of sedation to improve comfort or inhibit excessive respira- clude assisted pressure-controlled ventilation,84 pressure-
tory drive is common practice. Muscle relaxants should be support ventilation/ 8, 29 a nd variants o f airway pressure-
used sparingly, however, because of their injurious poten- release ventila tion. 30, 31
tial. These agents must not be used in the conscious or lightly
sed ated patient.
ASSISTED PCV
Better unders tanding of the sequelae of prolonged
paralysis, especially when associated with sepsis and Assisted PCV is similar to pressure-support ventilation
systemic inflammation,76 high-dose corticosteroids, and (PSV) in that the breaths can be triggered by the patient
hyperglycemia,77,78 has forced physicians to minimize (physicians set the sensitivity and triggering mechanism).
dosage and duration of paralysis in ventilated patients. The difference is that cycling off is determined by time in-
Recent work suggests that severe diaphragmatic d ysfunc- stead of flow. Another obvious difference is tha t assisted
tion occurs after only 2-3 d ays of controlled mechanical PCV possesses the same backup mechanism available w ith
ventilation,79, 80 independent of tl1e use of paralyzing agents, traditional assisted flow-controlled breaths: Breaths can be
with loss of more than 40% of power generation. It is triggered by patient effort or by elapsed expiratory time,
likely that paralyzing agents potentialize or trigger such whichever occurs first.
effects81 by blocking a protective mechanism ag ainst atro- Compared with assisted VCV at equivalent tidal volumes,
phy (maintenance of minimal muscle activity). Independent assisted PCV decreases peak airway pressures. Although
of its precise mechanism, critical illness polyneuropathy, irrelevant during invasive ventilation, this characteristic
whicll frequently is associated withdiaphragmaticdysfunc- is relevant during noninvasive ventilation, minimiz ing
tion, increases the duration of mechanical ventilation and leaks tluough the mask85 or avoiding uncomfortably high
intensive-care stay significantly.82 pressures in the upper airways.86 When comparing the
Given such evidence, deep sedation with short-acting level of patient assistance during invasive ventilation, the
sedative dmgs is preferable to an y form of paralysis. Para- characteristic decelerating flow (on demn11d) provided by
ly tics should not be used to totally suppress muscle activity PCV seems to reduce workload more efficiently than most
but instead to weaken the force of patient effort. Another flow-controlled, volume-cycled breaths.84 The reduction in
CHAPTER 10 PRESSURE-CONTROLLEDANDINVERSE-RATIOVENTILATION 261
inspiratory muscle load is especially prominent during sure (cough) can be counterbalanced promptly by a sudden
moderate tidal volume (8 ml/kg) ventilation or when decrease in demand flow, attenuating the potential raise in
inspiratory flow rates are set at low levels during VCV airway pressures. Once the demand valve is already closed,
(<0.7liter / s). however-because alveolar pressures have equalized air-
The algorithm configured for assisted PCV a lso may carry way pressures- the ventilator is no longer able to control
some advantages over PSV. First, in patients with unstable airway pressures. Because most ventilators do not actively
respiratory d rive, the backup rate works as a safety and control the exhalation valve during inspiration (they just
stabilizing mecl1anism, avoiding central apneas and sleep close it tightly until the end of inspiratory time), any un-
fragmentation, especially in patients with cardiac failure or expected increment in airway pressures is counterbalanced
in those receiving heavy sedation. 87 Second, although PSV only by closure of the demand valve, which is alread y at its
is popular during noninvasive ventilation, serious concerns minimum position. The end result is a steep increment in
have been raised about potential dyssynchrony at end in- airway pressures, as in flow-coutro/led breaths.
spiration. During PSV, transition from inspiration to expi- Physicians have to keep this limitation ofPCV in mind be-
ration is triggered by flow (i.e., w hen inspiratory flow de- cause it be responsible for undesirable increments in airway
cays below a certain threshold). Hence t11e presence of mask pressures above Pset in mos t ventilators. This situation has
leaks or severe airway obstruction can render this mecha- been observed during continuous traclleal gas insufflatio n
nism inefficient- both conditions falsely create a relatively (TG1),89 during cough, and during strong efforts in assisted
high inspiratory flow a t end inspiration. Leaks simply mis- PCV breaths. In the latter circumstance, marked elevations
lead the inspiratory flow regulator of the ventilator, which of airway pressures can be found even in the absence of ac-
cannot detect that inspiratory flow is not being delivered to tive expiratory efforts. This is so because the patient effort
patient. Conversely, severe obstruction changes the shape of can increase effective driving pressures in early inspiration,
inspiratory flow (see Fig. 10-6), making it less decelerating increasing tidal volume a nd, consequently, tile elastic recoil
and pushing end-inspiratory flows closer to peak flow. Witl1 pressure at end inspiration (when diaphragmatic contrac-
both conditions, the default expiratory triggering threshold tion already has ceased). An inactive exhalation valve could
for PSV (usually 25% of peak inspiratory flow) may never not release this extra tidal volume before the beginning of
be reached, causing excessive prolongation of inspiratory next exhalation, thus increasing airway pressures.
time and patient overinflation.88 Under such conditions, To overcome such limitations, some m odem ventilators
pressure-controlled, time-cycled ventilation could be conve- have incorporated improved hardware in tlleir exhalation
nient: The intensivist needs only to adjust inspiratory time system that allows the simultaneous control of both valves
to match tl1e pa tient's spontaneous inspira tory time, usu- (the inspiratory demand-flow valve and the exhalation
ally 0.6-1.2 seconds.88 By changing from PSV to PCV, the valve) during the inspiratory phase of PCV. The end re-
intensivist necessarily decreases the freedom of ventilation sult is a smoother control of airway pressures d uring cough
pattern (restraining, for instance, the possibility of a sponta- or during continuous tracl1eal gas insuffla tion.90 Whenever
neous sigh and potentially increasing discomfort) but a lso available, such active control of the exhala tion valve en-
avoids dangerous prolongation of inspiratory time. 88 TI1is hances ventilator operation.
is a difficult balance that has to be judged at the bedside. The opening of the exhalation valve and its active con-
During assisted PCV, especially under high fl ow de- trol during inspiration are tile teclmological basis for incor-
mands, a fast "attack rate" to peak flow (at the initial poration of airway pressure-release ventilation (APRV) in
phase) of the breath is desirable and decreases the work microprocessed ventilators.
of breathing.37 In general, when changing from totally
controlled (time-triggered) PCV to assisted PCV, it is com- APRV AND ITS VARIANTS
mon to increase the speed of pressurization (i.e., to decrease APRV is a form of partial ventilatory support intended orig-
the rise time). inally to offload a portion of the work required to ventilate
during a primary crisis of oxygenation. 30•31 ln its original
conception, APRV elevated mea.n airway pressure by main-
ACflVATION OF EXHALATION VALVE DURING PCV: taining a moderately high level of CPAP, delivered through
a specially designed high-flow CPAP system linked to a re-
AIRWAY PRESSURE-RELEASE VENTILATION
lease valve operated by a time controller. TI1e system was
OPENING OF THE EXHALATION VALVE design to work independently of any commercial ventila-
In theory, any pressure-controlled breath should limit air- tor. Spontaneous breaths were planned to occur around this
way pressures to Pset independent of patient demand, pressure baseline. Periodically, the airway was depressur-
dyssynchrony, premature expiratory efforts, or cough. In ized rapidly during one of the patient's deflation cycles,
practice, however, hardware and software limitations of exhaus ting waste gas from the expiratory reserve before re-
mos t ventilators preclude such ideal configura tion. Usu- placing it witll fresh gas as CPAP rebuilt to the baseline
ally, ventilators can overcome an increase in inspiratory- level. Total tin1e for both phases of the release cycle gen-
flow demands efficiently during PCV (caused by leaks or erally was brief, ideally occupying only a single breath of
strong inspiratory efforts) by boosting flow through the de- the patient's rhy thm. The release pattern was repeated at
mand valve. Airway pressures are raised quickly back to a clinician-selected frequency. As predicated by the mathe-
Pset. Additionally, d uring the period in which the demand matics of pressure-preset ventilation,35 ventilator support
valve is still open, any sudden increment in alveolar pres- (achieved by the machine) was necessarily a function of
the number of release cycles, the magnitude of the pressure Regarding the synchronized trans ition, it is important
drop during release, the duration of the release period, and to remember that whenever commercial ventilators allow
the impedance to inflation and defla tion. Synchronization the patient to trigger the CPAP transition, usually during a
between the patient's own exhalation and airway depres- window that spans the last 25% of the preset low-pressure
surization also affects the effectiveness of ventilation. Inef- phase, the actual time intervals at high and low pressures
fectual inspiratory efforts during the deflation phase could (equivalent to I:E ratio) may vary according to the respira-
impair the released volume. Despite such concems, the orig- tory drive of the patient.91 Furthermore, even when some
inal system was not designed to be synchronous. synchronization with CPAP transitions is attempted, most
Subsequently, different names were used for similar sys- spontaneous breaths during APRVare still nonsynchronous
tems and arrangements, biphasic positive airway pressure and because of the long duration of both phases. Under such
intermitte11f mandatory pressure-release ventilation. (Bilevel air- conditions, the real advantage of synchronized systems is
way pressure, the commercial BiPAP, is different, being sim- questionable. From a workload perspective, APRV is an
ply a combination of pressure-supported ventilation and inefficient way of assisting the patient, imposing a higher
CPAP; this product is designed for noninvasive use.) The workload and greater discomfort as compared with equiv-
basic difference among these systems was the duration of alent levels of PSV. 92•93 The benefit, if any, of providing
each phase, although all the systems could be approximated some synchronization has to be balanced against the loss
to a periodic alternation between two CPAP levels accord- of control over T1/ TTOT· Synchronization only makes sense
ing to a time controller. A longer period at the lower CPAP if applied to most spontaneous efforts, meaning that APRV
level, enough to allow one or more spontaneous breaths, should be set at higher frequencies and shorter inspiratory
was characteristic ofbiphasic positive airway pressure ven- times, as with assisted PCV.
tilation. The specific transition from low to high CPAP lev- Whenever APRV is applied in its common configuration,
els also was different among these variants, whether it was with long time intervals set for both phases, the intermittent
synchronized or not. mechanical assistance (applied only when the spontaneous
Adjustment of all these features is now possible in mod- effort coincides with transition from low to high pressures)
ern ventilators, and this does not represent any important shares some similarities with intermittent mandatory ven-
conceptual modification. Accordingly, we believe that the tilation (IMV). As with synchronized IMV, the presence of
confusing profusion of names should be simplified under alternating levels of assistance probably impairs smooth ac-
the acronym, APRV. commodation of patient drive,94 potentially causing some
Provided that the ventilator works with an active exha- distress in patients when sedation is removed. Therefore,
lation valve during inspiration, APRV can be perfectly imi- it is still an open question as to whether APRV will prove
tated by PCV breaths with a single difference. During APRV, helpful during weaning or for patients with extreme weak-
if the expiratory time is set long enough to allow the patient ness, very high workloads, or conditions in which release
to complete one or more spontaneous breaths during the cycles are relatively inefficient in achieving ventilation (e.g.,
low-pressure phase, the spontaneous breath will be assisted severe airflow obstruction).
by an efficient CPAP system (equivalent to PSV set at zero For the sake of simplicity, whenever the patient gets too
driving pressure). Conversely, during the exhalation phase distressed during APRV and sedation is contraindicated, it
of PCV, the spontaneous effort cannot be well assisted be- is preferable to change to PSV or assisted PCV, assisting the
cause the bias flow systems responsible for PEEP mainte- patient in a more predictable way. The combination of PSV
nance are not designed to support strong efforts. The end with APRV introduces unnecessary complexity, making lit-
result is some drop in PEEP unless sensitivity is adjusted to tle sense in terms of physiologic benefit or as an attempt
allow triggered inspirations (i.e., assisted PCV). to minimize driving pressures and ventilator-induced lung
During the inspiratory phase, both systems perform injury.
identically, allowing spontaneous breaths to occur around By extending the higher CPAP level furth er, APRV gets
highly sustained airway pressures. When s pontaneous closer to inverse-ratio PCV. The shorter the time at low
breaths are abolished by paralysis, APRV is not different CPAP levels, the lower is the ventilator contribution to
fromPCV. minute ventilation,91 and the higher is the Pac0 2 . On the
It is important to remen1ber that spontaneous cycles and other hand, Pao, tends to increase because intrinsic PEEP
ventilator cycles are completely uncoupled in the most fre- increases. The full consequences of the duty-cycle settings
quent usage of APRV. This means that spontaneous breath- on oxygenation are discussed below.
ingcan occur at any phase of the ventilator cycle without any Comparison of APRV associated with spontaneous
syndtronization mechanism. Switching between the two breaths versus APRV without spontaneous efforts (identical
CPAP levels obeys a timed-cycled mechanism, and patient to conventional PCV), when both modes are set at equiva-
inspiratory work is mechanically supported only when it lent end-expiratory and end-inspiratory airway pressures,
coincides with the restoration of the high CPAP phase. showed that the former achieved better oxygenation95 and
In view of such inherent dyssynchrony, more sophis- increased cardiac output,95·% renal blood flow,97 1ung aera-
ticated APRV algorithms have been introduced in recent tion, and functional residual capacity.83 The hemodynamic
years, although without a clear rationale or clinical benefit. benefits may be related to lower intrathoracic pressures
These include triggered transitions between low and high generated during spontaneous efforts,98 and the benefits
CPAP levels and use of PSV during one or both phases on in lw1g function may be related to higher transpulmonary
top of the corresponding baseline pressures. pressures.83
It is important to stress that equivalent benefits also can A m ajor advantage of such modes is their use in patients
be achieved during simple CPAP (matched to the high- in whom some level of spontaneous ventilation is desirable
pressure phase of APRV), in fact, with better outcomes in (to promote recruitment or to avoid some problems related
terms of oxygenation.99 These findings demonstrate that to paralysis). Provided that the patient is not extremely agi-
most of the benefits attributed to APRV relate to the replace- tated, a volume-cycled target promotes a decrease in airway
ment of mechanically applied driving pressures by patient- pressure in proportion to the magnitude of patient effort.
genera ted driving pressures. Such feedback limits transpulmonary pressures and may
When considering the overall implications on hemody- be a convenient strategy to avoid ventilator-induced lung
namics, lung injury, and muscle function, APRV still poses injury. Also, such feedback usually provides a smooth tran-
a well-defined set of potential problems. Central vascular sition from ventilator-imposed driving pressures to patient-
congestion and exacerbated pulmonary edema are natu- generated driving pressures.
ral consequences of lower intrathoracic pressures and in-
creased cardiac workload. In patients with cardiac failure,
APRV should be used with caution. Conversely, to un-
load inspiratory muscles significantly, the high-pressure
Inverse-Ratio Ventilation
CPAP in APRV first must be raised to a considerable de-
In 1971, Reynolds suggested that the infant respiratory
gree, obscuring the major advantage of APRV, which is
distress syndrome could be addressed effectively by a
the use of lower airway pressures. Moreover, inspiratory
ventilator stra tegy that extended the inspiratory period
muscles will be disadvantaged by the resulting hyperin-
beyond 50% of total cycle time, that is, in verse-ratio
flation, promoting a sense of dyspnea that APRV is d e-
ventilation (IRV).6 Enthusiastic but largely anecdotal
signed to r elieve. In the context of such disadvantages,
APRV circuits must be designed carefully to function prop- reports or w1controlled studies followed in the adult
erly because imperfections in demand flow are not com- litera ture? - 10•12•13•108- 110 With this mode, TifTroT is pro-
lon ged beyond the traditiona l values of 0.2- 0.4, and
pensated by any mechanically assisted driving pressure, as
pressure control has been the modality of choice for its
during PSV. Finally, the intrinsic design of APRV circuits
implementation (PC-IRV). Mean inspiratory flow rate
raises an important concern about ventilator-induced lung
injury: APRV does not re present any significant advantage (the quotient of tidal volume and inspiratory time) is
in terms of damage related to cyclic lung collapse100 - 103 and much lower than conventionally prescribed. IRV has been
overdistension. 38•104- "07 Therefore, the same principles of used with duty cycles ranging from 0.5 (the lower linut
conventional mechanical ventilation apply: the need to re- consistent with its definition) to 0.8. Extension o f Tt!TTOT
was supposed to increase ¢Jaw and ¢'A without violating the
duce effective driving pressures, whatever their source of
desired upper limits for airway and alveolar pressures.
generation, and the need to avoid cyclic collapse and tidal
recruitment. The practical implications are that the releasing
pressures of APRV should be titrated carefully (as during
IMPLEMENTING INVERSE-RATIO VENTILATION
any PEEP titration), and similarly, driving pressures should
be estimated carefully and minimized (as during any at- IRV can be applied either with pressure-colltrolled, time-
tempt to reduce plateau pressures during controlled venti- cycled forms of ventilation (abbreviated in this chapter as
lation). PC-IRV) or with flow-col/trolled, volume-cycled ventilatio n
In conclusion, the important message provided by studies (abbreviated as VC-IRV). During VC-IRV, inspiratory time
of APRV is that the preservation of spontaneous efforts is can be extended by either a pplying a very low inspiratory
an important aspect of mechanical ventilation that sh ould flow rate or by prolonging the inspiratory pause. The latter
be employed p rudently. The simple use of assisted PCV achieves a higher ¢Jaw an d tends to result in improved C02
instead of fully controlled PCV can have a positive impact removal when compared w ith VC-IRV promoted by low
on hemodynamics, lung recruitment, and oxygena tion. inspiratory flow. 32 When slowing down inspiratory flow,
most investigators used flow-controlled decelerating wave-
forms in an attempt to obtain better C02 exchange or to
better mimic the flow profile of PC-IRV.'111
COMBINED MODES
Among all forms of IRV, PC-IRV generates the highest
In recent years, attempts have been made to combine the de- possible ¢Jaw for any combination of peak pressure, PEEP,
sirable features of both flow-controlled, volume-cycled and and T 1/TTOT· Also, for the same I:E ratio, PC-IRV usually
pressure-controlled, time-cycled ventilation. These modes, results in the least dead space.m
which include pressure-regulated volume-control and volume- Because most modem ventilators provide PCV, the clini-
assured pressure-support (VAPS)25 ventilation, guarantee any cal use of VC-IRV has declined substantially in recent years .
tidal volume compatible with the physician-set upper pres- When usin g VC-IRV, any slight variation in expiratory time
sure limit. The former combination mode accomplishes its (frequently found during assisted ventilation or during a
dual target over a few breaths, whereas VAPS guarantees its physician's attempt to increase C02 removal) can cause dra-
dual-target w ithin the same breath. Despite the very limited matic variations in air way pressures, imposing a great risk
research in this field, there is a firm physiologic rationale of barotrauma and overinflation. The latter occurs because
and a need to apply the benefits of pressure control while plateau pressures are not controlled directly during VCV
avoiding its problems. and instead are dete.r mined by the end-inspiratory lung
volume imposed by the ventilator. Whenever there is fur- To explain the different responses in P02 and hemo-
ther shortening of expiratory time, the additional induced d ynamics between the two comparative categories, one
residual volume (intrinsic PEEP) adds to the set or imposed could invoke differences in rPaw: According to traditional
tidal volume, causing large increments in plateau pressures. teaching,3 2•33 the higher rPaw applied during IRV (at equiv-
This is why VC-IRV always has been recommended in as- alent total PEEP) is expected to increase Pao, and impair
sociation with deep sedation and paralysis.11 When using venous return, decreasing cardiac output and arterial pres-
PC-TRVat the same settings, one expects some drop in tidal sure. There are many reasons to believe that this is more
volume and minute ventilation but with safe preser vation complex: Many s tudies in the second category (IRV at equiv-
of end-inspiratory lung volume and plateau pressures. In alent to tal PEEP) also showed deterioration ofPao, and in-
other words, during PC-IRV, hypercapnia might ensue, but creased shunt levels after IRV application 16· 117-119 despite
lung structure is better protected. considerable increments in <Paw· To reconcile all these find-
Minute ventilation is simply a linear function of respi- ings, a deeper understanding about the process of lung col-
ratory rate during VC-IRV, but it is unpredictable during lapse and reopening is necessary.
PC-IRV (see Fig. 10-3). Nevertheless, given the adverse ef-
fects of deep sedation and r a ralysis,7S-80,S2,m the risks of
EFFECTS OF T OTAL PEEP AND
high platea u pressures,38•10 and the tolerance by patients
of permissive hypercapnia,l - 3, 75 it is hard to justify the use
¢ aw ON OXYGENATION
of VC-IRV (instead of PC-IRV) at the present time. Three potential mechanisms have been invoked tradition-
ally to explain the increase in Pa02 with IRV: (1) higher mean
airway pressure, (2) intrinsic PEEP elicited by short expira-
tory time, and (3) improved intrapulmonary distribution of
LATER COMPARATIVE STUDIES O N IRV
inspiratory flow. As discussed earlier, the third mecha nism
A d ecade after the original report on IRVin infants, 6 several is virtually irrelevant in terms of oxygenation, producing
investigators demonstrated oxygena tion benefits in adult jus t a mild increase in C02 elimination.
patients with ARDs_7- tO,t2 Most of the early clinical s tud- Regarding tl1e effects of rPaw and intrinsic PEEP on oxy-
ies were not controlled a nd did not address potential dif- genation, we now recognize that neither variable is linearly
ferences in the methods of delivering IRV. No study has related to oxygena tion, especially in ARDS. Lung hysteresis
sp ecifically addressed the effects of IRV on patient outcome. makes the whole system very sensitive to the boundaries
In most s tudies, total PEEP and <Paw likely increased dltl'ing of pressures a pplied during the previous breathing cycles
PC-IRV application, although the incomplete information and, tl1erefore, very sensitive to end-expiratory and end-
provided by the authors precludes a definitive s tatement. inspiratory alveolar pressures developed previously. The
Over the last 15 years, more rigorous studies attempted to same instantaneous value of intrinsic PEEP or r/>aw can re-
elucidate the mecl1anism of improved gas exchange during sult in completely different blood gases depending on lu11g
IRV compared with con ventional ventilation. Such studies history or on the previous trajectory of alveolar pressures.
can be divided in two types: (1) studies in which IRV was de- This somewhat complex behavior is linked to the phe-
livered at equivalent levels of rPaw as during conventional nomenon of airspace closure and reopening with its inher-
ventilation and (2) studies in wh ich IRV was delivered at ent hysteresis. A combination of factors, including viscosity
equivalent levels of total PEEP. In this latter case., most in- of the lining layer inside the alveolar spaces, plastic defor-
vestigators had to apply higher <Paw during IRV, associated mation and folding of alveolar walls, surfactant adsorption,
with lower levels of external PEEP, to compensate for oc- and chaotic sequence of airway reopening (never equivalent
currence of intrins ic PEEP. to the sequence of closure), a lways cause some energy to be
Whenever IRV was delivered at equivalent levels of r/>aw, lost during recruihnent/inflation of lung units, and this can
the following pattern of physiologic effects was found con- never be recovered during the closure/ d eflation process.
sistently: (1) lower peak and plateau pressures for equiv- This phenomenon prevents the lung from behaving as a
alent tidal volumes,17·114•115 (2) lower external PEEP and perfect elastic system: The same airway pressure results in
total PEEP because of attempts to keep <Paw constant, 17,114 two different volume states depending on tl1e direction of
(3) a decrease or no change (but never improvement) in ar- the previous variation in airway pressures . A given airway
terial P~ and shunt Ievels,17,18 •114•115 (4) a slight decreases in pressure always results in lower lung volumes if delivered
dead space and Paco, ( t:. Vo/Vr ~ -15%; t:.Pc~ ~ - Smm through an inflation process from lower pressures than if
Hg),1 7,t8,tts and (5) minimal alteration in hemodynamics reached from a defl ation from higher pressures. Lung in-
with no d etectable cl1anges in splanclmic perfusion.18,11 4 flammation, surfactant deactivation, and massive airspace
Conversely, in most studies where IRV was applied collapse are frequent conditions favoring the development
at equivalent levels of total PEEP, similar reductions of such marked lung hysteresis.
in peak pressures, 14•15•52·n2,116- n 8 dead space, and Paco2 An interesting way of interpreting lung hysteresis is pro-
levels 1 4.'1~.s2• 112• 11 6,1'l 9 were observed, but with tluee major vided in Figs. 10-8 an d 10-9. One can regard hysteresis as
differences: (1) plateau pressures were kept constant but representing an asymmetry of lung s tatus according to the
<Paw increased for equi valent tidal volumes (a necessary con- direction of pressure variations in the system. Hysteresis
sequence of study d esign), 14- 16,5 2.112•116- 119 (2) arterial P~ creates a transitional state (defining a corresponding win-
and shunt sometimes in1proved, 118• 120 and (3) hemodynam- d ow of pressures) in the system that keeps " memory" of
ics were impaired significantly in most studies.14 - t6,112,116,117 the previous s tate; if many lungs units were closed in the
state B (always opened) hemodynamics (the hig her <l> aw mig ht impa ir hemody-
Threshold opening pressure I namics without further benefit in oxygenation). This situ-
:=~:=:=:=:l[l ation likely occurred in some studies.14•112. l l6
transitional state
• Sometimes, when alveolar pressures are confined ins ide
Threshold ·'· . prP~"' '0 I the transitional w indow (situation B1 ), any further len gth-
ening of TJITTOT might cause hemody namic impairment
state A (always collapsed)
and an eventual drop in Pa(h, as occurred in some clinical
studies.16•117,-119 The d rop in cardiac output should relate
to the increased </> 3 w , whereas the drop in Pa<h is easily un-
d er stood after adding some heterogeneity to the mod el.
During prolonged inspira tion, if m ost d amaged units re-
main closed, the longer compression of capillaries in the
preserved units likely would divert perfusion toward the
collapsed tmits, increasing shunt levels.
• Sometimes, when peak alveolar pressures exceed the tran-
sitional w indow but end-expiratory pressures are low
enough to allow recollapse (situation B2 ), oxygenation im-
FIGURE 10-8 Representation of lung hysteresis according to the proves with prolongation of inspiration, as in some other
pressures applied on the system. The system changes its status studiesl'l8 •120 In contrast with the preceding example, now
according to the direction of the transition. The transitional state higher inspirator~ pressures can trans iently recruit d am -
keeps some "memory'' of th e previous state, beh aving as in state A aged lung units,l 1 and the prolonged inspiration will fa-
wh en coming from lower pressures or behaving as in state B vor a longer contact between perfused capillaries and the
when coming from higher pressu.r es . Once inside the transitional opened units, d ecreasing average shunt levels.
state, the situation can be stable for a long period, provided that
pressures do not trespass the boundaries, that is, the threshold
Therefore, most reported effects of IRV can be understood
opening/closing pre.ssures.
according to the preceding rationale. The concept of hystere-
sis and transitional status also explains why the impact of
previous state, it is likely that the system will stay partially total PEEP is usually greater than the impact of <l>aw on oxy-
or totally d osed during pressure oscillations up to a certain gena tion. The observation of Stewart et al122 in 1981 r emains
limit (d efined by the transitional v.rindow of pressm es). And valid today: In Fig. 10-9, a major difference in oxygen atio n
the o pposite is also tme: A previously opened lung state will can be expected when comparing situations in A versus in
favor an open lung state during application of airway pres- B simply because of minor changes in total PEEP. In con-
sures brought down to below the opening pressures, pro- trast, <l>aw might be increased largely in situa tions B1 or B2
vided that they do not trespass closing pressures, that is, (either by increasing driving pressures or by prolonging in-
that they stay w ithin the transitional window of pressures. spiration). As long as total PEEP was not increased , Pa~
The range of such a transitional window of pressures could never reach the levels found in situation A. In a re-
d epends on the distribution of opening and dosing pres- cen t study using ultrafast P<h sensors, Baumgard11er et al121
sures of lung units . The higher the mean thresh old opening have d emonstra ted tha t P EEP and respiratory ra te (prob-
pressures a nd the low er the m ean threshold closing pres- ably via intrinsic PEEP modulation) are the most impor·
sures, the larger is this transitional ra ng e, and the more tant factors determining arterial P~ oscillations. Because
the whole system depends on lung history. T his transi- <l> aw during PC-IRV does not d epend on respiratory rate
tional window of pressures may exceed 40 em H 2 0 in severe (see above), frequency could increase considerably without
trauma patients. 46 any visible change in </>nw· Therefore, oxygenation could in-
Obviously, the actual situation is a lways complicated crease m arkedly a t fixed levels of <l>aw· Such relationships
by heterogeneities in the distribution of opening/ closing expla in, once more, the poor correlation between <l>aw and
pressures among lung wuts. The basic concept of tra nsi- oxygenation.
tional state, h owever, is applied eas ily to complex situa- In the preceding model, ventilation-perfusion imbalances
tions, assuming that there is an average behavior of lung have n ot been considered. Because a high Fr~ was used in
units roughly d efined by such threshold pressures. For in- most studies on lRV, however, oxygenation can be assumed
stance, by extending this simple model to clinical examples to reflect d1an ges in true shunt rather than ventila tion-
of pressure tracings (see Fig. 10-9), one can easily gr asp the perfusion ratios. Finally, because some minima l alveolar
reason for man y a pparent contradictions in the repor ts on perfusion during inspira tion commonly is maintained in
the physiologic effects of IRV. mos t alveolar units, tidal recmitrnent is an important factor,
Several possible scenarios can be envisioned: transiently increasing capillary P<h during inspiration.12'1
• Two conditions matched for </>aw (e.g., A1 versus B1 or

INTRINSIC PEEP VERSUS EXTRINSIC PEEP
A3 versus B2) could result in completely differ ent Pa02
values, as occurred in some studies.17, 1B As discussed earlier, intrinsic PEEP is common during IRV,
• Two conditions matched for total PEEP (e.g., A1 versus being responsible for effects on oxygenation. It is possi-
A3 ) could result in equivalent Pa~ values but different ble, however, to extend inspiratory time (use IRV) without
I:E = I : 3 I:E = 1.6 : l T:E = 3: 1

PEEPE= 14 PEEPE= 14 PEEPE = 8
(A) PEEPT = l4 PEEPy = 14 PEEPT = 14
Mean-PAw= 18 Mean-PAW= 23 Mean-PAW = 21
'""") ,
r71 '
r-,
~--~
I
:t.:::
u: ~'-
If
~--
7
I ii'i'l'f - : _
:;:;;
-
-I ' 7•
~
~ ~------------------------~~.
T:E = 1.6: I I:E = 1.6 : 1

PEEPE= lO PEEPE = 12
PEEPy= 10 PEEPr = 12
(B)
Mean-PAW= 18 (B,) Mean-PAW= 2 1
~ ..... ... . ,... ....

, ::::! 1}/~::
'
~\. :::::: - - -- airway pressure
I tl)
\
\ I
I
\ tl)
::- 1\
r:::
\ I \
@
\\~
\ I \
\
\
I
I '' Q.. 1::::: :, ~::::: - ------- alveolar pressure
', ~
I \.
-· '0 I Inmmmm. closed alveolar status
l
I
I
I
~
~
l
"t:
~----------------------~
Increasing I:E ratio may worsen Pa0 2 Increasing I:E ratio will increase Pa02
FIGURE 10-9 A. Low-shunt situations: three ventilator settings producing the same effect on Pao 1 • In each, alveolar press ures exceeded
the threshold opening press ure after the first breath attd were kep t above the thres hold closing pressures for the rest of cycles. Provi ded
that a major part of lung units is adequately represented by the boundaries of thresh old pressures indicated, the three settings will result
in very low and equivalent shunt levels. Under such conditions, increments in mean airway pressure (produced by increased l:E ratios, as
in examples A2 and ~)will only put hemodynamics at risk. B. High-shunt situations: Because eud-expiratory alveolar pressures are now
trespassing on the clos ing pressures, the situation changes dramaticaUy. The effect of increased mean airway pressure differs according to
end-inspiratonJ pressures developed. In 8 1, because Pset is b elow the threshold opening pressures, prolongation of inspiratory time can
only impair hemodynamics, but the lung stays closed and producing high shunt levels. Conversely, if Pset and alveolar pressures trespass
threshold opening pressures during inspiration( ~), Pa02 becomes dependent on mean airway pressure. The longer the inspirato.ry phase,
the longer is the open status, and the higher is the Pao 2 •
intrinsic PEEP genera tion. 119•120 A great controversy has sur- of the nondependent parenchyma, increasing ventilation in
rounded this subject. Some authors have argued tha t intrin- dependent and more perfused lung regions. Consequently,
sic PEEP brings some advantages to the clinical situation. selective improvement of ventilation at low V/ Q areas may
Others argue that intrinsic PEEP is a lways deleterious. eliminate C0 2 more efficiently.124 Another way of formu-
According to the first perspective, intrinsic PEEP pro- lating such rationale is to propose a stra tegy in which "the
moted by IRV can be considered a "selective" form of PEEP absolute time of the expiratory phase is so short that the
that preferentially ventilates parts of the lung with short stiffest parts of the lung have no time for collapse.'' 123
time constants, placing at rest parts with prolonged time Recent evidence does not support this view but demon-
consta nts.123 In a theoretical exercise, if respirato ry rate ap- strates the opposite. 20,45, 52• 119• t21>- 127 Because different time
proaches infinity, alveolar pressures would remain practi- constants in individual lung regions are crucial for a "selec-
cally constant in the slow units, equilibrating a t an interme- tive effect" of intrinsic PEEP, intrinsic PEEP may allow the
diate value between PEEP and plateau pressures. Because "selective collapse" of regions with short time constants,
healthier w1its tend to have slower time constants and to be especially the edematous regions. When comparing intrin-
located in nondependent regions in patients with ARDS, insic PEEP with matching levels of external PEEP in patients
trinsic PEEP is expected to produce less cyclic overextension with ARDS, Zavala et al52 demonstrated that shunt levels
CHAPTER 10 PRESSURE-CONTROLLEDANDINVERSE-RATIOVENTILATION 267
increased by 6% with intrinsic PEEP. There was some in- it is clear that fast units are at a disadvantage during intrin-
crease in the efficiency of CO:~ removal, but this could °
sic PEEP generation.2 Figure 10-10 provides further insight:
be ascribed to better inspiratory flow distribution during Regional ventilation becomes more heterogeneous with in-
IRV rather than to intrinsic PEEP. Animal experiments in trinsic PEEP, and ventilation is increased in nondependent
dogs 119 reproduced the same results. Clinical studies in ob- regions. A recent CT s tudy revealed more hyperinflation
structed patients came to similar conclusions, suggesting with intrinsic PEEP than with equivalent external PEEP. 19
that partial or complete substitution of intrinsic PEEP by In terms of C02 removal, it is impossible to draw any con-
external PEEP improves gas exchange'126·127 without any im- clusion because the concomitant use of IRV in most stud-
pairment in C02 removal. ies precludes any estimation of the isolated impact of in-
The original perspective of considering absolute time for trinsic PEEP. In clinical practice, one also has to consider
collaps~instead of end-expiratory pressures- also carries that a combination of IRV plus intrinsic PEEP usually re-
some problems. A recent computed tomographic (CT) insults in a higher <Paw than conventional I:E ratios plus exter-
vestigation has demonstrated that the time window to pre- nal PEEP and thus greater hemodynamic compromise.'112
vent end-expiratory lung collapse without external PEEP Another major drawback of the intrinsic PEEP approach is
is extremely short ( <0.6 second) and might not be feasi- its complexity: Much closer monitoring an d more frequent
ble during mechanical ventilation of many patients with adjustments of ventilator settings are required, even with a
ARDS. 45•125 To avoid unnecessary confusion, it is also impor- computerized protocol. 21
tant to prove that time per se, independent of local alveolar Therefore, external PEEP in association with conven-
pressure, is an important variable affecting lung collapse. tional I:E ratio is preferable. If C02 removal is a clinical
To our knowledge, this has never been demonstrated. problem, an increased frequency-even if associated w ith
After reviewing available evidence, we conclude that low tidal volumes- may solve the problem (see Fig. 10-3),
there is no rationale supporting the preferential use of in- especially when using high PEEP levels. By increasing
trinsic PEEP. In terms of oxygenation, it seems inferior to fw1ctionaJ residual capacity, external PEEP usually causes a
external PEEP, slightly increasing the risk of collapse in un- decrease in airway resistance and lung compliance, both fac-
stable units.128 In lung models with different tin1e constants, tors contributing to a very short tin1e constant. Under such
FIGURE 10-10 Regional ventilation distribution measured by electrical impedance tomography in an animal model (pig) of acute lung
injury. The functional images display the standard d eviation of each pixel along 1 minute of ventilation. Bright colors represent regions
with h igher stand ard deviation an d hence high er regional ventilation. Perfusi on perturb ations were subtracted by tempo ral filtering.
Although total PEEP in both conditions was th e same (checked by end-expiratory occlusion), the right image was ob tained wh en 6 cmH 2 0
intrinsic PEEP was added to 9 cmH2 0 external PEEP. Th e net result was a more heterogeneous ventilation, wi th preferential ventil ation of
the right lung and marked hypoventilation of the left lower lung (LL). External PEEP produced a more even p attern of regional ven tilation.
PCV 1: 2 ; PEEPT = 15 ; PEEPi = 0 PCV 3:1 ; PEEPT = 15; PEEPi = 6
c
50 c 50
..,
.0 40
0
+:: 40
- -
-Ill
0 =
c
CQ)
Q)>
30
-Ill
o;
- c
CQ) 30
<D>
e-
Q)«l 20 e-
Q)«l 20
a..C a..C
0
g> 10
·§,
Q)
10
.... ....
0 0
upper up~er lower lower upper upper lower lower
nght le right left nght left right left
conditions, respiratory rates up to 40-50 cycles per minute cient ventilator solutions can be implemented at the bed-
could increase minute ventilation considerably, improving side. At first, physicians were enthusiastic about IRV be-
C02 removal. cause internal PEEP and peak pressures were hidden.
Later, physicians realized that total PEEP and peak alveolar
OTHER EFFECTS OF IRV pressures were not that different, yet IRV necessarily im-
posed higher levels of ¢ow and greater hemodynamic conse-
For many years, it was believed that the benefits of quences for similar clinical benefits. Whereas concepts such
IRV were time-dependent and that short-term evalua- as ventilator-induced lung injury and permissive hypercap-
tions would underestimate them.'129 The importance of sus- nia have boosted the use of PCV, the better understanding
tained traction and interdependence to alveolar recnutment of the dynamics of alveolar collapse have dampened enthu-
was propounded. As discussed earlier, subsequent stud- siasm for and use of IRV.
ies demonstrated no unique effect of IRV that could not
be reproduced by conventional I:E ratio plus appropriate
PEEP levels. 14,l6, t20 Slow benefits over time have been ob-
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Care Med 1994; 149:15SQ-6. 133. Vicillard-Baron A, PrinS, Schmitt JM, et al. Pressure-volume
130. Leatherman JW. Mecllanical ventilation in obstructive lwlg dis- curves in acute nc'Spiratory distress syndrome: Cli.nlcal demon-
ease. Clin Chest Mcd 1996; 17:577- 90. stration of the influence of expiratory flow lirnltation on the
131. Vieillard-Baron A, Jardin F. The issue of dynamic hyperinfla- initial slope. AmJ Respir Crit Care Med 2002; 165:1107- 12.
E:hapter 11 cally ventila ted patients, in which a irway pressure is main-
tained above atmospheric pressure throughout the respi-
POSITIVE ratory cycle by pressurization of the ventilatory circuit."3
TI1is definition makes clear that PEEP is not a ventila-
END-EXPIRATORY tor mode itself. Rather, it is an adjunctive treatment that
can be associated w ith all forms of mechanical ventila-
PRESSURE tion, both controlled and assisted,4 - 10 or applied to spon-
taneous breathing throughout the entire respiratory cycle,
PAOLO NAVALESI so-called continuous positive airway pressure (CPAP). 11 - 14
SALVATORE MAURIZJO MAGGIORE When PEEP is applied to a pressure-preset mode, the pre-
set inspiratory pressure is commonly intended as a n addi-
tion to PEEP. That is, the actual pressure applied during
inspiration is the sum of inspiratory and expiratory pre-
set pressures. When the terms expiratory positive airway pres-
sure(EPAP) and inspiratory positive airway pressure (IPAP) are
OVERVIEW OF PERTINENT PATHOPHYSIOLOGY encountered-mainly, but not exclus ively, with a turbine-
PHYSIOLOGIC RATIONALE FOR PEEP driven (so-called bilevel) ventiJator-IPAP indicates the to-
Effect of PEEP on Gas Exchange tal pressure a pplied during inspiration; thus the actual as-
Effect of PEEP on Respiratory Mechanics sistance a bove positive expiratory pressure is the difference
Effect of PEEP on Ventilator-Induced Lung Injury between IPAP and EPAP.
Effects of PEEP on Cardiovascular System Many pathologic conditions benefit from the mainte-
Non Cardiorespiratory Effects of PEEP nance of a positive expiratory pressure, as shown by the
INTRINSIC POSITIVE END-EXPffiATORY PRESSURE pioneering work of Poulton and Oxon11 and Barach et al.15
(PEEPJ) TI1ey demonstra ted in the mid-1930s that application of
Measurement of PEEP, positive pressure to the airway can treat patients with pul-
Physiologic Effects of PEEP1 monary edema effectively. Yet the "Medical Subject Head-
Clinical Consequences of PEEP1 ing" (MeSH), surprisingly, refers to PEEP as "a method of
Impact of External PEEP on Dynamic Hyperinflation mechanical ventilation in which pressure is maintained to
and PEEP1 increase the volume of gas remaining in the lungs at the end
USE OF PEEP IN THE CLINICAL SETTING of expiration, thus reducing the shunting of blood through
ALI /ARDS the lungs and improving gas exchange." Thus MeSH con-
Postoperative State siders only one effect of PEEP, albeit the most widely recog-
COPD nized one.
Acute Severe Asthma Despite several drawbacks and complications, 16- 28
Cardiogenic Pulmonary Edema intensive-care unit (ICU) physicians view PEEP as one of
Prophylactic PEEP the most powerful treatments available for acute respira-
COMPLICATIONS AND CONTRAI NDICATIONS tory failure (ARF); in a recent intem ational survey of ICUs
CONCLUSION on three continents, PEEP was being used in more than 90%
AKNOWLEDGMENTS patients with acute respiratory distress syndrome (ARDS)
and in more than 60% of patients with an exacerbation of
chr onic obstructive pulmonary disease (COPD).29
In the first edition of this book, Rossi and Ranieri began
their chapter on positive end-expiratory pressure (PEEP) by
stating how difficult it was review the topic because of the
enormous number of publis hed studies.1 Although ancient Overview of Pertinent Pathophysiology
Romans used to say, "Excusatio 11011 petita accusatio manifesta
[he w ho excuses himself accuses himself]," we approach The application of intermittent positive pressure is intended
PEEP 12 years later claiming that today it is impossible to principally to replace, completely or in part, the func-
cite, not to mention have detailed knowledge of, the en- tion of the respiratory muscles and therefore corrects hy-
tire literature on PEEP.2 We performed a search through poxemia caused by alveolar hypoventilation. The reversal
Medline of articles available in English on PEEP published of hypoxemia caused by intrapulmonary shunt and ve-
between 1964 and 2004 and found 6788 publications. Publi- nous admixture, however, requires interventions that re-
cations on PEEP continue to increase (Fig. 11-1). When the cruit more aerated lung units for ventilation. In patients
search was confined to randomized, controlled trials, the with an acute reduction of the lung volume secondary to
increase is even more pronounced. An identical search for lung edem a and/or atelectasis, PEEP can improve arterial
furosemide yielded about the same total number of articles oxygenation 4,12 by increasing funtionaJ residual capacity
in the last 40 years. Articles on furosemide, however, have (FRC),30- 35 reducing venous admixture, 16..36- 39 shifting tidal
declined over the last 10 years (see Fig. 11 -1). volume (Vr ) to a more compliant portion of the pressure-
PEEP has been defined as "a techniq ue of respiratory volume (P-V) curve,40 preventing the loss of compliance
therapy, in either spontaneously breathing or mechani- during mechanical ventilation,8A 1 and reducing the work
273
8000 800
7000 700
VI 6000 600
~
c:
0 5000 500
-·
::1
C1S :::t:;tl
CJ 4000 400 c: 0
:a 3 -1
I» Ill
.0 3000 300 ::1
::I Cll
0.. 2000 200
1000
100
0 1/ 0
64/74 74/84 84/94 94/04 All FIGURE 11-1 Publications on PEEP an d
furos~mid~ from January 1964 to Dec~mb~r 2004,
Years
obtained from Medlin~ through th~ National
Library of M edicine h tnvw. ncbi.ulm.nill.govl
~ PEEP entrezlq~teryfcgi). Articles on PEEP and
~
Field: Title/Abstract, Limits: Publication Date, Eng lish, furos·em ide are indicated by the gray and white
0 Furosemide
bars, respectively (left axis). Triangles and circles
r epresent randomized, controlled trials (RCTs) on
-+- PEEP
..... Furosemide
Field: Title/Abst ract, Limits: Publication Date, Eng lis h,
Random ized Cont rolled Trial, Human
PEEP and furosemide, respectively (rigl1t axis).
The left side shows articles distributed by
decades; the righ t side presents the sum totals.
of breathing. 42 Figure 11-2A summarizes the rationale for

PEEP in patients with ARF secondary to acute lung volume
reduction. FIGURE 11-2 Respiratory effects of PEEP/CPAP in acute
respiratory failure secondary to (A) lung volume reduction caused
Although there is general consensus about the useful-
by edema and/or atelectasis and (B) air way obstruction and
ness of PEEP in treating patients with hypoxemic ARF sec-
expiratory flow limitation.
ondary to lung edema and/ or atelectasis, several aspects
are conh·oversial. For many years it has been recognized A. PEEP/CPAP
that the actions of PEEP on gas exchange and pulmonary
med1anics are variable and somewhat unpredictable,43-47
depending on the cause of ARF, which may be sus-
tained by different pathways48 - 50 and pathophysiologic
mechanisms. 35•43•48•50 As with any treatment, PEEP is not 't FRC t Compliance
free of side effects. 24 In patients with acute lung injury (ALI)
or ARDS, PEEP recruits nonaerated regions but also dis-
tends normally aerated regions, 51•52 contributing to baro- l
,J, Shunt ,J, Work of
trauma throuah an increase in end-inspiratory plateau
pressure. 1 6• 21 • 2~ 53• 54 High levels of PEEP also have been
breathing
shown to augment the physiologic dead space18..39.55 and

worsen gas exchange51 and tissue perfusion. 56- 58 Extra-
pulmonary side effects of PEEP include decreased cardiac
output,l 7•27A 3•59- 62 increased intracranial pressure,19•63 renal
dysfunction,20•64 and decreased splanchnic perfusion25•65 - 68
and oxygenation.56,57 B.
Benefits and detriments of PEEP have been weighted
variously by authors. Both the lowest PEEP resulting in I PEEP/CPAP I
acceptable oxygenation56•69 - 71 and a PEEP level exceed-
ing the lower inflection point on the P-V curve (to maxi-
mize lung recmitment9•72 and mininlize shear stress caused
j
by repeated opening and collapse of alveolar units dur-
ing inflation73 ) have been proposed as the best strategy for J, Inspiratory threshold load (PEEPi)
ALl/ ARDS. After many years, debate on optimal PEEP18
and the best method for detecting it still flourishes.
PEEP is beneficial for reasons other than lung-volume re-
cmitrnent. In patients with COPD and ARF, hypoxemia is re- ,J, Work of i Triggering
versed by relatively low concentrations of oxygen (02 ),74•75 breathing of the
ventilator
although reversal of the associated respiratory acidosis76
CHAPTER 11 POSITIVE END-EXPIRATORY PRESSURE 275
often requires mechanical ventilation. 77•78 In these pa- sleepiness, 106 improves cognitive performance'107 and left-
tients it was thought initially that PEEP produced little ventricular function,l 08 - 110 and decreases daytime blood
or no additional benefit on gas exchange.79 Following the pressure.106•108 Detailed discussion of this topic is beyond
fundamental work of Pepe and Marini,80 it was recog- the scope of this chapter.
nized tha t, particularly in presence of airflow obstruction, Likewise, we do not provide detailed discussion of pos-
the lungs may fail to deflate to FRC at end expiration. itive expiratory pressure (PEP), a physiotherapeutic tech-
Consequently, alveolar pressure remains positive to an nique aimed at clearance of secretions. PEP is based on
extent that depends on the volume of trapped air, a the theory that its applkation might improve collateral
phenomenon referred to as auto-PEEP or intrinsic PEEP ventilation111 and enhance mucus progression toward the
(PEEP1). ln this setting, application of external PEEP central airways.112, 113 Altl1ough using different devices and
may be beneficial. Benefit is evident during spontaneous methods of administration, several studies suggest that PEP
breathing: CPAP has been shown to reduce dyspnea13•81 might be equally or more effective than other physiothera-
and work of breathing.'13·8U 2 Benefit is also evident w ith peutic techniques for aiding secretion cleara nce and reduc-
any patient-triggered mode of ventilation5 •83- 85 : PEEP ing the risk of atelectasis and superinfection.114•115 A recent
enhances triggering function,5 •83 - 85 reduces the patient's systematic review, however, has weakened enthusiasm for
respiratory drive,84 reduces inspiratory muscle effort,5•83- 85 PEP, failing to document any advantage over other phys-
and improves patient-ventilator interaction.85•86 PEEP iotherapeutic techniques and raising doub ts as to its accep-
replaces the amount of pressure that must be generated by tance by patients. 11 6
the inspiratory muscles to offset PEEP1 (necessary to initiate
inspiratory flow or trigger the ventilator). 5•84 The principal
effects of PEEP in patients with COPD are summarized in
Fig. 11-2B.
Physiologic Rationale fo r PEEP
If PEEP exceeds PEEP1, it may further hyperinflate the
EFFECT OF PEEP ON GAS EXCHANGE
lungs,87 increase the risk of barotrauma,88 place the di-
aphragm at an additional mecl1anical disadvantage,28•89 and Ensuring adequate 0 2 uptake and carbon dioxide (C02 )
further impair hemodynamics. 27•87 To achieve the best re- elimination is the chief function of the respiratory system.
sults, PEEP should be titrated according to a precise evalu- This function is altered in ARF. Hypoxemia [i.e., an arte rial
ation of the level ofPEEP1.90 In passively ventilated patients, 0 2 tension (Pao,) lower than 60 mmHg at sea level] is the
this evaluation is straightforward: The expiratory valve hallma rk of this condition. Mechanical ventilation does not
of the ventilator is kept occluded at end expiration.91 cure the disease that causes ARF. Rather, it buys time and
Evaluation is not easy when the respiratory muscles are allows tl1e patient to recover. Although correction of gas-
active,5•92·93 during spontaneous breathing and patient- exchange abnormalities is not the ultimate goal of the global
triggered ventilator assistance, the situation where PEEP therapeutic strategy, nevertheless, safe arterial blood-gas
is of paramount importance. values are fundamental for sustaining vital function while
PEEP has substantial effects on hemodynamics. When waiting for more specific treatment to become effective. The
left-ventricular function is normal, an increase in intratho- role of PEEP in increasing Pao, in patients with pulmonary
racic pressure causes a fall in cardiac output largely sec- edema and ARF has long been recognized 117•118 and docu-
ondary to a decrease in venous return (i.e., preload). 17•94•95 mented extensively.18•39•119- 122
In patients with poor left-ventricula r function, when fill- The transfer of 0 2 from air to mitocl10ndria is termed
ing pressure and left-ventricula r diastolic volume are ele- the 0 2 cascade. 123 0 2 tension (Po,) of moist inspired air
vated, cardiac ou~u t is relatively insensitive to a decline at sea level is 149 mmHg. P0z drops to about 100 mmHg
in venous return. 6 In this condition the dominant effect in the alveoli, depending on the balance between ~ sup-
of an increase in intrathoracic pressure is to decrease left- ply and removal, which is determined by alveolar venti-
ventricular transmural pressure (i.e., afterload), which im- lation and pulmonary blood flow. Blood equilibrates with
proves left-ventricular performance.97 - 100 These effects (Fig. the alveolar 0 2 while passing through the pulmonary cap-
11-3C) are also observed with relatively moderate levels of illaries. Hence, ideally, P0 , in the pulmonary capillaries is
CPAP; the impact on afterload is likely to result primarily the same as in the alveolar gas, whereas Pao, is slightly
from a reduction in the inspiratory negative swings of in- lower (90-95 mmHg) because of some venous admixture
trathoracic pressure 101 consequent to improvement in respi- from the bronchial and coronary veins. When the arterial
ratory mechanics.101 Application of CPAP in patients with blood reaches the peripheral tissues, Pao 2 falls dramatically
severe cardiogenic pulmonary edema may accelerate the because of 0 2 transfer to the ti.<;sues. Any fall in Pao, there-
physiologic improvement and reduce the need for endotra- fore should be reflected by a decrease in tissue Po, . The
cheal intubation. 14•102- 104 aforementioned process moves in the opposite direction for
Several investigators have studied the use of CPAP in the C02. Because there is essentially no C02 in inspired air,
treatment of the obstructive sleep apnea syndrome. Sleep under normal conditions, Pco2 at the arterial and alveo-
apnea is characterized by a reduction or cessation of breath- lar levels is the same, whereas mixed venous Pco2 is about
ing secondary to periodic narrowing and/ or collapse of the 45-47 mrnHg. Tissue Pea, is quite variable depending on
upper airway. It can be reversed by CPAP, whicl1 keeps several factors, sucl1 as metabolic rate. Any impairment of
the pharynx patent by acting as a "pneumatic splint."105 lung function that hinders C02 removal will increase tissue
In symptomatic patients, CPAP reduces excessive daytime Pea, ·
A
Normal subject
Atmosphere
SAP• t 20mmHg so• = 12~ liVI"otfiJ

n P :.OmmHg lfP "' • I n"'IIHg
I.Vll' = 120 t~~~Y~Hg "-P.flllo n i>l~Wt~M LVtttt • l ~hlmHG.
/ / I 'A
""........,;:;-
B
Cardiogenic pulmon•y edema
Atmosphere AtmC>Sphere
SAP •!OmmHq SAl' - &0 ~M~ttv

IT'P = ~ tiVIlHg rTP • -Z4 ntmHg
t.VTI\'I =eommHg LVTf\1 • 1041l\11Ut9
mv
c
CPAP I n cardlogenlc pulmon•y edema
SAP • IG 1111'11H9
SAP • ~ mrttig
nP-·4 mrii~
nP: tmmHt
L"""'= M rrtmHg ,
I:.Vlll t- 72 lrll'll6ig
'"' :::.,'"""'C"'"7] o"'"'IIi

· '>< ~.
FIGURE 11-3 H eart-lung interactions during spontaneous breathing in a normal subject (A) and in a patient with cardiogenic pulmonary
edema resulting from low cardiac output in the absence (B) and presence (C) of CPAP. The effects of variations in intrathoracic pressure
(ITP) on left-ventricular systolic function are shown at end expiration (left pa11els) and end inspiration (rigflt pa11elsl. SAP, systolic arterial
(intraventricular) pressure; LVTM, left-ventricular transmural pressure (SAP- ITP). In a normal subject (A), tidal excursions in ITP have
little effect on left-ventricular systolic function. In a patien t with pulmonary edema (B), more negative swings in ITP are needed to achieve
the s ame tidal volume. As a res ult, LVTM (after load) is increased independently of systemic vascular resistance. The rise in ITP produced
by CPAP of 10 cmH2 0 (C) results in a s light reduction in LVTM during expiration. CPAP remarkably decreases LVTM during irlspiration
b y decreasing negative swings in ITP because of improved lung mechanics .
Physiologic gas exchange requires that (1) air reaches the Alterations in diaphragmatic position and mecha1tics dur-
alveoli, (2) the membrane interposed between alveoli and ing anesthesia also contribute to impaired gas exchange
capillaries is intact, and (3) the flow of blood through the by inducing ventilation abnormalities in the dependent
pulmonary capillaries is not altered. Ideally, the greatest ef- zones.170·171 This phenomenon has been elegantly studied
ficiency of pulmonary gas exchange occurs when regional in anesthetized rabbits by Heneghan et al,170 who compared
ventilation (VA) and perfusion (Q ) are completely matched; PEEP and phrenic nerve stimulation adjusted to produce the
i.e., 'h! Q = 1. Because of slight heterogeneities in VAIO same increase in lung volume. Phrenic stimulation caused a
ratio (secondary to gravity and a small shunt caused by greater caudal movement of the diaphragm, particularly in
venous blood flow draining from coronary and bronchial the dependent regions, and produced greater improvement
veins into systemic circulation), VA/Q normally approxi- in gas exchange than did PEEP.
mates 0.8. Gas exchange is also affected by extrapulmonary Conflicting da ta on the effect of PEEP have been obtained
factors, such as the inspired 0 2 fraction (Fro,), minute venti- in postoperative patients who had developed res piratory
lation (VE), cardiac output, and~ consumption (Vo,) (i.e., failure. In two studies, PEEP up to 10 cmH20did not modify
metabolic rate). In absence of an intrapulmonary shunt, any Pao, significantly during the early postoperative course of
increase in F10 , produces a rise in Pao,; the extent depends patients who underwent cardiac or vascular surgery.172• 173
Conversely, other investigators fow1d that PEEP, combined
on the degree of VA/Q mismatch .124- 126 VE depends on the
with bilevel positive airway pressure ventilation adminis-
activity of the respiratory centers, provided tha t respiratory
tered via a nasal mask, improved oxygenation in the vast
mechanics are normal. The effect of change in VE on gas ex- majority of patients who exhibited respiratory distress after
change depends on the degree of VAIQ inequality.125- 127 various types of surgery. 174-177 A recent randomized clini-
TI1e consequences of increase in VE are greater for C0 2 re- cal trial found that the use of noninvasive positive-pressure
moval than for 0 2 uptake because the dissociation curve ventilation with low PEEP (about 4 cmH20) increased Pao,,
for C02, as opposed to that for 02, is quite linear. 125 This reduced the need for intubation, a11d improved s urvival of
is true even in case of substantial VAI Q mismatch, which patients who developed ARF after lung resection. 178
explains the high Pace, dependency on VE. 128,129 Through In summary, use of PEEP to improve oxygenation dur-
effects on mixed venous 02 tension (Pvo, ), cardiac output ing and after anesthesia in norma] subjects has generated
and metabolic rate can influence Pao, . Pvo, may decrease as contradictory results probably because of the deleterious
a result of decreased cardiac output, increased 02 u~ke by effects of PEEP on hemodynamics and lung overdistension.
tissues, or reduced a rterial 0 2 content. A reduced Pva,, in PEEP, however, can be effective in improving gas excl1ange
tum, may decrease Pao 2 to an extent tha t depends on VAIQ in selected patients.
mismatch.124,125,130,131
EFFECT IN HYPOXEMIC RESPIRATORY FAILURE

Most forms of hypoxemic respiratory failure, such as car-
EFFECT IN ANESTHETIZED SUBJECTS diogenic pulmonary edema, ALI/ ARDS, and unilateral
Arterial oxygenation often is impaired during anesthe- pneumonia, are characterized by a decrease in lung vol-
sia132·133 as a result of the intrapulmonary shunt134- 138 ume caused by atelectasis, interstitial and alveolar edema,
caused by atelectasis, predominantly in the dependent and small airways closure. The pivotal mechanism for
zones.133;l39- l4 5 Areas of collapsed pa renchyma occur in hypoxemia in these conditions is intrapulmonary shunt,
90% of all intubated anesthetized subjects during both spon- as demonstrated by the small increase in Pao, when
taneous breathing and muscle paralysis. 138·146- l48 Other pure 02 is administered 179 and, to a lesser extent, VAIQ
mechanisms, such as regional distribution of ventilation,'149 mismatch.180·181 Moreover, the high Fro, frequently used
airway dosure,1so-160 and fharmacologic inhibition of hy- in these patients may decrease lung volume by promoting
poxic vasoconstriction 161 - 1 4 also may contribute. Applica- alveolar denitrogenation and reabsorption atelectasis.179·182
tion of PEEP during anesthesia can prevent or reverse clos- In ALI/ ARDS, the altered blood flow distribution re-
ing of peripheral airways} 53 decrease atelectasis,138·148,165 sulting from widespread involvement of the pulmonary
and improve r egional VA/0. ratios and oxygenation,l 66,167 vasculature183 and impaired hypoxic vasoconstriction con-
although s hunt may be improved only in part. 138 In nor· tributes to gas-exchange worsening. 182
mal anesthetized dogs, however, Dueck et al 168 found that PEEP has long been recognized as an effective means
PEEP of 10 cmH20 or greater produced a reduction in Pao, of increasing lung volume and improving gas exchange. 4
and increases in dead -space ventila tion and Paco,. This was In cardiogenic pulmonary edema, CPAP (alone or in
caused mainly by a drop in cardiac output associated w ith association witl't an inspira tory assistance) improves gas
an increase in alveolar ventilation of both high VAIQ and exchange14·102•184 - 195 by increasing aerated lung volume'196
unperfused lung regions, suggesting overdistension of non- and improving cardiac o utput102· 184· 189 and VAIQ
dependent lung regions. Similarly, Pelos i et al169 showed distribution. 196,197 A d ecrease in extravascular lung water is
that PEEP values up to 10 cml-hO decreased, although not anotl1er possible m echanism whereby PEEP reduces intra-
significantly, Pao, during general anesthesia in normal sub- pulmonary shunt. 198 Yet PEEP does not d ecrease, and some-
jects. In contrast, Pao, increased in obese patients; tlus in- times increases, extravascular lung water when microvas-
crease was correlated with recruitment of atelectatic lung cular hydrostatic pressure is high. 199 Malo et al197 clarified
regions. this issue. They showed that PEEP of 13 cml-hO decreased
shunt and alveolar flooding without modifying extravascu- bilizing airways, PEEP also affects the regional distribution
lar lung water; indeed, perivascular cuff edema increased.197 of tidal ventilation. 210·238•270·271 When the predominant ef-
These findings indicate that PEEP redistributes the excess fect of PEEP is recruitment, alveolar ventilation is expected
alveolar water into the compliant perivascular space, thus to become more homogeneous, particularly in the depen-
reinflating previously flooded and collapsed airspaces, dent zones. Although an increase in lung volume is the
without decreasing the overall amount of lung edema. 200 main mechanism for PEEP-induced changes in oxygena-
Unilateral pneumonia and ALI/ ARDS are characterized tion, a small decrease in cardiac output also reduces in-
by severe impairment of gas exchange because of increased trapulmonary shunt and improves Pa~. 60 Finally, different
intrapulmonary shunt,l 80·182 resulting mainly from flooded etiologies and pathophysiologic mechanisms of ALI/ ARDS
and/or collapsed alveoli.201- 204 This observation is corrob- influence the response to PEEP,50•237 although unders tand-
orated by the correlation between the extent of lung den- ing is far from being conclusive.272
sities found mainly in the dependent regions on a com- Improved efficiency of alveolar ventilation and an ex-
puted tomo§!'af,hic (CT) scan and deterioration in arterial pected decrease in alveolar dead space should produce a
blood gases. ; r 1 In fact, the edema increases the total mass reduction in Pac 0 1 . Several authors, however, have failed to
of the lung (up to more than twice that of normal lungs); find any significant relationship between Pa co~ and PEEP.
consequently, the dependent zones collapse progressively The lack of response probably arises because PEEP both fa-
under the weight of the superimposed lung (compres- vors lung recruitment, which theoretically reduces Paco,,
sion atelectasis), and aerated lw1g decreases ("baby lung" and promotes pulmonary overdistension, which theoreti-
concept). 205- 207 cally increases Pac~ .210·273
Atelectasis in the lower lobes and in dependent lung re- The benefit of PEEP on gas exchange also might be ex-
gions may be caused by other mechanisms, such as expected in unilateral pneumonia and localized lung injuries.
ternal compression by the heart208•209 and the abdomi- In these conditions, however, high PEEP is more likely to
nal compartment.141 ·210·211 The severity of intrapulmonary produce overdistension of normally aerated regions be-
shunt also may be affected by surfactant abnormalities, 212 cause of the coexistence of areas with normal, low, and
increased airway resistance,2'13- 226 hyaline membranes, very low compliance.210·238 The net effect of PEEP on gas
and inflammatory proteins and cells accumulating within exchange depends on the balance between overdistension
the alveoli. Interstitial edema and the deposition of of already aerated alveolar units and recruitment of col-
cells and connective tissue in the interalveolar septa lapsed (nonaerated) alveoli and is also influenced by the
may contribute further to gas-excl1ange impairment in level of PEEP. 210·274 In patients with unilateral lung dis-
ALI/ ARDS. The amount of nonaerated lung volume also ease, PEEP may be d etrimental whenever it hyperinflates
may be increased by the combined effects of reabsorp- the normal lung, thus directing blood flow to the diseased
tion atelectasis 137·180•182. 227 and ventilation occurring at lung and increasing intrapulmonary shunt. 275- 279 To limit
low lung volumes. 228·229 Hypoxic pulmonary vasocon- this risk, unilateral delivery of PEEP to the injured lung has
striction appears greatly impaired in most patients with been proposed280; the technical complexity of this approach
ALI/ ARDS. 182•230 ln some patients with diffuse lung injury, greatly limits its feasibility in the clinical practice.
however, hypoxic pulmonary vasoconstriction is partially In summary, PEEP improves gas exchange in hypoxemic
preserved, explaining a lack of hypoxemia d espite diffuse ARF mainly through recruitment of previously nonaerated
loss of aeration. Conversely, hypoxic pulmonary vasocon- lung areas and the homogenization of regional distribution
striction is constantly impaired in some patients with lo- of tidal ventilation. PEEP remains the cornerstone of ven-
calized lung injury, explainin§o severe hypoxemia despite tilator treatment of most forms of hypoxemic ARF. Debate
well-preserved lung aeration.2 continues about the optimal level of PEEP (see below), not
Use of PEEP to correct gas-exchange impairment in about its usefulness.
ALI/ ARDS was proposed initially by Asbaugh et a1.4 It re-
mains the cornerstone of ventilator management of these
EFFECT IN OBSTRUCTIVE LUNG DISEASE
patients. Extensive literature supports the use of PEEP for
Impaired gas exchange in obstructive lung diseases is
improving oxygenation in hypoxemic respiratory failure
alone or in combination with various ventilator modes dur" caused by complex disturbances of regional VAIQ re-
ing both invasive8,18,J4, 71 , 119• 121,223•231 - 247 and noninvasive lationships associated with alveolar hypoventilation; dif-
ventilation.10·178·188·248- 260 Several mechanisms may explain fusion impairment is not a major factor. 281 During an
the effect of PEEP on gas exchange. PEEP promotes alveolar acute exacerbation of COPD, high VAIQ areas p redom-
recruitment and increases aerated lung volume, thereby de- inate in patients who mostly have the emphysematous
creasing intrapulmonary shunt.31·36•245·261 ·262 PEEP-induced variant with loss of blood flow consequent to alveolar
recruitment of aerated lung volume is strongly corre- wall destruction. 281- 283 Conversely, low VAIQ regions are
lated with arterial oxygenation34·71.119• 121 ·236, 263- 26s (Table seen mostly in patients with a predominant obstructive
11 -1). A redistribution of alveolar edema to the intersti- component.281- 283 In general, application of PEEP does not
tial spaces also may explain the benefit of PEEP on gas affect gas exchange.5•79-87,284·285 Nevertheless, Rossi et aJ286
exchange.197 Following the pioneering work of Webb and reported that low PEEP (50% of PEEP1) induced a moderate
lierney, 266 PEEP has been shown to decrease pulmonary increase in Pa~ and a slight decrease in Paco~ secondary
edema267- 269 partly because of a concomitant reduction in to improved VAIQ distribution without alteration in res-
cardiac output. 268 By recruiting nonaerated alveoli and sta- piratory mechanics or hemodynamics. 286 Further increases
TABLE ll·l Studies Assessing the Effect of PEEP on Lung Volumes and Other Physiologic Variables
PEEP FRC AEELV Vrec Vrec/ AEELV Voverdist APaO:!

Reference Technique emH 20 ml ml ml % mJ mmHg
Ranieri '1991 (71) P~V curve 15 720 230 0.32 50
Ranieri 1994 (2.19) P-V curve 15 690 248 0.36
Ranieri 1995 (240) P-V curve 10 1274 756 0.59 55
Jonson 1999 (40) P-V curve 10 205
Richard 2001 (242) P-V curve 11 175
Maggiore 2001 (236) P·V curve 15 764 304 0.40 79"
Mergoni 2001 (375) P-Vcurve 15 379 29
Koutsoukou 2002 (223) P-V curve 15 660 457 0.69 57
Richord 2()(l3 (241) P-Vcurve 14 384 20'"
Maggi<>re 2003 (360) P-V curve 15 650 235 0.36
N Vieillard·Boron 2003 076) p.. y rurve 12 358 69 0.19 44
'-J Yalta 1993 (246) 14
1.0 Static compliance 500 126 0.25
C.attinoni 1998 (50) Static compliance 15 576 721 131 0.18
C helucci 2000 (374) Static compliance 13 446 102 0.23
Vieira 1998 (52) CT scan 13 320 238 117
Vieira 1999 1274) CT scan 16 332 13 113
Puybasset 2000 (238) CT scan 10 1621 659 187 0.28 41 45
Malbouisson 200'1 (34) CT scan 'IS 155-3 820 499 0.61 24 99
Nicszkowska 2004 (371) CT sam 15 1105 1115 369 0.33 63 80
MEAN 14 1214 721 290 0.37 76 66

so 2 483 249 165 0.16 93 32
AII&R.EVJAT10NS. FRC: functionaJ residual c<~p...d ty. AEELV: change In end~pirntory IUI\g volumto, Vrec: recruited volume-. Vove-rdist volume of lung overdiStel\.Sion.. AP;I(J2: ch<tnge in arterial oxyge-n tension
comp3red to I'EEJ> 0 c.rnl·hO, P-V: pressure-volume, Cf: computOO tomogr-Jphy, SO: standard deviat-i(ln,
• OOillJMred to f'EP.J) 5 cmH20.
,... compared to PEEP 10 cmH20.
in PEEP (up to 100% of PEEP1) did not produce fur ther im- properties of the respiratory system satisfactorily in this
provement in gas exchange. 286 In other small studies, low range.
to moderate PEEP (5-9 cmH2 0) produced sinlilar improve- The dynamic behavior of the respiratory system de-
ments in Paco, and Pa 0 2 .287 - 289 Other authors, however, pends on its resistive properties. Modeling the airways as
reported little or no change in arterial oxygenation with a rigid tuJ;>e, the resistance (R) is described by the equation
PEEp5·81 •87, 285 unless high levels wer e appHed 87•285; Paco, R = t.P / V, where Pis the pressure d ifference between the
did not change with up to 15 cmH20 of PEEP.5•79•81•87, 285 extremities of the tube, and V is airflow. Poiseuille's law
PEEP may have some benefit on gas exchange. Unless states that R is proportional to fluid viscosity (IJ) and to
hypoxemia is caused by a large intrapulmonary shunt, the the length (l) of the tube and inversely related to tube ra-
benefit is small and of little clinical importance, and PEEP dius (r) raised to the fourth power (R = 81') 1/rrr"). Accord-
may have negative hemodynamic effects that worsen oxy- ingly, even small variations in airway caliber cause large
gen delivery. 79•87•285 The balance beh-veen positive and neg- changes in airway resistance. Because the intrapulmonary
ative effects depends to some extent on the level of PEEP airways are tethered to the surrounding parenchyma, they
applied; neverilieless, the chief reason for using PEEP in are pulled and widened by lung expansion and narrowed
COPD is not to improve gas exchange. by reduced lung volumes. Therefore, airway (ohmic) re-
sistance decreases with increasing lung volume, and vice
versa. A second resistive component exists, defined as tis-
EFFECT OF PEEP ON RESPIRATORY MECHANICS sue or additional resistance, that is consequent to the vis-
RESPIRATORY MECHANICS IN HEALTHY SUBJECTS coelastic pressure dissipation (stress relaxation) within the
The static behavior of the respiratory system is described lung and chest-wall tissues. 299 - 304 Gas redistribution (pen-
by the P-V curve.290 - 292 This curve provides an accept- delluft) among lung units with different time constants adds
able description of ilie elastic properties of the respiratory to this pressure loss and is included in the calculation of
system.293 In healthy subjects, the P-V curve, from res idual the additional resistance. Additional resistance is propor-
volume (RV) to total lung capacity (TLC), has a sigmoidal tional to increase in lung volume and inversely related to
shape. 292 Above FRC, however, the curve is linear. Thus the flow rate303•304; it is also characterized by a strong frequency
tangential s lope of the curve (i.e., the linear or chor d com- dependency.305
pliance, reflecting the elasticity of the respiratory system) is During constant-flow controlled ventilation, the elas-
consta11t over the range of tidal ventilation. FRC is ilie vol- tic and resistive properties of the respiratory system can
ume of gas in ilie lungs at the end of a passive expiration. It be assessed using the occlusion technique, which con-
corresponds to the point of equilibrium between lung and sists of occluding the airway at end inspiration for 3-5
chest-wall elastic recoiL seconds.299,300•303•304, 306- 308 As soon as flow is interrupted,
The shape of the P-V curve reveals two important fea- there is a rapid drop in airway pressure from the peak
tures: stiffening of the lungs at high lung volumes and (Ppeak) to a lower value (Pl), followed by a gradual de-
closure of periphera l airways and lung units at low lung cay to an apparent plateau (Pplat) (Fig. 11-4). Ohmic (flow-
volumes.294 At volumes above 75-80% of TLC, the slope of dependent) resistance (Rmax) is calculated as the initial
the P-V curve varies, wiili a sharp decrease in compliance, drop in airway pr"(:'ssure (Ppeak - Pl) divided by inspi-
indicating that U1e lungs are close to their maximum s tretch ratory flow. The slower pressure change (Pl - Pplat) di-
limit, whereas the chest wall normally is not stiffer. Further vided by the inspiratory flow preceding the occlusion yields
increases in pressure beyond this point, called the upper in- the additional tissue resistance (t.R). The sum of airflow
flectioll poi11t (UIP), have progressively less effect on lung vol- and tissue resistances provides the total respiratory resis-
ume. When lung volume falls below FRC and approaches tance [RroT = (Ppeak- Pplat)/V]. By occluding the airway
RV, the smallest airways tend to collapse under the influence at end-expiration, it is possible to determine the total PEEP
of surface tension of alveolar lining fluid. 295 - 298 During the (PEEPror), whicl1 is U1e sum of the externally applied PEEP
subsequent inflation, iliese structures remain closed until a and PEEP1 (Fig. 11-5). The difference between Pplat and
much higher pressure is applied. From this point on, com- PEEP10 1 is the recoil pressure. It is ilien possible to com-
pliance rapidly increases during inflation as the closed lung pute the static compliance (Cst) of the respiratory system
units progressively pop open. This action produces a knee according to U1eequation Cst = VT/(Pplat- PEEProT). The
on ilie P-V curve termed the lower inflection point (LIP). The failure to take into account PEEP1 may result in a substantial
difference between dosing and opening pressure is caused underestimation of Cst, especially when low or no PEEP is
by hysteresis in surface tension, which is greater during in- used.9t,309
flation ilian during deflation, and by surface tension and The mechanical properties of the respiratory system can
curvature, which are boili increased when the airspaces are be partitioned into lung and chest-wall components by mea-
collapsed.298 suring esophageal roressure, a s urrogate for intrathoracic
Static (effective) compliance is the ratio of volume change (pleural) pressure.3 o- 312 When the respiratory muscles are
over pressure change. Graphically, it describes the slope of a not active, esophageal pressure corresponds to intrathoracic
line drawn between two points corresponding to end inspi- (chest-wall) pressure; transpulmonary pressure then can
ration and end expiration. It is a simplified measure of the be calculated by subtracting esophageal pressure from air-
elasticity of ilie respiratory system. In contrast to patients way pressure. It is therefore possible to calculate resistance
with either ARDS or COPD,238• 294 normal subjects have a and compliance of U1e chest wall and the lung by replac-
linear P-V relationship in the range of VT at FRC; thus a ing airway pressure in the aforementioned equations wiili
single value of static compliance may describe the elastic esophageal and transpulmonary pressure, respectively.
1
~ ~
'
Flow I"
(Us)
- I
I
r-
I
-1
35 FIGURE 11-4 End-inspiratory occlusion

during constant-flow controlled ventilation .
Airway Pressure As soon as the airway is occluded, flow
I suddenly falls to zero, and airway pressure
(c:mH 2 0 ) I(
·----'
5 sec: drops from a peak (Pp eak) to a lower value
(Pl) and then declines slowly to an apparent
0 plateau (Pplat).
EFFECTS OF PEEP IN ANESTHETIZED SUBJECTS piratory system and lung sta tic compliance; the compli-
Anesthetized healthy subjects may have decreased aer- ance, however, decreased , ...,hen PEEP was raised above 20
ated lung volume consequent to the decline in FRC associ- cmH20, indicating lung overdistension. Dechman et al 321
ated with the supine posture141•313-318 and the potential for also observed an increase in ltmg compliance at PEEP of
airway closure and atelectasis.133;138- 145,147,148,229,315,319- 322 10 cmi·hO in the patients undergoing dosed-chest surgery
Both anesthesia and paralysis affect the mechanical char- but not in patients undergoing open-chest surgery, who ex-
acteristics of the respiratory system,m ·320- 324 which also hibited a progressive decrease in d ynamic lung compliance.
can be impaired by abdominal and thoracic surgical The mechanical characteristics of the ches t wall may influ-
procedures.325- 329 It is thought that anesthesia primarily al- ence the effect of PEEP in subjects with normal lungs during
ters the elastic properties of the chest wall, causing a fall anesthesia.320 In patients undergoing abdominal surgery,
in FRC, whereas the changes in lung compliance may result Pelosi et al169 reported that 10 cmH20 of PEEP did not im-
from breathing at low lung volumes. 320,330•331 Application of prove r espiratory function in normal s ubjects, although it
PEEP in anesthetized and paralyzed subjects produces an increased EELV and lung and chest-wall compliance in mor-
increase in end-expiratory lung volume (EELV)I69,323,332-336 bidly obese patients.
and upward displacement of respiratory system, lung, and In general, PEEP decreases airway resist-
chest-wall P-V relationships 169·322•333•335·336 (Fig. 11-6A). Sev- ance.169·32'1.335-337,339 The decrease in airway resis ta nce
eral authors, however, reported little or no increase in static is related mainly to an increase in lung volume, 335 although
respira tory compliance with PEEP.169, 322-332,333,335,337,338 In other mechanisms, s uch as a PEEP-induced modification
some studies, PEEP increased both chest-wall and lung of basal vagal tone,339 also may play a role.
compliance.335 In other s tudies, chest-wall compliance in-
creased and lung compliance decreased,337 or no effect was EFFECT OF PEEP ON LUNG VOLUME IN ALI/ ARDS
observed .169,332 Since the first description by Asbaugh et aV ARDS has
The effect of PEEP on the elastic properties of the respira- been recognized as a condition characterized by reduc-
tory system varies with the amount of PEEP a pplied 336 and tion in aerated lung and respiratory system mechanical
preexisting derangement in respiratory mechanics. Com- derangements.119•122•340 - 344 In AU/ ARDS, massive lung
pared with zero end-expiratory pressure (ZEEP), D'Angelo edema, atelectasis, and tissue consolidation cause a marked
et al336 found that PEEP of 9 cmH 20 increased both res- decrease in FRC.'I19,122 This fall in normally ventilated lung
1 - I
I
FIGURE 11·5 End-expiratory occlusion. Airway p ressure
rises followi ng an en d-expiratory ocd usion and reaches a
I ..
plateau, which corres ponds to total PEEP (PEEPToT>· Auto-
Flow
-- I '
or intrinsic PEEP (PEEP 1) is the difference between
(U s) ~
. L
• l ;!---' ,....-
PEEPTOT and the externally applied preset PEEP (PEEPE).
I
I PEEP 1 measured by an end-expiratory occlusion is termed
I static PEEP, .
-1 -
40
PEEPro ·
Airway Pressure
(c:mH 2 0 )
PEEPe
• PEEP 0 crr H1:J
A B c 0 PEEP 5 CrT H1 :J
0 PEEP 10 o.Jnt- 20
~500
e PEEP 15 crnt-p
::uw 0 PEEP 20 cmt-,0
:<500
-;::
..s ;nm
"'~ 1500
0
>
1000
500 :' t£=Lv

-
vr 0~--~--------------------~ ~~~--------~----~----~--~~ ~~---------------------------
·o 20 3D 40 50 o 10 20 3J 40 5J o 10 ~o :c '10 so
PrGssurE< (c11H20I Pr0ssur~ (cmt-20) Prassure (•;rn-ll~)
FIGURE 11-6 Pressure-volume (P-V) curves recorded &om different PEEP levels in a healthy subject (A), a patient with acute respiratory
distress syndrome (ARDS) (B), and a patient with an acute exacerbation of chronic obstructive lung disease (COPD) (C). All curves are
related to the relaxation volume of the respiratory system. For each curve, end-expiratory and end-inspiratory points are indicated by
circles. In the healthy subject, PEEP of 10 cmH2 0 generates an increase in end-expiratory lung volume (EELV) and a rightward shift of
the P-V curve. The new curve is superimposed on the curve acquired without PEEP, indicating the absence of recruitment. In the patient
with ARDS, increasing PEEP produces increases in EELV and a significant lung recruitment, as indicated by the upward shift of
the P-V curves. ln the patient with COPD, the application of PEEP results in an EELV increase with worsening of hyperinflation, as
indicated by the superposition of P-V curves and the progressive decrease in the slope (compliance) of the curves. The reducti on in
aerated volume in ARDS produces a lower inflection point and flattening of the P-V curve at PEEP of 0 cmH2 0. The presence of
intrinsic PEEP during ven tilation without PEEP in ARDS, and more so in COPD, induces a rightward shift of the initial P-V curve.
In the healthy subject (left pa11el), a PEEP-induced increase in EELV is indicated by the dotted line. Vr, relaxation volume of the
respiratory system.
volume is the main cause of the impaired respiratory FIGURE 11-7 Measurement of PEEP-induced change in
mechanics. 206 Conversely, an increase in aerated lung vol- end-expiratory lung volume (aEELV). PEEP of 10 cmH2 0 is
ume is long recognized as the main cause of the benefit of abruptly brought to zero. A prolonged expiration ensues,
PEEP on lung function.l8•119 TI1e increase in lung volume and relaxation volume is achieved. The difference between
may result from tvvo different mechanisms: recruitment of the volume exhaled during this expiration and the tidal
terminal lung units not accessible to ventilation because of volume delivered by the ventilator equals the increase
collapse or flooding and distension or overdistension of al- in EELV induced by PEEP.
ready open lung units.
Several authors have reported an increase in EELV and
Flovt
FRC follov,ring the application of PEEP in patients with
ARostS,30,34,50,52, 119, 121,122.233,238,246, 262, 332,340,345- 347 (see Fig.
11 -6B). In absence of PEEP1, the increase in lung volume

above FRC at end expiration, or delta end-expiratory lung
volume (t.EELV), depends on the amount of PEEP ap-
plied and the compliance of the respiratory system. Dif-
ferent techniques can be used to meas ure FRC and EELV,
such as helium dilution,348- 353 nitrogen350,3 53 - 355 and sul-
fur hexafluoride,353,356- 359 washout, and CT scan.52·121,238
These measurements are not obtained routinely in the clin-
ical setting because of technical limitations and I or logistic
complexities. 6.EELV
-,...._,__
A surrogate approad1 has been used for assessing PEEP-
induced t.EELV; this involves measuring the volume ex-
haled between PEEP and the elastic equilibrium volume
of the respiratory system40,71,236,239- 242,3Ul,360,36'1 (Fig. 11-7). I
While the ventilator is delivering VT, the preset PEEP is Pressure 4---t-- PEEP 10
brought to zero rapidly. During the following expiration,
sufficient time (5-1 0 seconds) is provided to enable complete
exhalation; thus the elastic equilibrium, the relaxation val-
tune, will be readled.40•71,215, 236•240 The difference between
the volume exhaled during this prolonged expiration and ment induced by PEEP was not attempted until Ranieri
the volwne insufflated during the preceding inspiration et al71 •239,240 proposed a simple method using P-V curve
represents the ~EELV produced by PEEProT· The excess analysis. This approach consists of aligning on the same
volume caused by PEEP1 should be assessed separately, P-V diagran1 curves obtained at ZEEP and varying PEEP
and accow1ted for, to avoid overestimation of PEEP- levels. With this technique, which assumes that FRC (i.e.,
induced ~EELV. PEEP-induced variations in EELV also the relaxation volume at ZEEP) remains constant,30•71, 239
can be measured by inductive246' 360' 362 - 365 or optoelectronic the ~EELV induced by PEEP is added to the volume in-
plethysmography. 35~ 366 sufflated during the maneuver for recording the P-V curve
An increase in EELV also may occur w hen PEEP distends at the corresponding PEEP level.236,294•36" Lung recruitment
or overdistends already aerated ltmg regions (see Table 11-1; then is computed as the difference in volume between P-V
Fig. 11-8). Hence measurement of ~EELV without quantifi- curves obtained at different PEEP levels at a given value of
cation of lung recruitment may be misleading. Lung recruit- elastic recoil pressure (generally 20 cmH2 0). Anatomic re-
ment refers to reaeration of collapsed or fluid-filled terminal cruitment is reflected by an upward shift of the P-V curve
airways and alveoli. These areas become accessible to ven- (see Fig. 11-8). If PEEP fails to recntit new regions, no vol-
tilation (anatomic recruitment) and may participate in gas ume gain at a given pressure will be observed; the resulting
exchange if local perfusion is preserved (functional recruit- P-V curve will be shifted rightward and superimposed on
ment). Ltmg recruitment can be quantified by using P-V the curve acquired at ZEEP.236,239
curves traced from different levels of PEEP or by CT scan The CT scan is used to m easure recruitment. 367•368 PEEP-
analysis (see Table 11-1). induced lung recruitment is computed as the decrease in
Measurement of PEEP-induced lung recruitment u sing volume of nonaerated lung parenchyma121•205· 264•2 70, 367 or,
P-V curves stems from the pioneering observations of Katz as proposed recently, as the increase in volume of gas pene-
et al30 on the time course ofPEEP-m ediated increases in lung trating nonaerated and poorly aerated lung regions.34•3 68 - 371
volume. After applying PEEP, these authors observed that With this technique, however, recruitment is assessed by
EELV increased to approxinlately 66% of its total change comparing scans taken at different pressures (ZEEP and
within the first breath; it reached 90% in about five breaths PEEP) and not at the same pressure, as is done with the
and was fully complete only after several minutes, suggest- P-V curve tedmique. Therefore, no matter how it is com-
ing time dependence for lung recruitment.30 For a given puted, recruitment at a given PEEP also will include a
pressure, lung volume measured during ventilation with certain volume of gas corresponding to lung units that
13 cmH20 of PEEP was larger than the volume predicted inflate nom1ally from end expir ation at ZEEP up to the
for that pressure by the static compliance computed a t pressure corresponding to that PEEP. This helps to explain
3 cmH20 of PEEP; this observation suggests that some lung some of the differences in the amounts of recruitment with
tmits were not ventilated at the lower PEEP but were re- the CT scan and P-V curve techniques.372 Conversely, theCT
cruited by the higher PEEP.30 Quantification of lung recruit- scan offers a unique opportunity to estimate the amount of
FIGURE 11-8 Pressun-volume (P-V) curves at different levels of PEEP (0, 5, 10, and 15 cmH 2 0) related to relaxation volume of the
respiratory system (Vr) in two patients with acute respiratory distress syndrome (ARDS). In the left panel (A), PEEP induces progressive
upward shifts of P-V curves, indicating recruitment. At PEEP of 15 cmH2 0, a PEEP-induced increase in end-expiratory lung volume above
Vr is indicated by the dotted line between the two open circles. Alveolar recruitment induced by PEEP of 15 cmH2 0 compared with PEEP
of 0 cmH2 0 and measured at a pressure of 15 cmH 2 0 is shown by the double-arrow solid line. In the right panel (B), P-V curves are
particularly flattened, suggesting a marked decrease in aerated lung volume. Increasing PEEP resul ts in minimal recrui tment: P-V curves
are almost totally superimposed and progressively shifted to right. In both panels, all P-V curves tend to converge at high lung volumes,
suggesting that total lung capacity is approached. PEEP-induced recruitment is greater when the slope of the linear s egment above the
lower inflection point (LIP), that is, linear compliance, of the curve recorded from 0 cmH20 (the lowest curve) is high (A). When the curve
at 0 cmH 2 0 has a very low linear compliance, PEEP-induced recruitment is trivial (B). PEEP-induced recruitment also proceeds far above
UP (up to pressures greater than 40 cmH2 0 ), suggesting that lung reopening is a pan inspiratory phenomenon (A).
"· 8
18JO
1200
c
~
~
f.
12JO
Q) Gl
!=" !="
!5 !5
0 EIJJ 0 ~00
:.> :.>
~~--
Vr +---~--~;_·~~
UP~~------~----~------~
0 10 20 30 50
PEEP-induced hyperinflation34·52•121·238•274•371.373 (see Table ARDS has different pathophysiologic med1anisms. 391 •392 In
11-1), computed as tl'\e increase in gas volume within n or- an animal model, Grossman et al 391 sh owed that the loss of
mally aerated lung regions; hyperinflation, however, does a era ted lung units secondary to alveolar flooding accounted
not necessarily mean overstretching.367 for virtually all the decreased static lung compliance. With
In patients with ALI/ ARDS,PEEPincreases EELVand pr- CT scan analysis, Gattinoni et al 206 found that several pa-
oduces varying recnti tmen t34AO,S0,71 . 119,121,210,236,238- 242,246)64, rameters of the P-V curve, including linear compliance, were
270,274,332.360,371·373 -Jn (see Table 11-1). Recent work236 shows correlated with the amount of aerated areas (mainly dis-
that PEEP achieves progressive recruitmen t from 84 ml tributed in the nondependent, ventral lung regions) but n ot
at PEEP of 5 cmH20 (range 41-156 ml) to 304 ml at with nonaerated areas (preferentially distributed in the de-
15 cmthO (range 114-545 ml). The large interindividual pendent, dorsal lung regions). Indeed, compliance was in
differences suggest tha t, in certain patients, PEEP increases the normal range when normalized to FRC (so-called sp e-
lung volume without achieving significant recntitment, cific compliance), su ggesting that the aerated areas had nor-
Likely reflecting overdistension of previously aerated lung mal intrinsic elasticity. 206 According to this concept, respi-
regions. Indeed, PEEP-induced overdistension has been ratory system compliance provides an indirect estimate of
shown in several studies.34,52,71,238,239,240,274,371 In most the amount of a era ted lung (see Figs. 11-6 B and 11-8).
cases, recruitment and overdistension occur concomitantly Through recruitment, PEEP prevents the fall in static
rather than sequentially in different regions of the lung compliance8 and restores the normal P-V pattern by sup-
following PEEP application. 238•274·368,369,3?'l,373 Vieira et pressing small airways closure and collapse of unstable
al52 found that applying PEEP of 10 and 15 cmH20 in lung units.73,346,394- 396 Data suggest that the effects of PEEP
patients with ALI who did not have a clear LIP on the P-V on recntitment and overdistension can be predicted by the
curve produced progressive recruitment of nonaerated shape of the P-V curve at ZEEP. 71 ·236·239-274,385,387,397 Three
lung areas and overdistension of aerated lung zones. distinct patterns of P-V curve have been described in pa-
The interplay between these two phenomena depends tients w ith ALI/ ARDS71• 239•274 A concave shape w ith a clear
on several factors, such as ARDS etiology,50 lung and LIP indicates that compliance is increasing progressively
chest-wall mechanics,328•378 stage of disease,379•380 lung above thisJgoint, suggesting ongoing recntitment during
morphology,238•274·369 and amount of PEEP. 274 The inte- inflation71· 9•397 (see Fig. 11-8). A convex shape showing a
grated analysis of respiratory mechanics and lung volumes UTP denotes pro~essive decrease in compliance and likely
may help in recognizing the effects of PEEP on recn1itment overstretching71 • (see Fig. 11-8). A linear P-V curve w ith
and overdistension and hence in selecting optimal PEEP at absent or very low LIP may be observed in localized lung
the bedside. injury.274
Rouby et al230,369· 370 hypothesized that a linear P-V curve
results from two separate regional curves: a concave curve
EFFECT OF PEEP ON RESPIRATORY related to normally aerated lung regions and a convex
MECHANICS IN ALI/ ARDS curve related to nonaerated areas. PEEP may have dif-
Contrasted with normal subjects, the rate of change per unit ferent effects on lung volumes and respiratory mechan-
of pressure is smaller, and linear compliance of the P-V ics according to these patterns. When a concave sh ape is
curve falls to very low values in patients w ith ARDS (be- observed at ZEEP, PEEP results in lung recruitment as doc-
cause of the decrease in normally ventilated alveolar units); umented by an upward shift of the P-V curve a nd disap-
the whole cur ve is also flattened and shifted downward, pearance of UP71 ·236•239·274 (see Fig. 11-8). With a convex
and the inflection knees, normally seen at low (UP) and profile and low linear compliance at ZEEP, PEEP-induced
high (VIP) lung volumes, may appear in the range of tidal recntitment is minimal or zero: The P-V curve is superim-
ventila tion 294 (see Figs. 11 -6B and 11-8). The presence of LIP posed on that obtained at ZEEP, with a further decrease in
and UIP in the VT range suggests considerable susceptibility compliance71•236•239·274 (see Fig. 11-8).
of the ARDS lung to detrimental shear forces generated by A linear compliance on the P-V curve at ZEEP may be
cyclic end-expiratory alveolar opening and collapse12!,206.381 a useful indicator of lung recnttability (see Fig. 11-8). A
and end-inspiratory overstretching.239·382 These forces are tight correlation between linear compliance at ZEEP and
considered the main mecl1anism of ventilator-induced lung amount of PEEP-induced recntitment has been suggested
injury.383·384 Recent evidence suggests that airspace reopen- recently. 236 Because compliance, as assessed o n the P-V
ing can occur along the entire P-V curve.236,264· 265,367,3S:>-387 curve, is a function of normally aerated lung regions,206
Moreover, the shape and characteristics of the P-V curve can two different situations can be imagined: (1) The lung is
be greatly influenced by several factors, including paUlo- principally characterized by unstable lung regions, which
physiologic mechanisms, stage of disease,50·381 chest-wall are collapsed at end expiration but pop open progressively
mechanics,237·328 breathing pattern, and differences in mea- during tidal inflation, and (2) the lung is predominantly
surement technique. 388 consolidated with n o large areas expanding during inflation
As already mentioned, one of the typical features of ALII (compliance is very low). Application of PEEP results in
ARDS is the fall in respiratory system complian ce (see Figs. significant recruitment in the former case; in the latter case,
11-6B and 11-8), described both in experin1ental389-392 and PEEP may overstretch already ventila ted areas without
clinical settings.18,119·215·381·393 Decreas ed compliance was at- producing significant recruitment. 71·239 Independently of its
tributed initially to increased lung stiffness.344 Subsequent effect on recruitment and overdistension, PEEP constantly
studies have demonstrated that the decreased compliance in and significantly decreases the linear compliance of the P-V
CHAPTER 11 POSITIVE END~ EXPIRATORY PRESSURE 285
curve. 40•23r,·239·385•387 This contrasts with the classical notion plex effect of recruitment on the P-V relations hip,385- 387
that compliance increases with recruitment and decreases static compliance (calculated as the P-V differences between
with overdistension. 18 Lung units that pop open at a certain two points) may not describe adequately the changes in
pressure have an infinitely high compliance and contribute respiratory mechanics produced by PEEP. 294•361 Indeed, as
to the higher compliance observed at ZEEP, as opposed shown previously 402 and outlined recently,22 1.386•403 static
to that observed when the lung is fully recruited at PEEP. compliance may vary for different Vr values. A mathemat-
A corollary is that U1P may indicate the end of tidal re- ical model suggests that the highest static compliance com-
cnJitment and/or the beginning of alveolar overdistension, puted at a low Vr during a d ecremental, but not incrementat
although both mechanisms may coexist at high PEEP trial may help to identify the level of PEEP needed to
pressure40•385 (see Fig. 11-8). Therefore, a PEEP-related prevent end-expiratory alveolar collapse.386 These theoret-
decrease in P-V linear compliance predominantly may ical findings are supported by data in animals404 but have
reflect recruitment below VIP; a decrease in compliance not been tested in patients.
above this point may reflect overdistension. Several studies218·221·224.374·405 reveal that PEEP in-
UP has long been considered the pressure at which col- creases additional resistance through increased viscoelas-
lapsed lung units open during inflation; it is therefore con- tic dissipation219 consequent to a PEEP-mediated increase
sidered the ideal pressure at which to set PEEP.381 Recently, in EELV, as suggested by the correlation between changes
however, no relationship between LIP and either opening or in tissue resistance and EELV.405 Other studies,332·406 while
closing alveolar pressures was found,236 indicating that UP confirming the rise in tiss ue resistance, also reported a de-
is not useful for optimizing PEEP setting. Other studies con- crease in airway resistance, especially at high PEEP. When
firmed that recruitment and derecruitment are continuous resistances were normalized for lung volume (i.e., specific
processes unrelated to LJP40·242•264·265•385·387 (see Fig. 11-8). resistance), these changes disappeared.332 Partitioning re-
Nevertheless, the presence of a clear LIP followed by a high sistance into lung and chest-wall components, Pelosi et al332
inflation compliance on the P-V curve recorded from ZEEP found that the increase in total and tissue respiratory system
may predict the effect of PEEP on recruitment206, 236,274,387 resis tance consequent to PEEP could be ascribed mainly to
(see Fig. 11-8). Vieira et al274 showed that patients with a the lung rather than to the chest wall. Recently, Gattinoni
diffuse loss of aeration had a marked LIP at ZEEP, whereas et al 50 found that total respiratory resistance increased with
LIP was absent or blunted in patients with a focal loss of aer- PEEP in pulmonary ARDS mainly because of a marked in-
ation. High PEEP induced progressive recruitment without crease in lung additional resistance. 50 In contrast, patients
overdistension in the former group, whereas it caused a sig- with extra pulmonary ARDS, d1aracterized by higher chest-
nificant overdistension of normally aerated regions in the wall tissue resistance and lower lung tissue resistance than
latter group.274 Some researcl1ers think that LIP is caused pulmonary ARDS, did not show any cl1ange in total respi-
by time-constant inequalities within the lung and/ or re- ratory resistance with PEEP.50
opening of compressed peripheral airway associated with
expiratory flow lirnitation. 222•223•398·399 Accordingly, the dis-
appearance of LIP following application of low or moder- EFFECT OF PEEP ON RESPIRATORY
ate PEEP might indicate that PEEP can prevent small air- MECHANICS IN COPD
ways closure and make the distribution of tidal ventilation In COPD patients, lung and chest-wall static compliance
more homogeneous. 223•399 This also could explain the differ- are reported to be similar to those of normal subjects407
ence between the reported values of LIP, i.e., 5- 15 cmH20, unless expiratory flow limitation and dynamic hyperin-
and the substantially higher pressures required to reverse flation cause lung overdistension. Depending on the level
atelectasis. 264•291·400 of PEEP, static compliance may decrease (if overdisten-
The mechanical properties of the chest wall may influence sion occurs),87•359•408,409 stay unchanged/ 10 or even increase
the effects ofPEEP.50•237·328 In some patients, Mergoni et a1 237 slightly (if recruitment of new lung units occurs)306 (see Fig.
found that the LIP on the P-V curve of the respiratory system 11-6C).
at ZEEP reflected the chest wall rather than the lung. Appli- PEEPmr may exceed preset PEEP markedly when PEEP1
cation of PEEP abolished LIP in all instances, but oxygena- is present (see Fig. 11-5). Rossi et al 91 demonstrated that
tion significantly improved, suggesting recruitment (only in failure to take PEEP1 into account caused static compli-
patientsexhibitinga UPon the lung P-V curve).237 Gattinoni ance to be underestimated by up to 48%. During volume-
et a1 50 found that increasing levels of PEEP decreased respi- targeted controlled ventilation, an increase in ins piratory
ratory and lung static compliance without any recruitment flow resulting in a prolonged expiratory time causes PEEPi
in patients with primary pulmonary ARDS; in patients with to decrease. Thus the value of static compliance calcu-
secondary extrapulmonary ARDS, PEEP induced signifi- lated without correcting for PEEP1 will increase falsely (and
cant recruitment and increased respiratory, lung, and chest- paradoxical! y).91 •306 The presence of an LIP on the P-V curve
wall compliance.50 These findings have not been confirmed at ZEEP may be partly caused by PEEP1, at least in patients
by other studies.40,236,238,274 with expiratory flow limitation. 4n
The change in static compliance produced by PEEP has Patients with COPD have a high resistance.80•87·410 •412A 13
been proposed as a guide for optimizing PEEP18 and as a In patients with expiratory flow limition, PEEP should
prognos tic factor for predicting mortality in patients with have little influence on expiratory flow until PEEP ex-
ALl/ ARDS. 401 Because of nonlinearity of the P-V relation- ceeds PEEP1•91 Recent data, however, suggest that PEEP of
ship in AU/ ARDS, however, and the aforementioned com- 5-10 cmH20 might partly decrease expiratory resistance,
particularly at the end expiration, and result in faster and overdistension of already aerated lw1g a reas in three
more uniform lung emptying.359,410,414,415 patients.52
Since the 1970s, high ventilator pressures have been
EFFECT OF PEEP ON VENTILATOR-I ND UCED
known to rupture alveoli and cause air leaks. 426 By
increasing airway pressure, PEEP may promote alveo-
LUNG INJURY
lar overstretching,26•239•24{)· 274•371 ultrastructural damage,422
VENTILATOR-lNDUCED LUNG lNJURY and worsening of pulmonary edema. 198 Several studies
Recent decades have brought the recognition that me- suggest that end-inspira tory lung volume, rather than
chanical ventila tion per se in ALI/ ARDS may damage high intrathoracic pressure, is the major determinant of
the lnng and/or aggravate preexisting lung injury. 384 This ventilator-induced lnng edema (" volutrauma"), at least
so-called ventilator-induced lung injury (VJLI)384.4"l6,417 is in normal lnngs.269•427•428 PEEP, however, also may pro-
now widely accepted and supported by a large number tect against edema accumulation during ventilation at
of animal experimental studies269A 18 and recent data in high end-insfiratory pressur~ an_d e~d-inspiratory lung
patients.9A 19•420 Attempts to prevent VILI have modified volume,266- 26 although alteratiOn U1 rrucrovascular perme-
the ventilator approach to patients with ALI/ ARDS. 383 ability may not be prevented. 268·269 Several factors may ex-
Two main mecl1anisms for VILI are (1) alveolar269A 18 and plain these apparent contradictions: {1) differences in ex-
bronchial overdis tension421 •422 occurring at high volume perinlental setup (isolated lnng versus intact animals), (2)
and transpulmonary pressure and (2) repeated alveolar and levels of PEEP and inspiratory airway pressure, and (3) dri v-
small airways collapse and reopening at low end-expiratory ing pressure (difference between end-inspiratory and end-
volume. 266A 21 ' 423 The common pathway for these two mech- expiratory alveolar pressures, which, for a given pulmonary
anisms is mecha nica l stress on the terminal units (including elastance, depends on VT size). 384 In isolated lung with con-
bronchiolar and alveolar walls). 424 A25 O ther factors, includ- stant perfusion, PEEP augments edema formation proba-
ing elevated Fio 2, high blood flow, high inspira tory flow, bly because of increased filtration across extra-alveolar ves-
and intensity of local inflammation, may play a role in ag- sels associated with lttng overdistension. 429·430 Conversely,
gravating or inducing lung injury. in intact animals, PEEP does not affect edema formation
probably because of balancing between the PEEP-induced
EFFECT OF PEEP ON VILI increase in end-inspiratory lung volume (which increases
PEEP may have opposing consequ ences depending on its fluid filtration) and concomitant reduction in cardiac output
effects on the two aforementioned mecl1anisms of VILI and blood pressure (which reduce filtration pressure). 431 - 433
(alveolar overdistension and cyclic alveolar collapse and The r ole of PEEP-induced changes in hemodynamics
reopening)274, 373 (Fig. 11-9).ln one study, PEEP (13 cmH20) on edema accumulation has been suggested by several
caused recruitment of nonaerated regions and induced authors.268•434 In an anirnal model, Dreyfuss and Saumon268
FIGURE 11-9 Postulated mechanisms by

High volume v entilation Low volume ventilation w hich mechanical ven tilation may lead to
ventilator-associated lung in jury and organ
.. inju ry. Beneficial (min us sign ) and
Overdistension detrimental (plus sign) effects of PEEP on
Atelectasis ---8 these mechanism s are shown.
1
Increased alveolar-capillary permeability
l 1
Cycli c opening and closing -8
Alveolar flooding
G-
1
Decrease in aerated volum e
1
Shear stress
Release of inflammatory mediators
Lung and distal organs damage

O -lAPTER 11 POSITIVE END-EXPIRATORY PRESSURE 287
showed that lung edema was reduced during ventilation ciated with decreased pulmonary and systemic cytokine
with PEEP of 10 cml-!2 0 as opposed to ZEEP despite iden- response, 419•420 less organ dysfunction, 454 and reduced
tical end-inspiratory pressures. When the drop in arterial mortality in patients with ARDS9, 420 compared with con-
pressure produced by PEEP was corrected by dopamine ventional, injurious mechanical ventilation. Although the
infusion, pulmonary edema increased in direct proportion mechanisms whereby VILI causes organ dysftmction are
to systemic blood pressure. The increase in permeability not completely understood, a recent s tudy suggests that
edema, however, was less than that observed during ven- cell apoptosis may be involved.453 Rabbits ventilated with
tilation at ZEEP, suggesting that hemodynamic modifica- a low VT and high PEEP showed less epithelial apoptosis in
tion is not the only factor explaining the effect of PEEP on the kidney and small intestine than did rabbits ventilated
edema formation. 268 Indeed, reduction in driving pressure with a high VT and low PEEP. 453 The former rabbits
while keeping end-inspiratory lung volume and pressure had more apoptotic cells in the lung, whereas the latter
constant (as obtained by increasing PEEP while reducing rabbits had less lung ~optosis and necrosis of alveolar
VT) may reduce edema and the severity of cellular dam- epithelial type Ill cells. 4 Analysis of plasma samples from
age; these findings suggest that a decrease in tissue stress a previous clinical tr ial419 revealed higher levels of soluble
may explain this protective effect of PEEP.266 - 269•435 PEEP- Fas ligand (a proapoptotic factor) in patients who received
associated preservation of surfactant may further explain conventional ventilation than in patients who received
the benefit of PEEP on high vol tune-media ted VILI. 266 Thus protective ventilation; changes in soluble Fas ligand were
severity of overinflation is one major determinant of VILI. 436 correlated with changes in plasma creatinine.454
When ventilator-induced lung edema is produced by high
VT, the combination of PEEP and VT reduction decreases
EFFECfS OF PEEP O N CARDIOVASCULAR SYSTEM
the severity of injury at the same end-inspiratory pressure.
When PEEP is not accompanied by VT reduction, however, The lungs and heart are subject to variations in intrathoracic
excessive inspiratory pressures and additional overstretch- pressure. How alterations in intrathoracic pressure affect the
ing occur, further increasing the rate of edema formation heart and intrathoracic vessels varies substantially depend-
and tissue injury. 268 ing on several factors, such as mechanical properties of the
In a mechanically heterogeneous lung, noninflating, col- lung and chest wall, type of ventilation (spontaneous ver-
lapsed tissue is surrounded by open airspaces. Mead et al 424 sus mechanical), blood volume, and left-ventricular func-
suggested thatrecruitmentofnonaerated lung units induces tion. The complex interplay of these factors and the ef-
a local stress to alveoli and bronchioles that is substantially fects of PEEP on heart-lung interactions have been reviewed
higher than the average transpulmonary or transbronchial extensively. 455 - 463
pressure, respectively, because of alveolar and small air-
ways interdependence. 421 •425 If this process recurs cyclically, EFFECT ON VENOUS RETURN
high shear forces may damage the alveolar and airway ep- Positive airway pressure causes a drop in cardiac out-
ithelium, overstretch fragile microvessels, deplete surfac- put secondary to a decrease in cardiac filling (preload);
tant, and initiate or worsen inflammation. By recruiting this was attributed initially to a reduction in the pres-
nonaerated portions and stabilizing airways and lung units sure gradient for venous return, determined by the rise
prone to repetitive opening and collapse, PEEP plays a key in right-atrial pressure consequent to increased intratho-
role in protecting the lung from the mechanical shear stress racic pressure. 61 •95.464 - 467 The PEEP-mediated decrease in
produced by ventilation a t low end-expiratory lung volume the gradient for venous return, however, is less than ex-
("a telectrauma"). 423,424,437- 439 pected because PEEP produces a concomitant rise in mean
A large body of animal data supports the pro- systemic pressure468 (the circulatory filling pressure repre-
tective effect of PEEP on low volume-mediated senting the upstream press ure for venous return). In pa-
VILJ. 73,266,267.423,435,437,439-443 By mirtimizing shear stress tients without lung disease undergoing implantation of de-
associated with cyclic opening and collapse, PEEP may fibrillator devices under general anesthesia, Jellinek et al469
attenuate inequalities in the regional dis tribution of tidal meas ured right-atrial pressure and mean systemic pres-
ventilation, thus avoiding or limiting overdistension in the sure at airway pressures of 0 and 15 cmH2 0 during 15-
less injured lung zones. 424~ 425 By increasing EELV, PEEP second periods of apnea when ventricular fibrillation was
also can prevent surfactant loss and preserve surfactant induced to test the defibrillator. Rising airway pressure pro-
function.441 •444 -44 7 By minimizing mechanical stress, PEEP duced a drop in left-ventricular s troke volume.469 Right-
also may ease the intensity of ventilator-induced lung atrial and mean systemic pressures, however, increased
inflammation437 and reduce the decompartmentalization of equally, showing that the reduction in venous return was
a number of irtflamrnatory mediators448 and bacteria from not determined by a decrease in the pressure gradient. 469
the lung into the circulation ("biotrauma''). 449•450 These The rise in mean systemic pressure may result from a reduc-
aforementioned mechanisms may play a role in initiating tion in vascular capacitance detem1ined by neurovascular
or propagating the systemic inflammatory response that reflexes,470 displacement of blood from the pulmonary to
contributes to the multiple organ failure often observed the systemic circulation,471 and descent of the diaphragm,
in the terminal stage of ARDS.451 - 453 Recent clinical trials which increases the upstream pressure for venous return
have shown that protective ventilator strategies, reduced by augmenting intra-abdominal pressure. 4n These homeo-
VT (to limit the end-inspiratory stretch),9•419 A20 and high static adaptations, however, may be counteracted by a con-
PEEP (to avoid cyclic opening and closing)9•419 were asso- comitant increase in venous resistance,468.473 suggesting that
PEEP may alter venous return by affecting the peripheral on left-ventricular function seems to be adjunctive rather
venous circulation. than a major determinant of the PEEP-mediated reduction
The effects of PEEP on hemodynamics strongly dein cardiac output.
pend on intravascular volume. Cardiac output can be re-
stored by increasing the ventricular filling through volume EFFECT ON CARDIAC CONTRACTILITY
infusion. 17.474 - 477 PEEP discontinuation produces a rise in Some researchers think that PEEP causes a humorally me-
cardiac filling proportional to the pressure withdrawn and diated impairment in cardiac contractility.489 - 491 So far this
the circulating blood volume.17·4'78 In hypervolemic and notion has not been confirmed. Indeed, it has been proven
hemodynamically stable patients who underwent cardiac repeatedly to be absent or, at least, irrelevant.4 76,488,492- 495
surgery, van der Berget al472 recently found that maintain-
ing airway pressure up to 20 cmH2 0 for 25 seconds pro- IMPACT OF RESPIRATORY MECHANICS ON THE
duced minimal variations in right-ventricular output de- HEMODYNAMIC EFFECT OF PEEP
spite a concomitant rise in right-atrial pressure. Application of positive pressure to the airway (Paw) in-
In summary, PEEP reduces cardiac output through a decreases lung volume. When the r~spiratory muscles are not
crease in venous return that is not a primary consequence of active, the ventilator gen erates the entire pressure applied to
a decrease in its pressure gradient. Regardless of the cause, the respiratory system (Paw = Prs). During inspiration, part
the drop in cardiac output can be counteracted by blood of Paw is dissipated in overcoming airflow resistance (Pres),
volume expansion. and the remaining part distends the elastic structures of the
lung (PI) and the chest wall (Pew). Accordingly, PI + Pew
EFFECT ON RIGHT-VENTRICULAR AFfERLOAD =Paw -Pres. When the respiratory muscles are not active,
AND VENTRICULAR INTERDEPENDENCE as occurs under controlled ventilation, Pew corresponds to
PEEP alters both left- and right-ventricular configurations intrathoracic pressure, whid1 affects the heart and intratho-
and reduces left-ventricular diastolic compliance by aug- racic vasculature. Because the lung and the chest wall are
menting right-ventricular afterload. 27.479 - 481 An increase aligned in series, the pressure is first transmitted to the lung
in lung volume causes a rise in pulmonary vascular re- and then to the chest wall. Therefore, Pew = Paw - Pres -
sistance by directly compressing the alveolar vessels. 482 Pl. PI and Pew correspond to the product of volume (V)
The interconnections between lung volume and pulmonary and lung (El) and chest-wall (Ecw) elastance, respectively.
blood fl ow are not straightforward because blood expelled Hence V x Ecw = Paw - Pres - (V x El); alternatively,
from the alveolar vessels can be retained in the extra- V/Ccw =Paw- Pres - (V / Cl), where Cis compliance (the
alveolar vessels. 483•484 When airway pressure is augmented, reciprocal of elastance). The lower Cl, the less airway pres-
right-ventricular outflow impedence (i.e., afterload) is also sure is transmitted to the pleural space (i.e., intrathoracic
increased.'l63•485 In patients with ALI/ ARDS, high levels of pressure) and the fewer hemodynamic consequences.
PEEP can cause or worsen tricuspid regurgitation. 486 In dogs, a reduction in lung compliance decreased the
The fall in cardiac output with PEEP also has been at- transmission of airway pressure to the pericardia! space. 495
tributed to the stress exerted by the right ventricle on The transmission of PEEP to the pleural space increased
the interventricular septum,4so which is displaced leftward when chest-wall compliance was reduced by bindi.ng. 496
and restricts left-ventricular filling. 27 Culver et al487 altered In another animal model, a decrease in lung compliance
right-ventricular after load through a partial occlusion of the decreased transmission of airway pressure to the pleural
main pulmonary arteries and found that this did not pro- space; an increase in chest-wall compliance by sternotomy
duce the same hemodynamic changes induced by increases further reduced airway pressure transmission. 497 Venus
in lung volume; these findings suggest that ventricular in- et a1 498 found that the fraction of PEEP transmitted to the
terdependence (caused by an increased right-ventricular af- pleura was reduced from 62 to 34% and to the pericardium
terload) is unlikely to be the main mechanism for the PEEP- from 54 to 36% in intact and acutely injured lungs, respec-
mediated fall in cardiac output. WlSe et al488 evaluated the tively. VT was kept constant throughout the study, and the
impact of PEEP of 15 cmH2 0 on left-ventricular compliance reduction in cardiac output produced by PEEP did not differ
in a study where they bypassed the right side of the heart before and after inducing lung injury because absolute peri-
to exclude the effects of interventricular interdependence; cardia) pressure at end expiration did not differ.498 When
they concluded that the elevation in left-ventricular filling lung compliance diminishes but VT remains constant, the
pressure was mainly a consequence of pericardia! compres- absolute amount of airway pressure transmitted to the pleu-
sion. In patients with ARDS, Dhainaut et al477 did not find ral and pericardia} spaces a t end inspiration remains the
any changes in ventricular diastolic compliance and ejec- same, although it represents a lower fraction of the higher
tion fraction when PEEP was increased up to 20 cmH2 0 airway pressure.50A 98
during controlled ventilation; they attributed the reduction At end expiration, in absence of flow (when Pres = 0),
in cardiac output mainly to the preload effect. Paw equals PEEP, and then V /Ccw =PEEP- (V / Cl). Ac-
In summary, PEEP increases pulmonary vascular resis- cordingly, the fraction of PEEP transmitted to the pleural
tance and right-ventricular afterload and therefore may in- and pericardia} spaces will be determined by the amount of
crease the stress exerted by the right ventricle, which has to lung recruited at that pressure, which varies substantially
maintain an adequate output to guarantee left-ventricular with the underlying disorder.50·499 The reduction in cardiac
filling. Right-ventricular systolic overload may result in left- output with PEEP also depends on overdistension (more
ward displacement of the interventricular septum; the effect likely at high VT).240
--1 l co : LVFailtn • [ I LV After1oad I

t
102
I
Delivery -I 1 Pa02 1-
'
T Venous
admixture - Pulmonary
Edema
TLV
Transmural
Pressure
1 P(Jimonary Compliance T Negative

Intrathoracic
T Airway Resistence Pressure
SWing
Respiratory 1WOJ1<
Musde of Breathing
FaJiure
T 0 2 Cost
of Breathing ..,._ _ _ _ _ _ _ _ _ _ _ ___,
'-----~
FIGURE 11-10 Pathophysiologic mechanisms and pathways of cardiogenic pulmonary edema. Deterioration in pulmonary mechan ics
increases negative s wings in intrathoracic pressure and left-ventricular afterload. Deterioration in gas exch ange decreases oxygen delivery
to the heart and the respiratory muscle. Sec text for further explanation. CO, cardiac output; LV, left ventricle; 0 2, oxygen.
EFFECT ON AFTERLOAD cost of breathing 507- 509 may precipita te respirato.r y muscle
Left-ventricular aiterload is the force opposing contraction. failure,509 which further worsens gas exchange.
It corresponds to the tension d eveloped by the contracting The impact on left-ventricular transmltTal pressure
cardiac muscle. It is determined by both the systemic arte- of the increase in intrathoracic pressure produced by
rial resis tance and the transmural pressure exerted on the CPAP of 10 cmH2 0 during expiration is rather small
left-ventricular wall, that is, the d ifference between the sys- (see Fig. 11 -3C). Conversely, the improvement in pul-
tolic pressure and the pressure surrounding the heart (i.e., monary mechanics509 generated by the same CPAP may
intra thoracic pressure). A reduction in left-ventricular af- minimize the swings in intrathoracic pressure509•510 and
terload is achieved either by decreasing systemic arterial hence d ecrease a fterload,510•5 11 thereby improving left-
resistance (through vasodilator adrninistration) 500 or by in- ventricular function 101 •511 (see Fig. 11-3C). CPAP simulta-
creasing intra thoracic pressure.99, 100•488 In healthy subjects neously may improve gas exchange101 •10 2. 187 by reducing
with normal cardiac function, the dominant action of in- venous admixture 14• 187 and avert failure of the respiratory
crease in intrathoracic pressure is reduction in venous re- muscles by improving their 0 2 balance14 (Fig. 11-11).
turn; the consequences of the lowered transmltTal pres-
sure are rather small (see Fig. 11 -3A). In patients with poor
left-ventricular fw1ction and congestive heart failltTe, car- EFFECT ON OXYGEN DELIVERY
diac output is relatively insensitive to reductions in venous 0 2 delivery <Do,) is the product of arterial 0 2 concentra-
return because left-ventricular filling pressure and dias- tion (Ca0 ,) and cardiac output, where C~ is (Hb x 1.39 x
tolic volume are elevated.96 Thus the net effect of a rise Sa0 2 ) + (Pa 0 , x 0.003). The effect of PEEP on D0 , depends
in intrathoracic pressure is a reduction in left-ventricular on its relative effects on cardiac output and Ca~, in other
transmural pressure97•501 •502 (see Fig. 11 -3C). Conversely, words, on the balance between its pulmonary and hemo-
a d ecrease in intrathoracic pressure raises afterload by dynamic consequences. Because Ca 0 , depends much more
aug menting left-ventricular transmural pressure390• 503 (see on Sa~ (0 2 bound to hemoglobin) tha n on Pao2 (02 dis-
Fig. 11-3 8 ) . solved in blood), little Cao, improvement is observed when
When afterload exceeds the capacity of the left ven- an increase in Paaz occurs on the upper part of the 0 2 disso-
tricle, pulmonary edema ensues, establishing a vicious ciation curve. Furthermore, PEEP-induced increase in Pa~
circle (Fig. 11-10). Because of worsening pulmonary and Ca~ may be accompanied by a decrease in Do, because
compliance390• 503, 504 and resistance/ 03•505 - 507 the inspiratory of concomitant decrease in cardiac output.59 Several studies
muscles must exert a stronger effort to acl1ieve adequate indicate tha t Daz is more influenced by cardiac output than
alveolar ventila tion. Thus inspiratory intrathoracic pressure by Ca~.512-514
becomes more negative, and afterload increases. The com- The impact of PEEP on Do, depends primarily on its
bination of reduced 0 2 delivery508 and increased metabolic hemodynamic effect. PEEP-mediated impairment of cardiac
I LV
Function
<01- -------,1
11 LV Afterload I
I LV
I
1 Venous
admixture I CPAPI PEEP TransmLnl
Pressur e
l Pulmonary Compliance I Negative

Intrath oracic
I Respiratory I Ahway reslstence Pressure
Muscle
Swing
Function
I Work
of Breathing
I 0 2 Cost
of Breathing
FIGURE 11-11 C<~rdiopulmonary effects of CPAP in cardiogenic p ulmonary edema. By improving pulmonary mechanics, CPAP red uces
n egative swings in intr athoracic pressure and left-ventricu lar afterload. By improving gas exchange, CPAP increases oxygen delivery to the
h ear t an d the respiratory m uscle. See text for further explanation. LV, left ventricle; 0 2, oxygen
output is inversely related to pulmonary compliance: The ologic mechanism for the development o f tissue hypoxia
lower lung compliance, the less PEEP is transmitted to the and multiple-organ failure.538 By decreasing cardiac output
intrathoracic pressure, and the smaller is the decrease in and consequently Do 1 , PEEP may worsen 0 2 balan ce and
cardiac output. The PEEP-media ted increase in Ca0 , is also promote pathologic supply dependence.43,S25,528,533,539
greater when producing a large rise in Sao, from a low Recognition o f methodologic errors (mathematical cou-
value. 5l2·515 Therefore, the effect of PEEP on Do, also d e- pling of data) subsequently challenged the notion of the
pends on ARF severity.71 •239•516- 518 In patients with severe pathologic supply dependence. 540- 542 Several investigators
ARDS (very low lung compliance a nd Pa0 , ), PEEP increases d id not find a correlation between D01 and V0 2 when these
Cao, w ith a moderate d ecrease in cardiac output, resulting two parameters were measured independently. 543- 548 Two
in a Do, increase. Conversely, in patients with moderate randomized trials failed to d emonstrate an y clinical bene-
ARDS (rela tively h igher lung compliance and Pao,), PEEP fit of a treatment strategy that achieved supran ormaJ Do,
will decrease cardiac output without causing much change values. 549•550
in Cao,; the net effect is a more remarkable reduction in Do,. Pathologic Do, / V0 1 dependency (assessed from indepen-
Under normal conditions, when the metabolic require- dent measures o f the two parameters) was reported recently
ments increase, physiologic homeostatic mechanisms act on in brain-dead patients with high plasma lactate levels but
central (pulmonary gas exchange, blood flow, hemoglobin not in patie11ts with normal lactate.551 In the former group,
concen tration, and hemoglobin affinity for 0 2) 519 and pe- PEEP of 10-15 cmH2 0 induced a marked decrease in Do,
ripheral (blood flow distribution, capillary-cell distance)520 and Vo 2 i in the la tter, the decline in Do, was associated only
d eterminants of 0 2 balance to enhance Do, and match V0 , . with a moderate reducetion in \/0 , .551
When Vo, is augmented, as during exercise, the first strat- The effectofprotective ventilation (high PEEP and lowVT,
egy to increase D0 , is to increase cardiac output. 123 If the permissive hypercapnia) on Do1 was evaluated recently in
increase in cardiac output is not sufficient to match the Vo, patients witl1 ARDS. 552- 554 In 48 patients with severe ARDS,
augmentation, tissue 0 2 extraction increases; thus Vo, is Carval11o et aJ553 found that PEEP of up to 24 cmH 2 0 (16
kept consta nt up to a threshold, above which energy sup- cmH2 0 on average) produced a n increase in cardiac out-
plies depend on anaerobic m etabolism, and lactic acidosis put, heart rate, and Do, and d ecreased systemic vascular
occurs.521, 522 A linea r relationship exists between Do, and resistance and plasma lactate. The authors speculated that
Yo, (supply dependence) below a critical Do, threshold; the good tolerance of high PEEP may have been a conse-
in anesthetized subjects, the threshold is 330 ml/ min.523 ln quence of the acute hemodynamic effects of hypercapnia
sepsis and ARDS, an a ltered supply dependence,43•515•524- 536 and the observed very low lung compliance. 553 No correla-
together with peripheral limitation in 0 2 diffusion and in- tion was found between changes in PEEP and cardiac out-
creased 0 2 hemoglobin affinity,537 is a major pathophysi- put. A strong inverse correlation existed between changes
in plateau pressure and cardiac output. These findings sug- who were receiving positive-pressure ventilation. PEEP de-
gest, in line with other reports/40 ,378 that the negative hemo- creased urinary output by 34%, renal blood flow by 32%,
dynamic effect classically attributed to PEEP may depend and sodium excretion by 33%; the associated drop in car-
more on the associated high inspiratory pressure (if v,. is diac output was 15%.558 PEEP also increased urinary ADH
not reduced concomitantly).553 and plasma renin and aldosterone levels. 558 ln a similar set-
ting, Payen et a1 573 found that 15 cmH20 of PEEP reduced
urinary output (55%) and fractional sodium excretion (39%);
NON CARDIORESPIRATORY EFFECTS OF PEEP
cardiac index fell by 21 %. Plasma ADH did not vary, and
PEEP may influence regional blood distribution555 and lead norepinephrine increased.s73
to inequalities in Do, to the different organs and potentially PEEP increases sympathetic activity.583 Nevertheless, the
affect their functions. 22,556 Renal and hepatic failure are in- observation by Fewell et al 577 tl1at the effects of PEEP on
dependently associated with increased mortality. 29 PEEP- renal function are mediated by sympathetic activity has not
induced alterations in regional blood flows have impor- been confirmed.562·574 PEEP also decreases plasma atrial na-
tant imglications for the development of multiple-organ triuretic factor.559,566,s67•569,575 This may contribute to there-
failure. duction in urinary output and sodium excretion probably
as a result of the reduced atrial transmural pressure conse-
RENAL AND HORMONAL EFFECTS quent to the raised intrathoracic pressure.566
PEEP decreases urinary output, 17,64,557- 582 sodium In summary, PEEP may alter renal function by reducing
excretion,64,557- 559,56 t - 563,565-572,575 and creatinine cardiac output and renal blood flow to an extent that de-
clearance. 557·561-562,565,572 Although there is general con- pends on the volemic state and the an1ount of applied pres-
sensus about these effects of PEEP, studies investigating sure. Other mechanisms, including several hormones, also
the mechanisms are conflicting. Discrepancies are related may play a role.
to differences in experimental design, such as diverse
subjects, trial duration, type and severity of underlying
disorder, volemic state, use of drugs and anesthetics (which EFFECTS ON SPLANCHNIC CIRCULATION
commonly cause sympathetic depression), and level of AND OXYGENATION
PEEP. The decrease in urinary output cau sed by PEEP PEEP decreases splanchnic blood flow56-65-67 -6S,S84,SSS and
has been attributed to multiple factors such as fall in causes hepatic congestion.65 The reduction in splanchnic
cardiac output558,573-579 and renal blood flow,558, S60.S68,573,S7S blood fl ow is consequent to a fall in cardiac output sec-
reduced intravascular volume, 579 reflex sympathetic ondary to impaired cen tral hemodynamic56,6S,6?,68,584,585; it
nerve activation,581 and altered release of hormones, in- is less pronounced when cardiac output is maintained either
cluding catecholamines,557 renin-angiotensin-aldosterone by expanding blood volume 67,68 or by inotropic dmgs.sss In
system,557,569,570,576,582 antidiuretic hormone (ADH),557,569 hemodynamically stable patients with ALI/ ARDS, Kiefer
and atrial natriuretic factor. 566,567,569,571,572,575 et al586 found that PEEP of 13 cmH20 (5 cmH20 incre-
In dogs receiving a constant fluid infusion, Berry et al 64 ment above the preset values) did not decrease cardiac in-
observed that the time needed for urinary output to approx- dex or splanchnic blood flow and metabolism, suggesting
imate the rate of fluid infusion was 20, 27, and 46 hours that PEEP does not affect spla ndmic blood flow. Other fac-
during spontaneous breathing, positive-pressure ventilators, however, sucl1 as hepatic outflow resistance may play
tion, a nd positive-pressure ventilation plus 10 cmH2 0 of a role. 68, 587 In swine, Brienza et al587 found that PEEP of
PEEP, respectively. Priebe et al579 found that renal impair- 15 cmH20 reduced portal vein flow through an increase in
ment caused by 10 cmH2 0 of PEEP in anesthetized dogs liver venous resistance; the authors postulated a direct com-
resulted primarily from a reduction in intravascular vol- pressive effect cau sed by diaphragmatic descent on the liver.
ume. In swine, Venus et al557 found that the addition of Sha et al 584 applied increasing PEEP (up to 20 cmH 20)
PEEP to positive-pressure ventilation caused a fall in cardiac and found proportional decreases in hepatic blood flow.
and urinary output associated with an increase in plasma Because th e rate of decrease in hepatic Do, exceeded that
ADH, renin, epinephrine, and norepinephrine in normo- of cardiac output and hepatic blood flow, the authors con-
volemic animals but not in animals that received volume cluded that hepatic Do, was reducedJrimarily because of
expansion through crystalloids. In six neurologic patients the drop in portal venous 0 2 content.5 More recently, Ane-
with intact cardiopulmonary and renal function receiv- man et al 66 evaluated tl1e impact of PEEP of 10 cmH20 on
ing positive-pressure ventilation plus 15 cmH2 0 of PEEP, mesenteric and hepatic blood flow in patients under general
an increase in lower-body pressure via military antishock anesthesia (during elective surgery for gastric or pancreatic
trousers improved systemic and renal hemodynamics and neoplasm). Neither arterial pressure nor arterial, portal, and
decreased plasma norepinephrine, with no change in total hepatic venous norepinephrine were significantly affected
blood volume.576 Urinary output and sodium excretion did by PEEP.66 A decrease in portal blood flow was associated
not improve. The authors concluded that increased plasma with a rise in mesenteric vascular resistance; conversely, an
renin and sympatl1etic activation were the main determi- increase in hepatic arterial flow was associated with a drop
nants of renal impairment with PEEP.576 in hepatic arterial resistance. 66 Mesenteric Do, was reduced,
Annat et al558 evaluated the short-term effects of 10 and h epatic Do 2 remained unchanged. 66 Mesenteric and
cmH20 of PEEP in normovolemic patients without cardiac hepatic Yo, did not significantly vary with PEEP.66 In
and renal abnormalities and little or no respiratory failure similar patients, Berendes et al56 found that hepatic venous
lacta te did not change with PEEP up to 15 cmH20 and con- affect the process of hmg repair604 and edema remova1. 605
cluded that a critical reduction in splandmic oxygenation Blood from the bronchial vessels is drained to the right side
d oes not occur. of the heart via the azygos and bronchial veins and to the
In ~ontaneously breathing normal subjects, Fournel! left atrium through anastomoses between the systemic and
et al5 recently reported that CPAP levels of up to 10 pulmonary circulation. In ventilated open-chest dogs, Baile
cmHzO progressively altered gastric mucosal microvascu- et aJ60"1 investigated the effect of increasing PEEP on systemic
lar 0 2 saturation, as assessed by reflectance spectropho- to pulmonary (anastomotic) flow (Q bra) and on bronchial
tometry. Lehtipalo et a l57 found that PEEP of 10 cmH20 blood flow (Q br), which was further partitioned into tra-
had little effect on intestinal perfusion pressure; mesenteric cheal, bronchial, and parenchymal fractions. Bronchial and
blood flow and oxygenation were maintained tmtil the in- parenchymal but not tracheal fractions of Q br decreased
testinal perfusion pressure exceeded 33 mmHg. In patients
with PEEP.601 Q b r and Q bra did not differ at PEEP of
with septic shock, Trager et al589 increased PEEP up to 15
3 and 10 cmH 20.601 At PEEP of 15 cmH20 , Q br exceeded
cmH2 0. PEEP decreased cardiac index and hepatic venous
0 2 saturation.589 Hepatic metabolic performance, assessed
Q bra, indicating a decrease in the anastomotic drainage.601
In patients undergoing cardiopulmonary bypass, Agostoni
by glucose production, fell at each PEEP level in patients
et aJ603 observed that an increase in alveolar pressure of
who did not survive, whereas it decreased only at the high-
about 10 cmH20 decreased Q bra by 40%.
est PEEP level among survivors.589
Local release of mediators, a rise in pulmonary vascular
In summary, PEEP may reduce hepatic and splanchnic
resistance, and reflex bronchial vasoconstriction may ex-
blood flow through a drop in cardiac output, although other
med1anisms, such as regional outflow resistance, are likely plain Q bra reduction. 602 To assess the influence of vagal
to be involved. reflexes on PEEP-mediated reductions in Q bra, Lakshmi-
narayan et al 606 isolated and perfused the !.eft lower lobe in
open-chest dogs and found that increasing PEEP froo1 5-15
EFFECTS ON INTRACRANIAL PRESSURE
AND CEREBRAL PERFUSION cmH20 halved Q bra. At PEEP of 5 cmH2 0, bilateral cervi-
High intracranial pressure OCP) and reduced cerebral per- cal vagal cooling decreased Q bra. 606 An increase of PEEP
fusion pressure (CPP) (the difference between mean arte- to 15 cmH2 0 did not further diminish it, suggesting that the
rial pressure and ICP) are common in several acute neu- effect of PEEP on Qbra might be partly vagally mediated.606
rologic and neurosurgical ICU patients, particularly those PEEP may obstruct lymph drainage from the thoracic
who have focal or generalized cerebral edema. Hypoxemic duct into the jugular vein. 605, 607 By altering thoracic lymph
respiratory failure secondary to ALI/ ARDS is a fearful com- return, PEEP might affect edema removal from the lungs.605
plication in these patients, leading to use of PEEP.590
ICP may be altered by PEEP through a rise in rig ht-atrial
pressure, '""hich increases superior vena cava pressure and
hence reduces cerebral venous return. 63, 591•592 The effects of Intrinsic Positive End-Expiratory
PEEP on ICP depend on the amount of intracranial compres- Pressure (PEEP1)
sion and are of little importance w hen cerebral compliance
is no t altered.19 In 25 head-injured patients, Apuzzo et al19 During passive exhalation, airflow is driven by the dif-
found that PEEP caused an increase in ICP in only 12 pa- ference between alveolar (Palv) and airway opening (Pao)
tients who had low cerebral compliance and reduced CPP pressures and opposed by expiratory resistance (Raw,exp).
below 60 mmHg in only six of them. In normal, healthy In the absence of expiratory muscle activity and externally
volunteers, Horma11n et al 593 found that alterations in ICP applied PEEP, Palv corresponds to the elastic recoil of the
and CPP produced by CPAP of 12 cmH20 were slight and respiratory system for a given VT: Palv thus is equal to
not of clinical relevance. Body position also affects the im- Ers/VT or VT/Crs, where Ers and Crs are respiratory sys-
pact of PEEP on ICP. PEEP raises ICP through an increase in tem elastance and compliance, respectively. The product of
the downstream venous pressure; thus, elevating the head Crs and Raw,exp is the expiratory time constant ("r). During
above the d1est should lessen the transmission of intratho- expiration, V = VTe-(t/ r>, where Vis the amount of VT not
racic pressure to the venous sinuses and mitigate the effects yet exhaled (i.e., above FRC), t is the time elapsed from the
of PEEP on ICP. In supine anesthetized patients undergoing onset of expiration, and e is the base of natural logarithms
posterior fossa surgery, Lodrini et al594 found that PEEP of (2.7189). When t = r, Vis roughly 37% (1/2.7189) of VT. It
up to 15 cmH20 caused proportional increases in central takes fiver to almost entirely (99%) exhale VT.
venous pressure and ICP; in the sitting position, PEEP also In healthy adult subjects, r is approximately 0.3 second.
increased central venous pressure, but ICP changed little in Therefore, the time required to exhale VT is about 1.5 sec-
most of the patients. onds. Assuming a respiratory rate of 12 breaths per minute
Several studies in neurologic, neurosurgical, or brain- and an inspiratory duty cycle (T, / TroT) of 40%, expiratory
injured patients found that judicious use of PEEP wa~ not time (T E) is 3 seconds, which considerably exceeds the time
d etrimental, provided that monitoring was adequate. 595 - 600 necessary for the lungs to deflate to FRC. If either breathing
frequency or T1/TroT increase, T E diminishes. Any condi-
EFFECTS ON BRONCHIAL CIRCULATION tion causing an increase in expiratory resistance, including
AND THORACIC LYMPH DRAINAGE an artificial airway, 608 or a loss in elastic recoil prolongs
By increasing intrathoracic pressure, PEEP a lters bronchial t and thus the time required for complete VT exhalation.
blood flow601 - 603 and thoracic lymph drainage, which could When shortened T E and/ or prolonged r impede a complete
0 -IAPTER 11 POSITIVE END-EXPIRATORY PRESSURE 293
1.5 .,.----------------~ specting airway pressure. During controlled ventilation,
PEEP1 can be measured by occluding the airway open-
1.2 . ing a t end expiration for a few seconds80•617 (see Fig. 11-
5), the end-expiratory occlusion maneuver. This value is
tJ. EELV 0.9 · sta tic PEEP, (PEEP 1 , 5~a 1 ). Unless some alveolar units are
(L) not at all communicating with the central airways (be-
0.6 • cause the correspond ing peripheral airways are completely
ocduded), 618 PEEP1,stnt represents the aver age pressure in
0.3 . the different lung regions. 13·87•619- 621 A second approach
is to measure the difference between preset PEEP and
o+-----------,-----------~
. --------~ airway pressure at the onset of ins piratory flow9·1,620,621 ;
0 2 4 this value is dynamic PEEP, (PEEPr,rlyn). PEEP1,dyn can be
Expiratory time considered as the lowest regional end-expiratory alveo-
(sec) lar pressure that has to be overcome to begin inspiratory
FIGURE 11-12 Ef fects of varying expiratory time on flow. 13·87 •619- 621 PEEP l,dyn and PEEP!,stat
. approximate each
end-expiratory trapped volu me in patients with airway other in animals a nd htrmail subjects 621 in the absence of
620
obstruction. AEELV indicates end-expiratory lung volume above severe airway disorders when PEEP, is consequent to TE
functional residual capacity. The shorter the expiratory time, the shortening and/ or increasing VE. In animals receiving high
greater is th e amoun t of end-expiratory trapped volume. Data are doses of aerosolized methacoline620 and pa tients affected
expressed as mean ± standard deviation (dosed circles) and mean
by severe airways obstruction,621 PEEP1,dyn is considerably
± stan dard error (open circles) and tak en from refs. 285 and 4U,
respectively. Tidal volume was always 1liter in ref. 285 and
lower than PEEP~st11t · A low ratio of PEEP1,dyn to PEEPr,stat
averaged 0.576 liter (± 0.026 liter) in ref. 412. In ref. 412, changes in suggests time-constant inequalities within the lung and
expiratory time were obtained b y manipulating th e ventilator high lung tissue viscoelastic pressure losses.222,620- 623
preset ins piratory time while leaving respiratory rate (and hence When the inspiratory muscles are contracting, assessing
minute ventilation) unmodified. In ref. 285, inspiratory duty PEEP, is more complex. When inspiration is active and ex-
cycle remained unchanged, and expiratory time was change by piration relaxed, PEEPI.dyn can be measured with a balloon-
modifying respiratory rate; accordingly, minu te ventilation also tipped esophageal cathet er.5•619·624·625 PEEP1,dyn equals the
varied. difference in esophageal (pleural) pressure between the on-
set of negative deflection (indicating th e s tart of the inspi-
exhalation to FRC, dynamic hyperinflation occurs. End- ratory effort) and the pressure at the transition between
expiratory relaxation volume will exceed FRC to an extent expiratory and inspiratory flow5·619•625 (Fig. 11 -14). When
that is proportional to r and VT and inversely related to TE the expiratory muscles are contracting, which is common
(Fig. 11-12). in flow-limited patients,93·626- 628 especially during partial
Expira tory flow also may be limited in the course of VT ventilator support,5•92•93·629 the pressure d eveloped in the
exhalation because the airways collapse at a choke point abdomen is transmitted thro ugh the r elaxed diaphragm
where intrathoracic pressure equals intrabronchial pressure and raises intrathoracic pressure. Consequen tly, assessing
(so-called equal-pressure point). The airways located down- PEEP, via esophageal pressure will overestima te the true
stream of the equal-pressure point are then compressed end-expiratory elastic r ecoil pressure.5,92,93,626- 630 With a
because intrathoracic pressure exceeds the intrabronchial second balloon-tipped catheter in the stomach, it is possi-
pressure. Thus Palv- Pao no longer represents the pres- ble to measure, and correct for, the amount of intrathoracic
sure driving expiratory flow. Expiratory flow limita tion is pressure rise caused by expiratory muscle contraction5' 92 •93;
very common in patients w ith an acute exacerbation of briefly, the expiratory rise in gastr ic pressure is subtracted
COPD. 87· 609~61 2 It also has been reported in patients w ith from the esophageal pressure at the onset of the subsequent
asthrna,613,614 obesity,334,615 and ARDS.222,223,669,616 inspira tion92•93 (Fig. 11-15). Another method is to subtract
Regardless the underlying mechanism, after a few brea- the rise in gastric pressure during a n end-expiratory oc-
ths, a steady state is achieved that depends on the variations clus ion from airway pressure.631 Partitioning the rise in in-
in the different components of respiratory m echa nics. For a trathoracic pressure from recording of airway, esophageal,
certain trapped volume, the amount ofPEEP 1is determined and gastric pressures is complex and is performed infre-
by the corresponding respiratory system complian ce. quently in the clinical setting.
MEASUREMENT OF PEEP! PHYSIOLOGIC EFFECTS OF PEEP1

PEEP 1can be detected qualitatively by observing the flow- During volume-targeted controlled ventilation, PEEP1does
time curve, available on most ventilators. In absence of not affect VT, whereas it elevates peak airway pressure,
PEEP,, expiratory flow is zero before the onset of the sub- which is a d ependent var iable (i.e., it varies depending on
sequent inspiration (Fig. 11-13A). The persis tence of expira- the impedance of the respiratory system) (Fig .11 -16A). Con-
tory flow at end expiration indicates the presence of PEEP1 versely, during pressure-targeted controlled ventilation, the
during either mechanica l ventilation (see Fig. 11-13 B) or independent variable is the preset positive pressure applied
spontaneous brea thing (see Fig. 11 -13C). to the airway during inspiration; the presence of PEEP1 de-
Because the ventilator built-in pressure gauge is open to creases the actual lung distending pressure and therefore
the atmosphere, PEEP 1 ca1mot be detected simply by in- VT (see Fig. 11-168).
0.5
A
Flow
(Us)
0 ------ ----- ---.---J
- 0.5
8 0.5
Flow
(L/5)
0 ----- -- ----------- --
• 0.5
c 0 . 75 FIGURE 11-13 Flow-time tracings during controlled

ventilation in a normal anesthetized subject (A) and in a
Flow patient with severe COPD during controlled ventilation
(Us) 0 (B) and during spontaneous breathing (C). In the
normal subject (A), expiratory flow reaches zero before
exp iration ends. In the patient with COPD, expiratory
" 0.5 flow remains below zero value before the subsequent
inspiration, denoting dynamic hyperinflation, during
1 sec both controlled ventilation and spontaneous breathing.
FIGURE 11-14 Measurement of dynamic intrinsic

Flo w
tlJ~}
.:J -·-
i
-- ------ -- ---- -
PEEP (PEEP1,dyn l in a spontaneously breathing
patient without expiratory muscle acti vity. The
dashed horizontal line indicates zero flow. The
do tted vertical line indicates the onset of the
.~ J
Esoph.1geal j
........ in spiratory effort. The solid vertical line indicates
Pressure !
(cmH,OI the start of inspiratory flow. Gastric pressure rises
~ during inspiration and falls du.r ing expiration,
Gastric
Pressure
(cmH10I
1: J indicating that expiratory muscles were not active.
PEEP1,dyn is the difference in esophageal pressure
between onset of inspiratory effort and start of
inspiratory flow.
'
2: J
Transdi..,hragma~ic
Pressure
(cmH101 1. /
1 we
0.5 ........ Volume
Flow _ _ Airway pressure
(Us) 0
·0.5 A
10
Esop hageal
.·· -..
Pressure
.·· ....... ..·.·· ··.... ..
(em H20)
·10 ....···
_
.......... _____
....-··
-';
··~-......
. _
..··.
"'- PEEPI - -
10 • _ ..•
0 0
Gastri c VOLUME PRESET VEN TILATION
Pressu re
(cmH,O)
B
0
20
I.-·t·. .·.
Tran sdi aph.-agmatic
Pressure
(cmHtOl
0
0
PRESSURE PRESE T VENTILATION
1 sec
FIGURE U-16 Simu lation of the effects of PEEP, on
FIGURE 11·15 Measu rement of dyn amic intrin sic PEEP volu me-tar geted (Al and pressure-targeted (8) controlled
(PEEP1,dynl in a spontaneously b reathing patient with expiratory ventilati on. Volume and airway pressure arc indicated b y dotted
muscle activity. The dash ed h orizontal line in dicates zero flow. and solid lines, respectively. In the left p an els, when PEEP1 is
The dotted vertical line indicates onset of inspi ratory effort. The absent, tidal volume is the sam e for both modes. In the
solid vertical line indicates the start of inspiratory flow . Unli ke in upper-right panel (A), during volume-targeted ventilation, PEEP1
Fig. 11-14, gastric pressure rises du ring expiration (APga) an d causes a rise in airway pressure, whereas p reset tidal volume is
descends at the following in sp iration, indicating expiratory unchanged. In the lower-right panel (B), during pressure-targeted
muscle recruitment. A Pga must be subtracted from the differen ce ventilation, preset pressure does not vary, and consequently, ti dal
in esophageal p ressure b etween onset of inspiratory effort and volume falls.
start of inspiratory flow to determine PEEP1,dyn·
PEEP1 resembles in several respects external PEEP. In pa- more freq uent at higher ventilator assistance85· 86· 641 because
tients with hypoxemic ARF consequent to ARDS or cardia- of higher PEEP1 consequent to increased lung volume85•86, 641
genic pulmonary edema, an increase in EELV, produced and diminished respiratory drive .64'~
byTE shortening, secondary to tachypnea or inverse-ratio Acute hyperinflation impairs the force-generating capac-
ventilation can decrease intrapulmonary shunt as much ity of the diaphragm by moving the diaphragm to an in-
as can external PEEP.632 In patients without COPD, Bran- efficient part of its force-length relationshlp2 8.643•644 and in-
dolese et al231 found that external PEEP produced more creasing the 0 2 cost of breathlng.645 In healthy volun teers,
consistent increases in Pa 0 1 than did an equivalent level Beck et al646 showed that greater d iaphragmatic activation
of PEEP1. The au thors attributed the less favorable impact to generate a certain amoun t of p ressu re increased with
of PEEP, on Pae>z to less homogeneous gas distribution increasing lung volume, and pressure generated by max-
between different lung units. 231 PEEP, decreases cardiac imal diaphragmatic activation decreased with increasing
output80·87·231 ·632 and blood pressure80•87 to a similar extent lw1g volume. In spontaneously breathing dogs, Kawagoe
to that produced by external PEEP for the same increase in et al 647 found that a threshold load associated w ith PEEP 1
lung volume. 632 Connery et a l633 reported fatal cardiac arrest produced p ulmonary artery hypertension and decreases in
and life-threatening hypotension during manual ven tilation cardiac output and blood flow to the liver, pancreas, and
with large Vr and high respir atory frequencies in two pa- sternomastoid an d parasternal muscles with little change in
tients "vith severe COPD. By increasing alveolar pressure, blood flow to the diaphragm. 647 An equivalent resistive load
PEEP1 also may cause barotrauma.68 increased diaphragmatic blood flow without changes in car-
In spontaneously breathing patients, PEEP1 poses a diac output or regional blood flow. 647 Both loads produced
threshold load that has to be overcome before inspiratory noncompensated respiratory acidosis, but the severity was
flow can be initiated13•619•624•634; this load is perceived as in- greater for the threshold load.647 An acute inspiratory
spiratory d ifficulty.6.15 With any mode of partial ventilator threshold load causes a greater diaphragmatic sarcomere
support, this thr eshold mu st be overcome before the ven- disruption in patien ts with COPD than in patients without
tilator can be triggered5•83•85•625•636- 639 (Fig. 11 -17). Inspira- lung disease648; hyperinflation explaines about 40% of the
tory efforts that are not intense enough to overcome PEEP1 injury.64s
fail to trigger the ventilator,85•86, 640- 642 a p henomenon re- The complex interaction of dynamic hyperinflation and
ferred to as WIISted or ineffective inspiratory efforts (Fig. 11-18). PEEP1 on preload has been reviewed by Ranieri et ai.649
Wasted efforts occur with all triggered mod es641 and are During spontaneous breathing o r triggered ventilation,
1
Flow I
(Us) 0
I
-------------------------
·1
15
Airway
Pressure
(em H2 0 ) FIGURE 11-17 Effect of intrinsic PEEP (PEEP 1) on
ven tilator triggering. The dashed horizontal line
0 indicates zero flow . The dash ed vertical line on
the left indicates the onset of the insp iratory
effort. The dotted vertical line on the right
corresponds to the start of inspiratory flow . The
15 solid vertical line indicates the point at which the
Transdiaphragmatic ventilator is triggered a.n d mechanical assistance
is initiated. The amount of effort sp ent in
Pressure overcoming PEEP 1 corresponds to th e difference
(emH2 0)
in transdiaphragmatic pressure between the
0 points crossed by the dashed and solid lines .
PEEP 1 increases the magnitude of the inspiratory
/ \0.09 s effort and remarkably lengthens the
0.22 s effort-to-assist delay.
venous return is decreased by the higher EELV and

intrathoracic pressure or increased by the larger negative
inspiratory swings in intrathoracic pressure, w ith the latter
FIGURE U-18 Ineffective or wasted inspiratory efforts. The dominating.64 9 PEEP1 also might affect left-ventricular
dashed horizontal line on the flow tracing indicates zero. The function by augmenting the afterload, although this
dashed vertical line indicates the onset of ventilator assistance. To
possibility has not been studied .
the left of the dashed line, the patient is breathing spontaneously
with the ventilator set in CPAP mode. The breathing pattern is
rapid and shallow. Initiation of pressure support increases tidal CLINICAL CONSEQUENCES O F PEEP1
volume and decreases respiratory rate, as assessed on the flow
The extra load imposed on the respiratory muscles by
and airway pressure tracings. The respiratory rate, assessed by
PEEP1 may be large (Fig. 11-19) and have relevant clinical
swings in esophageal pressure, is higher. The arrows show that
half the inspiratory efforts fails to trigger the ventilator. The consequences. In patients with COPD in ARF, Coussa et
dotted horizontal lines on the volume tracing indicate that al 650 found that work of breathing was increased because of
end-expiratory lung volume increased after institution of increas ed resistance and P EEP1. PEEP1 accounted for more
pressure support (dynamic hyperinflation). than 30% of the overall workload (see Fig. 11-19 A). In venti-
lator-d ependent patients w ith COPD, Appendini et a l86
found tha t the effort to overcome PEEP1accounted for more
Flow than 40% of overall inspiratory effortB6 (see Fig. 11-19 B).
(US)
Jubran et al651 studied 31 patients with COPD undergoing
aT-tube trial, 17 of w hom failed and 14 of whom were extu-
bated successfully (see Fig. 11-19 C). At the onset of the trial,
PEEP1 was higher in the failure group than in the success
Volume group.65l Between the start and end of the trial, the fraction
(l)
of inspiratory effort caused by PEEP1 more than doubled in
the failure group, whereas it did not change in the success
group.651
In 30 patients who failed an initial weaning trial but
w ho later succeeded, Vassilakopoulos et al 652 found that
dy namic hyperinflation and PEEP1 were higher at the time
of weaning failure.
I I 1 I
Esophageal
Pressure
(cmH2 0)
1]
-1
IMPACT OF EXTERNAL PEEP O N DYNAMIC
HYPERINFLATION AND PEEP1
Depending on the mecl1anisms of dynamic hyperinflation
10 sec
and PEEP1, external PEEP can have different effects, as
B c
lll ~~
-. - 22%
~
32.7'!'.
~"'
• woe A" a PTP~n PrP\l!£$.._1n

WOOe_ PTPtL.Inn ') PTPcs.lnn
• WOB l'rmor • PfP 1'!!1'• J""" • PTPft-er•l"'"'
FIGURE 11-19 Fractions of the respiratory load in ventil ator-depend ent patients with COPD. A. Elas tic (El), resistive (RES), and PEEP1
fractions o.f work of breathing (WOB) in sedated and paralyzed patients with COPD in acute respiratory fajJure whil e receivi ng controlled
ven tilation. (From CoriSSa et a/: J Appl Physio / 1993; 75: 1711- 9.) B. Elastic (EL), resistive (RES), an d PEEP1 comp onents of inspiratory effort,
assessed as esophageal pressure-time prod uct (PTP), duri ng a brief period of spontaneous breathing in patients wit.h COPD who cou ld not
b e weaned (From Appeml iui et al: Am J R espir Crit Care Med 1997; 149:1069-76.). C. Sam e measurement as in B in patients with COPD who
failed a T-tube trial (From Jubra el a/: Am J R espir Cri t Ca re Med 1997; 155:906.) Despite th e d ifferent settings, PEEP1 accO\mted for a
considerable fraction of inspiratory load.
elegantly pointed out by Marini653 (Fig. 11-20). When PEEP1 that PEEP of 10 cmH2 0 produced a small increase in total
is not caused by flow limitation, external PEEP is transmit- PEEP and alveolar recruitment bu t a significant increase in
ted entirely to the d istal airway, p rodu cin g a concomitant Pa0z; the latter was attribu ted to improved regiona l PEEP1
rise in alveolar pressure (see Fig. 11-208). In six patients inhomogeneity. In another group of patients who did not ex-
with acute as thma or a COPD exacerbation, Tuxen et al 285 hibit flow limitation and had little PEEP,, PEEP oflO cmH20
increased dynamic hyperinflation and PEEP1 by increasing
'ih from 10 to 16 and to 22 liters/min. Increasing levels of
FIG URE 11-20 Sd 1ematic representation of the effects of
PEEP up to 15 cmH20 produ ced increases in EELV and
PEEP on alveolar p ressure in normal conditions (A), high airway
intrathoracic pressure, accompan ied by a parallel hemody- resistance bu t no expiratory flow limitation (B), and expiratory
namic deterioration. 285 At the lowest VE, trapped volume flow limitation and dyn amic airway compression (C). The circles
was small, suggesting little, if any, flow limitation. 285 represent the alveoli, th e rectangles the ven tilator, and the tubes
When flow limitation and dynamic airway compression the bron chi. PEEP, positive end-expiratory pressure expressed in
are present, PEEP is not transmitted to the distal airway cmH2 0 ; Rexp, expiratory resistance, expressed in cmH 2 0/Iiter/s;
and does not increase alveolar p ressu re as long as it does ZEEP, zero positive end-expiratory pressure. A . At ZEEP
not exceed the critical p ressure corresponding to the choke (left panel), the alveolar pressure falls to zero. Applied PEEP (riglzt
p mrel) is transmitted entirely to the alveoli. B. At ZEEP (left panel),
point653 (see Fig. 11-20C). The waterfall analogy helps in
the high expiratocry resistance causes alveolar pressure to remain
w1derstanding this concept. The equal-pressure point is
positive at end expiration. Applied PEEP (righ t panel) is trans-
viewed as the crest of a waterfall, and the airway segment mitted entirely to the alveoli. C. At ZEEP (left panel), the alveolar
between the choke point and the airway opening is seen as as pressure is positive. Applied PEEP docs not exceed the critical
the downstream water. 654•655 Increasing the level of down- pressure at the choke poin t and does not affect alveolar pressure.
stream water (external PEEP) does not alter upstream water A
flow (airflow) as long as it does n ot exceed the cr est (critical
pressure at the choke point). 655 Jn flow-limited patien ts w ith Rexp 5 r-----. Rexp 5
COPD who had PEEP1 of 10 cmH 20 and trapped volume of ZEEP PEEP
l liter, Ranieri et al87 applied PEEP of 5, 10, and 15 cmH2 0. 10
Up to PEEP of 10 cmH 20, ch anges in peak and p lateau air--
way pressures, EELV, and total PEEP (i.e., PEEP1 +external e
PEEP) were minimal; hemodynamic impairment was ab-
sent. PEEP of 15 cmH 20 increased peak and plateau airway Rexp 30 ,.....---.
pressures, trapped volume, an d total PEEP, with worsen- ZEEP PEEP
ing of hemodynamics. 87 Ch anges in EELV and cardiac in- 10
dex started to occur when external PEEP matched about
85% of PEEP1,stat. 87 In flow-limited patients with COPD re-
ceiving triggered ventilation, Appendini et a15 found tha t c
PEEP slightly lower than PEEP1,dyn did no t cause furth er Fl ow Flow
hyperinflation.
Recent studies show that flow limitation associated with
small airways closure and P EEP1 may be present in venti-
---- Limitation
ZEEP
.--... Limitation
PEEP
lated patients with ARDS. 222 In patients w ith ARDS who 10
have flow limitation and PEEP1, Kou tsoukou et al223 found
increased total PEEP and produced greater alveolar recruit- tients with ALI/ ARDS to high or low PEEP levels to de-
ment, which was the chief reason for an increase in Pa0z.223 ter mine whether high PEEP, by enhancing lung recruit-
Analogous results were reported by Vieillard-Baron et at,399 ment, might reduce VILI and improve outcome664 (see Ta-
who found flow limitation and PEEP1in 73% of patients with ble 11-2). In both groups, VT and plateau pressure were
ARDS receiving volume-controlled ventilation. 6 ml/kg and less than 30 cmH2 0, respectively. PEEP was
In actively breathing patients, the threshold load imposed titrated, according to predefined combinations of PEEP and
by PEEP1 may be offset by applying CPAP13,81,82·656 or ex- F10z, to achieve an identical goal (Paol of 55-88 mmHg or
ternal PEEP.5 •83•85• 63'7 I£ excessive or improperly applied, 653 Sp0z of 88-95%).664 The study was interrupted after enroll-
external PEEP can worsen hyperin£lation,87, 65? ,658 placing ment of 549 patients because no difference was detected
the diaphragm at an additional disadvantage28·644·646 and in any predefined clinical outcome variable between the
causing further hemodynamic impairment.87.65 7 two groups.664 Some methodologic biases cast doubt on the
condusions.668
An imbalance occurred in baseline characteristics of the
Use of PEEP in the Clinical Setting two groups (higher Pa<h/F10z ratio and younger age in fa-
vor of the lower PEEP group). The protocol was amended
during the study in order to achieve a greater differ-
ALJ!ARDS
ence in PEEP between the groups, which raises concerns
The rationale for PEEP in patients with ALI/ ARDS is to in- about the validity of the analysis. 669 When analysis is con-
crease the amount of aerated lung volume, 71•236•270 improve fined to patients enrolled after the protocol was amended
respiratory mechanics/ 1•73•236 reduce intrapulmonary and after adjusting for differences in baseline characteris-
shunt182·659 and ameliorate gas exchange, 4•34•71 ·11 9•236 tics, the mortality is lower in the high-PEEP than in the
stabilize unsteady lung units,660 and reduce the risk of low-PEEP group (28% versus 33%), suggesting that the
VILI. 73•437 From its introduction a lmost 40 years ago,4 PEEP trial was interrupted prematurely.669 PEEP-induced recruit-
remains a cornerstone in management of patients with ment was estimated by improvement in oxygenation. It
ALI/ ARDS. 661 It is easy to see why no randomized trial is well known that changes in oxygenation depend not
evaluated ventilator strategies without PEEP in patients only on recruitment but also on cardiac output.60· 180·182, 230
with AU/ ARDS, except in the very early phase. 192•662 Thus oxygenation may have improved without any lung
Very few studies have assessed the effect of PEEP on recruitment.
clinical outcome of patients with ALI/ ARDS9 •70·663, 664 Grasso et al378 recently analyzed the physiologic effects
(Table 11-2). One early study reported that high PEEP of the ALVEOLI protocol. They demons trated that the pro-
levels did not improve survival and caused more adverse tocol has unpredictable effects on lung recruitment. Indeed,
events when compared with patients treated with low the protocol may increase the risk of overdistension when
PEEP. 70 high PEEP is applied in patients with a low potential for
In the last decade, research has focused on ventilato r recruitment. Moreover, a supplementary analysis of data
strategies that protect the lung from VILJ. As stated in a collected by a large international survey29 found that the
recent editorial, 665 these investigations have shown that use of low or no PEEP was an independent risk factor for
ventilator settings per se may affect outcome. 420 Two re- ICU mortality in patients with ARDS. 670
cent randomized, controlled trials suggest that high lev- In ARDS, lung units are unstable and have a s trong ten-
els of PEEP (15-20 cmH20), used in the context of a lung- dency to collapse. Thus any ventilator circuit disconnection
protective strategy, may improve both the physiologic419 or leakage leading to a complete or partial drop in pressure
and dinical 9 outcome in patients with ALI/ ARDS. Am- can cause harmful falls in lung volume and oxygenation.360
ato et al 9 found that low VT combined with PEEP set 2 Several approaches have been proposed for setting
cmH 20 above the LIP (16 cmH20 , on average) reduced PEEP, but none has proved to enhance any clinical
mortality compared with a conventional approach where outcome9, 16, 18,69,70,205,239,369,381,366,664,67H\76 (Table ll-3). Op-
PEEP was titrated to optimize oxygenation (see Table 11- timal PEEP in ALI/ ARDS should recruit as much nonaer-
2). Ranieri et al419 compared a strategy of high PEEP and ated lung as possible while avoiding lung overdistension,
low VT, respectively, based on LIP and UIP against a con- hemodynamic impairment, and global and regional distur-
ventional approach where lower PEEP and higher VT were bances of~ balance (Fig. 11-21 ). The choice of optimal PEEP
targeted to normalize gas exchange (see Table 11-2). The in patients with ALI/ ARDS remains an open issue. Two on-
control group exhibited more inflammatory mediators than going multicenter trials (in France and Canada) should help
the lung-protective group.419 The control group also had to resolve this question.
a higher rate of organ failure and mortality and fewer Despite strong physiologic rationale, no study to date has
ventilator-free days.419• 4~ The occurrence of PEEP1, conse- assessed whether setting PEEP according to respiratory me-
quent to a high resJ::iratory rate in the low VT group, may chanics improves outcome. An approach based on real-time
have contributed 66 ·667 to the positive results in the ARDS continuous analysis of the dynamic airway pressure-time
Network comparison of low and high VT in patients with profile has been prof.osed for optimizing ventilator settings
ARDS.420 in ALI/ ARDS. 239·3 9 •677 In animal studies, this approach
Only one randomized trial has compared the impact predicts a ventilator strategy that minimizes VILI. 397, 677
of different levels of PEEP on clinical end points.664 The The implementation of automatic tools that facilitate
second ARDS Network (ALVEOLI) trial randomized pa- standardized assessment and continuous monitoring of
TABLE 11-2 Randomized Contro lled Trials Evaluati ng the Effect of PEEP on C llnical and Physi ologic Outcomes
No. of Associ.\ ted PEEP Mean PEEP

R~ference Population Arm Patients Settings Setting (cmH2 0l Outcomes
Amnto 1995 Medical Interventi on 15 VT <6 ml/kg 2cmH20> LIP 18 Successful weaning: 87<'/o
(72) PIP < 40 cmH,O (minimum 5 cmH2 0) Mortality: 33%
CPAP recruitins Barotrauma: 13%
Control 13 VT=12ml/ kg Titrated to P / F mtio 7 Successful weaning: 46%
PII" unlimited (minimum 5 cmi-I20) Mort<'llity: 54%
Barotrauma; 31 %
Amato 1998 Medical intervention 29 VT < 6ml/kg 2cmH20 > liP 16 Mortality: 45%
(9) PlP < 40 em H20 (minimum 5 cmH20) Barotrauma: 7%
CPAP rc><:ruiting
Control 24 VT = 12ml/ kg Titrated to P / F ratio 7 Mortality: 71 %
I'll" Ul'llimited (mittimum 5 em H 20) Barotrauma: 42%
Ranieri l999 Medical-Surgical Tntervention 18 VT for Pplat < UIP 2-3 em H 20 > LIP 15 BA L/systemic levels of inllammatory media tors:
(419) (or VT =5-8 ml/kg) (minimum 15 cmH20) l
Ventilator-free days: 12•
N Mortality: 38%,.
(.0
(.0 Organ f:.ilure score: unchcmged
Control 19 VTforPaCO, Titrated to SaO, 7 BAL/systcmic levels of inflammatory media tors:
35-40 mmi-Ig (minimu m 5 etnl-120} t
Pplat < 35 cmH20 Ventilator-free days: 4 •
Mortality: W k•
Organ failure score: incrl.oased (mainly renal)
Browe:r 2004 Medical-Surgical h\tervention 270 VT = 6ml/kg lit rated to oxygenatiOJ\ 13 .... Mortality: 25%•"'•
(664) Pplat < 30 cmH20 (minimum 12 cmH20) Unassisted breathing: n%
Barotrauma: 11%
Days vdthout organ failure: 16
Control 273 VT=6ml/kg 11tratcd to oxyg·cnation 8 Mortality: 28"/o' ..
Pplat < 30 cmH,O (minimum 5 cmli20) Unassi!oted breathing: 73%
Barotrauma: 10%
Davs. without or an failure: 16
ABBREVJAnONS. VT: tidal volume, PlP: pt:~k inspir<'ltory pressure, CrAP: oonlinuous positive airway pressure, Pplat: plateau pressure, UP; lower iilflCction polnt Oll the pressure-volume curve, P/F: rntio between
nrterial oxygen tension and fr.'LctiOOt'll inspired oJCyge1,, 530.~: ortf'rial oxygen saturl.'ltion, BAl.: brOI\Choalvrolt~.r lavage.
"post hoc ann lysis.
"" ltller protocol ;•unenclment.
"""'after adjustmenl for differences in baseline oovariates:.
TABLE ll-3 Methods for Selecting Optimal PEEP
Reference Year PEEP Target Proposed Method

Suter (18) 1975 Maximal oxygen deliver y Maximal static compliance during stepwise
incrementa l PEEP
Kirby (16) 1975 Intrapulmonary shunt < 15% Stepwise incremental PEEP to reach the target, while
supporting cardiac output with fluids and
vasopressors
Hurewi tz (674) 1981 Drop of mix£-d venous oxygen tension Stepwise incremental PEEP to reach the target
Weisman (675) 1982 Adequate Pa02 with minimal Fi02 Stepwise incremental PEEP to reach the target
Murray (676) 1984 Min.imal arterial~nd-tidal CDl gradient Stepwise incremental PEEP to reach the target
Matamis (381) 1984 Best improvement in gas exchange, PEEP set at the lower inflection point on
in trapulmonary shunt and respiratory inspiratory P-V curve
mechanics
Albert (69) 1985 Adequate Pa~ with Fi~ < 0.6 Lowest PEEP to reach the target
Hartman (673) 1992 Maximal peripheral tissue per fusion Maximal subcutaneous oxygen tension during stepwise
incremental PEEP
Gattinoni (205) 1993 Prevention of compression a telectasis Maximal PEEP (equal to superimposed hydrosta tic
pressure) con-esponds to 70% of the dorsal-ventral
height of thorax (in em)
Ranieri (239) 1994 Linear airway pressure-time profile PEEP variations to reach the target
Amato (9) 1998 Maximal recruitment PEEP set 2 cmH2 0 above the lower inflection point on
inspiratory P-V curve
Hickling (386) 2001 Maximal static compliance Stepwise decremental PEEP trial
Rouby (369) 2002 Best oxygenation wi th the lowest Fi02 (> 0.6) Lung morphology, slope and inflection points of
the P-V curve, PEEP trial
Brower (664) 2004 Oxygenation (Pa02 55-80 mmHg, SpDl 88-95%) PEEP-Fi02 combination table
ABBREVL-\TIONs . Fi02 : fractional inspired oxygen, C~: carbon dioxide, Pa~: arterial oxygen tension, S~: percutaneous oxygen saturation.
respiratory mechanics might allow this approach to be in- received CPAP at the end of treatment had higher oxygena-
corporated into the clinical setting. tion and lower rates of pneumonia, infection, and sepsis
than the 0 2 group. 696 Although limited to selected patients
tmdergoing elective abdominal surgery, these data show
POSTOPERATIVE STATE
that improvement in physiologic parameters achieved with
Postoperative hypoxemia is mainly caused by a telec- CPAP can translate into a better clinical outcome. Of note,
tasis133·144·678 After various surgical procedures, atelecta- CPAP was applied almost continuous ly for a prolonged
sis develops in 30-50% of cases679 and leads to ARF re- time (19 ± 22 hours).696
quiring intubation and mechanical ventila tion in 8-10% In summary, CPAP is a simple, practical, and safe tech-
of patients.679- 682 The application of CPAP (5-10 cmH20) nique for managing postoperative hypoxemia. It may im-
via a face mask, alone or combined with pressure sup- prove outcome in selected patients, provided that it is a p-
port, reduces atelectasis and improves oxygenation after plied for a sufficient time.
both cardiac176·683 and noncardiac surgery248•684 - 687 with-
out increasing surgical complications, such as anastomotic
COPD
leaks. 688 By reducing atelectasis, CPAP may decrease bac-
terial growth in the lung, mitigating bacteria] transloca- ARF in patients w ith COPD is characterized by high air-
tion into the bloodstream and normalizing alveolocapillary ways resistance and PEEPt,215·619·624•650•697 which increase
permeability.689·690 respiratory muscle load.5 ·83 •86•624·•640 Hyperinflation s imul-
Ons et and duration of CPAP seem to be critical for avoid- taneously reduces the force-generating capacity of the
ing or reversing atelectasis. Studies that failed to demon- diaphragm.28,646 When the force-load balance is altered to
strate benefit used CPAP several hours after surgery691 or for a level that severe respira tory acidosis ensues, mechanical
a relatively short time.692- 694 Despite well-recognized phys- ventilation becom es necessary. 1l1e ventilator acts as an ac-
iologic benefits, only very recently have randomized trials cessory pump that helps to reverse the urtfavorable force-
assessed the effects of CPAP on outcome variables.695·696 In load balance. By reducing 02 cost of breathing and correct-
70 patients, Fagevik Olsen et al695 reported that compared ing arterial blood gases, mecl1ru1ical ventilation can improve
with breathing exercises, use of CPAP after thoracoabdom- respira tory muscle function (force). Inspiratory assistance
inal resection of esophageal cancer resulted in a lower intu- by the ventilator, however, does not reduce the inspiratory
bation rate. Squadrone et a1 696 r andomized patients w ho de- resistive load consequent to airway resistance or the thresh-
veloped hypoxemia following major abdominal surgery to old load conseguent to PEEPJ.
either 0 2 alone (FI~ of 50%) or 0 2 plus CPAP of 7.5 cmH20. Pharmacotherapy can have favorable effects on both
The study was interrupted after 209 patients were enrolled load reduction and force restoration.698 Agents act
because the intubation rate was lower in the CPAP group on bronchial smooth muscle ({3 2 agonists, a nticholin-
than in the 0 2 group (1% versus 10%).696 The patients who ergic)699- 702 or inflammatory process (glucocorticoids and
Plateau pressure= 30 cm~O
VT of S-8 ml/kg PBW
Pressure range within which PEEP shou ld be individually set
Evaluation of potenti al for recruitment and overdistension Hemodynamic consequences of PEEP
a Morphology of lung mjury (chest X-ray and/or CT scan) a. Arterial blood pressure
b. t!EELV and Vrec with different PEEP (5-10-15-20 cmH,O) b. Arterial systolic and pulse pressures variation
(JJ-V curve, equal pressure method)
c. Unear compliance of the P-V curve at ZEEP or low PEEP (I.e. 5 cmH,O)
(est1mated by sequential Cst calculation with incremental VT s1ze)
d Pa~ and PaC02 changes with different PEEP (5-10-15-20 cmH20 )
Low potential for recruitment I High risk of overdistension I Hemodynamic impairment: PEEP 7-12 cmH2 0
High potential for recru1tment I Low risk of overdistension I No hemodynamic impairment: : PEEP~ 15 cmH2 0
FIGURE 11-21 Proposed algorithm for setting PEEP in ALJ/ARDS. Firs t, a safe plateau pressure limit of 30 cmH20 is recommended; it
should not be exceeded except when chest-wall compliance is very low. Second, VT is preset, which corresp onds to a certain pressure
oscillation. Third, PEEP should not exceed the pressure difference between plateau pressure and the tidal press ure oscillation. After
hemodynamic stabilization, the potential for recruitment, the risk of overdistension, and the hemodynamic consequ ences are assessed
individually for different levels of PEEP. Potential for recruitment is greater when (1) lung injury is diffuse, (2) alveolar recruitment is
large (i.e., > 100 ml), (3) the ratio between alveolar recruitment and change in end-expiratory lung volume is high (> 15-20%), (4) linear
compliance of the pressure-volume curve at 0 cmH 2 0 is high (> 40 mUcmH 2 0), (5) static compliance measured at low or no PEEP
progressively increases with increasing VT, and (6) Pao 1 increases and Pac 02 decreases concomitantly. By contrast, the risk for
overdistension is greater when changes in the preceding parameters go in the opposite direction. PEEP-induced hemodynamic impairment
may be considered clinically relevant when arterial systolic pressure falls more than 20 mmHg and/or variations in both arterial systolic
pressure or pulse pressure appear or incr ease. Cs t, stati c compliance; CT, computed tomography; AEELV, change in en d-expiratory lung
volume; PBW, predicted body weight; Vrec, recruited volume; VT, tidal volume.
antibiotics).699•700, 702.703 These agents decrease aitways re- cliac function.649 During triggered ventilation, PEEP re-
sistance, dynamic hyperinflation, and PEEP1 in ventilated duces inspiratory effort5•83•85•637 and ventilato?' drive637 and
patients? 04- 709 Glucocorticoids and antibiotics commonly facilitates triggering of the ventilator'l·83•85•63 by reducing
are administered parenterally. In ventilated patients, bron- both inspiratory effort and the delay between the onset
chod ila tors are given more effectively and safely via a small- of inspira tory effort and initiation of assistance, improv-
volume nebulizer or a metered-dose inhaler connected to an ing patient-ventilator interaction and reducing ineffective
appropriate spacer? 10 inspiratory efforts. 85•86
External PEEP reduces the threshold load imposed on the Despite a large body of physiologic data, no randomized
inspiratory muscles. PEEP, however, does not reduce hyper- trial has evaluated the effectiveness of PEEP /CPAP in im-
inflation and its effects on diaphragmatic force-generating proving outcome in ventila ted patients with COPD. Most
capacity. Application of PEEP in patients with COPD may trials, however, that evaluated the effectiveness of nonin-
cause a decrease in expiratory r esistance and promote vasive ventilation in patients with acute hyp ercapnia sec-
a faster and more tmiform lung emptying,4" 0 although ondary to COPD exacerba tion used PEEP of 4-5 cmH2 0 in
the clinical relevance of these findings remains to be de~ addition to pressure support.711 - 71 3
termined. CPAP is effective in reducing d yspnea/ 3•81,656 A new ventilator has been described that uses diaphrag-
decreasing work of breathing,13•81 •82. 656 and improving car~ matic electrical activity, measured with an electrode array
in the lower esophagus, to trigger the ventilator. 714 The ven- pared CPAP versus bilevel positive airway pressure (BiPAP)
tilator is triggered, irrespective of PEEP1, as soon as the (i.e., PEEP plus inspiratory pressure support).195 Two re-
diaphragm contracts.714 The " neural trigger" may enhance cent trials have compared standard treatment alone versus
patient-ventilator coordination markedly by reducing the CPAP and versus BiPAP.726·727 That is, seven trials have com-
delay between onset of inspiratory effort and initiation of pared CPAP versus standard treatment14,Hl2,187,194,724,726,727
machine support without the need for external PEEP. Thus (Table 11-4) and four trials CPAP versus BiPAP195•725- 727
this system might eliminate the difficulties in selecting ap- (Table 11-5).
propriate PEEP and avoid further hyperinflation.714 Only four studies194; I9S,7>.5, n7 had been powered a pri-
ori, according to their primary end points. Three trials
ACUTE SEVERE ASTHMA were interrupted prematurely after interim analysis. L' Her
et aJ194 found that mortality after 48 hours was lower in
Patients with acute severe asthma have high airway resis- a CPAP group than in the standard therapy group. Park
tance, dynamic hyperinflation, and PEEP1, which increase et af27 suspended their study because the intubation rate
respiratory muscles load and decrease force-generation was higher in the standard therapy group than in the
capacity.715 These patients generally are less responsive to CPAP and BiPAP groups. Metha et al 195 interrupted their
external PEEP. 285 Although some flow limitation may be study because myocardial infarction was increased in the
present,613 the main cause of dynamic hyperinflation and BiPAP group. With the exception of the study by Lin et
PEEP1 is the prolonged time constant secondary to the al,1 87 the other studies included few patients (risk of type II
high expiratory resistance. In the absence of flow limitation, error).
PEEP increases hyperinflation and alveolar pressure.653•716 The seven studies comparing CPAP versus standard
Some alveolar units may be entirely occluded by mucus treatment14•1112•187·194·724·726·7i7 included a total of 191 pa-
plugs and thus completely disconnected from the central tients receiving CPAP and 197 control patients (see Table
airway. 618 11-4). CPAP was 10 cmH20 in four studies,14·102·724·726•727
Low levels of CPAP may decrease breathlessness? 17- 719 7.5 cmH20 in one s tudy,194 and varied beh-veen 2.5 and
Lin et al72° reported that CPAP reduced the broncllial re- 12.5 cmH20 in one study.187 CPAP produced a greater and
activity. In patients with asthma exposed to aerosolized more rapid (10-180 minutes) physiologic improvement in
histamine, Martin et al721 found that CPAP of 12 cmH20 all sh1dies but one.726 Five studies 14• 102. 187•194·n4 reported a
decreased both esophageal and transdiaphragmatic pres- prompter and greater improvement in oxygenation with
sure swings. VE increased, and thus inspiratory work did CPAP, although in only three studies14•194·724 was Pa02 /Fio2
not fall. 721 Meduri et al/22 in a series that included 17 pa- assessed. Only Bersten et al,14 who included patients w ith
tients with acute asthma, reported thatCPAP of3-5 cmH20 the most severe acidemia, observed improvements in pH
combined with pressure support via a face mask improved and Paco2 with CPAP. Dyspnea was reduced by CPAP in
gas exchange. Only two patients failed and required en- two studies194,727 but not in a third study. 726 CPAP produced
dotraclleal intubation.722 ln a randomized trial of 30 pa- a lower rate of therapeutic failure and intubation in four
tients treated in an emergency department for acute asthma, studies14•187·194·727 and decreased hospital mortality in only
Sorosky et al 723 found that noninvasive ventilation with low one s tudy. 726 None of the seven studies revealed differences
CPAP produced greater and faster improvements in lung in the length of hospital stay.
function and a lower rate of hospitalization than did stan- The four studies comparing CPAP with BiPAP195•725- 727
dard therapy. 723 included a total of 82 CPAP and 87 BiPAP patients (see Ta-
ln summary, use of PEEP in patients receiving mechanical ble 11 -5). All studies used CPAP of 10 cmH 20. The setting
ventilation for acute severe asthma is often detrimental and of BiPAP varied. Park et aJ127 added a small level of l PAP
thus is not advisable. Very few data suggest that low levels of to EPAP of 10 em H20. Mehta et al195 and Crane e t af26 de-
noninvas ive CPAP combined with pressure support in less creased EPAP from 10 to 5 cmH20 and raised IPAP to 15
severe and selected patients might be beneficial, although cmH20 in order to achieve a mean pressure of 10 cmH20
further evaluation is required. throughout the entire breath in both gro ups. Bellone et af25
also used PEEP of 5 cmH20 and an initial pressure support
of 15 cmH 20 (i.e., lPAP of 20 cmH2 0).
CARDIOGENIC PULMONARY EDEMA
Mehta et aJ 195 found a more rapid reductio n in Paco, and
The benefit of CPAP on the failing left ventricle has been other physiologic variables with BiPAP than with CPAP.
discussed already (see Fig. 11-11). Although most of pa- The other three studies725- 727 did not find differences in
tients may respond positively to standard medical treat- early physiologic variables. Three studies195•725·727 did not
ment, some do not and require endotracheal intubation and reveal differences in any clinical outcome variable. Crane et
ventilator assistance. al726 found hospital survival higher in the CPAP than in the
Over the last two decades, there has been growing BiPAP group. Bellone et al,725 Park et al,727 and Crane et al 726
interest in the delivery of CPAP via a face mask as a did not find differences in the incidence of myocardial in-
means of avoiding endotracheal intubation and invasive farction between groups.
mechanical ventilation. Five randomized, controlled tri- ln summary, there are sufficient data to support the use
als have performed head-to-head comparisons of CPAP of CPAP (10 cmH20) for achieving prompt physiologic im-
versus standard therapy in patients with cardiogenic pul- provement and a lower rate of endotracheal intubation in
monary edema.1 4· 102· 187·194•724 Two trials195·725 have com- patients with cardiogenic pulmonary edema. CPAP should
TABLE11-4 Randomized Controlled Trials Compari ng Medical T herapy Alone vers us Medical Therapy Plus CPAP
Early Physiologic Outcomes

In tervention (10 to 180 minutes)
SMT SMT C PAP CPAP Clinical Outcomes

Sotrrce, Sample + vs. vs. vs.
yr Size SMT CPAP Baseline Baseline SMT SMT CPAP
Rasanen, n =20 RR b a ns Treatment failure no (%) 13 (65) 7 (36)

1985 SMT HR a b c Intubation and /or MV no (%) 12 (60) 6 (31)
(ref. 102) n :;:;l9 CPAP SBP ns b ns Hospital Mortality no(%) 6 (30) 3 (15)
CPAP 10cmHz0 pH ns b ns ICU Stay (days) Mean ± SD NA A
PaCOz ns a ns Hospital Stay (days) Mean ± SD NA 1A
PaOz ns a c
Bersten, n =20 RR ns a c Treabnent failure no(%) 9 (45) 0 (0) c
1991 SMT HR ns b d Intubation and I or MV no (%) 7 (35) 0 (0) c
(ref. 14) n = 19 CPAP SBP ns ns ns Hospital Morta lity no(%) 4 (20) 2 (10)
CPAP 10cmHzO Pa0z/ Fi02 ns a c TCU Stay (days) Mean ± SD 2.7 ±2.0 1.2 ± 0.4c
pH ns a c Hospital Stay (days) Mean ± SD 7.9 ± 4.1 8.7 ± 8.3
PaCOz ns a c
Lin, n = 50 RR ns a c Treatment failure no (%) 25 (50) 12(24) c
1995 SMT CPAP HR ns a c Intubation and/or MV no (%) 18 (36) 8 (16) c
(rcJ. 187) n =50 2.5 to 12.5 MBP ns a c Hospital Mortality no (%) 6 (12) 4 (8)
CPAP cmH20 pH ns ns ns ICU Stay (days) Mean ± SD 4.5 ± 3.5 4.0 ± 3.0
PaC02 ns ns ns Hospital Stay (days) Mean ± SD 9.0±4.5 8.5 ± 4.5
PaOz ns b c
Moritz, n = 14 RR ns b d Treatment failure no(%) NA NA
2003 SMT HR ns b ns Intubation and/or MV no(%) NA A
(ref. 724) n= 14 CPAP SBP ns ns ns Hospital Mortality no (%) NA NA
CPAP 9.3 ± 0.3 PaOz/FiOz ns b ns ICU Stay (days) Mean± S O NA NA
cmHzO pH ns ns ns Hospital Stay (days) Mean ±SO NA A
PaCOz ns ns ns
Dyspnea NA NA NA
L' Her, n = 46 RR NA NA c Treatment failure n o (%) 17 (37) 14 (9) c
2004 SMT HR NA NA c Intubation and / or MV no (%) 14 (30) 4 (9) c
(ref. 194) n = 43 CPAP MBP NA NA ns 48 h Mortality no (%) 11 (24) 3 (7) c
CPAP 7.5cmH2 0 PaOdFiOz NA NA c Hospital Mortality no (%) 14 (30) 12 (28)
pH NA NA ns ICU Stay (days) Mean ± SO NA A
PaC02 NA NA ns Hospital Stay (days) Mean ±SO 9.7± 7.0 2.0 ± 11
Dyspnea NA NA c
Crane, n=20 RR b b ns Treatment failure no (%) 1 (5) 4 (20)
2004 SMT HR NA NA ns Intubation and/or MV no (%) 0 (0) 2 (10)
(ref. 726) n = 19 CPAP SBP NA NA ns Hospital Mortality no (%) 6 (30) 0(0) d
CPAP 10 cmH2 0 pH NA NA ns ICU Stay (days) Mean± SD NA A
PaCOz NA NA ns Hospital Stay (days) Mean ± SD NA NA
PaOz NA NA ns
Dyspnea NA NA ns
Park, n =27 RR NA NA c Treatment failure no (%) 11 (42) 2 (7) c
2004 SMT HR NA NA ns Intubation and/ or MV no (%) 11 (42) 2 (7) c
(ref. 727) n =27 CPAP MBP NA NA ns Hospital Morta lity no(%) 6 (23) 1 (4)
CPAP lOcmHzO PaOz/FiOz ns a c ICU Stay (days) Mean ±SO NA A
pH NA NA ns Hospital Stay (days) Mean ± SD 12.0± 8.0 11.0 ± 8.0
PaCOz NA NA ns
Dyspnea NA NA c
SMT =Standard Medical Treahnent, CPAP =Continuous Positive Ain'llay Pres._<;ure, RR = Respi ratory Rate, HR =Heart Rate, SBP =Systolic Blood Pressure, MBP =
Mean Blood Pressure, Pa02fFi0 2 = ratio of arterial blood oxygen tension to fractional inspired oxygen concentration, Pa~ = arteria l oxygen tension, PaC02 =
arterial ca rbon dioxide tension, ICU = Intensive Care Unit, S D = Standard Deviation. NA = not available, ns = non significant, a= p:::; 0.01 w ithin groups, baseline
vs. early assessment (10 to 180 minutes), b = p :::; 0.05 w ithin groups, baseline vs. early assessment (10 to 180 minutes), c = p :::; 0.01 between CPAP and SMT groups,
d = p :::; 0.05 between CPAP and SMT groups.
See text for further explanation.
304 PARTN CONVENTIONAL METHODS OF VENTILATOR SUPPORT
TABLE 11-5 Ran dom ized Con troll ed Trials Compari ng CPA P With BiPA P
Early Physiologic Outcomes

(10 to 180 minutes)
Intervention Baseline Baselin e C PAP O inical Ou tcomes

Sou rce, Sample vs. vs. vs.
yr Size CPAP BiPAl~ CPAP BiPAP BiPAP CPAP BiPAP
Metha, n = 13 CPAP IPAP 15 cmHzO RR b b ns Hospital Stay (days) Mean ± SO 9±4 10±6
1997 CPAP 10cmH2 0 EPAPS cmH20 HR ns b ns M l no (%) 4 (31) 10 (7l)d
(ref. 195) n = 14 SBP ns b d Treatment failure no (%) 1 (7) 1(8)
BiPAP pH ns b ns Hospita l Mortality no(%) 1 (7) 2 (15)
PaC02 ns b ns Major Complicatio ns no (%) NA NA
Pa02 ns ns ns
Dyspnea b b ns
Park, n = 27 CPAP IPAP 17 ± 2 em H20 RR NA NA ns Hospital Stay (days) Mean ± SD 11 ± 8 10 ±7
2004 CPAP l OcmH 20 EPAP 11 ± 2 emH20 HR NA NA ns MTno (%) 0 (0) () (0)
(ref. 727) n = 29 SBP NA NA ns Treatment failure no(%) 2 (7) 2(7)
BiPAP pH NA NA ns Hospita l Mortality no(%) 1 (4) 2 (7)
PaC02 NA NA ns Major Complication s n o (%) 4 (15) 5 (19)
Pa02/Fi02 NA NA ns
Dyspnea NA NA ns
Crane, n = 20 CPAP I PAP 15 o n H 20 RR b a ns Hospital Stay (days) Mean± SO NA NA
2004 CPAP 10 crnH2 0 EPAP5cmHp HR ns ns ns M l no (%) 3 (15) 9 (45)
(ref. 726) n = 20 SBP ns ns ns Treatment failure no (%) 4 (20) 1 (5)
BiPAP pH ns ns ns Hospital Mortality no(%) 0 (0) 5 (25)d
PaCOz ns ns ns Major Complication s no (%) NA NA
PaQz ns ns ns
Dyspnea ns ns ns
Bellone, n = 22 CPAP rPAP 20 onH20 RR a a ns Hospital Stay (days)Mean ±SO NA NA
2004 CPAP l OcmH20 EPAP5cmH20 HR a a ns MTno ('Yo) 3 (14) 2 (8)
(ref. 725) n = 24 SBP a a ns Treabnent failure no (%) 1 (4) 2 (8)
BiPAP pH a a ns Hospital Mortality no(%) 2 (9) () (0)
PaC02 a a ns Major Complications no (%) NA NA
Pa02/Fi02 ns b ns
Dyspnea NA NA NA
CPAP =Continuous Positive Airway Pressure, !PAP= Inspiratory Positive Ainvay Pressure, EPAP =Expiratory Positive Airway Pro-sure, RR =Respiratory Rate,
1-IR = Heart Rate, SSP= Systolic Blood Pressure, M1 = Myocardial infarction, Pa02 =arterial oxygen tension, PaO:dFi~ = ratio of arterial oxygen tension to
frnctiot\al inspired oxyg<m concentration, PaC02 =arterial carbon d ioxide tet\.'lion, ICU = !J1tensive Care Unit, SD =Sta ndard Deviation.
NA = not available, ns = non significant, a= p 5 O.Ql within groups, baseline vs. ea rly assessment (10 to 180 minutes), b = p 5 0.05 within groups, baseline vs. early
assessment (10 to 180 minutes), d = p 5 0.05 between CPAP and BWAP groups.
S<!e text for further explanation.
be consider ed first-line ventilator treatment in severe car- benefit of prophylactic PEEP. This concern is supported by
diogenic pulmonary ed ema . a barotrauma rate of around 50% in that s tudy. 662
Use of CPAP in the very early stage of ALI/ ARDS was
evaluated in spontaneously breathing patients and during
fiberoptic bronchoscopy. The investigators tested whether
PROPHYLACTIC PEEP
CPAP prevents the severe. ~~oxemia and respiratory fail-
The term prophylactic PEEP was u sed in early studies of ure requirin g intubation. 1 , 8 CPAP by face mask im-
PEEP in high-risk p atients aimed at reducing the incidence proved oxygenation but did not improve the need for endo-
of ARDS.662, 728 - 733 Both experimental433, 445•734 - 736 and clin- tracheal intubation, length of h ospital stay, or mortality 192
ical studies7 28-730, 737 suggest that PEEP might influence the (see Table 11 -6). Early use of noninvasive CPAP, with or
course of lung injury favorably in patients at risk fo r ARDS. without pressure support, may benefit specific high-risk pa-
The hy pothesis, however, was refuted by Pepe et al,662 who tients, such as inuntmocompromised patients.250,254,739,740 In
randomized 92 ventilated patients at risk for ARDS to rece- obese patients undergoing gastroplasty, Joris et al741 found
-ive no PEEP or PEEP of 8 cmH2 0. Early u se of PEEP im- that prophy lactic nasal CPAP with pressure support imme-
proved oxygenation but did n ot avert the development of diately after surgey reduced pulmonary dysfunction and
ARDS662 (Table 11 -6). Of note, the VT in the s tudy of Pepe accelerated recovery compared with 0 2 alone. CPAP is also
et ai662 was high (12 rnl / kg). Su ch a high VT might have useful during fiberoptic bronchoscopy/ 38 a procedure that
recruited240•242 and overdistended the lung, masking any can worsen oxygenation and respiratory mechanics.742 - 744
TAB LEU~ R.llldomi zed Controlled Trials Evaluating the Effiucy of Prophyl act ic PEEP
No. of Associated PEEP Mean PEEP

Reference Population Ann Patients Settings Setting (anH20l Outcomes
Pepe 1984 (662) M<'<lical·Surgieal Intervention 44 VT - llml/ kg Prc-<lelermlnod 8 Incidence of ARDS: 25%
AI ri>k for ARDS Mortality: J06.4
Barotrauma: 43%
Control 48 VT= 12 ml/ kg 0 h•c•dence of ARDS: 27%
Mort.llil)" 38%
w Barotrauma: 50"4
0 Dcldaux 2000 (192) M<odicalAU Intervention 40' ~ with CPAP for Sa02 > 90% Clinical rcspon<e 5- 10 Endotracheal intubation: 38%
c.n To iC!ran~ lCU length o f sla y (d ays): 9
ICU mort.llily: 23%
Hospilal mortality: 30%
Control 41.. Ch n1one For Sa(h > 90% 0 Eudotrflcheal intu b~, tion : 44o/o
ICU length o f stay (days): 9
ICU mortality: 22%
Hospital mortality: 27'Yo
Maitre 2000 (738) Medical Al.l Intervention 15 ~ with CPAP fo r Sa~ > 90% f'rt......dctcranincd 7.5 Oxyge-nation: \tnchanged
Undergoing FOB Ventilatory assistance after FOB: 0%
Control 15 ~ alone for S.1~ > 90% 0 Oxygenation: i
Ventilatory assistance after FOB: 33%
AatJt.F.VTATIONS ALl acute lun.g '"I""Y· AROS: ACute nspirntory diS~ syndrome. FOB: fi~--ropt•c bronchoscopy. vr: tkli'll \'Oiunw, o,~.. oxysen.. CPAP (() ntinuou ~ posibve "irway pressure, SaO!; ilrleri.1l oxygefl
S.liVral'on. ICU: lnt._'1,..,\'e c.ue un1t
"subgroup or JX-11tfl\t .. wilh ,•.trly ALl
TABLE 11-7 Complications of PEEP

Conclusion
Pulmonary overdistension
Barotrauma PEEP is used widely in runical practice.29 It is an essential
VfL[ component of ventilator management of patients with both
Increased d ead space hypoxemic ARF, resulting from lung edema caused by in-
Impaired C02 elimination creased microvascular permeabilty or hydrostatic pressure,
Reduced d iaphragmatic force-generation capacity and hypercapnic ARF, secondary to respiratory muscle fail-
Reduced cardiac output and oxygen delivery ure, in obstntctive lung diseases.
1mpaired renal function
Seventy years after the pioneering work of Poulton and
Reduced splanchnic blood flow
Oxonll and Barach et ai,15 a large body of physiologic data
Hepatic congestion
Decreased lymph drainage has produced a general consensus on the usefulness of PEEP
in the treatment of patients with acute respiratory failure.
Doubts remain about the optimal level of PEEP in different
clinical situations and the best manner to determine it. In
ln a double-b)jnd trial, Maitre et al 738 compared mask CPAP recent years, there has been a growing interest in assessing
with 0 2 therapy alone during bronchoscopy in severely hy- the effect of varied levels of PEEP on clinical outcome vari-
poxemic spontaneously breathing patients (see Table 11-6). ables, such as survival, complications, length of ICU stay,
During and immediately after the procedure, oxygenation and costs. Knowledge of pathophysiologic mechanisms and
was well preserved in the CPAP group, whereas it fell in the physiologic consequences of PEEP, however, remains an in-
0 2 group. CPAP prevented subsequent respiratory failure dispensable prerequisite for any decisions made at the bed-
necessitating ventilator support.738 side. Physiologic principles must serve as the foundation
PEEP of 5 cmH2 0 or less is sometimes used in intubated for designing meaningfull randomized, controlled trials.
patients to counteract the fall in lung volume secondary It is fitting to dose with the words of philosopher Charles
to intubation, supine positioning, and/ or muscle paralysis. Pierce (1878)747 : "lt is certainly important how to make our
The physiologic foundation is not clear. ideas dear, but they may be ever so clear without being true.
PEEP may prevent VILJ745 (see above). Despite robust How to make them so, w e have next to study."
physiologic rationale, no clinical evidence shows that PEEP
protects against VILI. In a retrospective cohort study, Gajic Aknowledgments
et aJ746 reported that approximately 25% of patients venti-
lated for more than 48 hours developed ALI. VT size was the We are grateful to Pamela Frigerio and Ritana Leo for
only ventilator setting that independently identified risk for continuous assistance and help with inserting references
ALI.746 No relationship was found between PEEP and risk and preparing figures and tables. We are also indebted to
for ALI; possibly, scatter was insufficient.746 Massimo Antonelli for invaluable support and to Jennifer
Beck for improving the clarity of the manuscript. We thank
Mrs. Chiara Vercesi and Mrs. Luciana Capella, from the
Scientific Library of Fondazione Salvatore Maugeri-IRCCS
Complications and Contraindications (Pavia), who provided hundreds of articles.
Table 11-7 summarizes the complications and side effects of

PEEP. Complications are directly related to level of PEEP.
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Care Med 2000; 28:3185-90. 1878 January.
!fl
PARTV tmderlying respiratory function has resolved I The criteria

used to determine when to terminate mechanical ventila-
tion essentially are based on the clinical and often subjective
ALTERNATIVE assessment by the intensive-care physician or by standard-
ized weaning methods. 2·3 The actual process of weaning the
METHODS OF patient from CMV is carried o ut by allowing spontaneous
breathing attempts with a T piece or continuous positive air-
VENTILATOR SUPPORT way pressure (CPAP) or by gradually reducing mechanical
assistance. 4·5 Not surpris ingly, gradual reduction of partial
ventilator s upport has been shown to benefit only patients
!fl who have difficulty in sustaining unassisted breathing.4
Chapter 12 _ _ _ _ _ _ _ _ __ Although introduced as weaning techniques, partial ~p
AIRWAY port modes have become standard methods of provtd-
ing primary mechanical ventilatory support in critically ill
PRESSURE-RELEASE patients.
VENTILATION Basic Principles of Airway

CHRISTIAN PUTENSE
HERMANN WRIGGE Pressure-Release Ventilation
Airway pressure-release ventilation (APRV)6 ventilates by
time-cycled switcl"ling between two pressure levels in a
high-flow (or demand-valve) CPAP circuit, and therefore,
unrestricted spontaneous breathing is permitted in any
phase of the mechanical ventilator cycle (Fig. 12-1). The de-
BASIC PRINOPLES OF AIRWAY PRESSURE-RELEASE gree of ventilator support with APRV is determined by the
VENTILATION
duration of the two CPAP levels and the mechanically deliv-
PHYSIOLOGIC EFFECTS
ered tidal volume (VT).6 •7 VT depends mainly on respiratory
VENTILATION DISTRIBUTIONS
compliance and the difference between the CPAP levels. By
PULMONARY GAS EXCHANGE
design, changes in ventilatory demand do not alter the level
CARDIOVASCULAR EFFECTS of mechanical su pport during APRV. When spontaneous
OXYGEN SUPPLY AND DEMAND breathing is absent, APRV is not different from conventional
ORGAN PERFUSION pressure-controlled, time-cycled mec11a mca. 1 ventilation.
. 78 ·
RATIONALE, ADVANTAGES, AND LIMITATIONS Synonyms u sed for APRV are biphasic positive airway pres-
IN DICATIONS AND CONTRAINDICATIONS sure (BiPAP) 7 and bilevel airway pressure (bilevel). BiPAP
INDICATIONS is identical to APRV except that no restriction is imposed
CONTRAINDICATIONS on the duration of the low CPAP level (release pressure).8
COMPARISON WITH OTHER MODES Based on the initial description, APRV keeps the duration
APRV VERSUS PSV
of the low CPAP level (release time) at 1.5 seconds or less.
APRV VERSUS IMV
VARIATION IN D ELIVERY AMONG
VENTILATOR BRAN DS
SYNCHRONIZED APRV Physiologic Effects
MODIFICATIONS OF APRV
ADJUSTMENTS AT THE BEDSIDE VENTILATION DISTRIBUTIONS
SETTING VENTILATION PRESSURES AND TIDAL Radiologic studies demonstrate that ventilation is dis-
VOLUMES DURING APRV tributed differently during pure spontaneous breathing and
SETTING TIMES DURING APRV CMV.9 During spontaneous breathing, the posterior muscu-
OTHER CONCEPTS OF SE1TING APRV lar sections of the diaphragm move more than the anterior
TROUBLESHOOTLNG tendon plate.9 Consequently, when patients are supine, the
ANALGESIA AND SEDATION DURING APRV dependent lung regions tend to be better ventilated dur-
IMPORTANT UNKNOWNS
ing spontaneous breathing (Fig. 12-2). If the diaphragm is
THE FUTURE relaxed, it will be moved by the weight of the abdominal
SUMMARY AND CONCLUSION cavity and intra-abdominal pressure toward the cranium;
mecl1anical VT will be distributed more to the anterior, non-
Controlled mechanical ventilation (CMV) traditionally is dependent, and less perfused lung regions. 10 When com-
provided via an artificial airway to completely unload a pa- pared with spontaneous breathing, the latter leads to lung
tient's work of breathing and ensure adequate gas exchange areas in the dorsal lung regions close to the diaphragm being
during the acute phase of respiratory insufficiency until the less ventilated (or atelectatic) in both patients with healthy
327
328 PARTY ALTERNATIVEMETHODSOFVENTILATORSUPPORT
CPAPhigh is supported by CT observations in anesthetized patients

demonstrating that contractions of the diaphragm induced
1~FRC =Vr by phrenic nerve stimulation favor distribution of venti-
lation to dependent, well-perfused lung areas, decreasing
CPAPiow atelectasis formation. 16
Spontaneous breathing with APRV in experimental in-
Tlow duced lung injury is associated with less atelectasis forma-
tion on end-expiratory spiral CT of the whole lungs and
Detenninants of Vr on CT scans above the diaphragm17 (Fig. 12-3). Although
• 6 Paw other inspiratory muscles may contribute to improvement
• Compliance in aeration during spontaneous breathing, the craniocaudal
• Re$istance gradient in aeration, aeration differences, and the marked
FIGURE 12-1 Airway pressure-release ventil ation ventilates by differences in aeration in regions close to the diaphragm be-
time-cycled switching between a h igh and low level of tween APRV with and without spontaneous breathing sug-
continuous positive airway pressure (CPAP) in the circuit. Thus gest that diaphragmatic contractions play a dominant role in
u nres tricted spontaneous breathi ng is permitted in any phase of the observed aeration differences. 17 Spontaneous breathing
th e mechanical ventilator cycle. Change between the two CPAP results in significant improvement of end-expiratory lung
levels results in a change in functional residual capacity ( ~FRO volume in experimental lung injury. 17 Experimental data
that equals the mechanical delivered tidal volume (VT). V T
suggest that recruitment of dependent lung areas may be
depends mainly on respiratory compliance and resistance and the
airway pressure difference (~Paw) between the CPAP levels.
caused essentially by an increase in transpulmonary pres-
Setting the time for the low (Tiowl and high (Thigh) CPAP
sure secondary to the decrease in pleural pressure with
produces adjustment of th e ventilator rate. spontaneous breathing during APRV.18
PULMO NARY GAS EXCHANGE

lungs and patients undergoing mechanical ventilation. Re-
cent results demons trate that the posterior muscular sec- In patients with ARDS, APRV with spontaneous breathing
tions of the diaphragm move more than the anterior tendon of 10-30% of the total minute ventilation ("VE) accounts for
plate when large breaths or sighs are present during spon- an improvement in VAIQ matching,intrapulmonary shunt-
taneous breathing.11 ing, and arterial oxygenation.15 These results confirm earlier
Computed tomography (CT) of patients with acute respi- investigations in animals with induced lung injtuy19-21 that
ratory distress syndrome (ARDS) reveals radiographic den- demonstrated improvement in intrapulmonary shunt and
sities corres ponding to alveolar collapse localized primarily arterial oxygenation during spontaneous breathing w ith
in the dependent lung regions, which correlates with intra- APRV. An increase in arterial oxygenation in conjunction
pulmonary shunting and accounts entirely for the observed with greater pulmonary compliance indicates recmitrnent
arterial h ypoxemia. 12·13 Formation of radiographic densities of previously nonventilated lung areas. Clinical studies in
is attributed to alveolar collapse caused by superimposed patients with ARDS show that spontaneous breathing dtll'-
pressure on the lung and a cephalad shift of the diaphragm, ing APRV does not necessarily lead to instant improve-
mos t evident in dependent lung areas during CMV. 14 The ment in gas exchange. Instead, improvement in oxygenation
cephalad shift of the diaphragm may be even more pro- continues over the 24 hours after the start of spontaneous
nounced in patients with extrapulmonary induced ARDS, breathing .22
in whom an increase in intra-abdominal pressure is invari- In patients at risk of developing ARDS, maintaining spon-
ably observed. Persisting spontaneous breathing is consid- taneous breathing with APRV resulted in lower venous ad-
ered to improve the distribution of ventilation to depen- mixture and better arterial oxygenation over a period of
dent lung areas and thereby improve ventilation-perfusion more than 10 days as compared with CMV with subsequent
(VAIQ) matching, presumably by diaphragmatic contrac- weaning. 23 These results show that even in patients requir-
tion that opposes alveolar compression.9 ·15 This concept ing ventilator support, maintaining spontaneous breathing
FIGURE 12-2 Dur ing spontaneous breathing, the posterior muscular sections of the diaphragm move more than does the anterior tendon
p late. Consequently, in the supine position, sp ontaneous ventilation preJer ably is directed to well-perfu sed, depen dent lung regions.
Conversely, a mechanically d elivered ti dal volume is d irected primarily to nondependent lung areas, away from regions with maximal
b lood flow. Thus spontaneous breathing con tributes to better ven tilation-perfusion (VA/Q) matching.
Mechanical ventilation Spontaneous breathing

CHAPTER 12 AIRWAY PRESSURE-RELEASE VENTILATION 329
APRV with spontaneous breathing APRV without spontaneous breathing
FIGURE 12-3 Computed tomography of a lung region above the diaphragm at end expiration in oleic acid- induced lung injury with and
without spontaneous breathing during APRV. Atelectasis formation is reduced with spontaneous breathing.
can counteract progressive deteriora tion in pulmonar y gas that w hen spontaneous breathing during APRV achieves
exchange. 10-40% of total VE, with no change in VE or airway pres-
Automatic tube compensation (ATC) compens ates for ensure limits, cardiac index increases. A simultaneous rise in
dotracheal tube resistance. The ventilator increases airway right-ventricular end-diastolic volume during spontaneo us
pressure during inspiration, reduces it during expiration, breathing with APRV indicates improved venous return to
and aims to keep the tracheal pressure constant and inde- the heart. 15 In addition, outflow from the right ventricle,
pendent of tube resistance. In patients w ith acute lung injury which depends mainly on lung volume (the major detenni-
(ALI), ATC during APRV achieved considerable inspira tory nant of pulmonary vascula r resistance), may benefit from
muscle unloading and increased alveolar ventilation with- decrease in intrathoracic pressure during APRV. 15
out decreasing functional residua l capacity or worsening Pa tients with left-ventricula r d ysfunction may not bene-
pulmonary gas exchange. 24 Apparently, the transient low- fit from the aug mentation of venous return to the heart and
ering of airway pressures during expiration w ith ATC does increase in left-ventricular afterload that occurs with lower-
not promote alveolar collapse or worsen gas exchange when ing of intrathoracic pressure. Thus, switching abruptly from
superimposed on APRV. CMV to pressure support (PS) with a simultaneous reduc-
tion in airway pressure can cause fmther decompensation
in patients with existing cardiac insufficiency.30 Rasanen
CARDIOVASCULAR EFFECTS et al3l.32 showed a need for adequate ventilator support and
Application of a ventila tor breath generates an increase CPAP levels in patients with respiratory and cardiogenic
in airway pressure and therefore in intrathoracic pressure, failure. Provided that spontaneous breathing receives ade-
which, in turn, reduces venous return to the heart. In normo- quate support and that satisfactoryCPAP levels are applied,
and hypovolemic patients, this action produces a reduc- maintaining spontaneous breathing d uring APRV should
tion in right- and left-ventricular filling and results in de- no t be a d isad vantage and is not contraindicated per se in
creased stroke volume, cardiac output, and oxygen delivery patients with ventricular d ysfunction.31- 33
(D~ ). 25 To normalize systemic blood flow during mechan-
ical ventilation, intravascular volume often needs to be in-
OXYG EN SUPPLY AND DEMAND
creased and/or the cardiovascular system needs pharma-
cologic support. Reducing mechanical ventila tion to a level An increase in cardiac index and arterial oxygen tension
that provides adequate support for existing spontaneous (Pao,) during APRV improves the relationship between tis-
breathing should help to r educe the cardiovascular side ef- sue oxygen supply and demand because oxy gen consump-
fects of ventilator support.26 tion re mains unchanged despite the work of spontaneous
Periodic red uction of intrathoracic pressure, achieved by breathing. In accordance with previo us experimental20 and
maintaining spontaneous breathing during ventilator sup- clinica115 findings, total oxygen consumption is not measur-
port, promotes venous return to the heart and right- and ably altered by adequately supported spontaneous breath-
left-ventricular filling, thereby increasing cardiac output ing in pa tients with low lung compliance. An increase
and D~.27 Experimental 21·28·29 and clinical15· 22 studies show in Do, with unchanged oxygen consumption indicates an
330 PART V ALTERNATIVE METHODS OF VENTILATOR SUPPORT
improved tissue oxygen supply and demand balance, as re- As a concept, APRV does not provide breath-to-breath
flected by a decrease in oxy gen extraction ratio and higher assis tance of spontaneous inspiration. Previous investiga-
mixed venous P~ . tions have demonstrated that separation from mechanical
ventilation in difficult-to-wean patients may be prolonged
with the use of IMV and may be expedited with breath-
ORGAN PERFUSION to-breath assistance of inspiratory efforts during pressure-
By reducing cardiac index and venous return to the heart, support ventilation (PSV).4 Thus APRV is not expected to
CMV can have a negative effect on the perfusion and func- be an advantage in difficult-to-wean patients.
tioning of extrathoracic organ systems. An increase in ve-
nous return and cardiac index secondary to the periodic
fall in intrathoracic pressure during spontaneous inspira- Indications and Contraindications
tion should improve organ perfusion and ftmction signif-
icantly during partial ventilator support. In patients with INDICATIONS
ARDS, spontaneous breathing with intermittent mandatory Based on tl1e clinicaJ15· 22•23· 37 and experimental20· 21 data,
ventilation (IMV) leads to an increase in glomerular filtra- APRV is indicated in patients with acute lung injury, ARDS,
tion rate and soditun excretion.34 Compatible with these and atelectasis after major surgery. APRV recrui ts atelectasis
results, renal perfusion and glomerular filtration rate of pa- adjacent to the diaphragm, thereby restoring pulmonary gas
tients with ARDS improve during spontaneous breathing exchange, and improves cardiovascular and extrathoracic
with APRV.35 organ function in patients with acute lung injury, ARDS,
Preliminary data in patients requiring ventilator support and atelectasis after major surgery.
for AU suggest that maintained s pontaneous breathing may
be beneficial for liver function. These clinical data are sup-
CONTRAINDICATIONS
ported by experimental observations using colored micro-
spheres in pigs with oleic acid- induced lung injury that Because lower levels of sedation (Ramsay score of 2 or 3)
demonstrated improved perfusion of the splanchnic area. 36 are used to allow spontaneous breathing, APRV should not
be used in patients who require deep sedation for manage-
ment of their underlying disease (e.g., cerebral edema w ith
increased intracranial pressure).
Rationale, Advantages, and Limitations To date, no data are available on use of APRV in patients
with obstructive lung disease. Theoretically, use of a short
Based on physiologic observations, APRV is advantageous release time should not be beneficial in patients with ob-
for recruiting atelectasis adjacent to the diaphragm, thereby structive lung disease who have prolonged expiratory time
improveing pulmonary gas exchange in patients with ALI, constants. Currently, use of APRV is not supported by clin-
ARDS, and atelectasis after major surgery. Because the inical research.
crease in transalveolar pressure is localized to areas near Likewise, use of APRV has no t been investiga ted in pa-
the diaphragm and is caused by a d ecrease in intrapleu- tieJ.ltS with neuromuscular disease and is not supported by
ral pressure, the concomitant d ecrease in intrathoracic pres- any evidence.
sure contributes to improved cardiovascular ftmction. Ar-
eas of atelectasis not adjacent to the diaphragm may not
be recruited successfttlly by spontaneous breathing during Comparison with Other Modes
APRV.
To enable spontaneous breathing, lower levels of sedati.on APRV VERSUS PSV
(Ramsay score of 2 or 3) are required. Less sedation helps
in reduceing the doses of vasopressor a nd inotropic agents APRV and PSV were compared in 24 patients with
while maintaining cardiovascular function stable and re- ALI/ ARDS using equal VE or airway pressttre limits. Be-
duces the duration of ventilator support. The use of APRV, cause insufflation during PSV is flow-cycled, alveolar end-
however, has to be limited to patients who do not require inspiratory pressure may not reach the preset level. Thus, in
deep sedation for management of their underlying disease patients with reduced lung compliance, equal airway pres-
(e.g., cerebral edema with increased intracranial pressure). sure limits achieve a lower VT during PSV as compared
Two periods during the APRV cycle are particularly with APRV. Consequently, a compensatory increase in res-
vulnerable to patient-ventilator asynchrony. When airway piratory rate is required during PSV to maintain alveolar
pressure release occurs during spontaneous inspiration and ventilation. To deliver APRV and PSV with comparable VT
when res toration of CPAP occurs during spontaneous ex- at an acceptable respiratory rate, the pressure level has to
piration, ventilation may be impaired because spontaneous be increased during PSV. 15
and ventilator efforts oppose each other. Rarely, a reduction In contrast to spontaneous breathing with APRV, assisted
in ventilatory efficiency, indicated by a decrease in alveola r inspiration with PSV did n ot produce significant improve-
ventilation and an increase in the work of breathing, may rement in intrapulmonary shunt, gas exchange, and cardiac
sult from temporary asynchrony. Synchronized APRV and output when compared with CMV.15 Apparently, the spon-
optimizing ventilator settings and sedation may be reqttired taneous contribution to a mechanically assisted breath was
in this rare event. 29 not sufficient to counteract the VAIQ maldistribution and
carctiovascular d epression caused by positive-pressure ven- TABLE 12-1 Modifications of APRV

tilation. A possible explanation might be that inspiration is
terminated by the decrease in inspiratory gas flow during Syncluonizcd airway prassurc-release ventila tion (APRV)
PSV, which may reduce ventilation in areas of the lung that Change between CPAP levels is synchronized with spontaneous
have a slow time constant. breathing.
Advantage of synchronization is not proven. 29
Intermittent mandatory p ressure-release ventilation (lMPRV)
APRV VERSUS rMV Spontaneous breathing on the high CPAP level is assisted with
PSV.
In a randomized multicenter trial in 52 patients with ALI, Advantage is not supported by data.42.43
APRV w ith lower peak airway pressures resulted in bet- APRV + pressure-support ventilation (PSV)
ter alveolar ventilation a11d equal arterial oxygenation as Spontaneous breathing on the low CPAP level is assisted with
compared with IMV.38 A similar trial in 58 patients with PSV.
ALI supports these findings but did not show a difference Advantage is not supported by data.
APRV + automatic tube compensation (ATC)
in mortality. 39 In eight patients recovering from open-heart
Spontaneous breathing on both CPAP levels is assisted with ATC.
surgery, APRV provided adequate ventilation with lower May reduce work of breathing in selected patients without
airway pressures and less dead-space ventilation than did deteriora ting gas exchange.24
IMV or PSV. 40 Arterial oxygenation was not different be-
tween the modalities. ABBREVIATIONS: CPAP, continuous positive airway pressure.
Variation in Delivery among Adjustments at the Bedside

Ventilator Brands SETTING VENTILATION PRESSURES
AND TIDAL VOLUMES DURING APRV
SYNCHRON IZED APRV Med1anical ventilation with positive end-expiratory airway
Asynchronous interferences between spontaneous and me- pressure titrated above the lower inflection pressure of a
chanical ventilation m ay increase the work of breathing and static pressure-volume curve a nd a low VT is thought to pre-
reduce the effective support during APRV. 41 Synchroniza- vent tidal alveolar collapse at end expiration and overdis-
tion of the switching between the two CPAP levels to spon- tension of lung units at end inspiration in patients w ith
taneous ins piration or expira tion has been incorpora ted ARDS. 44 This lung-protective strategy causes improvement
in all commercially available demand-valve APRV circuits in lung compliance, venous admixture, and Pa~ without
to avoid asynchronous interferences between spontaneous causing cardiovascular impairment in ARDS. 44 Mecha ni-
and mechanical breaths. A trigger window of 0.25 second cal ventilation using a VT of 6 ml/kg (ideal body weight)
usually is used to enable synchronization of ti1e S\Nitching has been shown to result in a better outcome when com-
between the two CPAP levels and spontaneous breathing pared with a VT of 12 ml/ kg in patients with ARDS.44 45
efforts. Bench-model data indicate that the synchronization Based on these results, CPAP levels during APRV should
of spontaneous ins piration with the switch to the high CPAP be titrated to prevent end-expiratory alveolar collapse and
level, but not the synchronization of spontaneous expira tion tidal alveolar overdistension.44•45 When CPAP levels during
with pressure release, may be beneficial. Patient data on the APRV were adjusted in patients with ARDS accorcting to a
advantage of synchronized APRV are lacking currentiy.41 lung-protective strategy, occurrence of spontaneo us breath-
Because patient-triggered mechanical cycles during IMV ing led to improved cardiorespiratory function without af-
are not ad vantageous for patients, there is no reason why fecting tota l oxygen consumption secondary to ti1e work
this should be different for APRV. 41 Synchronization during of breathing.15 Mo reover, pulmonary compliance should
APRV may produce inconstant times fo r the high and low be greatest in this range of airway presstues, and thus a
CPAP levels. Synchronization of APRV is switched off in small cha nge in transpulmonary pressure achieves normal
the APRV mode of the Drager EVITA 1V and XL ventilators. tidal breailiing w ith minimal elastic work of breathingu;
In ti1e Puritain-Bennett 840 and the Viasys Vela and Avea, (Fig. 12-4). Because APRV does not provide assistance on
APRV is synchronized with spontaneous ventila tion. every inspiratory effort, the CPAP levels need to be adjus ted
carefully to achieve efficient spontaneous ventilation w iili
minimal work of breathing.
MODIFICATIONS OF APRV
Most commercially available ventilators offer hybrid modes
SETTING TIMES DURING APRV
ofventilation such as APRV + PSV andAPRV + ATC (Table
12-1). Very few of iliese combinations have been shown to The duration of the high CPAP level needs to allow at least
benefit patients. 24 It is d oubtful that sinlply combining dif- complete inflation of the lungs, as indicated by an end-
ferent modalities will achieve an addition of ilieir positive inspiratory phase of no flow when spontaneous breathing is
effects. 42· 43 Indeed, it is possibile that proven physiologic absent. Spontaneous breathing occurs normally on the high
benefits of one modality may be minimized or even neu- CPAP leveL Thus duration of th e high CPAP level should
tralized when it is by combined with another mode. be adjusted so ti1at it is long enough to allow s pontaneous
flow at end expiration (Fig. 12-5). In the presence of PEEP1,

alveolar pressure amplitude will be reduced; consequently,
alveolar ventilation decreases, and Paco2 increases. To date,
data do not indicate that PEEP1 is superior to external PEEP
in preventing derecruitment of the lungs. Thus duration of
&
the low CPAP level should be adjusted to allow complete
E
:;,
expiration to the resting lung volume.
0
>
OTHER CONCEPTS OF SETTING APRV
Earlier approaches used high CPAP levels, which were re-
leased briefly to near-ambient pressure during APRV. De-
pendingon the time constant of the lungs, brief release times
may cause PEEP1. 47 Clinical studies, however, demonstrate
that external PEEP is superior to PEEP1 in restoring gas ex-
pressure
change in patients with acute lung injury. Not surprisingly,
in patients with ARDS, Cane et al49 observed an increase
FIGURE 12-4 During airway pressure-release ventilation, both in atelectasis on briefly releasing high CPAP levels to near-
CPAP levels should be titrated to achieve the greatest compliance. ambient pressure during APRV. Based on available scien-
Thus a small change in transpulmonary pressure achieves normal
tidal breathing, whereas elastic work of breathing (slta.d etl area) is
tific and cUnical data, this approach of adjusting ventila tor
minimal. If the CPAP levels are too high or too low (tlaslu d liue), settings during APRV cannot be recommended.
elastic work of breathing will be increased unnecessarily (slzacted
area).
Troubleshooting
breathing. If the release time is shorter than four times the
ANALGESIA AND SEDATION DURING APRV
time constant of the lungs (r = compliance x resistance),
alveolar pressure will not equilibrate at the low CPAP level, Analgesia a nd sedation are used not only to ensure satisfac-
and intrinsic PEEP (PEEP1) will result.47.48 Incomplete ex- tory pain relief and anxiolysis but also to help the patient
piration and the likelihood of PEEP1 are indicated by gas adapt to mechanical ventila tion. 5°-51 The level of analgesia
FIGURE 12-5 Computer simulation of airway pressure (Paw), volume (V), and gas flow (V) for the respiratory system and both a fast and
slow lung compartment with a short release tim e. Expiration in the slow compartment is not completed at end expiration; consequently,
gas flow is still p resent at e.n d expiration, associated with intrinsic PEEP.
•
--- -- ~-·-·-- ' ., P alv :
.1..,....::::::..__,...
,/
- ·-:-·- ·- ·- ·- ·- · \ , -:-..,/
·
:: . :: pmean
I _.,-""' '\.. ·-.............. : __.. .,. slow compartement
,/ ...... . . . ._ ~
•••
' ..__
- -.. .;:)
' ""'::....-- fast compartement
•
••
v ~ ,_.
---- --- ----- - ~
-·--·-
...,.--·
·- · - · - · - · -·- · - - --~
'....... --·-.... .
,-·
..........
...........
---......,;;;.
...
inspiration
..
v- lJt·~--·-~~·--~·~~~~~~~~RB~~------1:==-=~~~~~~~~-
--._:____
-.... c:::;--- ·- ;
---:-:::.. ...: end-ex-piratory
gas flow
7
I :
expiration I :
I .:
..
•
and sedation required during CMV is equivalent to a Ram- taneous breathing from the onset of ventilator support and
say score of between 4 and 5, that is, a deeply sedated patient to adapt the level of support continuously according to the
who is unable to respond when spoken to and who has individual needs of the patient.
no sensation of pain. During APRV, a Ramsay score of be-
tween 2 and 3 can be targeted, that is, an awake patient who
is responsive and cooperative. In nearly 600 post- cardiac References
surgery patients37 and in patients with multiple injuries,23
maintaining spontaneous breathing during APRV led to less 1. Marini Jj . New options for the ventilatory management of acute
consumption of analgesics and sedatives as compared with lung injury. New Horizons 1993; 1:4S9- 503.
initial use of CMV followed by weaning with partial ven- 2. Ely EW, Baker AM, Dunagan DP, et at. Effect on the duration of
tilator support. Higher doses of analgesics and sedatives mechanical ventilation of identifying patients capable of breath-
used in patients managed withCMV are associated with the ing spontaneously. New Engt J Med 1996; 335:1864- 9.
use of higher doses of vasopressors and inotropic agents to 3. Kollef MH, Shapiro SD, Silver P, et at. A randomized, con-
maintain stable cardiovascular function. 23 trolled trial of protocol-directed versu s physician-directed wean-
ing from mechanical ventilation. Crit Care Med 1997; 25:
567-74.
4. Brochard L, Rauss A, Benito S, eta!. Comparison ofthree methods
of gradual withdrawal from ventilatory support during weaning
Important Unknowns from mechanical ventilation. Am J Respir Crit Care Med 1994;
150:896-903.
Compared with an initial period of CMV followed by wean- 5. Esteban A, Frutos F, Tobin MJ, eta!. A comparison offour methods
ing, maintaining spontaneous breathing with APRV is asso- of weaning paticmts from mecllaJlical ventilation. Spanish Lung
ciated with significantly fewer days of ventilator support, Failure Collaborative Group. New Engl J Med 1995; 332:345-50.
earlier extubation, and a shorter stay in the intensive-care 6. Stock MC, Downs JB. Airway pressure release ventilation. Crit
unit (ICU) .23 These findings may be explained by a lower Care M('Ci 1987; 15:462-6.
level of sedation required during APRV. 7. Baum M, Bcnzer H, Putensen C, Koller W. Biphasic positive air·
way pressure (BiPAP): A new form of augmented ventilation.
Anaesthesist 1989; 38:452-8.
8. Stock MC, Downs JB. Airway pressure release ventilation. Crit
Care Mcd 1987; 15:462-6.
The Future 9. Froese AB, Bryan AC. Effects of anesthesia and paralysis on di-
aphragmatic mechanics in man. Anesthesiology 1974; 41 :242- 55.
Small randomized, controlled studies have demonstrated 10. Reber A, Ny lund U, Hedenstierna G. Position and shape of the
that early spontaneous breathing with APRV in patients diaphragm: Implications for atelectasis formation . Anaesthesia
with AU/ ARDS and in patients w ith pulmonary dysfunc- 1998; 53:1054-61.
'11. Kleinman BS, Frey K, VanDrunen M, et al. Motion of the di·
tion after major surgery leads to improved arterial oxygena-
aphragm in patients with chronic obstructive pulmonary d isease
tion and cardiovascular function. Also, sedation is less, and while spontaneously breathing versus during positive pressure
duration of ventilator support and ICU stay is shorter. In breathing after anesthesia and neuromuscular blockade. Anes-
the future, large-scaled randomized multicenter studies are thesiology 2002; 97:298-305.
needed to test the validity of these results in critically ill 12. Bernard CR, Artigas A, Brigham KL, et al. Report of the
patients. American·Europcan consensus conference on ARDS: Defini-
tions, mecl1anisms, relevant outcomes and clinical trial coordi-
nation. Intensive Care Med 1994; 20:225-32.
13. Cattinoni L, Presen ti A, Torresin A, et al. Adult respiratory
distress syndrome profiles by computed tomography. J Thorac
Summary and Conclusion Imaging 1986; 1:25-30.
14. Puybasset L, Cluzel P, Chao N, ct al. A computed tomography
Based on available data, it is suggested that spontaneous scan assessment of regional lung volume i11 acute lung injury. The
breathing during ventilator support should not be sup- CT Scan ARDS Study Croup. Am J Respir Crit Care Mcd 1998;
pressed, even in patients with severe pulmonary dys- 158:1644-55.
function, if there are no contraindications (e.g., increased 15. Putensen C, Mutz NJ, Putcnsen-Hi1mner G, Zinscrling J.
intracranial press ure). Improvement in pulmonary gas Spontaneous breathing during ventilatory support improves
exchange, systemic blood flow, and oxygen su pply to the tis- ventilation-perfusion distributions in patients with acute res-
sue, which have been observed when spontaneous breath- piratory dis tress syndrome. Am J Respir Crit Care Mcd 1999;
ing is allowed during ventilator support, are reflected in 159:1241-8.
16. Hcdenstierna G, Tokics L, Lundquist H, et al. Phrenic nerve stim-
improvement in the patient's condition. Maintaining spon-
ulation during halothane anesthesia: Effects of atelt>ctasis. Anes-
taneous breathing with APRV may help to decrease days thesiology 1994; 80:751-60.
of ventilator support and stay in the ICU. CMV followed 17. Wrigge H, Zinserling J, Neumann P, et al. Spontaneous breathing
by weaning with partial ventilator support is the s tandard improves lung aeration in oleic acid- induced lung injury. Anes-
in ventilation therapy, but the place of spontaneous breath- thesiology 2003; 99:376-84.
ing with APRV should be reconsidered in view of available 18. Henzler D, Dembinski R, Bensberg R, et al. Ventilation with
data. Today's standard practice should be to maintain spon- biphasic positive airway pressure in experimental lung injury:
Influence of transpulmonary pressure on gas exchange and 35. Hering R, Peters 0 , Zinserling J, et al Effects of spontaneous
hacmodynamics. lntemive Care Med 2004; 30:935-43. breathing during airway pressure release ventilation on renal
19. Putensen C, Rasanen J, Lopez FA. Interfacing between sponta- perfusion and function in patients with acu te lung injury. Inten-
neous breathing and mechanical ventilati on affect'> v~tilation· si ve Care Mcd 2002; 28:1426- 33.
per fusion distributions in experimental bronchoconstriction. Am 36. Hering R, Viehofer A, Zinserling J, et al. Effects of sp ontaneous
J Respir Crit Care Med 1995; 151:993-9. breathing during airway pressure rclease ventilation on intesti-
20. Putensen C, Rasiinen J, Lopez FA. Effect of interfacing betwe~ nal blood flow in experimental ltmg injury. Anes thesiology 2003;
spontaneous breathing and mechanical cycles on the v~tilation 99:1137-44.
perfus ion distribution in canine lung injury. Anesthesiology 1994; 37. Rathgeber J, Schorn B, Falk V, et al. The influence of controlled
81:921-30. mandatory ventilation (CMV), intermittent mandatory ventila-
21. Putensen C, Riisiin~J, LofX!Z FA. Ventilation-perfusion distribution (IMV) and biphasic intermitt~t p ositive airway pressure
tions during mechanical ventilation with superimposed sponta- (BiPAP) on d uration of intubation and consumption of analgesics
neous breathing in canine lu ng injury. Am J Respir Crit Care Med and sedatives: A prospective analysis in 596 patients following
1994; 150:101-8. adul t cardiac surgery. Eur J Anaesthesiol1 997; 14:576-82.
22. Sydow M, Burchardi H, Ephraim E, Zielmann S. Long-term ef. 38. Riisanen J, Cane RD, Downs JB, et al. Airway pressure release
fects of two differen t ventilatory modes on oxygenation in acute ventilation during acute lung injury: A prospective multicenter
lung injury: Comparison of airway pressure release ventilation trial. Crit Care Med 1991; 19:12.34-41.
and volume-controlled inverse ratio ventilation. Am J Respir Crit 39. Varpula T, Yalta P, Niemi R, et al. Airway pressure release v~ti
Care Med 1994; 149:1550-6. lation as a primary ventilatory mode in acute respiratory distress
23. Put~sen C, Zech S, Wrigge H, et al. Long-term effects of spon· syndrome. Acta Anaesthcsiol Scand 2004; 48:722-31.
taneous breathing during ven tilatory support in patients with 40. Valentine DO, Hammond MD, Downs JB, Sears NJ. Distribution
acute lung injury. Am J Respir Crit Care Med 2001; 164:43-9. of ventilation and perfusion with different modes of mechanical
24. Wrigge H, Zinserling J, Hering R, et al. Cardiorespiratory effects ventilation. Am Rev Respir Dis 1991 ; 143:1262-6.
of automatic tube compensa tion during ai rway p ressure release 41. Putensen C, Leon MA, Putensen-H immer G. Timing of p ressure
ventilation in patients witl' acute lung injury. Anesthesiology release affects power of breathing and minute ventilation during
2001; 95:382- 9. airway pressure release venti lation . C rit Care Med 1994; 22:872-8.
25. Pinsky MR. Determinants of pulmonary arterial flow variation 42. Riisanen J. JMPRV: Synchronized APRV, or more? Intensive Care
during respiration. J Appl Physiol1984; 56:1237-45. Mcd 1992; 18:65-6.
26. Kirby RR, Perry JC, Calderwood HW, Ruiz BC. Cardiorespiratory 43. Rouby JJ, Ben Ameur M, Jawish D, et al. Continu ous p ositive air·
effects of high positive end-expiratory pressure. AncstJ, esiology way pressure (CPAP) vs intermi ttent mandatory pressure release
1975; 43:533-9. ventilation (IMPRV) in patieJ,ts wi th acute respiratory failure. In·
27. Downs JB, Douglas ME, Sanfclippo PM, S tanford W. Ventilatory t~ive Care Med 1992; 18:69-75.
pattern, intrapleural pressure, and ca rdiac outpu t. Anesth Analg 44. Amato MB, Barbas CS, Medeiros OM, et al. Effect of a protective-
1977; 56:88-96. ve ntilation strategy on mortality in the acute respiratory distress
28. Falkenhain SK. Reilley TE, Gregory JS. lmproven,ent in cardiac syndrome. New Engl] Med 1998; 338:347- 54.
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1992; 20:1358-60. pared with traditional tidal volumes for acute lw'g injury and
29. Putensen C, Leon MA, Putensen-Hirnmer G. Timing of pressure the acute respiratory distress syndrome. The Acute Respiratory
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airway pressure release ventilation. CritCare Med 1994; 22:872-8. 46. Katz )A, Marks JD. Inspiratory work with and without continu-
30. Lemaire F, Teboul JL, Cinotti L, et al. Acute left ventricular dys- ous positive airway pressure in patients with acu te respiratory
function during unsuccessful weaning from mechanical ventila· failu re. Anesthesiology '1 985; 63:598-607.
tion. Anesthesiology 1988; 69:171-9. 47. Martin LD, Wetzel RC. Airway pressure release ventilation in a
31. Riisanen J, Hei kkila J, Downs J, et al. Continu ous positive airway neonatal lamb model of acute lung injury. Crit Ca re Med 1991;
pressure by face mask in acute cardiogenic pulmonary edema. 19:373-8.
Am J Card iol 1985; 55:296-300. 48. Neumann P, Golisch W, Strohmeyer A, et al. Jnfluel'ce of differen t
32. Riisiinen J, Nikki P. Respiratory failure aris ing from acute my· release times on spontaneous breathing pattern during airway
ocardial infarction. Ann C hir Gynaecol Suppl 1982; 196:43- 7. p ressu re release ventila tion. Intensive Care Med 2002; 28:1742- 9.
33. Nikki P, TahvanaincnJ, Rasanen J, Makelainen A. Ventilatory pat· 49. Cane RD, Peru zzi WT. Airway pressure release ventilation in
tern in respiratory failure arising from acute myocardial infarc· severe acute respiratory failure. Chest 1991;100:460-3.
tion: IT. Ptco2 and Ptcco2 compared to Pao 2 and PaCCh during 50. Wheeler AP. Sedation, analgesia, and paralysis iJ, the intensive
IMV4 vs TPPV12 and PEEPO vs PEEP10. C rit Ca re Mcd 1982; ca re unit. Chest 1993; 104:566- 77.
10:79-81. 51. Burchardi H, RatJ,geber J, Sydow M. The concept of analgosed a·
34. Steinhoff H, Falke K, Sd,warzhoff W. Enhanced renal function tion depend s on the concept of mechanical v~tilation. ln: Vincent
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piratory failure. Intensive Care Med 1982; 8:69- 74. New York: Springer-Verlag, 1995: 155-64.
t.hapter 13 How Can a Ventilator Deliver Pressure in
PROPORTIONAL-ASSIST Proportion to Patient Effort without
Directly Measuring Effort?
VENTILATION A simple PAV delivery system illustrates how this happens2
MAGDY YOUNES
(Fig. 13-2). Alveoli and chest wall are represented as an
elastic compartment that opposes expansion. Elastic recoil
pressure (Pel; hatched arrow) is a function of how much lung
volume deviates from passive functional residual capacity
(FRC) and the stiffness of the system (elastance E): Pel =
V x E. In a passive system, Pel increases alveolar pressure
HOW CAN A VENTILATOR DELIVER PRESSURE IN as the lung is artificially inflated. During assisted ventila-
PROPORTION TO PATlENT EFFORT WITHOUT tion, inspiratory muscles are active. These muscles decrease
DIRECTLY MEASURING EFFORT? alveolar pressure by an amount corresponding to their pres-
PHYSIOLOGIC EFFECTS sure output (Pmusc) (see Fig. 13-2). At any instant, alveolar
Relevant Physiologic Principles pressure (Palv) is the difference between Pel (V x E), which
Reported Physiologic Responses tends to increase it, and Pmusc, which tends to decrease it:
COMPARISON WITH OTHER MODES
Operational Differences between PAV and Other Palv = (V x E) - Pmusc (1)
Modes
Physiologic Consequences of Operational The elastic compartment is connected to the external tub-
Differences ing via airways and the endotracheal tube. The ventilator
Clinical Consequences of the Physiologic controls pressure at the extemal airway (Paw). Air flows
Differences into the lungs when Paw exceeds Palv. Flow is a func-
LIMITATIONS tion of the difference between Paw and Palv (resistive pres-
Runaway Phenomenon sure Pres) and the resistance of the intervening tubing (R).
Accuracy an d Stability of Respiratory Mechanics Thus
Values
Leaks Flow = (Paw- Palv)jR (2)
Dynamic Hyperinflation (DH)
Nonlinearity in the Pressure-Volume {P-V) Relation Substituting Eq. (l) for Palv in Eq. (2) and rearranging,
within the Tidal Volume Range we get
Ventilator Response Time
Excess ive Alarming Flow x R =Paw - (V x E) + Pmusc
INDICATIONS AND CONTRAINDICATIONS
Use of Sedatives in Patients on PAV or
COMMERCIALLY AVAILABLE PAV
DELIVERY SYSTEMS Pmusc + Paw = flow x R + V x E (3)
ADJUSTMENT AT THE BEDSIDE
Noninvasive Application This equa tion simply states that the distending force is the
Intubated Patients sum of patient-generated (Pmusc) and ventilator-genera ted
IMPORTANT UNKNOWNS (Paw) pressures and that this distending force is opposed
THE FUTURE by the sum of resistive pressure d rop (Pres, or fl ow x R)
SUMMARY AND CONCLUSION and elastic recoil pressure (Pel, or V x E).
ACKNOWLEDGMENT The gas-deli very system in Fig. 13-2 is a freely moving pis-
ton pressurized by a fast-responding linear motor. This ar-
Proportional-assist ventilation (PAV) is a form of synchro- rangement emphasizes that PAV gas-delivery systems must
nized ventilator support in which the ventilator gener- allow rapid a nd free flow of gas in response to changes in
ates pressure in proportion to instantaneous patient effort1 downstream (i.e., a lveolar) pressure. Flow and volume leav-
(Fig. 13-1). The ventilator simply amplifies inspiratory ef- ing the ventilator a re measured. The gains of the flow and
forts. Unlike other modes of partial support, there is no volume signals are adjustable by separate amplifiers: flow
target flow, tidal volume, or ventilation or airway pressure. assist (FA) and volume assist (VA). The sununed output of
Rather, PAV's objective is to allow the patient to comfortably the two amplifiers is the input to the motor. Thus the ven-
attain whatever ventilation and breathing pattern his or her tilator's pressure output is a function of instantaneous flow
control system desires.1 The main operational ad vantages and volume that left the ventilator since triggering.
ofPAV are automatic synchrony with inspiratory efforts and With this a rrangement (see Fig. 13-2), a greater effort
adaptability of the assist to changes in ventilatory demand (more reduction in alveolar pressure) will draw more gas
(see Fig. 13-1). from the ventilator. This, in turn, results in more assist. This
335
33 6 PART V ALTERNATIVE METHODS OF VENTILATOR SUPPORT
Diaphragm
Pressure
AiPNay
Pressure
Flow
FIGURE 13-1 Relation between

assist provided (airway pressure)
and independently measured
Volume diaphragmatic pressure in
proportional-assist ventilation .
Note that amplitude and duration
of assist correspond to amplitude
and duration of inspiratory efforts.
provides a positive relation between effort and assist but to middle inspiration and falls later. Thus the relative contri-
does not per se cause the assist to be proportional to in- butions of resistive and elastic pressures vary considerably
stantaneous effort. Proportionality is achieved through cus- during the inspiratory phase. If the same percent is used
tomized adjustment of the flow- (FA) and volume-assist for both components, total assist (Paw) represents the same
(VA) gains. The basis for these adjustm ents is as follows: percent of total pressure regardless of the relative contribu-
FA is the assis t pressure per unit flow (in cmH20 / liter /s). tion of each. Percent assist then is consta nt throughout. If
TI1ese are resistance tmits. If FA is 50% of R, the ventila tor different percent values are used for FA and VA, however,
provides 50% of the resistive pressu.re (i.e., 50% of flow x R, total assist (Paw) will represent a different percent of to-
Eq. 3). At 80% R, the ventilator assumes 80% of resistive tal applied pressure at different times. When percent assist
work, and so on. Likewise, setting VA gain to 50% of E (ventilator's contribution) is constant throughout inspira-
causes the ventilator to assume 50% of elastic pressure (i.e., tion, patient's percent contribution (i.e., 100 - %assist) is
50% of V x E, Eq. 3), and so on. The total assist (Paw) is the also constant throughout and the relation between Paw and
sum of the flow and volume assists: Pmusc (i.e., proportionality becomes constant) as given by
Paw = %flow x R +%V x E (4) Proportionality = %assist/ (100- %assist)
During the inspiratory phase, volume rises progressively, Thus a t 50% assist, proportionality is 1.0; Paw equals
peaking at end inspiration. By contrast, flow peaks in early Pmusc throughout. At 80% assist, proportionality is 4, and
Flowmeter FIGURE 13-2 Diagram illustrating how a PAV delivery

Elastic
pressure Patient system generates pressure in proportion to effort. The
(Pe~l Airwf!,J gas-delivery system consists of a freely moving p iston
Pressure pressurized by a fast-acting motor. Force exerted by
(Paw) motor is a function of flow and volume leaving the
ventilatoL A stronger effort resu lts in greater reduction
Muscle pressure
(PrmJSl ., in alveolar pressure (Palv), drawing more gas from the
p iston and resulting in more assist. If the volume-assist
I (VA) and flow-assist (FA) components are set to the
I
I same fraction of elastance and resistance, res pectively,
I I the pressure generated becomes proportional to effort
I I (Pmusc). See text.
I I
L-• ~low -•Volume-• @- --.J

~- ---------@---!
CHAPTER 13 PROPORTIONAL-ASSIST VENTILATION 337
- -
1n
A 90%
1 .~
1n / ~
0"
/ ............ ~: .............
0
~
\
J.> ::~· .... /
•••
~
0
No assist
-0 . •
~
0.... 50
:X:
E 40 12r-----------------~~~~--_,
.......
<.J
a..
w 30 ~ \
w
a.. 20 /
~ 4 1 / / ~
0
ro
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....., 10.0 10.0 t---------:::::;:;::;=-~--t---;
0 ...
:X: 7.5 7.51-----~~----~,.._.-+----1
E
<.J
..
....... 5.0 5.0 1----'7"---------__.,,........;,.-----;
a..~ 2.5 2.51--,&.-----------.3.-----1
0 o~-~-~-_.--~--~-~-~
0 0.2 0.4 0.6 0.8 1.0 1.2 0 0.2 0.4 0.6 0.8 1.0 1.2 1.4
Time from onset of inspiratory effort (sec)
FIGURE 13-3 Model simulation showing the impact of using equal (A) versus unequal (8) percent assist for the flow and volume
components. A. Three assist levels are shown: 20%, 50%, and 80%. When the same percent assist is ap plied to both comp one nts, the shape
of the assist [airway pressure (Paw)] is identical to that of muscle pressure (Pmusc), but the proportionality is different (Paw/Pmusc = 0.25,
1.0, and 4.0, resp ectively). Note also that flow reaches zero (end of m ech anical inspiration) at the same time during the declining phase of
Pmusc at all assist levels, including the no-assist situation (top p111wl). B. Flow assist is 80% of resistance, and volume assist is 20% of
elastancc (solid dots). Note that the assist (Paw) is more aggressive early in inspiration and terminates sooner relative to the balanced assist
(50/50 line). A relatively greater volume assist (opeu circles) offers less assist early while cycling off is delayed.
so on. Under these conditions, the shapes of the Pmusc and ventilator generates more flow (and volume), causing more
Paw waveforms are identical, and the decline in Pmusc a t pressure to be generated, and so on. Inflation continues un-
end inspiration \.vill be associated with a decline in Paw, en- til terminated by a ventilator or physiologic limiting mech-
suring synchrony (Fig. 13-3.A) . By contrast, if percent assis t anism. Under runaway conditions, technically, the patient
varies through inspiration (such as by using different per- is no longer in the PAV mode because assist no longer tracks
cent values for FA and VA), proportionality between Paw effort. The various runaway patterns and their mechanisms
and Pmusc is no longer constant, an d the shapes of the two ar e discussed tmder "Limitations," below.
waveforms differ (see Fig. 13-3B).
Another reason w hy FA and VA need to be cus tomized
to patient's Rand E is to avoid the occurrence of runaway.1 Physiologic Effects
Runaway occurs if FA exceeds the pa tient's Rand I or VA ex-
ceeds the patient's E.1 So long as FA is less than R and VA is RELEVANT PHYSIOLOGIC PRINCIPLES
less than E, the pressure assist (Paw, Eq. 4) is only a fraction
of the total pressure required to offset the prevailing resis-
(see ref. 3 for more details)
tive and elastic pressures, and the patient must contribute These principles w ill be discussed first because they not
the difference. Under these conditions, if the pa tient with- only help to explain PAV's reported effects but also make it
draws his or her contribution, the pressure provided by the possible to gain useful insights from a patient's responses to
ventilator can no longer offset the prevailing resistive and this mode. Responses to PAV may be mediated by changes
elastic pressures, and the cycle mus t end. If, however, FA in blood-gas tensions (chemical factors) or through modifi-
is greater than R and/ or VA is greater than E, Paw single- cation of nonchemical sources of respiratory drive. Chemi-
handedly may exceed the total opposing forces (right side cal responses are highly predictable, whereas the others are
of Eq. 3). A patient's contribution is no longer necessary to not. What happens, therefore, depends on what sources of
continue the inflation. The excess pressure provided by the respiratory drive a re operative at the tin1e of application.
SOURCES OF RESPIRATORY DRIVE by d1emical factors. Deviation from this expected behavior
During sleep and anesthesia, chemical factors are the sole then might be attributed to n ond1emical factors.
sou rce of respiratory drive; artificially reducing Pee, un-
der these conditions abolishes respira tory efforts.4- 6 Fur-
DETERMINANTS OF VE AND P Aco, IN THE ABSENCE
thermore, in these states, respirato ry muscle responses
OF NONCH EMICAL DRIVE SOURCES
to changes in load are m ediated exclusively via changes
in blood-gas tensions? Conversely, in alert individuals, Without Assist
other sources of respiratory drive exist; it is very difficult A stead y state in Pco2 and minute ventilation (VE) can oc-
to produce apnea by assisted ventilation d espite marked cur only if pulmonary carbon dioxide (C0 2 ) removal [the
h ypocapnia. 8- 11 These drive inputs, collectively called the p roduct of alveolar ventilation cV A) and alveolar C02 con-
consci.ousness factor, 4 presumably arise from behavioral cen- centration (FAco2 )] equals the C0 2 produced by the tissues
ters and from respiratory mechanisms that operateonlydur- CVco,). At a given Vco 2 , if ventilation is increased artifi-
ing consciousness (e.g., nonchemical load-compensatory cially, FAco,, and hence Pac 0 2, must decrease before a steady
mechan isms 7 ). Patients wh o require mechanical ventilation state is reached. Accordingly, at a given V co2 , there is an in-
cover a wide s pectrum of levels of consciousness. Therefore, verse rela tion between VE a nd Pace, in the steady s tate: the
it is difficult to make general conclus ions about their drive metabolic hyperbola.12 The actual equation is Pace, = 0.86
inputs . The next few sections d escribe what should happen [VcoJVE(1- V 0 / VT)],12 w here V 0 /VT is the dead-space
in response to PAV if respiratory output were driven solely ratio. Figure 13-4A illustrates this relation.
FIGURE 13-4 Effect •

of proportional assist on s teady-s tate ventilation CVE) and Paco2 . A metabolic hypl?l'bola is shown for a subject wi th
C02 production <Vco2 ) of 200 mllmin and dead-space ratio (VoNT) of 0.4. A. Unassisted breathing. The venti latory responses to C0 2 in
four subjects arc shown: (a) normal, (b) acute hypercapnic failure, (c) chronic hypercapnic failure, and (d) acute non-hypercapnic failure
with metabolic acidosis. In each case, the x intercept of the ventilatory response is the apneic threshold (AT). AT is shifted up in subject c
and down in subject d. The intersection of ventilatory response Line and the hyperbola g ives steady-state valu es of VE and Paco 2 • Vertical
dotted lines represent additional nonchemical inpu ts that cause ventilation to be higher and Pac 02 to be lower than in their absence. B, C.
Effect of 50% and 80% ass ist in the four subjects. In each case the venti latory-response slope doubles with SO% assist and increases
fivefold at 80%. Open circles off the h yperbola are immediate responses not consistent with steady state. Open circles on the hyperbola
are the steady-s tate values with assist. Note that the magnitude of change in VE and Paco 2 is a function of the difference between
unassisted Paco1 (solid circle) and the AT. D. Response to proportional assist in the presence of n on chemical input (vertical solid line).
Note that th e response is highly unpredictable (see text).
16 16
A VC0-=20 0 ml/min 8 80%
V0 1V1 0.4 •
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........ 12 12
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:::::.
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\. r . .. . . , , , - --' --,Q
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20 40 60 BO 20 40 60 80
Ventilation increases progressively as a function of higher percent assist. Because steady-state values must be
Pco, .13 The slope of the response depends on the sensitivity above the apneic threshold, and t..Pco, ,NA- AT is very small,
of chemoreceptors (the sensory ann) and the effectiveness VEand Paco, ccumot chcu1ge mud1. Furthermore, since "~h
of the motor arm in generating ventilation. Thus, for a given hardly changes, virtually all the assist (Paw) is used to re-
chemoreceptor response, ventilatory response is less if duce respiratory motor output, and percent reduction in
respiratory muscles are weaker or mechanics are abnom1al. Pmusc is similar to percent assist.
Without nonchemical drive sources, there is a Paco1 below A similar analysis for the patient with chronic respiratory
which apnea develops,4 - 6 the apneic threshold (AT; see failure (line c in Fig. 13-4B) shows that at 50% assist, Paco,
Fig. 13-4). decreases by 7 mmHg and VEincreases by 10%, whereas at
Four subjects with different disorders are illustrated in 80% assist, Paco, decreases by 13 mmHg and VE increases
Fig. 13-4A For each subject, there is only one possible by 20%. Because VE increased significantly, the decrease in
steady state, namely, the point of intersection of the C02 re- respiratory muscle o utput (Pmusc) is less than percent as-
sponse .line and the hyperbola. 13 At this point, pulmonary sist. For example, at 50% assist, Pmusc is contributing 50%
C~ elimination equals tissue C0 2 production. to a higher VE (11 0%). The decrease in Pmusc is 45% instead
Line (I represents a normal subject. Ventilatory respons e is of 50%. Because the difference between Pacaa at 80% assis t
normal (2.2liters/ min/mmHg), and AT is 40 mmH.g. The and AT is now very small, increasing assis t beyond 80%
intersection point is at a Pace, of 43 mmHg and a VE of would have little further effect, even though Paco2 is still
6.6 liters/ min. The difference between unassisted (no as- high. Thus, when AT is high, it is not possible to acuteJy nor-
sist, NA) steady-state Pco. and AT (i.e., t..Pc<>z,NA-AT ) is malize Pacaa using PAV (or any other strictly assist mode).
very small (3 mmH.g). Line b represents a patient with se- In the patient with severe acute hypercapnic failure Oine
vere acute hypercanic respiratory failure. AT is the same, b in Fig. 13-4C), the changes are even greater. At 50% and
but the ventilatory response to C02 is much depressed be- 80%, assist, Paco2 decreases by 14 and 25 mmHg, respec-
cause of abnormal mechanics. The intersection point is 76 tively, and VE increases by 23% and 50%. Even at 80% as-
mmHg a t a Vr: of 3.8liters/min. t..Pco,,NA- AT is very large sist, the difference be tween Paco, and AT is still large, and
(36 mmHg). Line c describes a patient with chronic res- further reduction in Pace, is possible. Because VE increases
piratory failure. Ventilatory response to C02 is depressed substantially, the decrease in Pmusc is much less than per-
because of abnormal mechanics a nd/ or weak respiratory cent assist (39% and 70%, for the 50% and 80% assist, re-
muscles. In this case, however, AT is higher. .6.Pco11 NA- AT spectively).
is larger than normal (16 mmHg), but for the same steady- Finally, in the pa tient represented by lined in Fig. 13-4C,
state Paco,, itis lower than in the patient represented by line increasing PAV assist results in progressive hypocapnia.
b. Line d represents a patient with a reduced ventilatory re- By normalizing mechanics, tl1e effect of the concomitant
sponse to C02 (0.6 liter /min/ mmHg) because of abnormal metabolic acidosis is now exposed.
mechanics or weak muscles but in whom the apneic thresh- In summary, in the absence of IWIIchemical drive sources,
old is low, for example, because of concomitant metabolic whether and by how much ventilation and Paco1 change
acidosis. 14 Steady-state Pco. and VEare near normal, but following institution of a given percent assist are deter-
t..Pcaa,NA- AT is large. mined by the unassisted ventilatory response to C02, the
apneic threshold, and the position of the metabolic hyper-
Exp ected Response to PAV Application bola. These determine the difference between unassis ted
With PAV, respiratory motor output is amplified by an Pacaa and AT. Because the more VE increases, the less Pmusc
amount that is related to percent assist (see Fig. 13-3A). decreases, the same three factors determine the extent to
Within the linear range of the pressure-volume and which the ass ist is used to increase ventilation versus de-
pressure-flow relations, the amplification of pressure results crease muscle output.
in a corresponding amplification of ventilation (see Fig. 13-
3A). Thus the net effect of PAV is to increase the slope of EFFECT OF NONCHEMICAL DRIVES ON
the ventilatory response to C02 (as well as to Po 2 and pH) . RESPONSE TO PAV
For simplicity, we will assume that Pco2 is the only stim- The action of nonchemical drive inputs can be viewed as
ulus and that resistance and elastance are constant in the additive with chemical drive. They cause ventilation to be
tidal volume range. Under thes e conditions, at 50% assist, higher at a given Paco. than if chemical drive were the sole
delivered assist equals Pmusc, and the combined pressure source (points b' and d' in Fig. 13-4A). Total drive is made
(patient + ventilator) is twice Pmusc. Accordingly, the slope up of a COrsensitive component and a component that re-
of the C02 response is doubled. At 80% assist, Paw is four flects consciousness-related reflexes and unpredictable be-
times Pmusc (see Fig. 13-3A), and pressure output is am- havioral influences.
plified by a factor of 5. The ventilatory response should Figure 13-4D illustrates how these inputs may modify
increase nearly fi vefold, and so on. the response to PAV. Without non chemical influences, Paco.
In the normal subject (line (I), 50% assist doubles the COz would be 76 mmHg. Because of tl1enonchemical input (solid
response (see Fig. 13-4B). VE immediately doubles (upper vertica l line), however, steady-state VEis 5.5 liters/ min at a
open circle). Pulmonary C02 output now exceeds Vco1 • Pacaa Paco, of 55 mmHg. A 50% assist results in an immediate
falls. Respiratory efforts decrease, and VEfollows along the increase in VE to 11liters/ min (both components are ampli-
new C02 response line until the metabolic hyperbola. A fied). Paco, must fall. What happens then depends on the
steady state is now possible. The same would happen at response of tl1e nonchemical component. At one extreme,
it may disappear (e.g., the patient may fall asleep when crease in VE as assist increased 27 - 30 to large increases in
assisted). VE would fall to the new C02 response line (di- VE and decreases in Paccn-16•19•25·31 These differences can be
agoHal dashed line). Should VE at this point be below U1e hy- explained readily if one considers the experimental circum-
perbola, Paco2 and VE will rise along the C02 response line, stances of U1e various s tudies or patients:
reaching the hyperbola at point 1. Here, the assist is fol-
lowed by an increase in Paco21 but ilie patient is working 1. Intubated ventilator-dependent patients with normocapnia.
much less. If the nonchemical stimulus remains the same, It is dearly not possible to establish steady-state values
Paco2 and VE will decr ease along a path parallel to the C02 of Va and Pac02 during unassisted breathing in these pa-
response line, meeting the hyperbola at point 3. Here, iliere tients; they rapidly develop distress. The effect of PAV is,
is no longer a C02 stimulus, and ventilation is sustained by accordingly, determined over a range of assist above a min-
the twice-amplified nonchemical influence. An intermedi- imum value (e.g ., 80% versus 40%). Furiliermore, in such
ate value (point 2) may result if the nonchemical influence patients, Paco2 at the minimum tolerable assist is normal.
partially decreases. Finally, at the other extreme, the pa- All such studies demonstrated very little change or even
tient may become agitated with ilie assist, increasing the a small decrease in VE as assist increased.27- 30 Pac~ de-
nonchemical stimulus, and this, when amplified, may re- creased, but the change was small (2-4 mmHg). These pa-
duce Pac02 to very low levels (point 4). It is dear that wiU1 tiet1ts, therefore, behave like Ule subject represented by line
nonchemical stimuli (alert individuals), the ventila tory re- a in Fig. 13-4, w ho has no nonchemical inputs and a small
sponse to PAY is ilieoretically unpredictable. llPc~ , NA-AT· This state, however, is read1ed only at some
finite assist. It therefore would appear that these patients
become comfortable only when their Pac~ is a few mil-
REPORTED PHYSIOLOGIC RESPONSES
limeters of mercury above AT. Under these conditions, VE
RESPIRATORY MUSCLE OUTPUT cannot increase furilier; the extra assist is used sin1ply to
PAY resulted in significant reduction in muscle output in decrease muscle output. The decrease in VE observed in
all studies where this was tested.15- 26 Typically, Pmusc de- some cases28, 30 is caused by a reduction in Vo/Vr and/or
creased by 30-45% at 50% assist and by 55-70% at 80% Vc02 (secondary to decreased respiratory muscle work) be-
assist. The less than expected reduction is caused by (1) cause in all such cases Pac~ was lower even though VE was
differences between assumed and actual E and R (see lower.28•30
"Accuracy and Stability of Respira tory Mechanics Values," The preceding observations lead to an interesting conclu-
below), (2) imperfect delivery by the ventilator (see "Ven- sion: Ventilator-dependent patients who show little change
tilator Response Time," below), (3) dynamic hyperinflation in VE and Paco2 over a rela tively wide PAV assist do not
[see " Dynamic Hyperinflation (DH)," below] or nonlinear- tolerate a Paco1 iliat is mud1 above AT. This indicates a high
ity in the pressure-volume relation [see "Nonlinearity in degree of chemosensitivity that likely contributes to their
the Pressure-Volume (P-V) Relation wiiliin U1e Tidal Vol- ventilator dependence. Chemosensitivity, as used here, does
ume Range," below], and (4) an associated increase in VE not refer to ventilatory responses (which are affected by me-
(see "Ventilation and Pc02,'' below). As indicated earlier, chanics and muscle strength) but to central effects of Pac~
when some of the assist is used to increase VE' less is used on respiratory sensation and muscle activation.
to reduce muscle output. 2. Chronic hypercapnia with and without acute exncerbation.
In virtually all reported studies, VE and Paco2 on PAV
VENTILATION AND Pc~ were compared with values obtained during a period of
Application of PAV to normal sleeping subjects results in an unassisted breathing. 16•19 - 21 •23•25, 26,3 4 Unlike the preceding
immediate increase in Vr and VE, which decrease over sev- group, there always was a significant increase in VE and
eral breaths to near-baseline levelsP Steady-state responses a d ecrease in Paco 2 • TI1e changes were modest, however
are minimal,6• 17 and the decrease in Pete~ is very modest (--25% increase in VE and 3-6 mmHg decrease in Paco2).
(- 3 mmHg6•17). These results are consistent with a small Such a response is consistent wiili a somewhat larger differ-
difference between w1assisted Pac02 and AT secondary to a ence between AT and unassisted Pc02 (subject represented
normal ventilatory response to C02 (subject represented by by line c in Fig. 13-48). Pac~ remained abnormally hit$h
line a in Fig. 13-48). in all cases, consistent with a high AT. The changes in VE
By contrast, in experienced, awake normal subjects, PAY and Paco2 likely would have been greater if the hypoxic
results in an important increase in VE and a more pro- stimulus did not change. In all but one study, 19 Pao 2 was
nounced reduction in Pac02, and the decrease in respiratory quite low during w1assisted breathing and improved w ith
muscle output is only modest.18 Paco2 generally decreases PAV. Because a higher Pao1 decreases the ventilatory re-
below the apneic threshold (e.g., 30 ± 5 mmHg18), reflect- sponse to CQz,13, an increase in Pao2 mitigates the increase
ing the presence of nond1emical drive inputs that fail to be in C02 response produced by PAV, resulting in a smaller
eliminated. PAV applied to inexperienced, awake subjects increase in ventilatory response. The assist provided in
is followed by unpredictable responses extending to severe this case is used preferentially to decrease muscle output
hyperventilation (personal observations), reflecting erratic as opposed to increasing VE. In one study, 19 the hypoxic
behavioral responses. drive was negligible at baseline (P~ = 99.5 mmHg). Here,
There are numerous reports on ilie dlanges in VE and the increase in VE was much greater (38%19). Although
Paco1 with PAV in patients with respiratory failure.15, 16,19- 33 the changes in Pac02 and Paa, undoubtedly contributed
Responses ranged from virtually no change or even a de- to the reduction in respiratory muscle output, m ost of these
CHAJYI'ER 13 PROPORTIONAL-ASSIST VENTILATION 341
patients were alert, so a reduction in nond1emical inputs is sensitive to drive and hence probably excessive, whereas
may have been partly responsible. failure of RR to change over a range of PAY assist indicates
3. Acute hypercapnic failure. Gay et al32 reported an aver- that respiratory drive is only mod est over this range. There
age 8 mmHg decrease in Paco2 (60-52 mmHg) within a half are important clinical implications to these observations on
hour of instituting noninvasive PAY. Considering that only PAY:
60% of patients were hypercapnic and that the nonhyper-
caneic patients likely did not contribute to the average de- 1. Failure o f RR to change over a range of PAY assist in-
crease (see 4, below), the d ecrease in Paco2 in the hyper- dicates that respiratory drive is only modest over this
capnic group must have been greater. In another study,31 range and iliat ilie RR observed in this range is the
there were four patients with acute hypercapnic failure not undistressed value preferred by the patient's control sys-
associated with central depression. In iliem, Paco 2 declined tem. Importantly, undistressed RR, so defined, ranges
17 mmHg on average (6~9 mmHg) within a half hour of from 12-46 breaths per minute. 27•28 That undistressed RR
instituting PAV. Although these observations are not rig- varies widely among patients is consistent with the wide
orous, iliey suggest that patients with acute hypercapnia range in normal subjects (8-25 breaths per minute).37 The
secondary to sever e acute mechanical abnormalities do sus- main differ-ence between ICU patients and normal sub-
tain la rge increases in VEand reductions in Paco2 on insti- jects is that the average undistressed rate is 10 breaths per
tution of PAV. Interestingly, Paco, remained above normal minute higher.27 A number of factors may contribute to
(---50 mmHg) for a few hours.31 It is possible that the apneic this, including body temperature, irritation of tracheal re-
threshold increased somewhat during the preceding period ceptors by the endotracheal tube, disease-related effects
of severe hypercapnia. on pulmonary and other receptors, neuropathology, drug
4. Acute hypoxemic failure. Information about this group effects, and so on.27
is scant. Although many wert! included in three previous 2. Because the undistressed RR can be quite low, a change
reports,3l -33 only in one study were the results of the nor- in RR as assist level is changed is more important than
mocapnic group (four patients) separated from tl1ose of hy- absolute RR at the low assist. For example, an increa se
percapnic patients .31 In these four patients, Pace, did not from 20-25 breaths per minute may indicate distress,
change despite distress decreasing dramatically. The likely although 25 breaths per minute is not usually consid-
explanation for failure of Pace, to decrease is that respi- ered a sign of distress. By contrast, RR in excess of the
ratory muscle output to a large extent was related to non- usual cutoff of 35 breaths per minute need not reflect
dlemical inputs, which d ecreased substantially on unload- distress.
ing (pailiway 1 in Fig. 13-4D).
Tidal volume responses mirror the VE responses and ob-
RESPIRATORY RATE AND BREATHING PATTERN viously share the same mechanisms (see ''Ventilation and
With one exception, 16 when there was no clinical distress Pea,,'' above) . It is important to note iliat in normocapnic
at the lowest level of assist, application of PAY or further patients, once a distress-free assist level is reached, further
increases in percent assist did not result in appreciable increases have little effect on VT. 27·28 Accordingly, every pa-
changes in respiratory rate (i.e., > 2- 3 breaths per minute). tient has a preferred or target VT tha t cannot be exceeded
This applied to normal sleeping subjects,6•17 intensive-care wiili more PAY assist. As with normal subjects,37 the pre-
w1it GCU) patients in whom percent assist was changed ferred VT varies widely an1ong patients (4-15 ml/kg27•28 ).
over a wide range above a comfortable level}7- 30 and am- PAY has made it possible to determine the undistressed
bulatory patients with chronic respiratory failure in whom breathing pattern in ICU patients. This proved quite vari-
the lowest level was spontaneous breathing. 19·20•24 - 26•34 In able. Figure 13-5 shows two extremes . With this wide range,
the only exception, 16 respiratory rate (RR) deceased sub- a one-siz e-fits-all strategy of mechanical ventilation (e.g.,
stantially when PAV was applied, but in this case iliere were setting a target VT) is dearly not ideal (see "Physiologic
clear signs of nma way (i.e., patient was no longer in the PAV Consequences of Operational Differences," below).
mode). Large breath-by-brea th variability in VT is d1aracteristic
In patients w iili acute exacerbation of duonic obstruc- of normal breatlung, particularly in wakefulness .38,39 Vari-
tive pulmonary disease (COPD), RR on PAY was lower than ability decreases in patients with abnormal mechanics.40·41
during spontaneous breathing (3- 5 b reaths per minute21,23) . Probably because PAY improves neuroventilatory coupling,
The pH, however, was low at baseline, and some degree of breath-by-breath variability tends to be large in this mode
distress may have been present then. When PAY is applied (see, for example, Fig. 13-1). Coefficients of variation o£25%
to patients with clear respira tory distress, RR decreases dra- or more are not unusual,23·25•29-31 and spontaneous sighs
matically a long with relief of distress.31 - 33 may be frequent. As with normal subjects,42 breathing vari-
From these observations it is clear thatPAV does notperse ability on PAY is less in sleeping and obtunded patients
change RR. RR changes only when PAY relieves respiratory (personal observations).
distress. In physiologic studies in which respiratory drive is
deliberately increased, RR does not increase until moderate VENTILATORY INSTABILITY
levels of stimulation.18•35 This applies whether stimulation The tendency for the respiratory system to become un-
is produced by hypercapnia, hypoxemia, academia, or an stable is d escribed by the so-called loop gain. 43- 45 A
increase in metabolic rate.36 Thus a change in RR with assist value of 1.0 indicates iliat recurrent cycling will occur
level indicates that respiratory drive is in a range where RR spontaneously [e.g., 01eyne-Stokes breathing (CSB)]. The
.B. t1f!: rr ·;r& ,.

II H .
~
l- lllf .
JUil
' ' :' . . ! .~ · · F· -. .
'
'-! f:· ' I··· I · 1: ... ~
,. lr .:.
~~~
~~~~f
I'
''
~~~ ~~w~~J: 't_,

~/ill
lr I
I,
... LL I·,~
. • .L
. H- ·-
HI\ 'I~~ W"
FIGURE 13·5 Tracings from two patients on high
'
l PAY assist showing extremes of u ndis tressed
1.12 secA:IIv breathing pattern. Paw, airway pressure.
lower the value, the more stable is the system. Ventila- RESPONSES DURING EXERCISE
tory response to chemical stimuli is an important determi- Application of PAV during submaximal exercise in patients
nant of loop gain. 43 - 45 Because PAV increases ventilatory with severe COPD increased endurance time and reduced
responses, we were concerned initially that it might precip- the rate of progression of dyspnea.53- 55 Patients with very
itate periodic breathing.1 This, however, did not materialize. severe COPD who received PAV during exercise in a reha-
Although PAV may aggravate preexisting CSB,46 there are bilitation program demonstrated greater improvement in
no reports of PAY-induced CSB in the usual ICU patient, unassisted exercise tolerance relative to a control group. 56
and we have observed only a few in whom breathing be- A beneficial effect of assist was not evident in mild COPD.57
came periodic o n high PAV support. Apart from its potential therapeutic role, PAV also has been
The resistance to CSB has been explained recently. Nor- used to examine the role of respiratory muscles in limiting
mal subjects require three- to fourfold amplification of venti- exercis e in normal subjects 58- 60
latory responses to develop periodic breathing.6•17•47 Thus,
when respiratory muscles and mechanics are normal, na-
tive loop gain is less than 0.3. In the average ICU pa- Comparison with Other Modes
tient, respiratory muscle strength is 50% of normal,48 resis-
tance is four times normal (14 versus 3-4 cmH 2 0 / Iiter /s49 ), OPERATIONAL DIFFERENCES BETWEEN
and elastance is two to three times normal (28 versus 10- PAV AN D OTHER MODES
14 cmH20/liter50) . Collectively, these abnormalities should With PAV, the assist (i.e., Paw) varies directly with the in-
decrease ventilatory responses to 20% of the normal value. tensity of patient effort (see Fig. 13-1). By contrast, with
For PAV to induce periodic breathing in the average patient, pressure-support ventilation (PSV), the assist is the same
it first must normalize ventilatory responses (i.e., a fivefold breath after breath regardless of intensity of effort. With
increase in the average patient) and then three to four times volume-cycled ventilation (VCV), assist varies inversely
more, a greater than 10-fold amplification. This is impos- with effort (Fig. 13-6). This is so because flow and vol-
sible because of technical and physiologic limitations (see ume are preset. If the patient's contribution increases,
"Limitations," below). the ventilator must deliver less assist (Paw), and vice
Accordingly, if periodic breathing develops o n PAV, it versa. Otherwise, delivered flow and volume will deviate
suggests that (1) respiratory muscles and mechanics are from set values. These different relations have been well
near normal, and the patient likely does not need venti- documented .18•22•61
lator support, and/or (2) the chemical control system is in- With PAV, the end of the ventilator cycle is synchr onized
herently unstable, and one should suspect disorders that automatically with the end of patient effort (see Fig. 13-1),
result in CSB, chiefly heart failure. A third condition that whereas with other modes it is not. Although ventilator re-
may precipita te periodic breathing is runaway. Here, large sponse delays tend to delay cycling off somewhat, 62 the ef-
tidal volumes may result, precipitating hypocapnia andre- fect is fairly trivial compared w ith the situation in other
current central apneas. The pattern is unlike the crescendo- modes (see "Ventilator Response Time," below). In VCV,
decrescendo CSB variety, however, and more like that pro- there is no relation whatsoever; the patient determines the
duced by pressure support (several large breaths a Iternating end of his effort, w hereas the caregiver determines the end
with apnea6•51 ) . of the ventilator's cycle. Any synchrony is happenstance.
The ability of PAV to increase loop gain by measurable The ventilator may continue inflation well after the end
quantities is cur rently being used to study mechanisms of of effort, when pa tient wants to exhale (e.g., breath 1 in
instability during sleep.45,52 Fig. 13-6), or may cycle off, withdrawing support before
FIGURE 13-6 Tracings from a patient on

volume-cycled ventilation. EMGdi, diaphragmatic
activity; Paw, airway pressure; Pdi: diaphragmatic
pressure. Note that ventilator cycles extend beyond
inspiratory effort in the first three breaths while
terminating during the effort in the last breath. Note
also that patient received little or no assist when h is
0.3seddlv effort was greatest (last breath).
the end of effort w hile patient is still trying to inhale (e.g., tient with an elastance of 25 o nH20 / liter and a resistance
breath 4 in Fig. 13-6). of 12 cmH 2 0 / liter / s, tl1e minimum VT at PSV of 7, 14, and
With PSV, synchrony between the ends of the ventilator's 20 cmH2 0 will be approxima tely 0.22, 0.43, and 0.64 liter,
and the pa tient's inspiratory phases may or may not occur respectively.6· 63 If the patient's RR near the AT is a conser-
depending on the patient's respiratory mechanics and the vative 16 brea ths per minute, and every effort triggers the
relation between PSV level and Pmusc.63·64 Ventilator cycles ventilator, minimum VEnear the ATwill be 3.5, 6.9, and 10.2
often extend well beyond inspiratory effort28·65 or may be liters/ minute for the three levels, respectively (see Fig. 13-
almost completely out of phase with them 65 (Fig. 13-7 A) . 9). A higher minimum RR (range 12-46 breaths per minute;
At times, inflation extends over two or more efforts28 (Fig. see "Respiratory Rate and Breathing Pattern," above) would
13-8A). increase minimum VE correspondingly.
For the patient in Fig. 13-9, applying PSV at level 1 will
boos t ventilation initially above the metabolic hyperbola.
PHYSIO LOGIC CONSEQUENCES OF Pac~ falls a long the response line of that level. Because min-
OPERATIONAL DIFFERENCES imum VEis below the hyp erbola (left end of linen a steady
RESPONSE TO DIFFERENT LEVELS OF ASSIST sta te can be read1ed (solid do t Oil line 1). For level2, a steady
Figure 13-9 illustrates what, theoretically, sho uld happen sta te still can be read1ed, but Paco2 will be just above the
when assist level is varied in different modes (see refs. 3 AT, a nd efforts will be very feeble. At level 3, a steady state
and 66 for more details). The response of RR to changes is not possible because minimum VE is above tl1e metabolic
in Paco, near the AT is key to understanding these plots. hyperbola. When Paco2 is above the AT, VE is above the hy-
As indicated earlier, RR is fairly constant over a range of perbola, and Pea,. must fall. When it falls below the AT, VE
Pac~ above the AT. For example, average difference be- becomes zero. The only steady-sta te VE is the open circle.
tween spontaneous RR and RR just before apnea is less than This is not possible, however, if all efforts trigger ilie venti-
1.0 breath per minute. 6 At AT, breathing simply stops. There la tor. For average VE to equal VE a t the open circle, venti-
is no gradual reduction in RR. lator rate must decrease below the patient's minimum RR.
The effect of different levels ofPAV (see Fig. 13-9A) was TI1is occurs in one of two ways depending on the time con-
discussed earlier (see Fig. 13-4). A steady state is possible at stant of the respiratory system (res istance I elastance (R/E)) .
all assist levels, except in rare cases where chemical control is If R/ E is very short (e.g., severe restrictive disease), venti-
highly uns table (see "Ventilatory Ins tability," above). Once lator cycles w ill not encroach on neural expira tion,63,64 al-
the AT is approached, it is not possible to increase\!E further. lowing lung volume to return to FRC befo re the next effort.
The relation between Pc~ a nd ventilation during PSV is Here, it is possible to continue triggering tmtil the AT, and
extremely complex.3•28•63·66 For simplicity, it is shown as a recurrent central apneas develop . When R/ E is lo ng, the
parallel shift in the ventilatory respons e, reflecting the fact ventilator cycle is also long 63' 64 and extends into neural ex-
that the assist is independent of PcD.J. Exactly what hap- piration. As efforts weaken, more and more efforts fail to
pens, however, to the slope of the ventilatory response is trigger the ventilator. Here, ineffective efforts are scattered
not terribly important here. What is important is that w itl1 between triggered brea ths. Depending on R/ E, ineffective
PSV a finite (i.e., minimum) VT is delivered once the ven- efforts m ay appear well before the AT. Because R/ E is more
tilator is triggered. This minimum VT is a function of PSV commonly long than short, intermittent ineffective efforts
level and respiratory mechanics.6·63 For example, in a pa- are m ore common than recurrent central a pneas.28,67
Airway
Pressure
(cmH2 0)
Flow
(Vsec)
Volume
(I)
El't'ort
0.2 sec/div 0.2 sec/div

FIGURE 13-7 Comparison of pressure-support (PSV) and proportional-assist ventilation (PAV) in a pa tient with severe dynamic
h yperinflation . With both modes, inspiratory muscles had to generate 10 cmH20 before inspiratory flow could be generated and the
venti lator triggered (verticnl dashed lines). Note that in PSV, ventilator cycle extends well into neural expiration. There also were many
ineffective efforts (not shown). This is not the cas e in PAV. Note also that diaphragmatic output is considerably higher in PAV. As a result,
d elay between onset of effort (nrrows) and triggering is much less. In addition, respiratory rate is higher w ith PAV. With severe dynamic
hyperinflation, it is difficult to maintain respiratory muscle output at a low level in PAV. See Fig. 13-13 for transi tion from PSV to PAV in
th is patient. (Bottom trncit1.g ) A semiquantitative effort signal genera ted without knowledge of respiratory mechanics92 that can be used to
identify onset and end of efforts noninvasively in real time (event marks). Note that the onset of effort (donmgoiug marks) can be
identified well before inspiratory flow crossing. If used for triggering, tllis essentially can eliminate the extra work associated with
dynamic hyperinflation.
In summary, with neither PAV nor PSV is it possible to in which it is self-triggered as Paco, oscilla tes about the AT.
decrease average Paco2 below the AT. What is different is If backup VE is above the hyperbola (line BU in Fig. 13-9),
that with PAV, VT is independent of assist level near the Paco2 must fall further. Depending on ventilator settings,
AT, and ventilator cycles cannot extend substantially into marked hypocapnia may develop.
neural expiration. Thus a steady state can be reached at all In summary, with PSV and VCV there is a limited range
levels without nonsynchrony. 28 With PSV, by contrast, VT of assist that is consistent with syncluony. Above this range,
increases monotonically with assist. At som e level the prod- ineffective effo rts or recurrent central apneas m us t develop.
uct VT x minimum RR exceeds the VE required for steady It is evident that the "appropriate" assist range depends
state, a nd nonsynchrony must occur. These differences have on the metabolic hyp erbola (a function of metabolic rate
been demonstrated experimentally.28 and V0 /VT) and minimum patient RR near the AT (see Fig.
With VCV, VE is constant over the range where RR is in- 13-9). Because these may change with time, a suitable level
dependent of drive and is given by patient RR x set VT. may become unsuitable at another time. Several studies
As set VT increases, VE increases and remains at that level have confirmed that nonsynchrony is quite common w ith
as efforts decline (horizolltal lines, right pa11el, Fig. 13-9). If PSV and VCV24.28 •65•67 while being virtually nonexistent at
stead y-state Paco, associated with this fixed VE is above all levels of PAV.19 •24•28 Ineffective efforts d o occur a t times
the AT, a steady state with maintained synchrony can result during PAV, but they are very infrequent28 and us ually
(e.g., line 1). If not (lines 2 and 3), and there is no or minimal occur when a large breath (spontaneous sigh or runaway
backup rate, ineffective efforts or recurrent central apneas breath) is followed by a weak effort.
must result (as with PSV), and nonsynchrony will increase
as set VT increases.67 With a backup rate, once the AT is RESPONSE TO CHANGES IN VENTILATORY DEMAND
reached, VE will decrease to set VT x backup rate. If this VE Fig ure 13-10 is a representative example of spontaneous
is below the hyperbola at the AT, periods in which the ven- changes in VE over a 2-hour period. The changes are not
tilator is triggered by the patient will alternate w ith periods trivial; the highest level was almost twice the lowest. This
A
30 I I
Pa•
(cmH:!O) 0
-i-~
I •I
1 r
Flow I i
(IIsee)
-1 I!
Volume
2
0) 0
10
0
PSV 12
30
Pa•
(cmH~)
0
1
Flow 0
(IIsee)
2
Volume
(I) 0
20
pdi
(cmH~) 0
EIV .64 sec/dlv
FRC - L - L - L - - J- J- _L1L
FIGURE 13-8 A dramatic example of a marked shift from slow, deep breathing to very rapid, shallow breathing following a small
reduction in pressure support CPSV). Paw, airway pressure; Pdi, diaphragmatic pressure. The increase in respiratory rate was artifactual
and related to improved synchrony (note that the rate of diaphragmatic efforts was unchanged). The small tidal volumes are related to
dynamic hyperinflation (note that Pdi increases substantially before flow becomes inspiratory) (vertical dotted lines). Inset sh ows
schematically the mechanism of sh allow breathing. Height of solid lines represents effort amplitude. EIV, end-insp iratory volume; FRC,
functional residual capacity. See text for additional details.
is not surprising because many influences that affect ven- Figure 13-11 illustrates two metabolic hyperbolas. Initial
tilatory demand can change in these patients, for example, settings resulted in identical VE (6 liters/ min) and Paco,
pain, anxiety, sleep-wake cycles, metabolic rate, pH, drugs, (48 mmHg). Ventilatory demand increases by 50%. Efforts
and so on. It is therefor e useful to examine what happens increase, but RR initia lly does not. With PAV, assist in-
with the three modes in response to such changes. creases, and VE increases along a relatively steep res ponse
FIGURE 13-9 Responses to different levels of assist with proportional-assist (PAV), pressure-support (PSV), and volume-cycled
vent ilation (VCV). Tile ventilatory response to C02 is shown for three assist levels in each case. The fonna t is as in Fig. 13-4. Note that in
PAV the ventilatory-response line intersects the metabolic hyperbola at all levels of assist. A steady state thus is possible at all levels. In
PSV and VCV, the response lines intersect the hyperbola over a limited range of ass ist. At higher levels, a steady state is not possible, and
nonsynchrony must r esult (see text). In this simulation, respiratory rate is shown to increase when Paco 2 exceeds 53 mmHg. This accounts
for the increase in ventilation above this Pac 0 2 in VCV. BU, backup rate.
16
14
PAV 90% vcv ~,.,3
1\ 80% ~
-!::: 1' • 1\ -- -~ 1;2
'B~
I ~
"
-
/
;JI'U 7C
I
.§
- 10 1
~ l ~- · '
>
c
0
·.;:;
ro 6
·.;:;
c
(!) 4
8
~~~~
( I
I/
I
/
"" I
l
I -.:::_
I
~
-"
.
(J
r, I
./
2
0 •
y v . •
20 ao 40 50 &0 ;o 20 3D 40 50 60 ;o 20 30 50 60 ;o
PaC02 (mmHg)
12T------------------------------------. following addition of dead space during PAY, VT increased

with no change in RR (20.1- 19.8 breaths per minute). When
added during PSY in the same patients, there was little
change in YT, and RR increased dramatically (16.4-33.2
breaths per minute).
RESPONSE TO CHANGES IN
RESPIRATORY MECHANICS
Substantial changes in resistance (R) may occur from time to
time. 49 Although similar information about elastance (E) is
not available, there is every expectation that it also changes
from time to time (e.g., secondary to changes in lung water,
4+---------.---------~--------,--------~ abdominal pressure, or atelectasis). Accordingly, it is impor-
0 0.5 1.0 1.5 2.0
tant to consider the response to changes in mechanics.
TIME (hrs)
Figure 13-12 illustrates the effect of a combined 50% in-
FIGURE 13-10 One-minute moving average of ventilation over a crease in R and E. At a given Pmusc, ventilation is inversely
2-hour period on PAV. Note large spontaneous changes in related to mechanical properties. Thus a 50% increase in E
ventilatory demand.
and R reduces the unassisted ventilatory response to C02
line, reaching the higher hyperbola at a Paco2 of 51 mmHg. to 67% of baseline.
With PSV, assist is constant. As a result, the ventilatory re- An increase in R and E will reduce tl1e slope of the ven-
sponse is no better than the unassis ted slope. The higher tilatory response under PAV for two reasons. First, percent
hyperbola is reached a t 57 mmHg. With VCY, ventilation assist is now lower. For example, if VA were 70% E, and E
cannot increase tmtil RR increases. Without tachypnea, the increased by 50%, VA would become 47% (70/ 150). This
metabolic hyperbola is reached a t a Paco, of 70 mmHg. reduces U\e amplification factor [from 3.3 to 1.88 in this
It is clear that the likelihood of respira tory distress and case; amplification factor = 100/(100 - %assist)]. Second,
tachypnea developing is higher with YCV and PSY. With the slope of the ventilatory response that is being amplified
VCY, there is the added problem that ventilator inspiratory also has decreased to 67% of the initial value. As a result,
time (T1) does not change as patient respiratory cycle time ventila tory response on PAY is now 38% of its initial value.
(TroT) decreases. Less time remains for exha lation, promot- VE mus t fall, Pac~ must rise, and distress may develop.
ing nonsynchrony. 67 Nonsynchrony occurring at a time of The situation is comparable with PSV. The already low
high respiratory drive may trigger anxiety. Of course, both ventilatory slope becom es even lower because the tmas-
PSV and YCV can be readjusted to provide adequate sup- sisted slope is now lower. Furthermore, the same pressure
port at the higher demand. This level, however, w ill be ex- assis t will be less effective in boosting YT because of worse
cessive when ventilatory demand returns to the lower level. mecl1anics. As a result, the ventila tory response is displaced
The different responses to C02 challenge under the downward as well (e.g., Figure 4 in ref. 22). A new steady
three m odes were well illustrated in norma l subjects. 18 ln sta te is reached at a lower VE and higher Paco2 • The changes
ventilator-dependent patients, Ranieri et aJ61 showed that in VEand Paco, are comparable in the two modes.
FIGURE 13-11 Responses to a 50% increase in ventilatory demand with proportional-ass ist (PAV), pressure-su pport (PSV), and
volume-cycled ventilation (VCV). The unassisted ventilatory response to C02 is given by the solid diagonal line in each panel. The three
modes were set during Ute low-demand period to produce the same ven tilation and Paco2 (solid circles/rlasluul liues). Because of the higher
ventilatory-response slope on PAV, the new ventilation could be reached with a much smaller increase in Paco2 (opeu circles). See text for
more details.
18 ,----------------- .
16 1---T...;..,;_'-----__,..-=----------i
c:14~--~~~----------~
.E 12 ~--~~------~--~
~
-c 10 1---''<-------"-.:----L..,_-------l
·-0ro 8 1---~'-"-..,.------4-'"'-<:;::-------l
-..:>6 1----"~------.:::::t~------....:::::j
·C
~ 4 ~::.::::::::...__;.~~~~~
2 1-----------,--,.,.C..---------i
0 L---~---Z'--~----~--~
20 30 50 60 70 20 30 40 50 60 70 20 30 40 50 60 10
P0 C02 (mmHg)
16
PA.V PSV vcv
14
t:12
I
~ 10
-c:
0 8
iE&R
'tu
·.::::: 6
c:
Q) 4
>
2
0
20 30 50 60 70 20 30 40 50 60 70 20 30 40 50 60 70
PaC02 (mmHg)
FIGURE 13-12 Responses to a 50% increase in elastance and resistance with proportional-assist (PAV), pressure-support (PSV), and
volume-cycled ventilation (VCV). (Solid rliago11allirws ) Unassisted ventilatory responses before an d after the change in mechanics.
(Dasl1ed li11es) Ventilatory responses on assisted ventilation. All modes were set before the change to produce the same ventilation and
Paco 2 (solid circlesltlnslletllilles). As mechanics worsen, Paco2 increases and ventilation decreases with PAV and PSV (open circles) but not
with vcv.
By contrast, with VCV, a change in E and R will have no crease in patient RR (20-33 breaths per minute). This cannot
effect on ventilation. The ventilator will deliver the same represent distress because it occurred immedia tely, and di-
Vy. Because there is no change in Pac<>z, there is no increase aphragmatic swings were still very low (~5 cmH20 ). Thus,
in effort. ln this respect, therefore, VCV is superior to both with PSV, nonsynchrony may reduce patient RR for reasons
PAVand PSV. that have little to do with relieving distress. As a corollary,
Grasso et a122 compared responses to an increase in elas- reduction in asynchrony, as would occur if PSV levels were
ta nce with PAV and PSV. Surprisingly, they found that with reduced,28•63 may result in acceleration of RR that is unre-
PAV, VT decreased less, RR increased less, and the increase lated to distress. This is not a problem with PAV becattse the
in dyspnea was less. It is not clear why this was so. Regard- ends of patient and ventilator inspiratory phases are syn-
less, the better results in this study were not expected and chronized. Therefore, changes in RR on PAV reflect level of
should not be viewed as intrinsic to PAV. dis tress m ore reliably.
An improvement in m echanics also can create problems
with PAV and PSV but not with VCV. If percent assist is
high before the change, a reduction in R orE may cause the TIDAL VOLUME IN DIFFERENT MODES
percent assist to exceed 100% of the new R orE, resulting in As indicated earlier (under "Respiratory Rate and Breathing
runaway. With PSV, improvement in mechanics at the same Pattern"), with PAV, VT is determined by the patient, and the
assist level will increase VE and decrease Paco1 • Asynchrony preferred VT ranges from 4-15 ml/kg, with an average of
may appear. 7 ml/kg. 27•28 With VCV, Vy is set without knowledge of the
In summary, on PAV, changes in mechanics may be fol- patient's preferred Vy . PSV is also usually adjusted to yield
lowed by distress or excessive ventila tor alarming (run- a given Vy. In either case, the set Vy almost always will be
aways). This problem for PAV is mitigated by the possibility larger than necessary. For example, if VT is set to 10 ml/kg,
of monitori11g passive Rand E contilmously a nd adjusting it will be greater than preferred VT in most patients. In the
assist accordingly (see "Noninvasive Mo nitoring of Respi- others, it will be inadequa te. If one individualizes the assist
ratory Mechanics, Pmusc, and Work of Breatheing," below) . to comfort level, VT still will be higher than with PAV for
two reasons: First, when Vy is titrated to the lowest level
consistent with comfort, the chosen Vy is greater than the
RESPIRATORY RATE IN DIFFERENT MODES average Vy during sponta neous breathing.8• 7 '~ Second, if Vy
With aU modes, patient RR will increase if assist is inad- or PSV level is set to comfort level at a given point, a change
equate. Patient RR, however, is also sensitive to reflexes, in ventilatory demand (see, for example, Figs. 13-10 and
independent of chemical drive. Continued inflation d uring 13-11) will cause it to become either excessive or too little
neural expiration prolongs neural expiration and, by ex- later. If it becomes excessive, it will not be adjusted down.
tens ion, reduces RR 68 - 70 This reflex is less pronounced in If it becomes inadequate (increase in demand), however, it
ICU patients70 than in alert pa tients68•69 but is still quite will be increased and rema in at the high level after, when
evident. Its gain varies widely among patients.7° Figure 13- demand decreases again. On average, VT will be larger than
8 shows a very weak response. Note that patient RR was if it were allowed to vary with demand (i.e., PAV).
the same whether efforts occurred during inflation or defla- Another peculiarity unique to PSV is that dynamic hy-
tion. By contrast, Figure 13-13 illustrates a strong response. perinflation may cause tidal volume to be inversely related
Here, on PSV, ven tilator cycle extended well into neural to inspiratory effort (see, for example, Fig. 13-8). TI1is is so
T E· When PSV was discontinued, there was a marked in- because a t a given PSV, the end-inspiratory volume, relative
30 i i i i i i i i i I i i i i I i i i i ! ! i i i I i i i i i ! i i i
l-Jrway
Pressure
(cmH20) I fi i I !!i
. . . . . . . . . I . . . . • .
;11il
f-1Ii:i:l]]ll Eiif ! 141:F1:-.! ~ lflt
... .j. .. ·i·...j.... i· ... ;....; ....; ....j ....i....,.... j .... j.... ; .... j .. .. i .... j ....i...
!~~~ = ! !~ !;;:;~;;l
. . • . . .
1
+.. ·i....I....;....
l!J!
j .•• ·( •••
. . . . . • . . . . •
+... j....i."
:
·i.. " i" ..i·".i". +... j"" i. " . j ...+
.j " .. j....; ... .....
;fli;;~!
. . .
=.
:
, ,....,....,....,....l ...., ....,....,....l ....,.... i...., ....,....,....,....l ....i....,....l....l ....i ....r
....i ....,....,....,.... ,....,....,....,....l ....!....,....,....,....l ....,.... t.........
0 " J""f'' j .. y : •t' "i ..,. ' ,.... . t" ·j ' 'f"' J"' ; ' l" ·i· "J.. j .. ~" " !" oJ""t ' i ' ,I l " i·· J ' f' ' ; "'to" i " l' "i' L. 'J" '!o"ol"'IOI
10
' ····i····~. ~····i····i····i····J····i····!····l··· : ·l····i····i····!····l····i····~····f· ..f....j....~····~····~····l····i····!····!····l····i····l····f····!····i····~····l····i····~····i·
Flow
(IIsee)
11. l t 1..: i n.: .... :J L I ;1 it . .JL: .• 1 .. t..lt l.1.... :. .. .11 .1

1 ... . u L.. , .iu. ! ~:. ..1.d lu . .rL .,J.u. .ft
, il . . 1..
J:
o.s ::::1:: ::!:: :: i·::::...:'::: ::!::::1::::I::::i::::l:::·1:::.:..::i :::!: :::1::::1::::1::::!::::1:..:!::::::·::!::::1::::1::::1::::!::::l::::1::::1::::1::::I:: ::1::::1:: ::!:: ::1::::1: :::!:::t
....!....!. .; ....!.......! ....L .. t ...!•.•.l....! ...!. ...!....! ...i .•..L...l....!....!.. .. ..!....!. .. ~ ....L ..t....!....!....t ...!...._L{j:~~:Lj·· ·.: ....!....!. ... L...!.
Volume
l::FFl:::}·t:t:t: J : : ' : : L Ft:JtL: t tJ::J::t::J::t:: : ! : : t:~: · ttfj:~fJ?ttfilf:·:t

0
(I)
iii i l ~ ilii ti
....i... ... .... l.... ..
iiii
-~· ~
l i i'i
~ - - ~·. ··~·- ·· ~·· !'..·j· ...!...'i....!.... iil
! ..!.. ·· ~· ··· ~ - ...~ ..• -~ ....I....,....,.... ~ ....~ .... '· · · ·~ ....~- · ..f.... ~- ..······j ... -~·· ..
:ii il
j···
; i:it
.. .. ..
-~· ,. -~ ··~ · ·~· ·~ · · · ·~.
Diaphragm
Pressure
( cmH2 0)
....!... -~.' ~ -~ ~ -~·- ~ ~- ~ ~'
sv .
... .I" ..I....!.... ! .... ' ... .. " .. t ....!..............!....i......" ......I . ...·p
.. .... !.... !... .... ... ..!....I.... .... ... .... ...!.... ..;....:... ~-·
I. .. t .........!....I"..!.. .1 .........'"..i....I... .."~AV ...... .!....I" ............!.
·! .... . ···~· ...~ .. ' .;... .~-- . ... -l··•. ~ .,. '~ ... -~ ....,. ·•·:'.··~ .... ~····! ....!....~-...!...-~·-· -~.
!~!i ; ~ f ~ i l ~~~~ ' ii~~ii~ i ~ i!~ ! ~ ; ! ll ~ i~ il!
0 .4 sec/cliv
FIGURE 13-13 Transition from pressure-support ventilation (PSV) to PAV in the same patient as in Fig. 13-7 with marked dynamic
hyperinflation. Efforts were quite weak on PSV and barely succeeded in triggering the ventilator. O n switching to PAV, the patient
receives very little assist because, unlike PSV, assis t cannot outlast inspiratory effort. Effort must increase in order to advance triggering
and obtain adequate ventilation (see Fig. 13-78). Note that respiratory rate increased suddenly on the switch . Because efforts were still
quite weak and the response was immediate, the increase in rate was not caused by a high respiratory drive (i.e., distress) and almost
certainly was reflexic in origin secondary to removal of inflation during neural expirati on (see text).
to passive FRC, at which the ventilator cycles off, in the ab- tient effort ceases regardless of the end-inspiratory volume
sence of effort (Vth), is fixed. 63 A stronger effort will trigger reached.
the ventilator at a higher volume relative to FRC, leaving
less difference between the onset of the breath and Vth (see
COMFORT
inset of Fig. 13-8). With high PSV, it is possible to reduce
Comfort, of course, cannot be compared in obtunded pa-
chen1ical drive to very near the AT, resulting in very weak
efforts (see, for example, Fig. 13-SA). Triggering then can oc- tients. Whenever PSV and PAV were compared in alert
cur only when volume is very dose to FRC. When a breath is patients with respiratory distress, however, PAV was
triggered, volume mus t increase by a large amount before preferred. 23•32. 33
the ventilator cycles off. Large protracted VTs result (see
Fig. 13-SA). If efforts increase, either spontaneously or after HEMODYNAMIC EFFECTS
reducing PSV level, breaths can be triggered at a higher vol- Mechanical ventilation has complex effects on the circula-
ume and hence closer to Vth. A small VTwill cause Vth to be tion (see Chapter 38). Data comparing hemodynamics on
reached. Once effort ceases, flow decreases to the cycling- PAV with other modes are very limited. Patrick et af2 found
off threshold, and the ventilator cycle ends. Synchrony is that cardiac output was 22% higher during PAV than dur-
reestablished, but breathing becomes faster and shallower ing VCV in eight patients with septic shock (see Fig. 15-9 in
(see Fig. 13-8). Thus, paradoxically, under these conditions ref. 73). Blood pressure also was higher. These results likely
VT is largest when effort is weakest, and changes in VT no were secondary to lower airway pressure, and hence mean
longer reflect effort. intrathoracic pressure, during PAV promoting higher ve-
This scenario can never happen with PAV in part because nous return. There is no information on the effect of PAV
in the presence of d ynamic hyperinflation it is not possible versus other modes in left-ventricular dysfunction. Such
to reduce efforts to the very low levels that can be reached information is needed because, in theory, a lower intratho-
with high-level PSV [see "Dynamic Hyperin!l ation (DH)," racic pressure may not be helpful in these patients (higher
below] and in part because the inflation cycle ends when pa- after load).
CLINICAL CONSEQUENCES OF THE VTs and plateau pressures from which confident estimates
PHYSIOLOGIC DIFFERENCES of the slope and pressure intercept can be obtained (Fig.
13-15). A positive intercept indicates either dynamic hyper-
PATIENT MANAGEMENT ISSUES
inflation or a res piratory system that is stiffer in the lower
Noninvasive Monitoring of Respiratory Mechanics, part of tidal ventilation [see "Nonlinearity in the Pressure-
Pmusc, and Work of Breathing Volume (P-V) Relation witl1in the Tidal Volume Range,"
PAY has unique features that allow estimation of passive below]. Because both abnormalities respond to increasing
mecl1anics no ninvasively.49 •50 In PAV, end of ventilator cycle PEEP, changes in intercept can be used to set the PEEP level
occurs during the declining phase of inspiratory Pmusc (see associated with best elastance.
Figs. 13-1 a nd 13-14A). A brief end-inspiratory occlusion Because Paw at the end of brief occlusions reflects pas-
coincides w ith the terminal part of the declining phase. This sive recoil a t end inspiration, it is possible to estimate pas-
phase ends shortly after the onset of occlusion, and its end sive expiratory resistance75 (see Fig. 13-14A). This approach
is readily recognizable50 (Fig. 13-14A). Paw a t the end of this was incorporated in the newly released 840 PAY+ option
phase provides the passive recoil press1.tre associated with (Tyco). Its main limitation is that expiratory resistance may
occluded volume. This is not tl1e case witl1 VCV or PSV overestimate inspiratory resistance when flow limitation
because the end of the ventilator cycle may occur during an exists. 76 When used to adjust flow assist in these patients,
active inspiratory or expiratory phase. This approach has flow runaway may occur. To circumvent this possibility, the
been validated,50 and an automated version was included manufacturer limited the maximum R to be used for PAV
in new 840 PAV + software (Tyco). A multicenter study adjustment, a reasonable but not ideal solution. An alter-
confirmed its reliability (r 2 = 0.92 compared with elastance nate method that estimates inspiratory resistance from brief
measured by esophageal catheter74 ). pulses has been described and validated. 49 It was incorpo-
Because VT is usually variable on PAY, random end- rated in a new Japanese PAV system (see "Commer cially
inspiratory occlusions frequently produce a wide range of Available PAV Delivery Systems," below).
FIGURE 13-14 Tracings from a patient on the 840 PAY+ option (Tyco) illustrating the random brief end-inspiratory occlusions. A . 40%
assist. B. 80% assist. Note the minimal change in breathing and lower amplitude of diaphragmatic pressure swings. Airway pressure rises
early during the occlusion in panel A, reflecting the fact the inspiratory phase ended during the declining phase of in spiratory pressure
(vertiCil I rlasl1ed line). During occlusion, airway pressure is inversely related to muscle pressure. By the end of occlusion, airway pressure
had plateaued, corresp onding to inspiratory pressure reachi ng its baseline level. In panel B, there is no ris ing phase during the occlusion
because inspiratory pressure had returned to baseline already; at high assist, th e inspiratory phase tends to end at a later p oint on the
declining phase. 62 Note that airway pressure is approximately the same at end occlusion in both cases. Elastance is determined from
((end-occlusion pressure - PEEP)NT]. Expiratory resistance is deteimined from flow early in expiration and ~p (the difference between
airway presslue and elastic recoil at the same point). Elas tic recoil is ob tained from end-occlusion pressure minus an am ount
corresponding to the volume expired and elastan ce (rlotterllille).
2on.J -~.:...~-.. ll.-··-~

...
.;. -t-- i-~f-.' -!+LLlJ-;.-1 . ; .'.. i,--1· -~--:· +·
··1-··J . .... . _ ,...l......_ I-·
..........._ ........L_,,_ .•
Diaphragm · I·; H· !·I ! H H· H .~ : ..;. i· I H· I

pressure -j ; · · . ; · : ; ; I ! , 1 ' H-:-t"
( em~ 0 ) -·-;-·· ......,._... rt··t- ..,, ...p ' ...,. T""i r:·-r ..
, '2 0 .j,. l ... I.... l "T i .., I , .. ' . ., .... ·I .... r+·~-
-+ --+-i··-}·--
i - {-·.!... .!.._. - 1
J
·i- j ·--,· -l·I ··-!··-~-~--
• ,
i--l·-f-·
Flow
(Lisee)
1.2.--- - - - - - - - - - - - - - ,
0 .6 1 - - - - - - - - - - - - - - - - - - - - 1 • FIGURE 13-15 Relation between
occlusion pressure and tidal
volume. Data collected over
approximately an hour of recording
with randomly applied occlusions.
The range of volumes was the
ro result of spontaneous tidal volume
"0
I= 0 . 21----""""'~,_....._ _ _ _ _ _ _--1 variability. In both cases, a highly
•
• significant correlation was
obtained. A. Pressure inte.r cept not
r=0.94 1-0.85 different from PEEP, indicating no
o~-----~~------~ o~-~--~--~--._-~ dynamic hyperinflation. B. Patient
0 5 10 15 20 0 5 10 15 20 25
with dynamic hyperinflation. Note
Plateau pressure- PEEP (cm~O) the positive intercept.
Apart from overcoming the major practical limitation to related (see "Respiratory Rate and Breathing Pattem,"
implementing PAV, namely, knowing passive mechanics, above). Such a test would not be feasible with oth er modes
continuous monitoring of passive R and E should help in because in such patients (high intrinsic RR), ventilator or
monitoring disease progression and in the timely identifica- even patient rate invariably will decrease as assist increases
tion of complications (e.g., changes in lung water, accumu- because of nonsynchrony.lt remains to be determined, how-
lation of secretions, bronchospasm, and so on). If a patient's ever, w hether tachypnea that is not relieved by ventilator
condition deteriorates, it should be possible to sort out w hat support is a reason to continue mechanical ventilation.
happened to mechanics by observing recent trends in Rand
E. Furthermore, when R and E are known, it is possible to Choice of Ventilator Settings
calculate patient-generated pressure (Prouse) and work of With VCV and PSV, one does not know what is appropriate
breathing in real time. for each patient. Given what we know now about variabil-
ity in undistressed (preferred) breathing pattern and time-
Improved Reliability of Ventilator Rate as a to-time cl1anges in demand, no general guidelines will be
Measure of Dis tress and Weaning Failure suitable for all patients; in m ost cases, the assist delivered
As indicated earlier (under "Physiologic Consequences of will exceed what is necessary (see "Tida l Volume in Differ-
Operational Differences"), an increase in ventilator rate is ent Modes," above). With PAV, there is no uncertainty about
not specific to distress in PSV and VCV. In either mode, a what the patient wants or needs or how to set the level of as-
simple increase in effort, occurring spontaneously or as resist. There is only one variable to consider (percent assist),
sult of reduction in assist, may decrease ineffective efforts and when percent assist is increased to a point where Vr
and result in an artifactual, sometimes dramatic increase in and RR no longer respond to further increases, the values
ventila tor rate (see Fig. 13-8). Although this artifact can be observed are what the patient needs.
identified from flow and Paw tracings,28 considerable exper- This apparent simplicity of setting PAV has been miti-
tise is required. Furthermore, even if true RR is counted and gated by a number of practical limitations, however, that
found to have increased, theincreasemaybereflexicand not proved problematic when simple PAV delivery systems
secondary to true distress (see "Respiratory Rate in Different were used (see " Limitations," below). In some patients these
Modes," above). With PAV, ineffective efforts are very rare, can cause frequent ventilator alarming and/ or the pres-
<md inflation extends minimally into neural expiration. Ac- ence of distress in the face of supposedly high assist lev-
cordingly, ventilator rate faithfully reflects patient rate.20.2s els. To compound matters, troubleshooting these problems
When it increases, distress can be inferred more reliably. requires considerable expertise. At present, there is a con-
Because a substantial increase in ventilator rate following sensus that PAV delivery systems must be able to monitor
a reduction in assist is used commonly to infer continued respiratory mecl1attics continuously and automatically16' 79
ventila tor dependence, this feature of PAV should reduce and that their alarm systems must be adapted to take into
false weaning failure verdicts. account the spontaneous variability of breathing in patients
The occurrence of an absolute RR of more than 35 breaths on PAV. Such systems have just become available (see "Com-
per minute during a weaning trial is used commonly as a mercially Available PAV Delivery Systems," below).
sign of weaning failure. 77' 78 Yet some patients breathe at
rates greater than 35 breaths per minute even when assist CLINICAL OUTCOME
is very high and efforts are very weak28 (see Fig. 13-SA). It is reasonable to enquire as to w hether the physiologic
Thus, in some patients, a high absolute RR need not indj- advantages of PAV translate into better clinical outcome.
cate distress. PAV can be used to determine whether abso- Unfortunately, information about outcomes is either inad-
lute tachypnea observed during a weaning trial is distress- equa te or nonexistent. This is so chiefly because, until very
related. Failure of RR to decrease as PAV assist is increased recently, available ICU ventilators [Winnipeg ventilator and
to high levels would indicate that tachypnea is not distress- Evita (Drager)] were not equipped with means to provide
smooth, nuisance-free PAV delivery over the extended pe- may increase blood pressure, depress immune function,
riods required for outcome studies. It is hoped that with and promote a negative nitrogen balance, actions that
newly available systems such s tudies will be carried out. can affect morbidity ad versely (for review, see ref. 82). By
In the meantime, one is limited to s peculation about how improving patient-ventilator interaction, PAV may help
physiologic advantages may improve outcome. to reduce these complications.
3. Barotrauma an.d ventilator-induced lung i11jun;. Excessive
Noninvasive Ventilation
lung distension may result in further lung injury (see
Two stud ies compared ou tcomes with PSV and PAV in acute
Chapter 46) and possibly multisystem organ failure83
respirator y failure. 32,33 Both found greater comfort and ac-
(see Chapter 44). There are a number of reasons why
ceptance ra te and a lower incidence of facial ulcers and con-
VT will, on average, be smaller in PAV (see "Tidal Vol-
junctivitis with PAY. One study found faster improvement
ume in Different Modes," above). Furthermore, neural
in respiratory rate and Pac~ with PAV.32 Neither study
reflexes terminate inspiratory muscle activity if lung
found a difference in intubation rate. Both studies, however,
distension exceeds a certain threshold tha t is well be-
were seriously underpowered in this respect. When faced
low physiologic total lung capacity (TLC) (e.g., Hering-
with a choice between severe distress and a somewhat un-
Breuer reflex). For example, when tidal expansion
comfortable way to relieve it, most people will opt for relief
approaches TLC during exercise, further increases in ven-
of dyspnea. Thus nonacceptance rate w ith PSV is low (15%
tilation are achieved automatically via increases in RR. 84
versus 3% in PAV33). Furthem1ore, intubation rate in such
Because the assist terminates automatically with PAV
patients is also low (-20-30%32, 33). It is estimated that more
w hen respiratory muscles are inhibited, overd istension
than 1000 patients are required to determine whether a new
beyond physiologic TLC (transpulmonary pressure ~ 40
intervention reduces rate of intubation.33 cmH2 0) is virtually impossible. Figu re 13-16 shows av-
Oinical Outcome in the ICU Setting erage plateau pressure on PAV in 48 patients with a wide
PAV may improve clinical outcome in a number of ways: range of elastance. Plateau pressure was less than 30
cmH20 above positive end-expiratory pressure (PEEP)
1. Sedative use. Most ICU patients are heavily sedated if they in all and less than 20 cmH2 0 above PEEP in all but four.
are not spontaneously unconscious. Sedatives may affect Considering that plateau pressure also includes chest-
clinical outcome adversely.80, 81 It is not dear to what ex- wall recoil, lung distension was even less. It is reason-
tent patient-ventilator interactions contribute to need for able to expect that this behavior will reduce barotrauma.
sedation. To the extent that they may, PAV may result in It also may make it possible to achieve the objectives
less sedative use and reduction in sedation-related com- of permissive hypercapnia (small VT) without the need
plications. for sedation or even hypercapnia (because RR increases
2. Impact on sleep. Poor patient-ventilator interaction may automatically as end-inspiratory volume approaches
affect sleep adversely in the ICU. 51, 82 Sleep deprivation TLC).
40 FIGURE 13-16 Average plateau

pressure (minus PEEP) in 48
patients with a wide range of
elastance.
,-....
0M
J:
E
30
---------------------------------------
•
........,
(,)
0..
w
•
w
0..
I 20 • •
....
<I>
•
, ,
... .:;.-. •
~
If)
If) ...
,_
Q)
..• ·'·
Q.
:::;
as
- Q)
(G
0..
10
• •
n=48
0 ~------~·------~------~------~------~----~------~1------~
0 10 20 30 40 50 60 70 80
Elastance (cmH 20 /I)
4. Wenning. The gr eater reliability of ventilator rate as a resistive and elastic pressures. Rw1away occurs when ex-
measure of distress (see "Improved Reliability of Ven- cess elastic pressure cannot be absorbed by the deficit (or
tilator Rate as a Measure of Distress and Weaning Fail- reserve) in resistive pressure.
ure," above) should decrease instances of false ventilato r With elastic overassist, excess elastic pressure increases
dependence. Tachypnea as the sole reason for a declara- progressively during inspiration because volume rises
tion of weaning failure accounted for 37% of all weaning throughout. By contrast, reflecting flow pattern, deficit/
failures in two large trials77•78 (A. Esteban, personal com- reserve in resistive pressure is highest in early and middle
mWlication). lt is tempting to speculate that some of these inspiration and decreases later. The point at which elastic
patients were not ventilato r-dependent, so their identifi- overassist will exceed the reserve in resistive pressure (i.e.,
cation under PAV will reduce ventilator time. rw1away) necessarily w ill occur late in inspiration. When
With PSV and VCV, Paco 2 may decrease to very near VA is just greater thanE, the runaway will occur at the very
the AT, resulting in extremely weak efforts, particularly end of the inspiratory phase when flow is near zero (Fig. 13-
during periods of reduced den1and (see "Physiologic 17 A). This fact has been put to use to measure actual patient
Consequences of Operational Differences," above). With E in sleeping or obtunded patients.6• 17•73 VA is dialed up in
VCV in the assist-control mode, it is also possible to pro- small steps Wltil the characteristic fWlaway pattern appears
duce protracted apnea. With PAV, a modest to moderate (see Fig. 13-17B). At this point, VA is just greater than E. The
level of activation is present at all times, including dur- more the elastic overassist, the sooner, in the inspiratory
ing sleep. The likelihood of disuse atrophy of respiratory phase, runaway will develop (see Fig. 13-17). Likewise,
muscles (see Chapter 45) may be less, and this may facil- runaway occurs earlier if the difference between Rand FA
itate weaning. is small because the deficit in resistive pressure w ill be less
Most ineffective efforts occur during mechanical ex- and more readily overcome by excess elastic pressure.
piration. Accordingly, the inspiratory muscles are being By analogy, with resistive overassist, runaway will occur
leng thened during their activation. This type of contrac- when the excess resistive pressure provided by the venti-
tion has been associated with muscle injury.85•86 Because lator [flow(FA - R)] exceeds the d eficit/reserve in applied
ineffective efforts are very common with PSV and VCV67 elastic pressure rv<E- VA)]. This point invariably will oc-
but not with PAV, this ty pe of injury may be mitigated. cur at the very beginning of inspiration, where volume, and
5. Continuous noninvasive monitoring of passive mechan- hence elastic assist, is near zero, and there is no possibility
ics, made possible by PAV, may lead to better PEEP man- for the elastic deficit/ reserve to absorb the excess resistive
agement a nd early detection and management of com- pressure.
plications. Notwithstanding the danger implied by the term, there
is in fact no danger for two reasons:
1. Modem ventilators limit the pressure and/or volume

Limitations that can be delivered. During normal PAV operation (i.e.,
no nmaway), the high-pressure limit rarely needs to be
The foll owing mechanisms often result in excessive sound- greater than 40 cmH20.
ing of alarms and occasional instances in which patients are 2. The na turally nonlinear pressure-volume relation of the
in distress despite a high percent assist. FortWlately, the Wl- respiratory system87 and the nonlinear pressure-flow re-
d erlying reasons for these difficulties are well w1derstood, lation in intubated patients88 effectively preclude danger-
and auxiliary algorithms have become available that should ous overdisten sion. Figure 13-18 illustrates this.
mitigate most, if not all, of these problems.
The pattern of flow runaway depends on whether
the pressure-flow relation is linear (Fig. 13-19). A lin-
RUNAWAY PHENOMENON
ear pressure-flow relation occurs when breathing via the
Runaway is a limitation because (1) it often results in trig- mouth, thereby excluding the nonlinear nasal pressure-flow
gering of alarms, which can be annoying and may promote relation, or when the nonlinear relation of the endo tracheal
anxiety in alert patients, (2) excessive delivered p ressure, tube is offset independently by automatic tube compensa-
flow, or volume may disturb the patient, and (3) the patient tion (ATC). Here, as FA just exceeds resistance, there is a very
is no longer in the PAV mode. rapid increase in flow and pressure that can be aborted only
The runaway pattern depends on whether the resistive by a ventilator limit (see Fig. 13-19 A). The inflation phase
or elastic component is overassisted. With elastic overas- is very brief. By contrast, when the pressure-flow relation
sist, the elastic pressure provided (V x VA) exceeds actual is nonlinear, there is no discrete change as FA exceeds R.
elastic pressure (V x E) by an amount that increases as a Rather, change is gradual and consists of a progressive shift
function of volume [excess elastic pressure= V(VA - E)]. If in peak flow to earlier points in inspira tion (see Fig. 13-19 B).
flow is not overassisted (FA < R), the r esistive pressure pro- Flow pattern at high levels of overassist resembles that of
vided is less than actual resistive pressure by an amoWlt that PSV. The ra pid increase in flow early in inspiration may
is related to flow [deficit in resistive assist= flow(R- FA)). truncate the breath, however, and sotmd an alarm if peak
So long as excess elastic pressure is less than the deficit in pressure limit is reached.
resistive pressure, a runaway does not occur because to- The d evelopment of algorithms to continuously moni-
tal a pplied pressure (Paw) is less than the sum of actual tor mechanics and their incorporation in commercial PAV
2.0
A
1.5
,..,
(.)
Q)
(/) 1.0
e.
~ 0.5
0
G: 101~E
o.o
50~E 95~E
-0.5
6 ~0
J:"' 40
E
~
0...
w 30
w
0...
Q) 20
>
0
.0
ro fO
M
0... . 0
12.5
,.., 10.0
I
0N
J: 7.5 /
E(.)
'-'
5.0
/ \
:::
e I \
2.S
v
Q.. .
"-.._
0.0
0 o.S 1 1.5 2 2.5
Time (seconds)
FIGURE 13-17 Runaway. A. Model simulation of effect of increasing percent of elastance used for volume assist (VA). Note that as soon as
VA exceeds elastance (101% E), flow fails to return to zero at the end of inspiratory phase. At higher levels, the runaway begins earlier, and
flow and p ressure increase progressively until the cycle is tem1inated by a physiological or ventilator limit. B. Patien t with COPD and
moderate dynamic hyperinflation, 90% assist. Note the spontaneous occurrence of a runaway breath (last breath). The pattern is
intermediate between the 101% and 125% in the left panel. Note that in the breath preceding the runaway, exhaled volume exceeded
inhaled volu me, suggesting less dynamic hyperinflation at the beginning of the runaway breath. See text for more details. The runaway
breath was terminated by the ventilator's high-pressure limit.
delivery systems (see "Noninvasive Monitoring of Respi- and FA are appropriate. In the usually obtunded ICU pa-
ratory Mechanics, Pmusc, and Work of Breathing," above) tient, subjective feedback is not possible, and setting PAV
should greatly reduce this problem. properly requires knowledge of passive mechanics. Tllis
Runaways need not occur on every breath (see, for ex- has created problems for two reasons: First, measuring pas-
ample, Fig. 13-17). Because elastance (E) may vary breath sive mechanics in the usual way (under sedation, hyper-
by breath [see "Dynamic Hyperinflation (DH)" and "Non- ventilation, and/ or paralysis) is cumbersome, requires ex-
linearity in the Pressure-Volume (P-V) Relation within the pertise, cannot be done frequently, and the results may
Ttdal Volume Range," above), volume assist may exceed E not reflect the E and R values on PAV (because of dif-
in some breaths even though it is less than 100% of average ferences in VT, flow rate, dynamic hyperinflation, and so
E. Assume that average E, determined from a number of on). Second, passive med1cmics frequently change (see ''Re-
end-inspiratory occlusions, is 30 cmH20 / liter, with a range sponse to Changes in Respiratory Mechanics," above). Val-
of 24-36 cmH2 0 / liter. At 90% assist (i.e., 27 cmH 20/liter), ues that a re accurate at one point may become inaccurate
some breaths may develop runaway. The closer VA is to later.
average E, the more frequent are the runaways. When differences between actual and assumed R and E
values are small (e.g., <25%) and percent assist is not high,
the impact is operationally insignificant. For example, w ith
ACCURACY AND STABILITY OF RESPIRATORY a 20% error at 50% assist, actual assist will be 42% or 60%.
MECHAN ICS VALUES
Either value is consistent with proper functioning, and if
Knowledge of R and E is not necessary in noninvasive ap- the assist is insufficient, there is room to increase it. By con-
plications. Feedback from the alert patient ensures that VA trast, with a 50% error at 80% assist, actual assist will be 40%
Volumre'-'(lc:!.)_ _ _ _ _ _ _ _ _ _ _ _--, Flow (Vsec)
A 8
TLC
70%E
,.
140%E170%E 200%E
' /
2.0
70%R
I
I
125%R 1ji0%R
I
I I
J I
I
J
/
~
J I I
I I I
I
'
I
I
I
I
I
I
I
I 1 I
I
f
I
1 I
I
I
1
I
1 1.5
, I
I
I
I
0.5 ....- .... - ...T .... ·-~L..... J...- ,!...--·-..-·- ·-. -·- 1
l I
I
I
.I
1 I I I I
I
I
1
I
I
I
1.0
I ' I
I
I
I
- - ..._.._.._,_..,_,_
I I I I I
f I
1 I
I
I
- _ ,. I
..... ...... .... ...... .. .... /.. ..... ...,.. I I
I I 1 I I I
I I I I I I
I I I I I I
I
I I I I II
I ; I I II
I I
t II I l ,,
I
I Itt
,,, ft;
/{
'r
It
r
'IJ;
FRC0~-~1~0--~2~0--~
3~0---4L0--'
'I '
0 ~--~~--~-----L----~--~
0 10 20 30 40
Elastic pressure (cmH2 0) Resistive pressure (cmH2 0)
FIGURE 13-18 Physiologic limits to ru naway. A. Typical pressure-volume curve in an average ventilated patient. Elastance (E) at a tidal
volume (VT) of 0.5 liter (the average VT on PAV in this case) is 25 cmHzO/liter (open cirde). FRC, functional residual capacity; TLC, total
lung capacity. (Left diagonal line) Volume assist = 70% E. The elastic pressure delivered by the ventilator is less than elastic recoil at all
volumes (n o runaway). The n~t three diagonal lines represent progressively increasing overassist. An ~cess elastic pressure is delivered
in the s pontaneous tidal volume range (horizontal distance between diagonal lines and pressure-volume line), forcing a volume runaway.
Because of the stiffening of the system near TLC, however, excess pressure decreases as volume increases. Runaway ends when the
diagonal line meets the pressure-volume line because there is no longer an excess pressure. Note that even with a marked overassist (200%
E), runaway stops at an elastic pressure of 40 cmH 2 0, corresponding to a physiologic TLC value. B. Typical pressure-flow relation in an
average patient (airway resistance is 10 cmH2 0/liter/s with a no. 8 endotracheal tube). Total resistance at a flow of O.Sliter/s is
15 cmH 2 0/liter/s. A flow assist in excess of this value will cause a Bow runaway (right two diagonal lines). Because the pressure-flow
relation is not linear, excess resistive pressure decreases as flow increases. Flow runaway s tops when the diagonal line meets the
pressure-flow line. Excessive overdistension of the lung is also mitigated in this case by nonlinearity of the pressure-volume curve. Note
that if VA is less than than E (left diagonal line, panel A), the deficit in elastic p ressure incr eases dramatically near TLC (lrorizontal arrow,
panel A). Th is helps offset the excess resistive pressure and aborts the flow runaway below physiologic TLC.
or 120%. In the former case, assist maybe insufficient, result- R (see preceding section), a small leak will not have much
ing in distress when the patient is "supposed ly'' receiving impact if percent assist is low or moderate and will cause
high assist, and there is little room for further increases. runaway if assist is high. Large leaks would res ult in run-
In the latter case, nmaway will develop, w ith frequent away a t all but the lowest assist levels.
sounding of the alarms, even though it should not happen In noninvasive applications, leaks can be huge. For
(percent assist <100). In our opinion, the discrepancy be- this reason, noninvasive PAY delivery systems must be
tween assumed and actual R and E is the most important equipped with leak-compensation algorithms. In the ICU
source of implementation difficulties. Fortuna tely, this has setting, leaks are usually very small, except in bronchocu-
now been largely resolved (see "Noninvasive Monitoring taneous fistulas. Nonetheless, checking for leaks should be
of Respiratory Mechanics, Pmusc, and Work of Breathing/' undertaken if alarms begin sounding excessively when they
above). did not before.
Inclusion of automatic mecl1anics in PAY delivery sys-
tems essentially should eliminate leak-related problems.
Thus, when a leak exists, the end-inspiratory occlusion tech-
LEAKS
nique (see Fig.13-14) will underestimate Eby an amount cor-
Leaks affect PAY delivery in much the same way overesti- responding to the leak (provided inspired volume is used
mation of E and R does. For example, if half the gas leaving to compute E). This should offset the error at the ventila-
the ventilator leaks out, assist will be twice that intended, tor level. Likewise, the pulse technique (resistance) will un-
or analogous to 100% overestimation of E and R. Thus the derestima te inspiratory resistance in the presence of leaks,
magnitude of overestimation is related directly to the mag- thereby offsetting the pressure-delivery error at the ventila-
nitude of the leak. As in the case of overestimation of E and tor level.
CHAfYI'ER 13 PROPORTION AL-ASSIST VENTILATION 355
3.• t A 8
•..- 105%. no limit ...............
• 105%. pressure limit
2j
105~ flow limit
2.0 ~
"8'
/~4- 150%.
~
:::.
:s:
0
I.A..
1.0
IJ
0.3 ~·
- \. .....
--..:.:::::
-
,26"1.
z-__,-"'
"\~rt'f..
~
~
..__ ~
~ ~
~
0.0 :--
.o.s I --. N t-
;o tI
,....
0 ('I 0
:-::
0
I .tO
E
..._,
w
w
<..>
a..
a..
30
I\/
- -.......
' r-....
Q)
20 .......
..._ 1,--
~
.0
ro
a..
~ 10
0
~Y.::
~ ~
:-.. ---
V-:::
-..,
12.3
---
,....
----
0N 10.8
I 7.3 \ \
E _/ _./"
~
5.0 \ \
'
::
e
a.. 2.i
/ /
/ /
0.2 0.4 0.6 0.8 1.0 1.2 0 0.2 0.4 0.6 0.8 1.0 1.2
Time (seconds)
FIGURE 13-19 Patterns of flow runaway. Paw, airway p ressure; Pmusc; respiratory muscle pressure. Percent denotes ratio of flow assist to
resistance at a reference flow (0.5 liter/sin panel B). A. Linear pressure-flow relation. FA is increased in steps beginning with 50% R. As
the assist approaches 100% R, some oscillations become apparent. At just above 100% R, there is a sudden change in response. Without any
ventilator limits, flow and pressure increase very rapidly to extremely high levels at the beginning of inspiration. Termination of runaway
depends on ventilator limits. With activation of peak-pressure limit, the cycle is aborted rapidly. If the maximum flow capability of the
ventilator (e.g., 2 liters/s) is reached before the peak-pressure limit, the cycle continu es a wh ile more at the maximum flow and then
self-terminates rapidly. With a constant resistance, therefore, transition of assist to above 100% is abrupt. B. Nonlinear pressure-flow
relation (e.g., in the presence of an en dotracheal tube). Runaway is blunted by the increasing resis tance at higher flow (see Fig. 13-lSB).
There is no clear change in response at 100% assist. Rath er, change is gradual and consists of a progressive shift in peak flow to earlier
points in inspiration.
DYNAMIC HYPERINFLATION (DH) ra te of rise of Pmusc is low, triggering may not occur
until near the end of inspiratory effort (see, for example,
DH presents occasional implementation difficulties, partic- Fig. 13-7 A). In PSV and VCV, once triggering occurs, a
ularly when severe and associated with marked respiratory substantial breath w ill be delivered. Although volume
muscle weakness. Thus delivery will be almost entirely during the patient's ex-
piratory phase, adequa te ventilatio n nonetheless w ill be
1. By definition, DH means tha t elastic recoil pressure is delivered, making it possible for chemical drive to remain
greater tha n zero at inspiratory onset. Inspiratory mus- low. In PAV, the ventilator will provide support only for
cles must generate enough pressure to offset this elastic the remaining duration of inspiratory effort. When trig-
recoil before the ventilator is triggered (see, for example, gering is much delayed, the duration of support may be
Figs. 13-7 and 13-8). Therefore, by the time the ventilator very brief, resulting in inadequate ventilation (see, for
is triggered, a finite fraction of the p atient's inspira tory example, Fig. 13-13). The only way the patient can re-
phase will have elapsed. This delay is a function of mag- ceive reasonable ventilation is to increase the rate of rise
nitude of DH and the rate of rise of Pmusc (see Fig. 13-7) . of inspiratory effort in order to advance triggering (see,
When DH is large (e.g., 10 cmH2 0 in Fig. 13-7A) and the for example, Fig. 13-7B). This will occur naturally at the
TLC A
TLC 8
r
EIV 1
I
Vr
t
FRC o~----,~o-----2Lo-----3+o----~
4~
o
Elastic pressure (cmH2 0)

FRC
0 10 20 30
Elastic pressure (cmH2 0 )
40
FIGURE 13-20 Impact of dynamic hyperinflation (DH) on PAV delivery. EEV, end-expiratory vo lume; FRC, functional residual capacity;
TLC, total lung capacity; Vy, tidal volume; VA, volume assist. A. No DH (FRC and end-expiratory volume are the same). If 80% assist is
dialed, the elas tic work done by the ventilator (slwded tria11gle) is 80% of the total elastic work (sum of s/Jaded and ope11 tria11gles). B. DH:
Elas tic recoil pressure at end-expiratory volume is 8 cmH2 0 (solid circle). Measured elastance (E = plateau pressurefVy) overestimates
actual elastance because Vy, the denominator, underes timates the difference between end-inspiratory volu me and FRC (compare the solid
diagonal line with the slope of the main pressure-volume curve in the VT range). At 80% of this inflated elastance (VA liue), the ventilator
is providing only SO% of elastic work (compare the shaded triangle with the pressure-volume area in the Vy range). There is little room to
in crease the assist. Forcing VA to exceed measured elastance will result in runaway. In such cases, therefore, the maximum assist that can
be delivered is limited.
expense of a higher chemical drive. When respiratory The preceding account should not suggest that patients
muscle reserve is high, the required increase in respira- with severe COPD or other causes of DH are difficult to sup-
tory muscle output may be tolerated. When DH is very port. As judged by numerous reports 19- 21, 24- 26,JO, l3,34 and
high and muscle reserve is quite low, distress m ay de- our own experience, the vast majority can be supported
velop. very comfortably. Even in patients with severe COPD,
2. As illustrated in Fig. 13-20, the effective assist received is elastic recoil at end expiration is usually approximately
less than the percent assis t dialed in. This is so because the 3-5 cmH 2 0,89- 91 a level that is accommodated easily by
ventilator is unaware of the Pmusc generated before trig- most patients. Nonetheless, a very high expir atory resis-
gering; the assist is a pplied only to that part of Pmusc in tance combined with a high ventilatory demand and weak
excess of that required for triggering. Thus not only does muscles may make it difficult to achieve adequate support.
the patient have to generate more pressure to advance The adverse impact of severe DH on PAY's performance
triggering, but the maximum percent assist that can be can be mitigated in some patients by increasing PEEP. This is
delivered effectively also is less. Distress may occur even effective only when the high expiratory resistance is related
at the highest possible assist. to expiratory flow limitation in the lung, however. Where
3. Even if an assist level is found with which the patient the high resistance is in the tubing, raising PEEP simply
is comfortable, runaway still may develop in occasional increases lung volume without relieving DH. The impact of
breaths, caus ing confusion (since VA is technically less DH can be eliminated completely if the ventilator is made
that 100% E). The dura tion of expiration of spontaneous to trigger at the onset of inspiratory effort instead of being
efforts can be quite variable. A breath preceded by a long triggered by inspiratory flow or airway pressure. A method
expira tory time begins at a lower absolute volume (less for noninvasive identification of the onset of effort in real
DH). The same VA that was not associated with runaway time has been developed recently92 (see "effort channel" in
w hen end-expiratory volume (EEV) was higher may now Fig. 13-7). With such a system, PAV assist continues to be a
cause runaway (see Fig. 13-178). This can be appreciated fw1 ction of flow and volume, but the reference flow is the
by moving the VA line downwards in Fig. 13-20B. It will expiratory flow at onset of effort (as opposed to zero flow,
be noted that at some point the VA line will cross to the as is currently practiced). In this fashion, assist would apply
right of the pressure-volume line. throughout inspiratory effort.
NONLINEARITY IN THE PRESSURE-VOLUME (P-V) when end-expiratory volume is close to residual volume
RELATION WITHIN THE TIDAL VOLUME RANGE (abdominal distension and obesity93 - 95 ) or when dere-
cruitment of airways or al veoli occurs within the tidal
The relation between volume and elastic recoil is sigmoid. 87
volume range. The impact of this abnormality on PAV
Most patients breathe in the linear midrange, and E is nearly
delivery is similar to that of dynamic hyperinflation [see
constant within the VT range. In others, the P-V relation is
"Dynamic H yperinflation (DH)," above]j the assist re-
not linear within VT. This creates some difficulties because
ceived by patient is less than intended (see Fig. 13-21 B).
there is no fixed E to use for the sake of setting the volume
When assist requirement is low, th is behavior presents
assist. The difficulties depend on whether VT falls within the no difficulty. When assist level must be high (e.g., 80%),
stiff upper range (high-end nonlinearity) or the stiff lower
however, the patient may be comfortable, but because of
range (low-end nonlinearity).
the usually large breath-by-breath variability in VT, nm-
aways may occur during large breaths, triggering alarms
(see Fig. 13-21 B). Therefore, in some patients it may be
1. High-e11d IIOHliHearity(Fig. 13-21 A). This occurs when end-
difficult to reach an assist level that is both adequate and
inspiratory volume approaches total lung capacity (TLC),
free offrequ en t a !arming. This problem can be eliminated
such as when external PEEP is excessive or in very severe
by increasing PEEP, thereby placing VT in the linear P-V
restrictive d isease (e.g., severe ARDS). H ere, the maxi-
range.
mum elastic assist that can be provided without nmaway
is limited, and the highestVT, with or without nmaway, is
constrained by physiologic TLC (see Fig. 13-21 A). Should
VENTILATOR RESPONSE TIME
this VT be inadequate for the patient's ventilatory de-
mand, distress will develop and catmot be relieved by Response delays are unavoidable in electromechanical sys-
increasing percent assist. Unless heavily sedated, su ch tems. In the original Wmnipeg ventilator, the delay was ap-
patients (high demand plus very stiff respiratory system) proximately 40 ms. We had assumed that the delay simply
require supraphysiologic distending pressures for ade- would result in a parallel shift relative to the target Paw
qu ate ventilation, and PAV is not suitable. waveform73 and felt that this would be acceptable. How-
2. Low-end 11011linenrity (see Fig. 13-21 B). Here, the system ever, Du et al62 recently demonstrated tl1at ventilator re-
is stiffest in the low range of tidal volume, for example, sponse delay becomes compounded during the inspiratory
FIGURE 13-21 Impact of nonlinearity in the pressure-volume (P-V) relation within tidal volume. EEV, end-expiratory volume; FRC;
functional residual ca.p acity; T LC, total lung capacity; VA, volume assist; VT; tidal volume. A. High-end nonlinearity. The P-V relation
becomes quite flat within 0.5 liter of FRC. Elastance at a volume of O.S liter is 75 cmH 2 0 /liter (pressure and volume values at the open
circle). The maximum VA that can be given without runaway is SO%. At high er assist, runaway develops until the flat region is reached . In
ei ther case, the maximum VT that can be obtained with PAV is limited by physiologic T LC. B. Low-end non-linearity. Elastance is deter-
mined at an average VT given by the open circle. At a VA of 80% E, .t he elastic assis t received is only 55% (compare the hatch ed area with
the total area inside the P-V line). Furthermore, if the patient makes a larger effort and obtains a Larger VT, elastic assist may exceed elastic
recoil, and runaway may occur ( arrow). At 50% assist, runaways would not occur, bu t the patient receives only 35% assist (not shown).
A TLC
VA 50%
0.5 1 EIV
I
Vy
r
Vr
I
FRC
0 10 20 30 40 / RV o
1
EEV
10 20 30 40
Elastic pressure above PEEP(cmH2 0)
358 PARTV ALTERNATIVEMETHODSOFVENTILATORSUPPORT
phase, resulting in cycling-off delays that are longer tha n the changes in Pac~, Pa~, and pH. Absolute contraindica-
nominal ventilator delay. In their s tudy, cycling-off delay tions therefore are patients with central apnea or very
was calculated as the difference between inspiratory flow weak efforts and no respiratory distress despite an abllor-
reaching zero and the end of neural inspiration, defined as mally low pH. Patients who are intubated for respiratory
peak Pmusc. This presentation ignores the fact that even depression (e.g., overdose or neuropathology) or who
without a ventilator, transition from inspiration to expira- had to be heavily sedated for intubation should not be
tion does not occur a t peak Pmusc but during the declining placed on PAV initially. The situation is different in pa-
phase of inspiratory activity. 42•96•97 The authors did not sub- tients alread y being ventilated with a nother mode. Here,
tract this physiologic delay. If one does that, the cycling-off weak efforts and even no efforts (e.g., on assist-control
delay attributable to the ventilator is 0.2 second w1der the ventilation or having recurrent central apneas on PSVS1)
worst conditions (80% assist, highest R/E). [The authors62 are a lmost invariably secondary to overventilation. The
also reported data in normal volunteers. These are meaning- assist with the o ther mode should be reduced first to es-
less because the time constant of the system was increased tablish that efforts resume at a reasonably normal pH
to unrealistic values (2-3 seconds) by addition of a high re- before switching to PAY.
sistance, and the rate of decline in Pmusc was not reported. Care should be exercised when initiating PAY in a pa-
In normal, awake subjects, Pmusc declines very slowly.98 ] tient with known or sus pected chronic C02 re tention
That response delays become compounded during PAV whose Paccn and pH were normalized by a no ther ventila-
delivery62 emphasizes the need for fast-responding gas- tion mode. Such patients often respond poorly to C02 un-
delivery systems in this mode. In practice, however, the til Pacol reaches a level commensurate with their prein-
reported cycling-off delays when the nominal delay is tubation value. This may result in acute hypercapnia and
40 ms (0.2 second under worst case) would be of little acidemia following a switch to PAV. Chronic C02 reten-
consequence,2° pa rticularly when one considers the perfor- tion per se is clearly not a contraindication, and m any
mance of PSV under comparable circumstances (i.e., high such patients were treated adequately with PAY. Patients
assist in a patient with a high R/ E ra tio). H ere, infla tion who develop shallow, relatively slow breathing with 110
may extend for greater than 1.0 second into neural expi- distress on PAV should have their blood gases checked,
ration (e.g., compare PSV and PAV panels in Fig. 13-7) and if they are acidemic, they should be switched to an-
or even into the next inspiratory effort (see, for example, other mode. These patients likely had undocumented
Fig. 13-8A). prior chronic C02 retention.
2. Bronchoctttaneous fistulas. Pa tients with bronchocuta-
neous fistulas should have their leak measured before
EXCESSIVE ALARMING switching to PAV. If the leak is high on another mode
Standard ventilator a larms that sound o ff every time a limit (e.g., exhaled volume less than 75% of inhaled volume),
is reached proved to be a considerable nuisance in the PAV it is better not to use PAV unless the ventilator is equipped
mode. Because of the spontaneous variability in breathing with automatic mechanics or leak-compensation algo-
pattern, one or more limits m ay be reached frequently. Fur- rithms.
thermore, without a utomatic mechanics, runaway breaths
were frequent. With incorporation of a utomatic mechanics
(see "Noninvasive Monitoring of Respiratory Mechanics, USE OF SEDATIVES IN PATIENTS ON PAV
Pmusc, and Work of Breathing," above), occurrence of nm- Seda tives are not contraindicated when PAV is used. When
away will be greatly reduced, but some may still occur [see the response of a patient to sedatives is not known, the
"Dynamic H yperinflation (DH)'' and "Nonlinearity in the dose should be titrated initially until the amount required
Pressure-Volume (P-V) Relation within the Tidal Volume to attain the desired effect without severe depression is
Range," above], and spontaneous variability will remain as learned. Because backup systems always must be available
a possible source for activating alarms. Accordingly, alarms on PAV delivery systems, the inadvertent use of an excessive
in the PAV mode should take into account the breath-by- amount of sedatives should no t be hazardous.
breath variability in breathing pattern and mechanics. A
reasonable approach (e.g., 840 PAY+ option) is to use spe-
cial filters whereby ventilator limits still function as such
for safety reasons, but alarms sound off only when the fre- Commercially Available PAV
quency of reaching a ventilator linlit exceeds a threshold
value. Delivery Systems
The BiPAP VISiOn (Respironics) is the only ventilator cur·
rently s uitable for noninvasive use. ICU ventilators have no
Indications and Contraindications leak-compensation capability. The Vis ion is equipped w ith
well-validated leak-compensation algorithms. It also has ex-
PAV is appropriate to use in all but a few situations: cellent response characteristics and trigger sensitivity and
has performed very well in several clinical trials. 21 ·23,32,33
1. Respiratory depression. Safe use of PAV requires that the The Vision offers pathology-specific default s tartup settings
patient's respiratory muscle output be responsive to as well as cus tom settings.
Until very recently, the Evita ventilator (Drager) was the Observe the screen display for the range of airway pres-
only commercial ICU ventilator capable of delivering PAV. sure and VT. Set the high limits a reasonable amotmt above
It is a basic system with no capability to monitor passive m e- the observed ranges. For example, if peak Paw ranges up
chanics in real time and with standard alarms. As indicated to 15 cmH2 0 and VT ranges up to 0.7liter, set the pressure
earlier, such basic systems (including the Winnipeg ventila- limit to 20 cmH2 0 and the volume limit to 1.0 liter.
tor) have proven difficult to use except by experts and for
short periods. SUBSEQUENT MANAGEMENT
Tyco recently released (outside the United States) a This is guided by clinical course. If distress progresses or
PAV+ option for the 840 ventilator. The ventilator moni- reappears, the values of E and R should be retitrated. Nasal
tors mechanics continuously by applying random brief end- congestion should be avoided. Ask the patient if his or her
inspiratory occlusions (see Fig. 13-14). The results have been nose is congested. If so, use decongestant, or switcl1 to full
validated? 4 In addition, the alarms were modified to al- face mask. If distress persists, then other methods of therapy
low for pressure and volume limits to be reached occa- should be consid ered . With clinical improvement, percent
sionally without the alanns sounding off. With this option, assist is reduced in steps guided by patient feedback. Be-
the maximum possible airway pressure, including PEEP, cause improvement may occur rapidly, it is a good idea to
is 35 cmH20. This may be a limitation in a few patients ask the patient at intervals whether the assist is too much
on high PEEP whose resistance is also high. Another lim- and to see whether a lower percent assist is tolerated.
itation is that the resistance measured is expiratory, so in
patients with severe expiratory-flow limitation, inspiratory TROUBLESHOOTING
resistan ce may be overestimated. Although the ventilator corrects for leaks, it takes it three
A new ventilator capable of PAV delivery is about to be to five breaths to adjust to a leak change. A sudden change
released in Japan (SSV, Kawasaki Safety Services). It is also (e.g., mouth opening or loosening of mask) may result in a
equipped with the automatic mechanics function, but there- transient increase in applied pressure (up to the set limit).
sistance is measured with an inspiratory-pulse teclmique.49 Patients should be instructed to keep their mouth closed. For
talking or feeding, percent assist can be reduced to zero (or
the ventilator disconnected) temporarily. When the prob-
Adjustment at the Bedside lem occurs without mouth opening, the straps need to be
tightened.
NONINVASIVE APPLICATION
Frequent activation of alarms may be secondary to the
General instructions regarding noninvasive ventilation are alarm levels being set too low relative to the prevailing ven-
similar to those for other modes and will not be discussed tilatory demand CVEand VT demands may have increased)
here (see Chapter 19). The following procedure pertains to or to improvement of mechanics since the last titration, w ith
BiPAP Vision (Respironics). the assist now becoming excessive. Note the range of VT on
the display, in particular the highest volumes. Reduce per-
STARTUP cent assist by 20% or so. If the large VTs are eliminated and
It is neither necessary nor recommended to attempt to mea- alarming stops, the problem was an improvement in me-
sure respiratory mechanics. Patients are alert, and settings chanics, and the large breaths were runaways. Retitrate E
are best accomplished using patient feedback. Before attach- and R. Conversely, if the large volumes continue to occur,
ing the ventilator to the mask, the limits should be set ini- then the problem is large ventilatory demand or marked
tially to a maximum pressure of 20 crnH2 0, a maximum breath-by-breath variability. In such cases, the limits should
volume of 1.5 liters, and a m aximum inspiratory duration be adjusted upward.
of 3 seconds. EPAP should be set to the minimum value
(4 cmH20). Many patients prefer a lower EPAP, but 4
INTUBATED PATIENTS
cmH20 is the lowest setting on the BiPAP VIsion. Set the
ventila tor in the "custom" mode to permit manual adjust- The following pertains to the PAV+option on the 840 ven-
ment. Percent assist should be set to 99%. In this fashion, tilator because it is currently the only ventilator available
theE and R inserted in the ventilator are the actual VA and with automatic mechanics and "smart" alarms. The pro-
FA delivered to the patient. Set E a nd R initially to 2 and 1, cedure for setting basic PAV systems has been d escribed
respectively. elsewhere. 99 As indicated earlier, such systems are d ifficult
After attaching the ventilator to the patient and waiting a to manage for extended periods. If other systems are used,
few breaths for the patient to adapt, inform him or her that full (i.e., 100%) automatic tube compensation (ATC) should
the assist will be increased in steps and that he or she should be avoided. With complete compensation for the nonlinear
signal approval/ disapproval by some agreed-on system. In- component of resistance, very small errors in estimated R
crease E insteps of one, waiting a few breaths between steps, may cause aggressive flow runaway with rapid loss of the
until the patient signals that the assist is too high. Go back assist secondary to ventilator limits (see " Runaway Phe-
one or two steps. Repeat using the R input. Increase EPAP nomenon," above).
by 1 cmH20. If the patient signals approval, keep increasing
EPAP. Most will not want more. Finally, perform final ad- STARTUP
justment of E. Some patients will prefer a somewhat lower 1. Enter ideal body weight (JBW). Tftis is an important
E setting once the other variables are optimized. step. IBW does not have to be precise but should be a
reasonable approximation of reality. It takes the venti- and switch to another mode until this issue is addressed
lator four breaths to de termine actual E and R. In the scientifically (see ''Important Unknowns," below).
interim, it uses default values based on normal E and • Breathing may be highly variable in some patients. This
R values for a patient of the specified size. Should the is normal.
specified IBW value be for a much smaller patient, the 2. Patient shaws signs (other than tachypnea) of inadequate sup-
first few breaths may be overassisted. port. No one, including the writer, has yet much direct
2. Enter endotracheal or tracheostomy tube size. This in- experience with the new 840 PAV+ option. The follow-
put is also quite important because part of the delivered ing are tentative recommendations based on previously
assist is based on stated tube size. documented mechanisms of distress on PAV and our un-
3. Set expiratory sensitivity (Esense) to 3 (default value). derstanding of the functioning of the 840 PAV+ option.
4. Set triggering to flow modality a t 3 liters/min. These apply whether distress develops soon after initia-
5. Enter humidifier volume if a pplicable. tion of PAVor develops later:
6. Set high tidal volume limit (Vn limit) to a value corre- • Increase percent assist to 85%. Further increases add
sponding to 15 m l/kg mw. very little actual assist and increase the likelihood of
7. Set high peak pressure (HIP) limit to 40 cmH20 (de- runaway and instability. If the patient s till appears to
fault). The ventilator caps the assist at the HIP limit less be in distress or uncomfortable:
5 cmH2 0 or 35 cmH2 0, whichever is less (i.e., breath • Ensure that the HIP limit is 40 cmH20 . Inspect the Paw
is not terminated, but pressure cannot increase beyond waveform display for several breaths. If Pawdoes not
this level). Setting HIP to a hig her value has no effect in reach 35 cmH20 or reaches it only in the occasio nal
this option. Setting it to a lower value may restrict the breath, proceed to the next step. If it reaches 35 cmH20
assist given unnecessarily. in the latter part of inspiration in most breaths, the pa-
8. Set percent assist to 60%. It is better to start on the low tient needs more assist than can be provided by the
side and increase if necessary. Most pa tients do very PAV+ optio n. Tl'lis scenario should be very rare and
well a t 60%. The use of higher values at the outset, before indicates high-end nonlinearity [see "Nonlinearity in
enough mechanics values have accumula ted, may result the Pressure-Volume (P-V) Relation within the Tidal
in overassist. Volume Range," above) plus high ventilatory demand.
9. Set PEEP to 5 cmH20 unless a higher value is deemed The patient needs to be sedated. If heavy sedation must
necessary for oxygenation. be used, consider switching to another mode (e.g., as-
10. Activate the PAV mode. sist control). If Paw reaches 35 cmH20 immediately af-
ter triggering and stays there until the cycle ends (i.e.,
squarewave pattem), flow runaway exists because of
overestimation of inspiratory resistance (the 840 PAV +
SUBSEQUENT MANAGEMENT option uses expiratory resistance to infer inspiratory
AND TROUBLESHOOTING resistance). Unfortunate ly, there is no direct way to ad-
1. Patient appears comfortable at initial settings. This is the typ- dress this problem in the current version of the PAV+
ical response. Subsequent management is similar to that option. Tl1e patient is not in the PAV m ode but is essen-
for other modes a nd consists of gradual reduction in as- tially receiving pressure-support ventilation (PSV) of
sist (percent assist in this case) as warranted by clinical 30 cmH20 plus 5 cmH20 of PEEP. The problem is more
condition . In clinically stable patients, percent assist is likely discomfort with excessive pressure rather than
reduced in 10-20% d ecrements. If respiratory rate does inadequate assist. Either switch to a different mode or
not increase and other manifestations of distress do not reduce the HIP limit. This reduces the pressure cap. For
appear over a few hours, it may be reduced further. If sus- example, if HIP is reduced to 30 cmH20 , the cap is 25
ta ined tachypnea (rela tive to the previous level) or other cmH 20, and this is equivalent to PSV of 20 cmH20 +
distress manifestations appear, percent assist should be PEEP of 5 cmH20 .
increased again, preferably to 20% higher tha n the level • If Paw is not capped at 35 cmH2 0 or reaches this level
that resulted in tachypnea to maintain some reserve. only occasionally, the problem is either severe dynamic
The following are some additional recommendations that hyperinflation or low-end nonlinearity (see "Limita-
pertain specifically to PAV: tions," above). PEEP needs to be titrated to an optimal
• Patients with suspected prior cluonic hypercapnia level. Note the displayed average E. Increase PEEP by 3
should have arterial blood gases checked a half hour cmH 2 0, and follow the change in E over a few minutes.
after initiation of PAV to exclude significant acidemia If it decreases, increase PEEP another 2 cmH20 . Repeat
(see "Indications and contraindications"). until E no longer decreases. Go back to the immedi-
• If breathing pattern is rapid and shallow (e.g., RR > ately preceding PEEP. If this procedure does not relieve
30 breaths per minute and/or VT < 5 ml/kg) but the the distress, the problem is almost certainly severe d y-
patient is comfortable, increase percent assist to 85%. namic hyperinflation not responsive to PEEP [i.e., high
If the pattern remains the same, then it is not distress- resistance is in the tubing (including the endotracheal
related. Return to 60%. Whether to maintain the patient tube)]. Until triggering is linked to onset of effort [see
on PAV in this case is debatable. There is currently no "Dynamic Hyperinflation (DH)," above and Fig. 13-7],
information to indicate tl1a t sucl1 a pattern is harmful, such patients cannot be supported adequa tely with
but some practitioners may prefer to be on the safe side PAV.
CHAfYI'ER 13 PROPORTIONAL-ASSIST VENTILATION 361
Important Unknowns Summary and Conclusion

Whereas the physiologic advantages of PAV have been When we wrote this chapter in the first edition of this book,73
proven, it is not clear whether these necessarily translate PAV was only an idea with very limited clinical data. The
into clinical benefits. There are reasons to believe that clini- chapter was mostly theory and speculation. In the interven-
cal outcome will improve (see " Clinical Outcome," above). ing 12 years, many studies have confirmed PAV's feasibil-
This needs to be confirmed, however. Questions may be of ity and its opera tional features and physiologic superiority
a general nature (e.g., "Are mortality, length of intubation, over other modes. These studies, however, also have iden-
and length of ICU stay less with PAV?") or may be directed tified a number of practical limitations that precluded it use
at specific aspects that we know affect outcome (e.g., by as a routine method of support or even for extended use
comparison with optimal protocols with other modes): in research studies. These limitations have made it difficult
to ask the most important question: Does better physiology
lead to better clinical outcome? Now that the practical lim-
• If sedation is used on an "as needed" basis, will patients itations have been resolved, it will be possible to carry out
need less sedation on PAV? such studies. Although there are good reasons to believe
• Will tidal volume over the course of illness be smaller on that clinical outcome will be better, critical illness is very
average? complex, and it may be that poor patient-ventilator interac-
• Is weaning faster? tion is an insignificant contributor to overall outcome. Only
time will tell.
We believe that two other questions need to be addressed.
These relate to management of tachypnea that is unrelated
to distress, a phenomenon that is evident only when PAV is Acknowledgment
used:
This work was supported by the Canadian Institutes of
Health Research.
• If a patient decides to breathe in a rapid, shallow manner
while on high PAV support (see, for example, Fig. 13-58),
should he or she be left on PAVor switd1ed to another References
mode?
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Chapter 14 _ _ _ __ _ _ _ __ pa ttern generato r and respiratory muscles on their own,
however, can operate only in an open loop in which there is
CLOSED-LOOP a unidirectio nal flow of info rmation from controller to effec-
tor. Responding approp riately to the changing ventilatory
VENTILATION demands of life requires a third crucial element, the sensors,
which continually p rovide the controller with an assess-
JASON H . T. BATES men t of how well the effectors are doing their job. This feed-
back of info rmation closes the control loop, allowing actions
to be modified continuously in light of their consequences.
There are a nu mber of respira tory sensors, the most im-
portant for every d ay life being the central chemoreceptors
that track carbon dioxid e (C0 2) levels in the blood via their
CONTROL OF SPONTANEOUS RESPIRATION effect o n the pH of cerebrospinal fluid .1 When these levels
CLOSED-LOOP CONTROL ALGORITHMS move above o r below the narrow norma l range, the con-
Control by Explicit Formulas troller commands the effecto rs to either increase or d ecrease
PID Control their pumping action, as the case may be, to return the arte-
rial partia I pressure of C0 2 (Paco2 ) to normal. Of course, the
Fuzzy Logic Control
control of ventilation d epends on other factors sucl1 as the
VENTILATION CONTROL STRATEGIES
THE FUTURE arterial pa rtial pressure o f oxygen (Pao,) and the degree of
SUMMA RY AN D CONCLUSIONS lung inflation 1 and can be overridden temporarily by con-
scious decision rna king. Also, there ar e an infinite number o f
combinations of f and VT in Eq. (1) that will produce a given
We breathe a ccording to our needs. Thus breathing fre-
quency <0 a nd tidal volume (VT) are chosen to produce an value of VA, yet f a nd VT var y remar kably little w ithin and
be tween ind ividuals, possibly because of additional con-
alveolar minute ventilation ("VA) appropria te to the prevail-
straints rela ted to minimization of muscular work.2 Never-
ing me tabo lic d ema nds. In simple terms, we can say that
theless, the controller-effector-sensor parad igm in Fig. 14-1
embodies the essential elemen ts in volved in the closed-loop
(1) control of natural ven tilation.
Mechanical ventilation replaces, either partially or com-
where Vo is the volume of the d ea d space in the lungs. pletely, the respiratory muscles in th eir role as effectors. It
Throug h independent choice of f and VT, the normal, also d oes away with the natural controller and sensors, re-
healthy ind ividual can adjust VA manyfo ld from rest to se- placing both with the attending health care professiona l;
vere exercise. Failure to choose an app ropriate level of VA medical opinion becomes the controller, whereas the role of
has significant negative consequences, so tight control of sensor is assumed by clinica l acumen aid ed by such techni-
ventila tion is essential. When the respiratory contro l sys- cal devices as the blood -gas ana lyzer and saturation moni-
tem fails to functio n pro perly, respira tory fa ilure itself may tor. These artificial controllers and sensors, however, fall far
ensue. short of their natural counterparts for a variety of reasons,
Pa tients in respiratory failure can be managed for ex- no t the least of which concerns their availability. It is typ-
tended periods with mechanical ventilation. This practice ical for patients in the intensive-car e unit (ICU) to be seen
has reached high levels of sophistication and effectiveness, by the attending physician once or twice per day and to be
with closed-loop contro l being a key component of the cur- evalua ted by other health care staff only somew hat more
rent sta te o f the art. Mechanical ventilation, ho wever, is still often unless there is a crisis. Resource limitations make this
far from being a per fect s ubstitute for the real thing and is inevitable, o f cou rse, but the result is a poor substitute for
associated with sig nifica nt morbidity and mortality. Indeed, the moment-to-moment con trol of the ventilatory pattern
weaning patients from the ventilator as quickly as possible (f, VT, etc.) that occurs naturally in the healthy individual.
is always a key management goal. Thus the d evelopment Thus, a lthough the contro l loop in Fig. 14-1 can be consid-
of imp roved m ethods o f mechanical ventilation remains an ered closed with respect to conventional mechanical venti-
active a rea of research. It is likely that closed -loop control la tion in one sense, a complete circuit of the loop for a typical
will play an increasingly important role in this effort. patient often takes so long that the control is effectively open
loop fo r much of the time. It seems logical to suppose that
this state of affairs would be improved markedly if sensing
Control of Spontaneous Respiration could rely entirely on medical d evices, and the physician
could be replaced by a compu ter algorithm (see Fig. 14-1).
The control o f sponta neous respiration is undertaken, for This is much easier said than d one, however, and the com-
the most part, by the central pattern gene rator in the bra in plete implementation and acceptance o f automatic closed-
stem. Periodic commands from this controller are sent via loop ventilation a re likely some dista nce in the future.
the respira tory motoneurons to the respiratory muscles, Nevertheless, many currently employed modes of venti-
which act as effectors in bringing about the alterna ting pro- latio n use closed -loop control in some way or other. Un-
cesses of ins pira tion and expiration (Fig. 14-1). The central d erstanding the p rinciples of closed -loop control is thus
365
calculate how f should be set for the subsequent breath. Ide-

Sensors Controllers
ally, this information should be available before mechanical
Chemo/Mechano- Central pattern ventilation is initiated so that the initial ventilatory param-
receptors generator (brain)
eters are suitable for the situation a t hand. 6
D
Clinical acumen
D
Clinical decisions
Another example of control by explicit formu la is that in-
volved in proportional-assist ventilation,1-9 also known as
D
Medical Devices
D
Computer algorithm
negative-impeda11ce ventilation. 10 Tracheal flow (V) and vol-
ume (V) above functional residual capacity are monitored
continuou sly so that a ventilator can be directed to generate
an airway pressure (P) according to
Effectors
Respiratory muscles P(t) = aRrsV(t) + ,BErsY(t) (3)
D
Mechanical ventilator where Rrs and Ers are respiratory system resistance and
elastance, respectively, and ex and fi are constants between
FIGURE 14-1 The controller-effector-sensor paradigm of 0 and 1. The ventilator thus takes care of a fraction a of the
ventilatory control. (Adapted, with pennission, from Ba.tes eta/:
resistive load of breathing and a fraction fi of the elastic
Respir Care Clin North Am 7:363-77, 2001.)
load, leaving the patient's respiratory muscles to deal w ith
the remainder. The values of a and .B are chosen by the
important for appreciating the limitations and promise of physician on the basis of how much ventilator assistance the
current and future approaches to mechanical ventilation. patient needs. The g reat advantage of proportional-assist
ventilation is that although the patient remains in charge of
how much flow and volume are going to enter his or her
Closed-Loop Control Algorithms lungs, he or sh e does not have to do all the work required.
The principal difficulty with implementation of
The essence of closed-loop control is feedback, which allows proportional-assist ventiation, however, is that the algo-
the pursuit of a target to be adjusted continuous ly according rithm becomes unstable if either rx or .B in Eq. (3) is greater
to the movement of the target itself. Good control is achieved than unity. 11 Ensuring that this does not happen requires
when the pursuer is able to respond rapidly to changes in that Rrs and Ers be known. Both these quantities may
target position and depends to a large extent on the capa- change during the course of ventilator support, cau sing
bilities of the effectors that are being controlled. Tl1us, for the work required o f the patient's respiratory muscles to
example, good control of airway pressure during mechani- change accordingly. Proportional-assist ventilation thus
cal ventilation requires a pump that is able to generate any would be enhanced by feedback on the values of Rrs and
desired presstJre within a small fra ction of the breath cy- Ers so that the values of rx and .B could be adjusted ap-
cle. Even when all the physical engineering requirements propriately. Unfortunately, evaluating Rrs and Ers during
are met, however, effective closed-loop control will not b e proportional-assist ventilation is problematic, which has
realized without a suitable servo-control algorithm that de- made it difficult to realize the full potential of this mode.11
termines how the pump is going to be driven. A promising approach to d ealing with this problem is to
use the patient's own neural drive as an index of how
much ventilator assistance is required, 12 although this
CONTR OL BY EXPLIC IT FORMULAS demands instrumentation of the esophagus with electrodes
to measure the diaphragmatic electromyogram.
In some situations, there may be an explicit formula that tells
the controller how to track the target precisely. An example
is the choice of f during adaptive-support ventilation,3-5 PID CONTROL
which is determined by the following formula based on the
notion of minimization of the work of breathing-2: In mos t pursuit situations, the pursuer cannot reacl1 the
target immediately but rather can only move in the di-
rection of the current target position. Consequently, when
J1 + 2aRC(VA/Yo) -1 the target position is finally reached, the target has already
(2)
f= aRC moved on to a new position. The pursuer therefore must
be content with being constantly on the target's tail but
where RC is the respiratory time constant (the product of never actually catching it. The classic way this is achieved
resistance Rand compliance C), and a is a constant that de- is through a proportional-integral-differential (PID) servo-
pends on the flow waveform. In order to implement this control algorithm, 13 some subset of which is u sed widely in
formula, the values of R, C, VA, and Yo must be known. Al- the control of mechanical ventilators. 14
though not a trivial undertaking, it is possible to measure all To see how PID servo control works, suppose that a piston
these quantities in an individual patient. If such measure- pump is to be u sed to generate a specified -volume wave-
ments could be m ad e fo r each breath, then, in principle, one form. In fact, precisely tl1is approach has been taken to apply
could feed these values back into the preceding formula to proportional-assist ventilation in humans 15 and to measure
CHAPTER 14 CLOSED-LOOP VENTILATION 367
Piston
pump
V(t) Err(t)
~ v(t) I
\..,/
v Motor
!
I
FIGURE 14-2 PToportional feedback control of a
mechanical volume ventilator. The volume output Vm(t)
is compared with a desired volume sig.nal V(t). The
difference between these two signals, Err(t), is then
IIIII ~ amplified (gain factor g) to produce a voltage si~;nal v(t)
Vtt) that controls a motor that, in tum, drives the ventilator
piston.
respiratory input impedance in small laboratory animals.16 totic approach to the target volume, the piston executes a
TI1e effector in this case is a motor that drives the piston series of damped oscillations known as ri11giug (Fig. 14-3).
back and forth (Fig. 14-2). TI1e volume change generated by Indeed, if g is large enough, the oscillations may not even be
the piston can be measured by a variety of sensors, but it is damped but may increase in size indefinitely as the system
perhaps easiest to imagine that a displacement transducer is becomes unstable. Instability also can be caused by a delay
used to register the position of the piston face. The product between the time the controller issues a command to the m o-
of the face a rea and the change of piston position then pro- tor and when it responds. The result is often a sequence of
vides volume as a function of time. This measured volume exaggerated oscillations known as hunting as the controller
signal (Vm) provides feedback to a controller that must di- attempts to chase a target that is always several steps ahead
rect the motor to move the piston in a prescribed manner. of it. An equivalent situation is seen in the spontaneous con-
TI1e question is, How should the controller use Vm to direct trol of respiration; periodic Cheyne-Stokes breathing may
the motor? be caused either by oversensitivity of the central chemore-
A simple algorithm suitable for this situation is propor- ceptor (equivalent to an increase in g) or by a delay in the
tional control (i.e., the P in PID). Here, the controller tries circulation tinle from the lung to the central chemoreceptor.1
to make the difference between Vm and the desired volume Further improvement in control of the piston thus may be
signal (V) as small as possible by always directing the motor acl1ieved by considering not only how far it is from the target
to move in the directio11 that reduces V- Vm. The voltage at any given instant but also how fast it is moving. Oearly,
signal v(t) sent to the motor is thus for a given distance from the target, a smaller push from the
controller is required if the piston is already approaching
v(t) = g[V(t)- Vm(t)] the target rapidly than if it is stationary. Thus the v(t) sent
to the motor should be supplemented by an additional term
= gErr(t) (4)
proportional to the time derivative of Err(t) (the Din PID).
The complete algorithm for PID control thus is
where Err(t) is the error signal, and g is a gain factor that
determines how vigorously the motor is going to make the
piston pursue V(t). This s trategy is called P co11trol because [' dErr(t)
v(t) = g1Err(t) + g2 Jo Err(t) dt + g3 dt (5)
it acts in direct proportion to the distance between the target
and the current position of the object being controlled.
A limitation of P control is that the force driving the pis-
FIGURE 14-3 lf the ventilator in Fig. 14-2 begins with its p iston at
ton tends toward zero as the target is approached. If there Vm(t) = 0 and is given a command at titne = 0 to produce
is a force and velocity below which the piston suddenly Vm(t) = 1, it may Tesponse sluggishly if the value of g is small
sticks, such as often occurs owing to static friction, then (dotted liue), briskly if g is increased (solid liue), and with an
there w ill be a limit to how close P control can get the pis- oscillating overshoot if g is too large (dashed liue).
.'.''.
ton to the target position. What is required when the piston '
sticks is a control signal that increases w1til the piston starts ••
to move again. Such a signal is provided by adding a sec- • •
ond term to v(t) that is proportional to the time integral ••' ''
' ,,
of Err(t) (the T in PID). When the piston initially becomes U) ''' '' ' '
stuck, this term may be very small, but it will build up lin- ""c::l 1 ' ''' '' ' ''' ,-,
'I ' '
early with time until the piston is finally able to break free (!- ' . . ... ~-··· • • ••••••
e '• \
...... ..... .
I ·--
''
\ ~
from the bonds of static friction and proceed on toward the 'I •
""
£ ' .•
target. ._.
<13 ' ,'..
\
,,. I ••
-
~
Control of the piston in Fig. 14-2 also depends o n its mass. ~
If the piston has significant inertia, it will take time to accel- ;[

erate, whid1 will increase the time it takes to reach the target.
Increasing the value of g can help to a certain degree. If the
acceleration is too great, however, then the piston will have
difficulty decelerating as the target volume is approached, 0
causing it to overshoot. Thus, instead of a smooth, asymp- Time (arbitrary units)
where g1, g2, and 8J a re separate gain factors that have opti- LOW HIGH
mal values depending on the physics of the particular con- 1
trol situation a t hand. This combined strategyofPID control
may result in significantly better target tracking than P con-
trol alone when the piston is affe.cted by friction and has
significant mass. Note also that we have used Err(t) here
A
to represent the difference between target and actual p is-
ton positions, but this error signal could be based on other ->
Q)
targets, such as flow measur ed at the airway opening.
PID-type controllers obviously are well suited to the con- -c. 0 30
Q)
40
trol of ventilators for the purposes of producing prescribed
flow or volume wavefom1s and have bee n used in various
·-
J: PC02 (mmHg)
50 60
0
guises for these purposes.1s-17 They also have been used in a...
Q)
the pursuit of physiologic goals, such as the control of ar- .a DECREASING STABLE INCREASING
terial oxygen saturation and end-tidal co2, 18 •19 as well as E 1
positive end-expiratory pressure (PEEP)_20,21 Q)
~
B
Fuzzy LOGIC CONTROL
Although PID controllers are the mainstay of servo-control
algorithms, they have some limita tions. First, they are lin-
ear, which means tha t they drive the effectors in direct pro-
portion to Err(t) and its integral and derivative. This is not
always appropriate. Second, evaluation of optimal values
fo r the gain coefficients g1, g 2 , and g 3 in Eq. (5) may be diffi- ~PC02 (mmHg/hr)
cult when the control variables are not readily quantifiable. FIGU RE 14-4 Example fuz:z.ifications of (A) Pco1 and (B)..O.Pco1 •
A useful heuristic alternative to PID control is provided by Re presentative m eas urem e nts of each variable a re indicated by
fuzzy logic,22·23 the principles of which are best explained the vertical das hed lines, which give m emb ership levels of abou t
through a simple example.22 0.45 in low and 0.55 in nonual fo r Pco2 and 0.5 in both decreasing
Suppose that we wish to control the minute ventilation and stable for ..O.Pcez. (Adapted, w ith permission, from Bates eta/:
Respir Care Clin No·rth Am 7:363- 77, 2001.)
(VE) that a pa tient receives and that the only information
available about the patient's status is an hourly measure-
ment of arterial Pc~· Each hour an adjustment must be
made to VE based on the current reading of Pco2 and how binations low and decreasing, low and stable, normal and de-
it has changed since the last reading (.6Pc~) .ln some cases creasing, and nonnal and stable.
the appropriate course of action w ill be obvious, whereas The next step is to decide what action should be taken for
for others there may be no clear g uidelines, so the physi- each pa ir of set memberships. For example, if Pc0z is normal
cian will have to rely on intuition and experience to make a and .6Pc0z is stable, then VE probably should be maintained
decision. unchanged, whereas if Pea, is high and .6PcD2 is incre11sing,
Fuzzy logic deals with this situation by dividing the range then VE should be increased a lot, and so on. We thus can
of possible values for Pco2 and .6Pco2 into overlapping specify rules for every possible pair of fuzzy set member-
fuzzy sets that are represented in terms of level of mem- ships for PcDl and .6PcO:z, as show in Table 14-1.
bership. For example, a value of Pc~ w ill have a member- For the rules in Table 14-1 to be implemented, sucl1 terms
ship level of 1.0 in the normal set for a range of values that as incre11se a lot must be translated into precise changes in
are definitely nom1al, whereas either side of this range the VEin temlS of liters per minute. This is achieved again us-
membership level decreases gradually to zero in a manner ing fuzzy sets. For the purposes of this illustratio n, we will
that reflects increasing levels of doubt about normality. Sets divide the range of .6 VE into five fuzzy sets labeled increase
corresponding to high and low values of Pcaz can be con- a !of, increase a little, maintain, decre11se a little, and decrease n
structed similarly. Figure 14-4 A shows an example of such
a fuzzification, whereas Fig. 14-4B shows a corresponding
TABLE 14-1 Ru le Tab le for All Pairs of Fuzzy Set
construction for .6PcOz·
M embersh ips in Fig. 14-4
Because the fuzzy sets depicted in Fig. 14-4 overlap, some
values of Pc~ and .6Pc~ have membership in two sets si- Pcea
mu ltaneously, with the respective levels of membership re-
flecting the probability of belonging to either set. Each pair t.Pcea Low Normal High
of Pc0z and .6Pc0z measurements thus leads to one or more
Decreasing Decrease a lot Decrease a li ttle Maintain
pairs of fuzzy set memberships. In the case of th e exam-
Stable Decrease a little Maintain Increase a little
ple shown in Fig. 14-4 with Pc0z = 38 mmHg and .6Pco2 = Increasing Maintain Increase a little Increase a lot
-0.5 mrnl-Ig/ min, there is finite membership in the set com-
CHAPTER 14 CLOSED-LOOP VENTILATION 369
DECREASE DECREASE INCREASE INCREASE that of a human engaging in subjective judgment. As such,
A LOT A UTILE MAINTAIN A UTILE A LOT
fuzzy logic is especially suited to certain aspects of med-
1
-Cl,)
ical decision making·24 and h.:"ls been used in a variety of
medical applications.25-30 Fuzzy logic also appears to have
>
-c.
Cl,)
promise as a means of automatically controlling mecl1anical
ventilation. For example, Nemoto et al31 developed a fuzzy
·- logic algorithm for controlling pressure-support ventilation
based on ongoing assessments of VT, f, heart rate, and ar-
terial 0 2 saturation, together with their respective rates of
change. Similarly, Schaublin et al32 used fu zzy logic to con-
trol VT and f during anesthesia to try to maintain end-tidal
c~ at a predetermined level.
11Ve (mVKg/min) Ven-tilation Control Strategies

FIGURE 14-·5 Example fuzzificalion of VE into five fuzzy sets . The preceding discussion has focused on the engineering
The hatched area indicates the weighting of the sets that problem of getting a mechanical ventilator to achieve a spec-
contribute to the final action to be taken. The precise value of the ified goal, for which the well-developed techniques of PID
final action for the example measurements of Pco2 and aPco2 control and fuzzy logic are at our dis posal. A more signifi-
(indicated by the dashed lines in Fig. 14-4) is equal to the area's cant challenge for the future of closed-loop ventilation, how-
centroid located at the position of the arrow. (Adapted, with ever, is the medical problem of deciding what the ventilation
pennission, f!'Om Bates et al: Respir Care Clin North Am. 7:363- 77,
goal, or goals, should be. A dog chasing a rabbit represents
2001.)
a complex closed-loop control problem for the do& but the
overall strategy is obvious- catch the rabbit. In mechanical
lot. Considering the example shown in Fig. 14-5, this leads ventilation, the goal frequently is less clear and depends on
to fuzzy set memberships of the clinical situation. During elective surgery, for example,
the goal of mechanical ventilation simply may be to main-
Pcez: 0.45 in /crw tain normal blood gases. Indeed, the earliest applications
0.55 in nonnal
of closed-loop ventilatory control aspired to precisely this11
~Pc0z : 0.50 in decreasing and date back as mucl1 as 50 years.~'1 • 33 - 35 Some of these
0.50 in stable
early efforts were rather impressive, such as that of Frumin
Invoking every pair combination of these sets in the rule et al, 34 w ho were able to maintain end-tidal C02 within 3
table (see Table 14-1) gives the following actions: mmHg of the desired value by controlling airway pressure.
More recently, Anderson and East21 used a dosed-loop PID
controller to adjust PEEP and inspired 0 2 fraction automat-
Low and decreasing = decrease a lot
ically in order to control Pao 2 and were able to maintain
Low and stable = decrease a little
control in 84% of a small group of patients with acute res-
Normal and decreasing =decrease n liHie
Normal and stable = maintain piratory distress syndrome.
During surgery for major trauma, on the other hand, ven-
tilating the lung in a manner that minimizes the risk for
The final action clearly is going to be some weighted sum ventilator-induced lung injury is likely to be an additional
of these four actions. The weighting factor for each action consideration. For example, Jandre et al 20 recently devel-
is taken as the smallest of the two set memberships in Pc0z oped a control scheme based on the simultaneous control of
and ~Pcez that produced it. Thus, for example, the action end-tidal Pc0z and PEEP, together with minimization of the
decrease a lot came from a membership of 0.45 in low for ratio of peak alveolar pressure to peak inspiratory resis tive
Pco, and 0.50 in decreasing for ~Pco,. Therefore, decrease pressure. The latter condition was postulated to minimiz~
a lot receives a weighting of 0.45. the risk of ventilator-induced lung injury. They tested their
These weightings finally are converted into "crisp" val- controller in piglets and found that it compared fa vorably
ues of~ VE as indicated in Fig. 14-5, where each of the fuzzy with manual titration of ventilation, being able to respond
action sets is highlighted to a level equal to its weighting to step changes in inspired C02 with a rapidity similar to
factor. If an action set is invoked more than once, as oc- that of the normal f hysiologic response. Along the same
curs in this example with decrease a little, then the largest lines, Tehrani et al1 developed a scheme that chooses val-
of the weighting factors is used. This defines a polygonal ues for VT and fbased on ventilatory needs while simultane-
shape whose centroid gives the predse value of ~VE to ously attempting to minimize the work of breathing. They
be applied to the patient, which in this example is close also achieved encouraging results in pigs, finding that un-
to -7 ml/kg/ min (see Fig. 14-5). der steady-state conditions, arterial 0 2 saturation and end-
Although fuzzy logic control can be used with systems tidal Pc~ exhibited standard deviations of 1.76% and 1.78%,
amenable to the classic PID algorithm, it really comes into respectively. Another example of control of multiple tar-
its own when the nature of the control problem is similar to gets is that developed by Iotti et al,36-38 who developed an
algorithm for incrementally adjusting the applied pressure Summary and Conclusions
level during pressure-support ventilation. Their goal was
to achieve satisfactory levels of both VE and patient effort Closed-loop mechanical ventilation involves the use of feed-
simultaneously, the latter being assessed in terms of Po:1 back to control how a ventilator delivers flow to a patient.
(the airway occlusion pressure measured 0.1 second after PJD-type control is used widely in modem ventilators to
the start of inspiratory effort). They were able to main- produce a prescribed flow or volume waveform. The ac-
tain P 0.1 at between 1.5 and 4.5 onH20 while preventing tual control strategy (i.e., whicl1 flow or volume waveform
hypoventilation. 38 should be applied), however, is still largely up to the attend-
Closed-loop ventilation thus can involve the s imultane- ing health care professionals. Using a computer algorithm to
ous pursuit of multiple situ ation-specific goals. A basic decide on the control strategy (i.e., replacing the physician
premise bel1ind any form of closed-loop ventilation, how- as controller) remains in the experimental s tage, although
ever, is that the information necessary to implement the ul- a number of promising approaches are being developed.
timate control strategy is contained within the quantities Among these are knowledge-based systems for weaning,
providing feedback to the controller. A case in point is au- fuzzy logic for control of ventilator assist, neural control of
tomatic weaning of patients from mechanical ventilation. It proportional-assist ventilation, and the use of PJD control
is compelling to think that automating either the gradual to pursue tl1e control of blood gases and the minimization
withdrawal of ventilator support or the decision to extu- of lung injury simultaneously.
bate would be advantageous in terms of both reducing time
on the ventilator and relieving the workload on medical
personnel. Indeed, much work toward this end has been
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30. Velasevic OM, Saletic DZ, Saletic SZ A fuzzy sets theory applica- Care Med 2000; 161:1161-6.
tion in determining the severity of respiratory failure. lnt J Med 45. Krishnan JA, Moore 0 , Robeson C,et al. A prospective, controlled
Inform 2001; 63:101- 7. trial of a protocol-based strategy to discontinue mechanical ven-
31. Nemoto T, Hatzakis GE, Thorpe CW, et al. Automatic control of tilation. Am J Respir Crit Care Med 2004; 169:eak 673-8.
Chapter 15 _ _ _ __ _ _ _ __ is tightly regulated, with minute ventilation potently en-
hanced in response to small elevations in C0 2 tension. Al-
PERMISSIVE though usually well tolerated, hypercapnia traditionally has
been considered to be ad verse. In fact, the extent and sever-
HYPERCAPNIA ity of acidosis are predictive of adverse outcome in diverse
clinical contexts, including cardiac arrest, 1' 2 sepsis,3 - 5 and
JOHN C. LAFFEY in the neonate. 6 Traditional approaches to C02 management
BRIAN P. KAVANAG H in the operating room and for patients with acute respiratory
failure have focused on the deleterious effects of hypercap-
nia, therefore targeting normocapnia or even hypocapnia.
This approach, however, has been questioned increas-
ingly.The potential for high tidal volumes to injure the lung
directly, a phenomenon termed ventilator-induced lung in-
RATIONALE jury, is dear from experimentaf,S and clinical9- 13 studies.
BASIC PRINCIPLES Strategies with lower tidal volumes (VT) generally neces-
Permissive Hypercapnia sitate hypoventilation and tolerance of hyper capnia. This
Therapeutic Hypercapnia "permissive hypercapnia" has been accepted progressively
Accidental Hypercapnia in critical care for adult, pediatric, and neonatal patients
Determinants of Hypercapnia requiring mechanical ventilation.
Effects on Alveolar Gas Exchange
PHYSIOLOGIC EFFECTS
C02 Versus Hydrogen Ion Rationale
Pulmonary Effects
Central Nervous System Effects The potential for mechanical ventilation to contribute to
Cardiovascular Effects lung and systemic organ injury and to worsen outcome
Renal, Hepatic, and Splanchnic Effects in patients with th e acute respiratory distress syndrome
Cellula r and Molecular Effects of Hypercapnia (ARDS) is clear. The use of high VT may cause injury via
USE IN SPECIFIC CLINICAL SETTINGS several mechanisms_?,S Increased mechanical stress may ac-
Acute Severe Asthma tivate tl-\e cellula r and humoral immune response directly in
Acute Respiratory Distress Synd rome the lung/ ' 14- 16 although tl1e exact role of this mechanism in
Neonatal and Pediatric Practice the patho~enesis of lung and systemic organ injury has been
COMPLICATIONS disputed. 7• 18 Intrapulmonary mediators and pathogens,
Complications Associated with Hypercapnic such as prostaglandins,19 cytokines,20 endotoxin,21 and
Acidosis bacteria,22 have been demonstrated to access the systemic
Complications Associated with Low Tidal Volumes circulation following high-stretch mechanical ventilation.
LIMITATIONS AND CONTRAINDICATIONS The demonstration that high-stretcl1 mechanical ventilation
Limitations causes systemic organ dysfunction in animal models may
Contraindications explain in part the high rate of multiorgan failure in ARDS.
ADJUNCTIVE THERAPIES Currently, hypercapnia is tolerated as the lesser of two evils
Buffering Hypercapnic Acidosis in order to realize the benefits of low lung stretch.
Augmenting C02 Clearance
ADJUSTMENTS AT THE BEDSIDE
TROUBLESHOOTING Basic Principles
Tidal Volume and Respiratory Rate
Rate of Change PERMISSIVE HYPERCAPNIA
Adjuvant Therapies: Control of Metabolic Acidosis
Adjuvant Therapies: Alternative Elimination of C02 Conventionally, the protective effect of ventilator strategies
Specific Evaluation of the Complication incorporating permissive hypercapni.a is solely secondary
Specific Treatm ent of the Complication to reductions in lung stretch, with hypercapnia permitted
IMPORTANT UNKNOWNS in order to achieve this goal. Protective ventilator strategies,
Hypercapnia Versus Acidosis however, that involve hypoventilation cause both limitation
Therapeutic Hypercapnia of lung stretch and elevation of systemic Pee,. Lung stretch
Mechanisms of Benefit (or Harm) is distinct from elevated Pco, and, by manipulation of res-
Monitoring during Hypercapnia piratory variables (frequency, VT, dead space, and inspired
THE FUTURE C02 ) can be controlled separately, at least to some extent.
SUMMARY AND CONCLUSIONS
THERAPEUTIC HYPERCAPNIA
Carbon dioxide (C02 ) is the "waste product" of aerobic res- If hypercapnia were proven to have independent bene-
piration. In health, arterial carbon dioxide tension (Paco, ) fit, then deliberately elevating Pac 02, termed therapeutic
373
CHAPTER 15 PERMISSIVE HYPERCAPNIA 3 75
C02 VERSUS HYDROGEN ION A
Hypercapnia generally results in acidosis (greater H+ con- 0.40
centration ) via its spontaneous and carbonic anhydrase- 0.35
catalyzed combination with water to form carbonic acid.
The protons thus generated can react with titratable groups 0.30
in certain amino acids, resulting in structural changes in
0.25
many proteins and enzymes in cell membranes and cellular
aqueous environments.30 Because acidosis suppresses most c: 0.20
cellular functions, the body uses a number of strategies to .Q
a!
defend its intracellular and extracellular pH within rema rk- 0.15
E
ably narrow limits. 23 The intracellular acidosis produced by ~ 0.10
hypercapnia may be corrected within a few hours, as op-
posed to 1- 2 days for renal compensation.31 This buffering 0.05
occurs via active cell-membrane ion transporters that ex-
trude protons and exchange them for extracellular sodium. 0.00
During hypercapnia, C02 per se may react directly with -0 .05
some free amine groups in proteins to form carbamate zero 0.001-.010.01-.1 0.1-1 .0 1.0- 10 10-100 Infinity
residues.32 - 34 This binding of C02 also modifies protein VA/0 Distribution
structure and function a11d may explain some of the dif-
ferences in the observed effects of C0 2 and H+ when both
8
0.8
lead to equal changes in pH. A good example is the Bohr
effect, where increased Pac02 results in a rightward shift of 0.7
the Hb-02 dissociation curve, reflecting a lowered affinity
0.8
of hemoglobin for 02.
0.5
~ 0 .4
PULMONARY EFFECTS u:
HYPERCAPNIA AND THE NORMAL LUNG 8
Ql
0.3
0.2
Pulmonary Vascular Effects
In contrast to the systemic circulation, hypercapnic acido- 0.1
sis produces vasoconstriction and increased resistance in
the pulmonary circulation35; such effects are exacerbated in 0.0
the setting of preexisting pulmonary hypertension.35 Hy-
-0.1
percapnic vasoconstriction generally is weaker than hy- zero 0.001-.01 0.01-. 1 0.1-1 .0 1.0- 10 10-1 00 Infinity
poxic pulmonary vasoconstriction; its more important ef-
VA/0 Distribution
fect rnay be in augmenting hypoxic vasoconstriction .30 Little
is understood about how C02 acts on pulmonary vascular FIGURE 15-2 Effects of room air and inspired C02 on the
smooth muscle. distribution of ventilation (A) and of perfusion (8). The lowest
values of VA/Q correspond to regions of intrapulmonary shunt
and the highest to regions of alveolar dead space. Addition of
C02 to inspired gas (throughout the respiratory cycle, •; restricted
Pulmonary Gas Exchange to late inspiration, 0 ) resulted in more homogeneous ventilation
Acute respiratory acidosis can alter shunt via autonomic and perfusion compared to no added C02 (room air + ). VA/Q,
or direct effects on pulmonary vasculature and on the air- ratio of ventilation to perfusion. (Reprotlu.ced, with permissiou,
ways. Acidosis enhances hypoxic pulmonary vasoconstric- from Brogatz eta/: J Appl pJ,ysiol96:1894-8, 2004.)
tion and therefore usually reduces shunt and increases Pa 0 2,
whereas alkalosis has the opposite effect.36 C02 administra- Airway Tone
tion improves matching of ventilation and perfusion and Hypercapnia has been reported to either increase44 or
increases arterial oxygenation by this med1anism in both decrease45 airway resis tance. These effects may be explained
health37- 39 and disease .40 A dose-response relationship ex- the direct dilation of small airways and the indirect (i.e., va-
ists wherein increased Frco2 results in progressive augmen- gally mediated) large airway constriction.30 These opposing
tation of Pa01 .39•41 In fact, administration of Fico., during but balanced actions may produce little net alteration in air-
late inspiration- limiting its exposure to the conducting way resistance.46
airways-results in most of the beneficial pulmonary ef-
fects (i.e., VAIQ matching and oxygenation) and less sys- Lung Compliance
temic acidosis42 (Fig. 15-2). Permissive hypercapnia in pa- Parend1ymal lung compliance increases in response to hy-
tients with ARDS appears to increase shunt secondary to percapnic acidosis. This may be secondary to increased sur-
a reduction in VT and airway closure rather than from factant secretion or more effective surface tension-lowering
hypercapnia. 43 properties under acidic conditions. 47
Physiologic Role of Hypercapnia in the Lung induced lung injury in the isolated rabbit lung-53 and in the
In health, C02 alters lw1g compliance as well as pulmonary in vivo rabbi ~ (Fig. 15-4). All the data are not positive.
vascular and airway tone.30 The combined effect of small Supplemental C~ exhibits more modest protective effects
airways constriction and decreased compliance explains the in the setting of more clinically relevant tidal stretch.
phenomenon of hypocapnic bronchoconstriction and pneu- Strand et al 55 demonstrated that significant hypercapnic
moconstriction that occurs following acute regional pul- acidosis (mean Pac~ of 95 mmHg) was well tolerated in
monary a rtery occlusions.48.49 These effects either may alter preterm lambs and also appeared to reduce lw1g injury.
regional ventilation to keep pace with a prinlary change in In the context of a clinically releva nt high VT strategy [VT
perfusion or may alter regional perfusion to match a pri- of 12 ml/kg, positive end-expiratory pressure (PEEP) of
mary change in ventilation. 30 0 em H20, respiration rate (RR) of 42 breaths per minute] in
an adult model, Laffey et al 41 reported that hypocapnia was
potentially deleterious and hypercapnic acidosis somewhat
HYPERCAPNIA AND THE INJURED LUNG: protective. Furthermore, inspired C02 did not significantly
LABORATORY DATA attenuate lung injury induced by an atelectasis-prone
Hypercapnic acidosis attenuates the increased lung perme- model of lung injury that mimics the neo natal respiratory
ability consequent to free radical- mediated lung injury5° distress syndrome.56 Ta ken together, these findings suggest
(Fig. 15-3). Although hypercapnic acidosis attem.tates xan- that w hile hypercapnic acidosis substantially attenuates
thine oxidase activity,50 this does not account for all its pro- injury secondary to excessive stretch, its e ffects in the
tective effects.51 context of more clinically relevant lung stretch or extensive
Subsequent in vivo studies confirmed and further char- atelectasis may be more modest.
acterized the protective effects of hypercapnic acidosis In lung injury induced by oleic acid, metabolic alkalo-
in ischemia-reperfus ion-induced lung injury. Hypercapnic sis increased shunt fraction and decreased Pa~. 57 Whereas
acidosis preserved lung mechanics, attenuated protein leak- metabolic acidosis decreased shunt and increased Sa0 2 and
age, reduced pulmonary edema, and improved oxygena- Pv~, hypercapnic acidosis did not affect Os/ Qr, Sao2 , or
tion in comparison w ith control conditions following in vivo Sv~ . Both Pa~ and Pv~, however, increased with hyper-
pulmonary ischemia-reperfusion,52 as well as in secondary capnic acidosis possibly in part because of a rightward shift
lung injury.41 Such protective effects of hypercapnic acidosis of the Hb-02 dissociation curve and increased cardiac out-
are not media ted via a decrease in pulmonary artery resis- put. When the hypercapnia was buffered with bicarbonate
tance; on the contrary, protection occurred despite elevated to maintain consta nt pH, gas exchange deteriorated during
pulmo nary artery pressures.41 hypercapnia, shunt increased, and Sa~ fell.57 The authors
The direct effects of hypercapnic acidosis in the setting suggested that the direct vasodilator effect of hypercapnia
ventilator-associated lung injury have been examined in in hypoxic lung regions is opposed by acidosis and results
both ex vivo and in vivo models. In two key s tudies, the in little overall effect on shunt from respiratory acidosis.
addition of inspired C02 res ulted in lessened ventilator- When the acidosis was buffered, the vasodilator effect of
CHAPTER 15 PERMISSIVE HYPERCAPNIA 3 77
• •' .
-
.. '. -
·~
-
••
FIG URE 15-4 Lung his tology following high tidal

volume ventilation in the in vivo rabbit. Th e extent of
histologic injury is far less with addition of inspired
C0 2 (Paco2 of 80-100 mmHg) (A) than with a Pac0 2 of
40 ntntHg (B). Symbols: Arrow, macrophage; arrowhead,
hyaline membrane formation; BR, bronchiole.
(Reprod11ced, with permissio11, from Si11clair et al: Am J
Respir Crit Care Med 166:403-8, 2002.)
C02 was unopposed, hypoxic pulmonary vasoconstriction regions, whereas hypercapnia caused by reducing alveolar
was inhibited, and shunt increased.57 ventilation may not be.58 These issues underline the need
ARDS common! y develops in the context of severe sepsis, to consider the means of achieving hypercapnia, as well as
where the potential for deleterious effects has been raised. 58 the diversity of experimental models.62
TI1e mechanisms of lung injury in sepsis-induced ARDS
are quite distinct from those in many experimental mod-
els. Lipopolysaccharide, a key endotoxin of gram-negative HYPERCAPNIA AND THE INJURED LUNG:
bacteria, initiates lung injury by activating a specific recep- CLINICAL DATA
tor called toll-like receptor-4. 59 Hypercapnia appears to exert Reduction of VT results in permissive hypercapnia. The lung
different effects in lung injury caused by pulmonary ver- alterations, however, involve the reduced VT, the ensuing
sus systemic administration of endotoxin. Hypercapnic aci- hypercapnic acidosis, and the potential influence of altered
dosis, induced by the administration of C02, protects di- respiratory frequency. No clinical studies to date have dis-
rectly against acute lung injury induced by intratracheal sected out these changes; it is difficult to conceive of how
endotoxin instillation.60 Conversely, hypercapnia induced this would be done. Nonetheless, conventional application
by reduced VT a nd respiratory rate appears to worsen lung of permissive hypercapnia involves reduction of VT, some
damage induced by systemic endotoxin adrninistration. 61 increase in respiratory frequency, and tolerance of hyper-
Inspired C02 is distributed uniformly through all ventilated capnic acidosis.
Pulmon ary Vascular Effects Pa01 (mmHg)

Pulmonary hypertension is almost invariable in ARDS.
While protective ventilation may augment pulmonary vas- 200
cular flow, the net effect of hypercapnic acidosis is usually to 180
increase pulmonary vascular resistance. Inhaled nitric ox-
ide usually can overcome such hypercapnia-induced pul- 160
monary hypertension and may increase cardiac output. 63 140
Pulmonary hypertension may result in high capillary wall
stress; therefore, worsening of sud1 stress by hypercap- 120
nia theoretically could exacerbate stretch-induced lung 100
injury. 31,64
80
Pulmon ary Gas Exchange in ARDS 60
In ARDS, hypercapnia usually results in a slight increase in 40
Pao, and a somewha t larger increase in venous and tissue
Po,. 65 The increase in Pao2 occurs partly because of an in- 20
crease in cardiac output and partly because of a rightward 0
shift of the Hb-02 dissociation curve, which facilitates oxy-
gen unloading to the tissues.23, 66 The overall effect, there-
fore, is likely to enhance tissue oxygen uptake. In patients
with ARDS, the reduction in mean airway pressure after ini- QsfQT (%)
tiation of pressure-limited ventilation (without high PEEP) 70
may result in lung derecruitment and increased shunt. 67
Three clinical studies shed light on these mechanisms. 60
Feihl et al43 provided a detailed assessment of pul-
monary physiology associated w ith a large reduction in VT 50
(mean ofl0-6 ml/ kg). Induction of permissive hypercapnia
markedly increased intrapulmonary shw1t, although there
was no effect on dispersion ofVA I Q43 (Fig. 15-5). Permissive 40
hypercapnia increased cardiac output and decreased Pao,
from 109- 92 mmHg apparently owing to a combined ef- 30
fect of reduced Vr, increased s hunt fraction, and decreased
alveolar ventilation.43 Thorens et al65 studied the rapid in-
20
duction of hypercapnia in 11 patients with ARDS. VT was
reduced such that Paco, rose from 40.3-59.3 mmHg, and
pH decreased from 7.4 to 7.26.65 There were significant in- 10
creases in venous mixture, cardiac index, and mean pul-
monary artery pressure, prompting the authors to caution
against rapid induction of permissive hypercapnia. Pfeiffer Phas~ I Phase:! Phase 3
et al 68 studied the effect of permissive hypercapnia conse-
FIGU RE 15-5 The effects of permissive hypercapnia and
quent to VT reduction in 22 patients w ith ARDS categorized d obutamine on arteri al oxygen tension (Pa~ ) and venous
into septic (i.e., hyperdynamic) or nonseptic groups. Mul- admixture Qs/Qr . Phase 1 (high VT, 10.3 ml/kg) represents
tiple inert-gas uptake measurements revealed an increase baseline conditions. Phase 2 (low VT, 6.5 mllkg) represents a
in intrapulmonary shunt but maintained- or increased- change to permissive hypercapnia, which was associated with a
Pao, .68 Overall, these data support two opposing ef- sligh t decrease in mean Pa~ and a large in crease in Q 5 /QT. Phase
fects on oxygenation: Reduced Vr worsens atelectasis and 3 represents resumption of baseli ne h igh VT (10.3 m l/kg) plu s
increases intrapulmonary shunt, countered by elevated car- infus ion of dobu tamin e; it res.ult~d in. sta~ilization of Pao 2
diac output (and perhaps reduced 0 2 consumption), which d espite residual elevation of Q s/Q T. Qs /QT, intrapulmonary
increases mixed venous 0 2 content. 68 These concepts have shun t. (Repro duced, with permissio11, from Feihl et al: Am] Respir
Crit Cnre M ed 1. 62:209- 15, 2000.)
been supported by mathematical models of oxygen kinetics
in ARDS. 66
CENTRAL NERVOUS SYSTEM EFFECT S tracranial pressure. 23 The mechanism of cerebral vasodila-
tion depends on the arterial bed and type of artery. Naka-
HYPERCAPNIA AND THE NORMAL BRAIN
ha ta et al69 demonstrated that hypercapnic acidosis in-
N eurovascular Regulation duced cerebral precapillary arteriolar vasodilation, which
Hypercapnic acidosis causes cerebral vasodila tion. TI1e in- depended on acidosis rather than C02• They demonstrated
crease in cerebral blood flow and blood volume must be that the ATP-sensitive potassium channel plays a major role.
considered carefully in any patient as a risk for raised in- Others have suggested roles for both ATP-sensitive and
CHAPTER 15 PERMISSIVE HYPERCAPNIA 379
calcium-activated potassium channels70 and the neuronal NEUROMUSCULAR EFFECTS OF HYPERCAPNIA
isoform of nitric oxide synthase?1 Recent studies highlight the potential for hypercapnia to
exert potentially deleterious neuromuscular effects. Di-
aphragm of rats exposed to prolonged hypercapnia (7.5%
Regulation of Ventilation
C02 for 6 weeks) undergoes significant changes.73 Hyper-
Hypercapnia is a potent regulator of ventilation. Mild hy-
capnia depressed diaphragma tic tension and time to con-
percapnia (increase in end-tidal Pee, of 8 mmHg) in healthy
traction and relaxation; it altered diaphragmatic compo-
volunteers resulted in a compensatory metabolic alkalosis
sition, increasing slow-twitch and decreasing fast-twitch
over 24-48 hours that was maintained over the course of
fibers. In fact, even short-term exposure (7% inspired C02 )
exposure. 72 While there was a modest increase in ventila-
may impair neuromuscular function transiently tl1rough ef-
tory chemosensitivity to acute hypoxia, no change occurred
fects on afferent transmission or synaptic integrity in healthy
in response to acute elevations in C02.
volunteers. 74
Cerebral Tissue Oxygenation HYPERCAPNIA AND THE INJURED BRATN:

Hare et al39 demonstrated that hypercapnic acidosis in- LABORATORY DATA
creases cerebral tissue Po2 through augmentation of Pao2 Several studies have demonstrated protective effects of hy-
and increased cerebral blood flow (Fig. 15-6). percapnia in brain injury. Hypercapnic acidosis attenuates
FIGURE 15-6 Increases in inspired C02

Percentage of Inspired C~ concentration produce progressive increases in brain
0% 5% 10010 15% 0% tissue 0 2 tension and cerebral perfusion.
(Reproduced, with permission, from Hare eta/: Canf
Auaestlr 50:1061-8, 2003.)
39
-
ci
:J 38 •
...........................
.. ············ ..... ................
i~
37
IIIIIII............... ...................
~ ..........
9e
~ 35 rutt• 1111 1'····"''
·@ 3-4
CD
33
'§:z: •
-~ 120
-
III -
·~i 100
~; 80
il eo
~ 80
'! ~
~!
60
•
oo
c: 05
40
'!~ 20
c:o
0
2
~
u:
l8
~;
z i5
!D 1
~
0 20 80 100 120
Time. Minutes
hypoxic-ischemic brain injury in the immature rat. Vannucci CARDIOVASCULAR EFFECTS

et af5•76 developed a model of hypoxic-ischemic injury in NORMAL CARDIOVASCULAR PHYSIOLOGY
the immature rat consisting of tmilateral common carotid
artery ligation, exposure to hypoxia (Fto, of 0.8%), and Hemodynamic Effects
thereafter exposure to varying concentrations of inspired Hypercapnic acidosis directly reduces the contractility of
C~ (0%, 3%, 6%, or 9%) for 2 hours.75 •76 Neuropathologic cardiac and vascular smooth muscle. 30 This is counterbal-
assessment at 30 days of age demonstrated that hypoca~ anced by the hypercapnic-mediated sympathoadrenal ef-
nia was deleterious and that elevated C02 was protective. 6 fects, causing increased preload, increased heart rate, and
The experimental model caused hyperventilation. With- decreased afterload, which lead to a net increase in cardiac
out supplemental C0 2, the animals were frankly hypocap- output.30 In intact animals at1d humat1 subjects, myocardial
nic, which was harmful Therefore, exposure to supple- contractility and cardiac output increase during hypercap-
mental C02 may have provided protection by preventing nia because of increased sympathetic activity.s1
hypocapnia rather than by producing hypercapnia per se.
The investigators subsequently demonstrated that cerebral Effects on Tissue Oxygenation
flood flow was better preserved during hypercapnia; the Hypercapnia results in a complex interaction of altered car-
greater oxygen delivery promoted cerebral glucose utiliza- diac output, hypoxic pulmonary vasoconstriction, and in-
tion and oxidative metabolism for optimal maintenance trapulmonary shunt, with a net increase in Pao,. Because hy-
of tissue high-energy phosphate reserves. 75 Cerebrospinal percapnia generall~ elevates cardiac output, global 02 de-
fluid glutamate levels were lowest with hypercapnia. It livery is increased. 2 Re~ional (including mesenteric) blood
is possible that inhibition of excitatory amino acid neuro- flow also is increased,8· thereby increasing organ oxygen
transmitter secretion may contribute to neural protection? 5 delivery. Because hypercapnia and acidosis shift the Hb-
Additional mechanisms of neural protection may involve 02 dissociation curve rightward and may cause an eleva-
inhibition of free radicals77 or attenuation of neuronal tion in hematocrit, 84 tissue oxygen delivery is further facili-
apoptosis. 78 tated. Acidosis may reduce cellular respiration and oxygen
consumption,as whicl1 further benefit a supply-demand im-
balance, in addition to enhanced 0 2 delivery. Acidosis may
HYPERCAPNIA AND THE INJURED BRAIN: protect against ongoing tissue production of further organic
CLINICAL DATA acids by a negative-feedback loop, providing a mechanism
Hypercapnia greatly increases cerebral blood flow and, if of cellular metabolic shutdown at times of nutrient short-
critical, may raise intracranial pressure, resulting in pa- age (e.g., ischemia) .86 In addition, hypercapnic acidosis in-
pilloedema and headache. In the clinical setting, cerebral creases Po. in both subcutaneous tissues and the intestinal
effects of hypercapnia often overlap with the effects of wall.s7 -
hypoxemia. 79 The resulting abnormalities include restless-
ness, tremor, s lurred speech, and fluctuations of mood. High CARDIOVASCULAR EFFECTS: LABORATORY DATA
levels of Paca; cause narcosis. 79 Raised intracranial pres- Hypercapnic acidosis protects the heart against ischemia-
sure, however, is not an absolute contraindication to per· reperfusion injury. This has been demonstrated in isolated
missive hypercapnia; in fact, it has been used successfully perfused neonatal lamb hearts, where greater degrees of
for management of acute lung injury in a patient with acute hypercapnic acidosis were associated with progr essively
meningoencephalitis and cerebral edema80 (Fig. 15-7). greater protection.88 Exposure to comparable metabolic
FIGURE 15-7 A chest radiograph an d brain

computed tomographic (Cf) scan of a child with
both ARDS and cerebral edema illustrating the
tradeoff that occurs when pennissive
hypercapnia is instituted to protect against
ventilator-associated lung injury. (Reproduced,
w-ith pemlissiot~, from Tasker et al: l1ttensive Care
Med 24:616-9, 1998.)
acidemia (pH 6.8), however, followed by buffering to where in the circulation) and avid tubular sodium reabsorp-
normal pH with bicarbona te and tris-hydroxym ethyl tion, causing d epressed glomerular filtration and increased
aminomethane (THAM), is not protective.88 In contrast, fluid retention.98 Patients with ARDS exposed to permis-
metabolic acidosis (pH 6.6) without buffering prevented sive hy percapnia demons tra ted no important alterations in
myocardial stunning following global ischemia in the iso- splanchnic circulation, although C02 was increas ed by the
lated perfused ferret heart. 89 The latter investigators have addition of dead space and n ot by reduction of V T.99
since demonstrated that both hypercapnic and metabolic
acidosis were equally effective in reducing u1farct size
in an in vivo canine model of coronary artery ischemia- CELLULAR AND MOLECULAR
reperfusion.90 Possible med1anisms for the protective effects EFFECTS OF HYPERCAPNIA
of acidosis include reduction of calcium loading to the my- A clear understanding of cellular and biochemical mecha-
ocardium through H+ inhibition of calcium uptake and, u1 nisms underlymg the effects of hypercapnia is essential. It is
the case of hy percapnic acidosis, il1duction of corona ry va- a prerequisite for successful transla tion o f labora tory find-
sodilation. Nomura et al88 found that the greatest coronary ings to the bedside. It enables prediction of potential side
artery flow occurred with maximal hypercapnia. In contrast, effects, so identifyfig patients in whom hypercapnia s hould
mcreases in regional coronary artery flow do not contribute be avoided.
to the protective effects of normocapnic acidosis. 91
ACIDOSIS VERSUS HYPERCAPNIA
CARDIOVASCULAR EFFECTS: CLINICAL DATA
The protective effects of hypercapnic acidosis in experi-
Critical Illness mental lung and systemic organ injury is primarily a fw1c-
The potential for h ypercapnia to exert detrimental effects tion of the acidosis generated. 5'~· 100 In the isolated lung ,
on cardiac output92 and the peripheral circulation93 may be the protective effect of hypercapnic acidosis in ischemia-
overstated , particula rly when hypercapnia develops grad- reperfusion was greatly attenuated if the pH was buffered
ually. As discussed earlier, the net hemodynamic effect is toward normal.5"' No s ignificant protective effect was de-
probably beneficial. 43•82 N evertheless, hypercapnic acidosis tected with buffered hy percapnia. Metabolic acidosis, how-
may exert adverse hemodynamic effects m critically ill pa- ever, attenuates ischaemia-reperfus ion injury, although less
tients, particularly where myocardial function is already d e- effectively than hy percapnic acidosis.51 The myocardial pro-
pressed. In addition, acute hypercapnia may cause h ypoten- tective effects of hypercapnic acidosis are a lso seen with
sion w here endogenous catecholamine production has been metabolic acidosis both in ex vivo89 and in vivo90•9 '~ models.
maximized or where ,8-blockin g drugs reduce the potential Metabolic acidos.is exerts protective effects in other mod-
for sympa thetic activation to overcome the direct depres- els of organ injury. Metabolic acidosis d elays the onset
sive effects of hypercapnia. Even in critically ill patients re- of cell d eath in isolatedhepatocytes exposed to anoxia96
quiring motropic drug infusions, however, cardiac output or chemical hypoxia .97 Isolated renal cortical tubules ex-
mcreases almost mvariably after an acute rise in Pam,, al- posed to anoxia have improved ATP levels on reoxygena-
though the mean arterial pressure may fall because of direct tion at acidotic (compared with alkalotic) pH. 96 In con-
hypercapnia-induced systemic vasodilation. 63 trast to the lung, the typ e of acidosis (i.e., hypercapnic ver-
In patients with ARDS, the rapid induction of hypercap- sus metabolic) appears to be of importance in the renal
nia to a target Paco2 of 80 mmHg for 2 hours resulted tubule.
m d ecreased systemic vascular resistance and increased
cardiac output.94 In addition, myocardial contractility was ANTI-INFLAMMATORY EFFECT'S
decreased, and mean pulmonary artery pressure was Several key components of the mflammatory response are
increased. 94 In stable patients w ith ARDS, reduction of V T attenua ted by hypercapnic acidosis. Hyper capnic acido-
(10- 7.7 ml/kg) associated with an increase m Pac~ (37.9- sis mhibits the release of tumor necrosis factor a (TNF-
56.7 mmHg) was not associated w ith changes in hemody- a ) and interleukin-1 (IL-l) from stimulated macrophages
namics or measures of oxygen delivery or consumption.95 in vitro,10.1 as well levels of TNF-a in the bronchoalveolar
fluid following in vivo pulmonary ischaemia-reperfusion.52
Cellular and molecular mechanisms underlying the in-
RENAL, HEPATIC, AND SPLANCH NIC EFFECTS
hibitory effects of hy percapnic acidosis in the neutrophil
In isolated hepatocytes exposed to anoxia96 and chemical are increasingly well understood . Botl1 hypercapnia and
hypoxia,97 acidosis d elays the onset of cell death markedly. acidosis impair neutrophil intracellular pH regulation. In-
Correction of pH accelerated cell death. This phenomenon tracellular pH decreases w hen neutrophils are activated by
may represent a protective adaptation against hypoxic and immune stimuli.1112 If pH is normal, there tends to be are-
ischemic stress. Isolated renal cortical tubules exposed to covery in neutrophil intracellular pH back toward normal.
anoxia have improved ATP levels on reoxygenation at a pH Hypercapnia decreases extracellular and intracellular pH
of 6.9 when compared with tubules incubated at pH 7.5.96 in the local milieu, resulting in a rapid fall in neutrophil
The marked sympathetic activation of hypercapnic aci- cytosolic pH,103 potentially overwhelming the capacity
dosis, particularly when combmed w ith arterial hypox- of neutro phils-especially when activated 104- to regulate
emia, can lead to intense renal vasoconstriction (unlike else- cytosolic pH. This failure impairs impo rtant neutrophil
--
( I)
~
Col
1000
•
-
=
'0
--
><
::::::
750
500
E
~
..._,
00
250
-
FIGURE 15-8 Hypercapnia (10% C02 ) inhibits, whereas
~ hypocapnia (0.04% C02 ) potentiates, the release of
interl euki n-8 from endotoxin-stimulated neutrophils.
Incubation with acetazolamide, which impairs the effect of
0.04 % S% 10% 0.04 % 10% extracellular C0 2 on intracellular pH, abolish ed the
+acet +acet influence o f extracellular C0 2 . IL-8, interleukin 8.
(Reproduccrl, tuitlr pcrmissiou, from Coakley eta/: 1 Leuk
pC02 Bioi 71:603-10, 2002.)
functions, such as chemotaxis lOS and release of IL-8 follow- REGULATION OF GENE EXPRESSION
ing endotoxin stimulation 102 (Fig. 15-8). Such effects also The effects of hypercapnia may be mediated by regulation
occur in vivo because lung neutrophil recruitment is inhib- of gene expression. Several unidentified proteins are upreg-
ited during ventilator-induced 54 and endotoxin-induced 60 ulated by hypercapnia in the normal lung.H19 Hypercapnia
lung injury. may regulate this process at the level of gene transcription
via alterations in the half-life of messenger RNA (mRNA)
FREE-RADICAL GENERATION AND ACTIVITY or by modulating protein synthesis. Molecular mechanisms
In common with most biologic enzymes, the enzymes that underlying hypercapnic acidosis-mediated control of gene
produce oxidizing free radicals function optimally at physi- transcriptio n include membrane acid-sensing ion channels
ologic pH. Oxidant generation by both basal and stimulated and acid-responsive gene promoter regions.110- 112 Further-
neutrophils appears to be regulated by ambient C02 lev- more, the coding for certain proteins for mRNA has pH-
els, with oxidant generation reduced by hypercapnia and sensitive regions. 11o
increased by hypocapnia. 102 Production of superoxide by Hypercapnic acidosis has been demonstrated to regulate
stimulated neutrophils in vitro is decreased at acidic pH. 106 the expression of genes central to the inflammatory response
In the brain, hypercapnic acidosis attenuates glutathione dein models of cell injury. N uclear factor-Kf3 (NF-K{3) is a key
pletion and lipid peroxidation,n which reflect free-radical regulator of the expression of multiple genes involved in in-
activity a nd tissue damage, respectively. In the lung, hy- flammatory response, and its activation represents a pivotal
percapnic acidosis reduces free-radical tissue injury follow- early s tep in activation of the inflammatory response. 113 NF-
ing ischemia-reperfusion52 and attenuates the production K/3 is found in the cytoplasm in an inactive form bound to
of the higher oxides of nitric oxide, such as nitrate and ni- inhibito ry proteins ca Ued iultibitory protein K/3 (IK{3). The im-
trite, following both ventilator-induced53 and endotoxin- portant isoforms are IK{3-a and lxfJ-{3. Ixf3 proteins are phos-
induced60 injury. Hypercapnic acidosis inhibits injury phorylated by the lx{J kinase complex and subsequently de-
mediated by xanthine oxidase and directly inhibits the graded, thus allowing N F-K{3 to trans) ocate into the nucleus,
enzyme.S<> bind to specific promoter sites, and activate target genes.·m
Hypercapnic acidosis inhibits endotoxin-induced NF-Kf3 ac-
Peroxynitrite-Mediated Tissue Nitration tivation and DNA binding in pulmonary endothelial cells
Concerns exis t regarding the potential for hypercapnia to by decreasing TK{3-a degradation114 (Fig. 15-10). H ypercap-
potentiate tissue nitra tion by peroxynitrite, a potent free nic acidosis also suppressed endothelial production of in-
radical. Peroxynitrite is produced in vivo largely by the re- tercellular adhesion molecule 1 (ICAM-1) and IL-8, which
action of nitric oxide with superoxide radical and causes are critically regulated by the F-Kf3 pathway.U 4
tissue damage by oxidizing a variety of biomolecules and
by nitrating phenolic amino acid residues in proteins. 107
The potential for buffered hypercapnia to promote the for-
matio n of nitratio n products from peroxynitrite has been
Use in Specific Clinical Settings
clearly demonstrated in vitro. 100•108 The potential, however,
for hyperca pnic acidosis to promote nitration of lung tis - ACUTE SEVERE A STHMA
sue in vivo depends o n the injury. Hypercapnic acidosis Although much current work on ventilator strategies in-
decreased tissue nitratio n following pulmonary ischemia- volving permissive hypercapnia concentrates on lung in-
reperfusion52 but increased nitration following endotoxin jury, its use was firs t described in s tatus asthmaticus by
exposure60·61 •1oo (Fig. 15-9). Darioli and Pettet. 115 Permissive hypercapnia decreases
... t
-.c,. •
~ t
sc
-.
u a
u
i
0
..
XJ
~·
-
::t
Ll. FIGURE 15-9 Hypercapnia and inhaled nitric oxide
significantly increased the formation of
0 3-nitrotyrosine following LPS pretreatment. HC,
hypercapnia; iNO, inhaled nitric oxide; LPS,
LPS • • + + + + lipopolysaccharide. (Reproduced, w ith permissiou,
HC • + • + • • from Lnug et at: Am TR espir Crit Care M ed
INO + + 171:147- 57, 2005.)
d ynamic hyperinflation in ventilated patients with acute se- gested initially by Hickling et al. 11, 12 Two studies by this
vere asthma by increasing expiratory time and decreasing group, one retrospective 11 and one prospective, 12 strongly
Vr . This reduces end-inspiratory lung volume and auto- indicated that use of low VT was beneficial. In the retro-
PEEP. Other investigators have confirmed that morbidity spective study, 50 patients with severe ARDS (lung injury
and mortality are reduced with the use of permissive hy- score ~ 2.5, mean PaoJ Fro2 = 94) were managed with lim-
percapnia in ventilated patients with acute severe asthma.116 itation of peak airway pressure to less than 30 cmH2 0. The
Modest levels of permissive hypercapnia ("-'60 mmHg) are mean maximum Paco2 was 62 mmHg, and the hospital mor-
employed widely in ventilated patients with acute severe tality (16%) was less than predicted by APACHE II score
asthma. 117 (39.6%). Importantly, the authors reported no differences be-
tween survivors and nonsurvivors in terms of lung injury
score, ventilator score, Pao2 /Fio,, or maximum Paco2 •11 The
ACUTE RESPIRATORY DISTRESS SYNDROME
prospective study12 investigated comparable patients and
The potential for protective lung ventilation strategies with also limited peak airway pressures to less than 30 cmH2 0,
varying degrees of permissive hypercapnia to improve sur· did not buffer hypercapnic acidosis, and commenced with a
vival in patients w ith acute lung injury and ARDS was sug- Yr of 7 ml/kg (as opposed to 12 ml/kg in the retrospective
NC FIGURE 15-10 Hypercapnia suppresses the

A HA degradation of 1"13-a (A) but not I K{j-{:J (B)
following exposure to lipopolysaccharide, thereby
CTL 0.5h lh 2h 3h 0. 5h lh 2h 3b inhibiting the nuclear translocation of NF-~~:,6 and
downstream cytokine production. The effects of
I KB-a isocapnic acidosis and buffered hypercapnia (C) on
In.{:J-a degradation were intermediate between
B
I KB- /3 - .... . . . .. - ~
----
normocapnic control and hypercapnic acidosis
conditions. BH, buffered hypercapnia; HA,
hypercapnic acidosis; lA, isocapnic acidosis; LPS,
lipopolysaccharide; NC, normocapnia; NF-n.{:J,
nuclear factor ,{:J. (Reproduced, with permission,
from Tnkesltita et at: Am. J Respir Cell Mol Bi"l
LPS (+) LPS (+) 29:124-32, 2003.)
c NC NC HA IA BH
I K B- a - - -~
LPS (+)
study). Again, hospital mortality ra tes were lower than pre- ~ 100
dicted by APACHE II score (26.4% versus 53.3%).12 :::,., --, - - - Normocapnia
The five prospective, randomized, controlled § 1'---,1 - - Permissive hypercapnia
9 10 118 120 :::: 80 I
trials • • - that measured survival in ARDS are .! L __ L p < 0.005
discussed in detail elsewhere (see Chapter 73). Two ~ -L
c L
were positive (the ventilator strategy had an impact on ~ 60 1 l-.1
morta1ity),9•10 and three were not.118- 120 To some extent, ~ ~I
pennissive hypercapnia developed in all the trials, al- .fa 40 ~-----------
though there was much variability. Among the four major ~
(II
trials, the postrandomization Paco. values (mean ± SD)
in the control (higher VT) trial groups were 35.8 ± 8.0,9
=
Q 20
l
:J
36.0 ± 1.5,10 41.0 ± 7.5,119 and 46.0 ± 10 118 mmHg. The
postrandomization Pac 0 2 values in the protective (lower .e= oL---~--~--~~~~
VT) trial groups were 40.0 ± 10,9 58.0 ± 3.0,1° 59.5 ± 15,119 ..s 0 12 24 36 48 60 72 84 96
and 54.5 ± 19118 mmHg. It is clear that ventilation strategy Duration or assisted ventilation (hours)
can have a n impact on mortality (in the positive trials), FIGURE 15-11 Duration of mechanical ventilation in neonates
yet there was no discernible rela tionship between levels of with respiratory failure randomized to conventional therapy or
hypercapnia and survival. Also, there was no controlled permissive hypercapnia. (Reproduced, wit/1 pennissiou, from
approach to the administration of buffers. Finally, one Mariaui et al: Pediatrics 104.:1082-8, 1999.)
of the reports suggested (without convincing evidence)
that the permissive hypercapnia might have increased the CONGENITAL DIAPHRAGMATIC HERNIA
incidence of renal failure.11B Permissive hypercapnia plays an increasing role in the ven-
The database of the largest of these studies9 has been an- tilator management of infants with congenital diaphrag-
alyzed subsequently to determine whether, in addition to matic hernia. 124 This contrasts sharply with traditional man-
the effect of V T, there might be an independent effect of hy- agement, which involved aggressive hyperventilation w ith
percapnic acidosis. 121 Mortality was examined as a function the aim of producing systemic alkalinization. High levels
of permissive hypercapnia on the day of enrollment using of barotrauma, poor long-term respiratory outcomes, and
multivariate analysis and controlling for other comorbidi- poor survival rates, however, have prompted the recogni-
ties and severity of lung injury. It was found that permis- tion that the hypoplastic lung is the major pathophysiologic
sive hypercapnia reduced mortality in patients randomized defect. Accordingly, avoidance of barotrauma has assumed
to the higher Vr but not in those receiving lower VT.121 If increasing importance, and ventilator s trategies involving
thes e data are confinned, there may be a good case for us- permissive hypercapnia are used increasingly. A retrospec-
ing hypercapnic acidosis to attenuate ventilator-associated tive analysis of three treatment protocols in high-risk in-
lung injury. fants with congenital diaphragmatic hernia reported that
permissive hypercapnia was associated with a substantial
increase in survival, decreased barotrauma, and decreased
NEONATAL AND PEDIATRIC PRACTICE morbidity at 6 months. In contrast, the earlier introduc-
tion of high-frequency oscillatory ventilation (which read-
Use of permissive hypercapnia in neonatolofJ has been ily controls Pacoz) had minimal inlpact. Despite limitations,
recognized since the study by Wung et aL They de- the increased survival associated with the use of permissive
scribed lower than previous mortality and lower incidence hypercapnia is persuasive.125
of chronic lung disease in neonates suffering from persistent
fetal circulation who were treated with low VT entailing a CONGENITAL HEART DISEASE
high Paco..13 Four s tudies of patients with congenital heart disease are
relevant.126- l29 In the context of single-ventricle physiology,
pulmonary vascular resistance can be controlled by induc-
NEONATAL RESPIRATORY DISTRESS SYNDROME ing alveolar hypoxia or alveolar hypercapnia. Two studies
Infants with neonatal respiratory distress syndrome have documented that the addition of inspired C02 increased
been studied in a randomized, controlled trial. 122 Although cerebral oxygenation and mean arterial pressure compared
not powered to detect differences in survival, duration of with reducing Fio. in hypoplastic left-heart syndrome 128
mecl1anical ventilation was shorter in the permissive hyper- and following cavopulmonary connection. 126 Hypove11ti-
capnia group, and no obvious adverse effects were seen (Fig. lation also improves systemic oxygenation after bidirec-
15-11). AlU1ough encouraging, such a small study would tional s uperior cavopulmonary connection, potentially via
not detect a subtle increase in adverse effect. More recently, a hypercarbia-induced decrease in cerebral vascular resis-
a prospective multicenter study of extremely premature tance, thus increasing cerebral, superior vena caval, and
neonates in Denmark (1994-1995) reported that a venti- pulmonary blood flow.127 Finally, a detailed recent study
lator strategy incorporating permissive hypercapnia and demonstrated that without a Hering VT or m ean airway pres-
early use of nasal continuous positive airway pressure and sure, the addition of C02 to inspired gas resulted in inl-
surfactant reduced the incidence of chronic lung disease proved cerebral blood flow and systemic oxygenation fol-
significantly. 123 lowing cavopulmonary connection. 129
Complications they are, do not suggest that all patients-certainly not those
who are already critically ill-would survive such exposure
The complications of hypercapnia relate primarily to those without incident or even survive at all. Nonetheless, they
caused by hypercapnic acidosis per se and those caused by do indicate that severe hypercapnic acidosis per se is not
the use of low VT. invariably harmful.
COMPLICATIONS ASSOCIATED WITH CONTRAINDICATIONS

HYPERCAPNIC ACIDOSIS As with almost any situation, there are few absolute con-
Although many physiologic effects are associa ted with hy- traindications and many relative contraindicatiof\S. Some
percapnic acidosis, there are few complications. The most authorities suggest that intracranial hypertension is an abso-
notable complications include intracranial and pulmonary lute contraindication,137 although this is disputed. 80 In any
hypertension. Complications are of mos t concern in patients case, the risks and benefits of hypercapnia in the setting of
with specific risk factors, especially where acidosis is acute, intracranial hypertension must be weighed and monitored
severe, or not buffered. carefully. Additional contraindications include pulmonary
hypertef\Sion, significant hypovolaemia, or uncontrolled se-
vere metabolic acidosis. 137
COMPLICATIONS ASSOCIATED WITH
LOW TIDAL VOLUMES
Reduced VT may lead to increased intrapulmonary shunt, Adjunctive Therapies
reducing Pa~ . 43 This is generally not a difficult problem
and can be countered by a recruitment maneuver, eleva- BUFFERING HYPERCAPNIC ACIDOSIS
tion of PEEP or mean airway pressure, prone positioning,
or other strategies. A more serious issue is w hether small Buffering of the acidosis induced by hypercapnia in patients
VT values increase mortality. This has been the source of with ARDS remains a common, albeit controversial, clinical
significant controversy. It was a major issue in the meta- practice. 138•139 The effects of buffering hypercapnic acidosis
analysis by Eichacker et al.130 They suggested that not only need to be considered because both hypercapnia and acido-
were very high VT values dangerous, but so too were very sis per se may exert distinct biologic effects. As discussed
small VT values. This was the basis of the U-shaped curve earlier, there is evidence that the protective effects of hyper-
that depicts a relationship between VT and mortality. The capnic acidosis i11 ARDS are a function of tl1e acidosis ratl1er
investigators suggested that the ARDS Network 6 ml/kg than the elevated C02 per se.51•100
VT protocol was potentially dangerous, should not be used,
and should not be considered the standard of care.B° Con- SODIUM BICARBONATE
siderable controversy ensued. Another group published an Buffering with sodium bicarbonate was permitted in the
abbreviated meta-analysis pooling the results of important ARDS Netv.rork study.9 Concerns with the use of bicarbon-
clinical trials. 131 They countered the analysis of Eichacker ate, however, have caused its removal from routine use in
et al and concluded that there was no statistical basis for the cardiac arrest algorithms. 140·141 Effectiveness of bicarbonate
assertion that low VT values are harmful. as a buffer depends on the ability to excrete C02, rendering
it less effective in buffering hypercapnic acidosis. In fact,
bicarbonate may further raise Paco, where alveolar ventila-
tion is limited, as in ARDS. 142 Bicarbonate may correct arte-
Limitations and Contraindications rial pH but worsen intracellular acidosis143 because the C02
produced when bicarbonate reacts with metabolic acids dif-
UM1TATIONS fuses readily across cell membranes, whereas bicarbonate
A substantial body of literature emphasizes the potential cannot. 144
for full recovery following exposure to extreme levels of In metabolic acidosis, the s ituation is also complex. Bi-
hypercapnia, termed supercarbia, in both adults and chil- carbonate infusion can augment the production of lactic
dren. Several children exposed to extremes of Pac~ (155- acid.145- I S'I In ketoacidosis it can slow the clearance of
269 mmHg)132 and one Jatient with asthma with a Pac~ ketoacids.152 Of greater concern, bicarbonate administra-
of 293 mmHg (pH 6.77) have been described, with excel- tion is associated with a fourfold increase in risk of cere-
lent recovery and no long-term sequelae. In adults, in the bral edema in children with diabetic ketoacidosis. 153 When
early 1950s, the accidental development of severe respira- compared witl1 an equimolar dose of sodium chloride, bicar-
tory acidosis was not uncommon in patients undergoing bonate administration does not improve the hemod ynanuc
certain surgical procedures; Paco2 as high as 200 mmHg status of critically ill patients who have lactic acidosis. 154
was reported during thoracotomy without apparent ad-
verse effects. 133 More recently, reports exist of StJrvival with- TROMETHAMINE
out sequelae following exposure to Pac~ values of up to There may be a role for the amino alcohol tromethamine
375 mmHg (pH 6.6).134•135 Indeed, a case report indicates [tris-hydroxymethyl aminomethane (THAM)] in hypercap-
complete recovery following a pH of 6.46 secondary to ethy- tuc acidosis. THAM penetratescells easily and can buffer
lene glycol poisoning. 136 These numbers, in1pressive though pH changes and simultaneously reduce P co2 • 155 Unlike
50 nale should be clear (e.g., to ameliorate potentially delete-

Mean Pulmonary Arterial rious hemodynamic consequences) and the responses mea-
mmHg Pressure ph-uncorrected
sured. THAM and Carbicarb may have a role in these clinical
T situations.
40
*
(~
AUGMENTi NG C02 CLEARANCE
fLI DEAD-SPACE GAS REPLACEMENT

30
Mean Pulmonary Arterial
Pressure pH-corrected
1 At the end of expiration, the ventilator circuit distal to the
Y piece and the anatomic dead space both contain alveolar
gas. This C02-rich gas then constitutes the first part of the
next breath delivered to the distal lung. The contribution of
20+-----~------,-------~-----, this dead-space gas to ventilation increases with decreased
Baseline One hour Two hours Baseline 2 • VT, given that dead space is relatively fixed. Teclmiques
FIGURE 15-12 Pulmonary artery pressure is elevated by rapid that aim to replace dead-space gas with fresh gas have been
institution (over 2 hours) of permissive hypercapnia (grt1y line) in advocated as an adjunct to protective ventilator strategies.
patients with ARDS. Institution of a comparable degree of These techniques may increase effective alveolar ventilation
p ermissive hypercapnia buffered with tromethamine (THAM, and facilitate htrtherreductionsin VT, minimizing transpul-
black line) atten uated the effects. (Reproduced, with permission, monary pressures.
from Weber et nl: Am T Respir Crit Care Med 162:1361-5, 2000.) Tracheal gas insufflation (TGI) delivers fresh gas into the
central airways either continuously or in a phasic fashion
during expiration (see Chapter 24). Experimental studies in
bicarbonate, which requires an open system for C02 elim-
animal models of ARDS and in lung models highlight the
ination in order to exert its buffering effect, THAM is ef-
potential role of TGI in clinical practice. 157 In a recent exper·
fective in a closed or semiclosed system.155 THAM rapidly
imental study, Zhu et aJ1° 8 reported that TGI, either alone
restores pH and acid-base regulation in acidemia caused by
or in combination with partial liquid ventilation, attenuated
C02 retention. 155 In a small but carefully performed clin-
the development of lung injury resulting from mechanical
ical study of 12 patients with ARDS, rapid induction of a
ventilation of surfactant-depleted lungs . Despite extensive
hypercapnic acidosis resulted in decreased systemic vascu-
investigation, however, concems persist witl1 regard to the
lar resistance, increased cardiac output, decreased myocar-
safety and monitoring of TGI that have impeded its intro-
dial contractility, decreased mean arterial pressure, and in-
duction into clinical practice. 158
creased mean pulmonary arterial pressure.94 Buffering of
Aspiration of dead-space gas (ASPIDS) during expiration
the hypercapnic acidosis with THAM rapidly attenuated
and controlled replacement with fresh gas are a related tech-
but did not fully reverse these cl1anges94 (Fig. 15-12). Thus
nique designed to minimize dead space. A feasibility study
it could be argued that although permissive hypercap11ia
of eight patients with COPD who were managed witl1 per-
generally is well tolerated in patients with ARDS, buffering
missive hypercapnia demonstrated that ASPIDS resulted
with THAM94 might be a useful cotherapy where hemody-
in a similar decrease in Paco, but with less intrinsic PEEP
namic instability supervenes.
compared to TGI. 159 -
Coaxial double-lumen endotracheal tubes, which elimi-
CARBICARB nate the contribution to dead space from the ventilator cir-
Carbicarb is an equimolar mixture of sodium carbonate and cuit distal to tl1e Y piece, may improve the efficiency of ven-
sodium bicarbonate (Na2C03 0.33 M, NaHC03 0.33 M) and tilation. No adverse hemodynamic effects or auto-PEEP has
may have advantages over the latter. Carbicarb has been been detected with use of the coaxial tube. 160 Reduction in
studied in mixed respiratory and metabolic acidosis and Paco, is inversely proportional to VT. Initial safety and effi-
has proved effective in raising arterial pH and preventing cacy evaluations of this promising adjunct in patients with
lactate elevation.142 Carbicarb corrects the systemic and in- ARDS are required.
tracellular acidosis seen with hypercapnia l56 without ele-
vating Paco, · This contrasts with sodium bicarbonate.143
ADDITIONAL TECHNIQUES
Carbicarb, however, did not appear to possess any advan-
High-frequency oscillatory ventilation and extracorporeal
tages in terms of restoration of hemodynamic stability over
C~ removal (ECC02R) are discussed in Chapters 20 and
iso-osmolar amow1ts of hypertonic saline or sodium bicar-
22, respectively.
bonate in a canine shock model.147 The similar responses
may relate to their identical sodium content, with no addi-
tional benefit attributable to correction of pH. 147
In summary, although common clinical practice, no out- Adjustments at the Bedside
come data (e.g., survival or duration of hospital stay) sup-
port buffering of a hypercapnic acidosis. In the absence of Adjustments at the bedside are specific to the patient and the
correcting the primary problem, buffering a hypercapnic clinical context. The following principles may guide ther-
acidosis with bicarbonate is not likely to be of benefit. If the apy, although in the end the physician must individualize
clinician elects to buffer a hypercapnic acidosis, the ratio- the risks and benefits for each patient.
First, in a patient who is being mechanically ventilated, Troubleshooting
confirm correct placement of the endotracheal tube and
the ventilation of both lungs. Consider and, where possi- To address problems that develop, it is key to understand
ble, correct reversible conditions that might have an im- the pathophysiology. This amounts to management of dys-
pact on oxygenation or C02 removal (e.g., pleural effusion, pnea, intracranial hypertension, pulmonary hypertension,
atelectasis, and/or pneumothorax). Next, decide whether and sometimes, hypoxemia. Troubleshootmg follows logi-
the patient is comfortable and whether there is patient- cally the principles used m initiating permissive hypercap-
ventila tor dyssynchrony. Then note the ventilator settings nia. In reality, it represents a work m progress, wherem the
(i.e., plateau pressure, VT, and rate) and the arterial blood- clinician considers risks versus benefits (real and potential)
gas values, and consider whether these are appropriate. for eacl1 patient at the bedside.
Concurrent with these considerations, evaluate the patient
for causes of high Pac0 , , and reduce or eliminate any that
are present. Such conditions include increased production TIDAL VOLUME AND RESPIRATORY RATE
of C~ (e.g., fever, sepsis, shivering, or more rarely, thyroid The first issue is to determine whether the VT (or perhaps
storm, maligna11t hyperthermia, or neuroleptic malignant plateau pressure) is actually in the range desired by the clin-
syndrome) or decreased C02 elimination (e.g., u1creased ician. If VT is far lower than desired, increasing it will alle-
Vo/VT). viate "wmecessary" hypercapnic acidosis. If the respiratory
The next step involves arbitrary decisions made by the rate is too low, increasing it also wiiJ lower the Paco,.
clinician at the bedside on the target tidal distension (VT, or
plateau pressure). It is important to recognize that optimal
values are unknown, which is not to say that the values are RATE OF CHANGE
w1important. They are definitely important. Across popu-
Was the permissive hypercapnia introduced too quickly?
lations, adverse effects are associated with very high VT·9·10 Overly rapid introduction of hypercapnia results in a
We do not advise on the ideal VT or plateau pressure, recog- greater degree of acidosis because the physiologic buffer-
nizing that these issues are both difficult and controversial. ing systems a re unable to cope. All unfavorable effects of
After clinicians select an appropriate VT for a given patient,
hypercapnic acidosis (e.g., dyspnea and intracranial hyper-
they next decide on the " maximal" allowable Paco, and the
tension) are far more pronounced where acidosis is greater.
degree of acidosis that they believe the patient can toler-
More gradual introduction of permissive hypercapnia may
ate. This is empirical. Although some authors suggest arbi-
prevent these problems.
trary limits, in the end the decision is based on patient com-
fort, presence of contraindications, and clinician "comfort."
When considering ventilator settings, consider the relative ADJUVANT T HERAPIES: CONTROL OF
values of VT, plateau pressure, and rate, and estimate the METABOLIC ACIDOSIS
relative contributions of changes in each. For example, if the
rate is inappropriately low, then increasing it will allow fur- Buffering sometimes can be appropriate for modifying the
therreduction in VT with less elevation in Paco,. Conversely, adverse effects of significant acidosis. The clmician needs
increasing the rate may induce a degree of hyperinflation to identify conditions otl1er than ventilator settings and
(auto-PEEP),l61 which, although potentially protective, can Paco, per se that have an impact on acid-base status. Hyper-
complicate ventilator management and could induce eleva- chloremic acidosis may have developed consequent to high
tion of the Paco2 - volwnes of intravenous saline, total parental nutr ition, or
Finally, having decided on the desired ventilator settings renal tubular acidosis and can be buffered easily or possibly
and the permissible limits of toleration, decide on the trade- prevented. Renal impairment, which slows the generation
offs involved and the time scale. One trades the benefits of endogenous bicarbonate or excretion of hydrogen ion-
of the approacl1-reduction of ventila tor-associated lung or generates endogenous organic acids-can be alleviated
injury-against the cost-conditions caused or exacerbated by renal replacement therapy.
by permissive hypercapnia. Such tradeoffs are inherent in
the practice of medicine162 but are addressed seldom by
ADJUVANT THERAPIES: ALTERNATIVE
clinical trials. Finally, the clinician decides on the rate of in-
ELIMINATION OF C02
troducing permissive hypercapnia. In some situations, there
is little choice. For example, in acute severe asthma, pernns- Adjuvant therapies can be directed at the elevated Pace>z-
sive hypercapnia is initiated immediately; otherwise, the Examples include high-frequency oscillation, transtracheal
patient is subjected to incredibly high airway pressures. gas insufflation, and extracorporeal tecl1niques.
Having decided on the target VT or plateau pressure, in-
crease the rate and decrease the VT slowly. There is no for-
SPECIFIC EVALUATION OF THE COMPLICATION
mula. Extremes of VT or plateau pressure should be reduced
immediately, and less extreme elevations should be reduced In some circumstances, clinicians suspect a problem, such
more gradually. For example, in ARDS, a VT of 15 ml/kg as pulmonary or intracranial hypertension, that leads them
could be reduced immediately to 10 ml/kg and further re- to completely avoid permissive hypercapnia. Such an ap-
duced over several hours with a concomitant increase in proach may not be appropriate u1 the absence of clear proof
rate. of the feared condition because the patient may be at a far
greater risk of ventilator-associated lung injury than of the cause the injury. While some mechanisms are understood,
feared condition or potential complication. In such a set- it is not possible for the clinician to extrapolate from mech-
ting, the clinician should consider appropriate monitoring. anisms discovered in the laboratory to the care of a patient
For example, insertion of an intracranial pressure monitor with lung injury.
or jugular oximetry catheter may provide evidence that al-
lows the clinician to gradually introduce, titrate, or clearly MONITORI NG DURI NG H YPERCAPNIA
avoid hypercapnia in a patient with head injury. Such an
There are no specific monitors for patients being ventilated
approacl1 has been described when managing children suf-
with permissive hypercapnia. Regular arterial blood-gas
fering from meningococcal septicemia complicated by ele-
analysis is a requirement, and clinicians will monitor pa-
vated intracranial pressure and severe acute ltmg injury80
rameters that lead them to detect or prevent complications
(see Fig. 15-7). Concerns about pulmonary hypertension
such as intracranial hypertension.
can be addressed by measuring, and monitoring the de-
gree of pulmonary hypertension or its sequelae (e.g., right-
ventricular failure, tricuspid regurgitation, or right-to-left The Future
shunting). In this case, transthoracic echocardiography or
pulmonary artery catheterization may be indicated. Future advances in the early diagnosis of acute respiratory
failure and the development of specific therapies may re-
SPECIFIC TREATMENT OF TH E COMPLICATION duce ilie need for ventilator strategies involving permissive
Direct testing for a feared complication may enable early hypercapnia. In the interim, ventilator strategies involving
detection. It also permits the direct " independent" treatment hypercapnia appear likely to play a central role in the man-
if perrnissi ve hypercapnia is still deemed necessary. Specific agement of these disease sta tes. This highlights the need to
treatment mi~ht include inhaled nitric oxide for pulmonary improve our understanding of the biology of hypercapnia,
hypertension 3 or sedation, osmotherapy, or hypothermia which should lead us to a better understanding of the ad-
for intracranial hypertension. Of course, the most common vantages, disadvantages, and contraindications pertaining
complaint, d yspnea, can be treated directly with sedatives to its use in the clinical context. If the requirement for venti-
and opioids163; neuromuscular blockade, while paralyzing lator strategies that are adverse lessens, the requirement for
respiratory muscle contraction, of course, does not alter the permissive hypercapnia will lessen, and concerns related to
perception of dyspnea. its use will become less relevant. Nonetheless, a fuller pro-
file of biocl1emical and physiologic responses to elevated
C02 is needed for the clinician to decide whether hypercap-
Important Unknowns nia is particularly dangerous-or likely beneficial- in the
management of a specific patient.
While mucl1 is known about hypercapnia, much remains
unknown. The principles underlying the approach to per-
missive hypercapnia have been established.2.3,29,31,137,164- 166 Summary and Conclusions
Sucl1 principles are inherently limited by the state of our
knowledge. The unknowns relating to permiss ive hyper· Permissive hypercapnia simply means reducing VT in order
capnia can be grouped as follows. to lessen the likelihood of ventilator-associated lung injury;
in so doing, the clinician accepts the inevitable development
HYPERCAPNIA VERSUS ACIDOSIS of higher Paco 2 • Elevated Pcol is associated with a long list
of physiologic alterations. Some of iliese effects are harm-
Most of the acute physiologic effects of hypercapnic acidosis ful, others may be neutral, and some may turn out to be
can be attributed to the effects of pH. C02 itself, however, has beneficial. In any case, there is ample evidence that high
significant biochemical effects, especially on tissue nitration. tidal volumes harm patients. In avoiding such high tidal
In tl1e context of endogenous or exogenous buffering, the volumes, the clinician must decide for eacl1 patient what
effects of elevated C02 are not understood. is the appropriate tradeoff between the benefits of avoid-
ing high VTS and the cost (and benefits) of the associated
THERAPEUTIC HYPERCAPNIA hypercapnia.
The role of tl1e deliberate elevation of C02, as opposed to
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102:1742-5. bra l edema in children with diabetic ketoacidosis. The Pedi·
135. Urwin L, Murphy R, Robertson C, et al. A case of extreme hyper· attic Emergency Medicine Collaborative Researm Committee
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thapter 16 _ _ _ _ _ _ _ _ __ in Fig. 16-1 ), the clinician sets an inspiratory pressure target
(with either time or flow as the cycling criteria). Under these
FEEDBACK conditions, flow and volume become dependent variables
that the machine adjusts according to respiratory system
ENHANCEMENTS ON med1anics and patient effort to maintain the set pressure
target.
VENTILATOR BREATHS The putative advantage of a flow-targeted, volume-
cycled breath is tha t a guaranteed volume is delivered (even
NEIL MACINTYRE though applied airway pressures may change). The puta-
RICHARD D . BRANSON tive advantages of a pressure-targeted breath (either tinle-
or flow-cycled) are that an airway pressure limit is guar-
anteed (even though volumes may change), that the rapid
initial flow may enhance gas mixing, and that the variable
flow pattern may enhance patient-ventilator synchrony.3 It
must be emphasized, however, that clinical outcome stud-
CO NVENTION AL POSITIVE-PRESSURE ies showing benefit of one breath-targeting strategy over the
BREATH-DELIVERY STRATEGIES/MODES other do not exist.
FEEDBACK CO NTROL OF RESPIRATORY RATE The availability and delivery logic of different breath
FEEDBACK CONTROL OF COMBINATION types define the "mode" of mechanical ventilator sup-
PRESSURE- AND FLOW-TARGETED BREATHS port.1-3 The mode controller is an electronic, pneumatic, or
Dual Control Within a Breath (DCWB) microprocessor-based system that is designed to provide the
Dual Control Breath to Breath (DCBB) proper combination of breaths according to both set and var-
FEEDBACK CO NTROL OF DCBB BREATHS ious feedback algorithms. Newer ventilators now can pro-
BASED ON RESPIRATORY SYSTEM M ECHANICS vide very sophisticated feedback and automatic controllers
AND EFFORT of both the breath-delivery pattern and the mode behav-
AUTOMATIC ADJUSTMENTS lN PRESSURE AND ior. These range from complex breath-rate adjusters to var"
FLOW BASED O N ARTIFICIAL AffiWAY ious algorithms designed to better match positive-pressure
GEOMETRY breath delivery with patient effort and respiratory system
CONCLUSION mechanics. It is important to note that the engineering data
supporting all these developments far exceed the clinical
data to support widespread application of any of them. Nev-
ertheless, there is at least some rationale for many of these
newer feedback features, and the remainder of this chapter
Conventional Positive-Pressure reviews their design and the available data supporting their
clini.eaI u tili ty.
Breath-Delivery Strategies/Modes
Positive-pressure breaths delivered by mechanical ventila-
tors can be classified by the behavior of three variables: Feedback Control of Respiratory Rate
(1) the trigger variable (what initiates the breath), (2) the
target or limit variable (what controls gas delivery during Several generations of positive-pressure ventilators have
the breath), and (3) the cyc.le variable (what terminates the had simple feedback systems for control of the mandatory
breath). 1- 3 Trigger variables are either patient effort (de- breath rate in assist-control ventilation (ACV) or synchro-
tected by the ventilator as a pressure or flow change) or a nized intermittent mandatory ventilation (SIMV). 4-6 These
set machine timer. Target or limit variables generally are feedback systems use a single input variable, spontaneous
either a set flow or a set inspiratory pressure. Cycle vari- patient effort, to set the controlled breath rate. In ACV, every
ables generally are a set volume, a set inspira tory time, or patient efforts triggers an assisted breath, and the machine
a set flow rate. Pressure is often a backup safety-cycle vari- provides a backup control rate. In SIMV, patient efforts trig-
able. Figure 16-1 uses this classification scheme to describe ger assisted breaths up to the backup control rate. Patient
the five most common breath types available on the current efforts above this backup control rate trigger either unas-
generation of mechanical ventilators. sisted breaths (pure SIMV) or pressure-support (PS) breaths
Conceptually, flow and pressure strategies incorporate (SIMV + PS).
a simple feedback system. With flow targeting (breaths Mandatory minute ventilation (MMV) is an extension of
1 and 2 in Fig. 16-1), the clinician sets an inspiratory these feedback controllers of rate. With MMV, however,
flow and generally a cycling volume. Under these condi- the feedback input variable is now total minute ventila-
tions, airway pressure becomes the dependent variable that tion (frequency and tidal volume), and a clinician-set tar-
the machine adjusts according to respiratory system me- get minute ventilation is required?-10 With most MMV
chanics and patient effort to maintain the set target flow systems, the ventilator monitors minute ventilation over a
and cycling volume. With pressure targeting (breaths 3-5 30-second moving time window. If the set minimum mint1te
393
Volume control Volume assist Pressure control Pressure assist Pressure support
Set pressure Set pressure Set pressure
,,,
u
;
...
,,,
1\_
;
,,
I
I I
"'-Set ti Setti , Set minimal flow
Set flow? Set flow .ii"' ' \
t
I \
..."' ..,' ''' '' I \

1\ \
.. " ", J
,g~
~'
\ \
in I ' ' I ' '~
0 I--_._-+_ _,_. ' '
out ~
II Set volume
/
G
Set volume
/
,,'"',~
,. '
let '
,
I
FIGURE 16-1 Airway pressure (upper plluel), flow (middle plllrel), and volume (lower parre() profiles over time of the five "basic breaths"
available on most modem mechanical ventilators. Note that patient-initiated breaths have a small deflection in airway pressur e preceding
the ventilator flo w delivery, whereas machine-initiated breaths do n ot. The solid lines and arrows represent clinician-set parameters; the
dashed lines represent the variable ventilator adj ustments to respiratory system mechan ics and patient effort. (R eproduced, with
p errrrissiou, from M nclutyre.3)
ventilation is being met by either s pontaneous or pressure- Feedback Control of Combination

supported breaths, no further ventilator control breaths are
given. If the set target minute ventilation is not being met, Pressure- and Flow-Targeted Breaths
clinician-set volume- or pressure-controlled breaths ar e de-
livered to provide it. MMV is available as MMV (Drager), As noted earlier, the downside to pressure targeting (and
augmented minute volume (AMV; Bear /Viasys), and ex- either time or flow cycling) is the lack of any control of
tended mandatory minute ventilation (EMMV). A point of volume; the downside to flow targeting and volume cy-
confusion is that mandatory mi11imum ventilation (MMV) is cling is the lack of any control of pressure. Over the last
also the term used by one manufacturer to describe its dual- two decades, a number of engineering innovations have at-
control breath-to-breath algorithm (see below). ten1pted to produce feedback algorithms that allow some
Conceptually, the MMV feedback control of rate offers control of volume with pressure targeting and some control
the appeal of a positive-pressure breath-delivery strategy of pressure with flow targeting. Collectively, these are often
that supplies control breaths only when needed and allows referred to as hybrid breaths or dual-control brenths.~'~-15 On
either unassisted breathing or PS to be the predominant the current generation of mechanical ventilators, there are
form of support. Uncomfortable or excessively large control two basic approaches to providing these types of breaths:
breaths thus can be minimized. The breath-delivery pattern dual control within a breath (DCWB; intrabreath control)
with this form of MMV, however, depends heavily on how and dual control from breath to breath (DCBB; i11terbreath
the clinician sets the PS level and the desired minute ventila- control). The fonner uses a measured flow input to switch
tion, and this can lead to undesired effects. For example, in- from pressure targeting to flow targeting in the middle of
sufficient PS leading to respiratory muscle fatigue may lead the breath. The latter uses a measured volume input to ma-
to tachypnea but a minute ventilation that remains above nipulate the pressure level of subsequent pressure-targeted
the set minimum. 11 Needed additional support thus rna y breaths.
not be given. Alternatively, setting the minute ventilation
excessively high (i.e., above that desired by the patient's
D UAL CONTROL WITHIN A BREATH (DCWB)
oxygen a nd carbon dioxide needs) may lead to unneces-
sary pressure application, intrinsic positive end-expiratory The currently available DCWB breath begins with either
pressure (PEEP), or a reduction in spontaneous drive and patient or machine triggering and is followed by a pressure-
virtually complete takeover by the control rate.11 targeted flow-delivery a lgorithm. There is thus a high initial
A number of observational studies have demonstrated flow to rapidly pressurize the airway and then subsequent
that the MMV feedback control of rate works as designed flow adjustments according to respiratory system mechan-
and can be set to provide an appropriate backup feature to ics and patient effort to maintain the target pressure. As the
PS?-'~ 0 Studies showing improvements in clinical outcome lungs fill, flow decelerates until a flow-cycling mechanism
from this appr oach, however, are lacking. Because of this, terminates the breath. In these respects, this breath type is
and because of the concerns noted earlier regarding proper similar to the PS breath. Unlike PS, however, the clinician
setup, the popularity of MMV has been waning, especially also m us t set a minimum tidal volume, flow, and backup
since the introduction of more sophisticated feedback ap- rate with the DCWB breath. These backup settings take
proaches (described below). over control of the breath should the pressure-targeted flow
CHAPTER 16 FEEDBACK ENHANCEMENTS ON VENTILATOR BREATHS 395
PA =O PA =S PA :15 PA = 25
cloo
~
Patient:
• Flow demand (Umin) 0 120 120 120 120
• Volume delivered (ml) 500 500 500 500 500
• Work/breath (J ) 0 0.378 0.373 0.343 0.280
FIGURE 1.6-2 Airway pressure (11pper pane/) and flow (lower panel) profiles over time of the DCWB feature compared to volume
assist-control ventilation (VACV). Data are from a lung model with a set guaranteed tidal volume of 500 ml and a set flow of 50 Liters/min
under all condition s. The simulated flow demand is zero in the firs t breath and 120 li ters/min in the next four breaths. The pressure target
is inactive in th e first two b reaths (i.e., stand-alone volume-cycled ACV). Note that during the simulated patient b reath with stand-al one
volume-cycled ACV (breath 2), the simulated effort outstrips the delivered fl ow, and the airway pressure graphic is "sucked down." This is
reflected in a simulated patient work of 0.378 }/breath. ln breaths 3 through 5, a DCWB pressure target (PA) is set (5, 15, and 25 cmH2 0 ,
respectively) that increasingly pressurizes the airway early in the breath an d reduces simulated patient work. If the flow associated with
the pressur e target is inadequate for the set 500-ml tidal volume, the minimum flow activates and guarantees this tidal volume (breath s 3
and 4). If the flow associated with the pressure target is adequate for the 500-ml tidal volume, the breath will terminate on flow like a PS
breath (breath 5). (Reproduced, witlt permiss ion, f •·om MaclntlJ re et a/: Crit Care M ed 22:353- 7, 1994.)
drop below the minimum required to deliver the set tidal breaths regardless of set flow pattern. In the original clini-
volume in the allotted inspiratory time. The breath thus be- cal trial of DCWB breaths, Amato et al16 found that DCWB
gins like PS and can either flow cycle like PS (if the volume breaths reduced patient work markedly during assisted
exceeds the set minimwn) or volume cycle like a flow- breaths as compared with flow-targeted, volume-cycled
targeted breath (if necessary to deliver the set volume).11-13 assist-control ventila tion (ACV). This was a ttributed to
This breath type is depicted in Fig. 16-2 and is available as both better patient-ventilator flow synchrony, as well as
volume-assuted pressure support (VAPS; Bird/ Viasys), pres- to higher inspiratory flows, resulting in a shorte r inspira-
sure augmentation (PA; Bear / Viasys), and machine volume tory time and reduced auto-PEEP with the DCWB breaths.
(Viasys). It must be pointed out, however, that the set flows dur-
The original description of DCWB used two flow sources ing ACV in this study m ay have been inappropriately
in parallel. 23 The firs t source provided a constant flow set slow.
by the clinician (10-120 liters/ min) to provide the minimal A subsequent larger study of 17 patients compared
volume. The second source of flow (up to 200 liters/min) DCWB breaths with flow-targeted, volume-cycled ACV,
was set to reach a pressure target. When the patient initiated with the set flows adjusted to match patient demand. 24 A
a breath, both flow sources were activated. If the pressure- significant reduction in the patient's pressure-time product
targeted flow was sufficient to deliver a tidal volume (VT) (PTP), a measure of effort, was observed with the DCWB
greater than or equal to the set minimum VT before the breaths, along with a trend toward lower auto-PEEP. Of
flow-cycling criterion was met, then the breath flow cycled note, VT w ith DCWB varied considerably above the set min-
and was essentially only a pressure-supported breath. In imum. This may be important in that as patient demands
contrast, if the pressure-targeted flow was insufficient for vary, the ability to increase VT may play an important role
the set VT, then the constant flow from the other source in controlling the sensation of breathlessness.25
continued until the desired VT was delivered . Both these clinical studies suggested that the initial set
The reasoning behind DCWB breaths is that the high pressure target should be less than peak pressure (and closer
initial flow would provide better gas mixing and also re- to plateau pressure) during flow-targeted, volume-cycled
duce flow dyssynchrony during assisted breaths, whereas ACV. An inspiratory flow of at least 40 liters/ min seems
the volume guarantee ensures a constant VT.17- 22 DCWB reasonable in order to have the constant flow activate at a
brea ths thus can be considered to be "more comfortable" reasonable point in the inspira tory cycle.
flow-targeted, volwne-cycled breaths. Alternatively, they As noted earlier, DCWB breath algorithms exist on several
could be cons idered PS with a VT "safety net." ventilators, but their clinical role remains unclear, and use
Both bench studies and small clinical trials have eval- is driven primarily by a clinician's belief in the underlying
uated DCWB breaths. In a lung model study with vary- concept. More important, however, the dual-control breath-
ing simula ted patient effort, 23 DCWB breaths allowed for to-breath (DCBB) approach described below appears to be a
more effective ma tcl1ing of ventilator output to simula ted simpler approacl1 to dual control and has appeared on more
patient demand than did flow-targeted, volume-cycled devices in recent years than the DCWB approach.
DUAL CONTROL BREATH TO BREATH (DCBB) With this approach, instead of setting a target pressure, the
clinician selects a VT. The ventilator then delivers one or
OCBB breaths are standard pressure-targeted breaths (ei-
more "test breaths" \'Vith a small amount of inspiratory pres-
ther PS or pressure-targeted ACV), but the ventilator has the
sure. The delivered VT is measured, and total system com-
ability to adjust the pressure target according to a clinician-
pliance is calculated. Thereafter, each subsequent breath
set V T and the delivered VT of previous brea ths.12•13•26 - 32
FIGU RE 16-3 Behavior of DCBB breaths in a lung model simulation of changi ng lung compliance. In both the top and b ottom panels,
pressure (Paw), flow, and volume (Vo l) are plotted over time. The target tidal volume in bo th panels is 600 mi. In the top panel, lung
compliance decreases after the fourth breath. Initially, there is a drop in tidal volume, but then the D C BB algorithm gradually increases the
target inspiratory press ure to restore the volume. In the bottom panel, lung compliance increases after the fourth breath. Initially, there is
a n increase in tidal volume, but then the D C BB algorithm grad ually reduces the inspiratory pressure target to restore the volume.
(Reproduced, witll penuissiou, fro m Braus otr eta/: Respir Ca·re 50:1 87-201, 2005.)
40
emH20
Paw
40 s
80 Flow
IJmin
·80
1200 Vol
ml
40 s
40
cmH20
Paw
40 s
80 Flow
Umin
-80
1200 Vol
ml
40 s
uses the previous calculation of system compliance to ma- and end-tidal C02 concentrations37•38 also may be incor-
nipulate the ensuing pressure target to achieve the desired porated into the mode-control algorithm to adjust either
VT (Fig. 16-3). TI1e maximum pressure change from breath the target VT or the breath-delivery pattern. If time-cycled
to breath on most systems generally is limited to a few cen- (ACV-like) and flow-cycled (PS-like) DCBB breaths are in-
timeters of water to prevent large swings in pressure and terspersed in a single mode, the machine is designed to
volume. The volume signal used for DCBB feedback control switcl1 between the two breath types depending on the pres-
is not exhaled VT but VT exiting the ventila tor. This prevents ence or absence of patient effort (flow-cycled breaths be-
a runaway effect, which could occur if a leak in the circuit ing delivered in response to patient effort, and time-cycled
prevented accurate measurement of exhaled VT. breaths being delivered in response to a machine-initiated
If the DCBB breath is flow-cycled, the flow-cycling cri- breath).39•40
terion is manufacturer-specific (e.g., 25-35% of peak flow), As with the DCWB breath, the putative advantage of
or it can be clinician-adjusted on many newer macllines. DCBB breath modes is to provide the mixing and synchrony
A secondary cycling mechanism may be present on some features of pressure targeting with the volume guarantee
devices if inspiratory time exceeds a certain fraction (e.g., of flow-targeted volume cycling. More specifically, propo-
80%) of a set total cycle time. Also, as with other pressure- nents of DCBB modes argue that applied pressure can be
targeted breaths, a rate-of-rise adjustment usually is avail- minimized "automatically" as mechanics improve or effort
able on DCBB breaths. increases.12· "' 3•39 TI1is, in turn, should keep the ventilator-
DCBB breaths are available in a variety of modes that can applied stretch of the lung to the minimum neces.sary for
supply patient-triggered, flow-cycled DCBB breaths and the desired VT and also may facilitate weaning.
patient- or machine-triggered, time-cycled DCBB breaths Both animal and human studies have shown that DCBB
either as stand-alone breaths or combined with each other, breaths function as designed using both flow-cycled and
with PS breaths, or with assist-control breaths (Table 16-1). time-cycled approaches.26-32·34-40 These studies emphasize
Although a clinician-set VT is always required to con trol the that the DCBB breath is similar to other pressure-targeted
DCBB breath pressure level, these modes also may require breaths with enhanced gas mixing and better patient-
a minimum rate setting by the clinician to either control the ventilator flow synchrony as compared with flow-targeted,
type of breath that will be given or, on some systems, to volume-cycled breaths and confirm that OCBB breaths do
enable automatic adjustments in the target VT. provide a volume guarantee without untoward side effects.
When tin1e-cycled (ACV-like) DCBB breaths are inter- Not surprisingly, several of these studies showed lower
spersed with either spontaneous w1supported or pressure- peak pressures with DCBB breaths than with volume assist-
supported breaths, or when flow-cycled (PS-Jike) DCBB control breaths. 26•28 This, however, is a finding consistent
breaths are interspersed with conventional ACV breaths, with the decelerating flow patterns of all pressure-targeted
algorithms similar to SIMV or MMV are often used to breaths (e.g., PS or PACV).
determine which breath type will be delivered. Airway Flow-cycled DCBB breaths, either alone or in combina-
occlusion pressu re (P0.1),33 oxygen saturation (Sp0 ),3"-36 tion with time-cycled DCBB breaths or various SIMV IPS
modes, have been used in several weaning studies; in gen-
eral, they have performed as well as (or sometimes better
TABLE 16-1 Proprietary Names an d Ch aracteristics of Newer than) stand-alone SIMV or PS protocols.30•32. 34- 39 A common
Dual-Contro l Breath-to-Breath (DCBB) Modes finding in these weaning studies is that the DCBB breath
modes required fewer ventilator manipulations. One must
DCBB Breath Type Examples of Proprietary Names
be cautious, however, in interpreting these weaning stud-
Patient- or machine- Pressure-regulated volume control ies. The SIMV or SIMV + PS control strategies have been
triggered, time-cycled" (Macquet/ Siemens, Viasys) shown in a number of clinical trials to delay weaning in-
Adaptive pressure ventilation appropriately compared with spontaneous breathing trials
(Hamilton) or stand-alone PS strategies.41 -4 3 A more appropriate eval-
Volume control plus (Puritan-Bennett) uation of DCBB breath weaning strategies would be a com-
Autoflow (Drager) parison with spontaneous breathing trials delivered accord-
Patient-triggered, Volume support (Macquet/Siemens, ing to a protocol. 42·44 •45 Further studies on the effect of both
flow-cycledb Puritan-Bennett) stand -alone and automated-switching algorithms for DCBB
Aow-cycled, pressure-regulated
volume control (Viasys)
breaths on important clinical outcomes are clearly needed.
Minimum mandatory ventila tion
before widespread use is recommended.
(Hamilton) Importantly, the DCBB breath may have unintentional
Combined patient/ Automode (Macquet/Siemens) outcomes w1der certain circumstances.11 For instance, if the
machine-triggered, set VT in a patient-triggered OCBB breath is higher than
time-cycled and patient demand, a recovering patient may never attempt
patient-triggered, to take over the work of breathing for that sized VT, and
flow-cycled thus ventilator-support reduction and weaning may not
progress. In addition, if the pressure level increases in an
• Some manufacturers all<~W pressure-support breaths to be provided in addi-
tion to the DCBB breaths.
attempt to maintain an inappropriately high VT in a patient
bSome manufacturers allow synchronized intermittent mandatory breaths to with airflow obstmction, intrinsic PEEP may result. Tilis
be provided in addition to the DCBB breaths. may be further complicated by the intrinsic PEEP reducing
398 PARTY ALTERNATIVEMETHODSOFVENTILATORSUPPORT
TABLE 16-2 Boundary Con di tions for Adaptive Lung/Support Ventilation
Parameter Minimum Maximum
Inspiratory pressure 5 above baseline airway pressure 10 below Pmax alarm settin g
(cmHzO) (PEEP / CPAP)
Tidal volume (ml) 4.4 • TBW 15.4 • TBW or VE/5, whichever is lower
(may be limited by Pmax alarm)
Target respiratory 5bpm 22 bpm • % min vol/100 (If IBW > 15 kg)
rate (bpm) 45 bpm • % min vol/100 (if IBW < 15 kg)
Mandatory breath 5 bpm 60bpm
rate (bpm)
Inspiratory time (s) 0.5 seconds or 1 • RCe, whichever 2.0s
is longer
Expiratory time (s) 2 • RCe (possibly 3 • RCe) 12 s
I:E ratio rru,ge 1:4 1:1
NOTE: These parameters set tl1e limits on the various parameters used during ASV. Pmax, clinidan-set maxin1al inspiratory
p ressure; IBW, ideal body weight; V£, exhaled minute volu me; bpm, allowable breaths per minute; % min vol, clinicia n-set
proportion of predicted minute volume needed by the patient that wiU be supplied by the ventilator; the percent minute volume
is based on predicted body weight, e.g., for a 80-kg patient, 100% of minute volume is a minute ventila tion of 8 liters/ min; l:E,
inspiratory to expiratory time ratio.
the VT, which causes yet further increases in airway pres- tory time constants (RCe = resistance x compliance) to en-
sure a nd intrinsic PEEP.31 Conversely, if the set VT is below sure an inspiratory time of at least one RCe and an expi-
patient demand, a patient may receive inadequate support. ratory time of at least three RCes.48 Boundary rules exist to
Under these conditions, a patient will perform excessive prevent excessive (runaway) settings (Table 16-2). Clinicians
work to maintain a certain VT even as the inspirato ry pres- must set the desired minute ventilation and the proportion
sure is being reduced because the delivered VT exceeds that of that minute ventilation that the machine is to supply. Ideal
set by the clinician. bod y weight a lso can be used to calcu late thedesired minute
Despite these concerns and the fact that no outcome stud- ventilation based on metabolic demands and predicted
ies have been performed using DCBB breaths, there are s pe- dead space. Clinicians also must set the PEEP and Fr0:1 .
cific clinical situations w here they may have some utility Conceptually, ASV has been proposed as a way to min-
(e.g., fluctuating patient demand and ra pidly recovering imize ventilator-delivered inspiratory pressure for a given
patient). Clinicians, however, need to be aware of the be- minute ventilation through the use of the " minima l work''
havior of DCBB breaths under a variety of circumstances to frequency- tidal volume pattern and the minimization of in-
use these m odes properly. trinsi.c PEEP.11 •46A7 It thus may reduce overdistension and
associated ventilator-induced lung injury. ASV also might
be considered an automatic weaning mode because the algo-
rithm responds with lower pressures and fewer mandatory
Feedback Control of DCBB Breaths breaths as patient effor t increases.
ASV has been evaluated in a number of ways. Initial lung
Based on Respiratory System Mechanics model testing 49 demonstrated that the ASV a lgorithm re-
and Effort sponded properly to abrupt changes in lung m echanics. Sev-
eral clinical s tudies have compared initial ASV settings with
A novel a pproach to automated feedback control of traditional clinicia n-selected settings and have found that
ventilator support combines the switching algorithm be- ASV tends to select a lower tidal volume and faster rate (and
tween DCBB patient-triggered, flow-cycled and machine- thus lower inspiratory pressures) than do clinicians.49-5 2
triggered, time-cycled breaths described earlier with a n Two other studies suggest that ASV also appropriately
automated VT/ frequency / inspiratory-to-expiratory (I:E) adapts to changes in patient position and double- to single-
ratio setup based on respiratory system mechanics. Known lung anesthesia. 52- 54 One other study suggested that the l:E
as adaptive lung ventilation 46 or adaptive support ventilation algorithm of ASV produced less air trapping in patients w ith
(ASV),11 •47 the breath-control algorithm a ttempts to parti- chronic obstructive pulmonary disesae (COPD).55
tion the frequency, tidal volwne, and I:E ra tio in order to Longer-duration clinical studies with ASV have shown
minimize the potential for the combination of ventilator- that the algorithm provided appropriate ventilator support
patient inspiratory work and intrinsic PEEP. ASV does this in anesthetized patients,49•52 as well as in pa tients with respi-
by calculating respiratory system mechanics using several ratory failure.56 One study noted decreased patient loading
"test breaths." It then uses a "mimimal work" calculation47 with ASV.57 A number of studies have evaluated ASV in
to set the frequency-tidal volume pattern tha t minimizes the patients being weaned from mechanical ventilation. 46•56-61
combined res istance and compliance components of work. In general, these studies showed that ASV safely provided
The ASV algorithm then uses a measurement of the expira- adequate ventilator support and had similar (or faster)
weaning times as compared with various SIMV a11d SIMV + of the breath and overcompensate the load at the end of the
PS protocols. These studies also generally showed fewer breath (see Fig.16-4, middle panel). Patient muscle unloading
ventila tor manipulations with ASV. As noted earlier for thus is uneven and rnay be suboptimaL
other DCBB approaches, a more appropriate evaluation of One way to address this is to use a pressure sensor at
ASV weaning strategies would be a comparison with use of the distal end of the ETI to target the PS applied pressure.
spontaneous breathing trials delivered by protocoi, 42A 4-45 This approach would provide a mo re even pressure bias to
not with SIMV or SIMV + PS. Larger trials in patients w itll the contracting inspiratory muscles. Unfortunately, this ap-
lung injury clearly are needed to establish the appropriate- proach is w1reliable because intra-airway sensors are sub-
ness of the ASV algorithms in various disease states and the ject to errors from positioning and mucus occlusion. An
effects of ASV on outcome. alternative is to have the ventilator calculate the ETI resis-
tat1ce properties and use those calculations to manipulate
applied pressure in such a way as to compensate for the ETI
effects67•68 (see Fig. 16-4, right panel). To accomplish this, the
Automatic Adjustments in Pressure and clinician must input the tube geometry (length and diame-
Flow Based on Artificial Airway Geometry ter) and the percentage of compensa tion desired (10-100%).
TI1e ventilator then uses these data to calculate ETI resis-
TI1e endotracheal tube (ETI) imposes a significant inspi- tance and incorporates this w ith measurements of instan-
ratory resistance on a spontaneously breathing pa tient62·63 taneous flow to apply pressure proportional to resistance
(Fig. 16-4, left panel). This imposed load can have an impact throughout the total respiratory cycle.
on flow synchrony during interactive assisted /supported The BIT-compensation concept was first introduced in
breaths and can make it djfficult to assess potential 1993 by Guttmann et aJ67 and was applied during both in-
for ventilator withdrawal during periods of unassisted/ spira tion and expiration. It was believed that the expiratory
tmsupported breathing. effect (i.e., circuit pressure actually going below set baseline
Low level (e.g., S-8 cmH20) PS has been p~o~osed as pressure to "assist" expiratory flow) might further improve
a way of eliminating the ETI resistive load. Unfor- patient-ventilator interactions by reducing expiratory work
tuna tely, the PS algorithm supplies a constant inspiratory and hyperinflation. In a series of ventilated patients, this
pressure, which, because of the high fixed resistance of the approach was shown to improve subjective patient comfort
ETT, tends to undercompensate the load at the beginning substantially.69
FIGURE 16-4 Effects of the endotracheal tube (ETI) resistance on the application of continuous positive airway pressure (CPAP), pressure
support (PS), and CPAP with ETT compens ation (CPAP-ATC) in a spontaneously breathing patient. Depicted are airway pressure profiles
over time in the ventilator circuit (upper panels) and the distal trachea (/ower panels). In the left breath, the CPAP tracing in the ventilator
circuit is appropriately constant, whereas the tracheal pressure downswing reflects the patient wo.rk required to effect flow trough the ETT.
In the middle breath, PS is applied in the ventilator circuit. This reduces some of the patient work, but because the "squarewave" PS breath
does not adequately pressurize the trachea rapidly enough, there still can be s ignificant work required by the patient early in the breath.
In the right breath, a similar mean inspiratory pressure to the PS breath is applied, but the pressure profile is altered to provide a higher
pressure early and a lower pressure later (CPAP-ATC). This profile is machine-determined, and knowl edge of ETT geometry accounts
more appropriately for the effects of ETT resistance. It thus creates a truer CPAP pattern in th e trachea. Note that this ETT-compensation
feature also can be combined with PS on some ventilators. (Reproduced, with permission, from MaclnhJre: Respir Care 50:275-86, 2005.)
+t
0
I1
Airway
pressuro
(em H20)
+l
0 ..,
-..../'
1 1
Variations on this computational approach to manip· 2. Branson RD, Chatbum RL. Technical d escription and classifi-
ulating applied pressure a re now available as automatic ca tion of modes of ventilator operation. Respir Care 1992; 37:
tube compensation (ATC; Drager, Puritan-Betmett, Ma- 1026-44.
quet/Siemens) and a utomatic airway compensation (AAC; 3. Madntyre NR Principles of mechanical ven tilation. In: Murray
Viasys) . Bench and clinical studies have verified that the J, Nadel J, editors. Textbook of respiratory medicine, 4th ed. New
York: Elsevier, 2005.
ETT-compensation algorithms on these commercial systems
4. Luce JM, Pierson OJ, Hudson LD. lnterrnittent mandatory venti·
generally perform as designed during both continuous pos- lation. Chest 1981; 79:678-85.
itive airway pressure (CPAP) and PS?0- 72 Not all systems, 5. Weisman lM, Rinaldo JE, Rogers RM, et al. Intermittent manda·
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the Guttman design.67 tory ventilation: Is synchronization important? Chest 1980; 77:
It also must be recognized that the Err-compensation 598-602.
strategy is based on the input geometry of the artificial air- 7. Hewlett AM, Platt AS, Terry VG. Mandatory minute volume: A
way and cannot account for changes in tube characteris- new concept in weaning from mechanical ventilation. Anaesthe-
tics induced by kinks or partial occlusions or the relation- sia. 1977; 32:163-9.
8. Ravenscroft PS. Simple mandatory minute volume. Anesthesia
ship of the tube opening against the trad1eal wall Thus 1978; 33:246-9.
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for a tracheal pressure sensor, especially as the duration Chest 1991; 100:1421-9.
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13. Branson RD, Davis K. Dual control modes: Combining volume
An interesting extension of the ETT-compensation con-
and pressure breaths. Respir Care Clin North Am. 2001 ; 7:397-
cept is to u se a pleural pressure to target the positive-
401.
pressure breath. 73 This approach requires an esophageal 14. Raneri VM Optimization of patient ventilator interactions:
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as to account for all the components of patient work, not 16. Amato MBP, Barbas CSV, Bonassa J, et al. Volume assisted pres·
just that caused by the ETI. At the present time, this ap- sure support ventilation (VAPSV): A new approad1 for reducing
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17. Marini JJ, Rodriguez RM, Lamb V. The inspiratory workload of
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Conclusion n,
18. Marini Capps JS, Culver BH. The inspiratory work of breath-
ing during assisted mechanical ventilation. Chest 1985; 87:
612- 8.
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is adequate for gas exchange and appropriate muscle un- breathing comfort during weaning with two ventilatory modes.
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breaths according to patient effort and respiratory system
1025-33.
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are not totally "closed-loop" systems because the automatic sure control versus volume control assis ted ventilation on patient
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FARTVI Conventional mechanical ventilation via endotracheal in-
tubation or tracheostomy in the treatment of acute res-
piratory failure (ARF) is a lifesaving procedure. Yet it
NONINVASIVE exposes patients to severe complications, including upper
airway trauma a nd nosocomial pneumonia, and may pro-
METHODS OF long the length of stay in the intensive-care unit (TCU)
and hospital because additional time may be necessary for
VENTILATOR SUPPORT weaning.1-4
Noninvasive ventilator techniques have been used re-
cently to treat ARF, and while their benefits, as compared
Chapter 17 _ _ _ _ _ _ _ __ _ with intubation, have not been firmly established, their use
is attractive. Advantages include the possibility of avoid-
NEGATIVE-PRESSURE ing sedative agents, facilitating communication between pa-
tients and care providers, and preserving such functions as
VENTILATION swallowing and coughing. Noninvasive mechanical venti-
lation consists of botl't negative- and positive-pressure ven-
ANTONIO CORRADO, MASSIMO GORIN! tilators. We discuss the basic principles, the physiologic
effects, and the more recent clinical application of negative-
pressure ventilation (NPV).
Basic Principles
BASIC PRlNOPLES
Negative-Pressure Ventilators NPV works by exposing the surface of tl1e thorax to sub-
Negative-Pressure Ventilator Pumps atmospheric pressure d uring inspiration. This pressure
Modes for Delivering Negative-Pressure Ventilation causes thoracic expansion and a decrease in pleural and
PHYSIOLOGIC EFFECTS alveolar pressures, creatin g a pressure gradient for air to
Gas Exchange move from the airway opening into the alveoli. When the
Respiratory Muscles pressure surrounding the thorax increases and becomes at-
Upper Airway mospheric or greater, expiration occurs passively owing
Lower Esophageal Sphincter to the elastic recoil of the respiratory system. The inspi-
Cardiovascular ratory changes with NPV, in pleural and alveolar pres-
RATION ALE, ADVANTAGES, AND LIMITATIONS sures, replicate those during spontaneous breathing. On
Rationale the contrary, positive-pressure ventila tion (PPV) causes
Advantages an increase in intrathoracic pressures during inspiration
Limitations (Fig. 17-1).
INDICATIONS AND CONTRAINDICATIONS All negative-pressure ventilators have two major compo-
Acute Respira tory Failure nents: an airtight, rigid cl1amber that encloses the rib cage
Chronic Respiratory Failure and abdomen and a pump that generates pressure changes
Other Applications in the chamber. 5' 6
COMPARISON WIT H OTHER MODES
Negative-Pressure Ventilation Versus Invasive
Mechanical Ventilation
Negative-Pressure Ventilation Versus Noninvasive NEGATIVE-PRESSURE VENTILATORS
Positive-Pressure Ventilation TANK VENTILATOR
VARIATIONS IN DELIVERY AMONG Tank ventilators enclose the body up to the neck. The ad-
VENTILATOR BRANDS vantage is that chest-wall expansion is not limited by con-
ADJUSTM ENTS AT T HE BEDSIDE tact v.ith the sides of the chamber, and only one airtight
TROUBLESHOOTING seal is required around the neck. Most modern tank ven-
Setting in Control Mode tilators are constructed of aluminium and plastic and are
Monitoring of Tidal Volume lighter than previously. The patient's body rests on a thin
Nursing Ca re mattress, and the head protrudes through a porthole at one
IMPORTANT UNKNOWNS end of the ventilator. A head a nd neck rest is provided
THE FUTURE in most designs to ensure comfort and to prevent upper
Inspiratory Trigger System airway collapse. Most tank ventilators have windows al-
Design of Tank Ventilato r lowing patient observation and portholes for catheters and
Potential Clinical Application monitor leads and w here procedures can be performed7
SUMMARY AND CONCLUSIONS (Fig. 17-2).
403
404 PART VI NONINVASIVE METHODS OF VENTILATOR SUPPORT
End-expiration Inspiration End-.xpiration
-I
+ 10 + 10
C't''= -5
FIGURE 17-1 Airway and intrathoracic pressures
during positive-pressure ventilation (upper panel)
and during negative-pressure ventilation (bottom
pa11el). Palv, alveolar pressure; PL, clastic recoil
pressure of the lung; PCW, clastic recoil pressure of
the chest wall; Ppl, pleural pressure; Pmusc, muscle
pressure; Paw, airway pressure; Plank, tank
Ptank = 0 -10 -10
ventilator press ure.
JACKET VENTILATOR (PULMO-WRAP, ventilator, a nd the peak pressure that patients can tolerate
PONCHO-WRAP) also usually is slightly less. 6
This ventilator is a windproof, water-permeable nylon parka
suspended over a rigid grid that includes the rib cage and CUIRASS
abdomen.lt allows the application of negative pressure over This consists of a rigid shell fitting firmly over the ante-
the anterior portio n of the chest wall.8 Airtight seals around rior portion of the chest. It applies negative pressure over
the neck, arms, and hips are required to prevent air leakage. a smaller surface area than either the iron lung or jacket
The jackets do not restrain expansion of the rib cage and and is the least efficient negative-pressure ventilator.8 Its ef-
abdomen but are awkward for many patients to put on and ficiency improves if the anterior abdominal wall is enclosed
often cold to wear because of air leaks. They are preferable to in the device and movement of the lateral aspect of the up-
tank ventilators for home use but less efficient for treating per rib cage is not restrained. Proper fitting can be difficult,
patients with ARF. The tidal volume they develop at any and tailor-made fiberglass shells often are necessary, partic-
given level of negative pressure is less than that of a tank ularly in patients with kyphoscoliosis.
FIGURE 17-2
Microprocessor-bas ed iron lung
(Coppa CA 1001, Coppa, lliella,
Italy).
CHAPTER 17 NEGATIVE-PRESSURE VENTILATION 405
0,5~
0,0
· 0,5 .
- c
..-..
c.=:...
~ E
10
-10
0
y
'-' -20
FIGURE 17-3 Recordings of tidal

volume by Respitrace (VT RT),
pleural pressure (Pp l),
transdiaphragmatic pressure (Pdi),
an d tank pressure (Ptank) in a
patient with an acute exacerbation
of COPD during assist
negative-pressure ventilation
Time (s) provided by iron lung.
NEGATIVE-PRESSURE VENTILATOR PUMPS ondary to the lack of coordinated activity between the up·
per airway and the inspiratory musdes.10 To overcome
Negative pressure is genera ted by bellows or rotary pumps this limitation, some negative-pressure ventilators have in-
that a re separate or incorporated into the structure of the corporated pa tient-triggered modes using pressure change
ventilator. Modern rotary pumps perform pressure-preset sensed via nasal prongs. There are da ta indicating that this
ventila tion.9 After a breath is initiated, these pumps apply technology is slow and relatively insensitive to patient in-
and maintain a targeted amount of suba tmospheric pres- spiratory efforts.11 Recently, the performance of a prototype
sure around the chest wall to meet a specified time-cycling microprocessor-based iron lung capable of thermistor trig-
criterion (Fig. 17-3). This mode is equivalent to pressure- gering was evaluated. 12 The device used to trigger the iron
controlled ventilation available with the lates t positive- lung was thermally sensitive and similar to that used in
pressure ventilators. As with positive-pressure-preset ven- sleep studies, and it was activated by temperature changes
tilation, tidal volume during NPV is a complex function of caused by the onset of ins piratory airflow (Fig. 17-4). In
applied pressure and its rate of approach to ta rget pres- normal subjects and patients with chronic obstructive pul·
sure, available inspiratory time, and the impedance to monary disease (COPD) recovering from ARF, we measured
breathing [compliance of the respiratory system, airway (1) the time delay between airflow onset and start of an as-
resistance, d ynamic hyperinflation with intrinsic positive sisted breath, (2) pressure-time product for the diaphragm
end-expiratory pressure (PEEP)]. per minute (PTPdi) during triggered breaths, and (3) non-
triggering inspiratory efforts (Fig. 17-5). At maximum trig-
ger sensitivity, the tin1e delay was about 0.21 second in both
groups. PTPdi was reduced markedly. Non triggering inspi-
MODES FOR D ELIVERING N EGATIVE-PRESSURE
ratory efforts were 1.1% and 2.3% of total breaths, respec-
VENTILATION
tively. Although the time delay of the thermistor trigger is
Traditionally, NPV is controlled mechanical ventilation, and longer than most recent flow- and pressure-triggering sys-
the device provides a fixed number of breaths per minute. tems of positive-pressure ventilators,13 the study suggests
If mechanical and spontaneous respiratory cycles do not that this system permits the use of assisted NPV with an
match, the patient "fights" the ventilator, resulting in dis- acceptable patient-ventila tor i11teraction.
comfort. For this reason, airway pressure or flow gener- Presently, NPV can be delivered by five modes: (1) in-
ally is used in pos itive-pressure ventilators to detect inspi- termittent negative pressure, (2) negative/positive pres-
ratory efforts and to trigger the mechanical breath (assist sure, (3) continuous negative pressure (CNEP), (4) negative
and assist-control ventilation).1 Unlike PPV, during NPV, pressure/ negative end-expiratory pressure (Fig. 17-6), and
the air way opening is free; consequently, it is not p ossi- (5) external high-frequency oscillation.
ble to monitor airway pressure or flow continuously and
to use these signals to trigger a mechanical breath. This INTERMITTENT NEGATIVE PRESSURE
patient-triggering inability may contribute to poor patient The ventilator generates targeted subatmospheric pressure
synchrony and induction of upper airway collapse sec- for the selected inspiratory time. Pressure around the chest
406 PART VI NONINVASNE METHODS OF VENTILATOR SUPPORT
FIGURE 17-4 Control panel of a

microprocessor-based iron lung
(Coppa CA 1001, Coppa, Biella,
Italy) capable of thermistor
triggering. The upper trace is the
thermistor s ignal, and the lower
trace is the tank pressure.
wall becomes atmospheric during expiration, which occurs chest-wall disorders, this combination has been found to
passively owing to the elastic recoil of the respiratory sys- increase tidal volume more than intermittent negative pres-
tem. sure alone by reducing the end-expiratory volume of the
respiratory system. 14 On a theoretical basis, it is unlikely
NEGATIVE/POSITIVE PRESSURE that positive extrathoracic pressure during expiration can
The ventila tor generates the preset extrathoracic subath- increase expiratory flow in patients with severe COPD
mospheric pressure during inspiration and preset extra tho- and tidal expiratory-flow limitation. A useful application
racic positive pressure during expiration. 1J1 patients with of this option is to assist cough and promote clearance of
0.8 FIGURE 17-5 Recordings of flow,

transdiaphragmatic pressure (Pdi),
and tank pressure {Ptank) in a
~-
0~ 0.0 patient with COPD receiving assist
-...::~ NPV. The continuous vertical line
~- indicates the onset of inspiratory
effort_ the d ashed vertical lin e
-0.8 indicates the start of inspiratory
PTPdiTr Bow, and the dotted vertical line
15 PTPdiPost indicates the start of an assis ted
....-
"Cl:t
0. . 10
breath. The partitioning of the
pressure-time product of the
diaphragm is shown: effort
~e 5
required to overcome PEEP1
~
~ (PTPdirEEP1), effort required to
trigger the assisted breath
0
PTPdiPEEPi (PTPdiTr), and effort exerted in th e
post-trigger phase (PTPdiPost).
TDrEEr1 and TDtr indicate the time
0 delay between the onset of
~s
d ... -10
II inspiratory effort and the star t of
inspiratory Bow and the time delay
~= TDl'UPi IDtr between the onset of in spiratory
~s -20 Bow and the start of assisted
~~ breath, respectively. (Used, with
-30 .
.1 .... L-1.---L---L---L---L---L---L---L_J
3.00
penuissio11, from Goriui et al:
Thorax 57:258-62, 2002.)
0.00 0.50 1.00 1.50 2.00 2.50
Time (s)
FIGURE 17-6 Control panel of a microprocessor-based iron lung (Coppa CA 1001, Coppa, Biella, Italy) during inte rmittent
negative-press ure (upper-left pauel), negative/positive-pressure (upper-right pauel), continuous negative extrathoracic pressure (lower-left
parrel), and negative-pressure/negative extra thoracic end-expiratory pressure (lower-right paucl) ventilation.
sputum in patients with copious secretions (i.e., cystic fi- to -70 cmH20) and peak expiratory (up to 70 cmH2 0) pres-
brosis, bronchiectasis).8 sures, frequency (8-999 cycles per minute), and inspiratory-
expiratory (I: E) ratio (1 :6-6:1) can be set on the control unit.
CONTINUOUS NEGATIVE EXTRATHORACIC Two studies suggest that external high-frequency oscilla-
PRESSURE (CNEP) tion can provide effective ventilation in healthy subjects15
The ventilator provides a constant subatmospheric pressu re and improve end-tidal carbon dioxide (C02) and oxygen
throughout the respiratory cycle, and the patient breathes (02) saturation (Sa02 ) in patients with severe stable COPD .16
spontaneously. In five patients with ARF, short-term application of external
high-frequency oscillation improved oxygenation by 16%
NEGATIVE PRESSURE/ NEGATIVE EXTRATHORACIC and reduced Paco2 by 6% compared with conventional
END-EXPIRATORY PRESSURE PPV. 15 ln a randomized, controlled study, a 4-hour period of
The ventilator generates the preset subatmospheric pres- external high-frequency oscillation improved cardiac index
sure during inspiration and maintains a preset level of neg- and tissue perfusion in adult patients after coronary artery
ative pressure throughout the expiration. bypass grafting compared with conventional PPV.17
EXTERNAL HIGH-FREQUENCY OSCILLATION

High-frequency ventilation using a jet system can be ap-
Physiologic Effects
plied via a tracheal tube or a tracheotomy. Alternatively,
GAS EXCHANGE
a cuirass can be used to apply high-frequency oscillation
externally. 15 The Hayek oscillator includes a cuirass, power Pioneering studies showed NPV, particularly that pro-
unit, and control unit. The power unit has (1) a diaphrag- vided by tank ven tilators, to be a highly effective form of
matic pump, which can operate over a w ide range of fre- mechanical ventilation, capable of maintaining normal ar-
quencies to generate an oscilla ting pressure wave, and (2) a terial blood-gas tensions in patients w ith little or no sponta-
vacuum pump, which enables the oscillation to be superim- neous respiratory activity.18-20 In stable COPD patients with
posed on a negative-press ure baseline. Peak inspiratory (up chronic respiratory failure, poncho-wrap NVP is able to
Pa02 PaC02 pH
RO __ __.. 90 7,42
r· 85 7,40
.. .
75
lr~ -.....___ 1!0
7,38
.
FIGURE 17-7 Values for Pao2 ,
,/ (;_.·--·/ 75 Paco 2, and pH in seven patients
-
....
.... .,~
/
,.-.r I [
: 1:.< 7,36 with acute exacerbation of chronic
./w··
t ·-
70 >= 70 obstructive pulmonary disease
e e during spontaneous breathing (SB),
e r? • -......... e 7,34
continuous negative extrathoraclc
~·· -- 65
pressure (CNEP), n egative-pressure
65
.,. //
60
7,32 ventil ation (NP V), and negative
..---·--· ~
55 7,30
extra thoracic end-expiratory
pressure added to NPV
(NPV-NEEP). (Used, witll
pemtission, from Gorini eta/: Am J
60 .. I so 7,28 R espir Crit Care M ed 163:1614-8,
SB CNEP l'i I'V NI'V-:\'l<:EP SB <:NF.P NPV l'i i'V-NEEP SB CNEP NPV CIIJ' V-~ 11.t: l'
2001.)
improve the pattern of breathing, minute ventilation, the pattern of breathing associated with a marked re-
and arterial blood-gas tensions.21 -22 Recently, the physio- duction in both pressure-time product o f the diaphragm
logic effects of CNEP, NPV, and NPV plus negative ex- and electrom yographic activity o f the parasternal muscles.
trathoracic end-expira tory pressure (NEEP) prov ided by The application of -5 cmH 2 0 of negative extrathoracic
a microprocessor-based iron lung in seven patients with end-expiratory pressure during NPV further d ecreased the
COPD recovering from ARF were studied. 23 The different pressure-time product of the diaphragm slightly a nd im-
types of NPV were able to improve ventilatory pattern, ar- proved patien t-ventilator interaction by red ucing dynamic
terial blood gases, and pH significantly (Fig . 17-7). intrinsic PEEP and nontrig gering inspiratory effort (Fig.
17-8). Reduction in diaphragmatic effort obtained during
RESPIRATORY MUSCLES assis t-control NPV23 is similar to that measured in patien ts
with an acute exacerbation of COPD with pressure-support
Two studies reported that NPV, carried out continuously ventilation.33, 34
for 6 hours by iron lung24 or intermittently for 7 d ays
by poncho-wrap,ZS was effective in improving respiratory
UPPER AIRWAY
muscle streng th and in d ecreasing Paca, . In pa tien ts with
chronic respiratory failure secondary to COPD and restric- The applicatio n of NPV during sleep in normal subjects35
tive diseases, NPV reduced electrical and mecl1anical activ- and in patients with chronic respiratory failure secondary
ity of theinspiratorymuscles.26- 30 Rodenstein et al 31 showed to COPD10 and neuromuscular disorders36,37 may result in
that controlled NPV provid ed by an old iron lung requires the development o f recurrent episod es of apnea and hypop-
a short period of adap tation to obtain inspiratory muscle nea, as well as alter ed sleep quality. Most obstructive events
rest. Other studies have shown that when inspiratory and during NPV were associated with mild oxygen d esaturation
expiratory times were adjusted carefully to approxima te the (<3%), and only one subject had marked d esaturation.10, 36
subject's spontaneous timing components, NPV results in Moreover, a recent controlled study in patients with neuro-
a substantial s uppression of electromyographic activity of muscular disorders sh owed that NPV resulted in a general
inspiratory musd es. 27•28 Assist-control NPV provided by a improvement in sleep quality and oxygen saturation. 38 It
cuirass is effective in relief of dyspnea induced experimen- has been reported that in normal subjects during v oluntary
tally in no rmal subjects by a combination of inspiratory re- respira tory muscle relaxation, NPV caused a decrease in
sistive loading and hypercapnia, probably reducing inspi- the caliber of the upper airw ay a t the glo ttic or supraglottic
ratory muscle workload.32 level. 39 In normal, awake subjects, the glottis width did not
The effects of NPV provided by a microprocessor-based decrease with the increase in negative pressure applied to
iron lung capable of providing CNEP and assist-control °
the chest wall. 4 Consequently, the increasing level of NPV
NPV on respiratory mechanics and inspiratory muscle effort resulted in progressive increases in tidal volume and minute
in patients with COPD with A RF were evalua ted by mea- ventila tion. On the contrary, control positive-pressure ven-
suring the pressure-time p roduct of the diaphragm and the tilation provid ed by m ask caused inspira tory adductio n of
electromyographic activity of parasternal muscles. 23 Com- the vocal cords, which reduced the tidal volume effectively
pa red with spontaneous breathing, CN EP (-5 cmH20 ) re- reaching the lungs.41 , 42
sulted in a significant d ecrease in d ynamic intrinsic PEEP The mechanisms of upper airway obstruction observed
and pressure-time product of the diaphragm, whereas with NPV at supraglottic level have not been elucidated
assist-control NPV caused a significant improvement in fully. During s pon taneous b reathing, activation of the
~
1,5 SB CNEP NPV NPV - NEEP
§ ~ J,O .
_.a
o·- 0,5
:>c 0,0
0,6
=:. ~
0,0 ·
£~
-0,6
6... 10
- ::z: 0
ce...,
-10
-20
6 lO
-----------
==
~e
~
0
-10
-20
20
6
~=5 10
---- - - ---
l
~ 0
~ 6:i -100
t e -2o
~ -30
0 5 10 0 5 10 0,0 5,0 10,0 0,0 5,0 10,0
Time(s)
FIGURE 17-8 Recordings of volume, flow , pleural pressure (Ppl), gastric pressure (Pga), transdiaphragmatic pressure (Pdi), and tank
pressure (Ptank) in a patient with an acute exacerbation of COPD during sp ontan eous breathing (SB), con tinuous n egative extra thoracic
pressure (CNEP), n egative-pressure ventilation (NPV), and n egative extra thoracic end-expiratory pressure added to NPV (NPV-NEEP). The
dashed lines indicate the level of zero in flow , Ppl, Pga, and Pdi recordings. (Used, with pt>rmissiou, from Goriui eta/: Am TRespir Crit Care
Merl163:1614-8, 2001.)
pharyngeal and laryngeal muscles precedes activation of determinants of cardiovascular performance.47"""9 The in-
the inspiratory muscles, resulting in stiffening of the up- crease in intrathoracic pressure caused by PPV decreases
per airway walls. When NPV is applied during sleep or both venous return to the right ventricle and left-ventricular
in completely relaxed subjects, this coordinated respiratory afterload. TI1e neteffectofthis reduction depends on the car-
muscle activity may be abolished. Consequently, the subat- diac function. When left-ventricular function is impaired,
mospheric pressure developed in the upper airway during cardiac output increases in response to the rise in intratho-
inspiration may result in their collapse.5 •10•36•39 Upper air- racic pressure because the decrease in left-ventricular af-
way obstruction has been reported in 2 of 10 patients with terload secondary to the reduction in transmural pressure
acute-on-chronic respiratory failure during treatment with has a greater effect than the decrease in venous return. 50
NPV 43 and was the reason for NPV failure in 16% of patients When left-ventricular function is normal, the increase in
in a large prospective cohort study. 44 intrathoracic pressure reduces cardiac output because the
decrease in venous return has more effect than the de-
crease in left-ventricular afterload. 51 In clinical situations
LOWER ESOPHAGEAL SPHI NCfER
such as hypovolemia, septic shock, and gas trapping as-
NPV may induce a lower esophageal sphincter dysfw1ction sociated with airflow obstruction, the reduction in cardiac
in healthy subjects45 and patients with COPD. 46 This dys- output is more relevant. 52
function may cause regurgitation of stomach contents and Although the hemodynamic effects of NPV have not been
expose patients to the risk of aspiration. It can be prevented studied extensively,53 the effects are assumed to be the op-
completely with metodopramide. 46 posite of those of PPV, that is, more physiologic and more
likely to maintain a normal cardiac output. The exposure of
the entire body (except for the airway opening) to NPV by
CARDIOVASCULAR tank ventilators, however, results in the same hemodynamic
TI1e hemodynamic effects of mechanical ventilation are effects as occurs with PPV. 54 These effects occur because in-
complex and are the result of changes in intrathoracic pres- trathoracic pressure actually is raised relative to body Slll'-
sure and lung volume, w hich independently can affect the face pressure, reducing the gradient for venous return. Tilis
consequence is not seen when NPV is confined to the tho- ability to minimize the amount of air leakage74 are major fac-
rax and upper abdomen using a cuirass or poncho-wrap.55•56 tors associated with failure of this technique. In clinical stud-
Unlike tank ventilators, these machines selectively decrease ies, NPV has been used successfully in patients with severe
intrathoracic pressure so that right-atrial pressure becomes respiratory acidosis or impaired level of consciousness.75- 77
more negative relative to the rest of body, potentially en- During NPV, the airway opening is free, unlike in PPV, and
hancing the gradient for venous retum. In an aninlal model consequently, performing bronchial aspiration or fiberoptic
of acute lung injury, NPV plus NEEP, provided by poncho- bronchoscopy to remove excessive airway secretions is easy.
wrap, resulted in a similar improvement in gas exchange Finally, NPV can be used in patients who cannot tolerate a
and in higher cardiac output compared with PPV plus mask because of facial deformity or as a rescue therapy to
PEEP.55 In anaesthetized dogs, PPV plus PEEP and NPV avoid endotracheal intubation in those in whom mask ven-
plus NEEP applied by iron lung had a similar effect on car· tilation fails. Routine implementation of noninvasive PPV
diac output, whereas the latter was higher with NPV plus in critically ill patients with acute exacerbations of COPD or
NEEP applied by poncho-wrap compared with the other severe cardiogenic pulmonary edema was associated with
two modes.56 improved survival and reduction of nosocomial infection.78
NPV provided by cuirass does not induce adverse hemo- For Htese reasons, mask ventilation is recommended as the
dynamic effects in stable patients w ith COPD,57 whereas standard method of ventilator support for exacerbations
a significant reduction in cardiac output has been re- of COPD; invasive mechanical ventilation is regarded as
ported with mask ventilation with PEEP in patients with second-line rescue therapy when mask ventilation fails.79 To
COPD both when stable58 and during acute exacerbations.59 verify the hypothesis that using both noninvasive mask and
Short-term studies have compared the effects of CNEP iron-lung ventilation should further reduce the need for en-
provided by cuirass60 or poncho-w rap61 ,62 with those of dotracheal intubation in patients with acute on chronic res-
PEEP in intubated patients with acute lung injury receiv- piratory failure, a prospective cohort study was carried out
ing volume-controlled ventila tion. CNEP was adjusted to in 258 consecutive patients44 : 77% of patients were treated
obtain the same change in transpulmonary press ure62 or exclusively with noninvasive ventilation (40% with NPV,
functional res idual capacityOO as with PEEP. The combina- 23% with mask, and 14% with tl1e sequential use of both)
tion of volume-controlled ventilation with CNEP, compared and 14% with invasive ventilation. In patients in whom
with volume-controlled ventilation with PEEP, resulted in NPV or mask ventilation failed, sequential use of the al-
significant increases in oxygen delivery and cardiac index, ternative technique allowed a significant reduction in the
whereas arterial oxygen content and Pa02 / Frcn ratio did not failure of noninvasive mechanica ventilation (from 23.4%
differ between the two modes of ventilation.6o--62 Further to 8.8%, p = .002, and from 25.3% to 5%, p = .0001, respec-
studies are required to define the feasibility of long-term tively). Overall hospital mortality (21 %) was lower than that
clinical treatment with CNEP during controlled ventilation estimated by APACHE II score (28%). This study shows that
via endotracheal intubation and its effects on clinical out- use of N PV and mask ventilation made it possible to avoid
comes. Children with congenital heart diseases, submitted endotracheal intubation in the vast majority of unselected
to right-sided heart surgery w ith Fontan-type procedures, patients with acute-on-chronic respiratory disorders need-
have unique cardiopulmonary physiology. In the absence ing ventilator support. 44 Another recent study reported that
of a right ventricle, pulmonary blood flow, the major deter- using both modalities of noninvasive ventilation in patients
minant of cardiac output, is exquisitely sensitive to changes with acute-on-chronic respiratory failure, the total rate of
in intrathoracic pressure. In these patients, NPV, provided success in avoiding endotracheal intubation was 81.6%.80
by cuirass, markedly increased pulmonary blood flow and
cardiac output compared with volume-controlled PPV. 63-64
ADVANTAGES
As with other modalities of noninvasive ventilation, the ma-
jor advantage of NPV is the avoidance of endotracheal in-
Rationale, Advantages, and Limitations tubation and its related complicationsH 1 while preserving
physiologic functions such as speech, cough, swallowing,
RATIONALE
and feeding. Moreover, because the airway opening is free,
NPV can be used to widen the field of application of nonin- airway suction and therapeutic and diagnostic maneuvers
vasive ventilator techniques. It is well known that compared by fiberoptic bronchoscopy are performed more easily dur-
with standard medical treatment, mask ventilation reduces ing NPV43 tl1an during mask ventilation.
the need for endotracheal intubation65-<>7 and reduces hos-
pital mortality65-68 in selected patients with an acute exac-
LIMITATIONS
erbation of COPD. A recent randomized study comparing
mask with conventional mechanical ventilation in patients The following limitations should be considered when treat-
with exacerbations of COPD who failed medical treatment ing patients with NPV. First, the lack of upper airway pro-
has shown that mask ventilation avoided endotracheal in- tection, as with all modalities of noninvasive ventilation,
tubation in 48% of patients. 69 Mask ventilation, however, is may result in aspiration, especially in unconscious patients.
not without its problems, and failure rates of 7-50% have Second, upper airway obstruction may occur or be enhanced
been reported.7° Severe respiratory acidosis71 - 73 and illness in unconscious patients, patients with neurologic disorders
at presentation,7'l·74 excessive airway secretions,74 and in- that cause bulbar dysfunction, and patients with obstructive
TABLE 17-1 Side Effects an d Complicatio ns during with ARF had uneasiness and back pain, and a further
Negative- Pressure Ven tilation in 153 Patien ts Treated w ith Iron 2 suffered from vomiting during NPV 76 The inciden ce of
Lung for Acute-on-Chronic Resp iratory Fai lu re complications and side effects of NPV delivered by iro n
N umber of Patien ts (%) lung has been evaluated recently in 153 pa tients witl1 acute-
on-chronic respiratory fa ilure44 (Table 17-1). While NPV
Patients with complications 38 (25%) outcomes, s uch as complications and mortality rate, are
Upper airway obstruction 24 (16%) within the ranges reported for noninvasive PPV,81 it must be
Large air leaks 0 (0%) stressed that there ar e some difficulties in introducing this
Back pain 8 (5%) modality in the vast majority of ICUs, w here m ask ventila-
Claustrophobia 17 (11.4%) tion is preferred as a noninvasive means of ventilation.s2,83
Gastric insufflation 2 (1.3%)
TI1e main reasons are that the iron lU11g is cumbersome
Major complications and needs a large amount of sp ace, a nd most caregivers
Patients with complications 3 (2%)
presently have little or no experience with NPV, rather than
Pneumonia 1 (0.6%)
problems associated with NPV per se.
Pneumothorax 0 (0%)
Gastrointestinal bleeding 3 (2%)
souRcE: Used, with permission, from Gorini et al.44

Indications and Contraindications
ACUTE RESPIRATORY FAILURE
sleep apnea syndrome. 10• 3~37 This effect compromises
the effectiveness of ventilation with negative-pressure CHRONIC OBSTRUCTIVE PULMONARY DISEASE
ventila tors and requires shifting to PPV In unconscious pa- Sauret et al 84 studied 17 patients w ith sever e COPD in hy-
tients with normal bulbar function, the positioning of an percapnic ARE All patients tmderwent NPV, delivered by
oropharyngeal a irway can minimize the risk of airway col- poncho-wrap for 6 hours, w ith significant improvement in
lapse. Third, tank and wrap ventilators restrict patients to arterial blood gases and pH, suggesting that this technique
the supine position, which may induce muscular back and may prevent the need for more aggressive ventilation.
shoulder pain. Fourth, severe obesity and kyphoscoliosis Large studies w ith different experimental designs have
often compromise the possibility to pu t the patients in an confirmed the effectiveness of NPV i11 the treatment of
iron lung or other negative-pressure ventilators. patients w ith acute-on-chronic respiratory failure caused
Most reports of side e ffects of NPV com e from sta- mainly by COPD44 •76,80,S5-90 (Table 17-2). In a pioneer s tudy
ble, chronically ventilated patients. In these studies, the in 560 patients, 475 of whom had exacerbations of COPD,
mos t common side effects were poor compliance secondary NPV, provided by iron lung, was applied successfully, re-
to claustrophobia, upper airway obstruction, and muscu- sulting in improved gas exchange with an overall mortal-
loskeletal pain. NPV has been associated with rib fractures ity rate of 10.5% .85 TI1is rate was comparable with that re-
and pneumothorax. 21 In an acute setting, 2 of 26 patients ported in a more recent study tha t analyzed retrospectively
TABLE17-2 Clinical Studies on the Effects of NPV in Patients with Acute-on-Chronic Resp iratory Failure
Experimental Number of COPD Success"

Au thors Design Patien ts (%) Setting Ventilator (%)
Gunella et al: RS 560 84 Respiratory TCU Iron lung 90

Ann Med Physique, 1980
Corrado et al: RS 2564 78 Respiratory ICU Iron lu ng 90
M onald i Arch C hest Dis, 1994
Corrado et al: RS 105 100 Respiratory ICU Iron lung 89
Chest, 1992
Corrado et al: RS 150 79 Respiratory ICU Iron lung 70
TI1orax, 1996
Todi~co et al: PCS 152 72 Respiratory ICU Iron lw1g 84
Chest, 2004
Gorini et al: PCS 258 70 Respiratory ICU Iron lw1g 77
lntensive Care Moo, 2004
Corrado et al: ccs 66 100 Respiratory ICU Iron lung 77vs 73
Eur Respir J, 1998 (NPV vs invasive MV)
Corrado et al: ccs 106 100 Respiratory ICU Iron lw1g 79 vs 75
Chest, 2002 (NPV vs mask ventilation)
Corrado et al: RCS 44 '1 00 Respiratory ICU Iron lung 82 vs 73
Eur Respir J, 1998 (NP V vs invasive MV)
• Avoiding endotracheal intubation ordeath;RS, retrospective study; PCS, prospective cohort study; CCS, case-control study; RCS, prospective, randomized, controlled
study.
16 years of activity in a respiratory ICU.86 Between 1975 tory failure secondary to bronch opulmonary dysplasia and
and 1991, 2564 pa tients with ARF (2011 w ith COPD and neonatal distress syndrome. Of 40 patien ts intuba ted at the
553 with restrictive thoracic d isorders) were treated with start of treatment, 28 were extubated successfully with the
NPV, &rovided by iron lw1g, and hospital mo rtality rate was aid of NPV and 24 survived. More recently, Samuels et a1104
9.9%. NPV u sed as first-line treahnent in patients with se- performed a prospective, randomized, controlled trial over
vere COPD in ARF is also associated with a good long-term a period of 4 years in 244 neonates comparing CNEP (-4 to
prognosis. 87 In 105 patients with COPD treated with an iron -6 cmH20 ) w ith standard therapy that included CPAP of
lung for ARF, the survival ra tes after 1 and 5 years were 4 cmH20. They found that need for intuba tion was slightly
82% and 37%, respectively.8 7 Although comparisons w ith less v,rith CNEP than with standard therapy (86% versus
previous studies can be subjected to biases, this long-term 91%).
survival is better than that reported previously in patients Infants with ARF who fail to respond to conventional ven-
with COPD treated with conventional ventilation. 91 tilation are considered elective candidates for extracorpo-
The effectiveness of NPV provided by iron lung in pa- real membrane oxygenation. Although this technique can
tients with hypercapnic encephalopathy was evaluated ret- be lifesaving, it is associated with significant complica-
rospectively in 150 consecutive patients (79% with COPD)?5 tions105 and a hig h mortality rate. 106 In 1989, an uncon-
On admission, severe hyp oxemia (Pao, =56 ± 22 nunl-Ig) trolled study rep orted that the use of CNEP adminis tered
and hypercapnia (Pace, = 112 ± 21 mmHg) with respira- by a tank ventilator in conjtmction w ith invasive ventilation
tory acidosis (pH 7.13 ± 0.13) were present, Glasgow coma was successful in five neonates suffering from respiratory
score ranged from 3 to 8, and the mean APACHE II score failure and persistent pulmonary hypertension, thus avoid-
was 31.6 ± 5.3. The failure rate of NPV (death or need fo r ing the use of extracorporeal membrane oxygenation.'107
endotracheal intubation) was 45 of 150 (30%); the observed The benefit of combining invasive ventilation and CNEP
mortality rate was 24% versus 67.5% predicted mortality in these patients has been confirmed by the same group
based on APACHE II. Nine patients (6%) required intuba- in a crossover prospective, randomized study.ws Patients
tion because of a lack of control of the airway. In recent treated with CNEP s howed a greater increase in Pao, than
years, the effectiveness of NPV for the treatment of acute- those treated \-vith PEEP without any increase in morbidity.
on-chronic respiratory failure in patients with COPD has
been confirmed in two case-control studies and in one ran-
CHRONIC RESPIRATORY FAILURE
domized, prospective control study 76' 89' 90 (see Table 17-2).
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
NEUROMUSCULAR DISORDERS Based on the hypothesis that chronic hy percapnia in p a-
Few uncontrolled studies have investigated the effect of tients with severe COPD may be caused by an excessive
NPV in the treatment o f neuromuscular patients with ARF. load on U1e inspiratory muscles, several studies have evalu-
NPV, provided by iron lung92~94 orpneumowrap,95 was suc- ated the effects of NPV provided by poncho-wrap in tenns of
cessful .i n avoiding endotracheal intubation a nd in facili- improvement in arterial blood gases, muscle function, and
tating weaning from invasive ventilation in small groups exercise p erformance. 21 ,28, 109- 111 These studies, carried out
of patients. We h ave reported in a retrospective study the in small number of patients, produced conflicting results.
effects of NPV provided by iron lung in the treatment of In 1992, Shapiro et al112 publish ed the results o f the la rgest
15 neuro muscular patients with ARF. 96 On admission, all trial on the effects ofNPV in 184 patients with COPD (92 p a-
patients exhibited severe hypoxemia (Pa 0 , = 37.6 ± 12.4 tients and 92 controls, with mean Paco, of 44 ± 7 mmHg).
mmHg) and hypercapnia <Paco2 = 88.2 ± 20.4 mml-Ig) with The d istance walked in 6 minutes was the primary outcome
uncompensated respiratory acidosis (pH 7.25 ± 0.08). The variable, with severity of dyspnea, quality of life, arterial
treatm ent was successful in 12 of 15 patients (80%). A re- blood gases, and respiratory muscle strength as secondary
cent retrospective stud y, published in abstract form, ana- outcomes. There was no evidence of significant difference in
lyzed the outcome of 65 neuro muscula r patients with ARF any outcome m easurements between the two groups. Com-
treated with NPV or mask ventilation.97 There w as no signif- pliance of the patients was poor, and the m ean duration
icant difference in mortality rate and need for endotrad1eal of the ventilator use was 2.4 and 3.0 hours in the active
intubation between the groups despite more severe clinical and control groups, respectively. In summary, there is no
condition on admission in the NPV than in the mask ventila- evidence that long-term NPV treatment can improve respi-
tion group. Although these reports suggest that NPV can be ratory muscle function, exercise endurance, quality of life,
effective in the trea tment ofARFin patients wiU1 n euromus- and survival in p atients w ith severe COPD. Also NPV, pro-
cular diseases, prospective, controlled studies are needed to vided in control mode b y cuirass or pneumowrap, is poorly
clarify the impact of noninvasive ventilation on clinical out- tolerated by stable patients with COPD in a typical outpa-
come in these patients . tient setting. It is important to stress that until now, no other
ventilator techniques has been shown to be effective in the
PEDIATRIC DISEASES long-term treatment of stable patients w ith COPD.
During the 1970s, several uncontrolled 98-100 and contro-
lled101•102 studies sh owed that NPV was effective in the man- RESTRICTIVE DISORDERS
agement of the neonatal respiratory distress syndrome. In Many studies, although uncontrolled, have shown that NPV
1989, Samuels and Southall103 reported, in an uncontrolled can be used successfully for long- term home ventilation in
clinical trial, the effects of NPV in p atients with respira- patients with restrictive ventilatory impairment secondary
to neuromuscular and chest-wall diseases.113- 118 NPV de- cations related to mechanical ventilation. Compared w ith
vices, however, are more cumbersome and difficult to use baseline, NPV and IMV induced a similar and significant
than recent home positive-pressure ventilators. Although improvement in Pao,/FJo2 , Paco2 , and pH after 1 hour and
direct comparisons between the efficiency of NPV and mask at discontinuation of treatments . Among patients treated
ventilation are rare, in patients with muscular d ystrophy with NPV, four (18.2%) needed endotracheal intubation.
and bulbar weakness, NPV tends to predispose patients to Major complications tended to be more frequent in patients
obstructive apneas during sleep.119 For these reasons, NPV treated with IMV than in those treated with NPV (27.3% ver"
largely has been supplanted by mask ventilation in the last sus 4.5%), w hereas mortality ra te was similar (27.3% versus
decade. In experienced hands, NPV remains a second choice 18.2%). Ventilator-free days and length o f hospital stay were
in patients who, for technical or other reasons, cannot be of- significantly lower in the iron-lung group than in the IMV
fered mask ventilation. Brief discontinuation of mask ven- group. This study suggests that iron-lung ventilation is as
tilation secondary to intolerable nasal irritation or upper effective as IMV in improving gas exchange in patients with
airway congestion may result in significant worsening of COPD and ARF and is associated with a tendency toward
the arterial blood gases in some patients with chronic res- a lower rate of major complications.
piratory failure .120 In these patients and in those with other
clinical conditions, such as facial deformity or lack of teeth,
NPV should be used as an alternative to mask ventilation. NPV VERSUS NONINVASIVE PPV
A direct comparison between the two noninvasive venti-
lator techniques in the treatment of patients with COPD
OTHER APPLICATIONS
in ARF has been recently reported in a retrospective case-
NPV DURING RIGID BRONCHOSCOPY control s tudy involving 53 pairs of patients treated with
Some studies have evaluated the effectiveness of NPV pro- iron-lung and mask ventilation.89 The two groups were
vided by poncho-wrap121- 123 or cuirass123 compared with matdled according to age, sex, causes of ARF, APACHE
spontaneous assisted ventilation (manual assisted ventila- II score, pH (7.26 ± 0.05 versus 7.27 ± 0.04), and Paco, (88.1
tion with an anesthesia bag if Sa0 1 fell below 90%) in pa- ± 11.5 versus 85.1 ± 13.5 mmHg) on admission. Treatment
tients submitted to interventional rigid bronchoscopy un- failure (death and/ or need for endotracheal intubation) was
der general anesthesia. In non paralyzed patients, NPV was 20.7% in the NPV group and 24.5% in the mask ventilation
able to prevent apnea and significant intraopera tive d e- group. Duration of mechanical ventilation (29.6 ± 28.6 ver"
rangement of add-base balance. 121 A s ubsequent study has sus 62.3 ± 35.7 hours) and length of hospital s tay (10.4 ± 4.3
shown that NPV reduced administration of opioids, short- versus 15 ± 5.2 days) were significantly lower in patients
ened recovery time, and prevented respiratory acidosis in treated with NPV than in those treated with mask ventila-
anesthetized and paralyzed patients who underwent rigid tion. These findings suggest that both ventilato r techniques
bronchoscopy.122 Both intermittent NPV and external high- are equally effective in avoiding endotracheal intubation
frequency oscillation ensure effective ventilation and a com- and death in patients with COPD in ARF. This finding has
fortable operating condition in most patients during rigid been confirmed recently by preliminary results of a multi-
broncoschopy.123 center prospective, randomized, controlled study 124 carried
out in 73 patientc; (39 assigned to NPV and 34 to mask ven-
tilation). The rate of success was s inlilar for the two tech-
tuques. Among the failures of the first ventilator treatment,
Comparison with Other Modes endotracheal intubation was avoided in 64.3% of patients
NPV VERSUS IMV when one of the two techniques was used as rescue of the
other. Hospital mortality rate and hospital stay were similar
Two studies have compared the effects of NPV and conven- for patients treated with NPV and mask ventilation. These
tional mechanical ventilation in patients with COPD and data show that NPV is as effective as mask ventilation for
severe ARF. 76•90 A retrospective case-control study was car- the treatment of patients with COPD in ARF; when the two
ried out in 66 patients who underwent NPV or invasive me- techniques are combined, endotracheal intubation can be
chanical ventilation (IMV).76 The primary end points were avoided in a high percentage of patients.
in-hospital death for both groups and the need for endotra-
cheal intubation in patients treated with NPV. Mortality rate
was 23.1% in the NPV group and 26.9% in the group trea ted
with IMV. The duration of ventilation in survivors was sig-
Variations in Delivery among
nificantly lower witl1 NPV than with IMV, with a median Ventilator Brands
of 22.5 hours (range 2-114 hours) versus 96 hours (range
12- 336 hours). Leng th of hospital stay was sinlilar in both The characteristics of modern negative-pressure pumps are
groups. These findings have been confirmed recently in a reported in Table 17-3. A study by Smith et al9 on five
prospective, randomized, controlled study. 90 Forty-four pa- negative-pressure ventilator pumps, u sing a lung model,
tients with an exacerbation of COPD and severe respiratory showed that tidal volume during NPV is related both to tar-
acidosis (mean pH 7.20 ± 0.04) were assigned eitl1er to iron- get pressure and tl1e pressure waveform generated by the
lung ventilation (22 patients) or IMV (22 patients). Primary pump. For the same target negative pressure, pumps able
end points were improvement in gas exchange and compli- to generate a square wave produce a tidal volume up to
TABLE 17-3 Characteristics of Some Negative-Presslue Ventilator Pum ps
Inspiratory Expiratory
Pressure, Pressure, CNEP, T1, TE, Ventilation Inspiratory
Model cmH2 0 cmH2 0 crnH20 s s Modes Trigger Pump Alarms
Iron Lung 0 to - 80 - 30 to +80 0 to - 30 0.4-9.9 0.4-9.9 C,A/C,CNEP Thermistor Inside the model Pmax, MF
Coppa CA 1001
Porta Lung 0 to - 90 Yes Upto5 • C, A/ C, A, CNEP Pressure Outside
.0
Emerson 33=CR
Porta Lung Life - 5 to - 100 - 30to + 30 - 5 to - 30 0.5-5 b C, A/C, C+S, A/C+S Pressure Outside Pmin, MF
Care NEV-100,
Respironics
New Negavent - 5 to - 99 - 25 to + 99 - 5 to - 99 c C, A/C, CNEP Pressure Outside Pmax, Pmin
Respirator Mod
DA-3, Dima
a Rate Q-49 cycles/min; J(E ratio: 1/ 3 to inverse ratio.

bRate ~0 cycles/min; 1/E ratio: 1/ 0.5 to 1/29.
<Rate 5-50 cycles/ min; 1/E ratio 1/99 toS/1.
ABBREVJATIOKS: CNEP, continuous negativeextrathoracic pressure; Tt, inspiratory time; TE, expiratory time; 1/ E, inspiratory expiratory ratio; C, control; A/C, assist
control; A, assist; S, sigh; Pmax, maximum pressure; Pmin, minimum pressure; MF, machine failure.
30% greater than pumps that generate a half sine wave. 9 changes. During NPV, oxygen is supplemented by nasal
Most modem negative-pressure ventilator pumps respond cannula, venturi mask, or mask with reservoir. The flow is
rapidly to changing leaks to maintain the preset pressure9 adjusted to keep 0 2 saturation usually between 92% and
and allow independent setting of the pressure to be deliv- 94%. Bronchodilators aL<;o can be administered by metered-
ered during inspiration and expiration, as well as inspira- dose inhaler or by aerosol.
tory and expiratory duration.
Troubleshooting
Adjustments at the Bedside
Many problems must be considered when treating acute
Guidelines conceming the bedside management of patients patients with negative-pressure ventilators.
ventilated with NPV are scarce.6•8 The effectiveness of NPV
depends on strict supervision by well-trained nurses and
physiotherapists with considerable expertise in this tech- SETTING IN CONTROL MODE
nique. Proper fit of the airtight seal around the neck and
correct position of the head and neck res t are very impor- The old iron-lung models have only this mode of ventila-
tant in optimizing comfort and preventing kinking and up- tion, which may cause patients to "fight the ventilator," re-
per airway obstruction.6 Values ranging from -30 to -40 sulting in discomfort and ineffective ventilation. In order to
cmH2 0 have been recommended for the setting of nega- "capture" the patient to the superimposed frequency of the
tive pressure during inspir ation. 6 In our experience, the set- machine, we can operate mainly on the timing. Table 17-4
ting of pressures and timing depends on the clinical condi- reports some examples of iron-lung settings in the control
tion and chest-wall impedance of patients. In patients with mode to overcome this concern.
severe respiratory acidosis and hypercapnic encephalopa-
thy, we used control NPV with a frequency of 12-15 TABLE 17-4 Typical Setting of Iron Lung Used in Control
M ode for the Treatment of Patients w ith Acute-on-Chron ic
cycles per minute and an I:E ratio of 1:3-1:4, whereas assist- Resp iratory fajlure
control NPV is used preferentially in patients with tachyp-
nea and respira tory distress to facilitate patient-ventilator
• Negative inspiratory pressure: Usually from - 30 to - 40 cml·hO
synchrony. Inspiratory negative pressure is set initially at at first and then adjusted in order to obtain a tidal volume of
values ranging from -30 to - 40 cmH20 and then adjusted about 6 ml/kg
in each patient to obtain a tidal volume of about 6 ml/kg.89 • Expira tory positive pressure: From +10 to + 15 cmH20 in patients
Positive expiratory pressures of 10-15 cmH2 0 are set to with excessive secretions to assist cough or to improve patient-
assist cough in patients with excessive secretions8 or to ventilator synchrony
increase tidal volume in restrictive disorders14 ; negative ex- • The timing must be adjusted some breaths below patient's
trathoracic expiratory pressure is set to counterbalance in- spontaneous rate
trinsic PEEP in patients "'rith COPD (usually ranging from • Typical setting for a ventilatory rate of 15 cycles/ min: Tr = 1.2 s;
- 4 to - 6 cmH2 0 )12 or to improve oxygenation in patients TE = 2.8 s; (TI/TTOT = 30%)
• Typical setting for a ventilatory rate of 27 cycles/ min: Tr = 0.8 s;
with severe hypoxemia (ranging from - 5 to - 10 cmH2 0).
TE = 1.4 s; (Tt / TTOT = 36%); when patient is "captured,"
Arterial blood gases are checked approximately 30 min- respiratory rate is reduced progressively
utes after mechanical ventilation starts and after any setting
20 dmg administration, and other procedures. The total time
---
-~;;!(
~ 15
spent by nurses for these procedures was 250 minutes. Even
though there are no studies comparing nursing workload
in patients submitted to NPV and IMV, Nava et al 125 have
reported that nursing workload in patients treated with
~ IMV was 527.5 ± 51.1 minutes in the first 48 hours after
~
I
0
~
- admission.
0 10
~ r-'
~ ,---- '
--=
~
~
I r'-
Important Unknowns
r--
5 r-'- It is completely unknown if NPV may play a role in the

0
{#').
treatment o f patients with acute lung injury. Physiologic
~
studies60-62 have s hown the advantageous hemodynamic
< effects of NPV applied to the chest wall in patients wiili
0 acute lung injury, although studies on clinical outcomes are
I 2 3 4 5 6 completely lacking. The absence of this information is par-
ticularly relevant because some physiologic studies suggest
COPD Patients that NPV may result in reduced lung biotrauma compared
FIGURE 17-9 Error of in ductance plethysmograph y (Respitrace, with PPV.126-129 Physiologic studies54' 56 show that NPV by
RT) in estimating tidal volume during NPV in patients with an iron lung has the same hemodynamic effects as PPV. Fu-
acute exacerbation of COPD. The error of the Res pitrace was ture studies should determine whether iron-lung ventila-
assessed as (VT,Rospitra<'< - Vr,pn<umotachograph)/ tion may be applied successfully to patients with cardia-
Vr,pncumotachograph X 100. Individual values are shown.
genic pulmonary edema.
MONITORING OF TIDAL VOLUME

During NPV, the patient airway opening is free, which is The Future
a disadvantage for continuous monitoring of tidal volume.
Currently, tidal volume is monitored intermittently using INSPIRATORY TRIGGER SYSTEM
a Wright spirometer connected to a face mask. Continu- Sinderby et al130 used diaphragmatic electrical activity,
ous monitoring can be achieved with the use of inductance recorded by electrodes attached to a nasogastric htbe, to
plethysmography (Respitrace), which permits an indirect trigger ventilatory support. This signal is directly related
evaluation of tidal volume. Recently, we have compared to phrenic nerve activity and probably to the output of the
tidal volume measured by a pneumotachograph an d by respiratory center; unlike ajrway pressure or flow, it is not
Respitrace in patients with COPD in acute exacerbation affected by mechanical dysfunction (dynamic hyperinfla-
treated by iron lw1g. The error of the Respitrace, assessed tion and intrinsic PEEP). By overcoming tl1e problem asso-
as (VT,Respitrace- Vr, pneumotach<>graph)/Vr, pneumolacograph X 100, ciated with the current technology for triggering, this "neu-
ranged from 3% to 10% (Fig. 17-9). These observations sug- ral trigger" has the potential to improve patient-ventilator
gest that inductance plethysmography may be a useful tool, interaction during both positive- and negative-pressure me-
allowing continuous estimate of tidal volume during NPV. chanical ventilation.
NURSING CARE DESIGN OF TANK VENTILATOR

The major problems related to the assistance of patients with Most iron lungs, although improved in design, remain cum-
NPV by iron lung are transfer from ilie bed to inside the bersome and need a large amount of space. A lighter and
chamber of the tank ventilator and access to patients for completely transparent chamber incorporated into the ICU
nursing procedures during ventilation. Well-trained nurses, bed would enable tl1e posture of patients to be changed from
however, can manage both transfer, by using aids (e.g., a supine to semirecumbent. This step should permit a major
roll mattress and a mechanical elevator), and nursing proce- implementation of NPV in the ICU.
dures (e.g., insertion of a urinary cailieter and venous lines,
placement of electrocardiograph electrodes and Sa02 probe
POTENTIAL CLINICAL APPLICATION
for monitoring the level of oxygenation) easily using the
portholes in the tank ventilator. We have measured the time The clinical relevance of intra-abdominal pressure, which
spent by nurses in the second day after admission in pa- may cause organ dysfunction, is being recognized increas-
tients with COPD in ARF treated with the iron lung.77 The ingly in the ICU settings.131•132 Decompressive laparatomy
following procedures were considered: transfer of patients is recommended when intra-abdominal pressure exceeds
from the bed to inside the tank ventilator, measurement of 25 mmHg, 133 although there are no definite techniques of
tidal volume and minute ventilation by a Wright spirom- intervention for pressures between 12 and 25 mmHg. It has
eter, tracheobronchial suction, arterial blood-gas sampling, been suggested that NPV applied around the abdomen by
a cuirass might be a potential tool to treat intra-abdominal ll. Aaron J, McCool FD, BendittJ, Hill NS. Evaluation of trigger sen-
hy pertension.134 This hypothesis has been investigated re- sitivity of patient-triggered negative pressure ventilators. Am J
cently in a physiologic study of 30 patients admitted to an Respir Crit Care Med 1995; 151:A237.
ICU. 135 Continuous NPV decreased intra-abdominal pres- 12. Gorini M, Villella C, Ginanni R, e t al. Effects of assist nega·
sure from 8.7 ± 4.3 to 6 ± 4.2 mmHg ( p < .001). There was tive p ressure ventilation by microprocessor-based iron lung on
breathing effort. Thorax 2002; 57:258-62.
a further decrease in intra-abdominal pressure when more
13. As lanian P, Atrous S, Isabcy D, et al Effects of flow triggering on
nega tive pressure was applied. These data suggest that in a breathing effort during partial ventilatory s upport. Am J Respir
popula tion of critically ill patients, NPV may be used to d e- Crit Care M~-d 1998; 157:135-43.
crease intra-abdominal pressure. Future studies with clin- 14. Kinnear W, Petch M, Taylor G, ShneersonJ. Assisted ventilation
ical outcome will be necessary to assess the effectiveness using cuirass respirators. Eur Rcspir J 1988; 1:198-203.
of this technique for the treatment of increased abdominal 15. Al-Saady N M, Fernando SSD, Petros Aj, e t al. External high
pressure. frequency oscillation in normal subjects and in patients with
acute respiratory failure. Anaesthesia 1995; 50:1031-5.
16. Spitze r SA, Fink G, Mittelman M. External hig h-frequency ven-
tila tion in severe chronic obstructive pulmonary disea~e. Chest
Summary and Conclusions 1993; 104:1698-1701 .
17. SidenO B, Vaage J. Ventilation by external high-frequency oscil-
Evidence now exists that (1 ) NPV unloads respiratory mus- lations improves carruac function after coronary artery bypass
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ARF, (2) volume-controlled ventilation with CNEP, com- 18. Lassen H CA. A preliminary report on the 1952 epidemic of po-
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Cri t Care Med 19%; 153:1616-23. 63. Shekerdemian LS, Shore OF, Lincol.t' C, et al. Negative pressure
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mg iron lwlg mechanical ventilation in nonintubated patients. Circulation 1996; 94:49-55.
j Bronchol 1995; 2:200-5. 64. Shekerdemian LS, Bush A, Shore OF, et al. Cardiopulmonary
44. Gorini M, Gillanni R, Villella G, et a!. Non-invasive negative i11teraction after Fontan operations: Augmentation of cardiac
and positive pressure ventilation in the treatment of acute on output usmg negati ve pressure ventilation. Circulation 1997;
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46. Marino WD, Pitchumoni CS. Reversal of negative pressure ven- trial of noninvasive positive p ressure ventilation in acute respi-
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metoclopramide. Am ] Gastroentcrol 1992; 87:19()-4. 67. Plant PK, Owen JL, Elliott MW. Early use of non-invasive
47. Pinsky MR. The effects of mechanical ventilation on tile cardio- ventilation for acute exacerbations of chronic obstructive pul-
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48. Pinsky MR. The hemodynamic consequences of mechanical randomised, controlled trial. Lancet 2000; 355:1931-5.
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493-503. trial of nasal ventilation il1 acute ventilatory failure due to
49. Takata M, Robotham JL. Effects of inspiratory diaphragmatic chronic obstructive airways disease. Lancet 1993; 341:1555-7.
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1992; 72:597-607. tional mechanical ventilation in patients with chronic obstruc-
50. Pmsky MR, Summer WR. Cardiac augmentation by phasic high tive pulmonary d isease after failure of medical treatment m the
mtrathoradc support m man. Chest 1983; 84.370-5. ward: A randomized trial. Intensive Care Med 2002; 28:1701-7.
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Positive pressure breathmg. Ann Biomed Eng 1987; 15:373-83. 71. Ambrosino N, Foglio K, Rubini F, et al. Non-mvasive mechanical
52. jardm F, Farcot JC, Boisante L, eta!. lnfluence of positive end- ventilation m acute respiratory failure due to chronic obstruc-
expiratory pressure on left ventricular performance. New Engl ti ve pulmonary disease: Correlates for success. Thorax 1995; 50:
J Med 1981; 304.387-92. 755-7.
53. Knm1pe PE, Zidulka A, Urbanetti J, et al Comparison of the 72. Plant PK, Owen JL, Elliott MW. Non-ilwasive ventilation m
effects of continuo us negative external chest pressure and posi- acute exacerbations of chronic obstructivt:? pulmona ry disease:
Long-term survival and predictors of in-hospi tal outcome. Tho- liotic patients from mechanical ventilation. Respir Care 1994;
rax 2001; 56:708-12. 39:21- 9.
73. Carlucci A, Ricl1ard JC, Wysocki M, ct al. Noninvasive versus 93. Garay SM, Turi110 GM, Goldring RM. Sustained reversal of
conventional mechanica l ventilation: An epidemiologic s urvey. chronic hypercapnia in patients with alveolar hypoventilation
Am J Respir Crit Care Med 2001; 163:874-80. syndromes: Long-term maintenance with noninvasive noctur-
74. Soo Hoo GW, Santiago S, Williams A. Nasal mechanical venti- nal mechanica l ventilation. Am J Med 1981; 70:269- 74.
lation for hypercapnic respiratory failure in chronic obstructive 94. Libby BM, Briscoe WA, Boyce B, et al. Acute respiratory failure
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75. Corrado A. De Paola E, Gorini M, et al. Intermittent nega- pressure ventilation in the treatment of respiratory failure in
tive pressure ventilation in the trea tment of hypoxic hypercap- progressive neuromuscular disease. Neurology 1987; 37:1874-
nic coma in chronic respiratory insufficiency. Thorax 1996; 5: 5.
1077- 82. 96. Corrado A, Gorini M, De Paola E. Alternative techniques for
76. Corrado A, Gorini M, Ginanni R, et al. Negative pressure ven- managing acute neuromuscular respiratory failure. Sernin Neu-
tilation versus conventional mechanical ventilation in the treat- rol1 995; 15:84-9.
ment of acu te respira tory failure in COPD patients. Eur Respir 97. Corrado A, Vianello A, Arcaro G, et al Noninvasive mechani-
J 1998; 12:519- 25. cal ventilation for the treatment of acute respiratory failure in
77. Corrado A, Gorini M. Negative pressure ventilation: ls there still neuromuscular diseases. Eur Respir J 2000; 16:542s.
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78. Girou E, Brun Buisson C, Taille S, eta!. Secular trends in nosoco- ing continuous negative pressure in infants with TRDS. Pedi-
mial infections and mortali ty associated with n oninvasive ven- a tries 1973; 52:128-'30.
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79. Elliott MW. Non-invasive ve11tilation in acute exacerbations of positive airway pressure in its treatment. Am J Dis Chest 1979;
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80. Todisco T, Baglioni S, Eslami A, et a l. Treatment of acute sure in the management of severe respiratory distress syn-
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2217- 23. 101. Fanaroff AA, Cha CC, Sosa R, et al. Controlled trial of continuous
81. Mehta S, Hill NS. Noninvasive ventilation. Am J Resp ir Crit negative external pressure in the treatment of severe respiratory
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82. NavaS, Confalonieri M, Rampulla C. lntcrmroiate respiratory 102. Silverman WA, Sinclair JC, Gandy GM, et al. A controlled trial
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84. Sauret JM, Guitart AC, Frojan GR, et al. In termittent short- treatment of respiratory failure in infants and young children.
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une serie de 560 cas. Ann Med Phys 1980; 2:317- 27. cations during extracorporeal membrane oxygenation: Preven-
86. Corrado A, Gori ni M, De Paola E, et al. Iron lung trea tment tion and treatment. J Pediatr Surg 1986; 21:1087- 91.
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89. Corrado A, Confalonieri M, Marchese S, ct al.lron lung versus 109. Cropp AJ, Dimarco AF. Effect of intermittent negative pressure
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Chapter 18 _ _ _ _ _ _ _ __ _ quently by the British Navy as the recommended means of
resuscitation for drowning vict.irns. 2 Later studies demon-
NONINVASIVE strated that tl1is tilting method compared quite favorably
v.tith other resuscitation methods of the day, a nd it remained
RESPIRATORY AIDS: an acceptable means of r esuscitation until mouth-to-mouth
resuscitation gained acceptance during the 1960s.3A
ROCKING BED, Automatic rocking beds were first introduced as venti-
latory aids during the late 1940s. Wright5 was the first to
PNEUMOBELT, AND describe the management of respiratory insufficiency using
an oscilla ting bed that had been designed originally to as-
GLOSSOPHARYNGEAL sist circulation. This experience led to the development of
the McKesson Respiraid rocking bed, which was accepted
BREATHING by the Council on Physical Medicine and Rehabilitation in
1950. 6 Intended mainly as an aid to weaning patients w ith
NICHOLAS S. HfLL poliomyelitis from dependence on the tank respirator/ it
facilitated nursing care and enhanced patient freedom but
was quite noisy, bulky, a nd heavy (455 kg). 6•7 The Emer-
son rocking bed (J. H . Emerson Co., Cambridge, MA), also
introduced during the late 1940s, was quieter and lighter
than the McKesson bed and became the dominant model
ROCKING BED AND PNEUMOBELT during the 1950s. Hundreds of rocking beds were manufac-
Historical Development tured between 1950 and 1960 (Emerson JH, personal com-
Mechanism of Action munication), but after introduction of the Salk and Sabin
Application vaccines and control of the polio epidemics, demand fell
Indications drastically. Many survivors of the polio epidemics contin-
GLOSSOPHARYNGEALBREATHrnNG ued to use rocking beds for ventilator support, sometimes
for decades,8 but most have since died or switched to other
ventilators, and present-day use is rare.
The intermittent abdominal pressure respirator or insuf-
fla tor (pneumobelt) was introduced at the end of the po-
Rocking Bed and Pneumobelt lio epidemics in an attempt to address the limitations of
existing ventilators.9 The pneumobelt was designed to al-
The rocking bed and pneumobelt are noninvasive ventila- low complete freedom of the upper extremities and mouth
tors that were developed and saw their greatest use during during use in the sitting position and was intended mainly
the latter years of the polio epidemics but are used rarely to- as a daytime ventilatory aid during meals or wheelchair
day. They both rely on the effect of gravity to assist diaphrag- use. Several modifications of the pneumobelt have been re-
matic motion and are particularly well suited to patients ported since the or iginal description, but these have never
with severe diaphragmatic weakness or paralysis. Neither gained wide acceptance. These include a piston-like device
one should be used in the management of acute respiratory that compresses the abdomen while the patient s its .in a
failure, and both have limited present-day applicability. De- wheelchair10 and a combination of the pneumobelt and in-
spite the similarities, there are also important differences, termittent positive-pressure breathing. 11 Like the rocking
such as portability and suitability for nocturnal versus day- bed, the pneumobelt has seen only limited use since control
time use. This chapter reviews the historical development, of the polio epidemics.
mechanisms of action, and present-day uses of the rocking
bed and pneumobelt. Glossopharyngeal breathing, another
noninvasive approach to ventilator assistance, will be dis- MECHANISM OF ACTION
cussed briefly at the end of the chapter. Eve compared the rocking-induced motion of the abdom-
inal viscera within the thorax with that of a piston within
a cylinder.1 As the head moves down, the viscera and di-
HISTORICAL DEVELOPMENT
aphragm slide cephalad, assisting exhalation (Fig. 18-1).
The conceptual groundwork for development of the rocking In the foot-down position, the abdominal contents and di-
bed was laid during the early 1930s by Eve,l who described aphragm slide caudad, assisting inhalation (Fig. 18-2).
the use of manual rocking to assist ventilation in two pa- A number of early studies on the efficacy of rocking
tients with acute respiratory paralysis. The technique con- compared it as a method of resuscitation with others then
sisted of placing the patient supine on a stretcher that was used commonly.3A These studies used fresh corpses or
pivoted on a fulcrum placed at waist level. The patient then live subjects with pharmacologically induced paralysis or
was rocked up and down approximately 45° in either di- voluntarily suspended respirations to show that rocking
rection. Eve noted that the "weight of the viscera pushed produced tidal volumes ranging from a few hundred
the flaccid diaphragm alternatively up and down," achiev- milliliters to a liter, and success in the resuscitation of
ing artificial respiration.• The technique was adopted subse- near-drowning victims was reported. 2 Later, Plum and
421
LI TERS
3''NORMALS"
16
1.4
I2
t.O
+ 0.8
0.6
0.4
HEAD-DOWN
ANGLE (• J
R E.E P.
FIGURE 18-1 Rocki ng b ed in 10° head-down position. Sliding of 80 60 20 40 60 80
the viscera and diaphra~;m cephalad assists exhalation. -0 2 FOOT - DOWN
ANGLE ( 0 1
J
Whedon12 found that the automatic rocking bed was n ot as -06

effective as the tank respirator but produced adequate alve- FIGURE 18-3 Relations hip between angle of rocking bed and
olar ventilation in 11 convalescent patients with respiratory static lung volume in three normal individuals and in patients
paralysis secondary to poliomyelitis. The bed, however, was with poliomyelitis, as indicated by letters. Note that the greatest
unable to sus tain adequate ventila tion in 5 patients during volume shift occurs between 0° and the 40° foot-down angle.
the acute stages of r espira tory paralysis. Plum and Whed on Note also the marked variability between individuals. REEP,
resting end-expiratory position. (Used, with pennissiou, from
recommended that use of the rocking bed be reserved for
Colville eta/: J Appl Pflysiol 9:19-24, 1956.)
stable patients who ar e capable of at least som e spontaneous
breathing, a recommendation that holds true today.
Colville et ai1 3 subsequently examined the physiologic
the greatest passive motion could be achieved b y applying
effects of rocking on respiratory mechanics and identified gravitational force in the caudad direction.
factors responsible for the w ide individual varia tions in
Along these lines, Joos et af 14 found that tidal volumes
tidal volumes generated during rocking. They found that
were g reater in some patients when rocking was achieved
the greatest displacement of the diaphragm occurred dur- entirely in the head-up position (5-42° above the horizontal
ing rocking from horizontal to the 40° foot-down position plane) r ather th an between the head-down and head-up po-
(Fig. 18-3). Beyond this angle, relatively little further d is- sitions (1 0" below to 27° above the horizontal plane). In ad -
placement of the diaphragm occurred. Likewise, rela- dition, others found that relatively little increase in minute
tively little displacement of the diaphrag m occurred dur- volume could be achieved by increasing the rate of rocking
ing rocking from the horizontal to the head-down position. beyond 15-16 per minute.3 At higher rocking frequencies,
This indicated tha t in the horizon tal position, the resting the tidal volume tended to diminish, negating the effects of
diaphragm was fairly close to its uppermost position, so the increased rocking rate.
With regard to the large individual variation (see Fig.
18-3), Colville et al13 found that as the compliance of the
FIGURE 18-2 Rocking b ed in 27° foot-down position. Slidin g of abdominal wall increased, the greater was the tidal volume
the abdominal viscera and diaphr agm caudad assists inhalation. during rocking. Thus rocking was relatively ineffective in
(Used, witlt permissiou, from Hill: Cl1est 90:897- 905, 1986.) patients with severe kyphoscoliosis, who have low abdom-
inal and diaphragmatic compliance and short abdominal
lengths. Taken together, these findings indicate that the ef-
, ficacy of the rocking bed is highly dependent on patient
bod y characteristics and that function is likely to be optimal
when rocking is between the near-horizontal and the 40°
foot-down positions at rates between 12 and 16 per minute.
Wider manipulations of rocking rate and arc, however,
may be useful in optimizing alveolar ventilation in some
patients.
Thepneumobelt9 operates by a mechanism similar to that
of the rocking bed in that it assists diaphragmatic motion by
causing piston-like motions of the abdominal viscera w ithin
the thoracic "cylind er." The major difference is that the
pneumobelt assists exhalation by applying positive
pressure to the abdominal surface rather than using
CHAVfER 18 NONINVASIVE RESPIRATORY AIDS 423
air flows out air flows in
- inthrothorocic
pressure rl$es -- inthrothoracic
pressure falls
• diaphragm falls
bladder inflated bladder deflated
L) t'
\.... ..
--. ~
\.
FIGURE 18-5 The pneumobelt functions by exerting positive

pressure on the abdominal viscera, forcing tile diaphragm up and
assisting exhalation (left). When the bladder deflates, gravity
returns the djaphragm to Hs original position, assisting inhalation
(rigllt). (Used, witl1 permissiotl, from Hill: Cltest 90:897-905, 1986.)
High abdominal compliance favors efficient functioning of

the device, but high chest-wall compliance may allow ex-
pansion of the chest wall during bladder inflation, reduc-
ing efficiency.9 Thus, like the rocking bed, body habitus is
FIGURE 18-4 Pneumobel t is sh own attached via a connecting also an important determinant of ventilator efficiency for
hose to a Bantam positive-pressure ventilator (Puritan-Bennett the pneumobelt. Although thin patients can be ventilated
Corp, Lenexa, KS). (Used, w ith permisiou, from Rondinelli et al. In: effectively, 16 both devices work Jess efficiently in extremely
Delisa fA editor. Rel111bilitatiou mediciue: P rinciples and practice.
Philadelphia: Lippincott, 1988.)
thin or obese patients and in those with severe kyphoscol-
iosis. The sitting position in patients with severe kyphosco-
liosis often brings the lower rib cage in contact with the
gravitational force. It consists of an inflatable rubber blad- thighs, rendering proper positioning of the pneumobelt
der held firmly over the abdomen by an adjustable corset impossible.
(Fig. 18-4s). Inflation of the bladder squeezes the viscera,
forcing the diaphragm cephalad and actively assisting exha-
lation. On deflation of the bladder, gravity pulls the viscera APPLICATION
and diaphragm back to their original positions, assisting Rocking beds are no longer available commercially. The for-
inhalation (Fig. 18-5). Because of this dependence on grav- mer manufacturer, J. H. Emerson Company, can no longer
itational force, the pneumobelt must be used in a sitting makes them (Emerson G, personal communication). Pneu-
position, optimally at angles of 45° or greater. Below 30°, mobelts (small, medium, or large) can be obtained via
the ability to assist ventilation is diminished markedly (Fig. home medical equipment vendors from Respironics, Inc.
18-6B). Thus nocturnal use of the pneumobelt is limited to (Murrysville, PA). Respironics supplies the NEV-100 venti-
patients who can sleep in a sitting position. 15 lator to power the pneumobelt, but other positive-pressure
Despite this limitation, the pneumobelt can be a very ventilators with sufficient pressure- and volume-generating
useful device in appropriately selected patients. As shown capabilities can be used. Most portable "bilevel" positive-
in Fig. 18-7 A, the ability of the pneumobelt to augment pressure devices, however, are insufficient.
tidal volume is linearly related to the inflation pressure Consisting of a bed frame that is suspended on an axis
of the bladder between pressures of approximately 15 and 100 em above the ground, rocking beds are bulky (193 em
50 cmH20. Pressures exceeding 50 cmH20 are rarely tol- long by 84 em wide) and heavy (approximately 136 kg).
erated because of abdominal discomfort. As with the rock- Although the axis of rotation can be adjusted, they usually
ing bed, the ability of the device to augment tidal volume are set to rotate 10° in the head-down direction and 27° foot-
varies considerably among individuals (see Fig. 18-6A). Im- down. As noted previously, maintaining the rocking arc in
portant factors that contribute to the variability among in- the head-up range may improve efficacy in some patients. 14
dividuals include abdominal and chest-wall compliances. Adjustable cranks allow raising of the head and knees to
11 I R
0.7
- I -f-'
II I
........
l!II
....
o.e
I v
;:::3
._, 0.5 I I
"~ I /
>
-0
0.4 I Vj
ii
....'tl I I / II
E-<
0.3
v
/
/ 75
eo
0 I FIGURE 18-6 A . Pressure-volume curves for
individual patients show that augm entation of tidal
/ u.' I /
I
volume is linearly related to the increase in
pneumobc]t pressure within certain pressure ranges,
0.2
~n· / but variations between individuals are wide. B.
Pressure-volume curves obtained at different trunk
o.o 1~.._...J.._--1._......t_ ___.~-L------l{ 1~..._ _.__--~._......t_ ___.L-_L------l{ angles in an individual patient. Efficiency of the
o 10 20 30 40 60 eo o 10 20 30 40 50 eo pneumobelt falls with trunk angle. (Redrawn, w ith
penuissio11, from A damson et al: JAMA 169:161:l- 7,
Pneumobelt Pressure (em H1 0) 1959.)
minimize slippage. Excessive flexion of the hips, however, patients require help from one or two attendants depend-
may impair functioning. 14 A foot res t a lso may be a ttached ing o n bod y weight. The patient lies supine with the head
to prevent downward sliding, but with proper positioning and knees raised slightly to maximize comfort. A baseline
of the head and knees, this is usually unnecessary. minute volume is measured using a portable spirometer.
The most attractive feature of the rocking bed is its ease of Rocking then is commenced at rates between 12 and 16 per
application. With use of a foot stool, most patients can po- minute, again adjusted to optimize patient comfort. The pa-
sition themselves on it with minimal assista nce. Paralyzed tient is coached to exhale during head-down rocking and
FIGURE 18-7 Nocturnal

polysomnogram in patient 1
I
obtained in August of 1991 during
~ spontaneous room-air breathing
shows periodic breathing with
sustained severe oxygen
desaturation. EOG,
electro-oculogram; r, right; 1, left;
EMG-S, s ubmental
electromyogran1; EEG,
electronencephalogram; THERM-N,
nasal th ermistor; EMG-0,
diaphragmatic EMG; THERM-O,
oral thermistor; EKG,
electrocardiogram; EM G-T,
temporal EMG; 0 2 SAT, oxygen
saturation.
CHAPTER 18 NONINVASIVE RESPIRATORY AIDS 425
to inhale while the head moves up. When synchronization In addition to measurement of minute volume, efficacy
has been achieved, further adjustments in rocking rate may is assessed using arterial blood-gas determinations that are
be made to optimize minute volume. An arterial blood-gas done as soon as tlle patient is comfortable and synchronizing
determination may be helpful after an hour or two during well. The desired amount of ventilator assistance will vary
the initial trial to assess adequacy of alveolar ventilation. depending on the patient, but a decrease in arterial carbon
Patients then are encouraged to initiate rocking at bed- dioxide tension (Paco1 ) of approximately 5-10mmHg below
time and to extend the hours of use gradually until they are spontaneous breathing levels is acceptable during the ini-
able to sleep through the night. Most patients find the rock- tial sessions. Subsequent use of the device also will depe nd
ing bed quite comfortable and encounter little difficulty in on the patient. Most often, because the pneumobelt must be
learning to sleep while rocking. Motion sickness is unusual used in the sitting position, it is used as a daytime ventila-
presumably because the bed rocks in one plane only, but tor aid to s upplement another device used nocturnally. As
it may disturb some patients. The bed limits daytime mo- illustrated by Case 2 (see below) and another case report,l5
bility, so most patients use it only nocturnally. If daytime however, occasional patients may adapt to nocturnal use.
ventilatory assistance is necessary, another technique, such The monthly rental for the belt itself is less than $100, but
as noninvasive positive-pressure ventilation or the pneu- ventilator costs and associated respiratory therapy services
mobelt, is recommended for daytime supplementation. raise montl1ly charges to the $500-$1000 range.
Application of the pneumobelt is slightly more difficult Long-term follow-up of patients using either the rock-
than that of the rocking bed, usually requiring at least one ating bed or pneumobelt should include assessment for
tendantunless the patient has full upper extremity strength. symptoms or s igns of chronic hypoventilation such as
The corset is positioned while the patient is sitting comfort- morning headache, hypersornnolence, and ankle swelling.
ably. The mbber bladder is positioned over the abdomen Daytime spontaneous arterial blood gas determinations are
with the curved lower border of the corset over the pubis particularly useful for assessing the adequacy of ventilatory
and the horizontal upper border over the xiphoid. Some cov- assistance,17, 18 and attempts should be made to increase as-
erage of the lower rib cage may serve to minimize paradox- sisted minute volume if Paco2 remains substantially above
ical motion of the ribs during assisted exhalation, altl10ugh 50 mmHg. Nocturnal oximetry or polysornnography are
some authors have found more efficient functioning if the useful not only to assess adequacy of nocturnal oxygenation
corset is placed below the xiphoid. 16 If the corset extends but also to detect obstructive apneas that may be induced by
too far below or above the lower rib margin, another of the negative-pressure ventilators19 and also may occur during
three available sizes should be tried. The corset then is tight- use of the rocking bed or pneumobelt.
ened using the three straps that surround the abdomen un- Complications of rocking bed or pneumobelt use are rel-
til tlle rubber bladder is held firmly but not uncomfortably atively few. Some patients using tl1e pneumobelt for many
against the abdomen. After baseline spontaneous respira- consecutive hours develop skin abrasions, and others have
tory rate and tidal volume are measured, the rubber blad- trouble coordinating their breathing with either of the ven-
der is attached to a positive-pressure ventilator using a con- tilators so that efficacy may be inadequate. If appropriate
necting hose. Volume-limited positive-pressure ventilators patients are selected, the risk of worsened respiratory fail-
that generate adequate pressures and volumes will oper- ure or arrest during use is low because such patients should
ate the pneumobel t successfully, but portable "bilevel-type" be capable of some spontaneous breathing. As deteriora-
pressure-limited devices that are popular to provide non- tion occurs with progressive neuromuscular syndromes or
invasive positive-pressure ventilation are not adequate be- acute respiratory infections, however, patients may have to
cause their pressure-generating capabilities are too limited . switch to other, more effective ventilators.
The ventilator is set at a rate that approximates sponta-
neous respiratory frequency and an inspiratory-expiratory
INDICATIONS
(I:E) ratio of approximately 1:1.5. Some authors have found
that function is optimal at rates of 12 to 14 breaths per Considering that the rocking bed and pneumobelt share
minute,16 but this may depend on the underlying respira- similar mecl1anisms of action, it is not surprising tllat they
tory disorder. Some patients prefer rates as high as the low also share indications for use (Table 18-1). Because both as-
20s per minute (see Case 2). Ventilator assistance is initiated sist ventilation essentially by augmenting diaphragmatic
by intermittently in.flating the rubber bladder with peak in- motion, they are particularly useful in patients with bi-
flation pressures of 20-25 cmH 2 0. Inflation pressure then lateral diaphragmatic weakness or paralys is. Abd et al20
is raised gradually until the patient's assisted tidal volume have demonstrated the utility of this application in patients
increases to the desired range, usually 30-50% over spon- with bilateral diaphragmatic paralysis following open-heart
taneous breathing or the patient reaches tlle limit of toler- surgery. In this study, 10 patients were weaned from con-
ance. Peak pressures of 30-50 cmH2 0 are usually sufficient, ventional positive-pressure ventilation to the rocking bed
but pressures up to 60 cmH20 may be necessary in some and continued to use it nocturnally until phrenic nerve func-
patients.16 Pressures exceeding 60 cmH20 rarely are toler- tion recovered after 4- 27 months.
ated because of discomfort. Considerable coaching usually The rocking bed and pneumobelt also may be u sed in
is necessary during initial adaptation to encourage synchro- the management of chronic respiratory failure caused by
nization of patient breatlling with ventilator cycling. Pa- a variety of slowly progressive neuromuscular syndromes
tients who will be successful usually learn to synchronize that weaken the diaphragm and leave upper airway func-
their breatlling with the ventilator after a few sessions. tion intact. Chalmers et al 21 described their experience witll
426 PARTVI NONINVASNEMETHODSOFVENTILATORSUPPORT
TABLE 18-1 Indications and Contraindications for the secondary to idiopathic diaphragmatic paralysis or
Rocking Bed and Pneumobelt slowly progressive neuromuscular conditions. Noninva-
sive positive-pressure ventilation administered via a nasal
Indications mask is unquestionably the mode of first choice because of
Chronic respiratory failure" caused by its convenience, ease of application, portability, and avoid-
Bilateral diaphragmatic paralysis
ance of the intermittent upper airway obstructions and
Muscular dystrophies
Duchcnne
oxygen desaturations associated w ith the use of negative-
Limb-Girdle pressure ventilators.19•23 Nevertheless, other noninvasive
Myotonic ventilators still should be considered in patients w ith
Postpolio syndrome chronic respiratory failure who are unable to use noninva-
Amyotrophic lateral sclerosis sive positive-pressure ventilation, as illustrated in a recent
Multiple sclerosis report of a woman with scapuloperoneal muscular dystro-
Traumatic quadriplegiab phy who used a rocking bed successfully w hen loss of upper
Contraindications extremity strength rendered her incapable of applying her
Acute respiratory failure or rapidly progressive neuromuscular nasal ventilator. 24
disease
Efficacy comparisons between the rocking bed and
Excessive secretions
Upper airway dys function
pneumobelt and other noninvasive ventilators are lim-
Excessive obesity or thinness ited because few relevant studies are available. In acutely
Severe kyphoscoliosis anesthetized intubated subjects, Bryce-Smith and Davis25
showed that the rocking bed produced barely adequate
"With intact upper airway and appropriate body habitus. tidal volumes when rocking through an arc of 40° and was
b Pneumobelt only. much less effective than negative-pressure ventilators, in-
cluding the tank ventilator and chest cuirass. Goldstein
et al26 demonstrated that cuirass-type negative-pressure
53 neuromuscular patients, 30 with postpolio syndrome, ventilators augment tidal volumes and suppress diaphrag-
12 with various muscular dystrophies, 4 with adult-onset matic electromyographic activity more effectively than did
acid maltase deficiency, and 4 with motoneuron disease the rocking bed in patients with neuromuscular disease.
[amyotrophic .lateral sclerosis (ALS)]. Forty-three of the pa- Both types of ventilators, however, were deemed effective,
tients used the rocking bed for an average of 16 years with and considering that this was an acute daytime study, the
good control of symptoms and stabilization of gas exchange rocking bed may have been more effective at reducing
in most patients. Seventeen patients discontinued use: 9 diaphragmatic electrical activity had patients been moni-
because of discomfort and 8 because progression of respi- tored overnight after a suitable adaptation period. Even so,
ratory insufficiency necessitated more efficacious therapy. the conclusion that the rocking bed is less effective than
The pneumobelt has been used in patients with high spinal negative-pressure ventilators seems justified. In one case,
cord lesions, mainly as a daytime supplement, often in com- the rocking bed was combined with noninvasive positive-
bination with positive-pressure ventilation administered pressure ventilation via a nasal mask to enhance efficacy
noninvasively or via a tracheostomy.16 In this setting, the and acl1ieve "necessary ventilatory support."27
pneumobelt frees the face of encumbrances and improves In summary, both the pneumobelt and rocking bed cur-
speech and mobility. It also may be used for total ventilator rently have limited indications (see Table 18-1). They are un-
support.22 Surprisingly, those with the least ability to sus- suitable for use in acute respiratory failure, must be used in
tain spontaneous breathing adapt best to pneumobelt use. 22 patients with a relatively "nonnal" body habitus, and have
Because both ventilators have limitations that are influ- marginal efficacy even under optimal circumstances. Non-
enced heavily by the patient's body habitus, however, a invasive positive-pressure ventilation has convenience and
number of caveats should be bome in mind (see Table 18-1). efficacy ad vantages over these devices. Nonetheless, there
Neither device is suitable for use in acute respiratory fail- are occasional patients who are unable to tolerate a nasal
ure mainly because a period of adaptation is necessary for mask or negative-pressure ventilator who may prefer the
optimal efficiency and also because excessive secretions in- relatively greater comfort of the rocking bed or the daytime
terfere with function. 12 In addition, care should be exercised freedom that the pneumobelt affords. The following cases
to select patients who have an appropriate body habitus, ad- illustrate such applications.
equa te upper airway function, and a condition tl1at is suffi-
ciently stable or slowly progressive so that the anticipated CASE 1: USE OF THE ROCKING BED
duration of use will justify the effort and time required for J.F., a 47-year-old man with myotonic dystrophy, first
adaptation. presented with symptoms of chronic hypoventilation,
Because the rocking bed is suited for nocturnal use and the including morning headache and daytime hypersom-
pneumobelt for daytime use, the two may be used in com- nolence. He was found to have global muscular weak-
plementary fashion. A patient might use the rocking bed ness, although he was still able to walk with a cane.
during sleep and the pneumobelt for daytime desk work or Pulmonary function studies demonstrated a severe re-
wheelchair use. strictive defect with a forced vital capacity (FVC) of
Many choices are available currently for noninvasive 1.5 liters (31% of predicted) and a forced expiratory
ventilation of patients with chronic respiratory failure volume in 1 second (FEV1 ) of 1.3 liters. Room-air
CHAPTER 18 NONINVASNE RESPIRATORY AIDS 427
arterial blood-gas determinations revealed a pH of7.36, using a pneumowrap brought about a rapid improve-
a Paco, of 53 mmHg, and a Pao, of 69 mmHg. Nocturnal m ent in symptoms and daytime gas exchange, with a
polysomnography showed mild obstructive sleep ap- room-air arterial blood-gas determmation showing a
nea and sustained mild oxygen desaturations consistent pH of 7.42, a Paco, of 55 mn1Hg, and a Pa02 of 65 mmHg.
with hypoventilation. A trial of noninvasive positive- The patient's wife, however, refused to consider use of
pressure ventilation via a nasal mask was initiated. De- the pneumowr ap at home because placmg the patient
spite much coaching and trials with different masks, the in it each night seemed too difficult.
patient declined further use after 2 montl1s because of Nocturnal ventilation using the rockillg bed then
intolerable mask discomfort. Megestrol, 40 mg PO tid, was begun at a rockmg rate of 16 per minute. Tidal
then was begun, followed within a montl1 by normal- volume during the initial rockillg trial ranged from
ization of blood gases and resolution of symptoms. 300-350 ml. The patient's wife found the rocking bed
Two years later, the patient again developed symp- more acceptable because of simpler application. Af-
toms of morning headache and daytime hypersom- ter a several-day adaptation period, ilie patient was
nolence. A daytime arterial blood-gas determination able to sleep for 4 to 5 hours using ilie device, and
showed a pH of 7.36, a Paco, of 65 mmHg, and a Pao1 of he was discharged home. Nocturnal polysomnogra-
42 mmHg. Nocturnal polysomnography was repeated phy obtamed after several months of use showed
(Fig. 18-7), showing periodic breathing and sustai11ed good synchronization of chest-wall motion with the
severe oxygen desaturations. Oxygen supplementation rocking bed, but some obstructive hyponeas and
was begun, but the Paco2 rose to 76 mmHg. Nasal venti- apneas continued to occur (Fig. 18-8). The oxygen
lation was tried once more and was rejected rapidly by desaturations associated with the obstmctive events
the patient. Initiation of negative-pressure ventilation were ameliorated by 2 liters/ min of nasal oxygen used
FIGURE 18-8 Continuous noch1mal recording of case 1 during rocking bed use without oxygen sup plementation . Tracing shows consistent
regular chest-wall mo tion s at a rate of 16 breaths per minute, indicating good synchronization with the rocking b ed. However, periodic
obstru ctive hypopneas are signified by decreases in ajrflow followed b y oxygen desaturations and arousals, as evidenced by dismption
of chest-wall synchrony. Channell is ch est-wall impedance, channel 2 is combined nasal a.nd oral thermistor, and channel 3 is finger
pulse oximetry. Vertical lines indicate 30-s intervals. Monitoring performed using Edentec monitor (Edentec, Inc., Eden Pra irie, MN).
.._,, ... 91'1 1\ RCI
I II I I' " f ' • f I
I I.
3,
I
;)2 :27 :86 r.pedAilee EJ!'.denTJoaee 82:29 :36 1..,...-1·-ee
~
lreat:b So '
I. I'I ' I ·~1~1· I

.....
8.-..a' b S......d8
I
I.
Sp02 Pen:.en t
3,
rI
- r
1
~
.......
l
I
I I E I
!:28:64 :r.p..woce ~olenThee I-deDCe
Alrflow
Breat b sa-n.t..
I llreatb s-.td8
I I I. I
.._, ------.,_,......,............,_
!
3
E I
FIGURE 18-9 Nocturnal recording of case 1 using rocking bed and 2liters/min Oz via nasal cannula. Tracing again shows excellen t
synchrony of chest-wall motion w ith rocking. A 50-s obstructive apnea ia apparent in the lower tracin g but is associated with only a mild
oxygen desaturation to 90%. Channels are the same as in Fig. 18-8.
noctumally (Fig. 18-9). The patient slept 7 to 8 hours both FVC and FEV1 to 0.5liter (14% of predicted). Arte-
nightly using the rocking bed with supplemental oxy- rial blood-gas determinations on room air showed a pH
gen, and a daytime unassisted room-air arterial blood- of 7.36, a Pacaz of 68 nunHg, and a Pao2 of 55 mmHg.
gas determination after 15 months showed a pH of The patient was admitted to the hospital for a trial of
7.42, a Paco2 of 52 mmHg, and a Pao2 of 78 mmHg. noninvasive ventilation.
After 3 years of clinical stability with nocturnal rock- Noninvasive positive-pressure ventilation was tried
ing bed use, the patient was hospitalized with pneu- initially, but the patient could not tolerate a face mask
monia and progressive respiratory failure; he declined or lip seal. (Comfortable nasal masks were not available
intubation and died. This case illustrates that trials of commercially at that time.) Negativ~pressure ventila-
a variety of noninvasive ventilators may be necessary tors were tried, but the patient found the iron lung too
before an acceptable one is identified. It also shows bulky and the pneumowrap too restricting and uncom-
that many considerations, including pragmatic limita- fortable. Standard chest shells fit poorly because of his
tions in the home, help to determine the final selec- mild scoliosis. Only the pneumobelt, which was quite
tion. Here the rocking bed was selected not because effective in augmenting his minute volume, was accept-
of greater efficacy or patient preference but because of able to the patient. His spontaneous respiratory rate
greater ease of application as perceived by the patient's was 28 breaths per minute, tidal volume was 90 rnl, and
wife. minute volume was 2.5liters/ min. The pneumobelt was
set at a rate of 22 breaths per minute and a positive pres-
CASE 2: USE OF THE PNEUMOBELT sure of 35 em H 2 0 , producing a tidal volume of 200 ml
M.C., a 24-year-old man with Duchenne muscular dys- and a minute volume of 4.4 liters/min. Arterial blood-
trophy, presented w ith a weakening voice, morning gas determination after 2 hours during the initial trial
headaches, and hypersomnolence. Pulmonary fw1ction showed a pH of 7.41, a Pacaz of 59 mrnl-Ig, and a Pao1
studies showed severe restriction with reductions of of78mmHg.
CHAPTER 18 NONINVASIVE RESPIRATORY AIDS 429
"tn afts at war: 1;'Wills are r m
FIGURE 18-10 Nocturnal recording of case 2. A

Spontaneous breathing at a rate of 20 breaths p er
Thenn minute. As expected, airflow increases, whereas
chest-wall dimensions decrease. B. During use of
pneumobelt at a rate of 22 breaths per minute, chest
wall and ventilator are synchronized. However,
ch est-wall motion is paradoxical, expanding during
expiration. Diaphragmatic electromyogram (D~1g)
failed to detect electrical muscular discharge during
eitlter sp on taneous breathing or venti lator use. s~'&'
submental EMG; Demg1 diaphragmatic EMG;
THERM, nasal thermistor; Cimp' chest-wall
imped ance; EKG, electrocardiogram.
The patient was discharged with instructions to use nal use while sleeping in the sitting position. The pneu-
the pneumobelt at night and as needed during the day- mobelt was an appropriate choice for him not only be-
time. Arrangements were made to a ttach a ventilator cause he preferred it but also because he had a favorable
platform to his wheelchair to facilitate daytime use. The body habitus and slowly progressive respiratory fail-
patient rapidly adapted to nocturnal use and encoun- ure that allowed a several-week adaptation period. The
tered little difficulty in sleeping while sitting upright. In pneumobelt proved to be temporizing in this patient, al-
addition to nocturnal use, he used the ventilator for 2-3 though it provided adequate ventilator assistance even
hours during the daytime. A daytime room-air arterial when he was almost entirely dependent on ventilato r
blood-gas determination during spontaneous breathing support. It was inadequate, however, when he devel-
after full adaptation 7 months after initiation showed oped a pulmonary infection, illustrating the limitations
a pH of 7.37, a Paco2 of 49 mmHg, and a Pao, of 84 of the device in the face of acute respiratory failure.
mmHg. A nocturnal polysomnogram showed excellent
synchrony of chest-wall movement with the ventila-
tor and no evidence of obstructive apneas (Fig. 18-10).
Oxygen saturations remained between 95% and 98% Glossopharyngeal Breathing
throughout the night while the patient was breathing
room air. Glossopharyngeal, or "frog," breathing was first described
The patient continued to use the pneumobelt both by Dail et al28 after they obser ved a polio patient who
nocturnally and during the daytime for the next 2 years had begun using it spontaneously. The technique consists
and found it particularly useful for reducing dyspnea of repetitive gulping motions in which the tongue thrusts
associated with eating. During this time, his pulmonary small boluses of air into the lungs (Fig. 18-11). The 40- to
function deteriorated gradually, necessitating more and 80-ml boluses take roughly 0.5 second and are repeated 8 to
more daytime use of the pneumobelt. Eventually, he 12 times in succession to achieve a tidal volume of 500-
had very little free time from the ventilator, amounting 600 ml, followed by passive exhalation. Roughly 10 of these
to 1-2 hours/ day. Shortly, in September of 1985, the pa- tidal volume maneuvers are performed each minute so
tient developed pneumonia and required endotracheal that a minute volume of 4-8 liters/min can be attained
intubatio n because of airway secretions that were un- (Fig. 18-12). In this way, persons with severely weakened
manageable w ith either the pneumobelt or an iron lung respiratory muscles can use the technique to sustain ventila-
despite manual cough assistance (mechanical assistance tion and free themselves from the need for continuous venti-
was not tried). He was unable to resume pneumobelt lator assistance. Patients who become adept at the technique
use, and a tracheostomy was performed. He lived at typically use it for periods ranging from a few minutes to
home for an additional3 years following tracheostomy several hours, but some ventilator-dependent patients can
placement but died unexpectedly when his ventilator use it for up to 14 consecutive hours without other aids to
inadvertently became detached from his tracheostomy ventilation (Sternburg L, personal communication).
tube. Glossopharyngeal breathing also may be used to aid
This case shows that the pneumobelt may be used spontaneous breathing in patients with marginal pul-
as the main mode of ventilator support in exceptional monary reserve by supplementing each tidal breath w ith
patients who prefer it to other forms of noninvasive ven- one to two boluses of air or to assist coughing. Cough-
tilation. This patient was able to adapt quickly to noctur- ing is assisted by repeating boluses until tidal volumes of
is of little value in patients with severe global weakness or

bulbar dysfunction. Efficiency is also impaired by reduced
chest-wall or lung compliance or increased airway resis-
tance, limiting use in patients with chest-wall defomuties
I.AitVNl or chronic o bs tructive pulmonary disease. In addition, be-
· C.i.05EO cause the upper airway contractions are voluntary, it cannot
be used during sleep. Use of the technique complements any
of the noninvasive aids to ventilation to extend "free time"
STEP1 STEP 2. from the ventilator.30
Glossopharyngeal breathing was used widely during the
1950s w hen it was taught to many patients \-vith respiratory
paralysis secondary to poliomyelitis. It is used less com-
monly tod ay, however, partly because skiJJed teachers are
few and also because most conditions leading to chronic
respira tory insufficiency are associa ted with global muscle
weakness or alterations in respiratory system complian ce
or airway resistance. N onetheless, occasional glossopha-
STEP3 STEP 4 ryngeal brea thers are found among survivors of the polio
epidemics,29 and some patients with muscular d ystrophy
FIGURE 18-11 Steps taken dUiing one "stroke"of or cervical spinal cord lesions learn to use the techniq ue,
gloss opharyngeal breathing. In s tep 1, lips are open, and air fills sometimes spontaneously. lllustrative is a recent case study
the mouth and oropharynx as the tongue and jaw are maximally of a 6-year-old boy with a high cervical lesion secondary to
depressed. In step 2, Lips are closed, and soft palate is raised to
tumor resection who learned glossopharyngeal breathing
trap air. In step 3, the tongue is raised against roof of the mouth as
th e laryn x is opened, forcing air into lungs. In step 4, the larynx is
on his own and was able to use it for ven tilator-free breath-
closed, trapping air in lungs, and the cycle is then repeated. (Used, ing for up to 12 hours a day d uring a 16-year period. Despite
w itlr permission, fro m Dail et a/: JAMA 158:445-9, 1953.) ha ving a tracheostomy, he was able to achieve a vital capac-
ity of 3.3 liters to augment cough. 30
2-2.5 liters/min are adueved, allowing greater expiratory

flows. 28, 2'J Complications are infrequent, w ith occasional pa- References
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FIGURE 18-12 Spirogram tracing obtained during 4. Gordon AS, Raymon F, Savode M, Ivy AC. Manual of artificial
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I
~ ~~
!' 12. Plum F, Whedon CD. The rapid -rocking bed: Its effect on the
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I 'I
~ ~
I New Engl J Med 1951; 245;235-41 .
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\ tory m"-'Chanics. J Appl Physiol1956; 9:19-24.
' 0
14. joos TH, Dickinson DC, Talner NS, \Nilson JL. The rocking bed
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CHAVfER 18 NONINVASIVE RFSPIRATORY AIDS 431
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20. Abd AG, Braun fMT, Baskin Ml, et al. Diaphragmatic d ysfunc- 28. Dail CW, AHeldt JE, Collier CR. Clinical aspects of glossopharyn-
tion after open heart surgery: Trea tment with a rocking bed. Ann geal breathing: Report of use by one hundred postpoliomyelitis
Intern Med 1989; 111:881-6. patieJ\ts. JAMA 1953; 158:445-9.
21. Chalmers RM, Howard RS, Wtles CM, SpeJ1cer GT. Use of the 29. Bad1 JR, Alba AS, Bodofsky E, eta!. Glosopharyngeal breathing
rocking bed in the treatment of neurogeJ\ic respiratory insuffi· and noni nvasive aids in the management of post-polio respira-
ciency. Q J Med 1994; 87:423-9. tory insufficieJlC)'. Birth Defects 1987; 23:99- 113.
22. Bach JR, Alba AS. Total ventilatory support by the intern1ittent 30. Bianchi C, Grandi M, Felisari G. Efficacy of glossopharyngeal
abdominal pressure ventilator. Chest 1991; 99:630-6. breathing for a ventilator-dependent, high-level tetraplegic pa-
23. Ellis ER, Bye PT, Bruderer JW, Sulli van CE. Tr"CatmeJ\t of respi· tieJ\t a fter cervical cord tumor resection and tracheotomy. Am J
ratory fa ilure during sleep in patieJ\ts with neuromuscular dis- Phys Med Rehabil2004; 83:21 6-9.
[!I
Chapter 19 _ _ _ _ _ _ _ _ __ Selection of Patients with Cluonic Respiratory Failure
and Obstructive Lung Diseases to Receive
NONINVASIVE Noninvasive Ventilation
Congestive Heart Failure
POSITIVE-PRESSURE Pediatric Uses of Noninvasive Positive-Pressure
Ventilation for Chronic Respiratory Failure
VENTILATION PRACTICAL APPLICATION OF NONINVASIVE
POSITIVE-PRESSURE VENTILATION
NICHOLAS S. l-ULL Initiation
Location
Masks (Interfaces)
Selection of Interfaces
Selection of a Ventilator
Selection of a Ventilator Mode
WHY USE NONINVASIVE VENTILATION AND Ventilator settings
H OW DOES IT WORK? Adjuncts to Noninvasive Ventilation
Rationale Noninvasive Techniques to Assist Cough
Med1anisms of NPPV Action Role of the Clinician: Time Demands, Importance
NONIN VASIVE POSITIVE-PRESSURE VENTILATION of Experience, and Guidelines
IN THE ACUTE-CARE SETTING MONITORING
Evidence for Efficacy Subjective responses
Obstructive Diseases Physiologic Responses
Restrictive Diseases Gas Exchange
NONIN VASIVE POSITIVE-PRESSURE VENTILATION Sleep
FOR CATEGORIES OF PATIENTS WITH ADAPTATION
ACUTE RESPIRATORY FAILURE Acute
Do-Not-Intubate Patients Long Term
Postoperative Patients ADVERSE EFFECTS AND COMPLICATIONS
Facilitation of Weaning and Extubation SUMMARY AND CONCLUSIONS
PATIENTS UND ERGOING
BRONCHOSCOPY Noninvasive ventilation (NlV) refers to the prOV1SlOn of
SELECTION OF PATIENTS FOR NONINVASIVE mechanical ventilation without the need for an invasive
PO SITIVE-PRESSURE VENTILATION ar tificial airway. Many different approaches to assisting ven-
IN THE ACUTE SETTING tilation noninvasively have been used in the past, including
Determinants of Success negative-pressure ventila tors, pneumobelts, and rocking
Selection Guidelines beds 1 (see Chapters 17 and 18). By vir tue of its effective-
NONI NVASIVE POSITIVE-PRESSURE VEN TILATIO N ness and convenience compared with other noninvasive
FOR CHRONIC RESPIRATORY FAILURE approaches, however, noninvasive positive-pressure ven-
Evidence for Efficacy tilation (NPPV) using a mask (or interface) that conducts gas
Selection of Patients with Restrictive Thoracic Disease from a positive-pressure ventilator into the nose or mouth
to Receive Noninvasive Positive-Pressure has become the predominant means of administering NIV
Ventilation throughout the world. NPPV has long been used to treat
When to Start Long-Term Noninvasive chronic respiratory failure caused by chest-wall deformi-
Positive-Pressure Ventilation for Restrictive ties, slowly progressive neuromuscular disorders, or cen-
Thoracic Disorders tral hypoventilation.2 1n more recent years, NPPV has been
CENTRAL HYPOVENTILATION, OBSTRUCTIVE increasingly used to treat patients with various forms of
SLEEP APNEA, AND OBESITY HYPOVENTILATION acute respiratory failur e. 3 For the purposes of this discus-
central hypoventilation/obs tmctive sleep apnea sion, noninvasive positive-pressure ventilation (NPPV) refers
Obesity-Hypoventilation Syndrome to active ventilator assistance achieved by the noninvasive
Selection of Patients with Central Sleep provision of a mechanical positive-pressure breath during
Apnea/Obesity-Hypoventilation Syndrome for inhalation, and continuous positive airway pressure (CPAP)
Noninvasive Positive-Pressure Ventilation refers to the provision of a nonfluctuating positive pres-
OBSTRUCTIVE LUNG DISEASES sure. This chapter discusses the rationale for use, evidence
Ouonic Obstructive Pulmonary Disease for efficacy of noninvasive positive-pressure techniques in
Noninvasive Positive-Pressure Ventilation to Enhance both acute and chronic settings, selection of appropriate pa-
Rehabilitation in COPD tients, techniques for administration, and pitfalls and com-
Cystic Fibrosis and Diffuse Bronchiectasis plications.
433
Why Use Noninvasive Ventilation preclude home discharge in p atients with limited caregiver
and financial resources.
and How It Works? NIV can avoid many of these complications if candidates
are selected properly using guidelines that will be discussed
RATIONALE in detail later. NlV leaves the upper airw ay intact, preserves
NIV has become an integral component of ventilator sup- airway defense mechanisms, and allows patients to eat,
port in both acute and duonic settings because it avoids drink, verbalize, and expectorate secretions. NPPV reduces
the complications of invasive ventilation. Invasive mechan- the infectious complications of mechanical ventilation, in-
ical ventilation is highly effective and reliable in support- cluding nosocomial pnetmlonia and sinusitis 13 •14 (Fig. 19-1).
ing alveolar ventilation, bu t endotracheal intubation carries
well-known risks of complications that have been described
elsewhere in detail 4 (see Chapter 39). These complications
FIGURE 19-1 Percent of initiations of mechanical venti lation that
h ave been lumped into three main categories: complications
were noninvasive (top pauel), mortality (middle paue(), and
related to insertion of the tube and mechanical ventilation, occurren ce of health care- acquired pneumonias (bottom pauel) in
those caused by loss of airway d efense med1anisms, and patien ts with COPD and cardiogenic pulmona.r y edema over an
those that occur after removal of the endotracheal tube. 4 8-year period in the ICU of Henri Mondor Hospital in Paris.
h1 the first category, aspiration of gastric contents; trauma (Used, with permission, from Girou et al: fAMA 290:2985- 91, 2003.)
to the teeth, hypopharynx, esophagus, larynx, and trachea;
arrhythmias; hyp otension; and barotrauma may occur dur- No.ninvaslve Ventllation Use
100
ing plac"(?ment of a translaryngeal tube. 5 - 7 Tracheostomy
90
tube placement incurs risks of hemorrhage, stomal infec-
80
tion, intuba tion of a fa lse lumen, mediastinitis, and acute
10
injury to the trachea and surrow1ding structures, including
the esophagus and blood vessels? In the second category,
"$. eo
endotracheal tubes serve as a source of continual irritation, ~Q) ~
interfere with airw ay dJiary function, and require frequent ""

~ 40
suctioning that contributes to airway injury, p a tient discom- 30
.L
P<.()()l
fort, and mucus hypersecretion. They also provide a direct 20

d1annel to the lower airways for microorganisms and other 10
foreign materials, leading to biofilm formation, chronic bac- 0
terial colonization, and ongoing inflammation. As a conse-
quence, health care-acquired pneumonias are seen in up
Nosocomial Infections
to 20% of med1anically ventilated intensive-care unit (ICU) 60
patients8 (see Chapter 46), and sinusitis is seen in 5-25% 45
of nasally intubated patients, related to blockade of the si- 40 P•.01
nus ostia and accumulation of infected secretions in the 35
paranasal sinuses9 (see Chapter 47). m the third category, I! 30
hoarseness, sore throat, cough, sputum production, hemop- .;
i
25
tysis, upper airway obstruction secondary to vocal cord d ys-
20
fun ction or laryngeal swelling, and tracheal sten osis all may
15
follow extubation.10
maddition, from the point of view of the p atient, transla- 10
ryngeal intubation is uncomfortable and compromises the 5
ability to eat and communicate, contributing to feelings of 0
powerlessness, isolation, and anxiety. 11 This increases the
need for sedation, delaying weaning, prolonging the dura- Intensive Care Unit MOf1elit y
tion of invasive mechanical ventilation, and potentiating the 40
risks of further complications. If tracheostomy placement 35
becomes necessary, sophisticated equipment including su e-
30 Pa.04
honing paraphernalia a nd a high level of technical expertise
among caregivers a re required. Tracheostomies promote "# 25
upper airway colonization with gram-negative bacteria, in- !1
j 20
creasing the ris k of pneumonias.8 Further, long-term tra-
cheostomies are complicated by tracheomalada, granula-
l 15
tion tissue formation, a nd tracheal stenoses that sometimes 10

obstruct the airway, chronic pain, and trad1eoesophageal o r
even tracheoarterial fistulas. 10 These consid erations and po-
5 1
0 ~--~--~----r---~--~----r---,----,
tential complications may limit the o ptions for chronic-care 1994 1995 1996 1997 1998 1999 2000 200 I
placement, add substantially to the costs of care,12 and even (n~39) (ne52) (n=64) " = 61) (n=70) j'l = 63) tn=58) (n=72)
CHAPTER 19 NONINVASIVE POSITIVE-PRESSURE VENTILATION 435
It also enhances patient comfort, convenience, and mobility venous lines,14 and this also likely contributes to a lower rate
at no greater15 or even less12 cost than endotracheal intu- of health care-acquired infections and episodes of sepsis.
bation. NIV can be administered outside the ICU setting as Despite the ad vantages of NPPV related to the a voidance
long as adequate nursing and respiratory therapy support of airway invasion, the lack of a direct connection to the
can be provided, allowing for more rational use of acute- lower airway also poses a number of challenges. The patient
care beds, and it greatly simplifies care for patients with must be able to protect his or her airway and clear secretions
cluonic respiratory failure in the home. adequately, or failu re is inevitable. The patient's tlpper air-
way must permit airflow into the lungs, so NPPV cannot
be used in patients w ith high-grade fixed upper-airway ob-
structions. In addition, air leaks around the interface seal or
MECHANISMS OF NPPV ACTION via other routes are nearly ubiquitous with NPPV and may
ACUTE RESPIRATORY FAILURE interfere with the eHicacy of ventilation. Further, the patient
NPPV improves the respiratory status of failing patients must be able to cooperate and synchronize breathing with
via a number of mechanisms. Most important, NPPV re- the ventilator, or no reduction in the work of breathing can
duces the work of breathing by the same mechanis m as be acl1ieved, but the patient cannot be heavily sedated or
invasive positive-pressure ventilation (PPV): By applying paralyzed in order to achieve synchrony. Thus patients to
supra-atmospheric press ure intermittently to the airways, receive NPPV mus t be selected carefully and managed w ith
it increases transpulmonary pressure, inflates the lungs, an eye to these limitations in ways that differ from the ap-
augments tidal volume, and unloads the inspiratory mus- proach used for invasive mechanical ventilation.
cles. Exhalation is achieved by passive lung recoil. Stud-
ies in patients with severe stable chronic obstructive pul- CHRONIC RESPIRATORY FAILURE
monary disease (COPD) or restrictive thoracic disorders Long-term NPPV is used mainly nocturnally during sleep,
show that NPPV reduces or, if inflation pressure is sufficient, when intermittent air leaking through the mouth or under
even eliminates diaphragmatic work.16•17 In patients with the mask seal is universal, but sufficient air usually enters
severe COPD exacerbations, the addition of positive end- the lungs to assist ventilation.21 TI1e adaptations that per-
expiratory pressure (PEEP) to inspiratory pressure support mit air entry into the lungs while NPPV is administered
further reduces the work of breathing by counteracting the duri11g sleep are poorly understood, but resistance to air-
effects of auto-PEEP. This combination (pressure support flow in the upper a irway is tmdoubtedly an important fac-
plus PEEP) lowers diaphragmatic pressure swings even tor. In one study, large amounts of air leaking through the
more than with either pressure support or PEEP alo.ne.18 mouth during nasal CPAP increased nasal res istance,22 an
l11ese actions lead to a prompt reduction in respiratory rate, effect that was countered by provision of heated, humid-
sternocleidomastoid muscle activity, dyspnea, and carbon ified air, consistent with the idea that nasal mucosal cool-
dioxide (C0 2) retention. ing was res ponsible. Increases in nasal resistance secondary
Other benefi cial actions include an increase in functional to this mechanism, upper airway infection, or allergy is
residual capacity (FRC) that open s collapsed alveoli, re- likely to reduce delivered tidal volumes during nasal NPPV.
ducing shunt and enhancing ventilation -perfusion ratios in Passive positioning of the soft palate is also important in
certain forms of respiratory failure, such as acute cardia- maintaining patency of the upper airway, 23 as underlined
genic pulmonary edema. These effects improve oxygena- by tl1e observation that patients treated with nasal CPAP
tion and may further reduce the work of breathing because experience increased air leaking through the mouth after
the respiratory system is shifted to a more compliant posi- t1Vu1opharyngoplasty.24
tion on its pressure-volume curve. In addition, CPAP alone Glottic aperture is also important in determining the flow
(and with NPPV) may improve left-ventricular function by of gas into t11e lower airways during NPPV. Compared w ith
virtue of an afterload-reducing effect of increased intratho- the awake state, the glottic aperture narrows and delivered
racic pressure. 19 This effect occurs mainly in patients with tidal volume falls when NPPV is administered during stage
dilated, hypoco ntractile left ventricles whose heart func- 1 or 2 sleep. 25•26 In deeper sleep (stages 3 or 4), the glot-
tion is more dependent on afterload than on preload. The tic aperture widens, permitting more ventilation; if minute
increased intrathoracic pressure reduces both preload and volume is increased excessively, however, the glottic aper-
afterload, but the latter effect predomina tes, lowering trans- ture narrows once again, partly related to the reduction in
myocardial pressure and enhancing cardiac output. 20 Pac~· These findings indica te that both sleep stage and the
A major effect of NPPV that appears to be responsible for amount of ventilator assistance influence glottic aperture,
benefits reported in ma ny studies, including reduced com- which is a potentially important determinant of the effi-
plication rates, mortality, and hospital lengths of stay, is a cacy of NIV. They also apply mainly to controlled modes
reduction in health care- acquired infections. Two prospec- of venti1ation27; glottic aperture is not as important when
tive surveys"13, 14 observed roughly a fourfold reduction in NPPV is administered via a pressure-limited ''bilevel" ven-
the risk of health care-acquired pneumonia compared with tilato r in the spontaneous mode.28
physiologically matched endotracl1eally intubated patients, Three theories have been proposed to explain the mech-
even after controlling for severity of illness. Patients trea ted anism by which stabilization of daytime gas exchange is
with NPPV also tend to receive fewer other invasive inter- achieved in patients with cluonic respira tory failure '"'ho
ventions, such as urinary bladder catheters or central intra- are receiving ventilator assistance for as little as 4-6 hours
nightly. One postulates that NN rests chronically fatigued curve, whereas the maximal inspiratory p ressure remained
respiratory muscles, thereby improving daytime respira- tmchanged.42 These studies suggest that amelioration of
tory muscle function. 29•30 Supporting this theory are studies nocturnal hypoventilation with resetting of respiratory cen-
demonstrating that respiratory muscles do indeed rest dur- ter C0 2 sensitivity and improved sleep quality may be the
ing NN31 - 33; also, indices of respiratory muscle strength most important mechanisms contributing to the efficacy of
and endurance may improve in patients with chronic r espi- long-term NPPV. The three theo ries, however, are not mu-
ratory failure after varying periods of noninvasive ventila- tually exclusive, and all could contribute more or less, de-
tory assistance.31 - 33 Conversely, chronic respiratory muscle pending on the patient.
fatigue has never been defined adequately or demonstrated Clearly, much remains to be learned regarding specific
convincingly; other studies have failed to demonstrate im- mechanisms of action of NN. Understanding of these mech-
provement in respiratory muscle function after initiation of anisms is complicated by the application of NN in both
NIV,35 and some studies have demonstra ted that patients acute and chronic settings using many different techniques
with neuromuscular disease have stable Pac~ values for for patients with varying etiologies of respiratory failure.
years despite a progressive decline in pulmonary function.36 The ability to unload respiratory muscles appears to be key,
A second theory proposes that NIV improves respira- particularly in the acute setting. Mechanisms controlling
tory system compliance by reversing microatelectasis of upper ain.vay responses and respiratory center adaptations
the lung, thereby diminishing daytime work of breathing.37 are less well understood but appear to be critical to success
This theory derives from studies showing improvements in the long-term setting.
in forced vita l capacity (FVC) without changes in indices
of respiratory muscle strength after periods of PPV. Once
again, however, data are conflicting, with a number of stud- Noninvasive Positive-Pressure Ventilation
ies showing no changes in vital capacity after periods of
NIV.34,35 In addition, computed tomographic (CT) scarming in the A cute-Care Setting
of the chest indicates that microatelectasis is not an impor-
tant contributor to chest-wall restriction in patients with EVIDENCE FOR EFFICACY
respiratory muscle weakness. Numerous acute applications o fNPPV have been described,
A third theory proposes that NIV lowers the respi- but only a few are supported by strong evidence (Table 19-1).
ratory center "set point" for C02 by reversing chronic The following will discuss important applications according
hypoventilation. 29· 38 During deeper stages of sleep, par- to the type of respiratory failure.
ticularly rapid-eye-movement (REM) sleep, upper airway
muscle tone and the activity of nondiaphragmatic inspi-
OBSTRUCTIVE DISEASES
ratory muscles dirninish. 39 This response may be exagger-
ated in patients with ventilatory impairment, leading to CHRONIC OBSTRUCTIVE PULMONARY DISEASE
progressive nocturnal hypoventilation. Repeated episodes Patients with exacerbations of chronic obstructive pul-
of nocturnal hypoventilation are thought to lead to a monary disease (COPD) ttS\.Ially a re good candidates for
gradual accumulation of bicarbonate, desensitization of NPPV because they respond to partial ventilator support,
the respiratory center to C021 and worsening of daytime hypoxemia is usually mild to moderate, and the condition
hypoventilation. 38 Nocturnal ventilator assistance reverses is most often reversible within a few days. Thus numer-
nocturnal hypoventilation and allows excretion of bicar- ous earlier uncontrolled studies have reported that NPPV
bonate and a gradual downward resetting of the respira- avoids intubation in patients with COPD, with success rates
tory center set point for c~, thereby reducing daytime ranging from 58-93%. Some studies have reported the use
hypercarbia. In addition, NPPV may improve the quantity of CPAP alone to treat acute exacerbations of COPD,43•44
and quality of sleep by preventing hypoventilation-related based on the rationale that by counterbalancing auto-PEEP,
arousals that lead to sleep fragmentation,40 reducing fatigue it will reduce the work of breathing. 45 In these studies, rela-
and improving daytime function. Evidence for this theory tively low levels of nasal CPAP (5-9.3 cmH2 0) were associ-
derives from studies showing that when ventilator assis- ated with improvements in Paco2 and arterial oxygen ten-
tance is discontinued for a night in patients with chronic sion (Pa 02 ),and few patients required intubation. The lack
respiratory failure who have been using nightly NIV, the of controls, however, renders these studies inconclusive.
degree of nocturnal hypoventilation is less than before ini- The first controlled study on NPPV for acute exacerba-
tiation, suggesting a resetting of respiratory center sensi- tions of COPD reported that patients treated with face-
tivity for C02 . 41 Also, nocturnal ventilation, oxygen (02 ) mask NPPV were endotracheally intubated less often (1
saturation, sleep quality, and daytime symptoms deterio- of 13 versus 11 of 13), weaned from the ventilator faster,
rate without reductions in respiratory muscle strength o r and spent less time in the ICU than historically matched
vital capacity w hen nocturnal NPPV is discontinued tem- controls. 46 Historical controls, however, may bias results in
porarily in patients with restrictive thoracic disease and favor of the treatment group. 47 Subsequently, these findings
improve promptly when NPPV is resurned.34'40 Moreover, have been buttressed by randomized, controlled trials that
in 16 patients with chronic respiratory failure secondary lend support to the earlier observations. In a study by Bott
to restrictive thoracic disorders followed prospectively for et al,48 patients with acute exacerbations of COPD random-
3 years after starting NPPV, Paco2 improved in association ized to receive nasal NPPV had improvements in Paco,
with an increase in the slope of the ventilatory response (65-55 mmHg in the first hour) and dyspnea scores,
TABLE 19-1 TyPes of Acu te Respiratory Failure Treated with group during the first hour; intubation (26% versus 74%),
Noninvasive Ven tilation G raded complication (16% versus 48%), and mortality (9% versus
References
29%) rates and hospitallengths of stay (35 versus 23 days) all
were significantly lower in the NPPV versus control group.
A. Stron g Evi dence-Recommended Additional controlled trials have compared the effects of
Exacerbation of COPD 46,48-62 NPPV with those of doxapram over 4 hours in patients w ith
Acute cardiogenic pulmonary edema 9Q-105 acute exacerbations of COPD; although doxapram tran-
Irnmunocompromiscd (hematologic malignancy, 109- 114 siently improved Pa0z, it had no effect on Pac0z.50 Also,
bone marrow or solid-organ transplant, ATDS) three deaths occurred in the doxapram group. NPPV was
Facilitation of weaning/ extubation patients with 130-136 deemed more effective than doxapram because it brought
COPD
about sustained improvements in both PacOz and Pa0z. An-
B. Intermediate Evidence-Guideline
Asthma 66-70
other randomized, controlled trial compared the efficacy of
Community-acquired pneumonia in patients 105 standard medical therapy with NPPV in 30 patients w ith
with COPD acute hypercapnic respiratory failure caused by exacerba-
Extubation failure in patients with COPD 141" tions, pneumonia, or congestive heart failure.51 Those ran-
Hypoxemic respiratory failure 81- 88 domized to NPPV had greater improvements in pH and
Do-not-intubate patients (COPD and CHF) 117- 122 respiratory rate within 6 hours, higher success rate (93%),
Postoperative respiratory failure (lung resection, 123- 129 and shorter hospital lengths of stay (11.7 versus 14.6 days,
bariatric, CABG) p < .05) than controls. The largest study to date on NPPV for
C. Weaker Evidence-Optional exacerbations of COPD randomized 236 patients to receive
Acutt'-respiratory d istress syn drome (ARDS) 115 NPPV or standard therapy at 14 British centers. 52 NPPV was
with single-organ involvement
Community-acquired pneumonia (non-COPD) 105-109
administered in general respiratory wards by nurses who
Cystic fibrosis 72- 74 had a few hours of in-servicing training with the technique.
Facilitation of weaning/ extubation failure 137-140,142 Patients b·eated with NPPV had lower intubation (15% ver-
(non-COPD) sus 27%) and mortality (1 0% versus 20%) rates than controls,
Neuromuscular disease/chest-wall deformity 77- 79 but the benefit was seen only in patients w itl1 pH values of
Obsh·uctive sleep apnea/ obesity hypoventilation 75,76 7.30 or greater. The authors concluded that although NPPV
Trauma 116 proved to be effective in their study, these sicker patients
Upper airway obstruction probably should have been treated in an ICU.
D . Not Recommen ded In addition to the favorable findings regarding the use of
Acute deterioration in end-stage interstitial 80 NPPV for acute exacerbations of COPD, some studies have
pulmonary fibrosis
Sever e ARDS with multiple organ dysfunction
fo und that 1-year survival rates are better and the need for
Postoperative upper airway or esophageal rel1ospitalization and consumption of ICU beds over the
surgery next year are less for patients treated with NPPV as opposed
Upper airway obstruction with high risk to conventional therapy. 53' 54 Although these latter studies
for occlusion were not randomized, so the results could have reflected a
selection bias favoring less ill patients in the NPPV group,
Level of evidence: A = multiple randomized, controUed trials and meta-
it is also possible that NPPV avoids late complications of
analyses; B =single controlled trial and cohort series or multiple randomized
studies with conflicting findings; C =anecdotal reports and ca$e series; D = invasive ventilation, such as sustained muscle weakness or
not recommended based on contra ry evidence or expert opin ion. swallowing d ysfw1etion. 9
ABBREVIATIONS: AIDS, acqu ired immune deficiency syndrome; COPD, chronic Among the m any controlled and uncontrolled studies ex-
obstmctive pulmonary disease; o;F, congestive heart failure; CABG, coronary amining the efficacy of NPPV in exacerbations of COPD,
artery bypass graft.
only two have obtained unfavorable results. In one,55 25 of
49 consecutive COPD patients with acute exacerbations
whereas no significant changes occurred among con- were treated with nasal NPPV, and 24 were intolerant and
trols. In addition, mortality rate was lower among NPPV- served as the "control" group. Blood gases in both groups
treated patients than in controls (10% versus 30%), al- improved at similar rates, and no differences in outcome
though this reduction became statistically significant only were apparent between the two groups. In the second, Barbe
after exclusion of four NPPV patients who never acet a! 56 randomized 24 patients with acute exacerbations of
tually received the therapy. Kramer et al49 randomized COPD to receive nasal NPPV or standard therapy. Four of
31 patients with various etiologies for respiratory fail- 14 patients randomized to NPPV were in tolerant; among the
ure, 21 of whom had COPD, to receive NPPV or con- remaining patients, blood-gas improvements and hospital
ventional thera py. Among COPD patients w ho received lengths of s tay were similar, and no differences in intuba-
NPPV in their study, respiratory rate and Paco, fell more tion or mortality rates were apparent, leading the authors
rapidly during the first hour of therapy than among con- to conclude that NPPV is ineffective in COPD. Both studies,
trols, and intubation rates were reduced to 9% compared however, enrolled consecutive patients who, on average,
with 67% in controls. In a multicenter European trial16 had less severe blood-gas abnormalities than patients en-
of 85 patients w ith COPD randomized to receive fa ce-mask rolled in favorable studies; none of the patients in tl1e study
pressure-support ventilation (PSV) or conventional therapy, of Barbe et al 56 required intubation, as did almost three-
respiratory ra te but not Pac0 , fell significantly in the NPPV quarters of the controls in tl1e studies of Kramer et al49 and
Ucual Rilk ratio Weight Risk ratio

Study NPPV medical care (fixed 95% Cl) (%) (fixed 95% C1)
Avdeev e1 al 1998 19 3129 9!29 15.6 0.33 (0.10 1o 1.11)
Barbe et aJ 19961&< 011 0 ono 0.0 Not es1imabte
Bol1 et al19932 3130 9!30 15.6 0.33 (0.1 0 10 u 1)
3
Brochard et al1995 4143 12/42 21.1 0.33 (0.1110 0.93)
Celikel e1 al1998 1' 0/15 1ns 2.6 0.33 (0.0110 7.58)
Oikeowy e1 al 20022> 111 7 2/1 7 3.5 0.50 (0.05 1o 5.01)
Plant et a1 200015 121118 24n1a 41.6 0.50 (0.2.610 0.95)
Total {95% Cl) 231262 57!261 100 0.41 (0.2.610 0.64)

Test for heterogtuleity. r=0.82. df=5, P::0.98
Test for ovenll effect Z~3.96. P=0.00008 0.1 0.2 1 5 10
NPPVbetter Usual care
than usual better
medical care than NPPV
FIGURE 19-2 Forest plot of eight randomized, controlled studies on N PPV in patients with acute respiratory failure secondary to COPD.
The reduction in mortality rate was consistent among studies. (Used, with pennissiou, from Lightowler: Br Med T185- 9, 2003.)
Brochard et al.16 These observations support the contention 2:: 70 mmHg, respiratory rate 2:: 35breaths per minute). Sixty-
that the patients in the two unfavorable studies were less fo ur such patients had similar mortality rates and hospital
ill than those in the favorable studies and argue that NPPV lengths of s tay but fewer serious complications (mainly in-
should be reserved for sicker pa tients with COPD who are fectious) and a trend toward a higher weaning rate at 30 days
at risk of requiring intubation. compared with a historically matched control group of in-
Multiple randomized, controlled trials lend themselves vasively ventilated patients. The authors concluded that
to meta-analysis. An earlier meta-ana lysis by Keenan et al57 NPPV can be used as an alternative to invasive mechanical
concluded that NPPV significantly reduces mortality and ventilation in severely ill patients with COPD, but consider-
reduces the cost of hospitalization by an average of $3244 ing that the failure ra te approached two-thirds in the NPPV
Canadian dollars compared with conventional therapy. group, this approach should be applied with grea t caution.
Peter et al 58 examined both COPD and non-COPD causes As pointed out previously, the use of historical controls is
of acute respiratory failure in their meta-analysis, conclud- a serious design limitation that may favor the treatment
ing that NPPV significantly reduces the need for intubation group.
as well as mortality. More recent meta-analyses by Keenan Few data provide guidance on selecting patients who
et al59 and Lightowler et al60 (Cochrane analysis) observed might benefit from continued use of NPPV after hospital
absolute and relative risk reductions of 28% and 0.42 for in- discharge. In an uncontrolled retrospective study, Tuggey
tubation, 10% and 0.41 for m ortality, and 4.57 and 3.21 hos- et al64 found that patients treated with NIV during their
pital days, respectively (all p < .05) (Fig. 19-2). The analysis acute admissions and sent home with it had many fewer
of Keenan et al also concluded that there is little evidence hospital days per year (25 versus 78 days; p = .004) and
to support NPPV use in milder COPD, although they an- incurred much lower costs per year ($7407 versus $23,065)
alyzed only two s tudies of mild patients. The analysis of after starting domiciliary NIV than before. Despite the small
Lightowler et al also fo und that Paco1 , heart rate, and dyp- number of patients and uncontrolled design, these results
nea scores improved more rapidly than in conventionally support the idea that domiciliary NIV should be considered
treated patients. These studies lend strong support to the use in ''revolving-door patients" who require repeated hospital
of NPPV fo r patients with COPD in the acute-care setting, admissions and highlight the need for more definitive stud-
leading consensus groups to recommend that the modality ies addressin g this question.
"be considered" in selected patients.61 •62 The need for careful
patient selection cannot be overemphasized (see "Selection ASTHMA
Guidelines," below). NPPV is best used to avoid intuba- Although acute asthma would be anticipated to respond
tion, not to replace it. Although NPPV should be viewed as favorably to NPPV because it shares pathophysiologic fea-
the ventilator therapy of first choice for appropriate COPD tures with COPD, much less evidence supports this applica-
patients, those with contraindications to NPPV should be tion. One earlier study of 158 patients with acute respiratory
intubated and ventilated w ithout delay. failure of diverse etiologies treated w ith face-mask NPPV in-
In view of the idea that NPPV is bes t used to avoid intuba- cluded 5 patients w ith acute asthma (average initial Paco1
tion, Squadrone et al 63 asked w hether it can serve as an alter- of 67mmHg).65 Only one of these required intubation, and
native to intubation in patients with COPD and advanced there were no mortalities. The same group later described
acute hypercapnic res piratory failure (pH ~ 7.25, Pac 02 17 patients with asthma who had an average initial pH of
7.25 and a Paco1 of 65 mmHg and were treated with face- chronic C02 retention (initial Paco2 ranging from 63-112
mask PSV. 66 Only two required intubation (for increasing mmHg) were treated with NPPV for periods of 3-36 days;
Pac02), average duration of ventilation was 16 hours, and four survived until a heart-lung transplant could be
no complications occurred. performed.72 The same investigators re ported more re-
More recently, Fernandez et al 67 reported on 58 patients cently on 113 patients with CF treated with NPPV for
with status asthmaticus, 33 of whom were retrospectively acute deteriorations.73 Ninety of these patients (median
deemed candidates for NPPV because of persisting C02 re- FEV, / FVC ratio of 0.5) were listed for lung transplantation,
tention (Pac~ > 50 mmH g) and because they met other 28 survived to transplant, 10 remained on the list at the time
clinical criteria.67 Of these, 11 were intubated according to of reporting, and the remainder expired. NPPV improved
clinician preference, and 22 were managed noninvasively. hypoxia but not hypercapnia. These case series suggest that
The noninvasively and invasively treated groups had sim- NPPV may serve as a rescue therapy to provide a ''bridge to
ilar initial Pac02 values, which improved less rapidly in transplantation" for patients with acutely deteriorating CF,
the noninvasive g roup. Only 14% of the NPPV-treated pa- but morta lity still will be substantial ifthe wait is prolonged.
tients eventually required intubation, and they had shorter
ICU and hospital lengths of stay than the intubated group . UPPER AIRWAY OBSTRUCTION
Thus far two randomized, controlled trials have been re- NPPV has been deemed contraindicated for patients w ith
ported . Holley et al68 were able to enroll only one-tenth of upper airway obstruction in the past,65 and the inappropri-
the roughly 350 patients their power analysis had projected. ate use of NPPV in patients with tight, fixed upper airway
Not surprisingly, their major outcome va riable, intubation obstntction should be avoided so as not to delay the institu-
rate, was not reduced significantly in their NPPV group tion of definitive therapy. In the author's experience, how-
(1 of 19 versus 2 of 16 in controls), and they observed no ever, NPPV can be used to treat patients with reversible
deaths. Their major finding was that physicians who a priori upper airway obstruction, such as that caused by glot-
believed that NPPV was effective were less likely to en- tic edema following extubation, sometimes in combination
roll patients in tl1e trial because of concern that tl1e patients with aerosolized medication and/or heliox. Although no
might require intubation if randomized to the control group. controlled trials demonstrate the efficacy of this approach
Soroksky et a1 69 randomized 33 patients with severe acute in adults, a controlled trial in 10 infants with respiratory
asthma [average initial forced expiratory volume in 1 second failure showed that NPPV74 and CPAP were equally effica-
(FEV1 ) roughly 33%] to receive NPPV or sham therapy via cious in lowering respiratory rate, but NPPV contributed to
a face mask. The NPPV group had a sig nificantly greater patient-ventilator asynclu-ony. If used, NPPV should be ad-
increase in FEVt within the first hour (53.5% versus 28.5%) ministered cautiously and monitored closely because these
and fewer hospitalizations (3 of17 versus 10 of 16) compared patients are at risk for precipitous deteriorations.
with the sham g roup. Both groups received aerosolized
bronchodilators via a nebulizer, not the ventilator. The au- DECOMPENSATED OBSTRUCTIVE SLEEP APNEA
thors speculated that the greater improvement in airflow in OR OBESITY HYPOVENTILATION SYNDROME
the NPPV g roup might be related to a bronchodilator effect Patients with acute-on-chrome respiratory failure caused
of positive pressure. by sleep apnea syndrome, often in combination with
These studies suggest that NPPV may be effective in obesity hypoventilation, have been treated successfully
improving airflow, correcting gas-exchange abnormalities, with NPPV and transitioned to CPAP once stabilized?5
avoiding intubation, and reducing the need for hospitaliza- but no controlled trials have evalua ted this application.
tion in patients with acute severe asthma. Published stud- Sturani et al 76 described the successful use of nasal NPPV
ies, however, are either uncontrolled or underpowered or administered with the BiPAP device (18 onH2 0 inspira-
the findings have not been replicated. A recent Cochrane tory and 6 cmH20 expiratory pressures) in five morbidly
analysis concluded that evidence for use ofNPPV for acute obese patients [mean body mass index (BMI) of 50 mg/m2 ]
asthma was "very promising" but "controversial" and tat with severe sleep apnea. Anecdotally, high inflation pres-
more controlled studies are needed.7° Furthermore, medi- sures, sometimes necessitating use of volume-limited ven-
cal therapy alone may be quite effective.71 Lacking more ev- tilators that have greater pressure-generating capabilities
idence, no firm conclusions can be drawn regarding tl1e rel- than portable pressure-limited ventilators, may be needed
ative effectiveness of NPPV versus conventional therapy in because of high respiratory system impedance.
exacerbations of asthma. The British Thoracic Society Stan-
dards of Care Committee opined that NPPV s hould not
RESTRICTIVE DISEASES
be used routinely for acute asthma. 62 Nonetheless, a trial
of NPPV might be considered in patients not responding Although NPPV to treat patier1ts with chronic respiratory
promptly to standard medical therapy if selected accord- failure secondary to restrictive thoracic diseases is well ac-
ing to commonly used criteria (see "Selection Guidelines," cepted (see "Chronic Respiratory Failure," above), it is used
below). for only a small portion of patients admitted to acute-care
hospitals with respiratory failure. Accordingly, few stud ies
CYSTIC FIBROSIS on the management of acute respiratory failure in these pa-
NPPV has been used to treat acutely deteriorating patients tients have been reported. In the large trial that treated all
with end-stage cystic fibrosis (CF). In one study, six patients eligible patients admitted to an ICU over a 2-year period,
with FEV1 ranging from 350-800 rn1 and severe acute-on- only 5 of 158 patients had restrictive lung disease.65 Small
uncontrolled series have reported success using NPPV to al- 9 versus 15 d ays, respectively) compared w ith intubated
leviate gas-exchange abnormalities and to avoid intubation controls. Another randomized , controlled trial o f 61 patien ts
in pa tients with acu te respiratory failure secondary to neu- with various fonns o f acute respiratory failure found a sig-
romuscular disease77 and kyphoscoliosis ? 8 Despite the lack nificantly reduced intubation rate when patients with acute
of evidence, the British Thoracic Society Standards of Care hy poxemic respira tory failure were treated with NPPV as
Committee considers that NPPV " is indicated" in patien ts opposed to conventional therapy (7.5 versus 22.6 intuba-
·w ith acute or acute-on-chr onic respiratory failure secondary tions per 100 ICU d ays); mortality rates, however, were n ot
to restrictive thoracic d iseases.62 significantly different. 85
A regimen for managing acu te d eteriorations in patien ts More recently, Ferrer et al86 rand om ized patients with
witl1 cluonic respiratory failure secondary to neuromuscu- severe hy poxemia (defined as a Pao, of less than 60 mmHg
lar disease, reported by Bach et al,79 requires that patients or an Sa02 of less than 90% on 50% F10 , for a t least 6-8 hours)
receive NIV at h ome 24 hours a day during the exacerbation . to receive NPPV o r conventional therapy. Intubation rate
When 0 2 saturation falls below 90% as d etermined b y con- was decreased from 52- 25%, the incidence o f septic shock
tinuous pulse ox imetry, airway secretions are removed ag- was reduced, and both ICU (39% versus 18%) and 90-d ay
gressively using manually assisted coughing a nd mechan- mortality were lower in the NPPV group compared with
ical aids such as the cough insufflator-exsuiflator un til 0 2 con trols. In contrast to some previous studies, substa ntial
saturation returns to the 90% ran ge. In this small series of benefit was observed in patients with severe pneu monia,
patients, the need for hospitalization was reduced dramat- whereas patients with cardiogenic pulmonary edema had
ically after institution of the regimen. 79 no reduction in intubation rate.
Limited infor mation is available on NPPV therapy fo r The fa vorable resu lts of these latter studies mig ht be in-
patients with acutely d eteriorating restrictive lung dis- terpreted to show broad support for the use of NPPV in
eases such as interstitial fibrosis. Such patients far e poorly patients with hyp oxemic respiratory failure. A system atic
wiili mechanical ventila tion.80 It is d iscouraged unless review, however, n oted that althoug h intubations in pa-
an acutely reversible superimposed condition is thought tients with acute hypoxemic respiratory failure seem to be
to be responsible for the deterioration, or the pa tient or reduced by NPPV, the heter ogeneity between studies pre-
family desires temporizing therap y, perhaps to finalize cluded any finn conclus ions and recommended against the
affairs. routine use of NPPV in these patients.87 Also, when overall
results are favorable in a heterogeneous group of patients,
HYPOXEMIC RESPIRATORY FAILURE it caru1ot be assumed that each subg roup benefits equally.
Hypoxemic respiratory failure is d efined as a Pao, /Fie, It is possible that harm to a particular subgroup could be
ra tio of less than 200 and a respira tory rate greater than obscured b y benefit in other subgro ups . The following sub-
35 breaths per minute, and diag noses include acute pneu- sections examine evidence regarding the use of NPPV in
monia, acute pulmonary edema, acute respira tory d istress specific su bgroups of patients with acute hypoxemic res-
syndrome (ARDS), and tra uma.81 It is an extremely broad piratory failure that may be more appropriate to apply to
ca tegory of acute respiratory failure . Hence, perhaps n ot individual patients .
surprisingly, studies of NPPV to treat it have yield ed con-
flicting results. Meduri et al 82 were the first to report the suc- Acute Cardiogenic Pulmonary Edema
cessful application of NPPV in such patients. Subsequently, Continuous positive airway pressure (CPAP), a lthough n ot
Wysocki et al83 found that h ypercapnia was a strong predic- a form of mechanical ventila tory assistance per se, was d e-
tor of NP PV success in patients w ith hypoxemic respiratory scribed as a treatment for acute pulmonary edema d ating
failure: seven of nine patients with an initial Pac02 of greater back to the 1930s.88 Over the past 15 years, a number of
than 45 mmHg hav ing been treated successfully and seven studies have d emonstrated that CPAP (10-12.5 cmH20 ) is
of eight patients with a Paco2 of less than 45 mmHg having effective in treating acute pulmonar y edema. Rasanen e t a l89
failed . In a later randomized trial, 84 the same authors found randomized 40 patients with card iogenic pulmonary edema
no benefit of NPPV over con vention al therapy among all to either face-mask CPAP or standard medical therapy and
entered patien ts. Once again, initial h ypercapnia predicted d emonstrated that CPAP m ore rapidly improves oxygena-
a fa vorable outcome: Patients with an initial Pace, of greater tion and respiratory rate. In a study on 55 patients with pul-
than 45 mmHg had significantly lower intubation a nd fCU monary edema, Lin and Cha ng 90 found that those random-
mortality rates and shorter TCU lengths of stay than n or- ized to fa ce-mask CPAP (adjusted to maintain a Pao2 of 80
mocapnic patients. The authors concluded tha t hypoxemic mmHg or greater) had a lower intubation ra te (17 .5% versus.
respira tory failure without C02 reten tion resp onds poorly 42.5%, p < .OS) tl1an conven tionally treated controls. Bersten
to NPPV. et al91 a nd Lin et al92 subsequently per formed randomized
Conversely, Antonelli et al 81 randomized 64 patients w ith studies on 39 and 100 patients, respectively, d emonstrating
hy poxemic respirato ry failure to NPPV or immediate intu- more rapid improvements in respiratory rates and oxygena-
bation. Improvements in oxygenation were similar in the tion and a reduced need for intubation in patients treated
two groups, and only 31% of the NPPV-treated patients re- with CPAP. The study of Bersten et a191 also showed a sig-
quired intubation. NPPV-treated patients had significantly nificant reduction in the len gth of ICU stay among CPAP-
fewer sep tic complications such as pnemnonia or sinusitis treated pa tients, and the study of Lin et al94 showed a trend
(3% vers us 31 %), and there were trends toward d ecreased for a lower hospital mortality rate. The average reduction in
mortality and ICU length of stay (27% versus 45% and intubation rate a mong these studies was 28% (from 47% in
controls to 19% for CPAP). These studies provide strong ev- The question of whether NPPV (the combination of pres-
idence to support the use of CPAP to treat acute cardiogenic sure support and PEEP) is superior to CPAP alone is impor-
edema. tant because CPAP can be delivered more simply and less
As discussed earlier, the combination of increased in- expensively. An earlier randomized trial comparing the two
spiratory pressure and positive expiratory pressure (i.e., to treat acute pulmonary edema showed significantly more
pressure support plus PEEP or NPPV) might be expected rapid reductions in respiratory rate, dyspnea scores, and
to reduce work of breathing more effectively than CPAP hypercapnia in the NPPV group compared with the CPAP-
alone, bringing about more rapid relief of dyspnea and treated group. 99 The study was stopped prematurely after
improvement in gas exchange. Thus more recent studies enrollment of27 patients, however, because of a greater my-
have focused on the use of NPPV to treat acute cardiogenic ocardial infarction rate in the NPPV group (71% versus 31%
pulmonary edema. One prospective, uncontrolled study in controls). This difference may have been attributable to
found that face-mask PSV improved pulse oximetry, pH, unequal randomization because more patients in the NPPV
and Pac0z within 30 minutes in 29 patients with acute pul- group presented with chest pain. The results nonetheless
monary edema, only one of whom required intubation.93 raise concerns about the safety of ventilator techniques used
A second prospective, uncontrolled study94 reported sim- to treat acute pulmonary edema.
ilar effects on gas exchange, but 5 of 26 patients required More recent randomized, controlled trials comparing
intubation, and successfully treated patients had higher NPPV with CPAP have not detected similar differences in
Paco, (54 versus 32 nunHg) and lower creatine phospho- the myocardial infarction rate. Crane et al100 randomized
kinase levels (176 versus 1282 IU) (both p < .05) than 60 patients with cardiogenic pulmonary edema to three dif-
failure. Further, four patients died in the first study and ferent therapies: conventional, CPAP (10 cmH20), or bilevel
five in the second, three and four with myocardial infarc- ventilation (15 cmH2 0 inspiratory and 5 cmH 2 0 expiratory
tions, respectively. The authors concluded that NPPV is a pressures). Treatment success was 15% in the control group,
"highly effective technique."The accompanying editorialist, 35% in the CPAP group, and 45% in tl1e bilevel group (p =
however, cautioned about applying NPPV to patients witl1 .116). Altl1ough myocardial infarction rate did not differ
acute m yocardial infarctions.95 among the groups, hospital mortality was 30% in the control
Several randomized, controlled trials have been per- group, 0% in the CPAP group, and 25% in the bilevel gro up
formed subsequently comparing NPPV with conventional (p = .029). The difference in mortality was not statistically
0 2 therapy to treat patients with acute cardiogenic pul- significant until after the first week of hospitalization, af-
monary edema. Masip et a196 found that inspiratory and ter patients had stopped using the devices. Two additional
expiratory pressures of 15 and 5 cmH20, respectively, low- studies that ra11domized 46 patients with acute cardiogenic
ered the intubation rate from33% in 18controls to 5% among pulmonary edema to CPAP or noninvasive PSV plus PEEP
22 patients randomized to NPPV (p = .037). NPPV also im- found similar myocardial infarction rates. 101 •102 Physiologic
proved oxygenation more rapidly, but hospital lengths of variables improved equally in both groups, intubation and
stay and morta lity rates were similar in the two groups. mortality rates were similar, a nd troponin I levels and the
Sharon et ai 97 randomized 40 patients to receive NPPV speed of clinical resolution were nearlyidentical.ln addition
plus low- or high-dose nitroglycerin. The NPPV group had to finding no increase in the myocardial infarction rate in
higher ra tes of intubation (80% versus 20%), myocardial in- NIV-treated patients, these latter studies also found no dear
farction (55% versus 10%), and death (10% versus none) advantage of NIV over CPAP alone. These findings must be
compared with the nitroglycerin controls (all p < .05), lead- interpreted with caution, however, because patients w ith
ing the authors to conclude that NPPV was less effective myocardial infarction or acute ischemia were excluded.
and potentiaLly harmful compared with high-dose nitro- Deciding which patients with acute cardiogenic pul-
glycerin. This inference, however, is suspect because the monary edema should receive NPPV can be challenging
treatments were not comparable, and the inordinately high because they may respond rapidly to conventional therapy.
intubation rate in the NPPV group (80%) is difficult to ex- Using their single-center registry, Mas ip et al103 obtained
plain. In tl1e largest study to date, Nava et al98 random- data on 80 conventionally treated patients with cardiogenic
ized 130 patients with acute pulmonary edema to receive pulmonary edema to identify those at risk for intubation.
NPPV (average 14.5 cmH2 0 of pressure support and 6.1 em Patients with a pH of less than 7.25 or hypercapnia and a
H20 of PEEP) or 0 2 therapy; hypercapnic and normocap- systolic blood pressure of less than 180 mmHg were found
nic patients were prospectively distributed equally between to be at high risk. The authors recommended that such pa-
groups. As in the earlier studies, NPPV improved oxygena- tients should be "promptly considered" for NIV. Because
tion, respiratory rate, and dyspnea more rapidly than con- studies have not shown definitively that NIV is more effec-
ventional therapy, but mortality and hospital lengths of s tay tive than CPAP, however, the most sensible current recom-
did not differ between the groups. Overall, the rates of in- mendation is to use CPAP (10 cmH2 0) initially and consider
tubation were not significantly different (25% in controls switching to NPPV if the patient has unrelenting dyspnea
versus 20% for NPPV); in the hypercapnic subgroup, how- or persisting tachypnea o r hypercapnia. Furthermore, ei-
ever, the intubation rate was lower in the NPPV group than ther CPAP or NPPV should be used w ith great caution, if
in controls (6% versus 29%, p = .015). These studies suggest at all, in patients with acute myocardial infarction or active
that NPPV is effective therapy for acute pulmonary edema, ischemia. These recommendations are in line w ith the con-
but whether this is true only for hypercapnic patients awaits clusion of a meta-analysis by Pang e t a1,1 04 as well as the
further evaluation. consensus of the British Thoracic Society Standards of Care
442 PART VI NONlNVASTVE METHODS OF VENTILATOR SUPPORT
Committee, which recommended that NPPV be reserved NPPV with acute respiratory fail ure complicating hema-
for CPAP failures. 62 tologic malignancies, although patients were excluded if
they had more than two organ-system failures or were re-
Pneumonia sponding poorlh to antineoplastic therapy. More recently,
An earlier retrospective stud y found that acute severe Antonelli et a1 1 2 randomized 40 patients with acute res-
pneumonia is a predictor of NIV failure, perhaps because piratory failure of various etiologies following solid-organ
NPPV does little to facilitate the clearance of secretions. 105 transplantation to receive NPPV or standard therapy. NPPV
Confalonieri et al 106 randomized 56 patients with severe reduced the need for intubation and lowered lCU mortal-
community-acquired pneumonia to receive NPPV or stan- ity rate (both 20% versus 50% in controls, p < .05), but total
dard 0 2 therapy. The NPPV g roup had fewer intubations hospital mortality was similar. Trends for fewer health care-
(21 % versus 50%) and shorter JCU lengths of stay (1 .8 versus associated pneumonias and episodes of severe sepsis also
6 days) than controls (both p < .05). In addition, NPPV- were apparent among NPPV-treated patients. In a subse-
treated patients with COPD had significantly better sur- quent study of 52 immunocompromised patients with res-
vival at 2 montlts, thought to be related to fewer late com- piratory failure, 58% with hematologic malignancies, ran-
plications of intubation. The most important observation, domized to receive NPPV for at least 2 hours three times
though, was that all the benefit was attributable to the daily or s tandard 0 2 therapy, those treated with NPPV had
subgroup with COPD, and no clear benefit of NPPV was fewer intubations (46% versus 77%) and mortalities (50%
seen in patients without COPD patients. More recently, a versus 81%, both p < .05).113
prospective s tudy on NPPV to treat patients w ith severe The sizable reductions in mortality among these high-risk
community-acquired pneumo nia but without COPD found patients strongly supports the use of Nrv as the ventila-
that oxygenation and respiratory rates improved initially tory modality of first choice in selected imunocompromised
in 22 of 24 patients after starting NPPV, but 66% eventually patients with acute respiratory failure. Patients developing
required intubation. 107 Based on the preceding evidence, respiratory insufficiency should be started on NPPV rela-
initiation of NPPV is justifiable in appropriate patients with tively early, 105 before progression to severe respiratory fail-
pneumonia and COPD. The benefit of NPPV in patients with ure, watd1ed closely, and intubated without delay if needed.
pneumonia but without COPD has not been established. As
such, NPPV should be used selectively and with caution in Acute Respiratory Distress Syndrome (ARDS)
su ch patients. No controlled trials have been reported on the efficacy of
The severe acute respiratory syndrome (SARS) epidemic NPPV to treat ARDS. One cohort series reported that NPPV
was characterized by a hig h rate of respiratory failure maintained adequate oxygenation and averted intubation in
among afflicted individuals, many of whom were other- 6 of 12 episodes of ARDS in 10 patients. 114 Thus, although
wise healthy health care workers. Jnitially, use ofNPPV was NPPV can be tried in pa tients with early, relatively mild
discouraged because of concerns about aerosolization and ARDS in an attempt to avoid intubation, routine use is not
transmission of the highly contagious coronavirus to other ad vised. NPPV should be avoided in patients with multiple
health care workers. Two retrospective studies, however, organ-system failure and very severe oxygenation defects
one from Beijing on 28 patients treated with NPPV 108 and who are likely to require prolonged ventilatory support us-
the o ther from Hong Ko ng o n 20 patients, 109 suggest that ing sophisticated ventilator modes. If a trial of NPPV is ini-
NPPV is effective in avoiding intubation in some patients . tiated, patients sho uld be monitored closely and intubated
Intubatio n was requ ired in only 33% and 30% of NPPV- without undue delay if they deteriorate or even fail to im-
treated patients in the two studies, respectively. Stringent prove sufficiently.
infection-control measures, including the use of a face mask,
an in-line viral/ bacterial filter in the bilevel ventilator tub- Trauma
ing, and a hig h-efficiency particulate accumulator mask by Traumatic chest-wall injuries such as flail chest or mild acute
all health care workers having contact w ith the patients, pre- lung injury might respond favorably to NPPV, but other eti-
vented transm ission of SARS to any caregivers. Both studies ologies mig ht not. In a retrospective survey o n 46 trauma
reported high rates of barotraumas, 22% and 20%, respec- patients with respiratory insufficiency treated with NPPV,
tively; it was unclear that this was rela ted to NPPV. Given Beltrame et ai 115 found rapid improvements in gas exchange
the lack of controls, these studies cannot be used to assess and a 72% success rate, but bum patients responded poorly.
the efficacy of NPPV in SARS, although the lack of transmis- Despite these promising initial results, the lack of controlled
sion to health care workers should allay fears about NPPV studies limits the ability to draw conclusions or make rec-
spreading the virus so long as stringent isolation and pre- ommendations on the use of NPPV in trauma patients.
vention measures are employed .
Immunocompromised Patients Noninvasive Positive-Pressure Ventilation
The use of NPPV to avoid endotracheal intubation in im-
munocompromised patien ts is appealing because, by as- for Categories of Patients with
sisting ventilation without having to invade the airway, it Acute Respiratory Failure
reduces infectious and hemorrhagic complications. Encour-
aging results derived from an uncontrolled series that re-
D O-NOT-INTUBATE PATI ENTS
ported NPPV success rates as high as 67% (in 48 patients
with AIDS a nd Pneumocystis cnri11ii pneumonia) 11 Conti° One could argue that there is little to lose by using NPPV
et aJ1 11 avoided intubation in 15 of 16 patients treated with in almost any tenninal patient. NPPV could be used to
lessen dyspnea, preserve patient autonomy, and permit ver- surgery125 and better than 0 2 therapy alone in improv-
bal communication with loved ones during a terminal pa- ing oxygenation after lung-resection surgery. 126 NPPV also
tient's final hours.116 Some patients might be salvaged in ameliorated postgastroplasty pulmonary dysfunction in
the near term who otherwise would die without ventilatory morbidly obese patients.127 More recently, a randomized
assistance. This application is controversial, however, with trial of NPPV in 48 post-lung-resection patients with acute
some arguing that it merely could prolong the dying pro- respiratory insufficiency, most with COPD, showed signif-
cess, diminish patients' comfort in their waning hours, and icant improvements in oxygenation and reductions in the
promote excessive resource utilization.n 7 need for intubation (21% versus 50%) and mortality rate
Among reports on NPPV to treat patients who have de- (13% versus 38%) compared with conventionally treated
clined or are reluctant to undergo intubation, Benhamou controls (both p < .05). 128 Thus, accumulating evidence now
et al118 retrospectively studied 30 such patients, mostly el- supports the use of NPPV in selected postoperative patients
derly men (mean age 76 years) with COPD. Despite severe to maintain improved gas exchange and avoid reintubation
respiratory failure (mean Pa02 of 43 mmHg and Pac~ of and its attendant complications.
75 mmHg), NPPV was successful initially in 60% of pa-
tients. The authors considered NPPV to be preferable to
endotracheal intubation because short-term prognosis was FAOLITATION OF WEANING AND EXTUBATION
better, and the modality appeared to be more comfortable FACILITATION OF WEANING
with fewer complications. Jn another uncontrolled series, Udwadia et af129 first reported ilie use of NPPV to facilitate
Meduri et al119 observed a similar response to NPPV among weaning from mechanical ventilation in tracheostomized
26 patients with acute hypercapnic and hypoxemic res- difficult-to-wean patients. Restrick et a1 130 found that NPPV
piratory failure who refused intubation. In their random- was successful in weaning 13 of 14 difficult-to-wean pa-
ized, controlled trial in patients with acute exacerbations tients, expanding this experience to patients with transla-
of COPD, Bott et al48 used invasive mechanical ventilation ryngeal tubes. Munshi et al131 found that 451 hypoxemic
in only one of the nine control patients who died. Thus postextubation trauma patients could be treated withNPPV
the survival advantage they observed among NPPV-treated rather than 0 2, saving an estimated $50,000, although the
patients was, in effect, in comparison with do-not-intubate cost calculation did not allow for therapist, nurse, or physi-
patients. cian time attributable to the administration of NPPV.
In a prospective survey of 113 do-not-intubate patients These reports St1ggested that NPPV could be used to
treated witll NIV,120 amounting to 10%of all patients treated shorten tl1e duration of invasive ventilation, thus reducing
with NPPV, survival to hospital discharge was 72% and 52% the occurrence of associated complications. Nava et af132
for patients with acute pulmonary edema and COPD, re- tested this hypothesis in a randomized, controlled trial of
spectively, whereas it was less than 25% for patients with 50 patients intubated for acute respiratory failure secondary
pneumonia or cancer. In addition, ilie absence of an effective to COPD. If they failed a T-piece weaning tria l performed
cough and the inability to be awakened were significantly 48 hours after intubation, patients were randomized to extu-
associated with hospital mortality. Thus the use of NTV may bation followed by face-mask PSV or continued intubation
be justifiable in do-not-intubate patients who have a high and routine weaning. The NPPV patients had higher overall
likelihood of surviving the hospitalization. Longer-tenn sur- weaning rates (88% versus 68%), shorter durations of me-
vival of these hospital survivors, however, is poor; Chu chanical ventilation (10.2 versus 16.6 days), briefer stays in
et al121 found a 30% 1-year survival for do-not-intubate pa- the ICU (15.1 versus 24 days), and improved 60-da y survival
tients with COPD as compared with 65% for patients desir- rates (92% versus 72%) (NPPV-treated versus controls, all
ing intubation. Also, no studies have yet assessed effects on p < 0.05). In addition, no NPPV-treated patients had noso-
patient comfort or family satisfaction. Nonetheless, NPPV comial pneumonia compar ed with 7 pneun1onias among
may offer significant benefits such as the ability to finalize the controls. Jn a similar trial, Girault et al133 randomized
affairs or alleviation of dyspnea even in patients who do 33 patients with acute-on-chronic respiratory failure to re-
not survive the hospitalization. If NJV is to be used for s ucl1 main intubated or to be extubated to NPPV after failure of
patients, patients and/ or their families should be informed a 2-hour T-piece trial. The NPPV group had a shorter du-
that it is being used as a form of life support that may be ration of endotracheal intubation (4.6 versus 7.7 days, p =
uncomfortable and can be removed at any time. .004), but the total duration of mechanical ventilation was
longer in the NPPV group, and weaning and mortality rates
and ICU and hospitallengtl1s of stay were similar between
POSTOPERATIVE PATIENTS
the groups.
Several early case series on the use of NPPV to treat res- More recently, Ferrer et al134 randomized 43 patients with
piratory insufficiency in postoperative patients with Paco2 "persistent" weaning failure (three consecutive failed T-
values of greater than 50 mmHg, Pa~ values of less than piece trials) to be extubated to NIV or to remain intubated
60 mmHg, or evidence of respiratory muscle fatigue re- and be weaned using conventional methods. Patients ran-
ported prompt reductions in respiratory rate and dyspnea domized to NJV had shorter periods of intubation (9.5 ver-
scores, improvement in gas exchange, a11d high success rates sus 20.1 days), shorter ICU (14 versus 25 days) and hospital
(roughly 75%) in avoiding the need for reintubation.122- l24 stays (14.6 versus 40.8 days), a lower rate of nosocomial
Subsequent studies found that NPPV was more effective pneumonia (24% versus 59%), and improved ICU and 90-
than CPAP or chest physiotherapy in improving lung day survivals (roughly 80% versus 50%, all p < .05). This
mechanics and oxygenation after coronary artery bypass study lends s trong support to the use of NJV to facilitate
extubation, but it is worth noting that two-thirds of the pa- evidence to support the routine use of NPPV to avoid ex-
tients had COPD or congestive heart failure. In a prelimi- tubation failure is lacking. Conversely, this approach still
nary study examining the use of NPPV as a routine measure holds promise in patients w ith COPD and in those at high
to facilitate weaning in selected patients failing T-piece tri- risk of extubation failure, although further s tudies examin-
als, the extubation failure rate was significantly greater than ing these subgroups are needed.
in the conventionally weaned group (41 % versus none).m Another approach to treating extubation failure is to
Thus, overall, the evidence is strong to support the use of await the development of overt respiratory failure before
NPPV to facilitate weaning a nd extubation in difficult-to- initia ting NPPV. Hilbert et al140 found that NPPV used in
wean pa tients with COPD. The following caveats, however, this fashion lowered reintubation ra te (20% versus 67%) and
should be borne in mind: (1) This approach should be re- shortened ICU lengths of stay in30 patients with COPD and
served mainly for COPD patients, (2) patients should be se- postextubation hypercapnic respiratory insufficiency com-
lected carefully, ascertaining that they are good candidates pared with 30 historically matched controls. Keenan et al'141
for NPPV (see "Selection Guidelines," below), (3) patients randomized 81 patients to receive NPPV or conven-
should not have been difficult intubations, and (4) patients tional therapy if they developed respiratory failure within
should be comfortable on levels of PSV tha t can used via 48 hours of extubation. The reintubation rate in this trial
mask after extubation. was roughly 70% in both the NPPV group and controls,
and no significant differences were found in hospital length
NONINVASIVE POSITIVE-PRESSURE VENTILATION of stay or survivaL Patients with COPD, however, were ex-
TO TREAT EXTUBATION FAILURE cluded after the first year for ethical reasons, and only 12%
Another potential application of NPPV in the weaning proof the patients had COPD. Furthermore, the pressures used
cess is to avoid reintubation in patients who fail extubation. (10 cmH 2 0 inspiratory and 5 cmH2 0 expiratory) may have
Epstein et al136 reported that extuba tion failure is associ- been insufficient to provide adequate ventilatory assistance.
ated with much higher morbidity and mortality rates (43%) Thus, once again, firm evidence is lacking to guide the use
than successful extubations (approximately 10%). Some in- of NPPV in patients with overt extubation failme, but pa-
vestigators have used NPPV prophylacticall¥ to see if ex- tients with COPD appear to be helped, and a trial seems
tubation failure can be avoided. Jiang at al13 randomized reasonable in patients with other diagnoses that are likely
consecutive extubated patients to receive NPPV or conven- to be reversible, such as congestive heart failure or glottic
tional therapy a nd found a trend for a higher reintubation edema.
rate in the NPPV group (28% versus 15%), suggesting that
indiscriminate use o f NPPV is not effective for preventing PEDIATRIC APPLICATIONS
extubation failure. Other investigators have attempted to Fewer reports of pediatric than adult applications ofNPPV
prevent extubation failure by initiating NPPV when patients for acute respiratory failure have appeared. A 1993 case se-
develop risk factors for extubation failure. Esteban et af138 ries of acute pediatric applications of NPPV by Akingbola
tried this approach in a multicenter, multinational random- et al 142 reported the successful use of nasal ventilation in two
ized trial of 221 patients d eveloping risk factors for respi- 12-year-o ld boys with atelectasis and pulmonary edema. In
ratory failure within 48 hours after they were extubated, a retrospective series of 28 pediatric pa tients with hypox-
including hypercapnia, tachypnea, or hy poxemia. Reintu- emic respiratory failure ranging in age from 4 months to
bation rates (48%) and ICU lengths of stay (18 days) were 16 years, Fortenberry et al143 found that respiratory rate,
identical in both groups, and the study was terminated pre- Pac(h, and oxygenation improved promptly after initiation
maturely because of a significantly increased ICU mortality of nasal bilevel NPPV, and only 3 patients required intuba-
in the NIV grou p (25% versus 15%, p = .048). The mor- tion. Padman et al 144 subsequently reported similar results
tality difference was attributable to a higher mortality in in a prospective series of 34 pediatric patients with both
the reintubated NIV patients, reintubation occurring almost hy poxemic and hypoventilatory respiratory insufficiency,
10 hours later than in the standard-therapy group. The au- again witl1 only 3 patients requiring intubation.
thors concluded that NIV is not effective in unselected pa- Favorable responses to NPPV in older cl1ildren are not
tients at risk for extubation failure and speculated that the surprising, particularly when they are suffering from condi-
greater delay in reintubation was responsible for the higher tions reported to be treated successfully by NPPV in adults .
mortality rate. It is worth noting, however, that 28 patients Concerns have been raised, however, about treating very
in U1e control group crossed over to NPPV when U1ey met yotmg children and infants w ith NPPV because of increased
failure criteria. Thus U1e controls likely would have had a nasal resistance145 and inability to cooperate. 146 In a series
substantially higher reintubation rate if not crossed over to reported by Fortenberry et al143 of 28 patients, NPPV was
NPPV. The overall results are not really relevant to patients successful in avoiding intubation in the 10 children younger
with COPD, which comprised only 10% of the enrollees than 5 years of age. More recently, a retrospective trial ob-
and had a trend toward lower reintubation rates than in ser ved successful application of NPPV in infants following
controls. In a preliminary report, Nava et a1'139 used NPPV liver transplantation.147 In a randomized, prospective trial
prophylactically in patients deemed to be at "high risk" for on infants (median age 9.5 months) with various causes of
respira to ry failure by virtue of their having failed at least upper airway obstruction, CPAP and BiPAP proved to be
one weaning trial after more than 72 hours of intubation. equally efficacious in reducing respira tory rate and breath-
These authors demonstrated significant reductions in rein- ing effort; both were well tolera ted, although BiPAP was
tubation rate, ICU mortality, and hospital length of stay. The associated with more asynchrony.148 The lack of controlled
conflicting resuJts render any firm conclusions difficult, but trials makes it difficult to formulate selection guidelines for
CHAPTER 19 NONJNVASIVE POSITIVE-PRESSURE VENTILATION 445
NPPV in children, although reported success rates appear two of NPPV initiation..105, 153- 156 Confalonieri et a1155 have
to be comparable with those in adults, and tentative guide- incorporated some of these predictors (APACHE II score ~
lines have been proposed 149 that are based on those used 29, pH < 7.25, Glasgow coma score !S 11, and respiratory
for adults. rate ~ 35 breaths per minute) into two risk charts for NPPV
failure, one to be used at baseline and the other at 2 hours
(Fig. 19-3). If these abnormalities were all present at base-
Patients Undergoing line, the likelihood of failure was 82% and rose to 99% if
they persisted at 2 hours.
Bronchoscopy Ttming of initia tion is another determinant of success.
Ambrosino et al105 advised that NPPV "should be instituted
NPPVadministered via T connector attached to a face mask
early in every patient before a severe acidosis ensues." Ini-
can be used to assist ventilation and enhance oxygena-
tia tion of NPPV should be viewed as taking advantage of a
tion during fiberoptic bronchoscopy in high-risk patients. "window of oppor tunity." The window opens w hen acute
First reported to improve oxygenation and be well toler- respiratory distress occurs and shuts when the patient dete-
ated in a small series of immunocompromised hypoxemic riorates to the point of necessitating immediate intubation.
patients, NPPV was shown subse<.1uently to improve and In this context, it should be emphasized that NPPV is used
sustain oxygenation better than conventional Oz supple-
as a way of preventing intubation, not replacing it.
menta tion in a randomized, prospective tria l in 26 patients
with Pao 2 / FIOt ratios of 200 or less and suspected noso-
comial pneumon.ia.150 More recently, NPPV to assist ven- SELECflON GUIDELINES
tilation during fiberoptic bronchoscopy was administered
The preceding predictors of success and failure and the en-
successfully using a "helmet" device (see techniques section
try criteria used for enrollment of patients into the many
below). 151 NPPV also has been used to assist ventilation dur-
studies have served as a basis for consensus g uidelines on
ing upper endoscopy for gastric tube placement in patients
the selection of patients to receive NPPV for acute respi-
with neuromuscular disease.152
ratory failure.157 These guidelines use a simple two-step
approach outlined in Table 19-3. The first step identifies
patients a t risk of needing intubation. Patients w ith mild res-
Selection of Patients for Noninvasive piratory distress are excluded from consideration because
Positive-Pressure Ventilation they should do well w ithout ventila tor assistance. Those
needing ventilator assistance are identified using clinical
in the Acute Setting indicators of acute respiratory distress and gas-exchange
derangement, as listed in Table 19-3. These criteria are most
DETERMINANTS O F SUCCESS applicable to patients with COPD but can be used to screen
Retrospective105, 153 and prospective154- 156 s tudies have those with other forms of expiratory failure, although some
identified predictors of NPPV success (Table 19-2). Patients modifications are advisable. For example, studies on NPPV
with baseline hypercapnia fare better than those with hy- in acute pulmonary edema and acute hypoxemic respira-
poxemia alone, but successful patients have lower baseline tory failure have used higher respiratory rates as enrollment
Paco2 values (79 versus 98 mmHg) and higher pH values criteria (> 30-35 instead of > 24 breaths per minute) and a
(7.28 versus 7.22) than failure patients. 105 Pneumonia pre- Pa0t/Fi02 ratio of less than 200.96- 99
disposes to failure whether alone or in combination with The second step is to screen out patients in whom use
COPD (odds ratio 5.63 for COPD).154, 156 The s trongest pre- of NPPV is contraindicated (see Table 19-3). Most are rela-
dictor of success, though, is prompt improvement in gas tive contraindications, and judgment should be exercised in
exchange and heart and respiratory rates within an hour or implementing them. Also, some conditions that have been
listed as contraindications in the past no longer preclude
the use of NPPV. For example, patients with coma, if re-
lated to hypercapnia, may be managed successfully with
TABLE 19-2 Predictors of Success during Acute Applications NPPV. Diaz et aJ1 58 demonstrated that patients (mainly w ith
of NPPV COPD) w ith hypercapnic coma (Glasgow coma scores !S 8)
Ymmger age had outcomes just as good as those with higher Glasgow
L.ower activity of illness (APACHE score) coma scores. In another report,118 nearly ha lf the patients
Able to cooperate, better neurologic score were obtunded or somnolent initially, yet most were man-
Able to coordinate breathing with ventilator aged successfully with NPPV.
Less air lea king, intact dentition The underlying etiology and potential reversibility of
Tachypnea, bu t not excessively rapid (>24 but acute respiratory failure are also important considerations
<35 breaths per minute) in patient selection. As discussed previously, the strongest
Hypercarbia, but not too severe (Paco 2 > 45 but < 92 mmHg) evidence supports the use of NPPV for COPD and either
Acidemia, but not too severe (pH < 7.35 but> 7.10) NPPV or CPAP for acute cardiogenic pulmonary edema.
lmprovements in gas exchange, heart and respiratory rates within
As illustrated in Fig. 19-4, a reversible etiology pennits the
first 2 hoursa
use of NPPV as a "crutch" that assists the patient through
" Most powerfu l predictor a critical interval, allowing time for other therapies such
souRcE: Adapted, w ith perm ission , from refs. 106, 154, a nd 156. as bronchodilators, steroids, or diuretics to reverse the
wall deformity), muscle w eakness (as with neuromuscular TABLE 19-4 Restrictive Thoracic Dis eases Treated with
diseases), or both. Experience gained during the polio epi- Noninvas ive Ventilation
demics of the 1930s through 1950s and subsequently w ith Recommended for the following diagnoses:
other neuromuscular disorders demonstra ted that "body Chest wall deformity
ventilators/' even when used intermittently, were effective Kyphoscoliosis
at stabilizing or even reversing chronic res~iratory failure Post thoracoplasty for tuberculosis
secondary to restrictive thoracic disorders. 1 9•160 Although Slowly progressive neuromuscu lar disorders
NPPV had been available for the thera py of restrictive tho- Postpolio syndrome
racic diseases for decades,161 its use beyond a few centers High spinal cord injury
with special expertise was quite limited until the la te 1980s. Spinal muscular atrophy
Mo uthpieces or full-face masks des igned mainly for admin- Slowly p rogressive muscular dystrophjes
istration of anesthesia were the only interfaces a vailable, Duchenne muscular dystrophy
Umb-girdle muscular dystrophy
posing challenges for patient adaptation . Despite this, one
Myotonic dystrophy
center reported remarkable success with mouthpiece ven- Multiple sclerosis
tilation in a cohort of 257 patients with neuromuscular dis- Bilateral diaphragmatic paralysis
ease and chronic respiratory failure that was treated for an More rapidly progressive neuromuscula r disordersn
average of 9.6 years.162 Bulbar function was intact, includ- Amyotrophic lateral sclerosis
ing speech and swallowing, but the patients were other- Not recommended forb:
wise severely compromised. One-hundred and forty-four Rapidly p rogressive neuromuscular d isorders
of these pa tients required 2Q-24 hours of ventilator support Guillain-Barre synd rome
daily and had vita l capacities of only 10.5% of pre- Myasthenia gravis
dicted. Nonetheless, 67 were switched successfully from tra- • Tracheostomy ventilation should be considered in far-advanced cases.
cheostomies to NPPV, a nd only 38 died during the follow-up bUn less upper airway protective tnechanisms intact
interval of up to 37 years. Although the study was w'\con-
trolled, the authors concluded that mouthpiece NPPV pro-
longed survival and enhanced convenience and communi- ally occurring over a period of weeks, as pa tients increase
ca tion in these severely compromised patients. their hours of use, mainly at night. In addition, nasal NPPV
Despite this favorable experience, however, wider use has been s hown to a meliorate chronic hypoventila tion in pa-
of NPPV awaited further developments during the early tients with severe whoscoliosis w ho fail to improve w ith
1980s. One was the development of nasal CPAP for therapy nasal CPAP alone. 1 1
of obstructive sleep apnea tha t encouraged the creation of
more comfortable commercially a vailable nasal masks.163 EFFECTS ON NOCTURNAL GAS
Another was the suggestion by French inves tigators tha t EXCHANGE AND SLEEP
nasal ventilation could be used in patients with muscular Neuromuscular and chest-w all disorders cause protean
dystrophy to halt progression of the disease. 22 In 1987, sev- sleep-related breathing disturbances depending on the
er al small series an d case reports appeared describing suc- specific syn drom e and the involvement of respiratory
cessful managem ent with nocturna l nasal ventilatio n of pa- muscles.172 Abnormalities include obs tructive and cen-
tients with chronic respira tory failure secondary to a variety tral sleep apneas, intermittent desa turations, particularly
of restrictive thoracic disorders.164 - 166 Subsequently, addi- during REM sleep in patients with diaphragma tic weak-
tional small series have confirmed the earlier findings, but ness, and sustained hypoventilation as global weakness
no prospective, randomized series have been performed, and/ or chest-wall restriction ad vances. These a bnormali-
mainly for ethical reasons. Despite this, NPPV has gained ties often lead to sleep disruption, characterized by dimin-
wide acceptance as the modality of first choice to trea t pa- ished s leep duration, fragmentation rela ted to arousals, and
tients with chronic respiratory failure.157 Because most se- poor sleep quality secondary to diminished slow-wave and
rieshave combined patients with different etiologies, the fol- REM sleep.
lowing w ill discuss evidence for benefits a ttributed to NPPV NPPV ameliorates nocturnal hypoventilation and has
for restrictive thoracic diseases in general, making reference been s hown to eliminate the intermittent obstructive apneas
to individual diagnoses as appropriate. Table 19-4 lists in- and severe 0 2 desaturations that occur during negative-
dividual diagnoses of neuromuscular diseases reported to pressure ventilation, particularly during REM sleep.172
benefit from NPPV. Although no randomized, prospective trials have been
performed, investigators have evalua ted efficacy using
EFFECTS ON SYMPTOMS AND temporary w ithdrawal of nocturnal nasal NPPV from
DAYfiME GAS EXCHANGE long-term users with restrictive thoracic diseases w hose
Numerous studies on the efficacy of NPPV in a wide gas excha nge had been improved by prior NPPV use.34,'173
variety of neuromuscular and chest-wall disorders have Temporary withdrawal of NPPV caused a deterioration of
shown tha t intermittent NPPV consistently improves symp- nocturnal oxygenatio n and ventila tion 34 (Fig. 19-5) and in-
toms of fa tigue, daytime hypersomnolence, and morning creased frequency of arousals.173 All changes were reversed
headache.32,t6?- t69 Daytime gas exchange also improves, promptly on resumption of NPPV. These findings indicate
Paco, dropping on average from 63 mmHg to 48 mmHg that NPPV is importa nt in preventing deteriora tion of noc-
and Pao, increasing from 54-71 mmHg among multiple turnal gas exchange tha t is thought to predispose to chronic
studies.1 The improvement in gas excha nge is gradual, usu- hypoventila tion and contribute to frequent arousals and
448 PART VI NONII\TVASIVE METHODS OF VENTILATOR SUPPORT
100
90
eo
0 2 SAT (%) FIGURE 19-5 Effect of w ithdrawal of nocturnal nasal
or ventilation (N NV) on mean an d nadir Oz saturations
70
Pre C02 an d mean transcutaneou s Pco2 levels obtained during
(torr) nocturn al moni toring. Valu es on the left labeled "on
60 NNV" were obtaine d during NNV usc on the night
before NNV withdrawal, values in the middle were
obtained on the last night of the NNV withdrawal
period, and values on the r ight labeled "on NNV"wcre
obtained a week after NNV was resumed. Data are
mean ± SE. Asterisk indicates p < .05 compared with
"on NNV"values (u = 6). (Used, w itll pen uission, from
ONNNV OFFNNV ONNNV Riel et a/: Am Rev Respis Dis 145:365-71, 1992.)
fragmented sleep. Stabilization of nocturnal gas exchange

and improved sleep quality are thought to be major reasons
for the improvement in symptoms associated with NPPV
use. Although sleep quality is improved compared to no FIGURE 19-6 Serial data for the Short Form-36 Mental
ventilator assistance, air leaking during NPPV, however, Component Summary (S F-36 MCS), Sleep Apnea Quality of Life
can contribu te to sleep fragmentation. 174 Index (SAQLI) symptoms domain, and ALS Functional Rating
Scale (ALSFRS) immediately before starting nonin vasive
ventilation (NlV) and after 1, 3, 5, and 7 months of NlV. The slight
EFFECTS ON QUALITY OF LIFE improvement in the ALSFRS score at 7 months is secondary to a
NPPV improves health-related quality of life in patients survivor effect. (Used, with pennissiotl, f rom Lyall eta/: NeuroloSIJ
with restrictive thoracic disorders.175· "76 The nature and du- 57:153-6, 2001.)
ration of improvement, however, depend on the natural
* ... ... ...
history of the underlying disorder. Among patients with 50
(/)
amyotrophic lateral sclerosis (ALS), the mental-component (.)
summary score 177 and the vitality score178 on the SF-(short ~ 45
form-36) questionnaire register sustained improvements. (!)
("'")
I 40
These improvements are seen even when the functional rat- LL.
ing declines (Fig. 19-6), but attrition rates a re high over time en
35
related to the high mortality of the underlying condition.179
More sustained benefits would be expected, of course, in 30
Pre 1 3 5 7
conditions with lower rates of progression. Likewise, mus- Months o n N IV
culoskeletal functional gains would not be expected unless
en NIV
the und erlying cond ition offers the potential for improve-
ment (i.e., no quadriplegia).
Some studies have compared quality of life during use
-E
0
c ..
E
>-
1/)
6
5
* * * *
...... 4
of NPPV w ith that d uring use of tracheostomy PPV among
patients with restrictive thoracic diseases. 180- l82 Both 0
<(
(/) 3
groups have high levels of satisfaction, but NPPV was
rated as p referable to ventilation via a tracheostomy 2
with regard to comfort, convenience, portability, and
Pre 1 3 5 7
overall acceptability. 180 Although tracheostomy ventilation NIV Months on N IV
received higher scores for quality of sleep and p roviding 25 * * * *
a sense of security, the vast majority of patients preferred
NPPV. Another survey of 35 ventilator users, with 29 NPPV 20
users and 6 with tracheostomy ven tilation, found satisfac-
tory levels of psychosocial function ing and mental well- 15
being, as determined by standard questionnaires.181 The
ratings compared favorably with those o f a general popula-
tion, and NPPV and tracheostomy ventilation received simi- 10 ~------------------------
Pre 1 3 5 7
lar scores. In another survey of home mechanical ventilation Months on NIV
users, patients with scoliosis receiving tracheostomy ven-
NIV
tilation had higher health-index ratings than those receiving * p <0 .05
NPPV.182 Thus NPPV offers many advantages over correspond closely with survival for most diagnoses. The
invasive mechanical ventilation, including comfort, porta- studies found very favorable continuation rates for postpo-
bility, cost, and convenience, but some ratings, including lio and kyphoscoliosis patients (approxin1ately 100% and
overall health and sense of security, may favor invasive 80%, respectively, after 5 years). Patients with sequelae
mechanical ventilation. of old tuberculosis had higher continuation rates in the
British compared with the French study (94% versus 60%,
EFFECT ON HOSPITAL UTILIZATION respectively), perhaps reflecting the greater morbidity of
In their long-term follow-up study of patients with the French patients at the time of enrollment. Also, patients
kyphoscoliosis, sequelae of tuberculosis, and Duchenne with Duchenne muscular dystrophy (DMD) in the French
muscular dystrophy, Leger et al183 observed significant re- study had lower continuation rates (47%) than those with
ductions in hospital days per patient per year from 34, 31, other neuromuscular diseases, with 28% u ndergoing tra-
and 18 days for the year before starting NPPV to 6, 10, and cheostomy and the remaining 25% dying. A more recent
7 days for the year after, respectively. These findings sug- follow-up on the English cohort observed much better s ur-
gest that NPPV may cut health care resource utilization in vival rates for patients with DMD treated with NPPV than
these patients, with the potential for substantial cost sav- those previously reported by the French group: 85% for
ings. More recently, Janssens et al184 observed a si.Jnilar re- 1 year and 73% for 5 years.186 This disparity may reflect
duction in hospital days per patient per year (median of 17 differences in the severity of illness between patients when
for the year before and 6 for the year after NPPV) for patients begun on NPPV, how cough was assisted, or practices on
with restrictive thoracic disorders in a long-term retrospec- switching to tracheostomy. Overall, the continuation rates
tive study from Switzerland. Although these uncontrolled from these long-term fo!Jow-up studies are similar to those
studies do not preclude the possibility that changes in hos- observed for patients treated with invasive ventilation re-
pitalization practices over time could have been responsi- ported earlier by the French group.'187
ble for the reductions, it appears highly likely that NPPV Survival would be anticipated to be shorter in patients
reduces the need for hospitalization among these patients . with ALS than in those with more slowly progressive neu-
romuscular diseases. In a prospective, nonrandomized trial
EFFECT ON SURVIVAL on 20 consecutive patients, Pinto et al 188 treated the first 10
Despite the lack of randomized, controlled trials, long-tem1 with medical therapy alone and the next 10 with NPPV. Af-
follow-up series p rovide strong evidence that NPPV pro- ter 2 years, 50% of the NPPV patients were alive, whereas
longs survival in comparison with unventilated patients. all the medical therapy patients had died. Aboussouan et
The ability to prolong survival is obvious in patients us- al189 compared the survival of 31 patients with ALS who
ing NPPV continuously who would die if ventilator assis- continued NPPV with that of 21 patients who were intol-
tance stops for more than a few minutes.162 Studies from erant of NPPV. The intolerant patien ts had a significantly
France 183 and England 185 have reported on several hundred greater risk of dying over the 3-year study period than those
patients with chronic respiratory failure of various etiolo- who remained on NPPV (relative risk 3.1). As might be an-
gies treated with intermittent nasal NPPV for periods of ticipated, patients with bulbar involvemen t were unlikely
up to 5 years (Fig. 19-7). Rather than survival rates, these to be tolerant of NPPV (only 6 of 20); if they could toler-
studies used the rate for continuation of NPPV, thought to ate the therapy, however, it imparted an apparent s urvival
FIGURE 19-7 A. Survival after tracheostomy in 222 patien ts wit.h chronic respiratory failure of various etiologies followed for as long as 10
years. (Redrawn, with pennissiorr, from Robert et al: R ev Fr M al Respir 11:923-36, 1993) B. Lik elihood of continuing noninvasive positive
pressure ventilation (NPPV} in 276 patients with chronic respiratory failure followed for as long as 3 years. (Redrawn, with pennissiot1,
from Leger et nl: Clrest 105:10()-5, 1994.) BRO, bronchiectasis; COPD, chronic obstructive pulmonary disease; DMD, Duchenne muscular
dystrophy; KS, k yphoscoliosis; MYO, myopathy; PP, p ostpolio syndrome; TB, history of tubercul osis.
A SURVIVAL AFTER TRACHEOSTOMY B CONTINUATION OF NPPV
....... _.. ,
"r.:······,, ··········.
,:. , ·.,
---------------.pp (41)
100
\ ·•;-,...•.,
. ', ........... I
KS (1 05)
80
'·..,,''\ ......·.
··.. 80 '·\ ,.... .. ·····
~
'·.' ·. -··-·· ......., . ~,-... 'TB(80)

, ' ,..
.....
2
w
(.)
a:
60 ~
\
...
";, ,
., .,
MYO (13)
.................... .. .... KS (53) 60 ............ .. ..
''·4 ·-·- COPD (50)
"----·sAO (25)
w 40 \ .,_ ' 'DMD (16)
a.
.. '·......... TB (55)
20 \ ....... ·-·-·- COPD (50) 20

BR0(10)
0 2 4 6 8 10 0 1 2 3
YEARS YEARS
advantage. Bach190 has reported that NPPV prolongs sur- TABLE 19-5 Selection Guidelines: Long-Term Noninvasive
vival and postpones the need for tracheostomy in ALS. Ventilation for Restrictive Thoracic Disorders or Obesity
H ypoventilation
Based on these observations, NPPV is now used in approxi-
mately 15% of patients with ALS compared with only 2% us- Indications
ing invas ive mechanical ventilation, according to one recent 1. Symptoms: fatigue, morning headache, hypersomnolence,
cross-sectional U.S. survey. 191 On the other hand, Bacl1'190 nightmares, enuresis, dyspnea, and so on
also found that after 5 years of follow-up, only 8 of25 (32%) 2. Signs: cor pulmona le
patients with ALS using NPPV were alive compared with 3. Gas-exchange criteria:
27 of 50 (54%) patients receiving tracheos tomy ventilation. Daytime PacOt > 45 mmHg
This suggests that NPPV is less effective a t prolonging sur- Nocturnal oxygen dcsaturation (Sao2 ~ 88% for more than
vival than tracheostomy ventilation, as might be anticipated 5 minutes sustained or > 10"/., of total monitoring time)
4. Sleep evaluation:
among patients with neuromuscular diseases such as ALS
Unnecessary in restrictive thoracic disorders if other criteria
that impair bulbar function.
met
Should be obtained for obesity hypoventilation to assess OSN
5. Other possible indications
SELECTION OF PATIENTS WITH RESTRICTIVE Recovering from acute respiratory failure with persistent COz
THORACIC DISEASE TO RECEIVE NON INVASIVE retention
Repeated hospitalizations for acute respiratory failure
POSITIVE-PRESSURE VENTILATION
Contraindications
Guidelines for the selection of patients with restrictive tho- Inability to protect airway
racic disorders to receive NlV based on American College Impaired cough
of 01est Physicians (ACCP) consensus and Medicare guide- fmpaired swallowing with chronic aspiration
lines in the United States are listed in Table 19-5.192 Patients Copious secretions
Need for continuous or nearly continuous ventilatory assistance
should have symptoms attributable to d1ronic hypoventi- Anatomic abnonnalities that interfere with mask fitting
lation and poor sleep quality, such as morning headache, Poorly motivated patient or family
daytime hypersomnolence, and low energy in combination fnability to cooperate or comprehend therapy
with daytime or sustained nocturnal hypoventilation. The Inadequate financial or caregiver resources
duration of nocturnal 0 2 desaturation used as an indicator
of nocturnal hypoventilation ( <88% for more than 5 consec- • Jf OSA (obstructive sleep apnea) is present, trial of CPAP may be wa.r ranted
see (Table 6).
utive minutes) was suggested by consensus192 but has never
souRCE: Adapted, with pennis.~ion, from Mehta and Hill.1
been validated. Even if symptoms are minimal or lacking,
patients with severe C02 retention (> 50 mmHg) and those
recovering from bouts of acute respiratory failure are con-
sidered for long-term NlV, particularly if there is persistent ALS may respond well temporarily, but as debility pro-
C~ retention or a history of repeated hospitalizations. The
gresses and bulbar function deteriorates, NPPV loses its effi-
consensus group also recommended NPPV for patients with cacy. Those who wish to optimize their chances for survival
may prefer invasive ventilation, and others may desire hos-
severe pulmonary dysfunction (FVC < 50% of predicted or
pice care. Patients with rapidly progressive neuromuscular
maximal in.c;piratory pressure < 60 cmH2 0), even in the ab-
conditions such as Guilla in-Barre syndrome or myasthenia
sence of C02 retention, despite the lack of evidence from
gravis in crisis usually are poor candidates for NlV because
clinical s tudies to support the initiation of NN on the basis
swallowing frequently is impaired when ventila tory dys-
of pulmonary function alone.
function becomes severe.
Relative contraindications to the use ofNPPV for chronic
respiratory failure (Table 19-5) include inability to protect
the upper airway because of impaired cough or swallow-
ing or excessive secretions. Aggressive treatment with tech- WHEN TO START LONG-TERM NONINVASIVE
POSITIVE-PRESSURE VENTILATION FOR
niques or devices to assist cough 193 may permit the use of
RESTRICTIVE THORACIC DISORDERS
NPPV in such patients who otherwise would not be can-
didates, but if the condition is too severe, tracheostomy is NPPV to treat chronic respiratory failure secondary to re-
indicated if the patient desires maximal prolongation oflife. strictive thoracic diseases has gained w ide acceptance, but
Tracheostomy ventilation has been recommended when the the optimal time for initiation has been debated. Prophy-
need for ventilator assistance exceeds 16 hours daily} 94 al- lactic initiation in progressive neuromuscular diseases, be-
though many patients still prefer NPPV.180 Other relative fore the onset of symptoms or daytime hypoventilation, has
contraindications to NPPV are listed in Table 19-5. The clin- been proposed to retard the progression of respiratory dys-
ician must render a judgment as to w hether these are suffi- function. Raphael et a1 195 tested this hypothesis in 76 pa-
cient to preclude a tria] of NIV. tients with DMD who had not yet developed symptoms
The na tural history of the restrictive thoracic disorder also or daytime hypoventilation, randomizing them to receive
should be considered when deciding about NPPV. Patients nasal NPPV or standard therapy. Not only did NPPV fail
with cl1est-wall deformities and stable or slowly progres- to slow disease progression, but it also was associated with
sive neuromuscular disorders res pond well to NPPV and greater mortality, leading to premature termination of the
remain stable for long periods of time.183•185 Patients with trial. The authors surmised that mortality was increased
more rapidly progressive neuromuscular disorders such as because NPPV gave patients a false sense of security that
caused them to delay seeking medical attention when they have persistent C02 retention after use of nasal CPAP alone.
developed respiratory infections. The study had numerous Among 13 patients with severe obstructive sleep apnea
shortcomings, including failure to document patient adher- whose hypercapnia (average Paco, of 62 mmHg) was unre-
ence or to consistently use techniques to assist cough, but sponsive to CPAP, NPPV using volume-limited ventilators
it has stemmed any enthusiasm about using prophylactic lowered the Paco, to 46 mmHg, and 9 of the patients even-
NPPV in patients with DMD. tually stabilized on CPAP alone. 201
Early initiation of NPPV also has been proposed to treat Independently adjusted inspiratory and expiratory pres-
patients with Al5.196 Current guidelines based on expert sure or ''bilevel" positive-pressure ventilation was first de-
consensus recommend starting NPPV if FVC drops below veloped as a way of controlling obstructive sleep apnea
50% of predicted197 or maximal inspiratory pressure drops while using lower expiratory pressures than with CPAP
below 60 cmH 20. In a preliminary study, 196 20 patients with alone, thus potentially enhancing comfort and adherence
ALS and FVC values ranging between 70% and 100% of with therapy. 202 Reeves-Heche et al203 were unable to
predicted were randomized to receive NPPV if they had demonstrate improved adherence rates in patients with ob-
an Sa02 of less than 90% for more than 1 minute during structive sleep apnea treated with bilevel ventilation com-
nocturnal oximetry(" early intervention") or to await a drop pared with CPAP alone. Even so, bilevel devices are s till
in FVC to less than 50% of predicted ("standard of care''). used commonly to treat patients intolerant of CPAP alone,
TI1e early-intervention group had a significant increase in but a stronger rationale supports the use of bilevel NPPV
the vitality subscale on the SF-36, suggesting that earlier for obstructive apnea if patients have persisting hypoventi-
intervention might be beneficial in patients with ALS, but lation despite adequate CPAP therapy.
more research is necessary.
Presently, awaiting the onset of symptoms of nocturnal
hypoventilation before initiation of NPPV is the most prag-
OBESITY-HYPOVENTILATION SYNDROME
matic approach because adherence to therapy is often poor
w1less patients are motivated by the desire for symptom Respiratory impairment is common among obese patients,
relief. Symptomatic patients who have only nocturnal but including those with restricted lung volumes secondary to
no daytime hypoventilation, as demonstrated by frequent, increased cl1est-wall and lung elastance, abnormal blood
sustained nocturnal~ desaturations, are good candidates gases, and breathing disturbances during sleep. When obese
for initiation. Masa et al198 showed improvements in dysp- patients hypoventilate, the term obesity-hypoventilation 51)11-
nea scores, morning headache, and confusion after 2 weeks drome is applied, a condition that is multifactorial in eti-
of nocturnal NPPV in 21 such pa tients, whose proportion of ology. The altered chest-wall mechanics are accompanied
sleep time with an Sao2 of less than 90% averaged 40-50% on by reductions in res piratory drive (either acquired or con-
room air before initiation of NPPV and fell to 6% afterwards. genital), as well as obstructive s leep apnea (in 80-90% of
The timing of initiation requires a judgment based on the an- patients), giving rise to the hy poventilation.204 This is a
ticipated progression of the disease (sooner for more rapid morbid condition associated w ith cor pulmonale and a
progression), the patient's symptoms, pulmonary function, high mortality rate over time, but it responds favorably to
and daytime and nocturnal gas exchange. The aim is to be- NlV.
gin when there are symptoms with significant pulmonary Morbidly obese subjects have significantly increased
function and/or gas-exchange abnormalities when the pa- work of breathing at baseline, and NPPV (inspiratory pres-
tient still has time to adapt but well before the occurrence sure of 9-12 crnH2 0 , expiratory pressure of 4 cmH2 0) low-
of a respiratory crisis. ers that work. 205 NPPV also raises tidal volumes and lowers
end-tidal Pc 02 more in patients with obesity hypoventila-
tion than in obese patients without sleep-disordered breath-
ing or in nonhypoventilating subjects with obstructive sleep
Central Hypoventilation, Obstructive apnea. 205 NPPV lowers Paco, and improves symptoms as
Sleep Apnea, and Obesity Hypoventilation effectively in patients with obesity hypoventilation as in
those with severe ky phoscoliosis,2°6 associated ""ith an in-
crease in respiratory drive. 207 CPAP alone, however, may be
CENTRAL HYPOVENTILATION/OBSTRUCTIVE
as effective as NPPV in some patients.204 Some investigators
SLEEP APNEA
also have started with NPPV and converted to CPAP once
The first case reports describing the use of nasal ventila- hy poventilation has been controlled. 201 These studies sup-
tion for chronic respiratory failure were in young children port the use of NPPV for obesity h ypoven tilation to improve
with central hy poventilation, who had resolution of gas- symptoms and gas excl1ange.
exchange abnormalities and symptoms after initiation of As obesity has become an increasingly prevalent prob-
therapy. 199,200 No controlled studies have examined this ap- lem, obesity-hypoventilation sundrome has become an in-
pLication, but enough anecdotal evidence has accrued that creasingly common indication for using long-term NPPV. A
consensus groups consider therapy of central hypoventila- Swiss survey found that during the 1990s it became the most
tion as an appropriate indication for NPPV. 157, 192 common diagnosis among patients using long-term NPPV
Nasal CPAP is considered the therapy of first choice for at home in the Geneva region1S4 (Fig. 19-8). Adherence was
obstructive sleep apnea. NPPV, however, may be success- excellent with the therapy, exceeding 70%, average Paco,
ful in improving daytime gas excl1ange and symptoms in normalized, and hospital days fell significantly following
hypoventilating patients with obstructive sleep apnea who NPPV initiation.
452 PART VT NONINVASIVE METHODS OF VENTILATOR SUPPORT
Nwromuscutar 0 /so rdats consumption, and mobilization of secretions would benefit

• Obesity· Hypov.nhllttion patients with COPD treated with negative-pressure ventila-
140
m Posf · T8 tors. During the early 1980s, Brawl andMarino 209 tes ted the
120 • P~· Porto
theory that respiratory muscles are cluonically fatigued and
~ KypfloscOlkn/s
will benefit from intermittent rest. They treated 16 patients
100
• COPO
with severe COPD using wrap negative-pressure ventila-
tors for 5 hours daily over 5 months and observed improve-
10
ments in vital ca pacity, maximal inspiratory and expiratory
60
pressure, and daytime Pac~ during spontaneous breathing.
Although these results were interpreted as su pporting the
"muscle rest" hypothesis, controls were lacking, and other
as pects of rehabilitation or passage of time alone could have
been responsible for the improvements.
0
Subsequently, several controlled studies showed im-
<1992 1992 1993 19U 199S 1996 1997 199& 1999 provement in respiratory muscle strength after short-term
(days to a week) use of negative-pressure ventilation.21G-2l2
FIGURE 19·8 Yearly co un t o f the cumulative popu lation of
patients treated by NPPV during the s tudy peri od (1992- 2000)
These studies documented respiratory muscle rest by show-
accord ing to d iagnostic category. (Used, w ith pennissiou, from ing significant reductions in the diaphragmatic electromyo-
fanscens eta /: Chest 128:67- 79, 2003.) graphic (EMG) signal. Subsequent controlled tr ials, how-
ever, ?f lonr,er duration (up ~o several months) showed no
beneflt. 213 - 15 Notably, basehne Pac~ among the latter un-
SELECTION OF PATIENTS WIT H CENTRAL SLEEP favorable trials was approximately 47 mmHg, substantially
APNEAfOBESITY-HYPOVENTILATION SYNDROME lower than that in the favorable studies (57 mmHg). TI1is
FOR NONINVASIVE POSITIVE-PRESSURE raises the possibility that respiratory muscles in patients
VENTILAT ION with severe C02 retention are more likely to benefit from in-
Firm indications and selection guidelines for central hy- termittent negative-pressure ventilation than patients with
poventilation/central s leep apnea/ obesity-hypoventilation little or no C02 retention, perhaps because of relief of the
syndrome have not been established. The contentious is- unfavorable effect of hypercapnia on respiratory muscle
sue is that patients with obstructive apneas might respond function .216
to CPAP alone. Patients who are symptomatic with frank Negative-pressure ventilation was tolerated poorly in the
hypoventilation o r who have prolonged central apneas preceding trials, so subsequent trials tested NPPV to see if
dearly are good candidates fo r NPPV. The more severe the better tolerance might achieve more consistent benefits. In
hypoventilation, the more important it would be to start addition, patients with severe COPD are known to have
with a mode that augments minute volume, and using a more frequent nocturnal desaturations related to hypoven-
backup rate would be important for those with prolonged tilation than normal subjects. These desaturations are asso-
central apneas. Medicare guidelines in the United States ciated with arousals tha t shorten the duration and diminish
(Table 19-6) require a polysomnogram to document the cen- the quality of sleep, an effect that can be ameliora ted by 0 2
tral apneas, prolonged 0 2 desatu rations (::; 88% for more supplementation, at least in "blue and bloated" patients.217
than 5 minutes) as evidence of nocturnal hypoventiJation Furthermore, patients with COPD have a 32% drop in inspi-
and, if the patient has obstn1ctive sleep apnea, evidence of ratory flow rate during REM sleep associated with a reduced
CPAP failure with improvement o n NPPV, as determined tidal volume. 2111 By assisting ventilation, NPPV offers the po-
by oximetry or a repeat polysomnogram. tential of res toring inspiratory flow, eliminating episodes of
hypoventilation, and improving nocturnal gas exchange, as
well as the duration and quality of sleep.
Studies using NPPV in patients with severe obstructive
Obstructive Lung Diseases lung diseases have yielded conflicting results. Initial small
uncontrolled cohort series on the use of nasal NPPV in pa-
CHRONIC OBSTRUCTIVE P ULMONARY DISEASE tients with severe stable COPD lent support to the idea
During the 1960s, McCiement et al208 speculated that that NPPV would improve s leep efficiency and daytime and
improved ventilation-perfusion relationships, reduced 0 2 nocturnal gas exchange. 219·220 A 3-month crossover trial by
Strurnpf et al, 35 however, found improvement only in neu-
TABLE 19-6 Guidelines for No ninvasive Positive-Pressure
ropsychological function but not in nocturnal or daytime
Ventilation in O bstructive Sleep Ap nea/Centra l Sleep Apnean gas exchange, sleep quality, pulmonary functions, exercise
tolerance, or symptoms. This study also encountered a high
1. Polysomnogram demonstrating OSA, CSA, or mixed apneas dropout rate, with 7 patients withdrawing because of mask
2. If OSA, patient failed to improve or tolerate CPAP alone intolerance and only 7 of 19 entered patients actually com-
3. Sustained oxygen dcsaturation nocturnally(;:;: 88% for >5 min) pleted the trial. Tn contrast, in a study of nearly identical
4. Significant improvement in nocturnal gas exchange during design, Meecham-jones et al221 enrolled 18 patients with se-
NPPV usc, as documented by oximetry or polysomnography vere COPD, 14 of whom completed the study. Nocturnal
• B~sed on Center for Medicare and Medica id Services Guidelines. and daytime gas exchange, total sleep time, and sym ptoms
ABBREVIATIONS: OSA, obstructive sleep apnea; CSA, centra l sleep apnea. improved during NPPV use. These salutary effects of NPPV
on sleep duration and efficiency in patients with severe sta- mortality. In addition, the two large follow-up studies o n
ble COPD also were observed in a 2-night crossover trial NIV183•185 found that patients with COPD had substantially
in 6 patients with an initial Paco2 of 58 mmHg. 222 Some lower continuation rates than patients with neuromuscular
of the disparity between these studies may be explained or chest-wall disorders (see Fig. 19-7). This suggests that pa-
by the observation that patients in the study of Strumpf et tients with COPD are less tolerant of or benefit less from
a! had more severe airway obstmction (FEV, of 0.54 versus NPPV than most neuromuscular patients. Criner at a! 228
0.81liter) despite having less C02 retention (Pac~ of 47 ver- initiated NPPV in 20 patients with neuromuscular disease
sus 57 mmHg) than did patients in the study of Meecham- and 20 with COPD during a several-week stay in a special-
Jones et al. This suggests that different subsets of patients ized ventilator wut. Despite these optimal conditions, only
with COPD were entered into the studies and that those 50% of patients with COPD as compared with 80% of those
with greater C02 retention ("blue bloaters") may be more with neuromuscular disease were still using NPPV after
likely to benefit from NPPV. 6 months.
Two other ra ndomized, controlled trials failed to sub- Overall, the results of these long-term trials testing the
stantiate the hypothesis that greater C0 2 retention predicts efficacy of NPPV in severe stable COPD have been dis-
NPPV success in patients with severe COPD, despite at- appointing, and this application remains controversial. 229
tempts to enroll hypercapnic subjects. Gay et al 223 screened A meta-analysis of these trials concluded that the stud-
32 hypercapnic patients, but only 13 remained after exclu- ies were too small to discern a "clear clinical direction."230
sion for obstructive sleep apnea or other terminal illness. It should be acknowledged, however, that two random-
Only 4 of the 7 patients randomized to NPPV completed ized trials221, 226 have yielded favorable findings, and
the trial, and not surprisingly, no signi ficant differences several small uncontrolled series show rromise among the
emerged. Lin et al 224 performed an 8-week crossover trial patients with marked C0 2 r etention. 23 ·232 The conflicting
consisting of consecutive, randomized 2-week periods of results lughlight the need for more studies with greater sta-
no therapy, 0 2 alone, NPPV alone, and NPPV combined tistical power to test outcomes such as reductions in hospital
with 0 2 . Among 12 patients with a mean initial Pac~ of days per year and event-free survival rather than just phys-
50.5 mmHg, NPPV not on! y conferred no added benefit over iologic or sleep-related outcome variables.
0 2 alone w ith regard to oxygenation, ventricular function,
or sleep guality, but it also reduced sleep efficiency and to-
tal sleep time. The authors, however, used inspiratory pres- NO NIN VASIVE POSITIVE-PRESSURE VENTILATION
sures of only 12 em H20, which may have provided insuffi- TO ENHANCE REHABILITATIO N IN COPD
cient ventilator assistance, and 2 weeks may have been too NPPV may serve as an adjunct to exercise training in re-
brief to permit adequate adaptation to NPPV. habilitation for patients with severe stable COPD. Two dif-
Several longer-term controlled trials have been performed feren t approaches have been used: One employs NPPV to
subsequently. Casanova et al225 performed a randomized unload the inspiratory muscles during exercise and to per-
year-long trial in 44 patients with severe COPD, finding no mit a greater exercise intensity to magnify the training ef-
improvements in gas exchange, survival, or hospitalization fect; the other rests muscles between sessions (mainly at
rate, although one test of neuropsychological function im- night) to enhance daytime function d uring the sessions. In-
proved. This study, however, also used relatively low inspi- vestigations show that CPAP and PSV singly and in com-
ratory pressures and did not assess sleep quality or health bination increase exercise capacity in patients with severe
status. In an Italian multicenter trial, Clini et al226 screened COPD.233,234 Bianchi et al235 showed that compared w ith
120 patients with severe COPD and chronic C0 2 retention CPAP or PSV, proportio nal-assist ventilation (PAV) brought
(Paco, of 50 mmHg or more). Ninety patients were enrolled . about the greatest improvement in cycling endur ance and
After dropouts and deaths, 47 were left, divided between reduction in dyspnea in 15 stable hypercapnic patients w ith
the NPPV plus 0 2 and 0 2 alone groups. Patients treated COPD. This enhanced exercise capacity during ventilator
w ith NPPV had less of an incr ease in Paco2 over the 2-year use, however, has not yet been shown to translate into a
period than controls (55-56 versus 55-60 mmHg, respec- greater training effect or functional im~rovement during
tively, p < .05), less deterioration in the MRF-28 functional spontaneous breathing. 236 Garrod et al2~ tested the second
score (although the St. George's Respira tory Questionnaire approach among 45 patients with severe COPD (FEV1 <
was no different), and a trend toward fewer hospital days 50% of predicted), showing that nocturnal NPPV between
per patient per year (20 days before and 14 days after intia- rehabilitation sessions increased the shuttle-walk distance
tion ofNPPV). No differences were detected in the 6-minute and improved quality of life compared with standard ther-
walk distance, d yspnea score, sleep symptoms, or mortal- apy. These studies indicate that NPPV, used either during
ity rate. One other multicenter European trial reported thus or between exercise sessions, has the potential to enhance
far only in prelin'linary form observed no significant differ- benefits accruing from pulmonary rehabilitation, but con-
ence overall, but a post-hoc analysis revealed a reduction in firmatory studies a re needed .
mortality in the subgroup of patients older than 65 years of
age. 227
These studies have lacked statistical power, and even CYSTIC FIBROSIS AND DIFFUSE BRONCH IECTASIS
in those w ith favorable results, benefit has been shown Small case series238·239 have reported stabilization and some-
only for physiologic var iables such as respiratory muscle times even improvement of gas-exchange abnormalities
strength and Paco2 o r total sleep time and symptoms but for periods ranging up to 15 months in severely hyper-
not for functional sta tus, resource utilization, morbidity, or capnic <Paco, > 54 mmHg) patients with end-stage cystic
fibrosis (CF) awaiting lung transplantation. Gozal et al240 COPD.157 A subsequent consensus conference agreed that
observed markedly improved gas exchange in all sleep the data are scanty and conflicting but opined that the avail-
stages in 6 patients with CF treated with NPPV plus 02 able evidence suggests that certain subgroups of patients
therapy in comparison with patients treated with 02 ther- with COPD may benefit. 192 Most trials that have observed
apy alone, although sleep duration and architecture were benefit from either negative- or positive-pressure NIV in
similar in the two conditions. CF is now a common reason severe stable COPD have enrolled patients with more C0 2
among children for the use of NPPV at home, constituting retention at baseline than trials with negative results. Thus
17% of such cluldren in a recent French survey. 241 the consensus opinion was that a trial of NPPV in severe
The medta11ism by which NPPV assists CF patients is stable COPD patients is justified if C02 retention is severe
not entirely clear. NPPV reduces the work of breathing (i.e., Paco, > 55 mmHg).
significantly,242 but a study in 13 hypercapnic patients with Considering that one of the two controlled trials reportin~
CF (average PacOz of 51 mmHg) found no improvements beneficial effects of NPPV in severe stable COPD patients22
in sleep quality, daytime arterial blood gases, pulmonary enrolled patients w ith frequenthypopneas(10per hour) and
function tests, respiratory muscle strength, or exercise toler- ~ desaturations during sleep, another indication suggested
ance after 2 months of NPPV, even though 8 of the patients by the consensus group was sustained, severe nocturnal 0 2
felt improved symptomatically. 243 Madden et a l244 found desaturation ( <88% for more than 5 consecutive minutes).
improved hypoxemia but again no improvement in hyper- 02 therapy alone, however, has been shown to improve
capnia among 113 patients treated long term with NPPV; sleep quality, reduce drowsiness, and improve neuropsy-
these authors still considered NPPV useful as a bridge to chological function in such patients.217,218 Therefore, the
lung transplantation. NPPV also can be useful for adminis- recommendation was made that sleep monitoring be per-
tration of aerosol to CF patients. Fauroux et al245 found that formed during 0 2 supplementation and that NPPV not be
it was superior to a sta ndard nebulizer in a small group of initiated unless symptoms failed to respond to a trial oflong-
CF patients . Thus NPPV appears to have a role in support- term 02 therapy. This includes patients who retain more
ing deteriorating patients with CF and serving as a bridge C02 during 0 2 therapy, a group that responded favorably
to transplantation, even though improvements in gas ex- to NPPV in an uncontrolled trial.232 If patients have a Pacoz
change and sleep parameters are not seen consistently. of between 50 and 54 mmHg, the consensus group opined
In diffuse bronchiectasis patients, Benhamou et al246 that NPPV should be used if such patients have evidence of
found that the use of NPPV was associated with improved nocturnal hypoventilation, as indicated by nocturnal oxime-
Karnovsky function scores and a reduction in days of hospi- try, or if there is a history of repeated hospitalizations.
talization from 46 for tl1e year before to 21 for the year after In the absence of more controlled trials with favorable
starting NPPV. Compared with a historical control group, findings, however, these guidelines are tentative. Also, even
however, rates of deterioration in oxygenation were sim- for patients who meet the criteria, patient tolerance of NPPV
ilar, and no survival benefit was aplisarent. In fact, in the may be poor. 228 In order to maximize patient compliance,
long-term English follow-up study,1 patients with end- only motivated symptomatic patients, such as those w ith
stage bronchiectasis had poorer survivals than other patient fatigue or daytime hypersomnolence, who can cooperate
subgroups, most dying within 2 years. Dupont et al 247 retro- and comprehend the purpose of the therapy should be se-
spective! y reviewed the outcomes of 48 patients with diffuse lected. As outlined in Table 19-7, NIV should not be initiated
bronchiectasis following their first ICU admission over a unless other therapies have been optimized, including 0 2
10-year period; 27% were treated with NPPV, and 54% re- supplementation and CPAP (if indicated). These guidelines
quired intubation. One-yearmortalitywas40%. Age greater have led to reduced use of NPPV for severe stable COPD
than 65 years, a higher simplified acute phys iology score
(SAPS) II score (>32), and the need for intubation were iden-
tified as predictors of mortality. These studies suggest a role TABLE 19-7 Recommended Guidelines for Selection of
for NPPV in treating patients with CF and diffuse bronchiec- Patients with Obs tructive Lung D iseases to Receive
tasis who have developed severe C02 retention, as well as Long-Term N PPV"
in serving as a bridge to transplantation, but the capacity to
prolong life may be limited. Lacking controlled trials, defini- 1. Symptoms: fatigue, hypcrsomnolence, dyspnea, and so on
2. Failure to respond to optimal medical therapy:
tive recommendations on how to select patients with CF or
Maximal bronchodilator therapy and/ or steroids
diffuse bronchiectasis for NPPV or when to start are unavail- 0 2 supplementa tion if indicated
able; most clinicians use guidelines similar to those used for 3. Gas-exchange abnormalities:
severe COPD (see below), paying particular attention to the Paco2 ~ 52 mmHg
inclusion of tecl1niques to aid in secretion clearance. Sao2 < 88% for more than 5 cons~utive minutes nocturnally
despite 0 2 supplementation
4. Obstmctive sleep apnea excluded on clinical grounds or failure
SELECTION OF PATIENTS WITH CHRONIC to respond to CPAP therapy if moderate to severe obstructive
RESPIRATO RY FAILURE AND O BSTRUCTIVE sleep apnea detected on sleep study
LUNG DISEASES TO RECEIVE 5. Reassess after 2 months' therapy; continue if adequate
NONINVASIVE VENTILATION compliance (>4 hours a day) and favorable therapeutic
response
An earlier consens us statement noted the discordant results
of the available trials and concluded that more study is • Based on Center for Medicaid and Medicare Services reimbursement
needed before NPPV can be recommended in severe stable guidelines.
in the United States since the late 1990s, when certain home eluding Oz supplementation, for those with Cheynes-Stokes
respiratory companies were encouraging w idespread use. breathing. Despite the promising findings with ASV modes,
Use is currently more prevalent in certain European cowl- further studies a re needed before they can be recommended.
tries, such as Switzerland, where a recent survey found that
COPD was the second most common reason for use ofNPPV PEDIATRIC USES OF NONINVASIVE POSITIVE-
in the home. 184 A recent pan-European survey on home me- PRESSURE VENTILATION FOR CHRONIC
chanical ventilation showed enormous variability between RESPIRATORY FAILURE
countries in the proportion of patients receiving ventilation
for neuromuscular versus lung diseases and between those Since the first case reports on the successful use of nasal
receiving noninvasive versus tracheostomy ventilation.24S NPPV in dlildren with central hypoventilation,199,2oo rela-
tively few reports of NPPV have appeared in th e pediatric
literature. Nonetheless, some of the experience in adults can
CONGESTIVE HEART FAILURE be applied to children because sucl1 conditions as DMD
As discussed earlier, eviden ce supports the use of NIV (ei- or CF may impair respiratory function in older children,
ther CPAP alone or NPPV) in the therapy of acute heart fail- and these have been included in a number of the published
ure, and it also may have a role in chronic congestive heart reports. 1s3•185 In their experience with 15 children having
failure (CHF). Increases in intrathoracic pressure have long neuromuscula r disease or CF treated with nasal NPPV and
been known to have salutary hemodynamic effects in some followed for periods ranging from 1-21 months, Padman
patients with congestive heart failure. Naughton et al 20 et al144 found that average Paco 2 and hospital utilization fell;
found that CPAP (10 cmH20) reduced both ventila- only one child required an artificial airway. Fauroux et aJ 255
tory work (by minimizing negative intrathoracic pressure undertook a French survey on the use of NPPV by children
swings) and cardiac load (by reducing transmural pressure) at home. Of 102 children followed at 15 centers, 7% were
in 15 patients with congestive heart failure. A subsequent younger than 3 years of age, 35% were 4-11 years of age,
study found that longer-term nocturnal CPAP (9 cmH 2 0) and 58% were 12 years of age, and 34% had neuromuscular
improved inspiratory muscle strength (maximal inspira- disease, 30% had obstructive sleep apnea or craniofacial ab-
tory pressure increased from 79.3-90.7 cmH20) in a group normalities, 17% had CF, 9% had central hypoventilation,
of 8 patients with CHF. 249 One month of nocturnal CPAP and 8% had scoliosis. In a subsequent report, Fauroux et al 256
also increased left-ventricular ejection fraction (33.8% ver- described flattening of the face in 48% of patients. Nev-
sus 25%) and lowered systolic systemic pressure (116 versus ertheless, pediatric patients appear to r espond as well to
126 mmHg) in patients with CHF and obstructive sleep ap- NPPV as most adults with chronic respiratory fa ilure. In a
nea compared with healthy subjects. 250 long-term follow-up study of 30 pediatric patients (average
Whether NPPV is better than CPAP alone in these pa- age 12.3 years) with mainly non-Duchenne's neuromus cu-
tients has been controversial. Willson et al251 found dra- lar syndromes, Mellies et al257 observed clinical stability ex-
matic improvements in sleep parameters (apnea-hypopnea ceeding an average of 2 years in duration. Nocturnal and
index 49-6, arousal index 42-17) in patients w ith CHF and diurnal gas exchange, quality of sleep, and symptoms were
Cheynes-Stokes respiration after treatment with a portable improved, and these deteriorated promptly on temporary
bilevel device. Conversely, Kohnlein et al252 performed a withdrawal of NPPV. The authors concluded that NPPV is
crossover trial consisting of randomized 2-week periods of effective and should be used in cl1ildren wiU1 symptomatic
NPPV and CPAP in 35 patients with Cheynes-Stokes res- sleep-disordered breathing associated with neuromuscular
piration. Both modalities improved apnea-hypopnea and syndromes.
arousal indexes dramatically, but there was no difference
between the two. TeschJer et al253 randomized 14 patients
with CHF and Cheynes-Stokes respiration to control, 02 Practical Application of Noninvasive
alone, CPAP alone, bilevel NPPV, and adaptive pressure- Positive-Pressure Ventilation
support servo ventilation (ASV) on five separate randomly
ordered nights. They observed equal reductions in apnea- Despite the accumulating evidence on NPPV indications
hypopnea and arousal indexes wiU1 0 2 alone and CPAP that helps in selecting appropriate patients, the delivery of
alone, a greater reduction with bilevel ventila tion, and the NPPV remains very much an art. After the decision is made
greatest improvement with ASV. This study supports the to treat a patient wiU1 NPPV, U1e clinician must decide on a
idea that customized modes designed to respond to U1e ap- mask (or interface), ventilator, settings, and adjuncts. NPPV
neas of Cheynes-Stokes respiration (such as ASV) may bees- must be delivered in a safe and adequately monitored loca-
pecially effective, but no adequately powered trials address- tion. Implementation of each step requires knowledge and
ing important clinical outcomes have yet been performed. experience. More than with invasive ventilation, the inter-
TI1e Canadian CPAP (CanPAP) trial is a large randomized action between patient and clinician is central to success.
trial examining the effects of long-term CPAP in patients The following will provide an overview of the steps in this
with CHF; it has provided disappointing preliminary find- process.
ings, with only a trend for improved left-ventricular func-
tion and no improvement in functional status. 254 Thus the
I N ITIATION
role ofNPPV in CHF patients is currently unclear. Most clin-
icians currently use CPAP alone for patients w ith CHF and Although little scientific evidence is available to guide
obstructive sleep apnea and optimal medical therapy, in- the decisions surrounding initiation, they should be made
TABLE 19-8 Goals of Noninvasive Ventilation LONG TERM

Stable patients with chronic respiratory failure may start
Acute applications
NPPV during an inpatient admission, in a sleep laboratory
Relieve dyspnea
Optimize patient comfort during the daytime or an overnight stay, in a physician's
Reduce work of breathing outpatient office (with therapists from the home respira-
lmprove or stabilize gas exchange tory vendor present), or at home. Although there are strong
Minimize complications proponents for one location or another, no evidence is avail-
Avoid intubation able to dictate the choice. Routine hospitalization is unnec-
Avoid dcJay of needed intubation essary unless warranted by the patient's medical condition,
Lo11g-term applicatious although some clinicians believe that this increases subse-
Ameliorate symptoms quent adherence rates and prefer the closer initial monitor-
Improve or stabilize gas exchange ing and opportunity for early adjustment that it affords. Use
Improve sleep duration and quality
of a s leep laboratory offers the advantage of precise titration
Maximize quality of life
Enhance functional status
of initial pressure or volume settings during sleep mon-
Prolong survival itoring but adds to costs and may delay implementation
because of scheduling problems. Also, no titration proto-
SOURCE: Adapted, with pe.rmission, from Mehta and Hill 1 col has been valid ated, and selecting pressures to eliminate
apneas and hypopneas, as is done with sleep apnea, may
not be adequate to reverse hypoventilation in patients with
carefully because success or failure depends on them. Fo- chronic respiratory failure. Until outcome studies demon-
cusing on the major goals ofNIV may help (Table 19-8) . NIV strate the superiority of one location over another, the choice
shares with invasive ventilation the goals of improving gas of location will be based on practitioner preference. Perhaps
exchange, either nocturnal, daytime, or both, and minimiz- more important than the specific location is the availability
ing complications. Even more than with invasive ventila- of skilled, attentive practitioners to help during the initia-
tion, though, NIV seeks to alleviate symptoms and optimize tion and adaptation processes.
comfort. Because of the open-circuit d esign of noninvasive
positive-pressure ventilators, success depends largely on
patient cooperation and acceptance. Patient tolerance is an
important goal because the other goals are not acl1ievable MASKS (INTERFACES)
unless the patient accepts the therapy. The goals of acute A d aunting array of interfaces has become available to
and long-term applications are overlappin& but alleviation deliver NPPV, and detailed descriptions can be found
of increased work of breathing is an important goal in acute elsewhere.260 In brief, the most commonly used interfaces
applications, whereas improvement in sleep duration and in both acute and long-term settings are nasal and oronasal
quality is more important during long-tem1 applications. (or full-face) masks. Nasal masks usually are triangular
The following gives recommendations for initiation, citing clear plas tic domes that have soft silicone sealing surfaces.
evidence when available, pointing out controversy where it Oronasal (or full-face) masks are similar in appearance but
exists, and offering opinion where necessary. Most sections are larger and fit over the nose and mouth. Nasal inter-
offer comments on both acute and long-term applications. faces offer many modifications, however, including nasal
pillows with soft rubber cones that insert directly into the
nares, so-called minimasks that fit over the tip of the nose,
LOCATION
and gel-filled seals designed to enhance comfort. Various
ACUTE oro nasal masks are available, including those with foam- or
NlV can be initiated wherever the patient p resents air-filled seals and a chin support. A larger version of the
with acute respiratory distress-in the emergency full-face mask is available that seals around the perimeter
d epartrnent,49,258 ICU, 16•51 intermediate- or respiratory-care of the face, potentially enl1ancing comfort and eliminating
wut, or hospital ward. 52 A survey of acute-care hospitals the development of nasal bridge ulcers.261 Oral interfaces
in Massachusetts and Rhode Island found that a third also are used occasionally, mainly in the long-term setting
of NPPV initiations were in the emergency department, in patients with neuromuscular disease. 162
and half were in the ICU.259 Following initiation, trans- More recently, a number of studies have evaluated the
fer to a location that offers con tinuous monitoring is "helmet," a novel interface for NJV that consists of a clear
recommended until the patient s tabilizes. The patient's plastic cylinder that fits over the head and seals on the
acuity of illness and risk of deterioration if an acciden- shoulders. The Food and Drug Administration has not yet
tal discotmection occurs should dictate the intensity of approved this application in the United States. It avoids
monitoring. During transfers, ventilator assis tance and contact with the nose and mouth, eliminating nasal ul-
monitoring should be continued because rapid deterio- ceration and potentially enhancing comfort. 262 CPAP de-
rations can occur. Recent preliminary evidence suggests livered via the helmet to patients with acute respiratory
that less acutely ill patients with COPD can be managed failure is better tolerated than the full-fa ce mask in his-
on a general medical ward, but if pH is less than 7.30, torically matched controJs. 263 Compared with the full-face
admission to a more i11tensively monitored setting is mask used to deliver PSV in patients with COPD in acute
advised. 52 respiratory failure26-l the helmet similarly improved vital
signs, acllieved similar intubation and mortality rates, and hypopnea index, gas exchange, and sleep quality, but the
reduced complications. Paco2 tended to be higher, however, nasal mask required chin straps to control mouth leaks, and
in patients treated with the helmet, raising concerns about sleep efficiency was less with the full-face mask.
rebreathin/f High flow rates must be used to avoid this Once again, clinicians must be prepared to try a number
problem,26 but this contributes to noise levels exceeding of different interfaces to optimize comfort. Fitting gauges
100 dB. 266 should be used w hen available to facilitate proper sizing,
Oral interfaces have been used successfuUy for many and strap tension should be the minimum that controls
years in patients with slowly progressive neuromuscular leaks. Headstrap materials, tightness, and attaclunents to
diseases. 162 Long-term nasal ventilation appears to offer im- the head and mask are also important for comfort. Many
proved tolerance compared w ith mouthpiece ventilation in different types of headstraps are available, although they
some patients, 168 although no studies have directly com- usually are designed for a particular mask.
pared nasal and mouthpiece NPPV. Either may be effec-
tive, even in patients with minimal pulmonary reserve, and
SELECTION OF A VENTILATOR
both may be used in the same patient, nasal ventilation dur-
ing sleep at night, for example, with mouthpiece ventilation ACUTE
used as needed during the daytime.168 A steadily expanding number of ventilators are available
for NPPV in the acute setting. Bilevel devices are portable
PSV ventilators, first developed for home applications,
SELECTION OF INTERFACES
that cycle between higher inspiratory and lower expiratory
ACUTE pressures. 202 These ventilators have been used widely in
Ideally, interfaces for the acute setting should be inexpen- acute settings because of their ease of administration and
sive and disposable or reusable without sacrificing comfort. low cost, but they have been limited by a lack of alarms,
A recent randomized, controlled triaJ in 70 patients with monitoring capabilities, and 02 blenders. Newer bilevel de-
acute respiratory failure showed that full-face and nasal vices have been designed specifically for acute applications
masks similarly improve dyspnea, vital signs, and gas ex- of NPPV. They have features aimed at enhancing leak com-
change, but the nasal mask had a higher initial intolerance pensation and patient comfort, such as adjustable triggering
rate (34% versus 12%), attributed to air leakirtg through the and cycling mechanisms and rise times (the time to reach
mouth.267 Thus the full-face mask usually is the mask of the preset inspiratory pressure).
first choice in the acute setting, although claustrophobic pa- "Critical care" ventila tors are tl10se designed for invasive
tients or those with a need to expectorate frequently may ventilation and, by virtue of microprocessor technology, of-
fare better with nasal masks. The larger full-face mask that fer a wide variety of modes, extensive alarm and monitoring
seals around the perimeter of the face was rated by patients capabilities, and 02 blenders. In the past, these devices have
as more comfortable than the standard full-face mask in a been limited by triggering of nuisance alarms and linlited
preliminary report. 268 Concerns have been raised about the leak-compensating abilities when used for NPPV. 274 Many,
dead space attributable to the large volwnes of these face however, now offer " NIV modes" that use a PSV mode, si-
masks, but "streaming" of airflow directly from the inlet lence alarms, and add leak compensation and algorithms
to the patient's nose and mouth appears to minimize this that facilitate triggering and cycling, even in tl1e face ofleaks.
problem.269•270 The oral interface is used sometimes in the A laboratory study that compared a number of bilevel ven-
acute setting to facilitate initial patient adaptation. 271 Clin- tilators w ith a critical-care ventilator found that triggering,
icians should have a variety of interfaces readily available; cycling, and leak-compensatory mechanisms were s uperior
a "mask bag" can be suspended from the ventilator so that in several of the bi1evel ventilators.275
individual patient needs can be accommodated. Whichever Because they use a single tube for both inspiration and
interface is chosen, optimal fit and comfort are critical to the expiration, bilevel ventilators contribute to C~ rebreath-
eventual success of NPPV. ing unless used with a nonrebreathing exhalation valve tl1at
may increase expiratory resistance and expiratory work of
CHRONIC breathing.276·277 This rebreathing can be minimized by us-
Comfort and tolerance are even more important in the long- ing an expiratory pressure greater than 4 cmH20 276 and
term setting because interfaces must be used for months, masks with an in-mask exhalation valve situated over the
mainly during sleep, before being replaced. Many differ- bridge of the nose.269, 270 Comparisons ofbilevel and critical-
ent interfaces are available partly because of the demand care ventilators in intubated patients have demonstrated
driven by the large population of patients witl1 obstruc- that gas exchange is equivalent, but work of breatlling is
tive sleep apnea using similar teclmology. Standard nasal increased during bilevel ventilation if minimal expiratory
masks are the most commonly used interfaces in the chronic pressure levels (2- 3 cmH 20) are used.278 When expiratory
setting, and a short-term controlled trial on naive patients pressures of 5 cmH20 are used, however, the two types per-
with restrictive and obstructive forms of chronic respira- form equally weB in supporting gas excl1ange and reducing
tory failure found that patients rated these nasal masks as work of breathing, presumably because of counterbalancing
more comfortable than nasaJ prongs or full-face masks. 272 of auto-PEEP. For delivery of NIV, clinical outcome stud-
A polysomnograph.ic comparison of the two masks in pa- ies using bilevel ventilators report success rates that com-
tients with chronic respiratory failure273 fotmd that nasal pare favorably with those for critical-care ventilators,49,52
and full-face masks were equivalent with regard to apnea- although no randomized, controlled trials have compared
the two directly. Thus the selection of either system can be be measured. These specific adjustments, however, are un-
justified, and the choice is often based on availability and necessary when PAV is used to deliver NPPV clinically. PAV
financial considerations. Further, recent developments have has been shown to be as effective and a more comfortable
blurred the distinctions between the ventilators, with bilevel means of administering NPPV than PSV delivered via a
ventilators adding monitoring and alarm capabilities as well critical-care ventilator285 or a bilevel device. 286 Ventilators
as 02 blenders. offering PAV are currently available in Europe and Canada
but have not yet been approved by the Food and Drug Ad-
CHRONIC ministration in the United States.
Blower- or turbine-based portable pressure-limited bilevel
ventilators are used most often in the long-term setting to CHRONIC
d eliver NPPV. In a 9-year Swiss survey, 184 volume-lirnited In the long-term setting, pressure-support and volume-
devices predominated initially, but pressure-limited de- limited ventilators achieve similar levels of ovemight
vices accounted for over 90% of ventilator applications dur- oxygenation.280 Thirty consecutive patients, mainly with
ing the latter years. This shift has been driven by the low restrictive forms of chronic respiratory failure, received
cost, ease of use, and portability of the pressure-limited de- nasal volume-limited ventilation for 1 month followed by
vices. In addition, manufacturers have steadily been adding pressure-limited ventilation. 279 Only 2 patients failed to im-
features that enl1cmce monitoring. Some now offer wireless prove with volume-limited ventilation, whereas 10 had in-
Internet connections that permit home monitoring of respi- creased Paco, or symptomatic deterioration when switched
ratory rate, oximetry, airway pressures, tidal volumes, and to pressure-limited ventilation. Conversely, 10 patients in
air leaks. Portable volume-limited positive-pressure venti- another study had improved daytime blood gases when
lators are still preferred by some clinicians for specific ap- switched from volume- to pressure-limited ventilation. 287
plications. Because they offer sophisticated monitoring, they Although these were not prospective, randomized trials,
are used in patients requiring nearly continuous ventila tor they show no clear advantage of one ventilator mode over
support. Because of their high pressure-generating capa- the other. Thus the choice between the two hinges on clin-
bilities, they may be preferred in patients with high res- ician preference and consideration of specific ventilator
piratory system impedances, such those with morbid obe- properties such as portability, pressure-generating capabil-
sity or chest-wall deformity, or they may be used to "stack" ities, backup-battery life, ability to stack breaths, and other
breaths to attain a higher inspired lung volume to increase factors. In general, though, volume-limited ventilators have
cough flows.193 Also, because volume-limited ventilators greater pressure-generating and alarm capabilities.
usually are driven by intermittent piston action rather than
continuously operating blowers, backup battery life can be
VENTILATOR SETTINGS
considerably longer. Studies in the long-term setting have
shown no consistent benefit of one type of ventilator over ACUTE
the other,279•280 however, and the choice usually becomes Two strategies have been described: the high-low approach,
one of clinician and/ or patient preference. which starts with a higher inspiratory pressure (20-25 em
H 2 0) and lowers it if patients are intolerant,16 and the
low-high approach, which s tarts with a low inspiratory pres-
SELECTION OF A VENTILATOR MODE
sure (8-10 cmH 2 0) and raises it gradually as tolerated by the
ACUTE patient. 49 The former approach prioritizes rapid alleviation
Although no studies have demonstrated superior efficacy of of respiratory distress; the latter aims to optimize patient
one ventilator mode over another in the acute setting, some comfort in an effort to maximize patient tolerance. Reported
practitioners have found enhanced patient comfort or com- success rates for the two approaches are similar, although
pliance w ith PSV.281•282 Thus, although either volume- and no studies have compared them directly. Paramount with
pressure-limited modes can be used with the expectation of both approaches is the realization that subsequent adjust-
similar rates of success, pressure-limited modes appear to ments are necessary depending on patient response. Higher
be accepted more readily by patients. Some newer hybrid initia l pressure often must be adjusted downward, and it is
ventilators designed specifically for NIV are able to deliver very important that low initial pressure be raised (us ually
both volume- or pressure-limited modes, with the capability to 12- 20 cmH20) within the first hour, if possible, to provide
of adjusting triggering and cycling sensitiv ity, rise time, and adequate ventilator assistance.
inspiratory duration to optimize patient comfort. 233 PAY, a Expiratory pressure (or PEEP) is used routinely w ith
tmique mode that tracks instantaneous patient airflow, is bilevel ventilators and is optional w ith volume-limited ven-
capable of closely matching patient breathing pattern and tilators. Bilevel ventilators require a bias flow during expi-
hence potentially enhancing synchrony and comfort284 (see ration to flush C02 from the single ventilator tube and avoid
Chapter 13). The flow signal is fed back to the ventilator rebreathing. 276 Minimal expiratory pressure with these ven-
as a raw signal (flow assist) or integrated over time (vol- tilators is in the 3-4 onH20 range. Higher expiratory pres-
ume assist). Gains are imposed on both these signals and sures (typically 4-8 cmH20) are used to counterbalance in-
on a composite signal (proportional assist) that can be ad- trinsic PEEP during treatment of exacerbations of COPD or
justed to assist a " proportion" of the patient's breathing ef- to enhance oxygenation. It is important to recall that the dif-
fort. Theoretically, flow and volume assist are adjus ted to ference betw·een inspiratory and expiratory pressure is the
match resistive and elastic \•vork, respectively, which must level of PSV, so inspiratory pressure must be increased in
tandem with expiratory pressure if the same level of ven- tory failure. Humidification may enhance comfort during
tilatory assistance is to be maintained. Adjusting the rate NPPV and is advised if NPPV is to be used for more than
of pressurization (or rise time) may be useful to enhance a few hours. A heated humidifier is preferred over a heat
comfort; patients with COPD prefer slightly more rapid and moisture exchanger because the latter adds to work of
rise times than restrictive patients. Very rapid pressuriza- breathing292 and may interfere with triggering and cycling.
tion rates minimize the work of breathing in patients with Also, with excessive air leaking, a heated humidifier lowers
COPD but may be sensed as less comfortable by patients nasal resistance. 22 In the long-term setting, humidification
than slightly lower pressurization rates. 288 usually is provided, particularly during the winter months
in colder climates. Nasogastric tubes are not recommended
CHRONIC routinely as adjuncts to NlV, even when oronasal masks are
No consensus has been reached on how to select ventilator used.
settings for patients in the long-term setting. In the sleep
laboratory, one approach is to increase expiratory pressure
NONINVASIVE TECHNIQUES TO ASSIST COUGH
until apneas are eliminated and inspiratory pressure un-
til hypopneas are eliminated without inducing excessive Because it provides no direct access to the lower airways, as
arousals. This approach, however, does not ensure that the does invasive ventilation, NPPV depends on the integrity of
pressures selected will alleviate hypoventilation, nor does airway protective reflexes for its success. In the acute setting,
it facilitate initial adaptation if the patient finds the rec- patients with excessive secretions or severe cough impair-
ommended initial pressures are intolerable. Thus the au- ment are intubated rather than managed noninvasively. In
thor prefers a gradual uptitration of pressures over weeks the long-term setting, however, a number of techniques have
or even months as tolerated by the patient. Initial inspi- been developed to enhance secretion removal in patients
ratory pressure is 6-10 cmH20, with increases weekly by with compromised secretion-clearance capabilities. These
1-2 cmH20 as tolerated. Expiratory pressure is set at 3-4 techniques are of greatest value in patients witl1 neuromus-
cmH2 0 and rarely is increased above 6 cmH2 0 unless sleep cular disease and weakened expiratory muscles. Severe bul-
apnea is deemed an important contributor. For volun1e- bar involvement such as occurs with ALS is treated most
limited ventilation, an initial tidal volume of 10- 15 ml/kg effectively with invasive ventilation. Secretion retention re-
has been recommended, in excess of the standard recom- lated to abnormal mucus, such as occurs with CF, is beyond
mendations for invasive ventilation, because of the need to the scope of this chapter.
compensate for air leaks. 289 Parreira et al290 found that a tidal An effective cough depends on the ability to gener-
volume of 13 ml/kg optimized assisted minute volume in ate adequate expiratory airflow, estimated at more tl1an
a group of patients with restrictive thoracic disorders. 160 liters/min. 293 Expiratory a irflow is determined by lung
A backup rate sufficiently high to control breathing noc- and chest-wall elasticity, airway conductance, and at least at
turnally has been recommended for patients w ith neuro- higher lung volumes, expiratory muscle force. By generat-
muscular disease to maximize respiratory muscle rest and ing an adequate vital capacity(> 2.51iters) to take advantage
prevent apneas. In patients with severe stable COPD, on of respiratory system elasticity, inspiratory muscle function
the other hand, the need for a backup rate is not clear, also contributes to cough adequacy. In addition, an effective
considering that one controlled trial of NPPV found signifi- cough requires the ability to close the glottis so that explo-
cant benefit using a spontaneous ventilator mode without a sive release of intrathoracic pressure can generate high peak
backup rate. 221 Compared with a spontaneo us mode, these expiratory cough flows. 294 v'lhen patients with severe neu-
authors found that use of a backup rate had no effect on romuscular disease a re too weak to take advantage of these
nocturnal gas exchange in patients w ith COPD and chronic mechanisms and have insufficient coug h flows, techniques
respiratory failure. On the other hand, Parreira et al290 found to assist cough should be appUed.
that minute volume was optimized when patients with re- The simplest maneuver to augment cough flow is man-
strictive thoracic disorders used a relatively high backup ually assisted or "quad" coughing. This consists of firm,
rate of 23 breatl1s per minute. quick thrusts applied to the abdomen using tl1e palms of the
hands, tin1ed to coincide with the patient's cough effort.'l93
The technique should be taught to caregivers of patients
ADJUNCTS TO NONINVASIVE VENTILATION
with severe respiratory muscle weakness with instructions
With bilevel ventilators, supplemental 0 2 can be provided to use it whenever the patient has difficulty expectorating
directly through tubing connected to a nipple in the mask secretions. With practice, the technique can be applied ef-
or to a T connector in the ventilator tubing, with liter flow fectively and frequently with minimal discomfort to the pa-
adjusted to keep Sa02 above 90-92%. Maximal Fio2 using tient. Peak expiratory flows can be increased severalfold
this setup is only 45-50%. F10 , delivered via bilevel ventila- when manually assisted coughing is applied successfully.295
tors depends on a number of factors, including 0 2 flow rate, To minimize the risk of regurgitation and aspiration of gas-
breathing pattern, ventilator settings, and location of the Oz tric contents, the patient should be semiupright when man-
connection (connection to the mask gives a higher F102 ). 291 ually assisted coughing is applied, and the technique should
With critical-care ventilators and some bilevel devices de- be used cautiously after meals. The technique can be used,
signed for acute applications, standard 0 2 blenders are used though, in patients witl1 gastric feeding tubes.
to accurately provide the desired F10z. Thus these latter ven- Although manually assisted coughing may enhance ex-
tilators are preferred for patients with hypoxemic respira- piratory force, it does not augment inspired volume. Thus
patients with severely restricted volumes may not achieve purpose of each piece of equipment and preparing the pa-
sufficient cough t1ows even when assisted by skilled care- tient for each step in the initiation process. Patients should
givers. To overcome this problem, the inhaled volume be reassured, encouraged to communicate a ny discomfort
should be augmented. One approach is to "stack" breaths or fears, and coached in ways to coordinate their breathing
us ing glossopharyngeal breathing296 or volume-linUted with the ventilator. When using nasal masks, patients are
ventilation and then to augment the cough using man- ins tructed to keep their mouths shut.
ual assistance. Another is to use a mechanical insufflator- Ttme demands on medical personnel have been a concern
exsufflator, a device that was developed during tl1e polio for the delivery of NPPV. Chevrolet et al303 were the firs t to
epidemics to a id in airway secretion remova1. 295 This device draw attention to this potential problem, reporting la rge
delivers a positive inspiratory pressure of 30-40 cmH20 via time demands on nurses during administration of NPPV.
a face mask and then rapidly switches to an equal nega- Bott et al 48 subsequently found that nurses rated NPPV as no
tive pressure. The positive pressure ensures delivery of an more demanding to administer than conventional therapy.
adequate tidal volume, and the negative pressure has the ef- Conversely, Kramer et al49 found that compared with con-
fect of simulating the rapid expiratory t1ows generated by a trols, NPPV patients tended to require mor~ time from respi-
cough. Use of the insufflator-exsttfflator has been combined ratory thera pists during the first 8 hours, an amount that fell
with manually assisted coughing in an effort to further aug- significantly during the second 8 hours. Nava et al 304 also
ment cough t1ows. 295 found that respira tory thera pists spent more time during
The mechanical insufflator-exsufflator increases cough the first 48 hours caring for NPPV patients than invasively
flows in patients with neuromuscular weakness but is less ventilated patients. These findings indicate that NPPV ini-
effective in patients with kyphoscoliosis and in one study tially requires more time to administer than conventional
actuaJly decreased cough t1ows of patients with COPD. 297 therapy, for interface fitting and initial ventilator adjust-
In another study, however, m echanical insufflation- ment, although these demands diminish rapidly after the
exsufflation decreased d yspnea and improved oxygenation first few hours. Nurses, respiratory therapists, physicia ns,
not only in neuromuscular patients but also in patients with or some combination of these must spend the additio nal
airflow obstruction.298 Although no controlled trials have time, depending on irlstitutional practices.
evaluated the efficacy of the cough insufflator-exsufflator, As might be anticipated, the experience of personnel also
anecdotal evidence suggests that it enhances removal of appears to be important for the success of NPPV. Girou
secretions in pa tients with impaired cough. It has been et al14 reviewed the experience of a 26-bed French TCU be-
reported to reduce failures (need fo r intuba tion) in neu- tween January 1994and December2001 on479patientswith
romuscular patients in critical-care settings,299 reduce the eitl1er COPD or cardiogenic pulmonary edema requiring
occurrence of atelectasis and pneumonias in children with ventilator assistance, invas ively or noninvasively. Use of
neuromuscular disease,300 and improve cough t1ows in pa- NIV increased from approxin1ately 20- 90% (of the patients)
tients with AlS unless there is bulbar dysfunction, which during the course of the study, associated with a decrease
may predispose to upper airway collapse.301 It has been in the rate of nosocomial pneumonias from 20-8% and in
particularly useful in patient homes to treat episodes of JCU mortality from 21-7% (all p < .05). The authors specu-
acute bronchitis, permitting avoidance ofhospitalization.302 lated that a "learning effect" over the course of the study was
Other devices that aid expectoration, such as the percussive responsible for the in1proved outcomes. Over a n 8-year pe-
ventilator, Hayek oscillator, and vibratory vest, have some riod in their ICU, Carlucci et al305 found tl1at NPPV su ccess
theoretical advantages over other techniques for assisting ra tes increased in patients with COPD despite a worsening
secretion removal. 193 Their use of high-frequency vibrations of the severity of illness as staff gained experience with the
(up to 10-15 H z) may facilitate mobilization of airway se- technique. Whether or not guidelines for NPPV implemen-
cretions. Unfortunately, even anecdotal evidence to support tation can improve patient outcomes remains to be estab-
their use is lacking. lished. Sinuff e t al306 found tha t clinician behavior cl1anged
Clinicians caring for pa tients with severely impaired after implementation of a guideline at their single academic
cough should be familiar with the various techniques avail- institution, but overall patient outcomes were not altered.
able to assist expectoration. These are particularly important
with NIV because there is no direct access to the airway, and
secretion retention is a frequent complication and common
cause for failure. Although controlled data are lacking, these M onitoring
techniques appear to help in maintaining airway patency in
patients with cough impairment during use of NIV in both Patients receiving NfV are monitored to determine whether
acute and chronic settings. the goals are being achieved (see Table 19-8).
SUBJECTIVE RESPONSES
ROLE OF THE CLINICIAN: TIME DEMAND S,
The key aims of NPPV are alleviation of respiratory dis-
IMPORTANCE OF EXPERIENCE, AN D GUlDELINES tress in the acute setting and of fatigue, hypersomnolence,
An experienced clinician conveying an air of assuredness and other symptoms of impaired sleep in the chronic set-
to patients is thought to be crucial to the success of NPPV. ting while achieving patient tolerance. Agitation and mask
TI1e clinician should motivate the patient, explaining the discomfort are challenges during NPPV. These aspects can
be assessed easily using bedside observation and patient noctt1mal oximetry are also unclear in follow-up of long-
queries. Some patients minimize or deny discomfort and term NPPV, but one pragmatic approach is to screen pa-
still may have great difficulty adapting successfully to NIV, tients using home oximetry and to perform more sophisti-
so clinicians not should only query patients but also should cated studies when the oximetry results indicate the need
observe for nonverbal signs of distress or discomfort. for further evaluation.
PHYSIOLOGIC RESPONSES Adaptation

Evidence of physiologic improvement within the first hour
or two, including decreases in respiratory and heart rates, ACUTE
diminished sternocleidomastoid muscle activity, and elim-
It is critically important to ascertain that the delivered pres-
ination of abdominal paradox, portends a favorable NPPV
sures are sufficient to alleviate respiratory distress; a com-
outcome.'105, 153 Patients should be breathing in synchrony
mon mistake is to fail to increase pressures quickly enough,
with the ventilator, and air leaking should be minimal. Some
and the patient fails because of inadequate ventilator sup-
clinicians also monitor tidal volumes, aiming for delivered
port. TI1e patient also should use the ventilator for more
volumes in excess of 7 ml/kg.307 Relying on ventilator mon- time initially, with increasing periods of time off the ven-
itoring to follow tidal volumes may be misleading, however, tilator as the underlying condition improves. Some clini-
particttlarly during use of bilevel ventilators, because these cians encourage use most of the time initially, as dictated
integrate the inspired flow signal and may be very inacctt- by the degree of respiratory distress during ventilator-free
rate in the face of air leaks.
intervals.49 Others employ sequential use,309 wherein pe-
riods of use alternate with lengthy ventilator-free periods;
GAS EXCHANGE total daily use averages only 6 hours, although this would
be suitable only for mildly ill patients. When no respira-
Improvement in gas exchange as determined by continuous
tory distress recurs dt1ring ventilator-free intervals, ventila-
oximetry and occasional blood gases is a key aim in acute
tor assistance is discontinued. Total duration of ventilator
application of NPPV, although improvement in ventilation
assistance depends on the speed of resolution of the respira-
may occttr g radually over hours.16 In chronic stable patients,
tory failure. Patients with acute pulmonary edema require
the improvementin daytime gas exchange occurs even more
an average of 6-7 hours of ventilator use, 99 whereas patients
slowly, over a period of weeks, depending on the duration of
with COPD average 2 or more days. 49 Some patients may
daily ventilator use. Some patients adapt slowly and require continue nocturnal ventilation after discharge from the hos-
up to several months before they sleep through the night us- pital, following guidelines for long -term use of NPPV.
ing the ventilator. Arterial blood-gas measurement should
be delayed until the patient is consistently using the ven-
tilator for a period of time likely to improve gas exchange: LONG TERM
usually at least 4-6 hours a day. No consensus on an ideal Patients start more gradually and increase periods of use
level for daytime Paco, has been reached; most investigators as tolerated. Anxious patients may begin with only an hour
target levels in the middle 40s. In t11e author's experience, a or two of daytime use followed by gradually increasing pe-
daytime Paco1 of up to 60 mmHg or higher may be tolerated riods of nocturnal use over several weeks or even months.
without hypersomnolence or evidence of cor pulmonale as Compared \vith the acu te setting, urgency in the chronic
long as oxygenation is adequate. Noninvasive C02 moni- setting is less, and because the intent is to use the ventila-
toring rna y be useful for trending purposes in patients with tor during sleep, great care must be exercised in optimizing
normal lung parenchyma such as those with netlromuscular patient comfort. During this period, visits from a home res-
disease. Transcutaneous Paco1 is probably the most useful piratory therapist are helpful to assess comfort and address
because variable air leaks and breathing patterns and di- any problems tl1at arise. Criner et al228 found that 36% of
lution secondary to bias flow with some ventilators render patients required further adjustments in mask or ventila tor
end-tidal C02 recordings inaccurate, particularly if the pa- settings, even after discharge from a several-week stay in
tient has parenchymal lung disease.308 an inpatient ventilator unit.
SLEEP
Adverse Effects and Complications
Little is known about sleep during NPPV in tl1e acute set-
ting, and the role of sleep monitoring in the long-term set- In properly selected patients, NPPV is safe and well
ting is controversial. As noted earlier, some clinicians pre- tolerated, and most of the adverse effects are related to the
fer to use the sleep laboratory to decide on initial settings interface or ventilator (Table 19-9). Approximately 10-15%
for NPPV. Others begin most patients, particularly those of patients fail to tolerate interfaces despite adjustments in
with neuromuscular disease, without a polysomnographic strap tension, repositioning, and tri.als o f different sizes and
evaluation. If both approaches prove to be equal in achiev- types of interfaces. These patients may have claustrophobia
ing the goals of NIV, it would be difficult to argue that or high levels of anxiety and fail even after multiple attempts
routine sleep studies are necessary. The relative utilities at mask readjustment and judicious use of sedation. Other
of polysomnograhy, multichannel portable recordings, and mask-related adverse effects include erythema, pain, or
TABLE 19-9 Frequency of Adverse Side Effects and CompUcations of NPPV with
Possible Remedies
Complication Occurrence (%)" Possible Remedy
Mask-related
Discomfort 30-50% Check fit, ad just strap, new mask type
Facial skin erythema 20-34% Loosen straps, apply arti fical skin
Claustrophobia 5-10% Smaller mask, sedation
Nasa l bridge ulceration 5-10% Loosen straps, artificial skin, change mask type
Ameiform rash 5-10% Topical steroids or antibiotics
Air pressur e- or Bow-related
Nasal congestion 20-50% Nasal steroids, decongestant/antihistamines
Sinus/car pain 10-30% Reduce pressure if intolerable
Nasal/oral dryness 10-20% Nasal saline/ emomen ts, add humidifier, decrease leak
Eye irritation 10-20% Check mask fit, readjust straps
Gastric insufflation 5-10% Reassure, simethacone, reduce pressure if intolerable
Air leaks 80-100% Encourage mouth closure, try chi n straps, oronasal
mask
If using nasal mask, reduce pressures slightly
Major complications
Aspiration pneumonia <5% Careful patient selection
Hypotension <5% Reduce pressure
Pneumothorax <5% Stop ventilation if possible, reduce pressure if not
Thoracostomy tube if indicated
"Occurrences estimated from Uterature and author's expt!l"ience

souRcl!: Adapted, with permission, from Mehta and liiiL1
ulceration on the bridge of the nose. Minimizing strap patient cooperation interferes with efficacy and may be ame-
tension and advances in mask technology, with softer liorated by judicious use of sedation, sucl1 as low doses of
silicon seals and routine use of a rtificial skin on the bridge benzodiazapines. Unremitting agitation should be consid-
of the nose, have been associated with less frequent nasal ered an indication for intubation. Aspiration is a reported
bridge ulceration, which had been as high as 40% in earlier complication311 but should be unusual if patients with swal-
studies.31 0 lov.ring dysftmction and problems clearing secretions are
Air pressure- and flow-related adverse effects include excluded. Routine insertion of nasogastric htbes has been
oro nasal dryness or congestion that may respond to humid- recommended at some centers to lower the risk of aspiration
ification or decongestants, sinus and ear pain, eye irritation during use of face masks,307 but there are no data available
from air leakage under the mas k seal on the sides of the to support this practice, and it is no longer recommended.
nose, and gastric insufflation. Readjusting the mask seal to Progressive hypoventilation occurs in a small minority of
reduce air leaking or reducing inspiratory pressure, if pos- patients, usually necessitating intubation. Uncooperative-
sible, may help. ness, lack of synchronization with the ventilator, inability
Air leaking is ubiquito us during NIY, either under the to tolerate adequate inflation pressures, and excessive air
seal or through the mouth with nasal ventilation. Air leaking leaking are common causes for this predicament, and mea-
adds to discomfort and may interfere with ventilator trigger- sures aimed at correcting these may be helpful. Rarely, nasal
ing and cycling, as well as efficacy of ventila tion. The leaks obstruction contributes and may respond to decongestant
usually are tolerated as long as the ventilator compensates sprays.
adequately, as most bilevel ventilators do. As discussed ear- In the acute setting, NPPV fails in roughly a third to a
lier, bilevel ventilators cannot ftmction properly without quarter of patients depending on many factors, including
a small intentional leak in the tubing, which is necessary skill and experience of the team, occurrence of adverse ef-
for removal of C02 to prevent rebreathing. Most volume- fects and complications as discussed earHer, and underly-
limited modes compensate poorly for leaks, but large air ing severity of the patient's illness. Progression of the un-
leaks may compromise the effectiveness of any form of derlying process, such as worsening hypoxemia, also may
NPPV. Attempts to control air leaks should start with a re- be responsible for failure. Close monitoring with proactive
assessment of mask fit and readjus tment of the head straps. efforts to address and minimize adverse effects should min-
To reduce air leaking through the mouth d uring nasal venti- imize failure rates.
lation, edentulous patients should not be treated with nasal
masks, others are coached to keep their mouths shut, chin
straps may be used, or an oronasal mask may be tried. Summary and Conclusions
Major complications s ucl1 as pneumothoraces are tm-
usual probably because inflation pressm es are low com- In the acute setting, evidence now supports NPPV in the
pared with those used with invasive ventilation. Lack of treatment of respiratory failure secondary to acute exacerba·
tions of COPD, acute cardiogenic pulmonary edema (whicl1 4. Pingleton SK. Complications of acute respiratory failure. Am
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longed intubation. Chest 1989; 96:877- 84.
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27:417-34.
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470 PARTVI NONINVASIVEMETHODSOFVENTILATORSUPPORT
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PART VII Over the past 25 years, high-frequency ventilators provided
an experimental tool tha t identified many of the mecha-
nisms that contribute to VILl. It became clear that VILI
UNCONVENTIONAL is minimized by ventilator patterns that achieve homoge-
neous aeration of as much of the lung as possible, avoid-
METHODS OF ing both injury from overdistension (volutrauma) and that
arising from the repetitive op ening and closing of lung units
VENTILATOR SUPPORT in regions of ongoing atelectasis (atelectrauma)1 (Fig. 20-1).
Failure to opera te in the "safe zone" initiates biotrauma.2' 3
The concept of a "safe zone" within which to ventilate
the atelectasis-prone lung has been reflected in numerous
thapter 20 _ _ _ _ _ _ _ _ __ clinical trials of lung-protective ventilation over the last
10 years. Conventional ventilator protocols have found sur-
HIGH-FREQUENCY vival benefit from shrinking the tidal volume and minimiz-
ing peak or plateau distending pressures. 4 Studies such as
VENTILATION that of Roupie et al5 suggest that very small tidal volumes
ALISON B FROESE may be needed in some patients to avoid overdis tension.
Very high positive end-expiratory pressure (PEEP) levels
would be needed in some patients to avoid derecruitment.6
Concurrently, HFV- both in oscillatory and jet forms-has
become an established lung-protective modality in neona-
tal and pediatric intensive care7 - 11 (see Chapter 25). The
ques tion now arises: In severe acute respiratory distress
IDSTORICAL OVERVIEW syndrome (ARDS) in adult patients, will use of a high-
BASIC PRINCIPLES OF HFOV frequency device result in clinically important outcome
Oxygena tion differences compared with lung-protective conventional
C02 Elimination ventilation?
PHYSIOLOGIC EFFECTS OF HFOV
Cardiopulmonary Interactions
Interaction v.rith Spontaneous Breathing Historical Overview
RAT IONALE, ADVANTAGES, AND LIMITATIONS
Advantages of HFOV Several existing reviews detail th e his tory of HFV.12' 13 Early
Limitations developments often were driven by issues peripheral to
INDICATIONS AND CONTRAINDICATIONS pulmonary critical care. Sjostrand et al14 wanted to elim-
Indications inate respiration-related variations in vascular pressures
Contraindications so that they could investigate carotid sinus reflexes a nd
COMPARISON WITH OTHER MODES developed high-frequency positive-pressure ventilation
VARIATIONS IN DELIVERY (HFPPV). Lunkenheimer et al15 wanted to use the lw1gs
ADJUSTMENTS AT THE BEDSIDE as a route to deliver oscillatory pressure pulses to the my-
Preparation for Initiation of HFOV (Table 20-3) ocardium. They needed apnea for this and were amazed to
Oxygena tion find gas exchange occurring while they applied their high-
C02 Elimination frequency flow oscillations. Emerson 16 thought that high-
Patient Positioning frequency flow oscillations might provide internal physio-
TROUBLESH OOTING therapy and help to mobilize secretions. In Toronto, Bryan17
Paco2 Problems initia lly was curious to see whe ther an external "shaker"
Oxygena tion Problems could enhance the gas mixing produced by cardiogenic os-
Air Leaks cillations. Klain and Smith 18 explored jet ventila tion at in-
Hemodynamic Compromise creasing frequencies to solve the problem of achieving alve-
IMPORTANT UNKNOWNS olar ventilation in respiratory systems w ith a big leak, such
FUTURE DffiECTIONS as a bronchopleural fistula .
Redesigned Machines These devices often became intriguing phenomena in
Clinical Lung-Volume Monitoring search of a reason for being. Devices sucl1 as HFPPV a11d
high-frequency jet ventilation (HFJV) were particularly use-
High-frequency ventilation (HFV) has been an unconven- ful for surgical procedures when both anesthesiologist and
tional option for over 30 years. Several varieties of high- surgeon needed access to the airway. The notion, however,
frequency ventilators have come and gone over that period. that high rates and small tidal volumes might be of broader
Currently, interest i11 H FV in adult critical care is part of therapeutic value needed a pathophysiologic rationale. An
a larger search for ventila tor patterns tha t can support gas emerging concept in the 1970s was that many of the pul-
exchange in the severely hypoxemic patient without con- monary perturbations tha t put patients into inte11sive-care
tributing additional ventilator-induced lung injury (VILI). units (ICUs) were problems of low lung volume. Low lung
473
474 PART Vll UNCONVENTIONAL METHODS OF VENTILATOR SUPPORT
(CPAP) to improve alveolar aerationw A crucial insight

ZONE OF occurred early in our experience with hig h-frequency os-
OVERDISTENTION cillatory ventilation (HFOV) when we explored a variety of
mean airway pressure settings while ventilating an infant
with neonatal respiratory distress syndrome20 (Fig. 20-2).
The infant was stable in terms of both hemodynamics and
carbon dioxide (C0 2) elimination over the whole range of
mean pressures tested, but oxygenation varied markedly.
VOLUME One could either ventila te with a low mean airway pressure
and hig h fractional inspired oxygen concentration (Fio 2 ) or
ZONE OF a higher mean pressure and low F~o, . A choice had to be
DERECRUITMENT made. We gave priority to the reversal of low lung volumes.
AND ATELECTASIS We argued that the small-volume cycles of HFOV should al-
low one to optimize alveolar aeration by using higher mean
pressures than were considered safe during con ventional
PRESSURE
FIGURE 20-1 Pressure-volume cu rve of a moderately dis eased
• mechanical ventilation (CMV) while still keeping peak pres-
sures less than those needed to eliminate C02 a t conven-
tional rates. This pathophysiologic rationale continues to
lung, as in a patient with acute lung injury. Ventila tor-induced
guide high-frequency applications to this d ay.
lung injury (VILO occurs at both extremes of lung volume. In the
Many d evices invented along the way, such as HFPPV,
zone of overdisteusiou, damage arises from edema fluid
accumu lation, surfactant degradation, an d mechanical disruption. have since d isappeared from use. HFJV was explored in
In the zoue of derecmitmettt aud atelectasis, Jung in jury arises many adult ICUs in the 1980s for difficult cases of b ron-
from the direct trauma of repeated closure and re-expansion of chopleural fistula or tracheal disruption. 21 It gradually be-
small airways and alveoli, through accumulation and activation came clear tha t any oxygenation benefits occurring during
of inflammatory cells with release of cytokines (biotrauma), HFJV resulted from increases in mean lung volume, not
through interactions with local hypoxemia, by inhibition of from some unusual p roperties of gas distribution. 22 With an
surfactant, and through compensatory overexpansion of the rest HFJV device, the end-expiratory lung volume is a complex
of the lung as the lung "sh rinks." Hig h end-expiratory pressures product of jet diameter and placement, driving pressure,
p lu s small tidal volume cycles are needed to stay in the safe
jet frequency, and the time available for expiration. 23•24 Safe
tvirrdow. (Reproduced, with perrnissiorr, from Froese: Crit Care Med
use requires accurate intrapulmonary pressure monitoring,
25:906-8, 1997.)
whicll was rarely provided with early devices. Inadvertent
hy perinflation could cause problems with both circulatory
volumes were associated with poor lung compliance, in- depress ion and / or barotrauma. No North American com-
creasing airway and vascular resistances, increased work mercial adult-sized jet ventilator was ever marketed w ith
of breathing, airway closure, low ventilation-perfusion a safe, effective humidification system such as that avail-
(V AIQ) ratios, atelectasis, hypoxemia, and high oxygen (02) able in Europe. The largest early compar ative trial of HFJV
exposure. Neonatal outcome was improvedin.g simply from versus CMV in hypoxemic lung disease was performed be-
the introduction of continuous positive airway pressure fore the importance of atelectasis reversal was established.
.30 FIGURE 20-2 Relationship of oxygenati on, as reflected

•
in the arterial-alveolar P01 (a-A) ratio, to the mean
airway pressure applied during HFOV, at cons tant tidal
volume and freq uency, in an infant with respiratory
.26 distress syndrome. No circulatory instabil ity occurred
over the entire range of mean pressures . C02
elimination could be achieved equally well using a
. 22 high Fio 2 and a low mPaw or a low F1o2 and a h igh er
tnPaw. A choice of operating conditions had to be
a/A
made. (Reproduced, w ith penuission, from M ardlllk
.1 8 et al: TPediatr 99:287- 92, 1981.)
.1 4
•
.10
f....t
0 9 10 II 12 13 14 15 16 17 18
MEAN AIRWAY PRESSURE (e m H20)
CHAPTER 20 HIGH-FREQUENCY VENTILATION 4 75
It therefore was carried out with the goal of supporting gas
exchange with the lowest possible peak and mean pressures
and proved of no benefit. 25 For all these reasons, HFJV in
adults has become a rare event. Jet ventilation at high or
low frequ encies continues to be a useful approach to situa-
tions in which airway access must be shared during su rgical
procedures26 or alveolar ventilation needs to be maintained
in the presence of severe bronchopleural fistulas.23
HFJV has persisted in neonatal and pediatric critical care
largely because of the continuous design refinements of the
Bunnell Life Pulse device. 27 Early problems with poor hu- Inspiratory
midification causing desiccation of tracheal mucosa were bias flow
corrected, appropriate pressure-monitoring systems were
devised, and expert training and technical support were
provided. Valve
A hybrid device combining HFV and con ventional
pressure-cycled ventilation [e.g., the high-frequency Valve
percussive ventila tion/ volume diffusive respirator
(HFPV /VDR; Percussionaire 4, Bird Teclmologies, Sand- Gas
point IO)] is used in many bum units . It has been reviewed outflow
recently.28 Currently, the main high-frequen cy ventilatory
options in the critical car e of adults or larger children are
HFOV or the HFPV/VDR Percussionaire. In neonatology
and small infants, high-frequency oscillatory ventilators,
high-frequency jet ventilators, and the high-frequency
percussive ventilator remain available. In view of its
increasing role in adult intensive care, this chapter will
focu s on HFOV.
Basic Principles of HFOV

HFOV achieves gas transport with stroke volumes approxi-
mating anatomic dead space. Quasi-sinusoidal flow oscilla- FIGURE 20-3 Schematic of a circuit for delivery of HFOV.
tions applied at the airway opening induce rapid gas mixing Q uasi-sinusoidal flow oscillations are generated by a diaphragm
within the lungs. A number of physical transport mecha- or piston p ump an d d irected to the endotracheal htbe. A bias flow
of humid ified gas flu shes the C02 th at is transp orted ou t of th e
nisms contribute to this mixing process. They have been re-
lungs out of the circuit. M ean airway p ressure is regulated by
viewed in detail elsewhere. 29 In practical terms, HFOV can adjus tments of the b ias flow and the resistan ce of the expiratory
be viewed as a mixing device that rapidly blends high-~/ limb. (Reproduced, w ith perm ission, from Krishnan et a/: Chest
low-C~ gas from the top of the endotracheal tube with 118:795-807, 2000.)
gas in the alveoli (Fig. 20-3). Net transport occurs along
the pa rtial-pressure gradients for 0 2 and C02, with C02
moving out of the lung along its partial-pressure gradi- separate control systems, unlike the situation with conven-
ent and 0 2 moving inward to the alveolar-capillary inter- tional ventilators, where it is often difficult to adjust one
face. These flow oscillations cause symmetric oscillations (i.e., the C02 level) without also a ffecting the other. Oxy-
of intrapulmonary pressure around a mean distending air- genation is regulated by reversing a telectasis and then find-
way pressure (mPaw) (Fig. 20-4). Although subambient ing the mean distending pressure that maintains alveolar
pressures can occur in the circuit, intrapulmonary air trap- expans ion. The F1 0 2 then is set at a level that maintains ap-
ping or"choke points" are unlikely with appropriate mPaw propriate arterial oxygenation goals. C02 elimination is rel-
settings. 30, 31 One can view HFOV as a means of deliver· atively independent of mean airway pressure,33 being reg-
ing "CPAP" with built-in C02 elimination. In contrast to ulated by frequency and stroke volume (i.e., power or 6P)
current conventional approaches to supplying CPAP w ith adjustments. 34 ' 35
assisted c~ elimination, the mean dis tending pressure
during HFOV is midway between the minimal and max-
OXYGENATION
imum values, introducing less risk of derecuitment dur-
ing the expiratory phase for any given peak distending ACHIEVING ALVEOLAR AERATION
volume / pressure. 32 One a ttraction of HFOV in neonatal Although lung-volume optimization has become an ac-
and pediatric use has been the way in which it unco uples cepted goal of HFOV, the ''best way" to achieve this o p-
the regulation of oxygenation and C0 2 elimination into two timization remains controversial (Fig. 20-5).
HFOV Pressure Waveform

Hz
Pressure A
~--+--+---+--~--~~--~~~BD~~cm H 2 0
! +30 em ~0 ('actlve exhalation')
- 5 em H20 fsubamblent pressure')
%IT Time
FIGURE 20-4 Wavefo.n n of high-frequency pressure oscillations in the circuit above the endotracheal tube. Both inspiratory and
expiratory flows are actively driven by the oscillator diaphragm . Pressure cycles equally above and below the mean level. When the
oscillatory pressure ampl itude (AP) is more than twice the mean airway pressure (mPaw), subambient pressures may occur in the circuit
without inducing air trapping or choke points in the lung.30 The endotracheal tube filters the pressure swings, decreasing AP in the
trachea and alveoli. Filtering is greater with smaller endotracheal tubes 63 •79 and higher frequencies (0 Hager, personal communication).
(Reproduced, witlr perm'issiou,from Derdak: Crit Cnre Med 31:5317- 23 2003).
1
Ventilating on the " Deflation Limb" relationshipY Recent investigations in both animal models
All initial animal studies and one early human trial used and humans reinforce the value of ventilating on the de-
a brief recruitment maneuver to near-total lung capacity, flation limb. 42- 49 After a recruitment maneuver, oxygena-
followed by reduction of mPaw to a maintenance level tion goals are achieved at substantially lower maintenance
that prevented derecruitment. 36- 40 This is termed getting mPaw values (near the point of maximum curvature),43,46,4 7
the lung onto the deflation limb of its pressure-volume (P-V) alveolar expansion becomes more homogeneous (which
FIGURE 20-5 Schematic repres entation of two approaches to alveolar rc-expansion during HFOV. The horizontal dashed line indicates the
desired maintenance mean lung volume. The solid line is the pressure-volume (P-V) relationship of a moderately diseased lung that still
exhibits hysteresis. The dashed line indicates the P-V relationship after some recovery has occurred. A. A brief sustained increase in mean
airway pressure (mPaw) from a to b inflates the lung to near total lung capacity (TLC), putting it on the deflation limb of its P-V curve.
After this discrete recruitment maneuver, the target volume cis maintained at an mPaw of 11 cmH 2 0. If the P-V relationship happens to
change (as with position, diuresis, etc), the operational lung volume remains constant. This is the approach used in the recent TOOLS
Trial.49 B. A gradual march up the inflation limb of the P-V relationship. Progressive increases in mPaw are used to achieve the target lung
volume. An mPaw of 19 cmH20 is now needed to maintain lung volume at c. Also, if the P-V relationship of the respiratory system
changes, overdistension of the lung c;ould occur (i.e., movement from point 5 to point 6). This is the approach u sed in the majo.r ity of
neonatal and adult trials of HFOV to date. When actual lung volumes are measured, settings felt to have optimized lung volume clinically
by these stepwise increases in mPaw often prove to b e inadequate.55 (Reproduced, by pennission of Routledge/Tnylor & Fraucis Group, LLC).
DISCRETE VOLUME RECRUITMENT PROGRESSIVE INCREASE IN MEAN

MANEUVER AIRWAY PRESSURE
w
--:,:---_-.-.--~)
::= ,'
' 6
::::>
.....J
''
'
0
> .
(!) I ''
I
z -·-"'··-- ... I
I
3 I '
I
10 20 30 20
A PRESS U RE ( em H2 0) B
should reduce shear forces during ventilation),45•50 and the Inadequate alveolar recruitment also may trigger inap-
percentage transmission of HFOV pressure cycles into the propriate increases in AP or decreases in frequency because
lung is decreased relative to settings producing equal shunt of hypercapnia, when what was really needed was alve-
reduction on the inflation limb.44 olar re-expansion. All high-frequency oscillators currently
available are load-dependent and deliver less tidal volume
Ventilating on the "Inflation Limb" at any given settin~ w hen the lung is stiffer, as with on-
Following the HIFJ Trial of the late 1980s,51 fear of intraven- going atelectasis. 65• If one's goal is to explore HFOV for
tricular hemorrhage in the fragile brain of the premature pa- the potential lung-protective effects of maintaining 02 and
tient led most neonatologists to pursue stepwise increases C02 transport at the smallest possible intrapulmonary pres-
in mPaw until either x-ray and blood-gas evidence of lung sure and volume swings, then lung-volume optimization is
reexpansion was achieved or the mPaw level reached what- essential.
ever level was deemed the "maximum allowable" level for
a given institution.52 Physiologically, this can be described Volutrauma: The Cost of
as "marching up the inflation limb" of the P-V curve, as iJ1 Excessive Recruitment
Fig. 20-SB. Most post-HIFI Trial neonatal/pediatric trials It costs less to pursue lung recruitment vigorously than to
(including the largest recent randomized, controlled trials accept ongoing a telectasis. 67 All clinical trials done to date-
in 200253,54) used stepwise increases in mPaw to "optimize" from neonate to adult- that have mandated lung-volume
lung volume to oxygenation and chest x-ray ta rgets. Unfor- optin1ization have reported similar or decreased incidences
tunately, when the actual lung volumes achieved by such of barotrauma, a transient need for inotropic support, and a
clinical protocols are measured, many lungs prove to be sub- decreased need for nitric oxide to reduce pulmonary vascu-
optimally expanded.55 All early adult trials of HFOV started lar resistance despite using mean pressures in the thirties or
at mPaw levels of 3-5 cmH20 above the mPaw on conven- forties when necessary to acltieve oxygenation.10·56,S7,68-70
tional ventilation and then increased mPaw incrementally- Recent computed tomographic (CT) studies during HFOV
again marching up the inflation limb.56- 60 in eight adult patients with ARDS documented substan-
A few human trials have used protocols that rapidly place tial (.-...sao ml) increases in normally aerated volume w ith
the lung "on the deflation limb" of its P-V relationship.48, 49 only a minor increase in hyperinflated hmg (<50 ml)? 1
Although large comparative trials of the relative safety Overdistension certainly can occur, particularly as the lung
of these different recruitment protocols are not available, normalizes during treatment. Avoidance of this requires
no evidence of risk from either barotrauma or IVH has awareness and periodic reassessment of lung expansion.
emerged using any of the neonatal/pediatric approaches Some algorithms warn against using mean distending pres-
since optimiz.ation of lung volume became an accepted goal sures on HFOV higher than the plateau pressure limit of
of HFOV. 7•8 What we do know is that lung-volun1e opti- 30 cmH20 currently advocated for conventional ventila-
mization is essential for H FOV to be protective of the lung. tion. This warning may produce inadequate volume opti-
The small volume cycles of HFOV simply are not powerful mization. It fa ils to take into account that the risk of a given
enough to reopen atelectatic alveoli without some type of "maximum pressure" will vary with the size of the lung and
recruitment measure. the size and rate of delivery of the tidal volume engender-
ing that plateau pressure. If 60% or 70% of the lung is not
Atelectrauma: The Costs of participating in gas excl1ange, then a tidal volume of even
Inadequate Recruitment 6 ml/kg may induce dangerous overdistension of the ven-
Ongoing atelectasis strongly affects the ~hasic pressures ex- tilated alveolar units, as well as exerting shear forces on any
erted on intrapulmonary structures. 61 - 3 Sakai et aJ64 mea- alveolar units re-expanded during the course of the breath.
sured "swing pressures" (i.e., peak-to-trough AP) at intra- If, instead, 70% or 80% of the lung is kept expanded through-
tracheal, bronchial, and pleural sites in rabbits with normal out the ventilatory cycle, then a mean distending pressure
and lavaged lungs. AP values at intratracheal and bronchial of 30 onH20 or more is safe, as proven in numerous clini-
sites were much higher in lavaged lung than in normal cal trials ofHFOV,56- 58•68 presumably because that distend-
lung at low levels of mPaw. These pressure swings reduced ing pressure is now accommodated within many more par-
rapidly to normal values following lung recruitment. The ticipating lung units, fewer units are sheared open during
authors postulated that failure to reverse atelectasis during the course of a cycle,32 and volume swings of only 1.5- 2
HFOV would expose airways and alveoli unnecessarily to m1/kg at high rates minimize peak distension. Conversely,
potentially damaging shear forces. Simila r messages come if one fails to open the lung during HFOV and then keep
from the data of van Genderingen et al, 44 who analyzed in- it open, one will expose the lung to unwanted shear forces
trapulmonary pressure transmission in terms of the ratio of many more times per minute, particularly if forced to use
intratracheal and proximal airway AP values, termed the lower rates and larger volume cycles because of inadequate
oscillatory pressure ratio. Pressure transmission into the lung recruitment.
increased sharply at low lung volume. In vivo, adequate
alveolar re-expansion optimized oxygenation while also MAINTENANCE MEAN AIRWAY PRESSURE (mPaw)
minimizing intrapulmonary pressure swings. For a given Numerous studies have tried to predict an optimal main-
level of shunt reduction, both the oscillatory pressure ratio tenance mPaw from some feature of the static P-V curve
and the mPaw were substru1tially lower after a recruitment of the respiratory system, such as the inflection point on
maneuver (Fig. 20-6). the inflation limb.46 These studies demonstrate a general
4 78 PART VII UNCONVENTIONAL METHODS OF VENTILATOR SUPPORT
0.5 0.5
0.4 0.4
0:: 0.3 0:: 0.3

Q. Q.
0 0
0.2 0.2
0.1 0.1
0.0 +----.---...----.----...---~ 0.0 -+----..------.----.----.----.

0 10 20 30 40 50 0 10 20 30 40 50
Paw (em Hp] Paw [emHp ]
0.6 0.4
0.5
0.3
0.4
0:: 0::
~ 0.3 ~ 0.2
0.2
0.1
0.1
0.0 +----r---r----r-----..----..,
0 10 20 30 40 50 0 10 20 30 40 50
Paw [em Hp] Paw (em Hp ]
FIGURE 20-6 Relationship of the oscillatory pressure ra tio (OPR) to th e mean airway pressure (Paw) during HFOV in pigs with lung
injury induced by saline lavage. Data are shown for four animals. Arrows show the order of Paw application starting from the baseline
mean Paw value. The OPR is the ratio of .6.P in the trachea to the .6.P (i.e., the pressure amplitude) at the top of the endotracheal tube.
Intrapulmonary oscillatory pressure swings arc strongly influenced by the degree of alveolar re-cxpansion and are substantially smaller
whe.n th e lung is operating on its deflation limb. (Repriuted toit11 permiss·i on of Wiley- Liss, Iuc., a subsid·i ary of jolm Wiley & So11S, Inc.)
property of the respiratory system, namely, that the mPaw the stroke volume (Vco, = VT- 2 ·f) . The endotracheal tube
needed to maintain a given level of oxygenation is substan- contributes a substantial impedance to gas transport dur-
tially less after the lung has been inflated briefly to a pres- ing HFOV. 77 If one uses an uncuffed endotracheal tube such
sure of 31)-W cmH2 0 so that it is "operating on the d efla- that the fresh-gas front moves to the bottom of the tube and
tion limb."44 Because recruitment/ derecruitment pressures CD2 exits around rather than through the tube, the stroke
vary markedly between lung regions45 •72 and between lung- volume n eeded to achieve normocapnia decreases by up to
injury models, however, generalizations to human ventila- 50% (Fig. 20-7). The bias gas-flow rate also influences trans-
tor management must be made cautiously. In clinical prac- port efficiency through its effect on gas tensions at the fresh-
tice, a gradual deterioration in oxygenation over time that gas front. 78 Uncuffed tubes are used routinely in neonates
corrects with a recruitment maneuver indicates that the and infants. Cu ff leaks substantially assist C02 elimination
mPaw needs to be increased 2- 3 cmH 20 to keep alveoli/ in adults as well34,59 and reduce intrapulmonary p ressure
airways above their closing pressures. Bedside regional swings. 79
lung-volume monitoring techniques have the potential to
clarify mPaw adjustments.43-73. 74
FREQUENCY SELECTION
Early I-IFOV trials used a frequency of 15 Hz and an
inspiration-expiration (I:E) ratio of 1:1. Demonstration of
C0 2 ELIMINATION
small inter-regional mean ~ressure gradients a t 15Hz and
The basic transport studies of the 1980s were executed 50% inspiratory p eriod (T,) subsequently induced a shiftto
with accurate measurements of delivered stroke volumes a lower operating frequency of 10 H z and a 33% T, in many
over a wide range of frequencies using sinusoidal flow centers. It is worth noting that although pressure gradients
oscillations.JS,75,76 They established that the volume of C02 definitely occur in the lung during HFOV, their magnitude
eliminated per minute Nco) was proportional to the prod- is small (i.e., on the order of 1-3 cmH 2 0 from apex to base).81
uct of oscillatory frequency and the approximate square of With a 33% inspiratory period, the mPaw displayed on the
CI-IAPTER 20 HIGH-FREQUENCY VENTILATION 479
Bias Flow
L Bias Flow
t1 Transport
distance
along
I partial
pressure
I
y
gradients
PvC02
A PVO2
FIGURE 20-7 Schematic of the gas transport pathways during HFOV before and after establish ment of a cuff leak. Transport distances are
shown for C02. On the left, with the endotracheal tube (ETT) cuff occluding tlte trachea, the fresh-gas front for both C02 and 0 2 is at the
top of tlte ETT. Gas-transport mechanisms must bring C02 from the alveoli to the top of the ETT before C02 is flushed away by the bias
flow . On th e right, with partial ETT cuff deflation, some of the bias flow passes down the ETT and flushes C0 2 molecules out beside the
ETT, in effect reducing the transport distance substantially. The ETT represents SO% of ilie trans port inlpedance during HFOV. 63 •77
In troduction of a cuff leak reduces the tidal volume needed to su pport C02 elimination and decreases ilie intrapulmonary ~p inlposed on
lung tissue.19 A cuff leak als o may increase tracheal contamination by oral secretions. The risk-benefit ratio of a cuff leak is not yet
established.
ventila tor exceeds the mPaw within the lung by an amount of the shifting boundary conditions for safe ventilator set-
that increases with tidal volume, frequency, and smaller en- tings with varying lung pathology. These plots demonstrate
dotracheal tube diameters. 52 the familiar reality that the normal lung can be ventilated
Frequency selection directly affects the pressure cycles a p- over a wide range of frequencies and PEEP levels without in-
plied to the lung. A smaller percentage of the circuit .6.P is ducing dangerous overdistension. The lung with poor com-
transmitted down an endotracheal tube at higher frequen- pliance but relatively normal airways, however, such as the
cies (D Hager, personal communication). infant or child with respiratory distress syndrome (RDS),
The most useful theoretical approach to conceptualizing has a very limited zone of safe frequency / PEEP combina-
the optimal frequency for HFOV has been that of Venegas tions. With this pathophysiology, the selection of PEEP be-
and Fredberg.83 They approached the optimization question comes critical, particula r!y at lower frequencies, with penal-
as a problem of providing adequate alveolar ventilation at a ties in terms of pressure cost and overdistension with either
minimal pressure cost. Their approach addressed the whole too low or too high a level of PEEP. As seen in Fig. 20-8,
lung, not just flow in a tt1be, and incorporated elements such at high frequencies, the zone of safe PEEP widens, making
as alveolar recruitment and derecruitment into the "cost it easier to maintain more of the lung homogeneously aer-
functions," as well as the effects of lung inflation and fre- ated. In lungs with increased airways resistance, the optimal
quency on dead-space volume and the dependence of lung frequency moves to a lower rate. This complex modeling
compliance on lung volume. The lung characteristics used supports practices that had evolved clinically in neonatol-
were those of infants w ith a variety of clinical scenarios. Re- ogy, where frequencies of 10-15 Hz are standard practice
sults were expressed as a series of three-dimensional plots in the management of diffuse alveolar disease. Currently,
of safe combinations of frequency and PEEP, with snfe being this analysis has been done only for the infa11t lung. One
defined as settings that resulted in a penk alveolar distension would predict that similar plots would shift to a somewhat
of less than 90% of total lung capacity (Fig. 20-8). The impor- lower frequency in adults. These plots concur with the per-
tance of this approach is that it provides graphic depictions ception of many neonatologists that it is simply easier to
480 PART Vll UNCONVENTIONAL METHODS OF VENffiATOR SUPPORT
Datv =(VEE+ Vr )jTLC

Normal infant Infant with RDS
Dalv Dalv
1 1
0.8 0.8
0.6 0.6
0.4 0.4 Dalv<0.9
, Dalv<0.9 I
I
0.2 0.2
P EEP P EEP
(cmH20) {em H20)
FIGURE 20·8 Three-dimensional plots providing a conceptual basis for the selection of frequency (f) and positive end-expiratory pressure
(PEEP) settings during mechanical ventilation. Normalized peak alveolar distension (Dalv) is plotted against f and PEEP for a normal
infant (/eft) and one with respiratory distress syndrome (RDS) (riglrt). Normalized peak alveolar distension (Dalv) is defined as lung
volume at end expiration (VEe> plus the tidal volume (VT) normalized by TIC. The safe zone for peak alveolar distension was set at 90% of
TIC. For clarity, combinations off and PEEP producing alveolar dis tension that exceeds this safe level are arbitrarily assigned a value of 1.
The combinations off and PEEP that produce peak volumes within this limit are given by the shaded zones projected on to the xz plane. In
the normal infant, the range of safe f-PEEP choices is very large (i.e., the shaded zone projected on the xz plane). Because of the tendency to
atelectasis in the infant with RDS (riglrt), lung peak distension encroaches on TLC for all but a small range of £-PEEP combinations. The
wid th of the safe zone become$ greater as frequen cy increases. This formulation graph ically depicts the twin dangers of both too little and
too much PEEP. Both Lead to potentially damaging alveolar overdistension. (Reprod11ced, witlr permissiou, from Veuegas et nl: Crit Care Med
22:549-57, 1994.)
keep an atelectasis-prone lung in the safe zone using the lung protection, one should use the smallest tidal volume
higher frequencies of HFOV than to attempt to track the and highest frequency that achieves Paco, elimination tar-
"right" freq uency- PEEP-tidal volume combination a t con- gets. Introduction of a cuff leak should be considered before
ventional rates. 9 decreasing frequency below 6 Hz. Even higher frequencies
and small tidal volumes may be preferable, but the rela-
TIDAL VOLUME tive risk/benefit of early cuff leak versus lower frequencies
Tidal volume delivery during HFOV is inJ!uenced by many requires further investigation.89-90 Resonant amplification
factors20, 84 (Table 20-1 ). Recent publications have chal- of the delivered volume has been demonstrated91-92 at a
lenged the notion that HFOV supports C02 elimination with median of 19 Hz in babies. Heliox can increase the tidal
small tidal volumes. 85 At a ~p of 60 cmH2 0 and 4Hz, the volume delivered at a given power setting by decreasing
SensorMedics 3100B oscillator delivered tidal volumes of cir cuit/lung impedance.93
4.4 ml/kg to 29-kg sheep. No Paco2 data were provided Although inability to eliminate C02 occurred in 1 of 17
at those settings. Such settings equate to a tidal volume ap- patients in the original report of Fort et al,56 the incidence
proximating 1.7 ml/kg in an 80-kg adult. Any ventilator has of ventilation failure (i.e., pH .:;:: 7.15 with bicarbonate :! 19
to be adjus ted to appropriate Paco2 targets. Old data with meg/liter) was the same in both HFOV and conventional
piston oscillators of known volume delivery,86-87 plus a re- ventilation groups in the subsequent larger MOAT trial57
cent case report from Japan, 88 demonstrate that adequate and is rare if one follows current recommendations (see
C02 elimination is achieved in adults with ALI/ ARDS us- "Troubleshooting," below).
ing tidal volumes of 1.5-2 ml/kg during HFOV. For optimal
TABLE 20..1 Factors Decreasing Delivered Tidal Volume

Physiologic Effects of HFOV
J, Endotracheal tube diameter (includes secretions, edema fluid)
j Endotracheal tube length CARDIOPULMONARY INTERACTIONS
t Frequency (most HFOV devices) HFOV is a sensitive detector of hypovolemia. Patients need
J, Power or amplitude
intravascular volume repletion before one initiates HFOV
J, Percent inspired time
J, Respiratory system compliance
and optimizes lung volume. Fortunately, clinical experience
and animal studies demonstrate that despite this need for
CHAPTER 20 HIGH-FREQUENCY VENTILATION 481
an adequate volume status, treatment w ith HFOV does not TABLE 20-2 Pulmonary Therapi es Decreasing Mortality in
induce "wet lungs." 94 Alveolar expansion has a powerful Neonatal RDS s ince 1970
impact on pulmonary vascular resistance. Pulmonary vas- Early use of CPAP
cular resistance goes up both in areas of atelectasis and Exogenous surfactant replacement therapy
overdistension. Therefore, the impact of HFOV on pul- HFOV / HFJV with "optimized lung volume"
monary artery pressure will be influenced strongly by the Conventional ventilation with "optimized lung volume" strategy
extent to which homogeneous alveolar expansion can be
achieved. This will vary with lung pathophysiology, deci- NOTE: All these produced more homogeneous lung aeration.
sions made about mPaw and recruitment techniques, and
body position. In clinical experience, pulmonary hyperten- that "safe" range of volume excursion. The key is to deci-
sion secondary to the use of higher m.Paw during HFOV has pher exactly when small pressure and volume excursions
not been a problem. Rather, HFOV often has enhanced the will make a difference. All therapeutic advances in neonatal
responsiveness to inhaled nitric oxide in both infants and and pediatric critical care over the past 30 years that have
aduJts.59•95 - 97 As with conventional lung-protective venti- had a significant impacted on survival exhibit one unifying
lator patter ns, patients with pre-existing right-ventricular feature: all have produced more homogeneous lung expan-
failure need to be watched closely for the possible ad- sion (Table 20-2).
verse effects of measures to optimize lmtg volume on right-
ventricular output.
ADVANTAGES OF HFOV
Cardiac output decreases as mPaw increases with any
ventilator modality.98 In early HFOV trials in the prema- It is much easier in theory than in practice to ventilate
ture baboon, cardiac output was less during HFOV39 unless the lung within the safe zone of pressme and volltmes
m.Paw was weaned as llmg aeration improved. 99 Similar in- in all lung regions. 105 Although much has been written
teractions of cardiac output and m.Paw occur in infants.100 about using the static P-V curve of the respiratory system
Lesser hemodynamic impact can be expected when venti- to guide ventilator settings, any single curve is only a
lating "on the deflation limb," where alveolar expansion can crude composite of the family of P-V curves occurring in
be maintained at a lower mPaw cost. 47 In adult clinical trials, different parts of the lungs. A safe peak or plateau pressure
such as MOAP7 and the recent IDOLS trial, 49 there were will be lower in nondependent and more normal lung
no s ignificant deleterious effects o n mean arterial pressure, regions; closing pressures will be higher in dependent,
central venous pressure, pulmonary artery occlusion pres- inflamed, or edematous regions than suggested by a single
sure, or cardiac output compared with conventional ventila- overall curve. 6.42.45•50•71 Studies in adults with ALI/ ARDS
tion. Small (1-2 mmHg), often transient increases in central demonstrate that derecntitment often begins at PEEP levels
venous pressure and pulmonary artery occlusion pressure substantially above the values recommended as protective
were observed after transition to HFOV. 60 Transesophageal of the lung. 6, 106 As one r aises PEEP levels, even acceptable
echocardiography has proven useful to assess preload ade- degrees of permissive hypercapnia may be unattainable
quacy when clarification is needed. without exceeding safe peak/plateau pressures at con-
ventional ventilator rates. In such patients, HFOV has the
INTERACTION WITH SPONTANEOUS BREATHING potential to keep that lung in the safe zone with a much
la rger margin of safety sin1ply because of its ability to
Spontaneous breaths contribute useful re-expanding sustain gas transport with small volume cydes32 (Fig. 20-9).
forces. 101 •102 Spontaneous breaths [as with airway pressure- This is particularly so a t higher frequencies because of the
release ventilation (APRV)] help to mainta in end-expiratory impact of time-constant variability on alveolar filling.
alveolar expansion in dependent lung regions'103 and im- A very old but elegant s tudy demonstrated some fun-
prove VA/0 distributions. 104 A significant decrease in ven- damental features of lung re-expansion risk. 107 In essence,
tilator days occurred when spontaneous efforts were main- unless one exceeds airwayI alveolar opening pressures, re-
tained in patients with ALI/ ARDS.102 Unfortunately, with expansion will not occur. If one exceeds opening pressure
current HFOV circuit designs, vigorous respiratory efforts with a long inspiratory period, atelectatic areas open, but
in large patients may cause pressure swings that activate normal areas become overdistended. Even very high pres-
alarms, interrupt oscillations, and produce significant de- sures, however, will not overdistend normal lung if applied
saturations. Initial oscillator trials in adults recommended very briefly (<0.15 second in this study) because the time
muscle paralysis for this reason. Current protocols attempt constant of highly compliant alveoli is long. Therefore, pres-
to maintain these valuable spontaneous breaths.34•90 Sucl1 sures high enough to exceed opening pressures are safer if
an approach also minimizes potential problems from the applied as brief pulses, as with HFOV. As one turns down
myopathy of prolonged neuromuscular blockade. the frequency, this safety feature diminishes.
Lung-volume optimization and outcomes equivalent to
HFOV have been achieved using recruitment maneuvers
Rationale, Advantages, and Limitations followed by rapid conventional ventilation with care-
ful PEEP titration in saline-lavaged animal mode1s.10S-'Ito
If we accept that both overdistension and ongoing atelec- Whether this equivalency extends to more established
tasis damage lung tissue, then HFOV offers the ability to disease with greater inhomogeneity of opening and dosing
cycle the largest possible percentage of the total lung within pressures has not been tested.
FIGURE 20-9 In vivo photomicrographs of s ubpleural al veoli of a rat after inducing lu~ng injury b y saline lavage. Animals were ventilated
to equal oxygenation and Paco 2 targets using either conventional mech anical ventilation (CMV) or high-frequency oscillatory venti lation
(HFOV). Alveoli in (A) were inflated at end insp iration dnri.n g CMV to a peak pressure of 34 cmH 20 but collapsed during expiration (8)
with a PEEP of 9 em H2 0 (arrows). Al veoli were very stable during HFOV at a mean airway pressure of 19 cmH 2 0 . The same alveolus is seen
at inspiration and expiration in panels (C) an d (D) (dots). (Reproduced, w itT! penuissiou, from Carney et al: Crit Care Med 33:5122-8, 2005.)
LIMITATIONS AEROSOL DELIVERY

Metered-dose inhalers are ineffective during HFOV. The
Most of the perceived limitations of HFOV currently are
Aeroneb nebulizer (Aeroneb Pro, Aerogen, Sunnyvale, CA)
really limitations of the machines available rather than the
technique per se. Even minor modifications trigger expen- delivered the highest percentage of drug in test lung
sive Food and Drug Administration (FDA) approval pro- studies:U 2
cesses. Therefore, oscilla tor design in North America has
been frozen for years.
TRANSPORT DURING HFOV
It is simples t to execute anticipated transports such as for
INCREASED USE OF MUSCLE PARALYSIS CT scan before starting HFOV. There is no transport version
A significant limitation of the adult-sized oscilla tor cur- of HFOV. Cartotto et al 59 describe an effective protocol for
rently available in North America is its inability to facili- transport during H FOV, such as to the operating room. It
tate spontaneous ventilation. Infants and children are rarely involves clamping the endotracheal tube while on HFOV,
paralyzed during HFOV. Paralysis of adults on HFOV can transition to a self-inflating bag with a 20 cmH2 0 PEEP
be minimized by titrating sedative agents, using higher valve, unclamping of the endotracheal tube with vigorous
bias flows to minimize air hunger, and reserving para- manual ventilation during transport, and reversal of these
lytic agents for as-needed bolus use rather tl1an constant procedures once an oscillato r has been set up at the d esti-
infusions.34,90,1ll Shallow breathing is tolerated in some nation. Recruitment maneuvers then are used as needed
adults without significant desaturation, particularly during to reestablish oxygenation at the pretra nsport HFOV
the recovery phase of their disease. The lack of d emand settings.
flow to augment spontaneous breaths requires adults to be
transitioned to conventional ventilation or APRV for final
weaning and extubation.90
MONlTORING
High-frequency oscillatory ventilators have few ventilator
INFECTION CONTROL alarms to alert one to a mainstem intubation, tension pneu-
The lack of an expiratory filter initia lly limited the use of mothorax, or endotracheal tube obstruction. Pa tterns of pos-
HFOV in patients with infections such as Severe Acute Res- sible changes in ventilator readouts w ith such events have
piratory Syndrome (SARS). A suitable filter is now available been modeled. 90 Also, ventilator noise necessitates brief pis-
(SensorMedics, Yorba Linda, CA). ton interruption to auscultate heart or breatl1 sow1ds.
UNFAMILIARITY OF PERSONNEL are avoided more reliably at higher frequencies. These are
A major limitation to the use of HFOV is the level of dis- the lungs in which HFOV improves outcome.
comfort of personnel (i.e., physicians, respiratory therapists,
and nurses) who encounter it rarely and usually as a mea-
sure of last resort.113 If one does not understand that a mean
NEONATAL/PEDIATRIC PATIENTS
pressure of 35 cmH20 that is stenting 70-80% of a stiff lung
Current criteria for using HFOV vary among institutions.
open while supporting C~ elimination with small volume
A switch from conventional ventilation to HFOV generally
cycles may well induce less lw1g injury than a PEEP of occurs at some combination of Fr0 2 and airway pressures
15 cmH20, plateau pressure of 30 cmH20, and larger tidal
needed to achieve goals for oxygenation and C0 2 elimi-
volumes being distributed to 30-40% of that lung_ then
nation . Experience in animal models, infants, and children
HFOV "feels" dangerous. Only experience gained in less
has demonstrated the impor tance of instituting HFOV
dire circumstances can produce a comfortable level of un-
early in the lung at risk. 52·69 •70· 115 In infants, an mPaw of
derstanding of the interaction of ventilator decisions and
10-12 cmH20 or greater with an Fro, of more than 0.6
lung pathophysiology. Then and only then can one really
and/or a falling aerated lung volume trigger a switch to
test the applicability of any high-frequency modality.89
HFOV in some units. Duval e t al 113 switched to HFOV at
PROTOCOL/ ALGORITHM LIMITATIONS an oxygenation index of greater than 13 or a pH of less than
When protocols are generalized to patients outside the pop- 7.25 despite a bicarbonate level of 20 mmol/liter or greater
ulation on which the protocol was devised, HFOV may be and peak pressures of more than 30 oni-hO. In older
used inappropriately. Several HFOV protocols specify max- children, Doctor and Arnold116 recommend institution
imum mean airway pressure limits that were derived in of HFOV if an "open-lung strategy" using conventional
patients with primary pulmonary diffuse airspace disease. ventilation generates a peak pressure of greater than
If these limits are applied to patients with major extrapul- 35 onH 2 0 despite permissive hypercapnia or mPaw values
monary factors, such as abdominal distension or chest-wall approach 15- 18 cmH2 0 and the Ft0 2 still exceeds 0.6. Some
burn eschar, adequate atelectasis reversal is w1likely be- pediatric units convert to HFOV at oxygen requirements of
cause 30-70% of the applied mPaw
71
""illbe lost to inflate
more than 0.4 with peak pressures of 30-35 cmH20 , PEEP
levels of 12-15 cml-120, and a pH approaching 7.30 in pedi-
the chest wal1.
atric patients with acute respiratory failure. The same group
considers a switch to HFOV earlier in neonates, in particular
Indications and Contraindications in premature infants presenting with iRDS. In this patient
population there frequently is echocardiographic evidence
INDICATIONS of pulmonary hypertension. Such pulmonary hypertension
can generally be reversed using HFOV to achive better C02
Is HFOV still needed in the current era of "gentler"
elimination and normalize pH values. (Rimensberger, per-
conventional ventilation? When HFOV first came into
sonal commwlication). Randomized, prospective studies
clinical use, large tidal volumes were considered safe dur-
indicate that when inhaled nitric oxide is needed, thera-
ing conventional ventilation as long as high peak pressures
peutic response is improved with concurrent institution
were avoided.10 In this milieu, ra ndomized, controlled
of HFOV in both neonates and children.95· 1'l7,118 All these
trials in neonates demonstrated substantial outcome ad-
guidelines represent an attempt to define the characteristics
vantages from HFOV. 114 Conventional ventilator protocols
of a lung for which HFOV might be more protective than
then were modified to pursue the same lung protection.
a conventiona l lung-protective strategy.
In two recent randomized, prospective studies, significant
differences between lung volume-optimizing HFOV and
conventional ventilation protocols were seen only in the
study in which just 40% of the infants meeting very low ADULT PATIENTS
birth weight criteria were randomized. These neonates Indications for HFOV are evolving in adult lung disease. A
required an F~o, of approximately 0.6 on an mPaw of 8 consistent theme in studies to date is that survival is better
onH20. In this trial, more neonates managed with HFOV with early (<3 days) rather than late (>7 days) institution
(until extubation) survived without chronic lung disease of HFOV.56, 58 Currently, a trial of HFOV is recommended
and were extubated successfully 1 week earlier than if Fro, requirements remain greater than 0.6, the plateau
neonates receiving lung-protective ventilation at conven- pressure is approacl1ing 30 cmH2 0, PEEP is greater than
tional frequencies. 54 When all very low birth weight babies 15 cmH2 0, or the high pressure is greater than 30 cmH2 0 on
were randomized regardless of 0 2 requirements, outcome APRV. 89·90 The current challenge is to define the pulmonary
with both ventilators was the same.53 This neonatal ex- characteristics that indicate that the lung is at risk of VILI
perience reflects the predictions of the Venegas-Fredberg using conventional frequencies and then to test whether
analysis. 83 If the lung is fairly normal, a wide range of HFOV is of benefit in that population. Indicators such as
tidal volumes, PEEP levels, and frequencies can be used PEEP responsiveness,119 dead-space measurements,120 and
without inducing atelectasis or overdistension. Ventilator biomarkers121 are being explored. Indicators ideally would
choice becomes a matter of user preference. As the lung include an accurate bedside method to determine the extent
becomes more prone to a telectasis, the range of safe PEEP of inhomogeneity of alveolar expansion across lw1g regions
values shrinks, and injurious extremes of alveolar volume both at end inspiration and at end expiration.42,71,74
CONTRAINDICATIONS differences were documented in maximum tidal volume

among ventilators tested at 15 Hz,65•66 and frequency de-
Early Uterature advised against the use ofHFOV in obstruc-
tive airway diseases such as asthma because of the theo- pendence of tidal volume varied substantially. It is amazing
retical risk of inadvertant gas trapping and hyperinflation. that HFOV has been used as safely and effectively as it has
Recent reports demonstrate that HFOV can be used in considering these major discrepancies i n ventilator perfor-
mance among the devices used.
such patients, even in patients demonstrating gas trapping
on conventional settings. Case reports of patients with se-
vere asthma and a series of infants with respiratory syncy- Adjustments at the Bedside
tial virus infection with severe bronchiolitis describe w hat
is being termed the open-ninvm; strategt; for the manage- PREPARATION FOR INITIATION
ment of such patients. 30·'122 The goal in these patients is
OF HFOV (TABLE 20-3)
to find the narrow window of mean airway pressure that
stents the diseased airways open enough to support high- Documentation of a pa tent endotracheal or trad1eostomy
frequency gas transport without inducing excessive lung tube is essential. 34 Partial obstructions impede gas transport
distension with hemodynamic impairment. Extensive ex- much more during HFOV than with conventional modes.
perience v.rith HFOV is recommended before one pursues Tubes that allow passage of a suction catheter still may have
this application.30 a narrow lumen. A preemptive bronchoscopy will verify
Before development of an expira tory gas filter, SARS and tube patency as well as provide opportunity for removal of
other highly contagious airborne pathogens were a relative any mucus plugs if the patient has been intubated for more
contraindication to HFOV.1 23 than 2-3 days. Hypovolemic patients will not tolerate the
high mean mPaw used with HFOV; adequate volume status
should be ensured before initiating HFOV.
Comparison with Other Modes Sedative and a na lgesic drugs should be titrated while the
patient is still receiving conventional ventilation. Although
Limited comparisons are available among various high- muscle para lysis was used in most adult published trials,
frequency modalities. When HFJV was introduced into subsequent experience has found continuous paralytic in-
adult and neonatal use, the primary goal was to support fusions unnecessary in m any cases when appropriate levels
gas exchange at the lowest possible peak and mean air- of sedation are established.34 Small as-needed doses of mus-
way pressures to facilitate resolution of barotrauma. When cle relaxa nts may facilitate the initial period of adjustment
HFOV was introduced in an early neonatal clinical trial, the to HFOV and may be needed intem1ittently during periods
primary goal was to optimize the volume of aerated lung. of agitation to facilitate retitration of sedative and analgesic
Both devices, in fact, can be used with either a low -pressure agents. 90·m Preservation of some spontaneous respiratory
or open-lung strategy.52 The strategy must be matched to effort is valuable as w ith any type of prolonged ventilation,
the patient's pathophysiology. Only one study systemati- provided those efforts do not produce marked fluctuations
cally compared three high-frequency options in an animal in mPaw (>5 crnl·h O) or 02 saturation (>3-5%). Careful ob-
model of the a telectasis-prone Jung. 124 Optimal outcome oc- ser vation for spontaneous breathing following transition to
curred with the mode (HFO) in which the end-expiratory HFOV allows proper adjustment of high- and low-pressure
pressure was closest to the mean pressure level and the least alarms. Patient comfort may be enha nced when bias fl ows
time was spent at the end-expiratory level. of 40-60 liters/min are used to achieve the target mPaw in
adults.
Variations in Delivery OXYGENATION
The performance of several commercially available devices Two conceptually different approaches are described for
for delivery of HFOV to neonates has been evaluated both initiation of HFOV in adult pa tients with respect to
in bench studies and in animal models. Substantial differ- oxygenation adjustments. The approach used in most pub-
ences in performance have been demonstrated. 65,66, 'l 2S Any lished algorithms a nd trials to date uses an Fr0 2 of 1.0 dur-
ventila tor introduced into an ICU should be thoro ughly un- ing transition to HFOV w ith the mPaw set approximately
derstood before clinical use. For example, all neonatal ven- 5 cmH20 higher than the mean pressure during conven-
tilators tested by Hatcher et al 65 a nd Pillow et al 66 showed tional ventilation.89 Fr01 levels are reduced as mucl1 a pos-
a decrease in delivered volume with a decrease in lung sible, keeping Sao, at 88-90%. Inability to reduce the Fro,
compliance, but one ventilator (no longer available) exhib- below 0.6 is managed primarily with stepwise increases in
ited the reverse phenomenon.125 That outlier cllaracteris- mPaw, in essence, gradually moving the respiratory sys-
tic may explain puzzling episodes of hypercapnia during tem up the inflation limb of the P-V relationship as the first
the weaning of infants with that ventilato r.125 One ventila- intervention. Derdak et al90 currently recommend initiat-
tor failed to increase delivered volume at settings between ing HFOV a t an mPaw of 30 cmH20. When hypoxemia is
50% and 100% of its amplitude dial. It also was the only severe at the time of initiating HFOV, intermittent hmg-
ventila tor that markedly increased tidal volume as mean recruitment maneuvers are used along with rapid upward
pressure increased.65, 125 Ventilators varied in the relation- titration of mPaw. Recruitment maneuvers are performed
ship of displayed mPaw and intrapulmonary mean pressure by resetting the high-pressure alarm to a higher value (i.e.,
measured during endotracheal tube occlusion.65 Threefold 50 cmH 2 0), eliminating a cuff leak if present, turning off
TABLE 20-3 Algorithm(s) for High-Frequency Oscillatory Ventilation in Adult Patients
Initial Steps Oxygenation Ventilation Weaning
Adequate analgesia and sedation Set initial mPaw 5 cmH20 higher Goal is highest frequency with Goal is Fro 2 of 40%, Sp~ of
Ensure adequate volume status than on CV89 lowest tJ. P for lung >88%, mPaw of 20-24
Set initial mPaw at 30 cmH20 after protection cmH20 before CV transition
setting cuff leak90
% IT =33
Neuromuscular blocker as FJ~ at 100% during transition Set initial ET cuff leak If required mPaw of >
required (if desaturntion with period (5-8 cmH20)90 35 cmH20, give equal
movement or spontaneous Use cuff leak before reducing f priority to reducing mPaw
breathing) below 5 Hz89 and F1o 2
Reduce mPaw earlier with
circulatory failure
Establish transcutaneous C02 Recmiting maneuvers Set initial tJ.P at 20 cmH2 0 + Reduce mPaw 2- 3 cmH20
monitoring to guide b.P and f (40-50 cmrhO for 40-60 s with Paco2 or to "chest vibration" cvery4-6 h
adjustments during transition piston off)-if severe hypoxemia, (usual range, 60-90 cmH20l
desaturation with suction,
postbronchoscopy, or circuit
disconnection89 •90 or on
initiation of HFOV49
Bronchoscopy to evaluate ET Jf Spo2 < 88%, increase mPaw Use f-tJ.P algorithm in ref. 90 When mPaw approaches
tube patency (especially if 3 cmH 20 every 30-60 min Set initial frequency at 5 Hz 20 cmH 2 0, transition to CV
prolonged time on CV) (maximum, 45 cmH 2 0) and Adjust f and tJ. P as in ref. 89 (e.g., TV, 6 ml / kg; PEEP,
consider additional recruiting 10 cmH2 0; Pplat, <30
maneuvers cmH2 0; I:E, 1:1; rate, 15-25
breaths/min) or to APRV
(e.g., Phi, 20 cmH 2 0; Plow
0 cmH 20; Thi, 4 s, Tlo, 0.8 s)
Bag-mask with attached PEEP Prone position ifFro 2 remains >0.6 ABG 15 min after initiating Conventional weaning
valve at head of bed or mPaw of >35 cmH2 0 90 HFOV: adjust tJ.P (5-10 progressin g to spontaneous
Prone patient if FJ~ > 0.~9 emH20 steps) and frequency breathing trit~ ls
(1- 2Hz steps) based on
Paco2 trends and pH (goal,
pH > 7.2) Bronclloscopy if
refractory hypercapnea
ABBREVIATIONs: mPaw, mean airway pressu re; CV, conventiona l ventilation; Ll.P, oscillatory pressu re amplitude; ET, endoiTacheal; PEEP, positive end-expiratory
pressure; TV, tidal volume; l:E, inspiratory-expiratory ratio; Pplat, inspiratory pressure plateau; S~ . oxygen saturation; Phi, high pressure; Plow, low pressure; Thi,
high pressure time; Tlo, low pressure time; ABG, arterial blood gas; APRV, aino,~ay pressure-release ventilation; HFOV, high-frequency oscillatory ventilation; %IT,
percent inspiratory time.
NOTE: Th is table outlines an overall approach while indicating areas in which different "experts" use somewhat different deci~ion algorithms.
the piston, raising the mPaw to 40-45 cmH20 (maximum With both approaches, the accepted target has been pro-
50 onH20) for 40-60 seconds, returning the mPaw to the jection of the diaphra gm onto the eighth or ninth rib
original setting (or 3 onH20 higher), and then restarting posteriorly on an anteroposterior film. An alternative
the piston and restoring cuff leak and alarms to the origi- reference in adults is visu alization of the fifth rib above the
nal levels. Recruitment maneuvers should be considered if diaphragm anteriorly or an apical-diaphragm distance not
desaturation occurs after suctionin~ bronchoscopy, circuit greater than 25 cm. 126 Emerging techniques for the eval-
disconnects, or patient repositioning. uation of regional ex~ansion hopefully will soon replace
An alternative approach in the recently published TOOLS these crude measures. 4 Information on the relative timing,
trial used one to three recruitment maneuvers immediately efficacy in terms of achieving the most homogeneous lung-
on initiating HFOV.49 The initial m a intenance mPaw was expansion pattern, and complication rate of these two ap-
set a t 30 cmH2 0 regardless of mean pressures on conven- proaches is needed before it will be possible to define an
tional ventilation. The conceptual framework here is to use "optimal" approach. The potential hazard of the first ap-
initial recruitment maneuver(s) tore-expand atelectatic re- proach is too little recruitment too slowly. The potential haz-
gions and then titrate the maintenance mPaw "down the ard of the second approach is excessive lung distension at a
deflation limb" of the P-V relationship in a timely fash- rote value of 30 on H20 mPaw if that value is not reduced
ion according to the patient's oxygenation response. This expeditiously enough in a lung that is very responsive to
methodology matches protocols used in many animal stud- recruitment. What is becoming clear is the importance of
ies of lung protection using HFOV. With this protocol, an ventilating "on the deflation limb," whether with conven-
Fro, of less than 0.6 was achieved in 68% of patients by the tional ventilation or with HFOV.47,t27
end of the initial recruitment cycle, which delivered 2.4 re- It remains speculative whether the target Fie, for optimal
cruitment maneuvers over a mean of 1.5 hours (Fig. 20-10). lung protection should be 0.4 or0.6. A substantial amount of
Change to
HFOV
Step 1
· Recruitment Maneu ver
F,0.=1.0 AP = 0
m f!w40 em H,Ox40s
• Begin oscillation
mPAW=30 FO
1 2
=1• 0
P=60-90 5H
1" repeat - resume HFOV Initial Cycle

using mP... 35 (1"set of up to
2"" repeat - use mR... 45- 3 RMs)
50x40 s for RM* and
resume HFOV at mP... 35
Max 3 cycles then wait 8 hrs
Step3
Wean F, O,ln increments
FIGURE 20-10 Protocol outlining
of 0.1 every 2 minutes
Stop When the sequence of recruitment
F,Of0.4 OR SPOf88-93% m aneuvers and HFOV settings us ed
in the TOOLS Trial to re-exp and
atelectatic alveoli at the time of
initiation of HFOV to get the lung
onto its deflation limb. 49 Patien ts
RMs· after disconnects and undenvent an initial cycle of u p to
at least twice dally IfF, 0?0.4
three sustained inflation
""""""'-"'- recruitment maneuvers (RM) (steps
Step4
Wean mf.'.ln Increments of 1 to 3). Ten minutes after the first
2cm H,O every 20 minutes RM, F1o1 was decreased in
To Step1 if Stop When: decrements of 0.10 every 2 minutes,
persistent stopping when either Ule F1o1 was
hypoxemia Step 5 0.40 or the arterial oxygen saturation
Wean F,O,In Increments or (Spo 2 ) was 88- 93% (step 3). If the
0.05·0.1 Q1 -12 Hrs to goal of Fio1 requirement remained greater
0.4 Ulan 0.60 after a iliird RM to 45-50
Steps cmH2 0, the recruitment procedure
Wean m':,.ln Increments of was repeated every 8 hours. Once
2 em H,O Q4-12 hrs to a goal the F1o 1 was less than 0.60,
ot22cm H,O maintenance mean airway pressure
(mPaw) was reduced in 2 cmH20
steps to
30 cmH20, keeping Spo1 at 88-93%
(s tep 4). F1oz was then weaned to
0.40 before further reductions in
Back to CV mPaw (steps 5 and 6). MPaw, mean
airway pressure; RM, recruitment
maneuver; .O.P, pressure amplitude
* Recruitment Maneuvers in cmH 2 0; Freq, frequency (Hz); CV,
• Pre-oxygenated with F, 0, = 1.0 x 5 mins conventi onal venti lation; ABG,
arterial blood gas. (Reproduced, with
• Aborted immediately if hemodynamic compromise
permission, from Ferguson
• Not performed if an active airleak present eta/: Crit Care Med 33:479--86, 2005.)
ongoing atelectasis remains at an F1~ of 0.6. As one moves The advantage of instituting a cuff leak when initiating
toward an earlier transition to HFOV-as in current neona- HFOV is the ability to use higher frequencies and smaller
tal and pediatric experience in many centers-lower F1~ volume cycles. The disadvantages are a need for more
targets become achievable a t "reasonable" mean pressures. nursing care to ensure removal of oral secretions and res-
At high F1 02 requirements, mPaw levels are reduced only piratory therapy involvement to remove and then reset
when doing so does not increase Fio 2 requirement. When the the cuff leak whenever a recruitment maneuver is per-
Fio2 is stable at 0.6, some protocols recommend reduction of formed. Endotracheal tubes with infraglottic suction ports
mPaw before further Fr~ decreases if the mPaw is greater may prove useful in this context. In cases of severe upper
than 35 cmH20. Whether this compromise between ongo- airway swelling, a pharyngeal airway positioned just above
ing atelectasis and the risk of higher pressures is necessary the larynx can be used to provide an exit pailiway for a cuff
likely will be best resolved when bedside methods of as- leak, as described by Cartotto et al59 in a burn patient. Fail-
sessing areas of overdistension become available. One pro- ure of mPaw to drop when instituting a cuff leak indicates
tocol that recommends this mPaw / Fr0 2 compromise also swelling around the cuff or upper airway.
recommends placing the patient in a prone position if the Protocols also differ in their approach to setting power or
F1~ requirement remains 0.6 or more (in order to potentiate AP. Some advocate starting at maximal power so that one
alveolar recruibnent in dorsal lung regions).34 can use the highest frequency possible89; other algorithms
manipulate botl1 ~p and frequency settings.34•90 Transcu-
taneous Pea, sensors can provide useful trend informa-
C0 2 EU:MINATION
tion (not absolute values) to guide power/ frequency ad-
The optimal approach to C02 elimination is currently con- justments during the initiation phase. Lower Paco, targets
troversial. When should the transport advantages of an en- are needed in patients with elevated intracranial pressure
dotracheal tube cuff leak be introduced? Inasmuch as the or head injury, as well as in neonates, in whom the risk of
lung-protective potential of HFOV lies in its small volume retinopailiy of prematurity may increase at high Pac~. 7
cycles, it would seem logical to introduce it a t tl1e time of
initiating HFOV in a large patient. With a cu.ff leak of 5- PATIENT POSITION IN G
8 cmH2 0, one can eliminate C02 a t a higher frequency,
deliver the smallest possible tidal volumes, and produce Patients should be placed a t 300 head up unless hemody-
the lowest possible ratio of intratracheal to airway open- namically unstable. The prone position also can be used
ing pressure swings. 79 With this approach, even very heavy during HFOV to optimize expansion of dorsal lung re-
patients generally can be ventilated at frequencies of 6 Hz gions, with appropriate protocols for caring for the prone
patient. '~ 28 If the prone position is not feasible but hypoxemia
or more. If reductions in frequency are required at any
remains severe, switching the patient from side to side in
stage, the first response to a decrease in Paco2 with recov-
true lateral positions (i.e., 90° to the mattress) may improve
ery should be an increase in frequency. Whether the fre-
lung recruitability.
quency target in adults should be 8 Hz or higher is presently
unknown. 89 Detailed protocols differing in their relative
weighting of amplitude (AP) and frequency are avai- Troubleshooting
lable.89·90
An alternative approach is progressive reduction of fre-
quency to 3Hz as needed to achieve target C02 levels, w ith Paco2 PROBLEMS
a cuff leak being added only w hen these much larger s troke It is particularly important to troubleshoot Paco. problems
volumes prove inadequate. appropriately (Table 20-4).
TABLE 20-4 Paco, Problems
Pac{h Too Low Pac{h Too High Acute Increase in Pac{h
t fin increments of 1-2Hz to t ~p if not al ready at 90 cm.HzO Verify EIT is patent:

90 89
8 or 12 Hz in increments of 5 cmH20 • Pass suction catheter
• Quick bronchoscopy
,J, ~Pin S cmHzO increments IMtitute a cuffleak if not present • Can one ventilate adequately
with manual bag/ mask?
Try RM(s) to reverse atelectasis Is there a pneumothorax?
Is a higher maintenance mPaw • Decreased vi brations
needed? u n ila tera ll.y?
(CXR or other measur e of lung • CXR
volume)
,J, f to a minimum of 3 H z in Progressive b1creasc Paco 2
1- 2Hz decrements Is chest wall compliance
decreasing?
• Abdomina l compartment
syndrome
• Burn eschar
DECREASED Paco2 HEMODYNAMIC COMPROMISE

As Pa<D! levels d ecrease during the course of lung recov-
Inability to tolerate the institution of HFOV or application of
ery, the first response should be to increase frequency back
recruitment maneuvers may reflect an inadequate intravas-
up to the 7-8 Hz range (1- to 2-Hz increments) and then
cular volume. Duval et al122 reported a need for a transient
to decrease power (5-10 cmH2 0 D.P decrements) in order
increase in fluids and inotropic agents in some infants dur-
to minimize volume and pressure swings in the lung. A de-
ing transition to HFOV. Interpretation of filling pressures
crease in D.P at a constant power setting maybe an indicator
(central venous pressure, pulmonary artery occlusion pres-
that lung volume is increasing.
sure) may be difficult in the setting of high mPaw. A fluid
challenge or transesophageal echo study may be needed in
INCREASED Paco 2 ambiguous situations. 34
An abrupt substantial increase in Pace: in a previously sta-
ble patient may reflect plugging of the endotracheal tube,
development of a pneumothorax, or a telectasis. One should
ensure passage of a suction catheter, check one's ability to
Important Unknowns
manually bag/mask ventilate, and perform a quick bron- HFOV protocols are under constant revision through ani-
choscopy while waiting for a chest x-ray to clarify the eti- mal experiments and clinical trials that evaluate both the
ology. Before decreasing frequency or increasing power in
gas-exchange and VIU impact of ventilator setting deci-
response to a gradual increase in Pac0 2, one must ensure
sions. We need criteria that indicate when any given ven-
that the lung is expanded adequately. An abdominal com-
tilator pattern needs to be replaced by one with a greater
partment syndrome should be considered. Available oscil- potential for lung protection. This is a complex question
lators all decrease delivered stroke volume when faced with considering that we do not even know when permissive
a greater load.65·66 Appropriate recruitment procedures of- hypercarbia becomes deleterious for patients.
ten can resolve Pace: problems while at the same time de- The optimal frequency or frequencies for minimizing the
creasing the phasic pressure swin gs within the airways and intrapulmonary pressure and distension "cos t" of HFOV
alveoli. A cuff leak should be considered before lowering
in the adult lung with varying pathophysiologies remain
frequency. unknown. Such information would clarify the risk-benefit
ratio of early use of a cuff leak. Existing algorithms differ
subs tantially in their management of f.89•90
OXYGENATION PROBLEMS
Optimal methods of aerosol delivery during HFOV need
As discussed earlier, oxygenation depends on achieving and further evaluation. Better bedside knowledge of which tech-
then maintaining end-expiratory lung volume. A gradual niques [e.g., recntitment maneuvers, ventilator settings, po-
downward drift of 0 2 saturation after a recruitment ma- sition changes (prone/ supine), a11d so on] produce tl1e most
neuver is indicative of too low a maintenance mPaw. Re- homogeneous lw-\g expansion across all lung regions would
cruitment should be repeated with a return to an mPaw greatly aid decision making. Emerging technologies such as
2- 3 cmH 20 higher than the previous level. If the Fie: re- electrical impedance tomography show promise.
quirement remains greater than 0.60 despite recruitment Neonates often are maintained on HFOV until extubation.
maneuvers, prone positioning should be considered. In- Premature transition to conventional ventilation can negate
ha led nitric oxide can be added, although whether this im- the benefit of HFOV. Because spontaneous breaths are not
proves outcome as well as oxygenation remains unknown. 97 augmented during HFOV, tl1is approach is not feasible in
large patients. The "optimal" timing of transition to conven-
tional ventilation may be difficult to determine until this de-
AIR LEAKS vice linlitation is resolved. It is well recognized that gross
Barotrauma occurs during HFOV but may be more subtle in deterioration of oxygenation after transition to conven-
its manifestations. Displayed mPaw will remain stable even tional ventilation should trigger an immediate re-evaluation
with a tension pneumothorax. The gradual development of the patient and possible return to HFOV. Whether
of hypotension and desaturation, with or without a unilat- keeping the lung splinted open with low Fio:, and small
eral decrease in chest-wall motion, should trigger a portable volume/ pressure cycles in a spontaneously breatlling pa-
chest x-ray. In an experimental model of pneumothorax dur- tient for an extra few days (as witll APRV) 90 would facilitate
ing HFOV, air leak was minimized by tl1e use of higher lung recovery biochemically and/ or s tructurally during the
frequency, lower ~P, lower mPaw, and shorter inspiratory resolution of ARDS remains to be tested.
period. 129 Excessive decreases in mPaw will promote a telec-
tasis with a resulting increase in intrapulmonary pressure
cost, delaying resolution of the air leak. .I n general, recruit- Future Directions
ment maneuvers are not advised in the presence of air leak.
This is not an absolute contraindication. In the presence of Hopefully, further pilot studies will clarify some of the is-
severe hypoxemia and unilateral air leak, recruitment ma- sues outlined herein before large-scale comparative trials of
neuvers performed with the patient in a full lateral position HFOV and other lung-protective options are performed. To
with the leak side down may achieve significant benefit by date, no large randomized, controlled trial of HFOV has
re-expansion of the nondependent lung. been performed with lung-volume optimization "on the
deflation limb" of the P-V relationship. Validation of var- 11 . Clark RH, Slutsky AS, Gerstrnann DR. Lung protective strate-
ious mPaw, recruitment maneuver, L'l.P, and frequency al- gies of ventilatio n in the neonate: What are they? Pediatrics 2000;
gorithms for their effect on VIU in large animal models is 105:112-4.
needed. Prospective, randomized trials can only be done in 12. Froese AB, Bryan AC. High frequency ventilation. Am Rev
centers comfortable with HFOV. Currently, many centers Respir Dis 1987; 135:1363- 74.
13. Slutsky AS. Nonconventional methods of ventilation. Am Rev
use HFOV rarely and only for severe, refractory oxygena-
Respir Dis 1988; 138:175-83.
tion failure or air-leak syndromes associated with end-stage 14. Sjostrand U. Review of the physiological rationale for and de-
lung disease. This is not the way to develop a cadre of physi- velopment of high-frequency positive-pressure ventilation-
cians, nurses, and respiratory therapists who can skillfully HFPPV. Acta Anaesthesiol Scand Suppl1977; 64:7- 27.
troubleshoot interactions between the machinery and the 15. Lunkenheimer PP, Rafflenbeul W, Keller H, eta!. Application of
patient's pathophysiology. transtracheal pressure oscillations as a modification of "diffus-
ing respiration." Br J Anaesth 1972; 44:627.
16. Emerson J. Appara tus for vibrating portions of a patients' air-
REDESIGNED MACHINES way. U.S. patent no 2,918,917, january 1959.
17. Bryan AC. The oscillations of HFO. Am J Respir Crit Care Med
Currently, high-frequency oscillators are still classified as
2001; 163:816-7.
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triggers expensive review costs, much in excess of that re- jet ventilation. Crit Ca re Med 1977; 5:280-7.
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Clulpter 21 racic surgical procedures, but it also raised the possibil-
ity that patients with severe acute respiratory failure not
EXTRACORPOREAL responding to mechanical ventilation also might benefit
from extracorporeal blood oxygenation and carbon ctioxide
MEMBRANE removal.
The first successful clinical application of long-term ex-
OXYGENATION AND tracorporeal membrane lung gas excl1ange for severe acute
respiratory failure was reported by Hill et al10 in 1970 in
EXTRACORPOREAL a young man following a motorcycle accident, with use
of the Bramson membrane lung. Subsequently, membrane
LIFE SUPPORT lung bypass was applied successfully in the treatment of
acute respiratory ctistress syndrome (ARDS) of various
ROBERT BARTLETI causes.11• 12
THEODOR KOLOBOW The many sporadic attempts at extracorporeal membrane
lung assist led to a concerted effort by the National Institutes
of Health (NIH) to launch a randomized, controlled multi-
center study13 in patients with severe ARDS (1975- 1977).
One group of patients was managed with conventional
methods; the other group, with extracorporeal membrane
CURRENTSTATUSOFEXTRACORPOREAL oxygenation (ECMO). Of the total of 90 patients divided
LIFE SUPPORT between the study and control groups, 4 patients in each
Venoarterial Access group survived. It was concluded that patients entered into
Venovenous Access this trial were far too advanced in their illness to benefit
THE PERFUSION CIRCUIT from any form of therapy.
THE TEAM To address fears that the study groups represented pa-
CLINICAL RESULTS tients who were unlikely to benefit from any extracorpo-
NEONATAL RESPIRATORY FAILURE real gas exchange, a follow-up study (as part of the same
PEDIATRIC RESPIRATORY FAILURE study) was performed on 702 patients who had required
ADU LT RESPIRATORY FAILURE only intubation for 24 hours or more and a fractional in-
CARDIAC FAILURE: CHILDREN spired oxygen concentration (Fx~) of 0.5 or greater. Overall,
CARDIAC FAILURE: ADULTS that study showed a mortality rate of 61%, much higher than
EXTRACORPOREAL CARDIOPULMONARY anticipated.
RESUSCITATION Over the years, a hard core of ECMO centers has contin-
OTHER APPLICATIONS OF ECLS ued to apply lessons learned through experience, as well as
CONCLUSIONS lessons learned from animal research, to the use of ECMO in
patients with ARDS or acute respiratory failure who were
The earliest development of the artificial lung (Fig. 21-1) was believed to be salvageable. Results have been encouraging.
ctirected to its use in the repair of congenital heart defects ECMO, when applied in a timely manner by experienced
in the surgical operating room using filming or " bubble" clinicians and investigators, remains an important adjw1ct
oxygenators. 1- 3 Such early blood oxygenators served their in the care of the patients with severe ARDS. A registry of
purpose well because most cardiac surgical repairs could cases in all age groups is com piled through the Extracorpo-
be completed in a few hours. Limitations in the use of both real Life Support Organization (ELSO). 14
bubble and the subsequently introduced filming oxygena-
tors for more that a few hours produced deterioration in
organ function, with coagulopathy, hemolysis, thrombocy-
topenia, and fluid retention being the more conspicuous Current Status of Extracorporeal
findings. There was a general consensus that direct expo- Life Support
sure of blood to oxygen largely was responsible for those
complications.4•5 Extracorporeallife support (ECLS)/ ECMO is now used rou-
The earliest prototype membrane artificial lung was tinely in every major childrens hospital, and use is grow-
based on a relatively low-permeability polyethylene ing in adult intensive-care units (ICUs). The inctication for
membrane. 6 Such membranes were replaced subsequently ECLS is acute severe cardiac or pulmonary failure when re-
by far more gas-permeable silicone rubber membranes?-8 versibility and recovery (or organ replacement) can be ex-
More recently, the latter membranes have been comple- pected within a few weeks. The measurements of severity
mented by microporous polymeric capillary tubes (the of ilh1ess and the likelihood of recovery (or replacement) are
capillary membrane lung) of various designs, 9 the use of different for patients with respiratory or cardiac failure and
which now assumes a commanding lead in cardiovas- also are different among patients of different ages groups.
cular surgery. Not only did membrane-based artificial- Hence evaluation of the use of ECLS requires information
lung technology allow for longer and safer carctiotho- on a variety of patient groups. Through the ELSO, which
493
494 PART VII UNCONVENTIONAL METHODS OF VENTILATOR SUPPORT
cess, monitoring variables, control of blood flow, goals of

FL AT SHEET management, and personnel are custom made for each
application.
VENOARTERIAL ACCESS
Venoarterial access (VA) is required for cardiac support or in
patients with respiratory failure w ho are in profound shock.
a In babies, VA is achieved by cannulation of the right atrium
through the right intemal jugular vein and the aortic arch
via the right common carotid artery. These vessels are ex-
posed directly, ligated distally, and cannulated. 15 There is
CAPILLARY
abundant collatera l circulation around the common carotid
artery, and the incidence of right cerebral ischemia is less
than 1%. Brain blood flow does not depend on an intact circle
of Willis because fo rward flow is established in the internal
o. Blood .nside copillory carotid artery distal to the ligated common carotid artery.
b. Blood around copi llory In adults and children older than 3 or 4 years, the femoral
artery is large enough for a rterial access, although perfusion
b to the distal leg poses a significant risk. The best m ethod for
VA access is to cannulate the right atrium through the right
SPIRAL COIL
internal jugular vein and to cannulate the femoral artery at
the groin. Access to both vein a nd a rtery are achieved by
the percutaneous Seldinger technique, altho ugh direct ex-
posure may be necessary in very s mall children. Draining
blood from the right atrium via the jugular vein a voids the
problem of differential circulatio n, which can occur when
c the inferior vena cava is cannulated via the femoral vein.
When the femoral artery is used for cannulation, distal per-
fusion can be established by direct cutdown and placement
LIOUIO-LIOUlO .. of a catheter in the superficial femoral artery. An alterna-
INTERFACE .: ..:
•
..
•: •
l • •
tive teclmique is to cannulate the posterior tibial artery by
"' •
Blood •:. , , • OqQCn
I I
direct cutdown after the pa tient is on extracorporeal sup-
[:;}-!..!-fluorocarbon port. If the pressure in the posterio r tibial artery is greater
Flui d than 50 mmHg, distal perfusion is usually not necessary.
d If the pressure is less than 50 mmHg, then the leg can
be perfused via the cathe ter in the posterior tibial artery,
employing a tubing extension off the arterial per fusion
line.
FIGURE 21-1 The four basic membrane lung design concepts. During VA bypass, extracorporeal flow is managed by
A. The flat-sheet membrane lung. Venous blood flows between measuring venous blood saturation; saturation should be
two sheets of gas-permeable membrane w ith oxygen-enriched gas between 70% and 80%. Patients usually exhibit some card iac
on the outside. For increased surface area, such units are stacked
one on top of the other with a screen spacer providi ng space for
function, and blood flow is regula ted to m aintain an arterial
gas (air, oxygen) flow . B. Capillary membrane lung. Venous blood pulse contour. This is usually equivalent to about 20-30%
flows either through the inside of gas-permeable plastic capillary of the venous return going through the native circulation
fibers or outside with oxygen-enriched gas on the other side. rather tha n through the extracorporeal circuit.
C. Spiral coiled membrane lung. A long ribbon of plastic screen is During VA access through the femoral a rtery, blood is
covered on both sides with a fabric-reinforced silicone rubber perfused retrogradely up the aorta. Unless the patient is on
membrane that is rolled into a spiral coil. Oxygen flows within total bypass, however, blood in the aortic root perfuses the
the coiled screen, with blood flow perpendicular to oxygen fl ow coronary vessels and car otid vessels. This blood has a gas
on the outside. D. liquid-liquid interface membrane lung. Blood content of blood passing through the lungs and out through
is exposed to microdroplets of well-oxygenated and C02·depleted
the left ventricle. If the pa tient is on ECI.S for cardiac fail-
fluorocarbon fluid to pick up 0 2 and w ash out col.
ure and the lungs are working adequa tely, the blood is well
oxygenated. If the pa tient is in combined cardiopulmonary
maintains a registry of ECI.S patients, this information is failure, however, some method must be undertaken to en-
readily available. sure adequate oxygenation of the blood in the root of the
The technology and personnel involved with ECLS are aorta. This can be accomplished by arterial perfusion via
evolving continuously. The concept of replacing cardiac the car otid artery or by perfusing oxygena ted blood off the
and/ or lung function by extracorporeal circulation is ba- arterial line into the venous circulation, a technique we refer
sic to all applications, but the m ethods of vascular ac- to as VAV access.
CHAPTER 21 EXTRACORPOREAL MEMBRANE OXYGENATION AND EXTRACORPOREAL LIFE SUPPORT 495
Often during the use of ECLS for cardiac failure, the heart oxygenators are very efficient at removing carbon
stops working altogether. If this occurs, the left atrium and dioxide. Thus patients with hypercapnic respiratory
left ventricle will overdistend gradually with blood return- failure (secondary to asthma, for example) can be managed
ing from bronchial and thebesian veins. The pulmonary with relatively low blood flow. Percutaneously placed W
vascular pressure can reach very high levels, creating pul- catheters can be removed when the patient has recovered.
monary edema and lung dysfunction. This is avoided by Hemostasis is achieved by local pressure.
draining blood from the left side o f the heart, generally by
doing a blade atrial septostomy in the cardiac catheteriza-
tion laboratory. The creation of an atrial-septal defect de-
compresses the left atrium into the right atrium. This atrial- The Perfusion Circuit
septal defect can be repaired at a later date when the heart
recovers, although most patients who require this extensive The extracorporeal perfusion circuit includes a membrane
step ultimately undergo cardiac transplantation. oxygenator, a blood pump, and conduit tubing. The cir-
When an infant has recovered and it is time to decannu- cuit usually includes a heat exchanger to maintain normal
late the VA bypass, this is done under direct exposure. The body temperature. Monitors include pre- and postoxygena-
catheters are removed, and the vessels are ligated proxi- tor pressure sensors, which are useful for detecting signs of
mally. Although it is possible to repair both the vein and oxygenator thrombosis or fail ure. Blood-gas or saturation
artery, our practice is to leave the vessels ligated because sensors can be inserted directly into the venous drainage
of the potential risks of distal embolization in a repaired tubing. T he extracorporeal circuit requires systemic anti-
vessel. If VA access has been achieved via the percutaneous coagulation. A device to measure whole-blood activated
route in a large child o r adult, it is usually possible to re- clotting time (ACT) is an important part of the bedside
move the catheters and apply local pressure. Even with a apparatus. A continuous infusion of heparin is titrated to
large catheter in the femoral artery, hemostasis usually is maintain the ACT at approximately 50% above normal. With
achieved without need for direct repair. the usual ACT system, for example, the upper level of nor-
mal is 120 seconds, and ACT during ECLS is maintained at
180 seconds. It is essential to use whole-blood ACT rather
VENOVENOUS ACCESS
than partial thromboplastin time or some other measure of
Venovenous (W) acces is the preferred method for patients plasma anticoagulation.
in respiratory failure who have adequate cardiac function.
Even patients who require high doses of pressors and in-
otropes to maintain the circulation before ECI.S are man-
aged successfully by W access. The ino tropes and pressors The Team
can be discontinued as soon as the ventilator is returned to
resting settings. A major advantage of W access is that all The team caring for the patient on ECLS varies from stan-
the blood flow passes through the pulmonary circulation dard TCU staff w ith extra training in ECLS to a independent
and left side of the heart, minimizing the risks of intrapul- team o f ECI.S specialists. In most programs, the latter ap-
monary and left-sided cardiac thrombosis and embolism. proach is favored because the patient is totally dependent on
In addition, sustaining the pulmonary circulation may pro- the circuit, and someone needs to be on hand to respond to
duce some beneficial effect on the healing of acute lung in- circuit emergencies within seconds. Improvements in tech-
jury. In infants and small children, W access is best achieved nology to simplify the bedside system will make it possi-
by cannulation of the right atrium through the right internal ble for any ICU team to manage patients on extracorporeal
jugular vein using a double-lumen catheter.16 The larger lu- support.
men is for venous drainage, and the smaller lumen for blood
return. Blood return is aimed toward the tricuspid valve to
minimize recirculation. Total gas-excllange support can be
achieved easily in this fashion, although there is some mix- Clinical Results
ing with the rest of venous blood.
ln the future, W access in larger children and adults will The most recent data from the ELSO registry and the Uni-
be achieved through large-bore double-lumen catheters. versity of Michigan are shown in Table 21-1. Participation
At present, however, these catheters do no exist, so W in the El.SO is voluntary, and yet, almost all patients treated
access is achieved by cannulating the inferior vena cava with ECLS in established centers are included in the registry.
via the femoral vein; the vena cava blood is drained, There are now over 30,000 patients who have been managed
with reinfusion into the right atrium via the rig ht inter- with ECLS. Extensive data are available on gas exchange,
nal jugular vein. 17 During VV support, cardiac function perfusion, coagulation, and so on, but the only important
is normal; indeed, the patients are dependent on their outcome is survival at hospital discharge because this tech-
own cardiac function for systemic perfusion. Pulse contour nique is applied only to patients who are not expected to
therefore is normal. W flow is regulated to maintain survive otherwise. The indication for ECI.S is a high risk
the desired gas exdlange: Arterial saturation remains (80-100%) of dying with continued conventional treatment.
in the 85% range for hypoxemic respiratory failure and The mortality risk is quantified differently in different age
normocapnia in hypercapnic respiratory failure. Membrane groups.
496 PART VII UNCONVENTIONAL METHODS OF VENTILATOR SUPPORT
TABLE 21-1 ECLS: Overall Survival results in ELSO Registry

and Un iversity of Mich igan, Jan uary 2005
El.SO R£GTSTRY UNIVERSITY OF MICJilGAN -...

0
.8.!!!
Survival Survival E c:
Patients Number Percentage Number Percentage ::a.!!
Z1ii
Neonatal
Respiratory 19,463 77 701 84
-
CiiQ.
0
1-
Cardiac 2,518 39 136 46
Pediatric
Respiratory 2,883 56 192 75
Cardiac 3,381 42 148 41 138 276 59 320 165 347
Adult Surv 171 471 111 288 193 395
Respi ratory 1,025 53 266 54 FIGURE 21-3 Survival w ith use of extracorporeal life support in
Cardiac 638 33 147 39 p ediatric p atients with respiratory failure according to diagn osis.
Overall 29,908 66 1,590 72
neurologic disability; the most common is some hearing

loss. This is lower than the incidence of complications
Neonatal Respiratory Failure in critically ill infants not treated with ECLS, indicating
that the complications are those of profound illness in the
The largest group of patients treated with ECLS a re new- newborn."' 8 The use of ECLS in neonatal respiratory fail-
born infants in respiratory failure. There are only a few ure has decreased after the introduction of nitric oxide in-
causes of severe respiratory failure in newborn infants. ha lation for treating pulmonary hypertension. 19 At present,
Survival for these diagnoses is 64-94% and 52% for con- approximately 1000 pa tients per year are entered into the
genital diaphragmatic hernia (Fig. 21-2). The reason fo r ELSO registry.
the excellent r esults is that respiratory failure in neonates
does not destroy lung tissue. The primary pathophysiology
in neonates is pulmonary hypertension w ith right-to-left
shunting through the ductus arterious (persistent fetal cir- Pediatric Respiratory Failure
culation). During ECLS, the pulmonary vasculature relaxes,
the ductus closes, and lung recovery occurs promptly. The Severe respiratory failure in older children is relatively rare
problem in congenital diaphragmatic hernia is mechanical compared witl1 the incidence in newborn infants a nd adults.
because the hernia compresses the lungs and causes lung TI1e most common cause is viral or bacterial pneumonia.
hypoplasia in utero, in addition to pulmonary vasospasm. Sta tus asthmaticus is another life-threatening problem in
children. ECLS is used when a patient is not responding to
Hypoplastic lungs may be too sm all to support the infa1~t.
other methods of management. The survival rate is approxi-
The early neona tal ECMO patients are now adults w1th
mately 55%, varying to some extent with the primary condi-
children of their own. There is abundant information on
tion (Fig. 21-3). Most children w ith respiratory failure can be
long-term follow-up. About 10% of survivors have some
managed successfully with VV access. In children who do
not survive, the most common cause of death is progressive
lung des truction from the primary infection or brain dam-
FIGURE 21-2 Survival with use of extracorporeal life support in age from hypoxia and ischemia that preceded ECLS: These
n eonatal respiratory failure according to diagn osis. MAS,
children are essentially all norma l at foLlow-up. Speofically,
meconium aspiration syndrome; CDH, congenital diaphragmatic
h ernia; PPHN, persistent pulmon ary h ypertension in the neonate; once the lungs recover pulmonary function, exercise toler-
RDS, respiratory distress syndrome. ance returns to normal.
8000
94%
--
(I)
c:
7000
.!!! 6000
52%
Adult Respiratory Failure
ARDS is a primary pulmonary disorder in about half the
-
[
...0
Gl
.c
5000
4000 1-
- 75% 78%
patients (e.g., pneumonia and so on) and secondary to ex-
trapulmonary causes in the rest (e.g., shock trauma, pa ncre-
atitis, and so on). Overall mortality for ARDS is 30-40% even
E 3000 1-
....._ 64%
z:::1 2000 1-
r-- - --=- I--
84% with excellent management. ECLS is indicated fo r patients
-
al
0
1-
1000 1-
......
r--
=
-
......
----
-
f-
at high risk of mortality within the first 5 days of intubation.
These patients are relatively easy to identify. They have an
alveolar-arterial oxygen gradient of greater than 600 on the
0 MAS CDH Sepsis PPHN ""' RDS Other
second to fourth day following initial intuba tion. The mor-
Non·Surv 410 2203 594 649 221 590 tality risk is approximately 80%, and the recovery rate with
Surv 6253 2426 1802 2347 1167 1039 ECLS in these patients is approximately 70%.20 - 22 Patients
TAB LE 21-2 Extracorporeal Life Support for Card iac Failure:
Infant ELSO Registry, Jan uary 2005
-...
G).,
0
.J:l- Patien ts umber

Survival
Percentage
E c:
j.!!
ZCij Posttrnnsplantation 80 50
s0
- Q.
Other postoperative
1- Not bridged 1263 40
Bridged 29 38
Not pos toperative
ARF Other Not bridged 271 48
91 33 14 99 22 180
Bridged 27 44
Surv 100 55 18 70 101 37 172
FIGURE 21-4 Survival with usc of extracorporeal liic support in the patient has been weaned off bypass and the chest is
patients with adult respiratory failure according to diagnosis. closed, vascular access is achieved by cannulation of the
right internal jugular vein and right common carotid artery,
on the ventilator for more than 5 days before ECLS have a as in newborn respiratory failure. This vascular access is
lower chance of recovery. Hence the overall survival rate also used for children with myocarditis or myocardiopathy.
for ECLS treatment of ARDS is approximately 55%23.24 (Fig. Because ECLS commonly is used directly after cardiopul-
21-4). The University of Michigan has reported the largest monary bypass, bleeding is a more common occurrence in
experience with ECLS for ARDS. In their series, overall sur- cardiac patients than in respiratory patients. This is best
vival was 52%. 23 A prospective, randomized trial of ECLS managed by maintaining the chest open with a sterile plastic
for ARDS is currently underway in the United JGngdom.25 sheet over the open wound and with blood drainage tubes
Another important application for ECI.S in children and placed in the chest. In this manner, bleeding can be observed
adults is status asthmaticus. These patients are unrespon- directly; it is easy to reexplore the chest, which frequently
sive to bronchodilators, intubation, ventilation, sedation, is required every 8-12 hours during the first day on ECI.S.
heliox, general anesthesia, and the other extreme measures. Bleeding is managed by maintaining the heparinization at
Pneumothorax occurs often and usually is fatal. Approxi- very low levels (1.25 times the upper limit of normal ACD,
mately 4000 patients die of acute asthma in the United States maintaining platelet count above 100,000, and adding a pro-
every year. This condition ideally is treated with EClS. Sim- tin in to enhance platelet function and amicar to minimize
ple VV cannulation and relatively low blood flow are all fibrinolysis. A combination of amicar, aprotinin, and low-
that are required to achieve normal C02 clearance and re- level heparinization can lead to thrombus formation in the
store normal blood gases. Once this occurs, bronchospasm extracorporeal circuit. rt is important to keep a primed ex-
invariably clears within a day or two.26 Because the risk tracorporeal circuit available so that the perfusion circuit
of pneumo thorax and death are significant, and because can be changed should clotting occur.
the ris k of ECLS is low, ECLS should be considered in any Generalized fluid overload is a common problem associ-
patient who has a severe asthma attack with a Pac<>z of ated with cardiac failure in children. Diuresis is begun im-
greater than 80 mmHg despite mechanical ventilation and mediately with ECLS. If satisfactory negative fluid balance
other optimal treatment. When ECI.S is used for status asth- cannot be achieved with continuous infusion of diuretics,
maticus, the gas fl ow to the membrane lung is increased continuous hemofiltration is instituted.
slowly over hou rs to avoid sudden changes in Paco, and When ECLS is used for cardiac support, pulmonary and
pH. left-ventricula r blood flow decreases in proportion to the ex-
tracorporeal flow. As described earlier, this can lead to two
problems. First, if the heart stops altogether, the left atrium
and the left ventricle g radually distends, and bronchial ve-
Cardiac Failure: Children nous blood produces high pulmonary venous pressures and
VA ECI.S is the only mechanical support system available
for children in the United States. The experience with car- TABLE 21-3 Extracorporeal Life Sup port for Cardiac Failure in
diac failure in children is listed in Tables 21-2 and 21-3. Children Aged 1- 16 years ELSO Registry, January 2005
Most children treated with ECLS have cardiac failure fol- Survival
lowing cardiac operation, usually for congenital heart dis- Patients Number Percentage
ease. ECI.S patients have myocardial injury from their pri-
mary disease or during cardiopulmonary bypass. These Posttransplantation 160 51
patients cannot be weaned off cardiopulmonary bypass in Other postoperative
the operating room, or if they are weaned, they remain in Not bridged 786 40
profound ca rdiac failure despite full inotropic support. Pa- Bridged 47 40
tients who cannot be weaned from cardiopulmonary bypass Not pos toperative
Not bridged 326 48
are attached to the ECLS machine using the same catheters
Bridged 115 55
used for bypass, typically in the right atrium and aorta. If
pulmonary edema. This condition is diagnosed by the lack TAB LE 21-5 Extracorporeal Life Supp ort as Resuscitation
of pulsatility in the systemic arterial system. If the arterial Adjunct (ECPR), ELSO Registry, 2005
pressure is nonpulsatile, VA flow is decreased gradually
Survival
until pulsatility is established. If left-ventricular function is Patients Number Percentage
inadequate to maintain emptying of the left side of the heart,
some system must be used to vent the left side of the heart, Neonatal 174 41
either direct catheterization of the left atrium or creation Pediatric 322 39
of an a trial-septal defect. Another problem with VA bypass Adult 139 37
in the totally failing heart is thrombosis in the left atrium
or left ventricle. This can occur even during systemic hep-
arinization. Thrombosis is diagnosed by echocardiography. Extracorporeal Cardiopulmonary
If a patient has a left-atrial or left-ventricular thrombus, it
is important to avoid spontaneous left-ventricular function Resuscitation
because the thrombus can embolize and enter the systemic
circulation. Usually these patients are candidates for left- ECLS can be used in association with resuscitation to sup-
ventricular assist devices or cardi.1.c replacement, and the port cardiac and pulmonary function in cases of cardiac ar-
dot is removed before embolism occurs. rest or profound shock. For this application, the ECLS circuit
must be primed and available within minutes. Hence ex-
tracorporeal cardiopulmonary resuscitation (ECPR) is used
Cardiac Failure: Adults primarily in established ECLS centers that have the equip-
ment and a team to institute ECLS at a moment's notice. The
The experience with ECLS for cardiac failure in adults is limiting factor in establishing ECLS is vascular access. It is
lis ted in Table 21-4. The most common indication is acute difficult to achieve rapid arterial and venous access in a pa-
cardiac failure following myocardial infarction or cardiac tient in cardiac arrest. Successful ECPR has occurred mostly
surgery. Vascular access usually is achieved by cannulation in patients who arrested and were resuscitated briefly, in
of the right atrium via the right internal jugular vein, and ar- whom simple vascular access had been gained following ini-
terial retum is retrograde via the femoral artery. If function tial resuscitation. The ECLS catheters can be placed through
is severely impa ired, it may be necessary to use the system smaller catheters if and when the patient arrests again or
of VAV access described earlier. proceeds to cardiogenic shock or intractable arrhythmias.
Intra-aortic balloon pumping is possible in adults and will At the University of Michigan Hospitals, we consider ECPR
support approximately 40% of cardiac output. Most patients for patients who have been in cardiac arrest for less than
treated with ECLS have already failed balloon pumping and 5 minutes. A few patients who arrested and r eceived full
full inotropic support. If a balloon pump is in place through resuscitation for over an hour have been treated s uccess-
a femoral artery, it is best to keep it in place because of fully. If the arrest is prolonged and profound metabolic
the risk of bleeding after pump removal. The contralateral acidosis exists, establishing ECLS is often futile. Overall
femoral artery is used for arterial access. healthy survival after ECPR is approximately 40%, much
Adult patients in acute cardiac failure are candidates for better than the 5% success rate of external massage30•31
a left-ventricular assist device as a bridge to recovery or to (Table 21-5).
transplantation. In acute cardiac failure, however, it is best
to institute ECLS first to stabilize the circulation and gas
exchange and to determine if other organs are functioning, Other Applications of ECLS
especially the brain. If severe brain injury has occurred dur-
ing the period of acute cardiac failure, ECLS is discontinued, T~e ability to totally control perfusion and gas exchange
thus avoiding futile thoracotomy and the expense of the left- With an extracorporeal system offers unique opportunities.
ventricular assist device. Survival for ECLS in adult cardiac Profound hypothermia can be treated. This is particularly
failure is 40-50%_27-29
important because hy pothermic patients may d evelop ven-
tricular fibrillation during external wamling. Hypothermia
TABLE 21-4 Extracorporeal Life Su p port for Cardiac Failure in associated with exsanguinating hemorrhage in the operat-
Adults, ELSO Registry, January 2005 ing room can be treated successfully with ECLS.32 Perfusion
Survival is maintained until bleeding is controlled, and hypothemlia
Patients Number Percentage can be maintained to protect organ function. Blood then is
returned to the patient to avoid the coagulopathy caused by
Posttransplant 79 32 low temperature. With a heat exchanger, hyperthermic per-
Other postoperative fusion also can be established either for total-bod y warming
Not bridged 278 31 or for regional warming as an adjunct to cancer chemother-
Bridged 22 50 apy.
Not postoperative
Septic shock was once considered a contraindication to
Not bridged 167 32
ECLS. Sepsis often dears during ECLS, however, and this
Bridged 25 36
has become a standard indication in our institution. It
is common for patients in septic shock to regain normal References
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Med 1997; 23:819-35. 35. Dreyfuss 0 , Basset G, Soler P, Saumon G. High inflation pressure
25. Conventional ventilation or ECMO for severe adult respiratory pulmonary edema: Respective effects of high airway pressure,
failure. Available at rvww.ct?sar-/ria/.org/; accessed April 12, high tidal volume, and positive end-expiratory pressure. Am
2004. Rcv Respir Dis 1988; 137:1159-64.
26. Shapiro MB, Kleaveland AC, Bartlett RH. Extracorporeal life 36. Kolobow T, Moretti MP, Furnagalli 0, et al. Severc impairment
sup port for sta tus asthmaticus. Chest 1993; 103:1651-4. in lung function induced by peak airway pressure during
27. Pagani FD, Aaronson KD, Dyke DB, et al. Assessment of an mechanical ventilation. Am Rev Respir Dis 1987; 135:312-5.
extracorporeal life support LVAD bridge to heart transplant 37. Tsuno K, Prato P, Kolobow T. Acute lung injury from mechanical
strategy. Ann Thorac Surg 2000; 70:1977-984; discussion 1984-5. ventilation at moderately high airway pressure. J Appl Physiol
28. Muehreke DO, McCarthy PM, Stewart RW, et al. Extracorporeal 1990; 69:956-61.
membrane oxygenation for postcardiotomy ca rdiogenic shock. 38. Berra L, De Marchi L, Curto F, et al. Adverse changes in lungs
Ann Thorac Surg 1996; 61:684-91. of sheep ventilated for 72 hours at a moderately high peak
29. Magovern GJ, Simpson KA. Extracorporeal membrane oxygena- inspi ra tory pressure and p rolonged inspiratory time. Am J
tion for adult cardiac support: The Allegheny experience. Ann Respir Crit Care Med 2004; 7:A785.
Thorac Su rg 1999; 68:655-61. 39. Lee WL, Slutsky AS. Ventilator induced lung injury and recom-
30. Younger JG, Schreiner RJ, Swaniker F, et al. Extracorporeal mendations for mechanical ventilation of patients v.rith ARDS.
resuscitation of cardiac arrest. Acad Emerg Med 1999; 6:70Q-7. Semin Respi r Crit Care Med 2001; 22;269-80.
31. Massetti M, Tasle M, LePage 0, et al. Back from irreversibility: 40. Brower RG, Matthay MA, Morris A, eta!. Ventilation with lower
Extracorporcal life support for prolonged cardiac arrest. Ann tidal volumes for acute lung injur y and the acute respiratory
Thorac Surg 2005; 79:178-83. distress synd rome. The Acute Respiratory Distress Syndrome
32. Hines M, Pranikoff T. Personal communication, 2004. Network. New Eng! J Med 2000; 342;1301-308.
t:hapter 22 tients with severe acute respiratory failure, whose main
problem often was altered gas exchange and not respira-
EXTRACORPOREAL tory muscle weakness or paralysis. The critical-care profes-
sion w itnessed both the pros and cons of optimizing gas
CARBON DIOXIDE exchange through u se of the ventilator: The focus shifted
from high to low tidal volumes, from high to low airway
REMOVAL pressures, and from high to lower inspired oxygen fractions
(FI~ ). It is provocative to consider how we support the fail-
ANTONIO PESENT! ing lung. In ARDS, we use an artificial organ (the ventilator),
LUCIANO GATT!NONI which is designed to substitute for the respiratory muscles
MICHELA BOMUJNO
rather than to act as a gas exchanger. Teclmology has been
the limiting factor for a w idespread application of artificial
gas exchange, 11 but research and development continues at
a promising pace.
ARTIFICIAL ORGANS FOR RESPIRATORY FAILURE

MEMBRANE OXYGENATORS, MEMBRANE GAS
Membrane Oxygenators, Membrane Gas Exchange,
and Membrane Lungs EXCHANGE, AND MEMBRANE LUNGS
Pioneers Extracorporeal oxygenation was first provided as a heart-
Why Did the NTH-ECMO Study FaiJ? lung machine to render major cardiovascular surgery fea-
THE CONCEPT OF ECC0 2R sible and safe. 12 The first oxygenators were based on bub-
DISSOCIATING RESPIRATORY FUNCTIONS bling of oxygen through the blood or filming of blood in an
ECC0 2R AND THE CONTROL OF oxygen atmosphere. To avoid the problems caused by the
SPONTANEOUS BREATHING direct contact between blood and gas,13• 14 Kolff designed
Apneic Oxygenation a membrane oxygenator, 15 which Clowes16 and Kolobow 17
Low-Frequency Positive-Pressure Ventilation developed further into clinically applicable membrane gas
Alveolar P~ Control during ECC02R exchangers.18 - 20 Attention was focused on extracorporeal
RATIONALE FOR ECC0 2R USE oxygenation, and the term e;'(tracorporenl membrane oxygena-
CLINI CAL APPLICATIONS: VENOVENOUS BYPASS tion (ECMO) was coined. Very little attention was paid to
Bypass Technique concurrent C02 removal: Hypocapnia was recognized as a
Anticoagulation common annoyance to be prevented by adding C02 to the
O inical Management gas ventilating the oxygenator.
Complications of Venovenous ECC02R
Clinical Results
PIONEERS
RECENT CLINICAL DEVELOPMENTS:
ARTERIOVENOUS BYPASS In 1967, Ashbaugh et al21 described ARDS. Soon this became
CONCLUSIONS a very common diagnosis in critical care, and mechanical
ventilation moved to center stage as the main s upportive
therapy.22 To optimize oxygenation, tidal volumes of 10-15
Artificial Organs for Respiratory Failure rnl/kg were recommended. The high minute volumes often
required the addition of dead space to avoid hypocapnia.
Extracorporeal carbon dioxide removal (ECCOzR) refers to Recommended levels of positive end-expiratory pressure
a technique of extracorporeal life support focused on the (PEEP) ranged from 5-60 cmH20. 23•24 With these ventilator
removal of C02 from blood rather than improving blood settings, patients w ith ARDS experienced high inspiratory
oxygenation.1 In this chapter we introduce the concept of pressures and gross disruption of lung parenchyma. Baro-
ECC0 2 R and discuss some of the experience and future traunla was common.25 - 27 In 1972, Hill et al 28 publis hed the
perspectives on this exciting topic. ECC0 2R has been de- first successful ECMO application in a patient with ARDS.
veloped mainly w ith a view to applying it in patients with Over the next few years, 217 patients with acute respira-
the most severe form of acute respira tory distress (ARDS).2 tory failure were supported with ECM0. 29 In 1973, a group
The possible role of ECC0 2 R in the prevention of hyaline of pioneers initiated a National Institutes of H ealth (NIH)-
membrane disease3 or in the trea tment of severe asthma4- 8 sponsored randomized trial of ECMO in severe ARDS. The
or multiple bronchopleural fistulas9 remains experimental entry criteria (Table 22-1) were intended to enroll a pop-
or anecdotal. ulation with a 70% mortality rate. In fact, final mortality
The mainstay of supportive treatment in ARDS is me- was 90% in both the control and ECMO groups. 30 The NIH-
chanical ventilation, a lifesaving procedure introduced ECMO study proved that long-term extracorporeallife sup-
in the management of patients with bulbar polio in the port was feasible, but it did not show any benefit on survival.
great epidemic that struck Copenhagen in 1952. These Consequently, adult ECMO almost stopped,31 with the ex-
patients, paralyzed by polio, required long-term artificial ception of a few centers, such as the one where Bartlett (see
ventilation 10; they became the first critical-care patients. The 01apter 21), conducted ilmovative studies on extracorpo-
use of mechanical ventilators later was extended to all pa- reallife support in infants and adults.
501
TABLE 22-1 ECMO Entry Criteria: Pao, < 50 mm Hg (Repeated Meanwhile, astute observers pondered the question: Why
Three Times) did the NIH-ECMO study fail?32
ICUCarc
Duration WHY DID THE NIH- ECMO STUDY FAIL?
Study Entry Bclore
Entry Testing PEEP, Paco2 Entry ECMO was aimed at buying time for the lung to rest and
Speed Period,h Fro2 cmH20 "Qs/Qt mmHg Testing, h heal .33 This could not be achieved under the persisting dam-
age caused by high tidal volumes and pressures, however.
Rapid 2 1.0 >5 30-45 Lung management in the ECMO group was not much dif-
Slow 12 ~0.6 ~5 ~0.3 30-45 > 48 ferent from that in the control group; this fact could explain
the similarities in survival. 32 The choice of a venoarterial
ECMO EXCLUSIONS
bypass, aimed in part at lowering pulmonary blood flow
Contrai11dication to anticoagulation (e.g., gastrointestinal and pulmonary artery pressure, might have contributed to
bleeding, recent cerebrovascular accident, chronic bleeding severe maldistribution of pulmonary blood flow. In turn,
disorder this might have deprived the lungs of enough blood flow
Pulmonary artery wedge pressure > 25 mmHg to defend against the damage of high-tidal-volume, high-
Mechanical ventila tion >21 days
pressure ventilation.34
Severe chronic systemic disease or another clinical condition that
in itself greatly limits survival, for example,
Irreversible central nervous system disease
Sevru-c chronic pulmonary disease (bFEV1 The Concept of ECC02R
< lliter, FEVJ!cFVC <30% of predicted, chronic Pac~
> 45 mmHg, chest x-ray evidence of overinflation or
interstitial infiltration, previous hospitali2ation for
In 1976, Kolobow et al1 noted that membrane oxygenators
chronic respiratory insufficiency) more appropriately constituted membrane lungs than just
Total body surface bums > 40% oxygenators. They observed that a membrane lung can ex-
Rapidly fatal malignancy change C0 2 much more easily than it can oxygenate blood.
Chronic left-ventricula.r failure They explored the potential of ECC02 R in a series of iru1o-
Chronic renal failure vative experiments.
Chronic liver failure
"Qs/ Qt =right-to-left shunt fraction.

bFBV 1 = fon:ed expiratory volume in 1 s. Dissociating Respiratory Functions
<PVC= fon:ed vital capacity.
souRCE: From Zapol et al.30 and NHLB1.83
Blood oxygenation and C02 removal take place through dif-
ferent mechanis ms .35 When normal venous blood reaches
the lungs, its mixed venous oxygen te.nsion (Pv~) is typ-
ically 47 mmHg, and Pvco, is 43 mmHg (Fig. 22-1). Let's
assume that oxygen consumption and C02 production
FIGURE 22-1 Dissociation of oxygenation and C0 2

OXYGENATION removal. For normal mixed venous blood (v),
Fi0 2=1 0.250 Vmin oxygenation requires normal pulmonary b lood flow
and a continuous 0 2 supply equal to Oz consumption
Pa02 = 99mmHg (250 ml/min in this example) without any ventilation.
BLOODFLOW
Sat 0 2 = 98 %
..
~0 2 Removal of C0 2 can be accomplished by a reduced
pulmonary b lood flow if this is matched by a
0.250 su fficiently high alveolar ven tilation. (Reproduced,
1/min with pen11.issio1"1, fro m Gattit'/Oiti et a.l: Itrt A11estlresiol
Hb : 15g/l Cliu 21:97- 117, 1983.)
Sat 0 2 = 82%
Pv02 = 47mmHg
C0 2 cont = 52 ml%
PvC0 2= 43 mmHg
PaC02 = 15mmHg
--...... ContC02 =34% .---.----,
1 1/min
BLOOD FLOW
vco2
0.200
1/mln
C02 REMOVAL
VA= 9.5 Vmin
CHAPTER 22 EXTRACORPOREAL CARBON DIOXIDE REMOVAL 503
mUd I
..- Reduced Hb ·.. ' --- • MECH. VENTILATION
·' ·•··...•. ·,.
60 ,/ / O xygenat ed Hb .. ' - THEORETICAL
···..... ' ........ SPONT. VENTILATION
"' / / ··.. ·,
_
/ 8 ··...._.'
X
=-~ -.::50
0
-u c:
0
50 2
o/o
-> ->
Cll
<
u
<
50
100
mmHg
0 50 100
FIGURE 22-2 Gas dissociation curves for 0 2 and C0 2 in blood. Vco2 (CDML) X 100
The solid rectangles re present arterial and mixed venous blood
Vco2 (Total)
points. The line connecting the C0 2 dissociation cur ves for
reduced and oxygenated hemog lobin (Hb) represents the nominal FIG URE 22-3 Alveolar ventilati on (percent of control values) as a
in vivo C0 2 dissociation curve as m ixed venous b lood b ecomes function of extracorporeal COz removal [p ercent of total C02
oxygenated in the lung (Haldan e effect). production, i.e., Vco 2 of carbon dioxide mem bran e lung (CDML)
plus natural lung]. The theoretical values are computed assuming
that Paco2 and total V co2 are constan t throughout the procedu re.
amount to 250 and 200 ml/ min, respectively. The (Reproduced, w ith permission, from Gnttinoui et nl: Jut Amstllesiol
hemoglobin carried in venous blood (150 g/liter) is nor- Clin 21:97- 117, 1983.)
mally 7()-..85% saturated; the lungs therefore can add just
40-60 rnl of oxygen per liter of venous blood. Thus, to fulfill moval (sum of membrane lung plus natural lung) constant
the requirements for oxygenation, we need a blood flow of a t and equal to the rate of C02 production by the body.
least 4-7 liters/min. Note that ventilation is not required to
oxygenate blood, whereas what is strictly needed is enough APNEIC OXYGEN ATION
oxygen to compensate for its consumption and maintain a
constant alveolar concentration. In summary, oxygenation When C02 production is entirely removed by a membrane
requires a high blood flow (4-7 liters/ min) and a small sup- lung, then ventilation is no longer needed. The lung can be
ply of oxygen (250 rnl / min). The opposite applies to C02 re- kept motionless, provided the alveolar oxygen concentra-
moval. Mixed venous C02 content is at least double the max- tion is kept constant by continuous ly supplying oxygen to
imum 0 2 content (Fig. 22-2). The normal C0 2 production match the body's 0 2 consumption.36 This process, known
per minute therefore can be removed easily from less than as apneic oxygenation,38 is otherwise nonnally limited by the
1 liter of blood, provided that ventilation is high enough. C02 rise. In this case, an increase in C02 is avoided by the
In conclusion, oxygenation requires a high blood flow, membrane lung. Apneic oxygenation therefore can be ma in-
whereas C~ removal can be acl1ieved at low blood flows. tained at will by ECC02R: The lw1g can be kept completely
Kolobow et al36 exploited the concept that if C02 is removed motionless, the ultimate goal being lung rest and recovery.
by a membrane lung through a low-flow, high-ventilation
venovenous bypass, then oxygenation can be maintained by
LOW-FREQUENCY POSITIVE-PRESSURE
the natural lung w ithout any ventilatory constraint. Physi-
cians now had an opportunity to adjust the ventilator set- VENT ILATION
tings free of the constraints of tidal ventilation. A decrease in respira tory compliance and functional resid-
ual capacity (FRC) was noticed during apneic oxygena-
tion. This led to the introduction of low-frequency pos itive-
pressure ventilation (LFPPV). LFPPV with ECC02 R39 is
ECC02R and the Control of simply apneic oxygenation to which a few (deep) breaths
Spontaneous Breathing per minute are added . The intent is to provide the physio-
logic role of sighs rather than remove C~. With LFPPV-
When C02 was ren1oved by the membrane lung, unseda ted ECC02R, respiratory compliance and FRC can be ma in-
lambs decreased their spontaneous ventilation, reducing tained at baseline for days or weeks.
both respiratory frequency and tidal volume.3 7 Changes in
alveolar ventilation were highly predictable, targeted to- ALVEOLAR P 0 2 CO NTROL DURlN G ECC0 2R
ward a constant pH and Pacor The greater th e removal of
C02 by the membrane lw1g, the greater was the d ecrease in During ECC02 R, the respira tory quotient (R), that is, the ra-
alveolar ventilation (Fig. 22-3). The amount of C02 excreted tio of C02 removal from the na tural lung to oxygen uptake,
by the natural lung decreased to maintain the total C02 re- changes according to the amount of C02 removed by the
TABLE 22-2 Natural (Patient) Lung Treatment and Goa ls :

ECMO versus LFPPV-ECC0 2 R
PAC02 = 35 mmHg
ECMQJO
>
1,,
\ GOALS
\\
•.\ ' ', Ventilation Minimize Flo 2 , Minimize Flo2 ,
. ' .. . . ..
\ -- ----------- - PA0 2 300 mmHg
TRADITIONAL
VT
LUNCREST
0.5 ~ -------------
' -. ---------------· Extracorporeal Arterial C02 removal (to
' ··--·- .. _ __ _ PA0 2 200 mmHg circulation Oxygenation rest he lung)
··- ··- ··- ··- ··- ··- ··- ··- ··- TREATMENT
~R ~~100mm~
!"'"-"'_______,_ ________, ... -----· - · . ... " .... . ·- "'":
Lung ventilation VT = 0.6 Liters VTlow
Ppeak =50 emH 20 Ppeak = 35-4D onH20
PEEP = 10 cmH20 PEEP = 17 cmHzO
0 VR = 15/ min VR = 2-4/ min
0 0.5 1 Lung perfusion Low (0.1 Qt) High (all Qt)
R VT = tidal volume; VR =ventilator rate; Q, = cardiac output.
FIGURE 22-4 Fro 2 required to maintain a PAo2 of 100, 200, and
tors come into play. Experimental data exemplify the com-
300 mmHg at constant P Aco2 as function of pulmonary
respiratory quotient (R) according to Riley's alveolar air equation.
plexity of these mechanisms. 41
(Reproduced, witll pennission, from Gattinoni eta /: Int Anesthesiol
C/iu 21:97- 117, 1983.) Rationale for ECC02R Use
The goals of ECC02 R are different from those of the 1974--
membrane lung. If baseline R equals 1, when we remove 1977 ECMO trial (Table 22-2). The reasons for these dif-
50% of the body's C02 production by ECC02 R, the new R ferences are rooted in ARDS pathophysiology. As already
of the natural lung will be 0.5. This affects alveolar oxygen outlined, mechanical ventilation was developed by many
tension (PAD.!), which follows Riley's alveolar gas equation: workers42 --49 who pointed out how positive pressure and
At any given F10!,when R decreases, PAD.! decreases . Fig- tidal volume interact in optimizing oxygenation. At the
ure 22-4 shows the changes in Fr01 required to maintain a same time, however, the dangers and drawbacks of me-
constant PA01 at varying R values. Note that Paco2 is held chanical ventilation became apparent.25 This was no sur-
constant through the effect of ECC02R.35 prise. Teplitz, a U.S. Army pathologist during the Vietnam
When ECC~R equals 100% of the C0 2 produced by the war, described ARDS as "an end-stage pathologic picture
body, then alveolar ventilation is nil, and Fr01 must be raised whid1 ... is not a new disease process ... but a result of ia-
to 1 to compensate for oxygen consumption. This does not trogenic modification of the pathology of noncardiogenic
at all mean that the alveolar oxygen concentrationmust be pulmonary edema." This view underlined the interaction
100%. At this extreme of physiology, the gas mixture venti- between the original insult and the evolution and damages
lating the membrane lung is of the utmost importance. At caused by treatment. 50
a steady state and during apneic oxygenation, the only gas Pontoppidan 47 suggested a tidal volume of 12- 15 ml/ k§
exchange taking place in the lung is oxygen consumption. as ideal for patients with ARDS. He also issued warnings26•2
No nitrogen, C02, or water exits or enters the alveolar gas. about the side effects of continuous positive-pressure ven-
If the gas ventilating the membrane lung is 100% humidi- tilation and the appearance of lung damage related to high
fied oxygen, then alveolar gas will be 100% oxygen minus FlO!, high pressure, and high volumes.
C02 and water. If nitrogen (N2 ) is added to the gas venti- In the late 1970s and early 1980s, the deleterious effects
lating the membrane lung, then mixed venous blood PN2 of mechanical ventilation were elucidated, and the concept
will equilibrate with PN2 of the gas in the membrane lung, of barotrauma evolved to that of volutrauma.st,S2 A third
causing a corresponding change in PA01 .36 During apneic mechanism of damage was proposed later: the release
oxygenation, despite the need to keep FrO! at 1, PAo 1 will of inflammatory mediators from the ventilated lung,
be determined by the PN2 of gas in the membrane lung. The leading eventually to multiple-organ failure and possibly
role of membrane lung PN, in preventing reabsorption at- deat11.53 - 57 The term ventilator-induced hmg injury (VILI)
electasis during ECC0 2 R is entirely speculative but based became popular. In the meantime, a revolutionary idea
on accepted physiology. 40 was gathering momentum: Why strive to maintain a
Because of the Haldane effect, Pac01 (and P AcO!) will be normal Pac01 in patients with ARDS? Trying to achieve
higher than Pvo2 secondary to changes in the C~ dissocia- this goal can damage the lung severely, whereas accepting
tion curve related to the oxygenation of hemoglobin. During a higher than normal Pac 01 may induce only minor side
LFPPV-ECC02R, PAD.! is mostly regulated by Fr~. If a con- effects. In 1990, Hickling et al58 reported that a better
tinuous oxygen flow is added to compensate for oxygen outcome could be achieved by lowering tidal ventilation
consumption taking place between breaths, then many fac- and tolerating high Paco 2 levels. They proposed the term
permissive hypercapnia, indicating the price to be paid for ovenous bypass: The common femoral and jugular veins
limiting barotrauma. The targets of gas exchange in ARDS were cannulated both distally and centrally through sur-
cl1anged quickly. 59 A similar croproach had been suggested gical cutdowns. Blood was drained from the two femoral
previously for severe asthma. 0 cannulas and from the distal jugular cannula, and it was
Several studies were performed to investigate the ef- returned centrally to the jugular vein. The wounds and the
fects of lun~-protective (low-pressure, low-tidal-volume) multiple cannulation involved continuous oozing of blood
ventilation.6 - 66 Only nvo studies 6 1.63 demonstrated benefit, and limitations in nursing care and patient mobility.n Sub-
but their effect has been striking. For the first tinle, the mode sequently, we developed a double-lumen cannulation of
of ventilation was shown to affect outcome. One limitation the femoral vein that allowed a single cutdown?3 With
with lung-protective ventilation, however, is hypercapnia. saphenosaphenous bypass/4 surgery became very super-
In selected patients, low-flow ECC0 2R offers a very power- ficial, distal drainage was unnecessary, and access to the
ful tool for overcoming these limitations while offering total inferior vena cava was excellent. The number of cannulas
lung rest. therefore was reduced to two. The most significant improve-
Hypoxemia, however, is the main characteristic of ARDS. ment in cannulation, however, came with the spring-wire-
Supportive therapy in ARDS is directed to its relief because reinforced percutaneous cannulas,9•75•76 which were placed
hypoxemia is a major determinant of organ dysfunction and by a modified Seldinger technique.
even may be the direct cause of death. Mechanical ventila- The main advantages of percutaneous cannulation are a
tion can be tailored to correct hypoxemia primarily by in- shorter procedure time, practically no bleeding, a reduced
creasing F1o, and airway pressures.67 Use of high airway risk of cannulation-site infection, and very simple decannu-
pressure, however, is limited by several fa ctors mainly relation. When a roller pump is used, a small (100-250 ml)
lated to hemodynamics and barotrauma. When PEEP is in- reservoir is placed in the drainage line; when it collapses, a
creased, then peak and plateau pressures also increase to servo control stops the pump. Blood is pumped through the
maintain ventilation. The solution is often to decrease tidal membrane lung(s) and then returned to the patient; flow is
volume and increase frequency; this solution culmina tes in normally kept at 15-30% of the patient's cardiac output. The
the use of high-frequency ventilation or oscillation. With system must have a capability of running at 50-60 ml/kg
high-frequency oscillation, the mean airway pressure is in per minute should we need to substitute for the natural lung
principle much higher than during positive-pressure venti- oxygenation (Fig. 22-5).
lation. High-frequency ventilation has proven safe and ef- We have experience in using both roller pumps and
fective in the treatment of adult patients with ARDS.68-69 Biomedicus centrifugal pumps, as well as Sci Med
Use of high airway pressures, however, combined with in- Kolobow spiral membrane lungs and Carmeda surface-
spiratory pressure limitation may lead to insufficient carbon heparinized77·78 hollow-fiber membrane lungs. Our current
dioxide removal. standard includes the use of two spring-wire-reinforced per-
In summary, the major aims of ECC02 R are to prevent cutaneous femoral cannulas (20-28F; Biomedicus), a Jostra
barotrauma by avoiding the maldistribution of ventilation centrifugal pump, and a plasma tight hollow-fiber poly-
in a nonhomogeneous lung, to put the lung to rest, and to methylpentene Quadrox 0 Jostra oxygenator. The entire cir-
foster healing w hile maintaining a selected Paco,. In addi- cuit is surface heparinized (Bioline coating) to minimize the
tion, ECC02R enables the application of a constant mean need for systemic anticoagulation. 79
airway pressure targeted to optimal oxygenation and free
of the constraints dictated by tidal ventilation.
ANTICOAGULATION
Anticoagulation is achieved by 100 IU /kg intravenous hep-
arin bolus at the time of cannulation. A heparin infusion
Clinical Applications: Venovenous Bypass is then started, aiming a t the selected activated clotting
time (ACT) (150-200 seconds in the case of Jostra Bioline
The main indication for ECC02R is severe ARDS secondary surfaces). Surface-heparinized circuits can be run without
to a potentially reversible cause. The main criteria are based any systemic anticoagulation80 for at leas t 12-48 hours as
on the original ECMO entry criteria, to which additional re- needed to stop or prevent incidental bleeding. Because hep-
strictions have been added over the years. 70•71 Generally arinized surfaces need a nom1al antithrombin III plasma
accepted contraindications to extracorporeal life support level, we routinely infuse antithrombin III at a rate of
and ECC02 R include the presence of significant bleeding, 500-1000 U/day. Platelets are transfused when lower than
surgery in the preceding 72 hours, severe brain damage, un- 50,000/!11. When heparinized surfaces are not in use, ACT
controlled severe sepsis, unresolved malignancies, severe and/or partial thromboplastin times (PTI's) of 1.5-2 times
chronic systemic disease, and ARDS of a known irreversible normal must be maintained at all times. In all instances,
origin. The length of the preceding mechanical ventilation ACT is measured at least four times per day. A laboratory
generally is not considered a contraindication to ECC02R. screen is ordered twice a day, including prothrombin time
(PT), PTf, fibrinogen, platelet count, fibrinogen degradation
product or equivalent, and antithrombin III. A continuous
BYPASS TECHNIQUE
prostaglandin h (PGI2) infusion may be effective in both
In 1979, Gattinoni et al2 reported the use of LFPPV-ECC0 2R decreasing a high pulmonary artery pressure and prevent-
in an adult patient with ARDS. The technique involved vening platelet aggregation.81
-
~
RESP r="~
PEEP
0
p Airway pressure
T Ambient
temperature control
DC Blood drainage
catheter
RC Blood return
catheter
ECBF Extracorporeal gas
flow
Gl Gas inlet
ML GF Gas flow monitor
GO Gas outlet
Intratracheal
lTC
catheter
Ml Membrane lung
Membran l ung
pml
pressure, In-out
GO
- RES Respirator
-
CP Centrifugal pump
Venous drainage
02% blood oxygen
monitor
FIGURE 22-5 LFPPV-ECC02R circuit. (Reproduced, with permission, from Gattiuoui et nl: JAMA 256:881-6, 1986.)
CLINICAL MANAGEMENT ment then is focused on achieving a viable oxygenation de-

spite an extremely reduced or even absent natural-lung oxy-
ECC02R normally is started in a sedated, paralyzed pa- gen transfer.
tient. After the initial adjustments (which normally take
1-2 hours), the ventilator is set to provide a low-frequency
sigh over a baseline constant PEEP [e.g., using intermit-
COMPLICATIONS OF VENOVENOUS ECC0 2R
tent mandatory ventilation (IMV) or biphasic positive air-
way pressure (i.e., BiPAP)]. PEEP is adjusted to maintain We have never stopped ECC02 R because of a technical acci-
mean airway pressure at the prebypass level and to pre- dent. From day to d ay, however, various changes of circuit
vent acute worsening of lung edema. A catheter inserted elements may be required, mainly involving the membrane
into the inspiratory line provides a constant 0 2 supply lung and/ or the centrifugal pump(s).
and constant PEEP during the long expiratory pause. As Bleeding always has been the major complication with ex-
soon as possible, attempts are made to reestablish spon- tracorporeallife-support techniques. The NIH-ECMO study
taneous respiratory activity, most often in the form of reported an average blood-product transfusion of 3575
pressure supported breathing with an intermittent sigh ml/day. 83 Half the 38 patients were managed in three of the
(e.g., BiPAP plus assisted breathing or IMV plus pressure nine participating centers; their average blood transfusion
support). requirement was only 1896 ml/ day, indicating that experi-
Hemodynamics are not affected by the venovenous by- ence had a lot to do with blood loss. In 1986, we reported84
pass, and cardiac output can be measured by regular ther- an average blood-product requirement of 1.8 liters/ day in
modilution. Changes in lung function can be followed our first 43 patients. The use of percutaneous ca1mulation
with venous admixture measurements. Very high values coupled with heparinized surfaces decreased the packed-
of mixed venous saturation and arterial 0 2 saturation sug- red-cell requirement to 200-300 ml/ day? 1 Bleeding from
gest decreased cardiac output with an increased proportion the chest drainage tubes is a major complication that of-
of extracorporeal blood flow /tota l cardiac output. When ten demands a surgical approach.85 We performed 17 tho-
lung function improves, weaning is attempted by decreas- racotomies or redo thoracotomies to control bleeding in
ing Fio2 and PEEP and by decreasing the C02 removal from 10 patients, of whom 4 survived.
the membrane hmg. 62 When necessary, the extracorporeal The major threat posed by extracorporeal support re-
circuit setup allows low-flow venovenous ECC02 R to be mains intracranial hemorrhage.ln our experience, this com-
converted into high-flow venovenous ECMO, and manage- plication accounted for 26% of deaths. We reported that a
prebypass Paco2 of greater than 75 mmHg, disseminated TABLE 22-4 Outcome with ECC02 R in Milan-Monz a
intravascular coagulation, or a positive brain computed to-
mographic ccnscan before bypass increase the risk of fatal
Survivors Non Survivors p
intracranial hemorrhage during bypass.71 No. Patients 46 (39%) 72 (61%)
Age 31.9 ± 14.7 29.1 ± 15.2 NS
Days from intubation 12.5 ± 13.8 10.9 ± 7.5 NS
CLINICAL RESULTS Qs/Qt" 0.46 ± 0.12 0.51 ±0.11 0.0284
PaC(h mmHC 53.6 ± 16.2 63.2 ± 21.4 0.0117
It is difficult to isolate from the literature the experience with
PEEPonH20 11.3 ± 5.1 13.5 ± 4.0 0.0104
venovenous ECC02 R because of undefined boundaries Cardiac Index 1/ min 5.04 ± 1.35
5.27 ± 1.62 NS
between venovenous ECC0 2R, venovenous ECMO, and Heart Rate bpm 134 ± 18 131 ± 20 NS
partial extracorporeal C02 removal (PEC02 R) 82 ECC02 R BPb mmHg 84.2 ± 14.9 79.4 ± 14.2 NS
refers more to a way of managing the diseased lung rather CVP" em H20 10.9 ± 5.4 11.4±5.1 NS
than to technical d etails, and the flexible handling of the pA_Pd mmHg 32.8 ±8.2 35.3 ±8.3 NS
circuitry is one of the advantages of ECC~R. We have sug- Wf'CmmHg 12.6 ± 6.1 13.8 ±5.0 NS
gested a minimum of three classification criteria71 : type of No receiving Vasopressor 2 (4'l'o) 20 (28%) 0.0012
bypass (venoven ous versus venoarterial or arteriovenous), Days of ECC~R 13.8 ± 13.0 13.8 ± 13.3 NS
proportion of cardiac output pumped, and the ventilator
"Qs/Ql = intrapulmonary shunt.
regimen for the natural lu ng. The technique can shuttle bBP = arterial b lood pressure, mean.
back and forth between venovenous ECC~R, venovenous <CVP = central venous pressure.
ECMO, and PEC02R in the same patient. dPAP = pulmonary artery p ressure, mean.
Table 22-3 is an attempt to collect the available experience =
•WP pulmonary artery wedge pressure.
on ECC02R, defined as such by authors, including our own
data (see also Table 22-4). Survival ranges between 33% and
76%. Variation p robably is explained by differences in selec- Only one controlled, randomized trial has been con-
tion criteria and in management ofthepatientssupported by ducted on the effect of LFPPV-ECC02R in patients with se-
extracorporeal means. Selection criteria, although derived vere ARDS.86 The investigators enrolled 40 patients meet-
from the original ECMO entry criteria (see Table 22-1), have ing the original NIH-ECMO entry criteria. Nineteen patients
been modified over the years and among centers.7° Our were randomized to LFPPV-ECC0 2R and 21 to control me-
present, very restrictive criteria are based on the original chanical ventilation. Survival was equivalent in the two
ECMO criteria; in addition, we require a total static respira- groups: 7 survivors in the ECC02R and 8 in the control
tory compliance of less than 30 ml/ em H 20 plus lack of im- group. The investigators and accompanying editorialists87
provement with PEEP, permissive hypercapnia, extravas- concluded that extracorporeal support is not recommended
cular lung-water reduction, prone positioning, recruitment in ARDS.
maneuvers, and nitric oxide inhalation. A more balanced interpretation of this study, however,
Newer therapies and better understanding of ARDS mus t take into account several considerations. 88 - 90 The in-
pathophysiology not only have changed the criteria for cidence of uncontrollable bleeding, leading to premature in-
ECC02R but also have restricted it more a nd more to a last- terruption of the treatment in 7 of19 patients, was extremely
ditch salvage role. Whether this is wise or not, we have high. More surprisingly, of 7 ECC02R surv ivors, 5 had been
our doubts . Patients are starting on ECC02R later and later disconnected as an emergency because of severe bleeding.
in their illness, and the time spent on bypass gets longer Average transfused blood products (packed red cells plus
and lon ger (50 days for our longest survival run), proba- fresh-frozen plasma) was 3.39 liters/ day (4.79 liters/ day
bly indicating increases in unmeasured elements of disease in the survivors). A problem in the m anagement of blood
severity at the time of connection. Despite these considera- clotting or the surgical procedure to control bleeding ap-
tions, many patients w ith ARDS suffer from complications pears obvious when related to contemporary published
related to vru and are d oomed to an unfavorable outcome. experience. This study suggests that despite a high rate
ARDS carries a substantial mortality, 31- 39.8% in the ARDS of catastrophic bleeding in the ECC02R group, the net
Neh.vork studies. 63 outcome was not worse in the ECC02 R group. As such,
TABLE 22-3 Veno-Venous ECC02R for ARDS: International Experience
Author Year Center No. 3 Survivors %Survival
Wagner (85) 1990 Marbu rg (Cennany) 76 38 50%

Bindslev (78) 1991 Stockolm (Sweden) 14 6 43%
Brunet (103) 1993 Paris (France) 23 12 52%
Morris (86) 1994 Salt Lake City (USA) 21 7 33%
Guinard (104) 1997 Paris (France) 10 4 40%
Cattinoni, Pesenti 2004 Milan, Monza (Italy) 118 46 39%
Total 262 113 43%
•No =Number of patients.

ECC02R may prove beneficial, provided that the associated Conclusions

bleeding problems are handled effectively.
ECC02 R is a fascinating approach to the management of res-
piratory failure and is a powerful tool for overcoming any
ventilatory problem. In contrast with venoarterial ECMO,
Recent Clinical Developments: ECC02 R can be performed at comparatively low blood
Arteriovenous Bypass flows and with a relatively simple technique. In its purest
conceptual application, ECC02R is achieved by an arteri-
Venovenous ECC02 R still remains a complex procedure, ovenous pumpless shunt. For patients witl1 the most severe
reserved for centers with experience and capabilities to form of ARDS, a venovenous circuit with the possibility of
run it safely in very diseased patients. In an effort to sim- shifting to modern full venovenous ECMO (if needed) may
plify extracorporeal respiratory assist, Barthelemy et al 9'~ be a better solution. Venovenous ECC02 R should be limited
reported that an animal could be supported for up to to centers where appropriate technical skills, motivations,
24 hours by a pumpless artery-to-vein extracorporeal sys- personnel, and experience are available. The arteriovenous
tem in combination with apneic oxygenation. Subsequently, approach appears very promising, but experience is still
Awad et al92 d emonstrated the feasibility of arteriovenous limited; the simpler approach and the essential technology
C02 removal (AVC02R) for up to 7 days in sheep. Young et involved increase tl1e feasibility of a formal prospective trial.
al93 evaluated AVC~R in a femorofemoral arteriovenous
(AV) model, both with and without a blood pump. A step
forward in pumpless AVC02R came with the design of very
low-resistance membrane lungs. 94 A pumpless system is
expected to minimize the foreign-surface interactions and
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Surg 2000; 17:608-13. optimization strategy in severe ARDS. Ch~t 1997; 111 :100()..7.
t hapter 23 History of Liquid Ventilation
LIQUID VENTILATION TI1e concept of liquid ventilation has been investigated for
almost 40 years. Although intrapulmonary saline was used
RUPA SEETHARAMAlAH
in the early twentieth century for both lung-lavage therapy
STEFANO TREDICI
RONALD B. HIRSCHL
and physiologic studies,8 - 12 the use of liquid as a n alter-
native medium was not investigated until 1962. Kylstra13
demonstrated the ability to sustain gas exchange in dogs
spontaneously breathing hyperbarically oxygenated saline.
These animals did not survive beyond the experimental pe-
riod because of hypercarbia and acidosis, which was at-
tributed to th e low solubility of carbon dioxide (C0 2) in
HISTORY OF LIQUID VENTILATION saline a nd to drainage limi tations. Repeating the experiment
PHYSIOLOGY OF PERFLUOROCARBON with a mecl1a11ical-assist device yielded similar results. 14
VENTILATION Subsequently, effort was directed toward finding a liq-
PARTIAL LIQUID VENTILATION uid for supporting gas exchange. Silicone and vegetable
Laboratory Studies oils were found to be too toxic for in vivo use.15 Interest then
Clinical Studies turned toward perfluorocarbons, w hich were first produced
TOTAL LIQUID VENTILATION as a by-product of reactions used during the Manhattan
Laboratory Studies Project (World War II). These liquids were noted to be clear,
Clinical Studies colorless, odorless, and biologically inert w ith remarkably
CONCLUSION low surface tension (15-19 d yn / cm a t 25°C) and high sol-
ubility for both oxygen (45- 55 ml 0 2 /dl at 25°C) and C02
(140-200ml C02 / dl a t 25°C).16- 18 Clark and Gollan 19 in 1966
demonstrated that spontaneously breathing mice could sur-
Acute respiratory distress syndrome (ARDS) is a com- vive when submerged in perfluorocarbon under normo-
plex life-threatening illness with many different etiolo- baric conditions. This established an acceptable medium for
gies associated with the diffuse alveolar damage leading gas exchange during liquid ventilation.
to hypoxemic res piratory failure. It affects a n estima ted Although effective in oxygenating an animal, the rela-
43,000-107,000 pa tients per year.1 Despite advancement tive high densities and low C0 2 content of per fluorocarbons
in supportive therapy, including positive end-expiratory imposed limitations in C02 clearance and acidosis in a spon-
pressure (PEEP), inverse-ratio ventilation (JRV), permis- taneously breathing mode1. 19 1n an effort to improve expi-
sive hypercapnia, and extracorporeal life support (ECLS), ratory flow and limit work of breathing, demand-regula ted
ARDS remains a highly lethal condition in the nonneona- ventilators were developed in the early 1970s by Moscowitz
tal population, with a mortality ra te of approximately 30- and Shaffer.20 - 23 Variations of the original device were de-
50%.2,3 veloped subsequently to allow the study of TLV in anum-
Liquid ventilation using fluorina ted organic liquids (per- ber of animal models ranging from preterm lambs to adult
fluorocarbons) is an alternative technique for the ma nage- sheep. 24-30 The use of inhaled perfluorocarbons for prevent-
ment of respiratory failure. Because of the high solubility ing decompression sickness du_ring deep-water diving a lso
of respiratory gases and low surface tension, 4 perfluoro- has been explored.31 , 32 The ability of TLV to improve gas
carbons are an attractive choice for gas excl1ange in liq- exchange and pulmonary compliance, as well as homoge-
uid ventilation. Liquid ventilation has been performed by neous alveolar inflation of the lungs, in premature animal
two methods. The first is total liquid ventilatio11 (TLV), in models with neonatal respiratory distress syndrome (RDS)
which the lungs are filled with perfluorocarbon to a volume has been demonstrated. 24,25•33•34 Studies also have been per·
equivalent to functional residual capacity (FRC) on which a formed in adult animal models with ARDS with encourag-
specialized mechanical liquid ventilator delivers perfluoro- ing results. 26- 28 Extensive investigation of the toxicology,
carbon tidal volumes to the ltmgs.5 The second technique, in uptake, and elimination of perfluorocarbons has show n no
which conventional mechanical ventilators supply gas tidal significant adverse pulmonary or systemic effects.35 - 39 The
volumes to lungs filled with perfluorocarbons, us ually to first demonstration of the ability to sustain gas excl1ange
a volume equivalent to FRC, is known as partial liquid ven- during liquid ventilation in humans was demonstrated in
tilatiou (PLV).6•7 There is growing evidence ill laboratory 1989 by Greenspan et al. Even though the severity of pul-
and clinical studies to suggest that liquid ventilation may monary injury precluded a successful outcome, this trial of
be effective as a supportive and therapeutic technique for TLV in three moribund, preterm newborns demonstrated
patients with severe respiratory failure. In this chapter, the the ability to support gas exchange and exhibited a trend
history and methods of liquid ventilation, as weJJ as a sum- toward improved pulmonary compliance.40· 41
mary of laboratory a11d early clinical evidence to support its In contrast to TLV, PLV avoids the use of relatively
development as a new therapy for sever e respiratory failure, large and complex ventilators with associated large per-
are discussed. fluorocarbon priming volumes. Even though the concept
513
TABLE23-1 Properties of Perfluorocarbon Liquids
Property FC-77 RM -101 FC-75 PFdecalin Perflubron
Boiling p oint ("C) 97 101 102 142 143

Density at 2s •c (g/ml) 1.78 1.77 1.78 1.95 1.93
Kinematic viscosity (centistokes at 25°C) 0.80 0.82 0.82 2.90 1.10
Vapor pressure (to rr at 3/"'C) 85 64 63 14 11
Surface tension (d ynes / em a t 25°C) 15 15 15 15 18
0 2 solubility at 25•C (ml gas / 100 mlliq.) 50 52 52 49 53
C02 solubility a t 37•C (ml gas/ 100 ml Iiq.) 198 160 160 140 210
ABBREVIATIONS: PFC, perfluorochemical, including FC77 and FC75 from 3M Corp., USA, RM101 from Miteni, ltaly ; PFdecalin,
perfluorodecalin from Green Gross Corp., Japan, and Air Prod ucts and Chemicals Jnc., Allentown, PA; Perflubron, generic name
for perfluoroctylbromide, developed for medical applications by Alliance Pharmaceutical Corp., USA.
souRCE: Used with permLo;sion, from Shaffer TH, et al: Pediatr Pulmonol 14:102- 9, 1992.
of transition from TLV to gas ventilation via PLY had been with water or a nonpolar solvent. They have excellent 0 2
explored by Shaffer, the technique was first reported in 1991 (45- 55 ml Od d!) and C02 (160-210 ml COd dl) carrying
by Fuhrman et al.42 Numerous laboratory studies of PLV in capacity.61 The oxygen content of perfluocarbons at 1 a tm
animal models of both neonatal and adult lung injury in- of oxygen is approximately 20 times that of water, twice that
duced by intra venous oleic acid administration, gastric aspi- of blood, and one-half that of an equal volume of oxygen
ratio n, and saline lavage have demonstrated enhanced lung gas. Some of the important physical properties of perflu-
compliance and gas exchange during PLV compared with ocarbons used in liquid-ventilation research are shown in
gas ventilation. 43 -49 Human trials were conducted in neona- Table 23-1. An ideal perfluorocarbon for respiratory appli-
tal, pediatric, and adult patients maintained w ith ECLS for cation should have the properties of high gas solubility and
severe respiratory failure.50- 53 Further trials followed with moderate vapor pressure and viscosity. These properties,
mixed results, as outlined later in this cha pter.54-59 however, may not be found in a single pure perfluorocar-
bon. Thus recent s tudies are focusing on the development
of new perfluorocarbons with physical properties that are
tailored to better suit a particular application.
Physiology of Perfluorocarbon Ventilation The potential toxicity of perfluorocarbons has been stud-
ied extensively in animals and in patients. They are ab-
Perfluorocarbons are produced by fluorination of com- sorbed in small quantities during TLV, reaching a steady
mon organic hydrocarbons. This is accomplished through state after 15-30 minutes of liquid breathing.38•39 These com-
a highly exothermic vapor-phase method using fluorine potmds deposit preferentially in tissues w ith high lipid
gas or thr01.1gh a less exothermic, more stable cobalt tri- content109 (Table 23-2 and Fig. 23-1) and do not appear to un-
fluoride technique.6 1 More recently, these compounds have dergo biotransformation.38 Perfluorocarbons are eliminated
been produced by electrochemical fluorination, as first primarily by evaporation from the lungs and are scavenged
described by Simmons in 1950.62 This results in a more by macrophages in both lungs and other tissues. Perfluo-
homogeneous product with less carbon-carbon bond cleav- rocarbons evaporate from the lungs of humans in approxi-
age. A large number of perfluorocarbon compounds have mately 3 weeks after discontinuing liquid ventilation.74 - 76
been produced using this technique for liquid-ventilation
research. The carbon chain may vary in length, and any ad-
ditiona l moiety that attaches gives each perfluorocarbon its TABLE 23-2 Perfluoroca rbon Tissue Levels as a Function
of Time
unique properties.
Perfluorocarbons are clear, odorless, inert liquids with Tissue 24h (II= 6) 72h (11 = 3) p Value
tmique physical properties.61 These compounds have a den-
sity approximately t\'\rice that of water and a kinematic Blood 6±0.24
viscosity (ratio of viscosity to density) similar to that of Heart 109 ± 18 117 ± 26 NS
water.63•64 These fluids have remarkably low surface ten- Liver 63 ± 15 44± 15 NS
sion (15-19 dyn/cm) secondary to weak intermolecula r Intestine 67± 18 112±6 NS
forces created by peripheral fluorine atoms and are rela- Kidney 79± 15 73±5 NS
Spleen 61 ± 16 67±6 NS
tively volatile, with vapor pressures ranging from 11-85 Thymus NS
110 ± 36 175 ± 63
torr at 37°C. The vapor pressure of an individual perfluo- Brain 119 ± 13 245 ± 19 <0.01
rocarbon determines the rapidity with which it evaporates Skeletal muscle 29±3 56± 12 NS
after intratracheal administration. In addition, the periph- Mean" 81 ±7 108 ± 15 <0.01
eral fluorine atoms make them both thermally stable and
chemically nonreactive. Perfluorocarbons are immiscible in NOTE: Perflubron levels expressed in microgram per gram of tissue. All data
are presented as mean ± SEM.
aqueous- and alcohol-based solutions but have varying de-
•Mean across tissues.
grees of solubility for hydrocarbons. Solubilities of respira- sou RCE: Used with permission, from Cox C, et al: Bioi Neonate 84:2.>2-242,
tory gases in perfluorocarbons are greater when compared 2003.
CHAPTER23 LJQUIDVENTILATION 515
PFC Levels as a Function of Lipids
1000~-----------------------------------------------------------,
l(x) - 5.6907E+0 ' exp(1.6664E·2'x)

R"2 = 8.2587E·1 Brain
lnlestlne
Q)
:::;)
fll
~ 100
0 0
Spleen
E
FIGURE 23-1 Pe.rflubron
f
0
concentrations as a function of
tissue lipid content.
u.. 10
a. Perfluorocarbon con centration
Blood
varied significantly among
differen t tissues (p < .001), and
these differences were related to
tissue ijpid content (r = 0.93,
p < .01). (Usen, witll pennission,
0 50 100 150 200 250 from Cox et al: Bioi Neo11at
Lipid mg/gm of Tissue 84:2..32-42, 2003.)
Perfluorocarbons have the potential to support gas ex- tors. They a lso have been explored in patients as possible
dlange under normobaric conditions because of the high blood substitutes, as ultrasound a nd oral contrast media,
solubility of respiratory gases.22 High densities of perflu- as vitreaJ replacement in vitreoretinal surgery, to enhance
orocarbons facilitate their distribution to the dependent oxygenation via peritoneal lavage, for organ preservation,
region of the lung, which leads to the recruitment of alve- and to distend and grow lungs in patients with congenital
oli that otherwise tend to be collapsed or filled with in- diaphragmatic hemia. 77- 81
flammatory exudate in the setting of severe pulmonary
injury.3•27 Perfluorocarbons-filled lungs redistribute pul-
monary blood flow to the better inflated, nondependent
lung segments.65 - 67 Albumin leak and water content a re re- Partial Liquid Ventilation
duced during liquid ventila tion in the setting of acute lung
injury. 67•68 These effects lead to in1provement in ventilation- PLV refers to a hybrid method of gas exchange achieved
perfusion matching and oxygenation in the setting of severe through gas ventilation of perfluorocarbon-filled lungs.
respiratory faiJure. Shaffer et al82 observed that there was a smooth transiti.on
Since fluid-filled lungs exhibit a r eduction in the gas- from TLV to gas ventilation during animal experiments,
liquid interface, surface tension and surface-active forces fa- even though a significant amount of perflorocarbon was
voring alveolar collapse are reduced.9•10 Perfluorocarbons still present in the respiratory tree. In 1991, Fuhrman et al42
increase alveolar stability by acting as an artificial s urfac- reported the first experience with PLY, achieving equiva-
tant, and they do not appear to reduce endogenous sur- lent gas exchange and pulmonary compliance compared
factant production or activity.62,69 This results in enhanced with gas ventilation in healthy piglets. With this technique,
alveolar recruitment at lower inflation pressures. the lungs are filled with perfluorocarbon, in general to a vol-
A pulmonary-protective effect, by reducing lung injury, ume equivalent to FRC (S-30 ml/ kg) depending on the dis-
is another potential benefit of using perfluorocarbons. This ease process, age, and weight, and then gas ventilated w ith a
is related to improved alveolar infla tion and to enhanced standard ventilator. During early clinical trials, perfluocar-
displacement and lavage of inflammatory mediators bon dosing consisted of 5-10 ml/kg aliquots, with repeat
and exudates from the affected lung. Perfluorocarbons dosing every 30 minutes to 3 hours as tolerated hemody-
facilitate exuda te clearance secondary to their relative namically or until the weight-adjusted estimated FRC was
densities, through lavage during TLV, or through simple reached or by visually identifying a perfluorocarbon menis-
displacement of dependent exudates during PLY. They cus in the endotrad1eal tube at end expiration with zero
also have been shown to have in vitro anti-inflammatory PEEP.52•54 - 56 Daily redosing was based on overall clinical
activity, such as reductions in neutrophil chemotaxis, nitric status, degree of dependent-lung filling on lateral chest ra-
oxide production, and endotoxin-stimulated macrophage diography, and the presence of a perfluorocarbon meniscus
production of cyto kines.7°·71 In vivo evaluation has in the endotracheal tube.
shown a reduction in release of tumor necrosis factor a , The advantage of PLV over TLV consists of relative sim-
interleukin-1 , and interleukin-6 in human alveolar plicity because the need for use of a new, complex device
macrophages in perfluorocarbon-exposed lungs.72• 73 or an understanding of physiology of fluid mechanics in
Besides their use in liquid ventila tion, perfluorocarbons airways or the endotracheal tube is eliminated . A number
have been used in the cosmetic indus try for their water- of studies have demonstrated the efficacy of PLV in respi-
retention properties and also as cooling agents and insula- ratory failure by improving gas exchange and pulmonary
t' t•
400
t• ·t
-ft- PLV
t• ·1 FIGURE 23-2 Pao 1 in four groups
300 Surfactant
-E)-
~ PLV
of premah u e lambs. Surfactant was
t:0 adm inistered at 30 m in utes. PLV
-"'
~
0
•
200
.._ Surfactant
+ CMV
was initiated at 30 minutes in the
PLV group and at 45 minutes (15
minutes after surfactant) in the
0..
.......- CMV
su rfactant plus PLV group. ' p < .05
compared w ith baseline value
100 within group; tp < .008 comp ared
with the CMV group at the same
time point; p < .008 compared
with the surfactan t p lus CMV
0
30 45 60 90 180 300 group at the same time point. (Used,
with permission, from Leach eta/:
Time (mi n~ f Pediatr 126:412- 20, 1995.)
compliance by recruiting a telectatic lung regions, redis- were facilitated during PLV in various neonatal and adult
tributing pulmonary blood flow, and lowering surface models of respiratory failure .
tension. Gas exchange and pulmonary function appear to be im-
proved during PLV by various mechanisms. Perfluoro-
LABORATORY STUDIES
carbons are effectively distributed into collapsed ltmg re-
gions during PLV 'v'.rith associated alveolar recruitment. 3·as
PLY has been studied in preterm and full-term neonatal, Gauger et al86 demonstra ted an increase in total lung vol-
pediatric, and adult lung-injury models. Leach et al44 re- ume during PLV in an oleic acid model of lung injury. Ad-
ported signifi cant improvement in gas exd1ange and pul- ministration of perfluorocarbon tends to redistribute pul-
monary compliance during PLV in premature newborn monary blood flow from the collapsed dependent to the
lambs with RDS above those associated with pulmonary better recruited nondependent lung regions.87 These data
administration of surfactant (Fig. 23-2). PLY in piglets after suggest that administration of perfluo rocarbon during PLV
lung injury by gastric acid aspiration demonstrated a signif- results in recruitment of atelectatic, consolida ted lung tis-
icant increase in a rterial oxygenation when compared with sue and redistributes pulmonary blood flow, resulting in
gas-ventilated controls over a 6-hour period as the injury improvem ent in ventilation-perfusion matching and gas
matured .47 Comparison of standard mechanical ventilation exchange.
and high-frequency ventila tion during PLV in a neona- Pulmonary compliance is increased during PLV in
tal model of RDS showed improvements in gas exchange smaller-animal models of respiratory failure, such as the
and pulmonary mechanics, even though high-frequ ency newborn model of congenital diaphragmatic hernia88•89
ventila tion did not offer an advantage over conventio nal and preterm RDS. 43 In midsized and large animal mod-
ventila tion.48• 49 els of oleic acid lung injury, however, only a small in-
Evaluation of PLV in an oleic acid-injured canine model crease or even a decrease in pulmonary compliance has
of ARDS by Curtis et al83 reported a dose-dependent in- been observed during PLV.26•50 This may be related to in-
crease in arterial oxygena tion, with the highest Po2 in homogeneous distribution of perfluorocarbon in the lungs,
the canines receiving the largest dose of perfluorocarbon most of which pools in the dependent portion of the
(60 ml/kg). Maximum improvement in pulmonary com- lungs, whether the patient is supine or upright. 52 The ef-
pliance was seen after the 40 ml/kg dose of perfluorocar- fect of this dependent/ nondependent distribution of gas
bon; further dosing resulted in a decrease in compliance. and perfluorocarbon is less in patients with a sma ller an-
Hirschi et al50 studied PLV for 2.5 hours in oleic acid-injured teroposterior diameter, w hich may contribute to the ob-
young-adult sheep on venovenous ECLS using a smaller served increase in pulmonary compliance in newborns and
FRC (35 ml/ kg). They demonstrated an improvement in infants.
gas exd1ange and pulmonary function, manifested by de- Of interest is the recent demonstration of enhanced gas ex-
creased pulmonary shunt (Qps/ Qt) a nd slightly improved change with aerosolized perfluorocarbon in saline-lavaged,
compliance.50 In a separate study from the same institu- surfactant-depleted piglets. Arterial 0 2 content was higher
tion in similarly injured sheep receiving PLV, the investi- and C02 lower during both PLV and administration of
gators identified a dose-related increase in 0 2 delivery and aerosolized perfluorocarbon when compared with animals
mixed venous 0 2 saturation that peaked at a perfluorocar- receiving standard mechanical ventilation.90 This response
bon lw1g volume of 40 ml/ kg84 (Fig. 23-3). These studies was sustained after discontinuation of aerosolization but
demonstrated that arterial oxygenation and C0 2 dearance not standard PLV.
CHAPTER 23 LIQUID VENTILATION 517
TV=30
100
90
--
#. 80 mVkg
5
;:;
70
...
cu
- 60
:::J
cu FIGURE 2.3-3 Arterial oxygen saturation at b aseline,
en 50 after lung injury, and for 150 minutes during
c
Q) conventional gas venti lation (control group), PLV
en 40 wi th 10 mllkg incremental increases in perflubron
~ dose from 11)..50 m l/kg (best fill, BF group), or PLV
0
•
30
-·c:cu Control Group
with 35 mllkg Perflubron dose followed by 5 ml/kg
incremen tal increase in gas tidal volume from 11>-30
Q)
t:
ct
20
10
•
--o-
Best Tidal Volume Group
Best Fill Group
mllkg (best tidal volume, BTV group). Values are
mean ± SEM. (BF: p = .01 by repeated-measures
ANOVA; p = .020 and .020 at 90 and 120 minutes
wh en BF and control data were compared post hoc;
01-------r------.------,-----~r-----~ BTV: p = .001 by repeated-measures AN OVA;
30 60 90 120 150 p = .025 and .022 at 90 an d 120 minutes when BTV
·=-~ ·~"'~
\1)
and control data were compared post hoc). "p < .025.
m- "' - (Used, witll permissiou, from Parent et al: Surgery
TIME (min) 121:32()...7, 1997.)
CLINICAL STUDIES gas exchange with reduction in 02 indices with use of high-
PEDIATRIC AND ADULT TRIALS frequency PLV in two infants with chronic lung disease and
severe respiratory failure.
In 1995, the first clinical study of PLV for respiratory fail-
ure was reported.51 PLV was used as an adjunctive ther-
apy to ECLS in 19 patients (10 adults, 4 children, and 5 PREMATURE NEWBORN TRIALS
neonates) with severe respiratory failure. Patients receiving In a multicenter noncontrolled trial, Leach et al57 reported
PLV demonstrated a significant decrease in the alveolar- significant improvement in gas exchange, a decrease in
arterial oxygen gradient [(A-a)Do,_ ] and an increase in pul- mean oxygen index (01 = mean airway pressure x F102 x
monary compliance when ECLS was discontinued for short 100 / Pa~ ), and a twofold increase i11 pulmonary compli-
periods. Associated complications were limited to pneu- ance during PLV in 13 premature infants (24-34 weeks of
mofluorothoraces. Overall survival was 58%. gestation) with surfactant-refractory RDS (Fig. 23-4). Sig-
Safety and efficacy ofPLV have been evaluated by anum- nificant complications occurring during the trial attributed
ber of phase I and II clinical trials in adults and children with to PLV included mucus plugging in 5 patients and pneu-
respiratory insufficiency.7, 51 Initial studies in adult and pe- mothorax in 1 patient. The overall survival of tl1e infants
diatric patients demonstrated a decrease in (A-a)Do,_ w ithin was 80%. A prospective, randomized trial involving 24 pre-
the first 48 hours after initiation of PLV. 54 ' 55 Prospective, mature newborns (gestational age 24-34 weeks and birth
controlled, randomized studies to evaluate the safety and weight 600-2000 g) who had failed surfactant administra-
efficacy of PLV in adult and pediatric patients have been tion showed a 62% survival with PLV when compared with
performed. A total of 200 pediatric patients were random- a 100% survival in the control group. This study was placed
ized to receive either PLV or conventional mechanical ven- on hold secondary to discontinuation of the pediatric trials,
tilation. A low mortality, 20% in the conventional group as noted earlier.
compared with 26% in the PLV group, made successful com-
pletion of the study impossible. The pediatric trial therefore FULL-TERM NEWBORN TRIALS
was discontinued, which led to simultaneous pausing of all In a phase I- II noncontrolled study in full-term newborns
other clinical PLV studies. In a randomized trial in adult pa- (two patients with congenital diaphragmatic hernia and
tients, no difference in pulmonary mechanics, gas exchange, four with ARDS) receiving ECLS but failing to improve,
or survival was noted between the PLY (n = 65) and con- PLV was evaluated for 96 hours. All patients demonstrated
ventional (n. = 25) groups. 60 A multicenter prospective, ran- improved lung compliance59 (Fig. 23-5). Four infants were
domized trial involving 311 patients with ARDS showed no weaned from ECLS, and two were long-term survivors. In
significant difference in mortality or 28-day ventilator-free a prospective, randomized trial in 24 full-term newborn
days between PLY and conventional ventilation groups. 91 patients, 100% survival was noted in the control patients
Migliori et al 92 recently demonstrated an improvement in as opposed to 86% in the PLV patients. Fewer patients
200 1.0 growth factor also has been reported in animals undergoing
P<0.001 perfluorocarbon-induced lw1g growth. 98
OJ 150 0 .8 Pranikoff et al93 evaluated the use of PLV in seven new-
J: Fi0 2 born patients with congenital diaphragmatic hernia on
E 0.6 ... ECLS for respiratory failure. Patients exhibited a significant
E 100 0
~
N 0.4 u:: increase in Po2 and doubling of the static pulmonary com-
0 Pa02 pliance during 5-{) days of PLV and/or perfluorocarbon-
p = 0.02
"'
Cl. 50 induced lllilg growth. This therapy was well tolerated.
0.2
Significant complications were limited to the development
0 0.0 of pulmonary hemorrhage in one patient 4 days after the
final dose of perfluorocarbon. A multicenter prospective,
80
randomized trial evaluating perfluorocarbon-induced lung
0> growth in 13 newborns with congenital diaphragmatic her-
J: nia was performed. Patients were randomized for treatment
E 60
E with standard conventional gas ventilation on ECLS (11 = 5)
0
.. p . 0.03 or perfluorocarbon-induced lung growth on ECLS (11 = 8).
0 Survival was 75% in the experimental group as opposed
~ 40 to 40% in the control group. The duration of ECLS was
9.8 ± 2.3 days in experimental group and 14.5 ± 3.5 days
0 in the control patients. This trial was placed on hold when
p = 0.01
p < 0 .001 the definitive pediatric trial closed, and the study numbers
~ ~ p < 0 .001 p = 0.0 07
~ l 0.4
were not adequate to demonstrate a significant difference
;.; :D
a. _
p • 0 .02 in any parameter between the two groups.
0E "'
:;:
0-
0
·- E
° 0.2
Eo
c«!-..
-
>. E
Total Liquid Ventilation
0
~
0.0 ..I.~G~V~_,--~P,ar~tl~al~l~i~u~
ld~v~e~nt~ll~at~
iorn~-r--~
TLV refers to the process of ins tilling and r emoving perflu-
0 4 8 12 24
orocarbon liquid tidal volumes from lungs for the purpose
Hours of gas exchange. During liquid ventilation, a volume equal
FIGURE 23-4 Mean(± SE) values for arterial oxygen tension to the estimated FRC of preoxygenated, prewarmed per-
(Pao 1 ), arterial carbon dioxide tension (Paco1 ), fractional inspired fluorocarbo n is instilled into the lung while residual gas
o xygen concentration (FTo1 ), and d ynamic compliance during gas bubbles are removed by gentle manipulation of the chest
ventilation (GV) in the initial 24 hours of partial liquid and gravitational positioning. The liquid ventilation then is
ventilation in 10 infants. P values pres ent comparisons between initiated with the inspiratory phase in order to prevent mas-
partial liquid ventilation and gas ventilation. The gray bar sive pulmonary hemorrhage secondary to excessive neg-
denotes the period during which the liquid functional residual
ative pressure.99 Unlike gas ventilation, in which minute
capacity was establish ed. (Used, w ith pennissiou, from Leach et al:
New Eugl J Med 335:761.- 7, 1996.)
ventilation and oxygenation can be achieved using a wide
variety of ventilator settings, the mechanics of the fluid-
filled lung dictate the use of long ins piratory and expi-
ratory times, low flow rates secondary to the relatively
receiving PLV (43%) required ECI.S compared with the con- high resistance to the flow of the liquid medium in the
trol patients (70%). This study also was closed before com- airways, and large tidal volumes owing to the diffusional
pletion because of discontinuation of the pediatric ARDS limitations of perfl uorocarbons. The elimination of the gas-
trial. liq uid interface a t the alveolar level minimizes the inflation
pressure despite the high tidal volume (i.e., 15-20 ml/kg)
necessary to ma intain adequate minute ventilation. Thus
CONGENITAL DIAPHRAGMATIC HERNlA pulmonary compliance and alveolar recruitment are en-
In utero tracheal ligation has been used to correct struc- ha nced markedly. Maintenance of lung distension al so is
tural and physiologic effects of pulmonary hypoplasia.94•95 facilitated. In addition, the distribution of the perfluorocar·
Fauza et al96 evaluated the ability to induce lung growth bon is relatively homogeneous thro ughout the liquid-filled
via distension of the isolated upper lobe in newborn sheep lllilg. Finally, TLV has the ability to lavage very effectively
with perfluorocarbon to a pressure of 7- 10 mmHg. This the exudate and potential intra-alveolar inflammatory me-
study also demonstrated an increase in the size and num- diators from the lungs. Together these advantages make
ber of alveoli in the right upper lobe while maintaining the TLV a potentially effecti ve tool in the treatment of lung in-
airspace fraction, the protein-DNA ratio, and the (A-a)D~ jury and ARDS.
ratio compared with nondistended control an.imals.96,97 Pa- The need of a fresh-liquid tidal volume requires the
tients exposed to perfluorocarbon-induced lung growth use of a specialized device. Although simple gravitational
(PILG) demonstrated radiologic evidence of ipsilateral lung drainage can be effective, a more complex device is essential
growth96 (Fig. 23-6). An increased expression of insulin-like to better control the tidal volume and the flow profile over
CHAPTER23 LIQUIDVENTILATION 519
0.6
..,__ PLV initiated
- . - -PLV ends
Q) R GURE 23-5 Change in pulmonary

0
c compliance with partial liquid
<U- 0.4
=0.-ll::
Ol
ventilation (PLV) in an infant with
E..._ the acute respiratory distress
oO syn drome (ARDS). There is no
o-L change whiJe receiving
c:-E
cu.g extracorporeallife support before
§ E 0.2 PLV. With PLV, there is a slow
E~
increase in compliance during the
::J
a. first 48 hours. The infant was
weaned off extracorporeaJ life
support after 72 hours of PLV, and
PLV was stopped after 96 hours.
0 Recovery con tinued, and the infant
2 4 5 survived. (Used, with pennission,
-1 0 3
from Greeusplltr et al: Pediatrics
Time (days) 99:E2, 1997.)
time. The d evelopment of liquid ventilators for th e study

of TLV is progressing continuously. Efforts have centered
on improving C02 cleara nce, limiting the work of liquid
FIGURE 23-6 Progression of the dis tended lungs ipsilateral to a
breathing, and simplifying the design . The first true me-
hernia over time (the perfluorocarb on is radiopaque) in the three
patients who received 7 days of pulmonary dis ten tion. Notice the chanical ventilator for liquid breathing was developed by
increase in lung size, wh ich was not observed in the contralateral Moskowitz in 1970.20 This d emand-regulated ventilator was
lung. (Used, w itlr permission, from Fauza et a/: TPediatr Surg modified by Shaffer et a! and was used extensively in prema-
36:1237-40, 2001.) ture animal m odels of RDS.21 - 23 The second-generation d e-
vices u sing a m odified ECLS circuit described by Curtis et al
in 1990 was simplified by Hirschi et al in the last decade .
Meinhardt et al 99, too were among the first to explore the
use of pis ton-driven liquid ventilation and found enhanced
expiratory flow when compared ·with a roller-pump tech-
nique. A double-piston pump ventilator, combined w ith
the development of more sophisticated computer program-
ming, then was used for the study of TLV in adult animal
models of acute respiratory distress. Recently, a multicen-
ter study was undertaken to evaluate the effectiveness of
the double-piston device in an oleic acid lung-injury model.
Liquid ventilation improved Pc02, 02 delivery, Sao, , Sv02,
and cardiac output w ith no change in pH and COz clearance
w hen compared with control ventilation. In addition, Jus to-
logie evidence of decreased lung injury was noted. Lately,
the ad vent of solid -silicone membrane technology has led to
a simplified liquid ventilator with a single-piston design30
(Fig. 23-7).
During liquid ventilation, not only is a simple desig n es-
sential, but also C02 clearance and low resistance to flow are
critical aspects. Thus research d esign is currently focusing
on optimizing th e gas exchanger used in the TLV system.
Several investigators are u sing commercial blood -circuit
membrane oxygenators, but excessive evaporative loss,
leakage thou gh the p orous membrane, and material com-
patibility are problems . As an alternative, spray-bubbler
column gas exchangers have been constructed , although
gas-exchange efficien cy is reduced and perfluorocarbon
loss is increased w hen compared with membrane gas-
exchange d evices.101 Thus, in the most recent devices, a
silicone hollow-fiber gas-exchange device 30 has provided
DAY 1 DAY 3 DAY7 low resistance to flow and excellent gas-exchange efficiency.
(1) Actuator
(1 5) (2) Piston
(3) Membrane Oxygenator
(4) ETI -
(5) Pressure transducer
(6) Flowmeter
(7) Bubble trap
(8) One-way Valves o
(9) Heater
(10) PFC syringe pump
(11 ) Oxygen sweep Gas Inlet
(10)
(12) Oxygen sweep Gas Outlet
(13) PFC vapor Condenser
(14) Recovery bag
(15) Oxygen Tubing
(16) PFC tubing -
(17) Oxygen Tubing -
(18) Weighing Table
FIGURE 23-7 Schematic diagram of the single-piston liquid ventilator. PFC is pumped by the actuator (1) from the piston (2) through the
oxygenator (3) and then directly to the animal via the endotracheal tube (4). During the expiratory phase, PFC is actively drained from the
animal back to th e piston, passing through a bubble trap (7) and heat exchanger (9). One-way valves (8) are used to control the direction
of flow (PFC flow direction is indicated by the unfilled arrows). Additional PFC volume is added to the system by a syringe-pump
system (10) connected to the expiratory limb. PFC vapor exhaled from the oxygenator is condensed b y a cooler coil (13) and collected
in a recovery bag (14). Countercurrent sweep gas flow (indicated by filled arrows), 5 liters/min of 100% of oxygen from a tank (15), is
p assed through the oxygenator from the gas inlet (11) sited on the top of the oxygenator to the gas outlet (12) at the bottom. PFC tidal
volume and end-expiratory and end-inspiratory volumes are recorded by a scale (18). (Used, wi th pennission, f rom Tredici et al: Crit
Ca.re Med 32:2104-9, 2004.)
The low resistance to flow, combined with simple design tion, or oleic acid inju ry) has demonstrated improvement
and ability to precisely control tidal volume and flow, pro- in gas exchange, cardiovascular stability, and pulmonary
vides a ventilator that allows maintenance of dynamic air- recruitment; effective lavage of puhnonary debris (i.e., exu-
way pressures in an appropriate range. One factor tha t lim- date, meconium, or mucus); and preservation of pulmonary
its the respiratory rate d uring TLV is flow limitation d ur- architecture when compared with gas ventilation and/or
ing expiration. This is also known as choked flow and leads PLV. During TLV, as explained by Kylstra et al14 (Fig. 23-8),
to upstream expiratory airway collapse. According to the the 0 2 gradient between the inspired liquid and the alveo-
wave-speed theory of Dawson and Elliot,102,103 maximal ex- lar surface is large secondary to a lower diffusion coefficient
piratory flow is limited by the wave speed of the liquid. when compared with gas ventilation. As a consequence,
Airway collapse is induced if the drainage flow exceeds during TLV in a normal lung, Pao2 is lower (approximately
the maximum flow determined by the wave speed. When 300-400 mmHg) than d uring gas ventilation with 100% 0 2
choked flow occurs, tracheal pressure decreases (becoming (""'600 mmHg). Cons idering the alveolus as a sphere, with
very negative) and results in the closure of airways, located gas exchange occurring at the periphery, the initial and final
more in the la rge airways than at the alveolar level. Liquid 0 2 concentrations depend o n the radius of the sphere, the
is trapped in the lungs, increasing the end-expiratory lung diffusion coefficient of 0 2 in the fluid, the flux of 0 2 into the
volume, which, in turn, increases the risk of barotrauma and alveolar wall, and time. In an abnormal lung, conversely,
compromises hemodynamics, similar to that seen with auto- the more homogeneous distribution of the perfluorocarbon
PEEP. Choked flow is avoided by allowing an adequa te ex- as compared with gas overcomes the diffusional limitation,
piratory time, although the initial lung volume, tidal vol- resulting in more efficient gas exchange during TLV.
ume, perfluorocarbon, and expiratory waveforms all affect Despite the use of a large tidal volume d uring TLV, the
the development of expiratory flow limitation.105-106 airway and alveolar pressures are less than those gener-
ated during gas ventilation. Because of the high viscosity
and density of perfluorocarbons, the proximal airway pres-
LABORATORY STUD IES
sures generally are high during liquid breathing when com-
The use of TLV in healthy animals or in models of respira- pared with the alveolar pressures, reflecting high resistance
tory distress (e.g., surfactant deficiency, meconium aspira- to flow. Thus a greater difference between peak airway
CHAPTER23 LJQUIDVENTILATION 521
Inspiratory PFC
Gas Exchange Unit
P10 2 = 496 mmHg
Airways
Mixed Expiratory PFC FIGURE 23-8 The theoretical model
of Kylstra ct al14•109 of an alveolus
in which a sphere, or alveolus, is
gas or liquid filled at a uniform
oxygen concentration. A gradient
from the center of the sphere to the
periphery is created as gas exchange
Arterial Blood occurs. This gradient depends on
the radius of the sphere, the
Pa02 = 170 mmHg diffusion coefficient of oxygen in
the fluid, the flux of oxygen into
PaC02 = 45 mmHg the alveolar wall, and time. (Useti,
witl·1 permissiou, from Cox et al: Biol
Q Neona t 84:232-42, 2003.).
pressure and alveolar pressure generally is observed dur- It has been suggested that during the delivery of a liquid
ing TLV. It is important to obtain an optimal balance be- tidal volume that the venous return is impaired and trans-
tween gas exchange and hemodynamjc effects during TLV. mural right-atrial pressure is increased, leading to a reduc-
Respiratory rate, tidal volume, and inspiratory-expiratory tion in the right-ventricular preload and right-ventricular
(l:E) ratio can be adjusted to alter the effect of TLV on stroke volume. While the lungs inflate, the left-ventricular
hemodynamics. preload initially increases secondary to the shift of the pul-
Use of large tidal volumes induces cyclic changes in lung monary blood content. Consequently, the initial stroke vol-
volume and intrathoracic pressure, producing a respiratory- ume is increased. After this initial increase in left-ventricular
related fluctuation in arterial blood pressure (Traube- stroke volume, the preload of the left side is impaired by the
Hering waves)104 (Fig. 23-9). These effects are exacerba ted low right-side stroke volume, resulting in a decrease in left-
during liquid ventilation secondary to the relatively high ventricular stroke volume.
density of perfluorocarbons . The weight of the lung at end The use of a high respiratory rate with consequent re-
expiration is increased, and this may lead to compression of duction in expiratory time and development of a uto-PEEP
central structures such as the heart, great veins, and aorta. also can impair hemodynamics. Such impairments, how-
This may affect both ventricular filling and cardiac ejection. ever, can be corrected by providing an adequate circulating
120 PLV 120 TLV .FIGURE 23-9 Typical tracing of

b eat-to-beat trend data of hemodynamic
variables: systolic, mean, and diastolic
systemic arterial pressures (SAPS, SAPM,
and SAPO), pulmonary arterial pressures
(PAPS, PAPM, and PAPD), and mean
values for cen tral venous p ressure (CVP)
~
0> 80 and left atrial pressure (LAP). The time
I
scale is constant for both PLV (/eft) and
E TLV (riglrt). (Used, with permissio11, from
~
E
60 60 Degrneuwe et nl: Ped·i atr Pulmouol
.... SAPO
30:114-21, 2000.)
_, -e. PAPS
40
40 ~ ~E::~=~==~==:-& -& PAPD
PAPM
'* LAP
-a- CVP
~ ·arr ~;;~.::;;~- ...,;=~'AA· ·w

0
0 10 20 30
Time (s)
blood volume. The ability of liquid ventilation to improve 4. Wolfson MR, Shaffer TH. Liquid ven tilation during early
pulmonar y mechanics with homogeneous expansion of development: Theory, physiologic processes and application. J
the lungs during early development was demonstrated by Appl Physiol1990; 13: 1- 12.
Wolfson et al. 107 When compared with gas ventilation, liq- 5. Hirschi RB, Merz 51, Montoya JP, et al. Development and
uid ventilation was able to sustain oxygenation and main- application of a simplified liquid ventilator. Crit Care Mcd
1995; 23:157-63.
tain c~ clearance and acid-base status without altering 6. Fuhrman BP, PaczaJl PR, DeFraJlcisis M. Perfluorocarbon
the cardiovascular status independent of the gestational associated gas exchange. Crit Care Med 1991; 19:712- 22.
age. Achievement of a balance between optimal gas ex- 7. Gauger PG, Pranikoff T, Schreiner Rj, et al. Initial experience
change and hemod ynamic effects is especially important with partial liquid ventilation in pt'Ciiatricpatients with the acute
with the useofTLVin premature newborns, where the oscil- respiratory distress syndrome. Cri t Care Med 1996; 24:16-22.
lation of blood pressure can result in intraventricular hem- 8. Wintemitz MC, Smith GH. Preliminary studies in intratracheal
orrhage. Another study showed that 0 2 consumption and therapy. In: Wintemitz MC, editor. Pathology of war ga~
C02 production do not change during TLV. 108 poisoning. New Haven: Yale University Press, 1920: 1~0.
9. Clements JA. Surface tension in lung extracts. Proc Soc Exp Bioi
Med 1957; 10:170-2.
10. Avery ME, Mead J. Surface properties in relation to atelectasis
CLINICAL STUDIES
and hyaline membrane d isease. Am J Dis Child 1959; 97:517- 32.
Unfortunately, clinical application of TLV is limited to one 11. Clements JA, Tierney DF. Alveolar stability associated with
study performed in 1990 by Greenspan et aJ41 on three mori- altered surface tension . In: Clements JA, editor. Handbook of
bund premature infants. TLV using a gravity-assisted de- physiology: Respiration . Bethesda, MD: American Physiolog-
ical Society, 1964: 1565-83.
vice was performed for two separate 3- to 5-minute intervals
12. Mead J, Whittenberger JL, Radford EP. Surface tension as factor
in these three infants with severe RDS that was refractory to in pulmonary volume-pressure hysteresis. J Appl Physio11957;
both high-frequency jet ventilation and surfactant therapy. 10:191-6.
All three infants exhibited increased pulmonary compliance 13. Kylstra JA, Tissing MO. Fluid breathing. In: Boerema I,
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oxygenation. Although positive, this study, because of its of hyperbaric oxygen. Amsterdam, Elsevier, 1964:371- 9.
short duration and small sample size, carmot be considered 14. Kylstra JA, Pagcnelli CV, Lanp hier EH. Pulmonary gas ex-
conclusive. The fact that the infants tolerated the trial, how- change in dogs ventilated with hyperbarically oxygenated
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Liquid ventilation is in the early stages of its evolution. Al- 18. Tham MK, Walker RD, Modell JH. Physical properties of and
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liquid equilibrated witl1 oxygen at atmospheric pressures.
needs to occur. Newer treatment modality of enhancing
Science 1966; 152:1755-6.
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Perflubron improves arterial oxygenation it1 acu te canine lung flow: A unifying concept. J Appl Phys io\1977; 43:498-515.
injury. Am J Physiol 1993; 75:2696-702. 103. Dawson SV, Elliot EA. Use of the choke point in the prediction
84. Parent AC, Overbeck MC, Hirschi RB. Oxygen dynamics of flow limi tation in elastic tube. Fed Proc 1980; 39:2765-70.
during partial liquid ventilation in a sheep model of severe 104. Degraeuwe PL, Vos GD, Geskens GG, et al. Effect of per·
resp iratory failu re. Surgery 1997; 121:320- 7. Auorochemical liquid ventilation on cardiac output and
85. Quintel M. Hirschi RB, Roth H, et al. Computed tomographic blood pressure variability in neonatal p iglet with respiratory
assessment o f Perflubron and gas distribution during partial insufficiency. Pediatr Pulmonol 2000; 30:11 4-24.
liquid ventilation for acute respiratory failure. Am J Respir Crit 105. Baba Y, Brant D, Brah SS, et at. Assessment of development
Care Med 1998; 158:249-55. of choked flow during total liquid ventilation. Crit Care Med
86. Gauger PG, et a\. Pcrfluorocarbon partial liquid ventilation 2004; 32:201 -8.
improves gas exchange while augme11ting decreased functional 106. Foley DS, Brah R, Bull JL, et al. Total liquid ventilation: Dy nam ic
residual ca pacity in an animal model of acute lung injury. Surg airway pressure and development of expiratory flow limitation.
Forum 1995; 46:669-71. ASAIO J 2004; 50:485-90.
87. Doctor A, Ibla JC, Grenier BM, ct al. Pulmonary blood fl ow 107. Wolfson MR, Greenspan JS, Deoras KS, et al. Comparison of gas
distribution during partial liquid ventilation. J Appl Physiol and liquid ventilation: Clinical, physiological and his tological
1998; 184:1540-50. correlates. J Appl Physio\1992; 72:1024-31.
88. Wilcox DT, Glick PL, Karamanoukian HL, et al. Partial liquid 108. Hirschi RB, Grover B, McCracken M, et al. Oxygen consurnp·
ventilation and nitric oxide in congenital diaphragmatic hernia. tion and carbon dioxide production during liquid ventila tion.
J Pediatr Surg 1997; 32:1211-5. J Pediatr Surg 1993; 28:513-9.
89. Wilcox DT, Glick PL, Karamanoukian H L, eta\. Perfluorocarbon- 109. Cox C, Stavis RL, Wolfson MR, et al. Long-term tidal liquid
associatL'Ci gas exchange improves pulmonary mechanics, ventilation in premature Jambs: Physiology, biochemical and
oxygenation, ventilation and allow nitric oxide delivery in histological correlates. Bioi Neonat 2003; 84:232-42.
rtthapter 24 _ _ _ _ _ _ _ _ __ the central airways for the purpose of improving the effi-
ciency of alveolar ventilation and/ or minimizing the venti-
TRANSTRACHEAL GAS lator pressure requirements?
Variants of TGI have been investigated for several
INSUFFLATION decades. In nonhospitalized, stable patients with chronic
lung diseases, administration of fresh gas into the tra-
LLUfS BLAN0-1 chea reduced inspired minute ventilation, improved dys-
AVI IAHUM
pnea and exercise tolerance, and lessened the work of
°
breathing.8- 1 Continuous apneic ventilation delivers oxy-
gen and maintains adequate blood oxygenation a t a sta-
ble level of hypercapnia.11 - 13 This chapter discusses TGI
as an adjunct to mechanical ventilation; other fom1s of
trans tracheal gas (airI oxygen) administration are consid-
BASIC PRINCIPLES ered briefl y.
Mechanism of Action
Modes of Operation
PHYSIOLOGIC EFFECTS Basic Principles
RATIONALE, ADVANTAG ES, AND LIMITATIONS
INDICATIONS AND CONTRAINDICATIONS MECHANISM OF ACTION
End-Stage Pulmonary Disease
Acute Lung Injury and Acute Respira tory Distress TGJ attempts to minimize d ead space by delivering fresh
Syndrome gas through an intratracheal catheter to flush the an atomic
Liberation from Mechanical Ventilation dead space free of C02. During TGI, low to moderate flows
OPERATIONAL CHARACTERISTICS OF TGI of fresh gas introduced near the carina, either continuously
Catheter Position or in phases, dilute the c~ residing in the anatomic dead
Catheter Flow Rate space proximal to the catheter tip. Because C02 is washed
Catheter Shape out during expiration, less C02 is recycled back into the
Humidification alveoli during the subsequent inspiration (Fig. 24-1). Any
Endotracheal Tube Design catheter flow during inspiration contributes to the inspired
ADJUSTMENTS AT TH E BEDSIDE VT but bypasses the anatomic dead space proximal (mouth-
Inspired Oxygen Fraction ward) of the catheter tip. At higher catheter flow ra tes, tur-
Airway Opening Pressure bulence generated at the tip of the catheter by the jet stream
Effect ofTGI on Lung Volume can enhance gas mixing in regions distal to the catheter
Tidal Volume tip, thereby contributing to C02 removal.l 4•15 The fresh-
Flow-Controlled, Volume-Cycled Ventilation gas stream exiting the catheter tip rapidly establishes a n
Pressure-Controlled Ventilation expiratory front beyond the catheter tip between C02 -rich
TGI-Ventilator Interactions alveolar gas and C02-free fresh catheter gas.15 This front is
MON ITORIN G AND TROUBLESHOOTIN G practically abolished by inverting the catheter tip and di-
IMPORTANT UNKNOWNS recting the catheter jet m outhward, thus eliminating the
THE FUTURE distal effect of TGI. 14 Consequently, the s traight catheter
SUMMARY AND CONCLUSION consistently outperforms the inverted catheter. Under ex-
ACKNOWLEDGMENT perin1ental conditions, the observed difference in Paco 2 be-
tv.reen the straight and inverted catheters during continu-
ous TGI amounted to 25% of tl1e total decrease in Pac~
Strategies for lung-protective mechanical ventilation use with a catheter flow rate of 10 liters/rnin.14 End-expiratory
sm all tidal volumes (V,.) to avoid high alveolar pressures a t C02 values at the tip of the endotracheal tube (ETT) during
end inspiration and alveolar overdistension, together with continuous TGI in dogs were comparatively higher using
moderate or high levels of positive end-expiratory press ure the straight catheter than the inverted catheter, indicating
(PEEP) to keep alveoli open at end expiration and thereby that projecting the TGTjet distally improved C02 removal
maintain alveolar recruitrnent. 1•2 These stra tegies have reat end expiration.16 Furthermore, a study on the penetra-
sulted in improved outcomes in patients with acute lung tion and mixing behavior of TGI gas in a simulated tra-
injury (ALI) and in patients with acute respiratory distress chea has shown that mixing of expiratory and TGI gases
syndrome (ARDS).3 - 6 Unfortunately, they also can decrease occurred dose to the TGI orifice; the oxygenated domain
alveolar ventilation, leading to carbon dioxide (C02) re- extended several centimeters beyond the ETT, even at high
tention and evenh1ally severe respiratory acidosis. Patients expiratory flows, but had a definite distal limit. Moreover,
with unstable hemodynamics or associated cerebrovascular more distally from the site of gas injection, the TGT gas
diseases might not tolerate moderate elevations in Pac~· tended to propagate a long the trad1eal wall rather than
In this context, trad1eal gas insufflation (TGI) has a role projecting centrallyY These observations indicate that the
as an ad junct to mechanical ventilation. This technique con- primary m echanism of C02 elimination during TGI is expi-
sists of the continuous or phasic injection of fresh gas into ratory washout, and the forward-directed TGI penetrates a
525
noTGI TGI
Continuous TGI
end-exhalation
Phasic TGI
e11d-inhalation
FIGURE 24-1 (Lcrft) With no tracheal gas insufflation (no TGI),

th e central airways contain C02 at end-expiration; this C02 is
v-.. . .
delivered to al veoli during subsequent inspirations. (Right) with
TG I, the C02 from the central airways is flushed during the
expiratory ph ase, wh ich reduces Ute C0 2 delivered to alveoli
d uring the subsequent inspiration. (Used, w itlr permission, from
.........- .......b.--
Ravenscraft: Respir Care 41:105- 11, 1996.)
FIGU RE 24-2 Tracheal gas insu fflation (TG I) can be provided as
a continuous flow of gas into the airway or specific to the phase
substantial distance into the central airways, extending the of the resp iratory cycle. D ifferent approach es can be used to
compartment susceptible to C02 washout with a smaller provide phasic TGI. (Used, w itlr permission, from Ravenscraft:
contribution of turbulence beyond the straight catheter tip. Respir Care 41:105- 11, 1996.)
Consequently, Paco, d uring TGI falls as a nonlinear func-
tion of catheter flow rate. Initially, mod est flow rates achieve
large decrements in Paco,, but once the anatomic d ead space occurred only during inspiration (inspiratory bypass), the
is flushed free of C02, the effect on Paco, diminishes as "anatomic" dead space proximal to the catheter tip (extend-
catheter flow rate is increased .7·18 ing from the ventilator's Y piece) was effectively avoided.
When insufflation occurred during late expiration (expira-
tory washout), fresh gas washed the proximal dead space
MODES OF OPERATION
free of C02 . Lin1iting TGI to the final 60% of expiration
During TGI, fresh gas can be delivered continuously, or de- achieved effective Paco2 reduction (not significantly dif-
livery can be timed to occur in phases during a specific ferent from panexpiratory TGI) while limiting exposure of
portion of the respiratory cycle by gating a solenoid valve the trachea to TGI gas and reducing the potential for TGI-
that either directs the flow to the catheter or diverts it to induced hyperinfla tion. 23 Differences between these phasic
the atmosphere. 19•20 During continuous TGJ, closure of the methods tended to na rrow at higher catheter flow rates.
expiratory valve during ins piration causes catheter flow to Early expiratory injection (i.e., where catheter flow was
deliver a variable portion of the inspired VT. 2'~, 22 The analog timed to occur early in expiration and terminated before
output o f the ventilator or fl ow signal from a pneumotacho- end expiration) was less effective, however, than late expira-
graph can be used to operate a metering d evice that controls tory injection.16 Even though C02-containing gas is washed
the solenoid (Fig. 24-2). out of the a irways during early expiratory injection by TGJ,
Phasic inspiratory TGJ can be used as the only source CD2-laden alveolar gas refills the proximal anatomic dead
of fresh gas, thereby bypassing the anatomic dead space space later in the expiratory period. This C02-ricl1 expired
proximal to the catheter tip. 20 It also can be combined w ith gas is then "rebreathed" during the subsequent inspiration.
a con ventional ventilator to augment alveolar ventilation. Consequently, fresh gas d elivered too early in expiration
During continuous or phasic inspiratory TGI, the catheter- cannot participate fully in d ead-space r eduction. 24 Lung-
d elivered portion of the inspired VT is a functio n of catheter model studies have shown that the marked increases in
flow rate a nd inspiratory time. During phasic expiratory system pressures and volumes caused by continuous TGI
TGI, catheter flow is timed to occur during all or part of ex- could be avoided with expiratory-phase TGI and volume-
pira tion and does not contribute appreciably to the inspired adjusted TGI. 25
VT. As an alternative to using a catheter, the apparatus dead Continuous TGI produced an effect superior to both in-
space and part of the tracheal dead space can be eliminated spiratory bypass and late-expiratory washout in augment-
by using a double-lumen ETT to separate the inspiratory ing alveolar ventilation. 20 When catheter flow is set to oc-
and expiratory limbs of the ventilator circuit.22 cur selectively throughout expiration (panexpiratory TGI),
The effect of insufflating fresh gas during specific phases however, the increase in alveolar ventilation is very similar
of the respira tory cycle has been examined using three to that acltieved by continuous TGJ.2° Because TGI does n ot
catheter-flow conditions: (1) continuous TGI, (2) flow only con tribute a pprecia bly to inspired VT during panexpira tory
during inspiration (see Fig. 24-2), and (3) flow during the TGI, it allows the use of ltigh catheter flows w ithout increas-
final third of expiration20-23 (Fig. 24-3). When catheter flow ing peak alveolar pressure. Studies are needed to define the
CHAPTER 24 TRANSTRACHEAL GAS INSUFFLATION 527
::=- 300 EWO

-EE
Q) 200
-0
;:)
100
>
0
0 2 4 6 8 10 12 14 16 18
20
-E 0
---
.!:
-20
~ OFF
-0
LL
-40
-60
0 4 6 8 10 12 14 16 18
-
10
q.,. 8
J: 6
E
-u
~
4
:. 2
0
0 8 10 12 14 ,6 18
Time (sec)
FIGURE 24-3 Simultaneous tracings during expiratory washout (EWO) at 10 liters/min catheter flow. (Above) Plethysmographic lung
volume relative to the end-expiiatory lung volume measured without cath eter flow. (Center) Flow tracing measu red in the inspintory and
expiratory limbs of the external circuit. (Below) Proximal airway press ure. Note that lung volume and proximal airway pressure tracings
show preinspiratory step changes. These deflections indicate that gas flows both antegrade (volume tracing) and retrograde (flow tracing)
from the catheter tip during this period. (Used, witll permission, Burke et al: Am Rev R espir Dis 148:561-8, 1993.)
optimal coordination of catheter injection with respect to The presence of the catheter and the TGI jet effect, how-
the cycling pattern of the ventilator. ever, oppose expiratory flow and favor air trapping at end
expiration and a uto-PEEP?·18, 25- 30
Physiologic Effects
The physiologic dead space consists of conducting air- Rationale, Advantages, and Limitations
ways (instnm1ental and anatomic dead space) and well-
ventilated alveoli that receive minimal blood flow. In the TGI reduces Pac~ during hypoventilation. 20·31 - 34 This ef-
second, or intrapulmonary, shunt compartment, little or no fect occurs whether hypoventilation is caused by a de-
gas exchange takes place because alveoli are perfused but crease in minute ventilation or an increase in respiratory
not ventilated. Because the anatomic dead space remains rate at constant minute ventilation. The efficacy of TGf in
relatively constant as VT is reduced, low VTs are associ- lowering Pac~, however, diminishes when an increased
ated with a high dead-space-to-tidal-volume ratio.18 TGI alveolar component dominates the total physiologic dead
applied together with conventional mechanical ventilation space.22,34,35
effectively reduces the size of the dead-space compartment The volume of gas injected per breath during expira-
and improves overall C02 elimination by replacing the C02 tion and the volume of gas flushed out of the dead space
that normally occupies the anatomic dead space with fresh during the expiratory period determine the effectiveness
gas during expiration. Consequently, less CD2 is recycled to of TGI, provided that inspired minute ventilation remains
the alveoli during the next inspiration, and the ventilatory unchanged and end expiration is included in the catheter
efficiency of each tidal respiration is improved. Therefore, flush period.36 Increasing catheter flow in clinical situations
TGI reduces anatomic dead space and increases alveolar where only a brief expiratory time is available may maintain
ventilation for a given frequency and VT combination. The TGI efficiency. In fact, an inverse correlation between respi-
main effect of TGI is to flush the dead space from the carina ratory rate and Pac~ has been observed,37 indicating that
to the Y of the ventilator circuit to enhance C02 removal. lower breathing frequencies (or longer expiratory times)
favor TGI efficiency (defined as reductions in Pac~ and provide continuous oxygen therapy and to decrease oxygen
physiologic dead space). flow requirements.8 - 10 •41 In patients with end-stage lung
A significant increase in airway pressure and in lung disease, TGI provides a method for oxygen delivery and
volumes is a well-known side effect of TGI and correlates confers the additional benefits of decreasing dyspnea and
with the flow used. 14•33 When TGI is limited to the expira- increasing exercise tolerance.42 A continuous low flow (4-5
tory phase, VT remains virtually unchanged during volume- liters/min) delivered to the tracheostomy tube produces a
control ventilation (VCV), but airway pressures still can in- reduction in dead space, VT, and minute ventilation with-
crease through expiratory flow limitation and auto-PEEP. out affecting Pac~ in the acute state, whereas it maintains or
Therefore, successful application of TGI is limited by the reduces Pac~ in the chronic state presumably secondary to
potential for overpressu rization of the airways and produc- reductions in dead space. In patients with the most severe
tion of dynamic hyperinflation.33 An increase in total PEEP forms of chronic obstructive pulmonary disease (COPD),
either may increase alveolar dead space, which counteracts TGI brought about a reduction in oxygen consumption and
the TGI clearance of C02 , or may recruit collapsed alveoli C02 production, as well as a less demanding respiratory
and improve C02 clearance. pattem ..10 These findings help to explain the improvements
Increase in lung volume is a serious limitation of TGI in exercise tolerance and decreased dyspnea and support
and should be avoided. Solutions to minimize expiratory the use of transtracheal gas therapy for indications other
TGI-induced auto-PEEP include using lower TGI flows, de- than oxygenation. Interestingly, when TGI was combined
livering TGI during pressure-controlled ventilation (PCV), with periodic tracheal occlusions in spontaneously breath-
and optimizing mechanical ventilation during TGI. Dur- ing tracheostomized animals, 43 a progressive increase in
ing PCV, a TGT-induced increase in airway pressure au- minute ventilation and reductions in Pac~ that ultimately
tomatically results in a decrease in VT, and the lack of led to the cessation of spontaneous breathing efforts were
expiratory TGI-induced auto-PEEP is associated w ith a observed. Further studies are necessary to determine the ef-
reduction in the effici ency of C02 elimination. Likewise, if ficacy ofTGI in supporting patients with chronic hypercap-
TGI flow is reduced, the ability to clear C~ also will be nic respiratory insufficiency during sleep and wakefulness.
diminished.28•38 - 40
ACUTE LUNG INJURY AND ACUTE RESPIRATO RY

Indications and Contraindications DISTRESS SYNDROME
Studies of TGI in patients with ARDS have focused on
END- STAGE PULMONARY DISEASE
demonstrating a reduction in VT and subsequently on air-
Continuous insufflation of fresh gas (oxygen/air) through way pressure while Pac~ is maintained constant or a reduc-
an intratracheal catheter has bee11 used in patients with tion in Pac~ during permissive hypercapnia36•39' 44' 45 (Fig.
end-stage pulmonary disease and chronic c~ retention to 24-4). Despite the fact that TGI was first tested in humans
120 120
100 100
<II
Cll
80 <II BO
Cll
::;, ::;,
Iii a!
> >
Cll Cll
c 60 .S 60
Cll Cll
"'ld ""
a!
-
.0
0
0~
40 -
.0
0
0~
40
20
0
0 4 6 0 0 4 6 0
Catheter flow (1/ min) Catheter flow (Vmin)
0 P8 C02 0 P8 C02
FIGURE 24-4 The effect of different TGI catheter flows in patients with acute respiratory failure. (Left) percent reductions in Paco2 while
tidal volume (VT) was maintained constant. (Right) Percent reductions in VT while Paco2 was maintained constant. (Used, witlt perm.issiou,
from Nakos et nl: lnteusive Care Med 20:407-13, 1994.)
0.010 OJml 0.010 0.010
100
80
-
Q
::J:
Stagrt 1
24mmHg
e 60
-
e
0~ 40
StageD
1&mmHg
. •
,.
..
,. ,.
;'
<J ..
. ....- · . ,#' .·
.,., ""'
Clll
Q. ...
• _,. ,..
-........ .,_
..__ _. .... ~
20
0+------,------~------r------r----~
0.0 0.2 0.8 1.0
FIGURE 24-5 The effect of TGI on Pa<;o1 as a function of the total physiologic dead-space fraction (VoNT>· The lin_es were constructed
u sing the equation Paco2 = 863Vco2 [VE(1 - VoNT)). The C02 p roduction rate <Vco2 ) and the minute ventilation (VEl used for each line
are specified. Symbols respectively represent before (stage 0, circles) and after (stage 1, trinugles) oleic acid inju ry in experimental animals
and after oleic acid injury with incr eased tidal volume (stage 2, sqttnres). Solid and open symbols correspond to baseline and TGI
conditions, r espectively. Despite a smaller decrease in VoNT during TGI after oleic acid injury (stage 1), th e decrement in Paco2 was
larger because the respiratory system operated on the most curvilinear portion of the curve. During stage 2, the increase in VEshifted the
curve to the right, causing the system to operate on the flatter portion of the curve. Consequently, the decremen t in Paco 2 resulting from
TGI was much smaller than it would have been if Ve had remained constant. During all TGI stages, the increase in Vc02 shifted the curve
to the left and attenuated the observed decrement in Paco2 for a given decrease in Vo/VT caused by TGI. (Usetl, with permissio11,from
Nalmm et nl: Am] Respir Crit Care Med 152:489- 95, 1995.)
receiving mechanical ventilation in 1969,46 randomized clin- mal airways. Adopting a permissive hypercapnia strategy
ical trials are still lacking. increases the amount of C02 that can be removed from the
In patients with ARDS, part of the dead space resides in proximal anatomic dead space and counterbalances the de-
the alveoli (alveolar dead space). The alveolar gas originat- creased efficacy ofTGI for C02 removal caused by increased
ing from those ventilated but hypoperfused lung regions alveolar dead space7, 47 (Fig. 24-5). Several studies39' 44' 48
is poor in C02, diminishing the impact of washing proxi- have shown that one of the most important features of TGI
PaC0 2 (mmHg) Qs/Qt Pa0 2

(%) (mmHg)
52
1 00
48 1 T
330
,/1 ',,, ',f

295
85
44
260
70
'
55
40
T/
0 1 225
36
40 1 190
PH PH PH PH PH PH
+ control + con1rol
EWO ewo
FIGURE 24-6 Individual changes in Paco 2 , true pulmonary shunt (Qs/Qt), and Pao2 during permissive hypercapnia (PH) and PH plus
expiratory washout at 15liters/min (EWO) in patients wi th acute respiratory distress syndrome. PH plus EWO reduced Paco2 and
pulmonary shunt and improved oxygenation. These effects were associated with a parallel increase in plateau and mean airway pressures,
suggesting the development of auto-PEEP and air trapping during EWO. ( Llsetl, with penuissiou, from Kalfou. et al: A11estllesiology 87:6-17,
1997.)
is that it can maintain normocapnia or a given level of Pac~ PaC0 2 Ppfat

while VT is decreased, allowing a reduction in minute ven- (mmHg ) e--e (cmHpl Q- 0
tilation. Therefo re, TGI can be used to decrease the forces
acting on the lung and thereby minimize ventilator-induced 25
lung injury in patients with ARDS. 104
In patients with ARDS ventilated with a permissive
hypercapnia strategy, 30 high expiratory washout flows (15 91 23
liters/min) are very useful in reducing Pa~ , although
there may be a considerable risk of favoring air trapping,
auto-PEEP, and a subsequent increase in plateau pressure
78
i21
(Fig. 24-6). The combination of increasing respiratory rate to 65 - *
the limit of originating auto-PEEP, eliminating unnecessary 19
instrumental d ead space, and reducing external PEEP when
52 .
TGI-induced auto-PEEP rises (to maintain the total PEEP *
constant) seems to be a suitable approach to delivering a ..L. 17
pressure-limited ventilator strategy in combination w ith
TGI in hypercapnic patients with severe ARDS39•49 (Fig.
24-7). PEEP Pa02
Severe unilateral lung pathology, such as lung contusion, (C111 H,O) o- 0 (rnmHg) ~
----------------~
unilateral pneumonia, or refractory atelectasis, is common 260
in the intensive-care setting and often requires mechanical 16
ventila tion w ith a high fraction of inspired oxygen (Fr02 ).
In this context, the application of PEEP usually does not 225
improve oxygenation because it may cause overdistension 13
of compliant lung regions and redistribute blood flow to P,.
1
I ! \
collapsed or fluid-filled alveoli. 50 In experimental studies 10
I ..:..., 190
on unilateral lung injury,51 •52 selective TGI application im- \.
I
I I
proved oxygena tion and decreased Pc 02 and airway pres- '\* I

\
\
sures, and functional residual capacity (FRC) remained con- 'd I 155
stant, whereas VT could be further decreased . Although se- 1 I
lective TGI improved pulmonary function without any side '*0

I
effects, it is hazardous to extrapolate experimental data to .L

120
the clinical setting because it is not known whether high TGI
flows could be ma intained for a long period. 0 0 > ·EWO
~
~
TGI-associated reduction in Paco2 may be a poten-

tially important maneuver in patients with cerebrovas-
"E
0
(.)
~ ......
a..
+
OPTIM V
0
cular injury with intracranial hypertension and concomi-
FIGURE 24-7 Changes in Paco1 , in s piratory plateau airway
tant ALI/ ARDS. These patients need aggressive treatment
p ressure {Pplat), PEEP, and Pao2 indu ced by op timized
to maintain intracranial pressure as low as possible, to- mechanical ventilation (OPTIMV), expiratory washou t (EWO),
gether with protective lun~ ventilatio n. Both anecdotal case and the comb ination of OPTJMV an d EWO in six patien ts wi th
reports 53• 54 and case series 5 have shown that TGI inpatients severe acute respiratory distress syndrome. Extrinsic PEEP had to
with ALI/ ARDS and severe head trauma allowed a more be reduced by 5.3 ± 2.1 cmH2 0 during EWO and by 7.3 ± 1.3
protective ventilator strategy while Pa~ was reduced o r cmH2 0 during the comb ination of OPTIMV and EWO, whereas it
remained constant; more important, no short-term deleteri- remained unchanged during OPTIMV alone. Plateau pressure did
ous effects on hemod ynamics or cerebral parameters were n ot ch ange s ignificantly, suggesting that lung hyp erinflation was
seen (Fig. 24-8). n ot produced. In patien ts w ith severe ARDS, th e combination of
OPTIMV and EWO has additive effects and resulted in Paco 2
LIBERATION FROM MECHANICAL VENTILATION levels close to normal values . (Used, witl1 permissiou, from
Ricl1ecoeur et al: Am J Respir Crit Care Med 160:77-85, 1999.)
Failure of the respiratory muscle pump is probably the
most common cause of failure to wean from mechanical
ventila tion. Indeed, patients w ith COPD who subsequently In spontaneously breathing sheep with AU ,57 the combi-
fail a weaning trial exhibit not only an almost immediate na tion of continuous-flow positive airway pressure (CPAP)
rapid and shallow brea thing pattern but also a progressive and TGI yielded a reduction in the inspiratory work of
worsening of pulmo nary mechanics with inefficient C02 breathing. The beneficial effect of TGI w ith CPAP o n the
clearance. Deterioration in respiratory system m echanics in work of breathing was attributed to a favorable balance be-
patients who fail the weaning trial is characterized by in- tween decreased ventilatory requirements and low work-
creases in auto-PEEP and in inspira tory r esistance, together load superimposed by the apparatus and TGI. In fact, when
with a decrease in dynamic lung compliance.56 Therefore, CPAP is delivered in combination with TGI, additional in-
TGI could facilitate liberation from ventilator support by spiratory effort is required to overcome the insufflation flow
enhancing C02 clearance. and trigger the ventilator valves. TGI may increase the work
25 11
20 g
Driving
Pre uure Tidal
t(lblQO) Volume 20
lntracrane.a
..........
15 7
...
Pres:Sure
~.
10
10 5
0 ~---------------------
T«<I 8ual - Pott 0 ~-----------------------
B•n•· Pr• TGI
oL----------------------
euat · Prt TGt Boul - P oot
FIGURE 24-8 Individual values of driving airway pressure (difference between plateau pressure and PEEP) (left), tidal volume (center),
and intracranial pressure b efore (basal-pre), during (TGI), and after (basal-post) application of expiratory TGI in patients with severe head
trauma and acute lung injury. Expiratory TGI allowed the targeted Paco2 level to be maintained, together with s ubstantial reducti ons in
tidal volume and driving pressure, without deleterious effects on cerebral parameters. (Usetl, with permission, from Martinez et nl:
Intensive Ca re M ed 30:2021- 7, 2004.)
needed to open the demand valve and trigger the ventila- Operational Characteristics of TGI
tor; this problem may be surmounted ~a system that stops
TGI flow before the end of expiration (Fig. 24-9). CATHETER POSITION
Case series37•59 on the effects of TGI on lung function in
patients undergoing weaning from mechanical ventilation In TGI, a single catheter usually is placed above the main
have reported that VT, minute ventilation, Paco2 , and phys- carina, making this technique simple to use. Nonetheless,
iologic dead space were reduced in a flow-dependent man- more distal catheter placement may improve the efficiency
ner when gas was delivered through an orotracheal tube. of TGI in two ways 33 (Fig. 24-10). First, with more dis tal
Moreover, distal pos itioning of the TGI catheter was more placement, a greater volume lies proximal to the catheter
effective than proximal positioning, and the effects were less tip, permitting additional expiratory flushing of COrladen
pronounced in patients with tracheostomy. Interestingly, dead space. Moving the catheter toward the carina also ad-
the improvement in ventilatory efficiency resulting from the vances the jet-generated turbulence zone closer to the lung
reduction of d ead space yielded a decrease in Paco, at the periphery, thereby improvingTGI efficacy. In support ofthis
same respiratory rate and a t lower Vy. hypothesis, advancing the catheter tip from 0.5 em proximal
FIGURE 24-9 Flow and inductive plethysmographic lung-volume tracing in a mechani cally ventilated patient (pressure support of 4
cmH 2 0) during panexpiratory TGI of 8 liters/min. In 6 of 11 breaths, TGI flow meets the patient's inspiratory flow demand and provides
the total inspiratory volume for the breath, and the ventilator is not triggered. (Usetl, with permission, from Ho yt et al: Chest 110:775-83,
1996.)
30
-§
.!:
0
20
10
-·10
.-4() TGI
-~~--------------------------------------------------
0
0.6
--
_ ,J
0.5
0.4
I I 0.3
§ 0 .2
0
> 0. 1
0.0
0 10 20 30
Time (sec)
-0 A
Palie nl 7
50
-5 40
Proximal
... Q JO
•E
0
0 !.. 20
(Q
Q.
- 10 ~
0
<l () 10
Cl.
</!.
0
- 15 Distal
0 z J • s
Tim• (M c o nds)
6 7
•
- 20
0 2 4 6
B Patient2
Catheter flow (Umin)
FIGURE 24-10 Percent reduction in Paco2 from the baseline 50
value as a function of catheter flow. Distal and proximal catheter
positions were 1 and 10 ern above the carina, respectively. 40
Increasing catheter flow caused a reduction in the percent change
of Paco2 from baseline at both catheter positions. At s tudied
catheter flows, the distal position provided a larger percentage
-~ 30
E
reduction in Paco2 • (Used, witl1 perm-ission, from Ravenscmft et al: E 20
Am R ev Respir Dis 148:345-51, 1993.)
~
0
...
~ 10
to 4.0 em distal to the main carina in normal dogs moved
0
the peak resistance to gas transport from second- to fourth-
generation airways.15 The clinical benefit of introducingTGI
catheters deeper than the mai11 carina is doubtful, however.
In a series of animal studies, the effect of TGI on Pac~ was
0 1 2 3 4 5
TirM (•c:onds)
6 7
•
strongly dependent on catheter flow rate, but catheter tip FIGURE 24-11 Represen tative exhaled capnograms in hvo
position was not crucial as long as it was within a few cen- patien ts without TGI and with TGI at 6 liters/min insufflation
timeters below or above the main carina. 15 •27•33 Sin1ilar find- flow. A greater reduction in end-tidal C02 {Petco2 ) from the
ings have been reported in critically ill patients.36 In sum- Petco1 base value corresponded wit.h a larger reduction in Paco1 •
mary, these results indicate that during TGI, bronchoscopic At a given ins ufflation flow, efficiency to clear C0 2 is a function
guidance may not be necessary for TGI catheter placement; of the time available to flush proximal dead space. (Used, with
this helps to keep its clinical application simple because the permission, from Rave11scraft eta/: Am Rev Respir Dis 148:345-51,
1993.)
position of the catheter can be verified on a recent chest
radiograph by estimating the distance from the tip of the
ETf to the main carina.
deflation on TGI efficacy has been studied in normal dogs
us ing short and extended duty cycles at a fixed respiratory
CATH ETER FLOW RATE
frequency.16 The expiratory flush volume of fresh gas, how-
TGI us ually employs m odest catheter flow rates. Most an- ever, ra ther than its delivery pa ttern or flow rate determined
imal and human studies of TGI have used a flow rates of the observed decline in Paco, with TGI. These observations
4-10 liters/ min. Carbon dioxideeliminationduringTGi de- suggest that as expiratory time is shortened, higher flow
pends primarily on catheter flow rate,33•36•44•60 with turbu- rates are required to preserve TGI efficacy. At high catheter
lence generated at higher flows enhancing distal gas mixing flow rates, bronchotrauma is possible because of the high
and C02 elimination.14 Once fresh gas sweeps the proximal impact pressure and shear of the inflow jet on the bronchial
anatomic dead-space compartment free of C02 , further in- mucosa. 61•62
creases in flow rate are unlikely to wash more C02 out of the The optimal flow rate in terms of the decrement in Pac~
proximal anatomic dead space. Because expiratory washout afforded by TGI is a complex function of the voltune of
of U1e proximal anatomic dead space is the primary mech- anatomic dead space proximal to catheter tip, volume of
anism of action of TGI, both curtailing expiratory time and fresh gas delivered per expiration, pattern of c~ exha-
prolonging lung deflation may diminish the efficacy of TGI lation from the lungs, and the C02 exchange characteris-
unless catheter flow rate is very high. Decreasing expira- tics of the respiratory system before initiation of TGI. Once
tory time would decrease the volume of fresh gas delivered dead space proximal to the catheter tip has been almost
to the central airways per respiratory cycle (Fig. 24-11). The completely flushed by the fresh gas during expiration, any
presence of expiratory flow at end expiration would deliver catheter-flow dependence of Pac~ is likely to be secondary
additional C02 into the proximal anatomic dead space and to enhanced turbulent mixing in the airways distal to the
thus decrease the efficacy of TGI. The effect of ongoing lung catheter tip. Consequently, Pac~ continues to decrease with
Basal ing the jet stream onto the bronchial mucosa, which may
40- cause bronchial injury.61 - 63 Alternatively, the catheter tip
can be positioned within the ETT so that the jet hits the
PaC02 ( ETT wall. The orientation of the ETT holes with respect to
mmHg the catheter (end or side) appears to have little impact on
catheter efficiency. 33 Nevertheless, catheter shape directly
influences the extent (or lack of) dynamic hy perinflation
caused by TGI. 13•64
HUMIDIFICATION
The fresh gas delivered by TGI should be heated and hu-
midified to prevent mucous plug formation and to prevent
TGI4 Umin TGJ gas from causing bronchial injury via cooling and de-
hydration of the bronchial mucosa. Few studies ha ve ex-
amined the occurrence of bronchial mucosal injury system-
PaC02 atically during TGI. Similarly, not many studies have ex-
mmHg amined the effect of conditioning TGI gas on the extent of
injury to bronchial mucosa. TGI can cool tracheal gas s ignif-
icantly. The extent of cooling was greatest at high catheter
flow ra tes with continuous TGI and could be compensated
only partially by conditioning the ventilator-delivered in-
spired gas during panexpiratory TGI. 65 •66 Case series have
reported either no damage or no encrustation,63 whereas
other investigators found intratracheal catheter obstruction
TGI6 Umin after 2 days of continuous use. 48
40 The drying and cooling effect of TGI can be eliminated
if the gas can be heated and humidified. Most humidifiers,
PaC02 however, cannot withstand the pressures needed to drive
mmHg gas at 5-10 liters/min through small-bore catheters. Most
commercially available humidifiers leak or burst when the
pressure w ithin their chamber exceeds 140 cmH20. This
pressure limit restricts the rate of catheter flow that can be
used. For example, approximately 140 cmH2 0 of driving
0 pressure is required to deliver air through 40-cm-long 6.5F
and 8.0F catheters at flow rates of 3.6 and 6.4 liters/ min,
respectively. Therefore, the pressure tolerance limits of cur-
rently available humidifiers cannot withstand the flow rates
Tiempo (s) of 5-10 liters/ min necessary for most TGI systems.
FIGURE 24-12 Effect of continuous TGI on exhaled capnogram in
patients with acute respiratory failure. Increasing catheter flows
ENDOTRACHEAL T UBE DESIGN
produced greater clearance of exhaled C02 • (Used, with
pcrmissio11, from Sa ura et al: Med Iute11siv a 20:246-51, 1996.) There is no standard method of introducing the TGI catheter
into the trachea. In mos t human studies, a small-caliber
catheter is introduced through an angled sidearm adapter
increasing flow rate as catheter flow rate rises but at a slower attached to the ETT and positioned just above the main
pace14·33 (Fig. 24-12). In most TGI systems, the effect of in- carina.36,44.45, 4S Catheter placement usually is performed
creasing flow rate diminishes considerably when flow rate tmder bronchoscopic guidance o r estimated from a chest
exceeds 10 liters /min. IfTGI-induced turbulent mixing con- radiograph. This type of system is simple to constmct and
tributes sufficiently to C02 removal during expiration, it is can be duplicated in most intensive-car e units but suffers
possible to calculate a negative physiologic dead space us- from some drawbacks. Placement of a catl1eter through the
ing the Enghoff modification o f the Bohr equation corrected ETT interferes with suctioning of patients and can increase
for the ca theter's dilutional effect on mixed expired co2. 49 airway resistance by partially occluding the airway. More-
over, the catheter is not fixed in space and may cause injury
to bronchial mucosae if it whips within the trachea at high
CATHETER SHAPE
flows. Alternatively, the catheter can be placed outside the
In order to benefit from the distal turbulence produced by ETT along the trachea. This technique requires visualization
TGI, the catheter needs to direct the jet stream toward the of the vocal cords and d eflation of the ETT cuff and risks
periphery of the lung. 14 Inverting the catheter mouthward puncturing the cuff.
eliminates the distal effects and decreases C02 removal. In- New designs that incorporate channels within the
verting the catheter within the ETT, however, avoids direct- ETT wall would solve these problems a nd simplify TGI
ourr-
alt:e or
inject ion
Q ~,
.,
~·
to curr
trachea l e nd
A
8 c
FIGURE 24-13 The LaBrune-Boussignac endotracheal tube. A. Schematic of the entire tube with a mid tube cross section. B. Photograph of
th e tube. C. Photograph of the tube tip. (Used, witlr permission, fro m Adams: Respir Care 46:177-84, 2001.)
application. Boussignacet al 67•68 embedded small capillaries cessfully to provide selective TGI in experimental models
in the walls of an ETI for TGI (Fig. 24-13). The same group of AU.51,52
also has used this mocliiied ETI to deliver high-velocity jets The combination of as piration of anatomk and instru-
of 02 at the carina! orifice in order to prevent arterial 02 mental dead space in the late part of expiration and replace-
desaturation during suctioning. 69 Although lung volumes ment of the aspired volume with fresh gas through the in-
did not change during suctioning when 02 was delivered spiratory line of the ventilator improves C02 dearance? 4
in this fashion, the rate of increase in Paco, was similar to This aspiration system has allowed reductions in airway
that observed during apnea. The modified EIT can be used pressure and Vr while keeping Paco, constant in health~
to reduce the aggressive nature of mechanical ventilation humans/5 as well as in patients with ARDS76 and COPD.
in different clinical scenarios.7°· 71 Most likely, ft1 ture clinical The aforementioned aspiration system has the potential for
applications of TGI will use a mocliiied ETI that incorpo- avoiding the problems associated with jet streams of gas
rates the catheter in its wall attached to a standardized cir- or with gas humidification without developing auto-PEEP
cuit for gas delivery. In any case, application ofTGI should (Fig. 24-15).
never require reintubation of the patient.72
Kolobow et al 63 developed a reverse-thrust catheter that
directs gas flow from the distal to the proximal part of the Adjustments at the Bedside
ETT, creating a venturi effect (Fig. 24-14). Inverted flow is
INSPIRED OXYGEN FRACTION
less effective at expiratory flushing compared with straight
flow but has the advantage that it avoids hyperinflation. 64•73 The actual Frm during TGI depends on two factors: contri-
Finally, EITs for single-lung anesthesia have been used sue- bution ofTGI to total inspired VT and the Fr02 of the catheter
Endotracheal Tube lung-volume changes a t end expiratio n accura tely, suggest-
\ ing that tracheal pressures sh ould be monitored beyond the

jet stream during TGI. 14 During panexpira tory TGI, catheter
flow ceases during inspiration, and inspiratory Pao pro-
vid es as much useful information regarding Pa lv as dur-
ing conventional mechanical ventilation. In contrast, dur-
ing con tinuous TGI, inspiratory Pao (measured at the tip of
the ETT) d iffers from the tracheal pressure (Fig. 24-16). The
magnitude of this difference depends on the fl ow throug h
the circuit spanning the two pressure-measurem ent points
and is usually less than 3 cmH20. During expiration un-
der both continuous and expiratory TGI conditions, h ow-
Reverse Thruat Catheter- Expiration ever, catheter flow pressurizes the respira tory system, and
(RTC) as a result, Pao underestima tes tracheal pressure.61 During
expiration, the extent Pao under estimates tracheal pressure
FIGURE 24-14 The reverse-thrust catheter used for intratracheal increases with catheter flow rate and d epends on the geom-
pulmonary ventilation. Reverse-thrust cathete.r design allows gas etry of the system and the orienta tion of the catheter with
exiting the d istal end of the catheter to be directed cephalad. respect to the trachea .
(Used, with permission, from. Hess et al: Respir Care 46:U9- 29,
2001.)
EFFECT OF TGI ON LUNG VOLUME

gas. However, if the Fr02 of the catheter gas is matched to In bo th animal and human experiments, TGI increased FRC
that of the ventilator, the actual inspired Fr02 always will
in a flow-d ependent fashion.14•36 TGI can increase FRC
be identical to that delivered by the ven tilator. On the other in three ways. First, part of the momentum of the dis-
hand, if 100% 0 2 is used as the insufflated gas, the actual charging jet stream is tra ns ferred to the alveoli. 78 Second,
inspired Fr02 will be increased b y an a mount d etermined the catheter d ecreases the cross-sectional area o f the tra-
by the contributio n of TGI to to tal inspired Vr. This effect chea, increases expiratory resistance, and delays emptying.
will be most prominent during continuous TGI and will be Third, catheter flow throug h the ETT, expiratory circuit,
minimized during expiratory TGI. and expiratory valve can build up a backpressure tha t im-
ped es d efla tion and is the major detenninant of dynamic
hy perinflation? 9 Continuous TGI increased FRC more than
AIRWAY OPENING PRESSURE
expiratory TGI, es pecially when the inspiratory time frac-
During TGI, the jet stream increases flow throug h the vention was prolo nged. 79
tilator circuit during expira tion and creates a region where Dynam ic hyperinflation caused by TGI may present ei-
bidirectional flow s exist. Both effects change the resistan ce ther a problem or a therapeutic option39 and can be ma-
characteristics of the respiratory system and mod ify the nipulated by using an inverted-jet insufflator to achieve a
relations hip between airway o pening (Pao) and alveolar venturi effect.14,63 Monitoring d ynamic h yperinflation dur-
(Palv) pressures observed at baseline a t a catheter flow ing TGI requires a means of external lung-volume measure-
rate of 0 liter/ min. Because expira tory resistance increases ment such as impedance plethysmography. Guided by the
during TGI, Pao tends to underestimate Palv (and FRC) plethysmograph signal, ventilator-set PEEP can be adjus ted
when the system is switched from baseline to TGI condi- to maintain FRC constant as fl ow rate is v aried. 27•34 Alter-
tions. In a n experimental study, monitoring tracheal pres- natively, if the TGI system allows an end-expiratory hold
sure 2 em beyond the tip of the catheter seemed to predict maneu ver to be performed , the ventilator-set PEEP can be
90 FIGURE 24-15 Comparison between aspiration of

dead space (ASPIDS) and phasic tracheal gas
-
~ 70 -
so - insufflation (PTGI) during conventional mechanical
ventilation (CMV) and permissive hypercapnia
E60 (PHC) that was induced by d ecreasing tidal volume
- . .. .. -·
by 30% in patients with severe COPD. The mean
..Sso
.,..___
Paco 2 reductions with PTGI fi.o ws of 4.0 and 6.0
~ 40-
:l
1,/1
en 30 -
... .._ liters/min and during ASPIDS (at 4.0 liters/min)
were 32.7%, 51.8%, and 53.5%, respectively.
~ 20 - Auto-PEEP in creased with PTGT but not with
a.. ASPIDS. (Used, w ith pennission, from Liu et a/:
10 - Respir Care 49:257-62, 2004.)
0
CMV PHC PTGI-4 PTGI-6 ASPIDS
A PCV vcv
with TGI
with TGI
I
0.6 0.6
-• u
0.4
0.2
I -:
u
0.4
0.2
fl 0.0 0.0 Flow at

-
::J
~ -0.2
-
::J
~
0
-0.2 lung model
ii: ii:
-0.4 -0.4 no TGI
-0.6 -0.6
-0.8 -0.8
0.8 0.8
-•¥ 0.6 ¥0.6

with TGI 1sec Flow at
::J with TGI ::J inspiratory
- o.4 -; 0.4 J
~ limb
/noTGI .!i!
i&: 0.2 ll. 0.2
0.0 0.0
8 PCV vcv
60 60
50
with TGI
with TGI
~40
!!
I Palv
30
:J
!• 20
Q.
10
noTGI
06------------------------
with TGI
with TGI
\
\ Pao
10
noTGI
oL-------------------- oL--------------------
FIGURE 24-16 A . Flow-versu s-time tracings of delivered gas flow measured both at airway opening and distal to the entr ance of tracheal
gas in sufflation (TGI) during boUt pressure-controlled ventilation (PCV) and volume-controlled ventilation (VCV) with and without the
addition of 12 liters/min TGI in a lung model. B. Pressure-versus-time tracings of sys tem p ressure measured both at the airway opening
(Pao) and distal to the entrance of the TGI flow (Palv) during boUt PCV and VCV with and without the addition of 12 liters/min of TGI
flow in a lung model. Regardless of wheU1er VCV or PCV was used, continuous TGI increases Pao and peak carina! pressure (B). In
association with these changes there is an increase in tidal volume. During VCV (A), the flow from TGI is additive to the flow from the
ventilator. During PCV, the addition of the TGI flow caused the flow from the ventilator to decelerate more rapidly; once ventilator flow
reached zero, a squarewave flow pattern derived entirely from the TGI system persisted. (Used, witlt permissiou, from Kacm arek: Rcspir
Care 46:167- 76, 2001.)
CHAPTER 24 TRANSTRACHEAL GAS INSUFFLATION 53 7
adjusted to maintain total PEEP cons tant. 40' 80 Alternatively, TG I-VE NTILAT OR INTERACTIONS
during PCV, a flow-relief valve automatically compensates
The interactions between TGI and ventilator mode, VT, and
for the extra gas that is introduced into the system by TGI
Pao that result in development of auto-PEEP deserve men-
and eliminates the need to make ventilator adjustments to
tion. During volume-controlled ventilation, when ventila-
control total PEEP.81
tor PEEP is left constant, VT remains constant, but there
is an increase in end-expiratory pressure and Pao because
of TGI-induced auto-PEEP. During PCV, when ventilator
TIDAL VOLUME PEEP and peak airway pressure are kept the same as base-
Catheter flow delivered during inspiration contributes to line, VT excursions (and hence minute ventilation) are re-
total inspired VT. This contribution is eliminated if TGI is duced because ofTGI-induced auto-PEEP. When ventilator
timed to occur only during expiration. 20 Even in this case, PEEP is reduced by an amount equivalent to TGI-induced
however, decompression of the TGI circuit within the venti- auto-PEEP, VT, peak airway pressure, and total PEEP re-
lator circuit during the inspiratory phase of solenoid closure main tl1e same as baseline during PCV40•65 (Fig. 24-17).
contributes to total inspired VT. 27 In most TGI circuits, how- During CPAP delivered by a mechanical ventilator in
ever, this volume is rather small (about 10-20 ml at a catheter combination with TGI, additional inspiratory effort is re-
flow rate of 10 liters /min). These problems are obviated if quired to overcome the insufflation flow a nd trigger the
an independent measure of VT such as inductive plethys- ventilator valves. Bench studies have found thatTGI might
mography is used. The effect of TGI on total inspired VT interfere with ventilator triggering at low peak inspiratory
depends on the ventilator operation mode. flow rates, and this suggests that weak patients may fail
to open the demand valve at high catheter flow rates83
(Fig. 24-18).
FLOW- CONTROLLED, VOLUME- CYCLED

VENTILATION
Monitoring and Troubleshooting
During continuous TGI, total inspired VT is the sum of two
components: that delivered by the ventilator and that deliv- TGI is a simple and apparently safe method of reducing
ered by the catheter (VTc). The contribution of continuous both minute ventilation and Paco2 • Regardless of the ap-
TGI to total inspired VT can be estimated from the volume proach used, TGI has the potential to alter volumes as well
of gas that is insufflated by the catheter during inspiration. as airway and alveolar pressures; careful monitoring of de-
Consequently, during flow-controlled, volume-cycled ven- livered volumes and pressures tl1erefore is necessary to en-
tilation, total inspired VT can be maintained relatively con- sure safe clinical application and to evaluate the effect on
stant during continuous TGI by decreasing the ventilator-set lung function. Moreover, the position of the TGI catheter
VT by that amount. 27•44 within the ETT should be controlled carefully. The presence
of a catheter inside the ETT may increase both inspiratory
and expiratory resistances, particularly when small endo-
tracheal or tracheostomy tubes are used?·1S· 32·84,ss
PRESSURE- CONTROLLED VENTILATION
Because TGI introduces an external flow source indepen-
During pressure-controlled ventilation (PCV), TGI applica- dent of the ventilator, it can adversely effect the ventilator's
tion does not change the total inspired VT, provided that TGI ability to monitor pressures and volumes and may cause
does not pressurize the respiratory system beyond the set the ventilator alarm to go off incessantly. The presence of
pressure. As catheter flow rate is increased, the ventilator- catheter flow during expiration disables the monitoring role
delivered VT declines, but the total inspired VT remains the of the ventilator's expiratory pneumotachograph, trigger-
same.27. 60 The respiratory system behaves in this manner ing som e ventilator alarms when the difference between the
as long as catheter-delivered VT is less than the VT gen- measured inspired and exhaled volumes exceeds a certain
erated by the set pressure under PCV conditions without value. More important, the presence of an external flow that
TGI. IfVTc exceeds the VT generated by PCV in the absence can pressurize the ventilator circuit interferes with the ven-
of TGI, then TGI will overpressurize the circuit, and peak tilator's ability to detect a leak. Using the end-expiratory oc-
Pao will be greater than that produced by the ventilator- clusion technique to measure auto-PEEP may increase lung
set pressure. Almost all ventilators allow pressures higher volume dramatically if TGI flow is not interrupted simul-
than that generated by the set pressure as long as Pao re- taneously. The same effect will occur "\o\ri.th continuous TGI
mains below the high-pressure limit of the ventilator. Con- during end-inspiratory occlusions. 7~ 32
sequently, excessive pressures can be produced within the Tracheal gas can be delivered throughout the res piratory
respiratory system if VTc is too large. When this happens, cycle, throughou t expiration, or only during a specific por-
the Pao-time profile becomes a hybrid ofPCV and constant- tion of the expiratory period. Continuous-flow TGT is the
flow volume-cycled ventilation, resembling that generated easiest method to implement but has the g reatest poten-
during volume-assured pressure-support ventilation. This tial to cause complications. Continuous-flow TGI could in-
problem can be circumvented by introducing a pressure- crease delivered VT, airway and alveolar pressures, and to-
release valve into the ventilator circuit that dumps circuit tal PEEP with both PCV and with VCV. Moreover, in PCV,
pressure above a set threshold.s2 when ventilator flow reaches zero, continuous flow from
Volume Control
r Pressure
Peak Baseline Control Adj usted TGI
Inspiratory
Pressure
End-
Expiratory
Pressure
I'EEP..,.
TGl=O TGI = 10 Llmin TGI = 10 L/min
FIGU RE 24-17 Theoretical framework that illustrates interactions between tracheal gas insufflation (TGI), ventilator mode, minute
ventilation (ti dal volume), and auto-PEEP. During volume-controlled ventilation, when ventilator PEEP is left constant, ti dal volume
(black bars) remains constant, but there is an increase in end-expiratory pressure and, con sequently, in pea.k inspiratory pressure. During
pressure-controlled ventilation, when set PEEP and peak airway p ressure are kept the same as baseline, tidal volume excursions are
reduced because of TGI-indu ced auto-PEEP. When set PEEP is reduced by an amount equivalent to TGI-induced auto-PEEP, tidal volume,
peak airway pressure, and total PEEP remain the same as baseline during pressure-controlled ventilation. (Used, w ith pennissiou, f rom
Delgado eta/: Respir Care 46:185- 92, 2001.)
the continuous TGT increases Vr and airway pressures. A tine measurement of Pete~ during TGTas a marker of its
similar phenomenon occurs during end-inspiratory pauses effectiveness35, 36A 5 •48 (Fig. 24-19).
in VCV. These increases occur because the exhalation valve
of the ventilator is not active during the inspiratory phase. 25
Overpressurization can be identified by examining the air- Important Unknowns
way pressure tracing18 and can be remedied by placing a
pressure-relief valve in the ventilator circuit to dissipate in- The effect of different gas mixtures (helium and oxygen)
sufflated flow that produces excess pressure.57,86 A com- during TGT has been studied in patients with respiratory
plete obstruction of the outflow can cause overinflation of failure.89 Helium is an inert gas that has a much lower den-
the lungs in seconds, with the potential for pneumothorax sity than oxygen or air. When given at tl1e same flow rate as
or hemodynamic compromise. a nitrogen-oxygen mixture, a helium-oxygen mixture pro-
TGI also may interfere with the clinician's ability to mea- duces a much lower Reynolds number and laminar flow.90
sure lung mechanics. Respiratory system compliance and TGI with helium seems to be more effective than TGI with
auto-PEEP measurements require a pause at end inspira- oxygen in treating hypercarbia because the use of helium
tion and I or at end expiration. If catheter flow persists dur- leads to a smaller increase in airway pressure accompany-
ing these measurements, the pressure within the respiratory ing the decrease in Paeo 2 . 89 Because the combination helium
system builds up with time. Consequently, a plateau pres- and oxygen for TGI has the potential to decrease Pam , pre-
sure caru1ot be reached, and alveolar pressure can increase cautions in the use of helium should be taken, particularly in
to hazardous levels if unnoticed. During panexpiratory TGI, patients who require high Fr02 values to provide adequate
depending on the timing and nature of the signal that gates oxygenation.
the solenoid to divert catheter flow to the atmosphere, these The delivery of catheter gas at higher flows needs to be
measurements still can be made safely. Nevertheless, it is ad- examined with regard to the need for humidification and
visable to test the TGI-ventilator system using a mechanical the potential for tracheal damage with long-term use. Only
lung model w1der controlled conditions before measuring limited data are available on tl1e clinical safety of TGI.
lung mechanics at the bedside. Application of TGI using a large-caliber reverse-thrust
The efficacy of TGI can be monitored by capnography catheter resulted in no damage to tracheobronchial mucosa
(see Figs. 24-11 and 24-12). Expiratory capnograms provide when minute ventilation was adjusted to achieve a simi-
an indicator of the effect of TGI on the C02 concentration lar level of gas exchange during intratracheal pulmonary
of the gas remaining in the proximal anatomic dead-space ventilation to that achieved with conventional mechanical
compartment at the onset of inspiration.36A 5•48 Although ventilation. 64•91 A similar experiment, however, performed
Pete~ is a poor estimate of Paeo2 87•88 in patients with res- in different species and lasting several hours was associated
piratory failure, changes in Petcm induced by TGI corre- with a significantly greater difference in tracheobronchial
late significantly with changes in Pac~ and justify rou- damage at the carina and main bronchus.62 Turbulent
-.....
-
0.20
0.15
Vc (llmln)
15
Servo 900C
0
..
~
s
0.10 -
-5
•• •
10~ • •
i
0.05 ('(
~
0 .00 2~5
0
0 -10
0
II
C1.
• •••
<l -15 •
0.20
0~
•
-
::::
0.15 15
Evita -20 r =0.68 • ••
3 0.10
~
•
:s 0.05 10 -25
~ 0 0.2 0.4 0.6 0.8 1.0
0 .00 5
2.5
0 ~ PuC02 / PerC02baae
FIGURE 24-19 Percentage reduction in arteria.! Pco2 (Paco 2 ) from
baseline as a function of the reduction in partial pressure of
0.20 end-tidal Pco 2 (Petco 2 ) from the baseline value <Petco2 ,base). As
the difference between Petco 2 and Petco,,b••• widened, larger
-..,-
0 ::
0.15
0.10
15 PB 7200 reductions in arterial Pc0z were observed. (Used, witl1 penuission
from Raveuscraft eta/: Am Rev Respir Dis 148:345-51, 1993.)
l 0.05
10 Future TGI systems for clinical aprlications ideally should
~
0.00 5 include a number of fea tures. 32, 6 ,9i First, intimate coor-
2.5
0 dinatio n with the ventilator is m andatory. This could be
accomplished by either a built-in or external device for
0 20 40 60
triggering and breath delivery. Moreover, safety and motu-
v pk (lfmln) taring capabilities must include an a utomatic TGiflow shut-
FIGURE 24-18 Work of triggering (W-trig) measured from the off to prevent overpressurization of the ventilator circuit and
respiratory muscle compartment (ben ch ) connected to a venti lator airways,82•86 as well as to display precise volume and pres-
(RM-ven tilator) for three demand-flow continuous positive sure measurements. Finally, ideal TGI catheters should form
airway pressure systems at catheter flow rates ('V c) of 0, 2.5, 5, 10, part of the artificial airway and be made available commer-
and 15 liters/min expressed as a function of peak flow ra te ('Vpk) cially.
of the RM-ventilator. None of the ventilators were triggered using
a Vpk and a Vc of 20 and 15 1iters/min, respectively. (Used, w it ll
permissiou, from Hoyt et al: C11est 110:775-83, 1996.)
Summary and Conclusion
conditions promote shear stress, increased gas impact on TGI is a promising complementary technique to mechanical
the walls of the airway, and the transfer of a higher ki- ventilation. TGI is very effective during permiss ive hyper-
netic energy to the tracheal mucosa.78•92 The end-hole TGI capnia in patients w ith ARDS, diminishing the complica-
catheter mode could, in theory, cause more airway dam- tions associated with both mechanical ventilation and res-
age than large-caliber reverse-thrust catheters because the piratory acidosis. Furthermore, some studies suggest that
flow exiting the end-hole catheter is closer to the carina and TGI-aided weaning may allow a reduction in the patient's
points directly at it. Further studies in patients a re needed respiratory demands. Further studies, however, including
to assess clinical safety.93 Until this information is available, randomized trials in patients receiving mechanical ventila-
all TGI techniques should be considered investigational. tion or with weaning difficulties, are necessary to improve
technical problems and to demonstrate the clinical benefits
and absence of adverse effects of TGI before this technique
The Future can be employed routinely in intensive-care units.
TGI should be weighed against therapeutically proven, cur-
rently available invasive and noninvasive modes of ventila-
tion. Evidence dem onstrating better patient-ventilator inter- Acknowledgment
action with TGI and tl1e absence of significant TGI-related
adverse effects needs to be accumulated before TGI can This work was supported by Fondo de Investigaci6n Sani-
be considered suitable for standard intensive-care practice. taria (FIS) G03/063 Red-Gira.
540 PART VTI UNCONVENTIONAL METHODS OF VENTILATOR SUPPORT
22. Lethvall S, Sondergaad S, Karason S, et al. Dead-space reduction

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PART VIII Bronchopulmonary Dysplasia in the Preterm Baby
Ventilator-Associated Pneumonia
IMPORTANT UNKNOWNS
VENTILATOR SUPPORT THE FUTURE
SUMMARY AND CONCLUSION
IN SPECIFIC SETTINGS
Respiratory disease in its various forms remains tl1e most
common cause of pediatric and neonatal morbidity and
Chapter 25 _ _ _ _ _ _ _ __ _ mortality. One of the most common reasons for admission
to an intensive-care unit (lCU) is the need for mechanical
MECHANICAL ventilation for acute or impending respiratory failure. Res-
piratory failure, characterized by inadequacy of oxygena-
VENTILATION IN THE tion and/ or ventilation, can occur as a result of airv.ray
and lung disease, cardiac dysfunction, multiorgan failure,
NEONATAL AND neurologic and neuromuscular disorders, or the effects of
surgery and/or cardiopulmonary bypass. Pediatric respi-
PEDIATRIC SETTING ratory failure is divided in two major pathophysiologic en-
tities: ltmg failure and pump failure. Primary hmg failure
PETER C. RIMENSBERGER can result from multiple causes, including pneumonia, in-
JUERG HAMMER halational injury, near-drowning, hemorrhage, aspiration,
and chest trauma. Pump failtm can result from upper air-
way obstruction, cardiovascular dysfunction, or systemic
septic disease characterized by increased work of breathing
that may lead, especially in the newborn and small child, to
respiratory fatigue; it also can result from neurologic injury
UNIQUE PATHOPHYSIOLOGY or neuromuscular disease. Such patients may require me-
Upper Large Airways: Anatomic and Functional chanical ventilation not only for hypoventilation but also
Considerations for airway protection.
Small and Peripheral Airways: Anatomic and The three major indications for mechanical ventilation
Functional Considerations in the pediatric and neonatal field a re to improve gas ex-
Static Properties of Lung and Chest Wall change, reduce work of breathing, and secure the upper
Pertinent Pulmonary Mechanics for Pediatric airways. Common objectives of ventilation are
Ventilation
CONSIDERATIONS PECULIAR TO NEONATES 1. To support or manipulate gas exchange by improv-
Circulatory Changes Pertinent to Ven tilation ing alveolar ventilation in order to achieve acceptable
Oxygen Transport oxygenation
Control of Breathing 2. To restore or maintain adequate functional residual ca-
DO VENTILATOR GOALS DIFFER BETWEEN pacity (FRC) in order to prevent or r eopen a tel ectasis and
INFANTS AND CHILDREN? improve oxygenation and lung compliance
COMMON CLINICAL CON DITIONS 3. To reduce work of breathing in the presence of high
Neonates airway resistance and/or reduced compliance, whicl1
Pediatric Patients causes ineffective spontaneous breathing
COMMON VENTILATOR MODES
CPAP in Neonates
Conventional Ventilation in Neonates and Infants The aim of mechanical ventilation is not only to sup-
Patient-Triggered Ventilation port impaired vital function and maintain adequate gas
Nonconventional Modes: exchange. It is also to provide time for resolution of the
High-Frequency Ventilation underlying disorder without adding further injury by
WEANING FROM MECHANICAL VENTILATION the ventilator. The respiratory s trategy takes into account
Correct Timing of Extubation the type and severity of tl1e underlying pathology, the clin-
Weaning Modes and Adjuncts to Weaning ical condition (e.g., neuromuscular weakness), and the age
UNIQUE NEONATAL AND PEDIATRIC [i.e., for age-specific pailiologies and conditions such as
MACHINES AND INTERFACES neonatal respiratory d istress syndrome (RDS) or bronchi-
High-Frequency Ventilators olitis in infants a nd toddlers).
Airway Humidification Systems Despite worldwide daily use of mechanical ventilation
MONITORING OF MECHANICAL VENTILATION in pediatric and neonatal ICUs, many questions are un-
COMPLICATIONS OF MECHANICAL resolved, and answers often are extrapolated from adult
VENTILATION studies. The latter may seem sensible for older children
Postextubation Stridor but not for infants and toddlers, in whom age-specific
543
544 PART Vill VENTILATOR SUPPORT IN SPEOFIC SETTINGS
FIGURE 25-1 Bronchograph y in patient with

tracheobronchomalacia withou t application of
positive airway pressure (left) and with 10 cmH2 0
of positive airway pressure (rigllt). Application of
positive airway pressure produces stenting of the
trachea and bronchial tree. (Courtesy ofQueeu Mok,
Great Ormoud Street Hospital for Children, United
K i11gdom.)
considerations of function and physiology in the develop- SMALL AND PERIPHERAL AIRWAYS: ANATOMIC
ing respiratory system have to be taken into account. AND FUNCTIONAL CONSIDERATIONS
In the presence of intrathoracic airway obstruction (e.g., tra-
Unique Pathophysiology cheobronchomalacia or asthma), the pressure within the air-
ways above the site of obstruction (during expiration) be-
Physiology of the respiratory system differs among babies, comes lower than pleural pressure. This predisposes the
children, and adults in a number of important res pects. compliant airways of children to collapse. Such expiratory
First, infants and small children have less respiratory re- flow limitation produces wheezing, prolonged expiratory
serve than adults and are prone to respiratory failure dur- times, and air trapping with dynamic hyperinflation. PEEP
ing any critical illness of pulmonary or nonpulmonary ori- may help to stent collapsing airways during expiration
gin. Second, some differences in the anatomic structure in some patients'~ (e.g., those with tracheobronchomalcia;
of the airways and respiratory mechanics of the respira- Fig. 25-1); in other patients who have dynamic hyperinfla-
tory system among infants, children, and adults must be tion without expiratory flow limitation, PEEP may lead to
stressed. further air trapping?
In infants and children up to about 6 years of age, the
small airways account for up to SO% (compared with about
UPPER LARGE AIRWAYS: ANATOMIC AND 20% in adults) of total airway resistance.3 Therefore, dis-
FUNCTIONAL CO NSIDERATIONS eases affecting predominantly the small airways, such as
viral bronchiolitis, can cause a significant increase in total
Infants are thought to be mainly nose breathers because airway resistance and work of breathing and may lead to
the large omega-shaped, soft epiglottis, positioned high in severe r espiratory failure in children.
the larynx (at the level of C4 in the infant versus C6 in the
adult), tends to obscure the laryngeal inlet. Partial or com-
STATIC PROPERTIES OF LUNG
plete occlusion of the nasopharyngeal airway (congenital or
AND CHEST WALL
acquired) may increase work of breathing and contribute to
respiratory failure. The ribs in infants are aligned horizontally, allowing for
The narrowest part of the infant airway is not the laryn- less anteroposterior movement during respiration and ren-
geal inlet (vocal cords) but the cone-shaped cricoid cartilage dering the intercostal muscles less efficient than in adults.
in the subglottic region. Any decrease in airway diameter-- Breathing is primarily diaphragmatic. The combination of a
acquired or congenital- results in a dramatic increase in soft and compliant chest wall and predominant diaphrag-
airway resistance in infants because resistance is inversely matic breathing can cause two specific pathologic condit-
related to the fourth power of the radius. ions: (1) rapid and sometimes serious impairment of breath-
The cross-sectional area between the vocal cords is ing efficiency (in the case of abdominal distension) and
widened during inspiration and narrowed during expira- (2) inward distortion of the rib cage and waste of en-
tion. This narrowing allows infants to brake flow during ergy through sucking in of the ribs rather than of air, as
expiration. By this action, infants can generate intrinsic pos- manifested by paradoxical thoracoabdominaJ movements.
itive end-expiratory pressure (PEEP) (grunting) to stabilize The latter is a typical sign of upper airway obstruction.
their cartilaginous, relatively elastic and flaccid chest, which This renders breathing less efficient because chest-wall dis-
has a tendency to collapse. tortion represents a pressure-induced change in volume,
CHAPTER 25 MECHANICAL VENTILATION IN THE NEONATAL AND PEDIATRIC SElliNG 545
100 100
I ,. ,..-" I
I
I
I chest wall , / /
ches wall:
I
80 I " I
/
80 I
I
I I I
60
:t=
c
::;)
I
I
I
I
I
I
I
I
60
-
·c:::;)
I
I
I
I
c:- I
I
I
>- I
I
Newborn (a
Adult
ctl
~
:t=
..0
(a I
I
I
I
I
I
I
-
:0
~
~
ctl I
I
I
I
40 I 40
~
0 I I
I
0~ FRC
I I
f
20 FRC 20
I
/. I
I ung lung
o~a_~~~~~~~~~~ o~~~--L-~~--L-~~--L--L~~L-~---
_10 0 10 20 30 40 -40 -30 -20 -10 0 10 20 30 40
FIGURE 25-2 Characterisitcs of lun g and chest-wall mechanics in newborns compared with adults. The compliant chest wall in the
newborn leads to lower functional residual capacity in the newborn. (Adapted, with permissiou, from Agostiui: I Appl Pltysio/14:909- 13,
1959.)
constituting a form of work with an energy cost; this is tant elements are elastic recoil, compliance, resistance, and
thought to be one reason for poor weight gain and devel- time constant.
opment of fatigue in infants recovering from respiratory
distress syndrome (RDS). 4 ELASTIC RECOIL
Static and elastic properties of the respiratory system The newborn has a low elastic recoil of the cl1est wall be-
cl1ange with maturation and the state of health (Fig. 25-2) . cause it is nonossified and has low total muscle mass, with a
In infants, the chest wall generates little outward recoil low percentage of slow-muscle fibers in both the diaphragm
compared with adults, whereas inward recoil of the lungs and intercostal muscles. Very little airway pressure
varies little with respect to size and age. Therefore, the rel- therefore is needed to expand the chest wall during in-
axation volume of the thorax is smaller than in the adult, spiration; this explains why muscle relaxation is rarely
resulting in a lower FRC in the infant (around 15% of vital needed in the yotmg infant during (nonassisted) controlled
capacity compared with 35% in the adult). This imposes a ventilation.
clear disadvantage in terms of alveolar stability, making the The major force contributing to elastic recoil in the new-
infant more vulnerable to changes in muscle coordination born is surface tension at the air-liquid interface in distal
and tone during rapid-eye-movement (REM) sleep, anes- bronchioli and alveoli. As described by LaPlace's law (P =
thesia, sedation, or central nervous system depression. 2T / r), the pressure (P) needed to counteract the tendency of
Whereas the volume-pressure relationship of the lungs bronchioli to collapse is directly proportional to the surface
is similar in infants and adults, the volume-pressure tension (T) and inversely related to its radius (r). A decrease
relationship of the chest wall is much s teeper in the infant. in surface tension in s urfactant deficiency states (infant RDS)
Relatively large changes in intrathoracic pressure therefore or after inactivation of surfactant [acute respiratory dis-
are accompanied by only small variations in chest-wall pres- tress syndrome (ARDS)) results in decreased stability of the
sure. Consequently, large changes in ventilator pressures small terminal air ways and alveoli, producing a tendency to
have only a limited effect on pleural pressure. This explains collapse.
the generally high cardiovascu Jar tolerance of infants to the
application of high airway pressures. COMPLIANCE
The tidal volume (VT) necessary to acl1ieve a given in- Lung compliance is very low (3.5 ml/cmH2 0) at birtl1
crease in airway pressure is less in a small person than in a and increases rapidly during the first week to about
large person. Thus noncorrected compliance values of the ~ ml/cmH 2 0 (corresponding to about 1.5-2 ml/cmH20
respiratory system cannot be compared between infants and per kilogram of body weight) in the full-term infant. Re-
adults. Correction is commonly made to body weight. It is duced lung compliance is seen in neonates with congenital
better to correct to a unit of lung volume, however, such as pathologies characterized by s mall lung volumes (e.g., con-
FRC. Thus specific s tatic compliance (Cst/FRC) is compa- genital pulmonary hypoplasia and diaphragmatic hernia),
rable between adults and children independent of age and with primary or secondary surfactant deficiency (e.g., RDS
disease stage. and congenital pneumonia), with restrictive lung disease
(including ARDS and viral or bacterial pneumonia), w ith
bronchopulmonary dysplasia (BPD; often a combination of
PERTINENT PULMONARY MECHANICS FOR restrictive and obstructive lung disease), or after correction
PEDIATRIC VENTILATION
of congenital diaphragmatic hernia. Reduced compliance
A basic understanding of pulmonary mechanics is neces- also can be seen in obstructive lw1g disease combined with
sary when ventilating an infant or child. The most impor- high lung volumes, such as asthma and broncl1iolitis.
546 PART Vill VENTILATOR SUPPORT IN SPECIFIC SETTINGS
RESISTANCE 20
Airway resistance in spon taneou sly brea U1ing infants is nor-
.,... __
0
;;,
mally 20-30 cmH20/liter per second; values in intubated f~

c.. :I:
infants are 50-150 cmH2 0 / liter per second, consequent to >-E
~u
a narrow endotracheal tube (ETD.5 For many years it was ! .....
:¢
thought that small infants could not breaUle spontaneously
0
through a small ETT (because of high resistance imposed 0 1 2
by the small lumen), but this view is no longer maintained.
Under nom1al tidal-flow conditions, resistance imposed by 20
a small tube is not substantially higher than that with larger
tube.
~
-:::0 .-
T
tidal volume
O..J
Clinically, an increase in airway resistance is manifested
by retractions of the soft tissue, contractions of accessory
>01 .....
c:
E
j_
:::0
muscles, and active participation of the abdominal muscles ..J
0
during expiration. 0 1 2
TIME CONSTANT 3
An understanding of tinle constant, Ule product of lung
compliance and airway resistance, is inlportant when ven-
tilnting infants and children, especially at high respiratory
frequencies. If lung compliance is decreased (RDS or ARDS)
and resistance is nom1al or only slightly altered, the time
constant, and the corresponding time for pressure equilib-
rium between proximal airways and the alveolar space, will
be shorter than for healthy lungs. Therefore, high respira-
tory frequencies leading to short inspiratory times (T1) may
be appropriate when RDS or ARDS is at peak severity. Dur-
ing recovery from RDS or ARDS (increasing compliance), ·3
however, high ventilator rates can lead to two major prob- FIGURE 25·3 Pressure, volume, and flow curves illustrating the
lems. Firs t, insufficient T, rna y limit delivery of an adequate phenomenon of alveolar gas trapping. Note that both inspiratory
volume. 6•7 Second, excessively short expiratory times (TE) and expiratory times are so short that flow does not decay to zero.
will not allow complete emptying of peripheral airspaces As a result, the tidal volume is less than it would be if complete
at end expiration (as indicated by the absence of expiratory inspiration and expiration were pemtitted. CRepril1ted, wit/1
flow termination before the next inspiration), with the risk permission, from Clmtbum: Respir Care 36:580, 1991.)
of generating intrinsic PEEP (Fig. 25-3).
Long time constants (slower filling and emptying) can
be seen in diseases characterized by increased airway resis- effectiveness of the respiratory pump. Other characteristics
tance (e.g., BPD, bronchiolitis, or asthma), and low respi- include circulatory changes after birth, special features of fe-
ratory rates should be selected. In some pathologies (e.g., tal hemoglobin (HbF) when considering oxygen (02) trans-
meconium aspiration) that can exhibit both obstntctive and port, and control of breaUung.
restrictive features, careful adaptation of frequency and
inspiratory-expiratory (l:E) ratio will be necessary in some
patients. An intervention that improves compliance (e.g., CIRCULATORY CHANGES PERTINENT
surfactant treatment or lung-recruitment maneuvers) pro- TO VENT£LATION
duces a longer time constant by inlproving compliance.s- lo Aeration of the lung must be matched to perfusion for satis-
Therefore, respiratory rates, especially expiratory times, factory gas exchange. Before birUl, only about 10% of blood
may need rapid adjustment, in addition to adjusting airflow passes through the lungs as a result of high pulmonary
way pressure. This must be taken in account when ventilat- vascular resistance, patent ductus arteriosus, open foramen
ing infants and small children at any stage of an evolving or ovale, and the low-resistance placental component to the
resolving lung disease. Thus use of fixed high rates (lead- systemic circulation. After birth, clamping of the umbili-
ing to relatively shortT, and T E values), which has become cal cord removes the low systemic resistance, and aeration
commonplace since the advent of small VT ventilation, is of Ule lungs leads to opening of the pulmonary capillary
not always appropriate. bed with consecutive reduction in pulmonary vascular re-
sistance. The increase in left-atrial pressure (by increased
pulmonary venous return) and Ule reduction in right-atrial
Considerations Peculiar to Neonates pressure (by reduced systemic venous return) lead to clo-
sure of the foramen ovale. Blood oxygenation lowers pul-
The neonate is not a small adult. Specific characteristics monary vascular resistance and initiates ductus closure. Al-
include (1) small and soft upper and lower airways, (2) though pulmonary vascular resistance falls rapidly in the
compliant chest wall and a low FRC, making the neonate first minutes oflife, it is still elevated and falls only gradually
susceptible to airway collapse and atelectasis, and (3) poor to normal levels over days to weeks. During Ule first days
CHAPTER 25 MECHANICAL VENTILATION TN TT rE NEONATAL AND PEDIATRIC SEl liNG 547
TABLE 25-1 Ma in Determ inants o f Pulmonary Vascul ar activated by various nonspecific factors (e.g., REM sleep,
Resista nce arousal, temperature, and pain), chemoreceptors, and
mechanoreceptors of the lung and chest wall. Function of
Increase in Pulmonary Decrease in Pulmonary
Vascular Resistance Vascular Resistance these components may be impaired when maturation is
not complete.
High interstitial pressure Low interstitial pressure Brain-stem neurons undergo rapid maturation between
High lung volumes (alveolar Normal lung volumes 30 weeks of gestation and term. 15 Accordingly, preterm in-
overdistension) fants are subject to "physiologic apnea." When this is asso-
Low lung volumes (atelectasis) ciated with recurrent severe bradycardia and hypoxemia,
Low Pa~ - alveolar P~ High P~ -alveolar P~ continuous positive airway pressure (CPAP) or intubation
Low arterial pi I High arterial pH
and mechanical ventilation may be necessary.
Carbon dioxide (C~), through its effect on brain-tissue
and weeks, the pulmonary circulation is therefore unstable. pH, is the major metabolic respiratory stimulant in neonates
Under certain circumstances (e.g., birth asphyxia, chronic and adults. Tn pretem infants, a decreased response to hy-
hypoxia, or neonatal septicemia wiU' or without metabolic percapnia, which improves with postconceptional age, is
acidosis), pulmonary vascular resis tance increases or re- observed often. 11; This fact may account for hypercapnia
mains high, leading to right-to-left shunting through the during quiet breathing in the absence of tmderlying lung
ductus arteriosus and sometimes even thr ough the fora- disease or sedatives.
men ovale. This persistent pulmonary hypertension of the In contrast to hyperventilation in infants, children, and
newborn (PPHN) leads to poor systemic oxygenation, as re- adults 17 (Fig. 25-4), hypoxem ia induces respiratory depres-
vealed by low postductal transcutaneous saturation levels sion in the newborn that may lead to apnea. This phe-
(e.g., lower limbs and left upper limb) or desaturation of all nomenon is best explained by the presence of brain-stem
four extremities when the right-to-left shunt at u,e level of inhibitory reflexes in the fetus that prevent breathing in
the foramen ovale is important. In this situation (poor oxy- utero.18 As a result, u,e brain-stem response to carotid affer-
genation because of an extrapulmonary shunt), a low arte- ent stimulation is still altered after birth.
rial 0 2 tension (Paoz) cannot be overcome by administration Feedback from vagal stretch reflexes, rib-cage muscles,
of high 0 2 concentrations, although supplemental ~ may and the changing mechanical state of the respiratory sys-
be useful in lowering pulmonary vascular resistance. High tem during each breath influence respiratory activity. If in-
inflation pressures to recruit lung volume and improve oxy- flation is small, there is less inhibitory vagal feedback. In-
genation should be used with caution because of the risk of spirato ry activity of the next breath increases to overcome
increased pulmonary vascular resistance by overdistension the increased respiratory load. If inflation is excessive, in-
and compromised cardiac output. First-line treatment is di- spiration is inhibited. This inspiratory-inhibitory reJlex, the
recting toward known determinants of pulmonary vascu- Heri11g-Breuer i11flntio11 reflex, is potent in the newborn and
lar resistance (Table 25-1) such as acidosis or high interstitial infant during the first weeks of life19 and may persist for
pressures. Second-line therapy includes specific pulmonary longer in preterm babies. 20 This inflation reflex facilitates
vasodilators, such as nitric oxide (N0), 11 - 13 after excluding passive measurement of respiratory mechanics (e.g., airway
congenital heart disease with duct-dependent systemic cir- occlusion technique) without a paralytic agent.
culation, which may d eteriorate when pulmonary vascular Conversely, the increased ability of infants to adjust
resistance is lowered (e.g., total anomalous pulmonary ve- to increased inspiratory load during s upport with CPAP
nous return or hypoplastic left heart syndrome).14 suggests a diminished Hering-Breuer reflex. 21 This reflex
OXYGEN TRANS PORT FIGURE 25-4 Age-related response to the b reathing of hyp oxic
gases for 5 minu tes. (Adapted, with permissiot~, from
Fetal hemoglobin (HbF) is the predominant type of Hb at
He11dersou-Smnrt: Regulnf'iou of breathiug iu tire periuatal period.
birth. It decreases steadily over the first 6 months, with adult lu: Snrmders NA, Sullivnu CE, editors. Sleep nud breatlriug: Lmrg
hemoglobin (HbA) predominating after about 3 months. biology i11 lrenltlr nud disease, Vo/20. New York: M arcel Dekker,
2,3-diphosphglycerate (2,3-DPG) has a lower affinity to HbF 1983: 605-647.)
and shifts the dissociation curve to the left, resulting in
higher 0 2 affinity and a lower P50 (P0 2 at which Hb is 50% +
,.-- - - - -- - - - Adults
saturated). This left shift facilitates loading and unloading rn ~--------- Infants
of~, ensuring, together with the high Orcarrying capacity t:
0
ofHbF, adequate tissue oxygenation despite low Po. values
in utero (15-30 mmHg). The predominance of HbF makes it ~
possible, if necessary, to tolerate lower P<>z values (but not
e>o
c:
reallySa02) more in early postnatal life than is possible later
·-
Term
in life.
Preterm
CONTROL OF BREATHING
Control of breathing depends on the interaction of brain· 0 1 2 3 4 5
stem centers, the reticular activating system that can be minutes
548 PART Vlll VENTILATOR SUPPORT IN SPECIFIC SETTINGS
activity also may interfere with successful ventilator trig- spaces. It typically occurs in preterm infants. The result is a
gering because an infant may becom e apneic secondary to stiff lung and a tendency to atelectasis in the early s tages. The
inhibitory activity (after an inflation),22 especially if the clin- main goals of therapy are to recruit collapsed alveoli, restore
ician selects an excessively long T 1, despite a nonalkalotic FRC, and achieve adequate alveolar ventilation. Technical
pH. and pharmacologic advances, with improved unders tand-
ing of pathophysiology and causes of lung injury, have al-
tered the strategy for ventilating pretenn infants with RDS
dramatically. Therapy is titrated to disease severity and in-
Do Ventilator Goals Differ between cludes noninvasive and invasive ventila tor support.
Infants and Children? CPAP is the primary respiratory support for RDS, al-
though a conclusive controlled trial has not been un-
The basic objectives of ventilator support remain the same dertaken. Several uncontrolled studies indicate that nasal
from early life to adulthood. 23•24 The physiologic objectives CPAP reduces respiratory failure and the duration and
are to (1) support gas exchange in terms of alveolar venti- invasiveness of respiratory support without impairing
lation and arterial oxygenation, (2) achieve sufficient end- neonatal outcome.25 - 28 Nasal CPAP improves respiration
inspira tory lung expansion to prevent or treat atelectasis, in preterm infants by increasing FRC and chest-wall stabil-
(3) maintain sufficient end-expiratory lung volumes to re- ity, as well as decreasing upper-airway collapsibility and
store reduced FRC, (4) reduce work of breathing by unload- upper-airway resistance. 29
ing the respiratory muscles in the setting of increased air- When positive-pressure ventilation (PPV) was first in-
way resistance or reduced compliance and to reduce work troduced in newborn infants with RDS, high peak inspi-
ofbreathingand thus 0 2 consumption in patients with heart ra tory pressures (PIPs) were used to oxygenate the stiff
failure or sepsis, and (5) to prevent small or large airway col- lungs. This was associated with high mortality rates, air
lapse in certain situations Oaryngotracheobronchomalacia; leaks, and the development of BPD.30 In the 1970s, uncon-
see Fig. 25-1). trolled studies in a small number of infants demonstrated
Historica lly, the main objective has been to restore nonnal a reduction in the incidence of pneumothoraces through
physiology by normalizing oxygenation and alveolar ven- use of long T1 values and slow rates.31 This strategy was
tilation. With recognition that the ventilator has side effects, widely adopted until PEEP was shown to have greatest ef-
this target of normalizing blood gases has become relative. fect on mean airway pressure.32 The availability of exoge-
There is, however, s till debate about how permissive one nous surfactant and ventilator capability of synchronizing
should be in terms of accepting hypoxemia or hypercap- ventilator breaths with spontaneous breaths has further al-
nia. Other objectives include to (1) relieve signs of distress tered ventilator management of RDS. It is now widely ac-
(e.g., indrawing, use of accessory muscles, or tachypnea), cepted that RDS, characterized by poorly compliant lungs
(2) reverse or avoid respiratory muscle fatigue, (3) reduce and very short time constants (026-0.34 second), is best
systemic 0 2 consumption, and (4) permit seda tion, analge- managed with short T1 values, rapid rates, and PEEP.33' 34
sia, and neuromuscu Jar blockade (intra- or postoperatively). The availability of fl ow sensors in neonatal venti.lators en-
The same guidelines can be used in infants and children ables continuous measurement of VT, eliminating much of
as in adults. The oxygenation goal is an Sao2 of more than the guesswork in setting the ventila tor.
90% (equivalent to a Pao, of 60 mmHg, assuming a normal The w1derlying pathophysiology, decreased lung compli-
"adult" 0 2 dissociation curve) . The ventilation goals are a ance, high chest-wall compliance, and d ynamically ma in-
VT below 8 ml/kg (8-10 m l/kg being about physiologic) tained FRC above closing volume make RDS a perfect can-
and plateau pressures of 35 cmH20 or less; permissive hy- didate for an open-lung strategy and use of high-frequency
percapnia entails accepting res piratory acidosis (pH 2: 7.25). oscillatory ventilation (HFOV). N evertheless, most studies
A rapid rise in Paco, should be avoided. Contraindications to date have not demonstrated a significant differ ence in out-
to increased Paco, (and/or low pH) include increased in- come measures with the use of HFOV versus conventional
tracranial pressure and increased risk for pulmonary hyperventilation and a lung-protective strategy.35 - 38 HFOV seems
tension. Conversely, any rapid reduction in Paco,, which to have a small benefit on pulmona ry outcome in very low-
may occur with surfactant therapy or change in ventilato r birth -weight infants without increasing the complications
mode, may lead to cerebral vasoconstriction, increasing the of premature birth.36,39
risk of cerebral hemorrhage and/ or leukomalacia in prema- Exogenous surfactant therapy has been part of routine
ture babies. care of preterm neonates with RDS since the early 1990s.
Animal-derived exogenous surfactantsare the present treat-
ment of choice, with few adverse effects largely related to
changes in oxy,rcenation and heart rate during surfactant
Common Clinical Conditions administration. 0 The optimal dose is usually 100 mg/kg.
Both prophylaxis and treatment are successful in infan ts
N EONATES with establis hed RDS, but prophylaxis appears to produce
RESPIRATORY DISTRESS SYNDROME greater clinical benefit. 41
(HYALINE MEMBRANE DISEASE) Persistent fetal circulation is a complication of RDS in
RDS is characterized by pulmonary surfactant deficiency preterm infants. At present, there is no clear-cut evidence in
and transudation of plasma proteins into the alveola r favor of using inhaled nitric oxide (iNO) for preterm infants
CHAPTER 25 MECHANICAL VENTILATION IN THE NEONATAL AND PEDIATRIC SE I I lNG 549
requiring mechanical ventilation.42 Clinicians will continue ting of pulmonary hypoplasia. lnappropria tely high airway
to make case-by-case decisions for the trea tment of pre term pressures also increase pulmonary vascular resistance and
infants with hypoxia unresponsive to other therapies.43 aggravate hemodynamic instability and lung injury. 53 iNO
is less effective in avoiding the need for ECMO than in pa-
PERSISTENT PULMONARY HYPERTENSION tients with meconium aspiration syndrome.54
OF THE NEWBORN CPPHN)
PPHN is the result of elevated pulmonary vascular resis-
tance to the point U1at venous blood is shunted to some
PEDIATRIC PATIENTS
degree through fe tal channels (e.g., ductus arteriosus and
foramen ovale) into the systemic circulation. By bypassing VIRUS-INDUCED HYPOXEMIC FAILURE
the lungs, it causes systemic arterial hypoxemia. It is associ- Two distinct patterns of disease occur in infa nts with virus-
ated wiili (1) pulmonary parenchymal d isease such as RDS induced respiratory failu.re.55•56 The primary causative
or meconium aspiration and (2) hypoplasia of the lungs, agent is respiratory syncytial virus (RSV). The most fre-
most often in the form of diaphragmatic hernia, and (3) it quent pattern is acute bronchiolitis characterized by an
also can occur without evident underlying disease. obstruction of small airways with air trapping and a
Traditionally, iliese infants have been hyperventila ted to moderate degree of parenchymal disease from atelec-
achieve mild hypocapnic alkalosis in a n attempt to atten- tasis. This leads to increased respiratory resistance, a
uate hypoxic pulmonary vasoconstriction. iNO is an ap- prolonged time constant, intrinsic PEEP, and decreas ed
proved adjunct to improve oxygenation in term infants respiratory compliance.57 Radiographic findings include
with severe hypoxemic respira tory failure secondary to hyperinflation, perihilar infiltrates, and atelectasis. The sec-
PPHN and has been shown to reduce ilie need for ex- ond pattern, which affects about 25- 30% of infants w ith
tracorporeal membrane oxygenation (ECM0). 44 Alveolar RSV-induced respiratory failure, consists of severe restric-
recruitment should be optimized before iNO because it tive parencl1ymal disease (usually termed RSV-pneumoni.a).
improves res ponslveness.14 An open-lung approach gen- Typically, respirato ry compliance and lung volumes are de-
erally is recommended, and HFOV has become the favorite creased markedly without significant airway obstruction
meU1od. or air trapping. Alveolar consolidation is the main radio-
graphic feature. This subgroup also usually fulfills the cri-
MECONIUM ASPIRATION SYNDROME teria of ARDS. Patients require prolonged ventilation com-
Meconium aspiration syndrome aHects mature infants and pared with a brief dura tion (4-8 days) for the bronchiolitic
is characterized by a mixture of inflammatory pulmonary pattern.55•56
disease, secondary surfactan t deficiency, obstruction of No consensus exists on optimal ventilator strategy. Nasal
small airways, and pulmonary hypertension. The result is CPAP appears useful in the early s tages of severe bronchi-
a very inhomogeneous lung with areas of atelectasis and olitis. It decreases work of breathing needed to overcome
hyperinflation. Setting the ventilator in disease with diHer" intrinsic PEEP but may increase dead space. In patients
ent time constants is challenging; the aim is provide suffi- with restrictive disease, nasal CPAP improves hypoxemia
cient alveolar ventila tion without development of intrinsic by recruiting lung volume and increasing FRC above dos-
PEEP. Studies have not conclusively demons tra ted any form ing volume. Reports do not provide definite conclusions
of ventilation to be superior to others, but stra tegies that on the benefit of CPAP in avoiding intubation and me-
recruit alveoli are recommended. Surfactant replacement chanical ventilation in children with hyp oxemic res piratory
or lavage may be beneficial.45•46 When hypoxic respiratory failure.58- 62
failure is progressive, iNO may improve oxygenation and Pressure-controlled ventilation (PCV) is the mode used
avoid ECMO. most commonly in virus -induced respiratory failure be-
cause the decelerating flow pattern achieves a lower mean
CONGENITAL DIAPHRAGMATIC HERNIA (CDH) airway pressure ilian d oes volume-controlled ventilation
CDH is characterized by lung hypoplasia, surfactant defi- (VCV). Mos t patients need PIPs of 25-35 cmthO to achieve
ciency, and an extremely reactive hypoplastic pulmonary adequate ventilation. Infants with obstructive disease have
vascular system. The hypoplastic lungs are very vulnera- long time con stants. They are best ventilated with slow
ble to injury from aggressive ventilation wiili high inspira- rates and inspiratory-expiratory (l:E) ratios of at least 1:3 to
tory pressures. Treatment is no longer focused on immedi- prevent breath "stacking" and further hyperinflation . Con-
ate surgery but rather on delaying repair until all reversible versely, patients with restrictive disease may require faster
problems ar e resolved. 47 These include pulmonary hyper- rates and shorter I:E ratios. Cautious application of PEEP
tension a nd parenchlmal injury from inappropriately high may decrease work of breaUU.ng (if intrinsic PEEP) in trig-
inflation pressures. 4 The new strategy has increased sur· gering of PSV and improving oxygenation in restrictive dis-
vival of infants with early respiratory failure from below ease. Permissive hypercapnia, to avoid high PIPs and baro-
50% to as high as 80%.47.49 Increased survival appears equiv- trauma, can be used with both pathophysiologic patten'\S.
alent to that with ECMO, HFOV, and pressure-support ven- Obstructive patients usually do poorly wiili HFOV. Patients
tilation (PSV) w ith permissive hypercapnia.49 - 52 Although with more restrictive disease might benefit from HFOV. iNO
high airway pressures may be required with secondary has no role in obstructive disease. Although it can improve
parenchymal injury to ensure adequate oxygenation, spe- hypoxemia in ARDS, it d oes not improve outcome in restric-
cial care is necessar y to avoid alveolar distension in ilie set- tive disease.'14,63,64 Other adjuvant strategies awaiting proof
550 PART VITI VENTilATOR SUPPOirr IN SPECIFIC SETTINGS
of benefit include glucocorticoids, surfactant (both under decreases the work o f triggering during PSV. PSV of 22-37
trialt and heliox. cmH20 has been used successfully in children with asthma
requiring full or near-full support, resulting in rapid im-
PEDIATRIC ARDS provement in gas exchange? 5 Noninvasive PSV is often
TI1e causes of ARDS in pediatric patients are the same as poorly tolerated w ithout sedation, and its ro le in avoid-
in adults, although viral or bacterial respiratory infections ing intubation in children with status asthmaticus remains
are more common in children.65 Ventila tor strategies are unclear? 6
almost the same as in adult patients and include PEEP to
recruit and keep open colla psed lung tissue and limit- CHRONIC RESPIRATORY INSUFFICIENCY:
ing peak inflation pressure to below 30-35 cmH20 to LONG-TERM VENTILATION
avoid overinflation. Although no single ventilation mode Chronic respiratory insufficiency can be defined as a
has proven superior, the most common modes are PCV life-a ffecting or growth-affecting situation caused by a
and HFOV66 despite the absence of solid data on the use long-term problem with oxygenation and/or ventilation.
of HFOV in pediatric patients beyond the neonatal period. Different ventilation techniques such as positive-pressur es
HFOV, using a high-volume strategy, can be used safely.67 ventilation v ia tracheostomy, noninvasive positive-pressure
Despite higher mean airway pressures during HFOV than mask ventilation (NIPPY), negative-pressure ventilation,
during conventional mechanical ventilation (CMV), baro- and diaphragmatic pacing are available for long-term or
trauma is less frequent. 68 Whether HFOV alters m orbidity home ventilator support in children. Selecting a technique
or mortality awaits prospective studies. depends on the underlying disease, age, expected duration
Prone positioning is used commonly, but without proven of assistance, patient acceptability, local experience, avail-
benefit.69,70 iNO cannot be recommended for routine u se, ability of eqt.1ipment, and cost. The simplest technology ca-
although it is used as rescue therapy (for a short time) in the pable of supporting the patient's lifestyle needs should dic-
very early stages of life-threatening hypoxemia and severe tate choice.
pulmonary hypertension. Diseases that cause chronic respiratory insufficiency in
infancy, such as BPD, may improve with age a nd allow
STATUS ASTHMATICUS withdrawal from mechanical ventilation. The respiratory
Most complications in patients with asthma receiving ven- system of infants is immature and prone to respiratory
tilation occur during or immed iately after intuba tion. They failure but has great potential for recovery as a result of
result largely from gas trapping causing hypotension, 0 2 growth of small a irway size and increase in alveolar number
d esaturation, pneumothorax, and cardiac arrest. Institution during the first d ecad e of life.77 Long-term ventilation en-
of positive-pressure ventilation in patients with asthma al- ables children to grow, preser ves physiologic function, and
ters cardiocirculatory and respiratory d ynamics dramati- prevents further damage from res piratory deterioration. In
cally, leading to diminished venous return and hy potension. older children w ith chronic lung disease, such as cystic fi-
The optimal ventilator mode for status as thmaticus is brosis, home ventilation can improve sleep-related hypox-
not established . Randomized, controlled trials comparing emia and hy percapnia and serve as a short-term bridge to
different modes in pediatric asthma patients are virtually transplantation.78 - 80
impossible. 71 Most clinicians prefer pressure-limited ven- Similar expectations for growth and development can be
tilation, keeping PIP below 35-40 cmH2 0 and accepting made for the infant's chest wall, whicl1 becomes stiffer and
hy percapnia.n Because of their decelerating flow pa ttern, more stable with increasing age. The most common rea-
PCV and pressure-regula ted VCV allow for lower PIPs but sons fo r home ventilation in children are neuromuscular
result in higher mean airway pressures than VCV with disorders and congenital central hy poventilation syndrome
identical VT. Ventilator rates are set well below normal (CCHS). In children with neuromuscular disorders, noctur-
and require an extremely long expiratory time. A T1 of nal NIPPY may prevent respiratory deterioration secondary
0.75-1.5 seconds allows ample time for inflation. Exter- to atelectasis or respira tory infections and d ecrease hospi-
na lly applied PEEP should be just below auto-PEEP to d e- talization ra tes. Ethical concerns regarding the institution
crease trigger work but no t increase hy perinflation. Du- of long-term invasive ventilation through a tracheotomy in
ratio n of mechanical ventilation for status asthmaticus is infants and small children with progressive neuromuscular
usually of 1-4 days. Children with rapid-onset near-fatal disorders relate to the fear of prolonging suffering from a
asthma may have a shorter duration of ventilation than miserable and unfavorable disease. Intermittent NIPPY of-
children with asthma tha t progresses slowly to respiratory fers an alternative a nd serves as a comfort measure to relieve
failure.73 anxiety fromhypoventilation and hypoxemia and probably
HFOV, PSV, and noninvasive ventilation have been tried has littleimpact on long-term survival. Death us ually results
in status asthmaticus. HFOV is believed to be contraindi- from ineffective cough and clearing of secretions in patients
cated in children with severe airflow obstruction, although with progressive respiratory muscle weakness rather than
recent experience challenges this belief. 74 PSV enables active from insufficient ventilation.
exhalation, which may decrease hyperinflation. PSVallows CCHS is a rare d isorder characterized by inadequate au-
patients to d etermine their own respiratory pattern (rate, tonomic control o f respiration. It is a common indication
T1, and VT) and may d ecrease pa tient-ventilator d yssyn- for pediatric hom e ventila tion. Most infants need ventilator
chrony. PSV d ecreases work of breathing by partially un- suppor t from birth a nd demonstrate adequate ventilation
loading the respiratory muscles. Careful selection of PEEP during wakefulness but not during sleeping. Nevertheless,
CHAPTER 25 MECHANICAL VENTILATION IN THE NEONATAL AND PEDIATRIC SETTING 551
CCHS varies in severity, ranging from complete apnea dur- the neonatal field, mainly for premature infants presenting
ing sleep and severe hypoventilation during wakefulness to with various forms of respiratory distress (classically, in-
mild hypoventilation during quiet s leep. Some infants re- fant RDS). Many w1answered questions remain, such as the
quire 24-hour ventilator support from birth. Some develop optin1al pressure and/or flow to be used,85 whether early
awake hypoventilation a t age 2-4 years as a result of in- CPAP for RDS reduces mortality and morbidity (chronic
creased physical activity. Therapy includes diaphragmatic lung disease remaining a significant problem in neonatal in-
pacing, negative-pressure ventilation, and various meth- tensive care) as compared with intubation and mechanical
ods of noninvasive and invasive ventilation. Long-term ventilation/6·28•86•87 and the lack of clear criteria to indicate
prognosis of CCHS is reasonable, and the necessary ther- when an infant is tmresponsive to nasal CPAP. Empirical
apeutical options should be offered.s1 criteria of failure in infants with RDS are presented as the
rule of 60s (Paco, > 60 mmHg or Flo, > 60 mmHg to main-
tain acceptable 0 2 saturation). Persistence of serious a pneic
Common Ventilator Modes episodes is also a clear indication. 88
After the neonatal period, observational reports of suc-
Tl1e following invasive and noninvasive techniques are cessful nasal CPAP in irtfants w ith viral bronchiolitis58•62
used in infants and children: have started to appear, opening a wider field for nasal CPAP
use.
1. CPAP during spontaneous breathing
2. PSV or volume-support ventilation to assist spontaneous
breathing CO NVENT IONAL VENTILATIO N
3. Intermittent mandatory ventilation (IMV) and syncl1ro- IN NEONATES AND INFANT S
nized intermittent mandatory ventilation (SIMV) using TIME-CYCLED, PRESSURE-LIMITED VENTILATION
pressure or volume control Pressure-control techniques have been used in neonates for
4. High-frequency ventilation (HFV) with or without spon- many years. Sucl1 neonatal pressure controllers deliver a con-
taneous breathing tinuous, constant flow during inspiration and expiration,
and the inspiratory and expiratory pressure levels cycle
Clinical experience with these modes in neonates and in- at regular intervals [time-cycled, pressure-limited (TCPL)
fants, although less in children, is distinctly different from ventilation]. In that inspiratory flow characteristics of TCPL
that in adults. There is a long-standing neonatal experience ventilation differ from classic PCV, w hich modulates in-
of nasal CPAP a nd HFV. Conversely, assist modes only respiratory flow in a decelerating pa ttern (Fig. 25-5), a clas-
cently became available in the neonatal field because of sic neonatal ventilator that offers TCPL ventilation is noth-
difficulties in providing sufficiently sensitive trigger sys- ing more than a simple and easy-to-operate flow driver. To
tems, especially for end-expiratory flow termination during acl1ieve an inspiratory plateau pressure, relative! y high flow
PSV. rates are required (6-10 liters/min), especially when short
T1 values (0.3-0.4 second) a re used to keep mean ainvay
pressures low. On several occasions, pressure-limited ven-
CPAP IN NEO NATES
tilators have failed to provide adequate alveolar ventilatio n
In 1971, CPAP was first used to support breathing in pre term in newborn babies; this can be a problem when T1 is too
neonates presenting with RDS. 82 In infants, CPAP is com- short o r with insufficient inspiratory flows. A second and
monly applied via the nasal route with a short binasal can- perhaps more important problem with TCPL ventilation is
nula (nasal prongs) or a soft nasal mask. Three systems are that delivered VT varies from breath to breath, coupled with
used: the fact that many flow drivers do not offer measurements or
display of delivered VT. The sam e problems, however, hold
1. An infant flow-driver system that generates CPAP in true for any pressure-control mode. A third problem with
the nasal interface. This needs relatively high constant TCPL ventilation is tl1e slow buildup of pressure and cycle
or variable flow rates (often above 8 liters/min) to en- to pause as the pressure target is acl1ieved. There is argu-
sure sufficient flow during inspira tion and avoid exces- ment as to whetl1er this leads to slow intra tidal recruitment
sive work of breathing. of the airways during the ins ufflation phase, the quantity of
2. An undenvater bubble CPAP device, with an underwa- which depends on the pressure delivered. This may create
ter blow-off syste m, positioned at a specific level on the less shear force in the airways than does classic PCV w ith
expira tory side to create PEEP. Flow has to be suffcient a decelerating flow pattern. Conversely, a potential disad-
to create continuous bubbling . vantage of TCPL ventilation is that as soon as the inspi-
3. A conventional neonatal ventilator that offers a continu- ra tory pause time commences, unstable airways are prone
ous flow to create CPAP. to collapse as gas is redistributed to areas with longer time
constants. Consequently, a situation arises whereby collapse
Randomized trials of appropriate design that compare is alread y commencing during the inspiratory phase. Con-
various CPAP systems (e.g., bubble versus irtfant flow) have versely, if a fast regulation system is used (variable flow
not been conducted, and no clear evidence favors one or delivery in a pressure-controlled mode) that promptly de-
the other system of nasal interfaces83 or design-related flow livers flow, tightly regula ted by pressure, previously col-
pattems.84 Nasal CPAP is now used as first-line support in lapsed airways will continue to expand; others with a longer
552 PART Vill VENTILATOR SUPPORT IN SPECIFIC SETIINGS
Inspiration Expiration Inspiration Expiration
20
f£..-~--~+-------. Time (s)

1 2
o+----------+--------~
0 , 2
20 20
!
~
--
::J
0 ...1
"'~
...!%
"'o ..
>e
co._..
c c;5
c-
3 ....::J
0
1 0 2
FIGURE 25-5 Graphic respresentatio n of the equation of motion for a cons tant ins piratory flow pattern (left) and a cons tant inspiratory
pressure pattern (rigllt). The dotted lines indicate mean airway and lung p ressures. The s haded sections represent equal geometric areas
proportional to the pressure re quire d to overcome flow resistance. The unshaded sectio ns represent equal geometric areas proportional to
the pressure required to overcome elastic recoil. Note that for the same tidal volume and mean inspiratory flow rate (i.e., tidal
volume/inspiratory time, Vr!T1), the constant-flow pattern produces a higher peak a irway pressure and lower mean airway pressure but
the s ame peak lung pressure. (Reprinted, Ulitlr permission, from Clrntbum: Respir Cnre 36:577, 1991.)
time constant experience a chance of opening throughout renee of an ETI leak (not using cuffed tubes), which can alter
inspiration. This implies that there is no pause during the effective delivery of volume substantially. All these concerns
inspiratory period and that the regulation system is active are mere assumptions and not supported by dear scientific
even during the "no flow" phase. Flow during this "no flow" evidence. Because of teclmological advances and discu ssion
phase is seen only on high resolution but adds to the effi- of small VT values for lung protection, there is growing in-
cacy of recruitment by providing extra time for ltmg infla- terest in this mode again. A recent single-center random-
tion; this behavior is best explained by the power law of ized, controlled trial has compared pressure-limited venti-
avalanches.89 lation versus VCV, with identical VT values in both arms,
in newborns presenting with RDS.90 There was a small ben-
PRESSURE-CONTROLLED VENTILATION efit, in terms of ventilator duration and significantly less
Classic PCV has been introduced in neonatal ventilation intraventricular hemorrhages and abnormal periventricu-
only recently. It differs from TCPL ventilation in that inspi- lar echodensities on ultrasound scans, in favor of VCV. The
ratory flow is variable (decelerating flow pattern). PIP can lower rate of cerebral complications with VCV may reflect
be reached early during inspiration. This leads to fast in- better Pea, stability.
creases in circuit and airway pressures, which may help to
overcome high airway resistance. For years, this was con- VOLUME-TARGETED VENTILATION
sidered harmful, but no evidence supports this concern. Recognition that volume rather than pressure causes
ventilator-induced lung injury has led to the development
VOLUME-CONTROLLED VENTILATION of various techniques that combine features of pressure- and
VCV in neonatology was abandoned in the early 1980s volume-limited ventilation in a mode, usually referred to as
mainly because of difficulties in measuring very small VT vo1Im1e-tnrgeted ven tilation (i.e., volume guarantee, pressure-
values under low-flow conditions. A second argument was regulated volume control, or volume-assured pressure sup-
the slow rise to peak pressures (with constant inspiratory port). With this, delivery of a set VT is guaranteed by
flow), eventually causing tmequallung volume distribution adjusting inspiratory pressure according to changes in
within the lung. A third argument was the frequent occur- compliance, resistance, or respiratory drive. This usually
requires a learning period over a number of breaths, dur· tain percentage of peak inspiratory flow. Algorithms such
ing which dynamic compliance and respiratory system reas this help to synchronize patient effort with ventilator
sistance are assessed by the ventilator. A few randomized assis tance. 96
studies in limited numbers of patients showed that these PSV increases inspiratory pressure to a preset level and is
modes can be used safely91 - 93 and may decrease ventilator- intended to overcome the work imposed by the ventilator
associated complications . Despite small studies showing and tubing system. Flow delivery is variable and p ropor-
only small breath-to-breath variability in VT,94, 95 there is tional to patient effort. Initially, PSV was viewed mainly
concern about overshooting volume delivery over several as a weaning mode, but subsequently, it was used more
breaths Oeaming-period eHect) if compliance or resistance widely.99 Since the development of sensitive flow triggers
change rapidly. The safety of these devices may need to be and variable inspiratory flow termination, PSV can be used
rethought. even in neonates. wo
SIMV, ACV, and PSV can be grouped under the generic
term of patient-triggered ventilation (PTV). In neonates and
PATIENT-TRIGGERED VENTILATION
especially in preterm infants, the trigger needs to sense
Babies often breathe asynchronously with the ventilator or any weak spontaneous brea thing effort. It also must mini-
agains t the ventilator. 96 Such asynchrony may cause poor mize a rtifacts that may result from other sources: heartbeat-
gas exchange and air trapping, leading to pneumothorax, induced variations in intrathoracic pressure or variations
hemodynamic instability, changes in cerebral blood flow, in pressure oscillations induced by rain-out in the venti-
and intracranial hemorrhage in newboms. 97 Synchroniza- lator tubing. Various trigger signals have been used: flow
tion of spontaneous inspiration with the ventilator has been or pressure triggers, abdominal or thoracic in1pedance
attempted, such as with SIMV, which conducts a search for methods, and detection of abdominal motion. Flow trig-
a spontaneous eHort within a predefined time frame (Fig. gering is more sens itive than pressure triggering for neona-
25-6). Although SIMV was thought to be superior to IMV, tal ventilation. 101 Two major sources of patient-ventilator
no evidence supports this suspicion.98 dyssynchrony are (1) inappropriate long delays in inspira-
Assist-con.trol ve11tilation (ACV) was developed to assist tory triggering (preterm infants with a short T 1 may have
all spontaneous breaths that exceed a trigger threshold; in completed much of the inspiratory phase before ventilator
the case of apnea, a mechanical breath is provided by the assistance commences) and (2) inappropriately selected in-
machine. Asynchrony occurs when the maclune's T 1 ex- spiratory flow termination (" cycling off" setting that is given
ceeds the infant's TJ. It is possible to terminate a machine as a percentage of maximum inspiratory flow; if set too low,
breath based on a decline in inspiratory flow to below a cer- inflation times will be too long). With this, the flow at which
FIGURE 25-6 Volume (nbove) and ftow (below) waveforms in a patient receiving synchronized intermittent man datory ventilation. The
STMV breaths occur at somewhat irregular intervals because of the timing windows, during which the machine waits to detect a spont-
aneous effort by the patient. VT, tidal volume; V, flow; Paw, airway pressure. (Used, witII permission, from Respir Cnre 48:426-39, 2003.)
20
VT
2
ml
-5
0.00 sec 2 4 6 8 10
v
0.00
1 pm
-5
18:45
554 PART VIII VENTilATOR SUPPORT IN SPECIFIC SETTINGS
the ventilator cycles to exhalation does not coincide with sistent criteria for assessment, however, and HFJV systems
the end of patient T1• have varied widely.
HFOV has become the mos t widely used mode of HFV,
and considerable experience with HFOV in acute neona-
NONCONVENTIONAL MODES:
tal respiratory failure now exists. The success of HFOV de-
HIGH-FREQUENCY VENTILATION pends on its ability to recruit lung volume, which is not
HFV is defined by a frequency that greatly exceeds the nor- always easy late in disease when substantial ventilator-
mal respiratory rate and a VT that approxima tes anatomic induced damage is superimposed on preexisting injury. The
dead space (see Chapter 20). There are three major types of first randomized study of HFOV, the HiFi trial,107 failed to
HFV: stress early intervention, volume-recruitment maneuvers,
and maintaining high mean airway pressures, as was dearly
suggested from experimental data.H18- m Recent trials, de-
1. High-frequency positive-pressure ventilation (HPPV;
signed to ensure "opening the lung and keeping it open,"
rate 60-150/minute) showed that HFOV is efficient and safe.35•36, 6S, l l 2 - 11' Re-
2. High-frequency jet ventilation (HFJV; rate 100-600/
cent neonatal data suggest improved pulmonary outcome36
minute)
compared with nonprotective, conventional ventilation.115
3. High-frequency oscillatory ventilation (HFOV; rate 180-
It is still unclear, however, whether HFOV achieves better
1500/ minute or 3- 25Hz)
overall outcome in infants with RDS than does careful con-
ventional ventilation.38•118 Use ofHFOV in pediatric patients
HFOV is the most commonly used method in pediatric with diffuse alveolar disease or ARDS is safe and improves
and neonatal ICUs. HPPV and HFJV promote gas exchange phys iologic endpoints but has not been shown to improve
in a conventional way with VT greater tl1an dead-space vol- clinical outcome.68
ume. Expiration is passive. In contrast, HFOV uses VT val- All these methods are highly effective in eliminating C02,
ues that are less than dead space, and expiration is active but the effect on oxygenation is less uniform. This is one rea-
(Fig. 25-7). son that these modes (especially HFOV) have failed to sus-
HFJV is used mainly during (adult) laryngeal surgery; tain their initial attraction. Within the context of ventilator-
few randomized, controlled trials exist in neonates, with induced lung injury and lung-protective strategies, HFV
conflicting results.102•103 Concerns have been raised about could be viewed as the optimal protective mode. By pro-
prolonged HFJV not only in neonates but also in adults re- viding very small VT values, it is possible to ventilate the
garding airway damage, ranging from focal necrosis to com- lllllg within a safe zone with the pressure-volume curve of
plete airway obstruction witl1 mucus and severe necrotizing the respiratory system119 (see Chapter 20). Side effects such
tracheobroncllitis_Hlo1,105 Increased risk of ad verse cerebral as from respiratory acidosis (permissive hypercapnia) are
outcome 106 has been reported. Studies have not used con- not associated with HFOV and spontaneous ventilation can
FIGURE 25-7 Range of respiratory rate and tidal volume for various methods of mechanical ventilation. HFO, high-frequency oscillation;
HFJV, high-fiequency jet ventilation; HFPPV, hig h-frequency positive-pressure ventilation; V 0 , dead space. (Adapted, with penuissiou,
from Slutsky: Am Rev Respir Dis 138:175-83, 1988.)
Conventional
Ventilation
HFPPV
Apneic Oxygenation (AO) HFJV

Tracheal Insufflation of 0 2 (TRIO)
Constant Flow Ventilation (CFV)
HFO
0 102
Respiratory Rate (b/min)
CHAPTER 25 MECHANICAL VENTILATION TN THE NEONATAL AND PEDIATRIC SE ll iNG 555
TABLE 25-2 lnital Settings of Frequency during Transition piratory muscle strength. Technological advances, however,
from CMV to HFO According to Age Group in patient-ventilator synchronization and improved man-
agement of sedative and narcotic drugs carry considerable
Frequency
potential for shortening weaning and reducing extubation
Preterm infant 12-5Hz failure. 127
Neonate at term and small children 10-12Hz
Children 8-10Hz
Adolescents 5-8Hz CORRECT TIMING OF EXTUBATION
Avoidance of unnecessary weaning delays is important
be often maintained, at least in neonates and small children. for reducing the risk of nosocomial infection, ETr dam-
Thus use of sedation is decreased, and muscle relaxants are age to the a irway, development of chronic lung dis-
avoided. In larger patients, inspiratory flow demands are ease in neonates, and prolonged dependency on narcotic
higher; thus spontan<:.'Ous breathing is not managed as eas- dmgs. 128·129 Aggressiveness with early weaning, however,
ily, and heavy sedation and/or paralys is may be required. mus t be balanced against the risk of extubation failure that
occurs in 6-15% of children and up to40% of neonates130-'132
INDICATIONS AND TIMING FOR HFOV and is associated with increased mortality.
Extubation failure may be caused by (1) reduced respi-
HFOV is still used mainly as rescue therapy despite dear
ratory drive (e.g., sedation, central nervous system infec-
indicators from experimental and clinical experience that it
is most beneficial when initiated before major lung injury tion or trauma, and hypocapnia), (2) increased respiratory
has developed 68• 115• 120•121 because no ventilator strategy can muscle load (e.g., unresolved lung disease, upper airway
repair pre-existing lung injury. 11 8,l22 Classic indications for obstruction including postextubation stridor, thick secre-
HFOV in neonatal patients include tions, and pulmonary edema including left-to-right shunt),
abdominal distension, sepsis, and metabolic acidosis, and
1. RDS characterized by surfactant deficiency, high chest- (3) impaired respiratory muscle function (e.g., neuromus-
wall compliance, and low FRC. This is the constellation cular disorders, diaphragmatic paralysis, cervical spinal in-
for easy and efficient lung recruitment, at least with early jury, malnutrition and severe electrolyte abnormalities).
disease. 115·118 Extubation failure is more frequent with chronic respi-
2. CDH, usually associated with alveolar and pulmonary ratory disorders, neuromuscular and chronic neurologic
vascular hypoplasia, l23 resulting in increased risk of disorders, and upper airway problems.131 The most com-
ventilator-induced lung injury48 and presenting with mon cause of extubation failure in preterm infants is
PPHN requiring aggressive P~ control. Lung recruit- apnea/brad ycardia. 132
ment should be applied with great caution because of the Objective weaning criteria have not been established
difficulty in estimating the degree of lung hypoplasia. for infants and children. A trial of spontaneous breathing
3. Air-lenk syndrome, such as pneumothorax or interstitial with a T piece and use of 10 cmH2 0 of PSV for up to 2
emphysema. HFOV can achieve early improvement and hours have been successful in allowing assessment of ex-
resolution of air leak in patients with interstitial emphy- tubation readiness and in predicting extubation failure. 133
sema, enabling better gas exchange and lower airway Baumeister et a1'134 modified the rapid shallow breathing
pressures than with CMV. 124 index (RSBT) and the compliance, rate, oxygenation and,
4. PPHN. Although iNO is the classic treatment for PPH N, pressure (CROP) index for weaning prediction in chil-
HFOV can enh ance delivery of iNO by achieving dren. RSBI is also known as the frequency-to-VT ratio; the
adequ ate lung recruitment 125 and enable easier C0 2 con- threshold that best discriminated between successful and
trol and correction of respiratory acidosis. failed extubation was less than 11 breaths per minute per
milliliter per kilogram. CROP is calculated as [CdynX P 1,,l'l.'lx x
The classic indication for HFOV in pediatric patients is (PaO;/P~))/RR, where Cdyn is dynamic compliance (cor-
diffuse alveolar disease (primary or secoudnry ARDS)68,126 as rected for body weight), P 1, ma.. is maximum negative inspi-
rescue therapy to improve o~genation. The only pediatric ratory pressure, Pa0;/PA0; is the ratio of arterial to alveo-
randomized, controlled trial did not show any difference lar Oz tension, and RR is the patient's respiratory rate. All
in survival or ventilator duration, although duration of sup- children with a modified CROP index of 0.1 ml x mmHg
plemental 02 was shorter with HFOV than with CMV. Rec- per b reath per minute per kilogram or greater were extu-
ommended strategies for use of HFOV (Fig. 25-8 and Table bated successfully. As part of a study not designed for wean-
25-2) are empirical and derive mainly from the neonatal ing prediction, the PAU SI inves tigators changed F~o. to 0.5
field and experience with HFOV in adult patients. 11 6 and decreased PEEP to 5 cmH2 0. Children who maintained
an S0; of 95% or greater were placed on minimal PSV for
2 hours. They were extubated if they maintained an S0; of
Weaning from Mechanical Ventilation 95% or greater, an exhaled VT of 5 ml/kg or greater, and a
respiratory rate within the acceptable range for age. 127
Weaning is largely determined by institutional practices or Developing reliable thresholds for indices for wean-
individual preferences. There is a traditional belief that sup- ing extremely low-birth-weight infants has proven more
port should be withdrawn gradually, certainly after pro- difficult. 135 The percentage of time spent below a tar-
longed respiratory failure, to enable children to regain res- get value of sponta1\eous expiratory minute ventilation
556 PART VITI VENTILATOR SUPPORT IN SPEOFIC SETIINGS
High Frequency Oscillatory Ventilation
lnitial Starting R ecommendations To lmprove Oxygenation
Target Fi0 2 is 0.6

Mean airway pressure: 5-7 cmH 20 above Incremental increases in MAP
conventional ventilator ( confrnn adequacy
t
by CXR showing 9-10 posterior ribs of
expansion)
Fi01 = 1.0
To Improve Ventilation
Power or delta P: Lncrease to achieve
adequate chest movement Increase delta P in increments of
5 cmH 20
Per cent inspiratory time: 33%
If PaC0 2 remains too high after
Flow rate >20 LPM (higher if needed to increasing delta P to maximum
achieve MAP setting) settings, then decrease frequency in
steps of 2 Hz and repeat the
Frequency: Infants: 10-15 Hz process (Minimum is 3 Hz)
Children: 8-10 Hz
Adolescents: 5-8 Hz For larger patients (>30 Kg), higher
flow rates may be needed to achieve
MAP or to accomplish ventilation
Weaning from HFOV
For oxygenation: step decreases in Fi0 2

to 0.60 then decreases in MAP
( 1-2 cmH1 0)
For ventilation: step decreases in delta P

(3-5 cmH 20)
Transition to conventional ventilation

can occur when MAP is 15-20 cmH 20
and Fi0 2 0 .4-0.6
FIGURE 25-8 Guidelines for instituting high-frequency oscillatory ventilation and the transition to conventional ventilation. (Courtesy of
Martha Curley, Clzildre11's Hospital Boston, Harvard Medical School; see ref 70.)
(<125 ml / min/ kg) during a 2-hour CPAP trial appears modes have been d eveloped to facilitate weanin g by re-
promising but requires further testing.136•137 ducing work imposed by respiratory apparatus, but their
use has not been investigated in children.138 •139 Some stud-
ies in adult patients suggest that protocol-directed weaning
WEANING MODES AND ADJUNCTS TO WEANING
implemented by nurses and res piratory therapists might
Weaning methods include PSV and volume-support venti- achieve extubation more rapidly than physician-directed
lation (VSV). Both methods involve patient-triggered pres- weaning.140,.141 One pediatric study (using as study end-
sure support. With PSV, the level of PSV is adjusted point the time a t which minimal settings were achieved
gradually by the physician to a minimal level that acl1ieves but not the time of extubation)142 reached a similar conclu-
acceptable respiratory parameters. With VSV, the level of sion. The largest pediatric weaning study, however, showed
PSV is adjusted continually by the venti.lator to achieve that weaning p ro tocols were no better than physician-
a minimum minute ventilation. Today, many ventila to r directed weaning and suggested that gradual weaning is not
CHAPTER 25 MECHANICAL VENTILATION IN THE NEONATAL AND PEDIATRIC SETIING 557
indicated in most infants and children.127 Studies have not ETT, (4) highly sensitive trigger device (flow triggering pre-
included children who are difficult to wean, especially those ferred to pressure triggering at least in premature infants/ 54
with disorders of the respiratory muscles. NIPPY may prove which provides adjustable inspiratory a nd expiratory trig-
helpful in weaning such children. Diaphragmatic plication ger criteria, ranging from5-25% o r more of peak inspiratory
can be of benefit in children with diaphragma tic paralysis flow), (5) built-in leak compensa tion, w hich can be turned
and may facilita te weaning. 143 off if there is a large leak around the ETI (this is important
The classic approach to weaning neonates from CMV is with PSV to enable inspiratory flow termination so as to
to extubate them from a rate of about 15 breaths per minute avoid excessive T1 in relation to pa tient need), and (6) air-
to supplemental 0 2 or nasal CPAP. Weaning strategies in- way humidification with cascade humidifiers and heated-
volve decreasing ra te (except for patient-trigger ventila- wire ventilator circuitry.155
tion) and positive inspira tory pressure to maintain the Vy The new-generation a ll-pa tient units offer all these neona-
at 4 ml/ kg or greater. PSV may be combined with SIMV. tal requirements a nd perform as well as those des igned
Newer options include volume-assured pressure support specifically fo r neonatal/ pediatric patients. 156 Detailed
and proportional-assist ventilation.144' 145 In neonates, direct specifications on "only neonatal" and "all-patient" venti-
extuba tion from a low ventilato r rate showed a trend to- lators are listed in Tables 25-3 and 25-4. Ventilator compa-
ward greater successful extubation than did extubation af- Iues have provided these data in response to the authors'
ter a period of endotracheal CPAP.146 Weaning from H FOV request.
is performed by switching to CMV or by direct extuba tion
directly after gradual reduction of mean airway pressure
HIGH- FREQUENCY VENTILATORS
and amplitude to ver y low values.
In preterm infants, methylxanthines, nasal CPAP, and Important differences in performan ce characteristics of de-
nasal NIPPY have been used to facilitate wean ing and ex- vices for HFV have been shown repea tedly. 157 -"~ 60 Thus it is
tuba tion, although only the latter two are recommend ed not possible to compar e settings from one form to another.
for routine use. 147 There is no role for glucocorticoids.148' 149 Three major systems are used: HFOV, H FJV, and HFV w ith
Methylxanthines (e~ecially caffeine because of its wide a flow-interrupter device (HFFI).
therapeutic margin1 ) increase the chance of successful ex-
tubation of preterm infants w ithin 1 week, but there is in- HFOV
sufficient information on side effects or long-term effects on HFOV is characterized by use of mean airway pressure (con-
cllild development. Nasal CPAP stabilizes the upper air- tinuous distending pr essure), on top of which squarewave
way, improves lung function, and reduces apnea. 151 It can or sinusoidal pressure swings are added by means of a pis-
prevent extubation failure in preterm infants, but the op- ton, diaphragm, or bidirectional high-velocity flow in the
timal levels and best m ethods of administration remain to expiratory limb. This leads to a more or less active as pira-
be determined .152 Synchr011ized N IPPV can augment the tion during the "expiratory" phase of the oscillatory cycle.
beneficial effects of nasal CPAP in preterm infants after The best studied and mos t widely applied HFOV system is
extubation.153 the Sensormedics 3100 high-frequency oscillator (VlASYS
In conclusion, neonates and children can be weaned much Healthcare, Palm Springs, CA). This exists in two versions:
quicker than adults, and weaning protocols have proven to the 3100A for neonatal use and the 3100B for pediatric and
be of little o r limited value in pediatric pa tients. ad ult use. The Humming V (Metran Medical Instruments,
Saitama, Japa n) exhibits sinillar performance to the Sen-
sormedics 3100A in in vitro and bench studies and also
can be switched to CMV. A new neonata l ventila tor offers a
Unique Neonatal and Pediatric slightly different technique of HFOV: The SLE 5000 (Spe-
Machines and Interfaces cialized Laboratory Eq uipment Limited, South-Croydon,
Surrey, UK) uses a bidirectional high-velocity flow in the
Conventional pediatric an d/or neonatal ventilators can be expiratory limb to genera te sinusoidal ven tilation with ac-
divided in three groups: (1) neona tal ventilators, (2) pedi- tive expiration. Thls ventilator also allows combined use of
atric ventila tors (which generally are identical to adult ven- CMV and HFOV. No clinical or experimental data exist for
tilators), and (3) all-age-group ventilators (from neonates this new ventilator, nor have safety issues been addressed.
to adults). Traditiona lly, a neona tal ventilator was used for
neonates or toddlers up to a body weight of 10 kg. Neona- HFJV
tal ventilators were m ainly constant-flow generators, whicl1 HFJV is characterized by the delivery of small, high-velocity
build up pressure and cycle to pause as the pressure target breaths at fast ra tes coupled with passive exh alation. HFJV
is achieved (TCPL ventilators). Today, some neona tal ven- allows the application of relatively low airway pressure to
tilators, ma inly all-age-group ventila tors, also offer classic maintain reasonable oxygenation. Pulses of gas are deliv-
pressure- and volume-control modes. ered at high velocity through an orifice at frequencies of
The followin g are the characteristics of a good neonatal 10-100 Hz. The orifice may be in a T piece connected to
ventila tor: (1) small apparatus dead space, (2) stiff but fl ex- a conventiona l ETT or a narrow tube incorpora ted in the
ible circuit tubing, (3) reliable tidal-volume measurement wall of a special ETT or at end of a fine-bore catheter placed
device (hot-wire or pressure-differential flowmeter or fixed- in the trachea. Available HF]Vs for neona tal and pediatric
or variable-orifice device) placed between the Y piece and use include the Acutroruc Monsoon Deluxe Jet Ventilator,
TABLE25·3 Conventiona l Ventilators: Limited to Neonatal (and Partial ly Pediatrid Use
&by log Bear Cub Sechrist

Ventilator 8000 plus 750psv Christina Fabian Millcnium SLE SOOO Stephanie
Drager Medical, VIASYS Healthcare, Stephan GmbH, Acutronic Medical Sechrist, Anaheim Spccialised Stephan Biomedical
Lubeck, Germany PalmSprings, CA Mediz.intechnlk, SystcnlS, Hitzel, CA Laboratory Incorporation..
C.ackenbach, Switzerland Equipme nt Cackenbach,
Germany Limited, Germany
South-Croydon,
Surrey, UK
Control principle Continuous now, Continuous now Continuous now Continuous flow, Continuous (low Continuous flow Aut.r/rontlnuous
Lime/flow cycled? time/flow-cycled. flow
pressure-limited pressure--limited
Modl'S IPPV/IMV SIPPV/ lPPV/IMV SIPPV/ fPPV/IMV, SIPPI// IPP\1/IMV SIPPV/ SIM\1/IMV,assist IPPV/lM\1 SIPPV/ IPP\1/IMV, S!PPV/
SIMV PSI/, CPAP SIMV PSI/, CPAP SIMV, assist· SIMI/ PSV, cPAP, control, CPA I' and SIMV PSV,CPAP SIMV, assist-
Volume guarantee Volume limit control • CPAP wi th C PAP with backup C PAP with backup target tidaJ volume control, PSV
(VG> backup frcqucney ventili'I.Hon ventilation Volume target in
ventilations~ Volume limit P·CMV.
leak-adapted
volume-<:ontrol in
V·CM\1, CPAP with
minute volume
target, and I'AV
with several
b..1ckup ventilations
Trigger type Leak-adapted Aow trigger (heated Aow trigger (0.1- Leak-adapted !low PrCSSt.are trigger Leak-adapted !low Aow trigger (0.1-
(type/response flow/volume "~re/0.02-5 2.0 ml)/pressurc trigger (hcatc'<l (pressure trigger (heated 2.9 ml)/pressure
sensibility/time) trigger. (heated liters/min) trigger optional wire/5-30% of the differential/0.1 wireftl.2- cycling optional
wire/0.2 Vmin + (0.1- 2.0 mbar) tidal volume/ cmH,O/S-40 ms) 20 liters/min) (0.1-2.9 mbar)
0.02-3 ml/ Pnet.JmOti'ldlOgraph 10 ms) Pneumotachograph
40-60 ms) !PNT)
Inspiratory llow 1-30 liters/min 1-30 liters/min !J-.20 liter$/min Neonatal: 1-20 2-32liters/min 8-60 liters/min 0-20 l i tc r~min
liters/min
Pediatrk: 4-40
liters/min
Expiratory flow 1-30 liters/min 1-30 liters/min 2- 20 liters/min Continuous now Continuous flow 3-5 liters/min cross..
(base flow), (equals inspiratory (equals hlSpiratory flo·w to wash out
independen tly flow) flow) theY piece
adjustable
End-expiratory Servo-controlled Elt'Ctric.-.Uy controlled Servo-controlled (}-20 em H20 (non Valvcll>sS expiratory Servo-controlled
pressure control nonocc:luding expiratory va l\•c nonocduding ocduding valve combinL'<i
d!!viC(' expiratory valve expiratory valve expir<1tory valve) _Inspiratory and
expiratory
propotional valve
Mechanica l dead 0.9 ml (with !SO 15 1.0 ml 0.56 ml (PNT B) 0.9ml 1.5 ml 1.0 ml 0.56 ml (PNT B)
space of flow sensor) 1.5 ml 1.1 ml(PNT C) 1; t m.l (PNT C)
flow/ prcssurL,_ (with integra ted
sensing Y~p i ec:e sensor)
de-vice
Incorporated g raph Flow ;md prC:SSure, Pressure, flow, and Prcssu..-e , Aow, and Pressure, flow, and n/ a Pressure, now, and Pressure, flow, a nd
monitoring integrated volume waveform; vo lume waveforms volume volume volume wavcf<>rms
wavefnrms (only pressure a nd flow over time; \'l.'f'lveforms; waveforn,s; over time;
one curve voJLUnc loops volwnc/prcssurc, flow/volume, flow/ volume, volume/pressure,
disph'lycd without flow/ volume, t~nd flow/pressure, and flO\\'/pressure, ilnd flow/ volume, i'lnd
optional screen) flow/ pressure volume/ flow l()()ps volume/ flow loops flowI p ressure-
optional se:reel''l loops (max. 2 curves loops
provides three dis played
simultaneous simutaneolL~ly)
waveforms and
loops
lung fu_nction Com pliant¢ C20/C n/a Compliance, Compliance C20/C n/a Compliance C20/C, Com pliance,
parameters Resistance tim~ n.--sistancc resistance resistance resistance,
C'.Onstant intmpu.lmOn3ry
CorreJation pressure,
c~fficien t inadvertant PEEP
(insp. or exp .
O<:dusion
mt~neuvc.r)
Additiol\al reatures HFV(HFFI) - Graphics display HFOV-oplional Battery pack HFOV-optional HFOV Variable
optional (not Transport op tion ventilatory
available in the US) resistance and
elastance (negative
ventilator
impedance, PAV)
Upper body weight 20 kg 10 kg (in the US) 30kg 16 kg 30kg 50 kg 42kg
limitation
TABLE 25-4 Conventi onal Ventilators: All Patient Ventilators
Puritan
Ventilator AVEA EvitaXL Galileo Gold Newport e500 Benett 840 Servo i
VIASYS Hoalthcare, Drager Medical, Hamilton Medic..,l, Newport Medical Pu rita n~Benett, Maquel Critical Care,
PalmSprings, CA Liibcck. Germany Rhiiziins, Instruments, Costa Pleasanton, CA Solna, Swed~.n
Switzerland Mcsa, CA
Control principle Variable-flow (adult/pediatric) lime-cyded, Variable·flow Servo-controlled, Time-cycled Variable-flow
Continuous~flow volumc·constant, mandatory and controlk>d flow or
ti m<Xyded (neonote) pressure-controlled spontaneous algorithmic.,lly
Nt'()Flow: baseflow variabk'-flov.~ controlled flow
combined with time-cycled, pressure--
demand system or volume- (Oow)
controlled
Bias flow w ith
A u tomatic Leak
Compensation to
pnwide a st<tble
3 l/min between
brea.ths
Modes A/C, PCV, VCV, SIMV, TCPL CMV, SIMV, A/C, CMV, SIMV, PCV, Volume control: A/C, PCV, VCV, A/C VCV, PCV,SIMV
(only nronalc) SI'ONT, PCV+ (BIPAP), SPONT,CPAP A/CMVSIMV S IMV. SPONT, SPONT, CPAI' PS and VS
CPAP assist (pressure or PCV+ assist (BIPAP A!isist (pressure or (± Psupport) SPONT CPAP assist assist (p ressure or volume)
volume) PRVC (= volumc- assist), MMV, CPAP, volume)APV (± psupportl (pressure or PRVC (= volume- targeted
targett."d ventilation, only ASB (PS) Automodc (= volume--tnrgett..~ Pressure control: V(llume) ventilation) S IMV(PRVC)
adult/pediatric) APRV (= voJumC"+targeted ventilation) ASV A/CMVSIMV Optional: bilevcl, +PS
Noninvasive ventilation (NTV) ventilation) I!!PAPI Duo PAP/ APRV (± psupport) SPONT APRV Bi-vent (optional)
Apnro backup BfPAP-ASB APRV Noninvasive (± psupport) Volume~vent:ilation Auto-mode(= automatic
Propottion~ l pre.'>sure ven tilation (NIV) Volume target pressure plus(= volume-- switch frorn control to
•-upport (PPS) Apnea backup controll a.nd volume targeted s pontaneous and
(optional., not target pressu re vcntilnti on) as spontanoues to cont-rol
available in the US) support volume ootnrol plus according patient's
Noninvasive Noninvasive ventilation or voulmc support rcspir~ tory activitys
ventilation (NIV) (NIV) Apnea backup o pti<mal)
Apnea ven tilation Apnea backup ventilation Noninvasive ventilation
[ndepc.ndent l\mg (NIV) PC a nd PS
ventilation (ILV) Nasal CPAP (optional for
infant only)
Apnea backup ventilation
Trigger type Pressure or flow trigger Leak-adapted flow Flow trigger and Leak-adapted, pressure Pressur<! or flow Flow or pressure trigger
(nconat~: flow trigge:ronl)r) trigger:. pr~ure t:rigget, or flo·w trigger trigger (neonate: (leak-adapted flow
leak-adapted fl<>w trigg~" only) trigger)
Optional: Proximal varittblc Proximal heated wire
4
Proximttl variable No spe:cial neon<Hnl Proximal fixed orifice flow
orifice (all patients) or fiow sensor (for orifice flow sensor flc.)w sensor, only and pressure sensor (for
proximal hc.)t•wire sensor neonatal and Neo-Mode Software neonate, pediatric and
(for nc'<lnate only) optionally ~>diatric f ixed inspiratOr}' adult)
Variable inspiratory backup patients) b:tckup trigger Expiratory Ultrasound
trigger (flow or pre$Sure, (pressure) flow sensor
r<'Spectively)
Trigger sen:o:;itivity 0. 1-20 liters/min ffow 0.3-151iters/min flow 0.5-J51iters/min flow 0.1 - 2.0 Jiters/min 1-20 liters/min (adult Row trigger sensitivity level
0.1- 20.0 cmH20 pressure O.S-10 mbar pressure (pediatric/infant) and pc>diatric) (fraction of bias flow
below PEEP below PEEP Q-5 cmNaO pressure 0.1- 10 lit~rs/min Q-JOO"!o of 33 ml/s
below PEEP (neonatal) (2 liters/ min) adult
Rcspon..:;e time 10 msec: 0. 1- 20 cml-laO 8 ml/s (O.Siiters/min)
p ressure below infant
l'EEP Pressure trigger0-20
(cm.H20) below PEEP
Inspiratory now 3-150 lite rs/min (adult) 6-120 liters/ min 1- 180 liters/onin (peak 1- 100 liters/min 3-150 liters/min Q-3.31iters/s
1-751ite.rs/min (pediatric) (adult) flow for aduJt and (~><tiatric/infant) (a dull) 3-60 (Q-200 titer.l/min)
0.4-30.0 liters/ min (neonate) 6-30 liters/ min pediatric liters/min (adult/ pedia tric)
(pediatric) applications) (pediatric) 1-JO o-o.ss liters/s
liters/mit\ (1\eonatc) (0-33 1iters/min) (ne.>nate)
(Continuous flow rate
is a-utomatically
ajustt~ to 1.5
liters/ min above
flow trigger
sensitivity)
Expiratory trigge.r Variable (Q-45% of peak flow) Fixed ot 25% of peak Variable (5- 70"!. of Variable (1 - 80%) Variable (1-70% o f peak
(flow termina tion) flow peak flow) flow)
Mcch(lnical VarFlcx: 0.7 ml (neonate), 9 ml (including 9-11 ml (adult a nd No p rox imt~ l None (flow/ pre.o:;surc N/A
dead-space of flow/ 9.6 ml (adult) Hot wire: 0.8 optional p<>diatric) 1.93 ml flow/pressure device sensing is integral Proximal fixed orifice sensor
pressure sensing ml (n(.'(mate) mainstream (neonate) available to the pneumatic <0.75 rnl infant
device capnograph) system) <6.9 ml adult
Neoflow: 0.9 ml Flow
S<"nsor (neonate)
(Cbuntltletf)
TABLE 25-4 (Cout.iuued)
Puritan
Ventilator AVEA EvitaXL Calileo Cold Newport eSOO Benett 840 Ser-vo i
Incorporated graph Pressure.., flow·, a nd Pressure ~, flow-, a nd Pressure.., flow-, and Pressurt...., flow·, and Prl."SSUrc, flow, a nd Pressure, flow, volume, and
m on_itoring v Q)I,lm¢-time W i'IVe£OTm$ volumfH:ime voh.tme--time volume--time volume, wav('(Orms col w aveforms
Flow/volume$ a irway; waveforms waveforms waveforms wlth a uto (two waveforms Flow/volume,
esoph<1geal, tracheal, a nd/or Pr~ssurd'volume, Any pair of th rl~ basic or manual scaling simuJtane<)ulsy pressure/volume loops
transpulmonary volume/flow, parameters for (multiloops: up to 5 displayed)
pressure/volume loops tr;~ thcn l loops: a irway di<played Pressure¥volume loop
p ressure/volume, p ressure, flow and simultaneously (with calculation o f
Aow/prE$s u~. volume presen ted Pres.'lute/vo lu mc, inspiratory area)
volume/C02 flow/volume loops
(optional) or w ith trace (unction
flow/tracheal and :;tore function for
pressure lcN)p$ two sets of loops, all
Long and short trends with a uto or ma nual
scaling
Lung fu nction Lung function package Compliance Compliance (Cstat) Compliance (Cstat, Com pliance Dynamic characteristics
parameters/ (inclusive in comprehensivl! Resistance Intrinsic Inspiratory Cdyn offcctive), Resistance Rapid T1 / TroT WOB patient
weaning nuxlel) with com pliance, PEEP-PEEPr Vtntp res istance (Rinsp) lnspirntory resistance shallow breathing WOB ventilator Rapid
parameters r<."Sis tance, rapid ~shallow (volume trapped Expiratory (Rinsp) Expiratory index (f/Vt) shallow breathing index
breathing index, negative due to PEEP1); resistance (Rexp) resistance (Rcxp), Total PEEP S tatic
inspiratory force, auto~ PEEP, Rapid-shallow Auto-PEEP PEEP10T,,,.,; lmpos<.>d Complia nce ln•1'iratory
chest~wa ll rompUance, lung breathing index Ins piratory time !tVOrk of breathing ResiStflnCC Expiratory
compHancc, imposed (RSBI); Negative cons tant (RCinsp) (WOBin>); Peak Resistance J:E ratio
resiSt<lnCe, lung resisttlnCe, inspiratory force Expiratory time inspi'ratoy flow, peak EJastance lime consl':~nt
peak inspiratory flow, pwk CNIFl; Occlusion constant (RCexp) expiratory flow; Delta 0 2 roncentrntion EtC02
expiratory now, delta airway pressure Po.1 a irway pressure concentration Vco.!
pr{.ossure, delta aut<,· PEEP_. Occlusion pressure Minimum expiratory minute elimination Tidal
esoPhageal auto·PEEP, (Po.rl; Rapid time (time etlnstant C02 elimination
transpulmonary p lateau s hallow breathing '3), f/ VT (ra pid Mvcsp/Mvc Spontaneous
pressure, Occlusion pressure index (RSBI); shallow breathing cxp. m inulc volume
(P0 . 1), ventilator work o f lmpos(>d work of index); Peak negative leakage fraction in NIV
breaU~ing, patienl work of breathing pres.~u re Po,J Dynamic Com pliance
breathing, imposed work of (WOBimp)
breathing, transpulmonary WW version (optional) :
auto-PEEP. ClO/C PV tool (with ma_n ual slow inflation
inflation and creates static PV curve
d eflation limb of
qu asi-static
pressure--volume
curve)
Additional features Hcliox modul (inclusive in Autom atic tube Tube resistance Scp;1rately ad justed Tube comp<.•nsation Automatic tube and leak
comprehensive model) cotnpcnsation cornpcnsation expiratory bias flow (assisting compensation
with automatic Jeak proportioanl to
CO:! incorporated Sigh feature comp:~nsation (up patients inspiratoty Open lung tool (optional)
(optional) to Sliters/ min) to flow) co! incorporated
Built in jctncbulizcr provide stable Proportional·assist (optional)
Sm<trtCarc/PS flow driver (cycled) 3 liters/min bchveen ventilation (PAV + )
knowledge-base><! breaths with automatic Ultrasound nebulizer
weaning sy~tcm calculation of (optional) and/or aeroneb
(optional, down to Sigh feature (1.5 x tidal clastan('(' and (nebuJization with
lS·k& pa ti cnl~, not volume se-tting every resist:. nee (optional) vibration technology)
available in the US) 100 breaths)
Ventilation record card
Lung·protcction Dual control breath recording data and
package (optional) 1nanagement w;~v~forms
(VTPC!VTPS)
Eve nt History
WW version (opl;onal): Tm'IC: constant controlle-d
Flc><Cyde (automatic exhalation valve
oxp threshold
adjustment) Consumable or
Au tomatic Slope/ Rise nonconsumable senS4')t for
adjustment, 01 measure ment
noninvasive Event log
ventilation, op<.-'ll
exhalation valve (for
biphasic pressure
re1ease ventilation)
Infant/neonate Standard Optional Slandard Standard Optiortal Standard
ventilation
564 PART VITI VENTilATOR SUPPOKI' IN SPECIFIC SETTINGS
the Acutronic Medical Systems (Hirzel, Switzerland), and textubation stridor, development of chronic lung disease or
the Life Pulse High Frequency Ventilator (Bunnell, Salt Lake BPD (classic in the pretem1 infant), a nd ventilator-associated
City, UT). pneumonia.
HFFI
HFFI offers CMV as the basic mode. Expiration is mainly POSTEXTUBATION STRIDOR
passive, but negative pressure generated by a ven- Acquired subglottic stenosis became a well-recognized
turi effect may enhance lung emptying. Examples in- problem with use of long-term endotracheal intubation.
dude the Draeger Babylog 8000 (Dragerwerk, Lubeck, Serious tube trauma and postextubation stridor have de-
Germany), the Stephanie (Stephan Biomedical Incorpora- creased markedly with improvements in material and tube
tion, Gackenbach, Gem1any), and the lnfrasonics Infant Sta r design, greater care in choosing appropriately sized tubes,
950 (Nellcor Puritan-Bennett, Inc., Pleasanton, PA). HFFis and meticulous care of the intubated patient. The old dic-
are available only for neonatal ventilation, and little data tum, "Cuffed ETTs should not be used in children under
exist on their clinical use.161 ·162 the age of 8 years," is incorrect given the development of
high-volume, low-pressure cuffs.171• m Tube complications
AIRWAY HUMIDIFICATION SYSTEMS usually arise from incorrect size, traumatic or multiple in-
tubations, up-and-down movements of the tube, and inad-
The objective of humidification in infants and children is equate analgesia and sedation, causing intubated infants to
to achieve a physiologic situation: 100% water saturation of struggle. Poor design can result in a cuff being positioned too
the inspired gas at 37°C, corresponding to 44 mg H 20 / liter. high within the larynx (Fig. 25-9), causing severe trauma.173
::: 30 mg H20/Iiter are considered to be acceptable. 163; l64 Other risk factors of postextubation stridor include dura-
This can be achieved with heated- moisture-exchange tion of intubation, gastroesophageal reflux, and tracheo-
(HME) filters that allow retention of the ten1perature and bronchial infection. Checking for a cuff leak is oflittle help in
humidity of a patient's expired gas. 164 HME filters, however, predicting postextubation problems in young children. 174
add considerable dead space and resistance to the circuit, 165 Most injuries causing postextubation s trido r are super·
which is problematic in neonates and small children. Cas- ficial and include nonspecific changes such as laryngeal
cade humidifiers interposed in the inspiratory limb, there- edema, granulation tissue, and ulcerations. Stridor usually
fore adding no resistance or dead space, are more efficient resolves with medical therapy. Inhaled epinephrine is suc-
for airway humidification166 and should be preferred. To cessful in treating subglottic edema. If reintubation is re-
avoid rain-out during transport of humidified and heated quired, a smaller EIT should be used to prevent additional
gas, gas temperature needs to be maintained by a heated traun1a. The nasal route is preferred to optimize tube sta bi-
wire in the inspiratory limb. Most recent circuits also allow lization and to minimize the tube shifting with head move-
for heating of the expiratory limb. ment. The child should be weaned rapidly from the venti-
lator to humidified 0 2 delivered via a light T tube. These
measures prevent infants from pushing out the tube w itl1
Monitoring of Mechanical Ventilation their tong ue a nd allow for better head movements, thereby
Several specific pediatric and neonatal issues about respi-

ratory monitoring must be noted. First, ventilator-circuit FIGURE 25-9 Positioning of the cu ff on various endotacheal
dead space should kept as small as possible when moni- tubes : (1) uncuffed tracheal tube, ID 4.5 mm, (2) Ruesch elit Super
toring devices are added. Second, flow measurements must Safety Clear, ID 4.0 mm, (3) Mallinkrodt Hi-Contour P, ID 4.0, (4)
be made as dose as possible to the airway opening to get Microcuff PET, ID 4.0 mm, and (5) Sheridan CF, ID 4.0 mm. Note
true delivered VT. 167 - 169 Third, C02 production is lower that only tube 4 has a cuff off appropriate size and positioning.
(Courl"esy of Markus Weiss, Pediatric Au esthesia, Children's
in neonates (~15 ml/min) and toddlers than in adults
flospi tal of Z uric/1, Switzerlaud.)
(~200 rnl/min). Accurate measuren1ents of exhaled C~ in
pediatric patients is more challenging because oflimitations
in size of the analyzer chamber, tl1e amount of flow that must
be s uctioned by sidestream devices, and the need for fast
response times because of rapid respiratory rates. There-
fore, mainstream sensors, which have a faster response time
(than side-strean1 devices) and do not need suction flow, are
preferred. 170
Complications of Mechanical Ventilation

In addition to barotrauma (e.g., pneumothorax and inter-
1 2 3 4 5
stitial emphysema), three other complications include pos-
minimizing risk of fur ther trauma. Alternatively, the d1ild VENTILATOR-ASSOCIATED PNEUMONIA
can be heavily sedated and eventually receive neuromuscu-
Although ventilator-associated pneumonia is the sec-
lar blockade. In most cases of simple subglottic edema, extu-
ond most common nosocomial infection in the pediatric
bation is successful after a rest period of about 2-3 days with
ICU,1 91 - 193 it has been little studied. Pseudomonas aerugi-
or without a short course of dexamethasone (1- 2 mg/kg
nosa, enteric gram-negative bacilli, and Stapllylococcus au reus
per day in divided doses). It is reasonable to administer
dexamethasone to patients at risk of stridor for 24 hours are isolated mos t commonly from endotracheal aspirates in
before and 24 hours after extubation. Sud1 prophylactic ventilator-associated pneumonia, particularly when of late
steroids may reduce postextubation stridor and the rate of onset. 191 Mortality and cost in pediatric patients are un-
reintubation.m known. Blind protected bronchoalveolar lavage194 has been
Endoscopy is recommended after failed attempts at extu- proposed as the most reliable diagnostic method. Diagnos-
bation. Soft granulation tissue secondary to early intubation tic bronchoscopy usually is not required 195 because pro-
injury often can be treated with a C~ laser. Severe and last- tected bronchoalveloar lavage is reasonably reproducible
ing trauma from prolonged intubation, such as perichondri- and provides acceptable sensitivity (72%) and specificity
(88%). 196 Treatment can be adapted from ATS guidelines
tis, subglottic stenosis, necrotizing tracheobronchitis, sub-
for adults. (American Thoracic Society, Infectious Diseases
glottic cysts, tracheal perforation, and tracheal s tenosis, is
Society of America. Guidelines for the management of
rare. Surgical options for subglottic stenosis include ante-
adults with hospital-acquired, ventilator associated, and
rior cricoid split, laryngotracheal reconstruction, tracheal
resection, and cricotracheal resection. health-associated pneumonia. Am J Respir Crit Care Med
2005; 171: 388--416.)
BRONCHOPULMONARY DYSPLASIA IN
THE PRETERM BABY
Important Unknowns
The etiology of BPD is multifactorial. The principa l risk
factors are lung immaturity, barotrauma, volutrauma, 0 2 Mechanical ventilation has increased survival of acutely ill
toxicity, prenatal and nosocomial infections, and increased neonates and children. A better understanding of patho-
pulmonary blood flow secondary to a patent ductus physiology has led to newer ventilator strategies. Many
arteriosus. 176•177 The complex interaction between inflam- of these strategies, however, have not been tested in the
matory mediators and fibrosis has not been defined. Neither pediatric setting but simply adapted from adult experi-
has the interference of inflammation with postnatal lung de- ence. Recent research suggests that comparable ventilator
velopment, especially alveolarization. settings are more injurious in the adult than in the infant
Changes in neonatal care of very low-birth-weight in- lung.l97
fants, including antenatal corticosteroids, postnatal surfac- Approaches to optimizing ventilation a re based on bed-
tant, and modified respiratory support, have improved side assessment of respiratory mechanics and blood-gas
survival. BPD is still frequent in very premature infants, response. Unfortunately, no characteristic of the pressure-
although the more severe forms are less frequent. The volume curve can predict end-expiratory atelectasis, over-
incidence ofBPD varies from 0-56%.35•36•62·178- 180 This wide stretching, or optimal airway pressure.198·199 Despite im-
range reflects the heterogeneity of study populations, man- proved understanding of pediatric diseases and mechanical
agement practices, and disease definitions. The initial de- ventilation, we still do not know the best settings for an indi-
scription of BPD by Northway e t al30 and subsequently by vidual child. To date, evidence is confined to bad ventilator
Bancalari et at'181 was based on 0 2 requirements at 28 days settings.
of age. As newborns of lower gestational age survived, Noninvasive ventilation has proven safe and feasible in
Shennan182 later proposed the term chronic lung disease, de- pediatric settings and can help to avoid intubation. 200•201
fined as~ dependency at 36 weeks' postconceptional age. Ventilator discontinuation is believed to decrease several
This definition seem ed to better predict pulmonary out- complications, but proof is limited.
come. Jobe and Bancalari183 introduced grading of BPD
severity.
Management of BPD includes minimizing ventilator du- The Future
ration and avoiding high 0 2 concentrations. Fluid restric-
tion, diuretics, and bronchodilators are helpful but do not Respiratory monitoring has been used to decrease com-
alter disease course. Pulmonary vasodilators are not bene- plications and improve patient-ventilator interactions. We
ficial for BPD-associated pulmonary hypertension. 184 Dex- need to develop approaches wher eby this knowledge can
amethasone can accelerate ventilator weaning and shorten be used to improve patient outcome. Tools that p rovide
the period of 0 2 supplementation but is associated with continuous recordings of pulmonary function have yet to
worse neurologic outcome (increased leukomalacia, im- be incorporated into ventilator equipment. For example,
paired brain growth) and more frequent severe gastroin- the continuous monitoring of FRC might improve ventila-
testinal complications.185 - 189 Dexamethasone therapy, if tor strategies and enhance assessment of lung recruitment.
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CHAPTER 25 MECHANICAL VENTILATIO N IN THE NEONATAL AND PEDIATRIC SE I I ING 571
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rtt:hapter 26 _ _ _ _ _ _ _ _ __ Basic Principles of ILV
INDEPENDENT LUNG Ail indications for ILV (see Table 26-1) are based on one or
two fundamental requirements:
VENTILATION
DAVID V. TUXEN
1. The need to protect one lung from harmful effects of fluid in
the other lung (blood, purulent or malignant secretions,
lavage fluid). Placing a fluid-filled lung in the depen-
dent position (lateral decubitus) minimizes the risk of un-
wanted fluid entering the other lung but also maxirt1izes
hypoxia 11 by maximizing blood diversion to the less func-
tional lung. Placing the fluid-filled lung in the nondepen-
BASIC PRINCIPLES OF ILV dent position improves oxygen. saturation (Sao2 ), but the
APPLICATIONS OF ILV risk from fluid spillage irt this position is unacceptably
Thoracic Surgery high. 11 The supine position is usually the best compro-
Selective Airway Protection mise, except durirtg thoracic surgery, where the operative
Bronchopleural Fistu la lung must be in the uppermost position.
Asymmetric Lung Disease 2. Potential benefit from different ventilator pntterns to each
Bilateral Symmetric Lung Disease lung. This could range from one-lung ventilation (OLV;
TECHN IQUES AND PROBLEMS WITH ILV e.g., thoracic surgery, whole-lung lavage) to ventilation
Lung Separation to each lung differing in only a single variable [e.g., pos-
Techniques for ILV itive end-expiratory pressure (PEEP)] or ventilation re-
Problems with ILV quirements differing in every variable [e.g., single-lung
CONCLUSION transplant for chronic airflow obstruction (CAO)].
If OLV is required, a broncl1ial blocker and endobronchial

Independent lung ventilation (ILV) was first reported for
tube or DLT (see " Lung Separation," below) may be used.
thoracic surgery by Gale and Waters in 1931. They passed a
If ILV is required, a DLT usually is used [some bronchial
single-lumen endobronchial h.tbe into the main bronchus of
blockers can allow limited ventilation such as continuous
the nonoperative lung. They ventilated that lung in the de-
positive airway pressure (CPAP) or jet ventilation!.
pendent position while preventing drainage of purulent se-
Irrespective of technique, tube or blocker position usually
cretion (if present) from the ope.rative lung. In 1936, Magill1
is checked using fiberoptic bronchoscopy imm ediately af-
reported endobronchial placement of a suction catheter
ter instigation, and lung isolation is leak tested (see "Lung
with a balloon to occlude the operative bronchus and tra-
Separation," below). This is important for all indications for
cheal placement of an endotracheal tube to ventilate the non-
ILV but is most critical when protection from secretions is
operative lung. In 1947, Moody2 encased the endobronchial
required.
balloon with metal sh.tds to reduce the risk of balloon
dislodgment.
A series of double-lumen tubes (DLTs) enabling ILV of
both lungs was reported next. The first, reported by Carlens3 Applications of ILV
in 1949, was a DLTsimilar to current left DLTs but with a rub-
ber " hook'' to engage the carina for accurate placement. This Applications of ILV (see Table 26-1) fall into five categories.
was a major advance, but it was unsuitable for left pneu-
monectomy. Moreover, the carina! hook caused trauma and
THORACIC SURGERY
difficulties with surgical dissection. It was not until 1960
that White4 reported a right DLT that did not occlude the A number of thoracic surgical procedures req uire OLV, usu-
right upper-lobe bronchus. In 1962, Robertshaw 5 reported ally in the lateral position. The common thoracic surgical in-
right and left DLTs, which served as the prototype of to- d ications forOLV are listed in Table26-1.12, 'l 3 Although OLV
day's DLTs. Current DLTs have replaced red rubber with is required during surgery, ILV may be required before and
polyvinyl chloride (PVC) to reduce mucosal injury and im- sometimes after the surgical procedure.14
prove malleability and airflow (Fig. 26-1). OLV may be undertaken with a DLT, bronchial blocker,
For many years, DLTs and ILV were used entirely for or endobronchial tube. A DLT has the advantage of en-
thoracic surgery. 2•6•7 In 1976, Glass and Trew8,9 and their abling ILV, which may be important in alleviating hypoxia;
coworkers reported ILV for nonsurgical purposes: respira- it has the disadvantage of high-resistance airways w ith
tory insufficiency from unilateral lung disease. Since then, more difficult suctioning. An endotracheal tube (ETT) w ith
application of ILV has broadened to a wide range of condi- a bronchial blocker (see "Lung Separation," below) has the
tions (Table 26-1) employing a variety of techniques. It was advantage of a wide-bore, low-resistance endotracheal lu-
used in about 0.5% of all ventilated patients 10 in an institu- men with better bronchoscopic and suction access, through
tion familiar with ILV. In most intensive-care units (ICUs), which either OLV (bronchial blocker inflated) or double-
ILV is used irt less than 0.5% of all ventilated patients. ltmg ventilation (bronchial blocker deflated)15 can be
573
574 PART VIII VENTILATOR SUPPORT IN SPECIFIC SETTINGS
with intra- or extraluminal blockers that are more subject

to movement and d islodgment, especially during suction-
ing, bronchoscopy, or patient m ovement. 15 Bronchoscopy is
easier and required less. 12•15 A disadvantage is that the in-
flated blocking balloon near the site of intended bronchial
surgery (e.g., pneumonectomy, single-lung transplant) may
hamper that procedure, and a DLT p laced in the opposite
lung may be technically easier.
PHYSIOLOGIC EFFECTS OF THE LATERAL

DECUBITUS POSITION
When a patient is in the erect or su pine position, gravita-
tional differences in ventilation and perfusion occur ver-
tically within each lung. In the lateral decubitus posi-
A B tion, these gravitational differences occur between the two
lungs.18•19 Up to two-thirds of perfusion shifts to the depen-
FIGURE 26-1 (A) Right and (B) left polyvinyl chloride (PVC)
(Mallinckrodt) double-lumen tubes (DLn shown agains t a dent lung.18' 20' 21 During spo11taneous veutilation, a smaller
sch ematic of the trach ea and major airways. increase in ventilation also occurs in the dependent lung in
the latera l position, thereby reducing ventilation-perfusion
misma tch.18 •19 When the patient is anesthetized and mechan-
delivered. The narrow lumen in some bronchial blockers can icnlly ventilated in the lateral decubitus position, however, re-
enable lung inflation, deflation, CPAP, o r high-frequency duced diaphragmatic activity allows the weight of abdomi-
jet ventilation (HFJV) but does not allow conventional ILV. nal contents to retard expansion of the dependent lung, 18, l9
OLV may be delivered to either lung, but repositioning of and most ventilation is diverted to the nondependent lung.
the bronchial blocker is required.'~ 5 When the blocker is In this situation, the nonde!;endent lung may receive up to
an integral part of the ETT (Univent tube),15- 17 it is easier two-thirds of ventilation.20' •23 Opening the nondependent
to insert and maintains a more stable position compared thorax further reduces ventilation to the dependent lung by
facilitating expansion of the nondependent lung. 21•24 The
net effect of these changes is overperfusion relative to venti-
TABLE 26-1 Indications for Independ ent Lung Ventilation lation (or shunting) in the dependent lung and overventila-
tion relative to perfusion (or dead-space ventilation) in the
Thorncic SurgL'ry nondependent lung with adverse effects on gas exchange.
Pneumonectomy Other factors affect the degree of hypoxia during OLV in
Some lobectomies the lateral decubitus position. Left thoracotomy achieves a
Thoracic aortic surgery higher Pa~ during OLV than does rig ht thoracotomy be-
Thoracoscopy cause the left lung normally receives 10% less cardiac out-
Some esophagea l surgery
put than the right lung.25 The presence of CAO is associated
Selective airway protection with bette.r Pa~ during OLV possibl~ because of dynamic
Secretions (tuberculosis, bronchiectasis, abscess)
hy perinflation in the dependent lung. 5 Pa0 , during double-
Whole lung lavage
Massive hemoptysis
lung ventilation is also predictive of Pa0 2 during OLV.
Bronchia I repair protection Some forms of ILV cannot be applied when the nonde-
Brollchopleuml fistula penden t lung is immobile, deflated, or removed, yet ILV has
been shown to improve many of these abnormalities. Ap-
Aszpnmetrical lung disease
Unilaternl parenchymal injury plication of PEEP to both lungs improves dependent-lung
Aspiration ventilation and oxygenation. 20 Synchronized ILV (SILV; see
Pulmonary contusion "Techniques for ILV," below) with delivery of equal tidal
Pneumonia volumes (VT) to both lungs26 or PEEP to the dependent
Massive pulmonary embolism lung23,27- 30 or both 29 improves oxygenation when com-
Repcrfusion edema pared with double-lung ventilation or generalized PEEP.
Asymmetrical ARDS When OLV is undertaken and the nondependent lung is
Asymmetrical pulmonary edema excluded from ventilation, the reduction in ventilation to
A teltctasis the dependent lung is eliminated, but all perfusion through
Unilateral airfioto obstruction the nondependent lung constitutes a shunt. fn this situa-
Single lung transplant for chronic airway obstruction tion, the amount of perfusion of the nondependent lung
Unilateral bronchospasm
is a major determinant of hypoxia. Hypoxic vasoconstric-
Severe bilateml lung disease tion (not opposed by anesthetic agents), lung collapse, and
ARDS
surgical occlusion of blood now (pneumonectomy) to the
As piration
Pneumonia
nondependent lung all have the potential to reduce shunt
and improve Pao, in OLV.
CHAPTER 26 INDEPENDENT LUNG VENTILATION 575
PEEP in the dependent lung may be beneficial by in- Procedure for Whole-Lung Lavage
creasing functional residual capacity (FRC) and improving To minimize hypoxia during the procedure, the worst lung
distribution of ventilation or be detrimental by increas- should be lavaged first. The worst lung can be identified by
ing alveolar pressure and diverting blood flow to the non- chest x-ray, ventilation-perfusion scan, or oxygenation3•65•66
ventilated lung. 19•31 - 36 Consequently, PEEP to the depen- during OLV to each lung before the procedure.
dent lung during OLV may improve Pae>z,3 1•36 decrease The procedure usually is ferformed w ith anesthesia, neu-
Pa0z,31• 32 ·36 or cause no change.34 - 36 During OLV, Cohen et romuscular paralysis, 11 •57•6 and a left DLT in the supine
al27 compared PEEP (10 cmH20) to the dependent lung, position. The supine position is chosen to balance the risk
CPAP (10 cmH20) to the nondependent lung, and both. between hypoxia and fluid spillage11 (see "Basic Principles
All three maneuvers increased Pao2 compared with OLV of ILV," above).
alone. PEEP caused the smallest (nonsignificant) increase in Complete ltmg isolation to prevent spillage from the
Pa0z. CPAP a nd PEEP+ CPAP caused larger (significant) lavaged lung into the ventilated lung is essential (see "Lung
increases in Pa0 2, whereas PEEP+ CPAP reduced cardiac Separation," below). Correct DLT position should be es-
output and oxygen (02) delivery significantly, w hich CPAP tablished using both auscultation and bronchoscopy, and
alone did not. Cohen et al27 concluded that CPAP alone (to leak testing should be verified by ventilating one lw1g at
the nondependent lung) had the most beneficial effect by a plateau pressure of 40-50 cmH 20 11•12 and connecting the
diverting blood flow to the dependent lung without reduc- airway of the contralateral lung to an underwater seaJ to
ing cardiac output. More recently, PEEP has been shown ensure the absence of bubbling. Both lungs should be pre-
to benefit oxygenation during OLV to the dependent lung oxygenated with 100% 02 to maxirruze gas exchange and
during thoracotomy.37 eliminates nitrogen, which may prevent full access of lavage
Because of these variable effects, it has been recom- fluid to the lung to be lavaged.
mended that CPAP (5-10 cmH20) be applied to the I so tonic saline, warmed to body ternperature, then should
nondependent lung, combined with no, low, or high PEEP be infused through wide-bore tubing into the lung to be
(5-15 cmH2 0) to the dependent hmg, depending on patient lavaged from a gravitational height 30 em above tl1e midax-
response. illary line11 in volumes compatible with the infusion pres-
Although function of the two lungs commonly differs sure (30 cmH20) and compliance of the lung (usually 500-
after thoracotomy, conventional mechanical ventilation or 1000 ml). Efflux of fluid may be commenced as soon as fluid
spontaneous ventilation usually are resumed after surgery. influx is complete; the drainage tube is placed below the pa-
ILV is required occasionally in the postoperative period tient, assisted by head-down posturing and percussion and
for marked asymmetry of lung function with hypoxia, 8•9·38 vibration of the hemithorax. 11•67 Fluid flow may be achieved
bronchopleural fistula,39 - 43 or following esophagectomy. 14 using separate clamped inlet and outlet lines or a single line
that is elevated for fluid influx and lowered for fluid efflux.
Total fluid exchange may range from 10- 50 liters a nd should
be continued untiJ efflux fluid is relatively clear.
SELECTIVE AIRWAY PROTECTION
When fluid influx into the lavaged lung is complete, the
WHOLE-LUNG LAVAGE alveolar pressure usually exceeds the pulmonary capillary
Pulmonary alveolar proteinosis is the most common indi- pressure, minimizing shunt through this lung and maximiz-
cation for whole-lung lavage. This condition was first de- ing arterial oxygenation at this stage of the procedure.57•67 - 70
scribed in 1958,44 and soon after, bronchopulmonary lavage When the lavaged lung is emptied of fluid, blood flow re-
became established as the main treatment. 45 - 53 turns, and significant hypoxemia can occur. 11,57,67- 69
Pulmonary alveolar proteinosis is most often acquired On conclusion of the lavage, double-lung ventilation
(90%) but may be congerutal or secondary to conditions should be recommenced with the DLT in situ using a single
such as acute silicosis and other inhalational syndromes, ventilator and a bifurcated circuit. If oxygenation is satisfac-
immunodeficiencydisorders, malignancies, hematopoietic tory, the patient may be weaned and extubated or reintu-
disorders, and lysinuric protein intolerance.54 Recent stud- bated with a regular ETT and later weaned. If oxygenation
ies suggest that acquired pulmonary alveolar proteinosis is unsatisfactory, ILV may need to be recommenced. Up to
may be caused by deficiency of granulocyte-macrophage 1000 ml of saline may be retained in the lavaged lung 67;
colony-stimulating factor,54•55 and administration of this although this is absorbed rapidly, lung function may not
factor is of value in about 50% of patients. Despite these improve for hours or days. The procedure is repeated on
advances, lavage remains the most effective therapy. 54•55 the second lung after an interval of 1-3 days.
The clinical course is variable: increasing dyspnea pro- Leakage of fluid into the ventilated lung may be recog-
gressing to respiratory insufficiency, static disease with min- nized by desaturation, crepitations, and rhonchi in the ven-
imal symptoms, asymptomatic disease, and spontaneous tilated lung; fluid in the tubing to the ventilated lung; or
resolution in some patients.54•56 Because the course is vari- air bubbles in the fluid from the lavaged lung. 11 If this oc-
able, the decision to undertake bronchopulmonary lavage curs, lavage should be ceased, and the patient should be
is based on disease progression and symptoms. placed in the lateral decubitus position with the lavaged
Whole-lung lavage has been used for asthma,57·58 chronic lung dependent and the head down to facilitate drainage
bronchitis, and cystic fibrosis 11 ·51·57- 63 but with doubtful from botl1 lungs. Active suctioning of both lungs should
benefit, and it is no longer recommended. Radioactive dust be undertaken. If the leak is only minor and adequate
inhalation is another indication.M oxygenation is restored, the correct DLT position may be
re-established, lung isolation rechecked, and the procedure placed in the head-down lateral-decubitus position, bleed-
continued. With a major leak and failure to restore ade- ing side down, clotting studies performed, blood typed,
quate oxygenation once fluid removal is complete, double- wide-bore intravenous access established, and cough sup-
lung ventilation with PEEP should be resumed and further pressed with an opiate, and resuscitation and suction equip-
lavage delayed until hypoxia has improved. ment should be in close proximity.
Hypoxemia during the procedure is common. Some pa- A number of alternatives exist for localization, isolation,
tients with severe lung disease are too hypoxemic before the and control of the bleeding. Their choice depends on the
procedure to tolerate OLV. Sever al options exist for such pa- rate of bleeding, ready availability, a nd skill of the personnel
tients. Extracorporeal membrane oxygenation (ECMO) may involved.
be instituted before lavaging the first lung.11 ·71 - 75 ECMO
may or may not be required for lavage of the second lung 1. Fiberoptic bronchoscopy and placement of an endo-
depending on the effect of the first lung lavage on s ubse- bronchial blocker (Fogarty catheter or Arndt endo-
quent oxygenation. Cohen et aJ13 reported successful lavage bronchial blocker) in the bleeding lung or segment should
of both lungs with ECMO during a single session, avoiding be done.92 - 96 This can be performed in a patient w ho
the need for a second procedure. Because of the complex- is not intubated but is easier in one who is. Fiberop-
ity and limited availability of ECMO, an alternative is to tic bronchoscopy is limited by the narrow suction chan-
perform limited bronchoalveolar lavage using a fiberoptic nel and rapid visual loss secondary to occlusion of the
bronchoscope/ 6•77 with or without an inflatable cuff on the lens by clot.91 Bronchoscopy allows accurate localization
bronchoscope, under local anesthesia. This may be under- of bleeding,56•80·91 •97•98 catheter placement in a bronchial
taken in a spontaneously breathing patient or during con- segment,80•92•99 and lavage w ith iced isotonic saline or
ventional mechanical ventilation (CMV) through a single- epinephrine.80•99
lumen E1T. Limiting lavage to a lobe or several subsegments 2. Rigid bronchoscopy has advantages over fiberoptic bron-
necessitates multiple procedures but minimizes hypoxemia. choscopy when blood loss is massive because of better
Nadeau et aJ78 reported that the combination of inhaled suction, visual access, and airway controL.88,90,91,97,100,101
nitric oxide and inflation of a balloon in the right pulmonary It allows easier placement of endobronchial blockers, iced
artery during right whole-lung lavage improved oxygena- saline, or epinephrine lavage and also allows diathermy,
tion sufficiently to avoid ECMO. laser and cryotherapy32 and placement of endobronchial
Randomized studies of whole-lung lavage for pulmonary tampons soaked in vasoconstrictor dmgs. 88 As use of em-
alveolar proteinosis have not been undertaken. Seymour bolization increases, rigid bronchoscopy is required less,
and Presneill 54 analyzed survival of 231 patients in mul- although it still has a place.97•1oo
tiple reports; 5-year actuarial survival from diagnosis was 3. Endotracheal intubation may be required where bleed-
94% ± 2% in patients who underwent w hole-lung lavage ing is sufficient to compromise oxygenation, particularly
(n = 146) compared with 85% ± 5% for pa tients who did if mentation is depressed or cough inadequate. If bleed-
not (n = 85). In 55 patients in whom duration of benefit ing is so rapid that acute asphyxic arrest is imminent de-
was reported,54 median duration of benefit from lavage was spite intubation,80 the ETI can be advanced beyond the
15 months; fewer than 20% of patients followed beyond carina (usually into the right main bronchus) and OLV
3 years rem ained symptom-free. In a series of 21 patients commenced.80•102 If blood does not flow out of the EIT
followed prospectively after whole-lung lavage, Beccaria (implying blood loss from the contralateral side), the cuff
et al 79 found that more than 70% remained free from recur- is inflated and the EIT left in situ. If bleeding continues
rent pulmonary alveolar proteinosis at 7 years. Although through the EIT, a Fogarty or Foley catheter is passed,
whole-lung lavage is labor-intensive, these data suggest that the main bronchus is occluded, and the ETI is withdrawn
it is worthwhile. to the trachea to ventilate the contralateral side.
4. Selective intubation is performed w ith a small (6-7 mm)
MASSIVE HEMOPTYSIS EIT, with o r without fiberoptic bronchoscope guidance,
Massive hemoptysis carries a high mortality80- 82 and re- or w ith a selective left o r right endobronchial tube.so,ss
quires prompt intervention. Common causes include tuber- Selective intubation must be preceded by accurate bron-
culosis, bronchiectasis, lung abscess, mycetoma, pulmonary choscopic localization of bleeding because it excludes one
carcinoma, cystic fibrosis, arteriovenous malformations, lung from ventilation. Selective intubation has the advan-
and trauma.56•80•83 The source of bleeding is the bronchial tage of reliable protection of thenonbleeding lung 88•91 but
art erial system in 90% of patients.84 Ia trogenic causes are the disadvantage of permitting OLV only and excluding
w1common but include pulmonary a rtery rupture by a the bleeding lung from endobronchial procedures and
pulmonary artery catheter-8°·85•86 and transbronchial lung suctioning. Bleeding then mus t be controlled by tampon-
biopsy. Death results from acute asphyxia and is related ade, bronchial angiography, and embolization or surgery.
to the rate and volume of blood loss and the underly- 5. DLT insertion is an alternative that isolates the lungs but
ing condition.80·81 ·87- 89 Factors increasing mortality include preserves access to both. In the pas t, DLTs were not rec-
pre-existing pu lmonaryinsufficiency, obtundation from any ommended as an early alternative80,88 to control bleed-
cause, poor cough, and coagulopathy.81.88,90.91 ing. Problems included difficulties w ith insertion under
Management consists of general measures, diagnosing adverse circwns tances, requirement for an experienced
the site of bleeding, isolating the bleeding lung, and con- operator, difficulties with suction and bronchoscopy ac-
trolling the bleeding. The patient should be given 100% 0 2 , cess, and easy blockage of DLT lumen w ith d ot. More
recently, use of PVC DLTs has been successfu1.83, 87,103 A one-lung high-frequency ventilation in the management of
DLT enables lateralizing of the bleeding, protects the non- a traumatic tear of tl1e bronchus in a cluld. After a right
bleeding lung, allows ILV, and allows therapeutic pro- main-stem bronchial rupture, Moerer et al110 used a left DTL
cedures to address the bleeding lung without compro- with bilevel ventilation to tl1e left lung and CPAP alone to
mising tl1e healthy lung.87•103 A left DLT is the tube of the right lung for 48 hours before switching to CMV. ln
choice.83,B7, SS, 103 Most commonly, a single ventilator with three patients with lower tracheal rupture (near the carina),
a Y connection to the DLT lumens is used 87 with distri- Wichert et ai'111 reported that standard DLTs position the cuff
bution of ventilation according to the relative impedance too close to the site of carina} injury and used bronchoscopy-
of the two lungs (see "Lung Separation," below). If there guided selective endobronchial intubation with two tubes
is risk of blood overflowing to the nonbleeding lung, or to undertake the repairs. After repair, tl1e tubes were rein-
if differential ventilation is required, a second ventilator troduced via tracl1eostomy, and ILV was performed for
with asynchronous TLV (AILV) should be used. OLV must 9-14 days to allow recovery from respiratory and other
be p resent during bronchial blockade or endobronchial complications.
intubation and may be required during iced-saline lavage
or massive blood loss.
BRONCHO PLEURAL FIST ULA
6. Embolization. Since 90% of major hemoptyses arise
from bronchial arteries,84 once bleeding has been local- Bronchopleural fistulas (BPFs) can result from trauma,
ized, bronchial artery embolization has a high success necrotizing pneumotua, lung abscess, tuberculosis, acute
rate .56, 84, 98, lo.t- 106 respiratory distress syndrome (ARDS), thoracic surgery,
7. Emergency surgery. Urgent resection is undertaken if overinflation from mechanical ventilation, central venous
bleeding overwhelms airway control or fai ls to respond catheter insertion, and intercostal catheters. Persisting BPF
to other measures. Resection is associated with a low often leads to infection of the pleural space. 114 If massive air
mortality in many series.56,81 ,91 •97•105,107 It should not be leak from a BPF occurs during mechanical ventilation, the
unduly delayed if bleeding is not readily controlled. consequences include respiratory insufficiency and some-
times tension pneumothorax. Persisting failure of lung ex-
Localization of bleeding usually is achieved by history, pansion can occur despite intercostal catheters if the rate of
fiberoptic bronchoscopy, or radiology [chest x-ray, com- air leak exceeds the rate of drainage through the catheters.
puted tomographis (CD scan, or angiography). Bleed- BPFs are estimated to occur in 2% of ventilated patients .m
ing is controlled by conservative measures, emboliza- Mortality depends on the size of the leak 115 a11d the cause
tion, or surgery.56•98•105 The relative requiren1ent for these and is reported to be 18-67%.114·115
three treatments varies widely56·98• tos depending on cause, Management includes antibiotics, pleural sclerosing
amount of bleeding, and local expertise. Supportive care, agents, surgical control of air leaks at thoracotomy, inter-
correction of coagulopathy, and time as the only measure costal catheter insertion, underwater seal drainage with
ranged from 13- 87% of patients with major hemoptysis. suction, conventional ventilation strategies to reduce air
Embolization was used in 7-51% with success rates of over leak, patient positioning114 positive pleural p ressure during
80%. Surgery was required in 6-50%. inspiration,114•11 6 HFJV, a variety of b ronchoscopic occlu-
sion techniques, and ILV. TLV generally is employed when
LUNG PROTECTION FROM SECRETIONS massive air leak persists despite conservative measures and
Spread of purulent secretions from a lung abscess, results in respiratory insufficiency. Before instigating ILV,
empyema, bronchiectasis, cavitating tuberculosis, or cav- conservative measu res should be optimized.
itating malignant disease to the dependent normal lung Inadequate drainage can occur despite actively bubbling
during chest surgery is associated with considerable intercostal catheters and can lead to failure of lung ex-
risk.1.2·6•7•108 A DLT not only allows thoracic surgery but pansion and respiratory insufficiency. Intercostal catheters
also protects the dependent normallung1A2, 108 and allows must be adequate in number and diameter; their patency
perioperative ILV if required.1•42•108 Although these condi- mus t be visualized and demonstrated by active bubbling.
tions have become less common, the requirement for ILV Underwater-seal drainage systems and wall-suction units
for lung protection, during or outside thoracic surgery, oc- must have an adequate maximum flow capacity. Air-fil ter
curs occasionally. 109 Essential during thoracic surgery, it is patency must be checked. High resistances and low max-
problematic outside that setting because viscous or tena- imum flow rates in either the drainage system or wall-
cious secretions drain poorly through the narrower lumen suction unit actually can retard thoraci.c drainage and in-
of a DLT. Appropriate antibiotic therapy, postural drainage, crease pneurnotl1orax size. Ideally, maximum flow capacity
and a standard ETT may be preferable. should approximate or exceed the percentage of VT lost to
the BPF multiplied by the inspiratory flow rate. Drainage
BRONCHIAL REPAIR PROTECTION devices vary widely in maximum flow capacity but rarely
Main-stem bronchi and lower tracl1ea (near the carina) can exceed a capacity of 35liters/min. Increased bubbling or ra-
be ruptured by severe blunt chest trauma, resulting in ten- diologic improvement after suction disconnection suggests
sion pneumothoraces, massive air leak, and the need for retardation b y the device. Persisting negative pressure on a
urgent surgical repair. Selective airway intubation usually wall-suction unit after disconnection suggests an occluded
is required for the repair, and ILV has been used pos toper- air filter. With massive air leaks, more than one underwater-
atively to protect the anas tomoses.110- 113 Pizov et al 11 3 used seal drainage system may be required.
578 PART VIll VENTILATOR SUPPORT IN SPECIFIC SETTINGS
The conventional ventilator stra tegy for a BPF has three lar resistance in the unaffected lung (diverting blood flow
goals: reduce air-leak rate (to facilita te h ealing), reduce to the injured lung). This hyperinfla tion also can elevate
pneumothorax size, and m aintain adequ ate gas exchange. intrathoracic Eressure, reduce arterial pressure and cardiac
These goals o ften have conflicting needs. The usual strat- output,' 29•130· 32· 133 and combined with arterial d esaturation
egy is directed toward lowering alveolar and airway pres- reduce 0 2 delivery.19,129,130, 136- 14t
sure to reduce air leak. VT and PEEP should be minimized The prime objective of ILV under these circumstances
and the rate reduced , especially if dynamic hyperinflation is differential PEEP, although different ventilator patterns
is present, although these steps m ay impair gas exchange. have been applied to achieve a similar effect and optimize
Inspira tory flow is controversial. Increasing flow may de- gas exchange and minimize barotrauma. ILV allows lung
crease air leak b y d ecreasing inspiratory time or increase recruitment maneuvers and high PEEP to the affected lung,
proximal air leak by increasing peak airway pressure. The permitting maximum benefit to that lung without adverse
impact of any change o n all three goals must be assessed. effects on the contralateral lung, intra thoracic pressure, car-
HFJV without ILV appears to benefit patients with a diac output, and the dis tribution of ventilation between the
proximal BPF and otherwise relatively normal lungs.n 4 two lungs. PEEP applied to the diseased lung can improve
Reported su ccess of HF]V in patients w ith paren chy- oxygenation b y alveolar recruitment and diverting blood
mal lung disease, w hose BPFs usua lly are peripheral, is flow to the more normal lung. Low or no PEEP in the more
variable. 114 ILV has been u sed in ma ny patients with a normal lung avoids h yperinflation and the adverse effects
BPF.39- 43,n S,l1 7 - 130 Conditions in w hich ILV has been used of high intrathoracic pressure.
for BPF include pneumonia with and without CA0,41 ·122,-126 ILV has been u sed in various unilateral or asymmetric
ARDS,l19 trauma,41•115•117•120·124 pulmonary contusion, 128 lung diseases (see Table 26-1). The m ost common indication
emphysema, asthma, 118 staphylococcal pneumatoceles,·12'1 has been pulmonan; contusion. Of 45 patients w ho received
and thoracic surgery.39-43 Most patients had air leaks ex- ILV for asymmetric lung injury,10.41·11 7·132- t35,142-144 three
ceeding50% ofVT, lungcollapsedespite multiple inter costal received SILV,132•133 but most received AJLV.10,117,134,tJS:I42
catheter insertions, and hyp ercapnic acidosis and hypoxia Two patients received no mechanical ventilation and
despite a ttempts at optimizing mechanical ventilation. breathed spontaneously through a DLTwith different levels
The most common form of ILV for BPF is asy nchronous of CPAP applied to the expired limb of each circuit. 144 All
ILV (AILV) using two ventilators 40•42• 123- 125 with low VT, methods improved gas exchange, and overall mortality wa s
low rates, and low or n o PEEP for the lung with the BPF. only 10%. In 12 trauma patients with unilateral contusion
The BPF lung also has been ventilated with syn chronous requiring ILV, Cinnella et a l142 monitored end-tidal C02 and
ILV (SILV) with low VT, PEEP, and inspiratory flow43·126·129; static compliance in each lung and reverted to con ventional
HFJV41 ·127; and high-frequency oscillation119 or excluded ventilation when these b ecame similar in the two lungs.
from ventilation by a Fogarty catheter passed throu gh a DLT ILV has been reported m patients with
after failing to respond to both CPAP and jet ventilation.'122 1
aspirati.on38, l23, 2 ·9 130 and pneumoma or corzsolida-
Successful u se of a DLT with a sing le ventilator and a tion.10,l26·129· 130, I45-150 As with contusion, a mixture of
varia hie-resistance valve in the inspiratory circuit to the BPF AILV and SILV has been u sed . In on e pa tient, high-
lung h as been reported in an animal model131 and in one frequency oscilla tory ventila tion (HFOV) was used w ith a
patient39 with a large BPF. higher mean airway pressure to the affected lung.147 SILV
Almost all authors report reduction in air leak with im- has been used in patients with unilateral consolid a tion on
provement in gas exchange. ILV was continued from 2 a background of co~enital heart disease with asymmetric
hours42 up to 10 days40 in some patients before CMV could lung blood suppl y. 1 · 146 Mortality was 48%.
be resumed. Improvement was reported in most patients SILV has been repo rted in patients with asymmetric
with ILV. Overall survival was about 50%, although a large ARDS secondary to trauma a nd sepsis (56% mortality151 ),
BPF is as a p oor prognostic factor.114 Outcome mainly was asymmetric acute pulmonary edema,130·145· 152 and massive
related to the prognosis of the underlying condition. pulmonary embolism.153 In a patient with a single-lung
transplant it enabled weaning from ECM0.152
All patients received differential PEEP: 0-10 cmH20 on
ASYMMETRIC LUNG DISEASE
the unaffected side and 7- 25 cmH20 on the a ffected side.
ILV has been u sed for a variety of unilateral or asymmetric In all cases, higher PEEP was u sed on the affected side. VT
lung diseases (see Table 26-1). Three main indications are values to the two lungs were equal in some studies, smaller
unilateral pulmonary parenchymal injury, unilateral atelec- to the affected lung in som e, a nd larger in one study.133 In
tasis, and unilateral airflow obstruction. two studies, PEEP administered to each affected lung was
carefully adjusted to the complian ce resp onse of that lw1g .
UNILATERAL PARENCHYMAL INJURY Carlon et al130 increased PEEP in the affected lung until its
Patients who receive ILV for asymmetric pulmonary in- compliance was similar to that of the unaffected lung . Siegal
jury have p oor compliance on the affected side, hypox- et al151 found that increasing PEEP in the affected lung ini-
emia refractory to high ~ concentrations, and high lev- tially improved compliance, but then it d ecreased secondary
els o f PEEP. Under these circumstan ces, PEEP may cause to overinfla tion. They set PEEP at the level that achieved
hyperinflation of the unaffected lung, collapse of the af- maximum compliance. Both methods improved oxygena-
fected lung,U2•133 barotrauma,132- 135 and worsening of tion, shunt fraction, and cardiac o utput. The duration of
hy poxemia 132 consequent to increased p ulmonary vascu- ILV ranged from 1 hour133 to 12 d ays.135
From these reports, several factors emerge as require- consequences of raised i11trathoracic pressure and is rec-
ments for ILV: ommended for lung collapse.154 In unilateral atelectasis, re-
cruitment maneuvers should be undertaken routinely dur-
1. Differelltiill PEEP with a higher level applied to the af- ing double-lung ventilation (unless contraindicated by a
fected lung is a key factor. PEEP may be applied to the af- problem in the nonatelectatic lung) before attempting ILV
fected lung until gas exchange improves, to an inflection and may prevent the need for ILV in many patients.
point15'1 on a compliance curve, until lung compliance
is equal on the two sides,130 or based on C02 excretion. UNILATERAL AIRFLOW OBSTRUCTION
PEEP most commonly is 10-20 cmH20. A recruitment Unilateral airflow obstruction ocetus most commonly fol-
maneuver and PEEP level that maximizes arterial oxy- lowing single-lung transplantation (SLT) but may occur
genation can be recommended. 154 PEEP may or may not with a mechanical or chemical insult to one lung in a pa-
be required in the contralateral lung. tient with asthma or partial occlusion of a major bronchus.
2. Equal Vr to both lungs was used most commonly and Under these circumstances, standard ventilation can cause
was most likely to maximize gas exd1ange22•23•26 corn- dynamic hyperinflation and high intrinsic PEEP in the ob-
pared smaller or larger VT values to the affected lung. structed lung. This can elevate intrathoracic pressure, re-
Maintenance of plateau pressure below 30 cmH20 is an duce cardiac output, and compress the contralateral lung.
important goal.155·156 To achieve hypoventilation of the obstructed lung, SILV
3. AILV or SILVis equally acceptable because there is no can be used with a much lower VT to the obstmcted lung. It
requirement for a different respiratory rate. AILV holds is better achieved with AlLV using reduced rate and VT (or
no disadvantages when compared with SILV38·157 and is CPAP alone) to the obstructed lung. 159,163
simpler and more flexible.
Sin gle-Lun g Transplantation
The primary goal of ILV and differential PEEP or CPAP Early reports suggested that SLT was contraindicated in
is improvement in gas exd1ange and hemodynamics and chronic obstructive pulmonary disease (COPD) because of
physical expansion of collapsed lung regions. the risk of dynamic hyperinflation in the native lw1g with
mediastinal shift.74.1 64 Initial experience supported these
UNILATERAL ATELECTASIS concems. 165- 168 Subsequent series 164,169- 178 combined with
Unilateral atelectasis that has failed to respond 210 SLTs at our institution result in a total of 733 pa-
to standard ventilator support, bronchoscopy, or tients. Overall early mortality is 18% and only 13% when
both9,38,103,129,130,133,136,149.158- 161 is another indication the primary diagnosis is CAO (emphysema, a1-antitryspin
for ILV. High PEEP has been applied to the atelectatic lung, deficiency, leiomyoangiomyomatosis) (Table 26-2). Thirty-
primarily for the purpose of reinflation without the risk day mortality varies widely (0%172 to 50%169). Small series
of overinflating the contralateral lung and generalized reveal that early mortality 164· 169, 176· 177 ranges from being
elevation of intrathoracic pressure. slightly lower with SLT than with bilateral lung transplant
In some studies,129· 130•136· 149·"59·162 high PEEP was applied (BLT)164·176•177 to higher with SLT.169 Larger series suggest
to the atelectatic lung during AILV orSILV with mechanical lower mortality with BLT,'~ 79 - 1 82 although selection criteria
ventilation of both lungs. The collapsed lung received 10- such as age may have contribute. 179
30 onH2 0 of PEEP, whereas the unaffected s ide received Despite this uncertainty, SLT is now a popular alterna-
0-10 crnH20 of PEEP. In other studies, the collapsed lung tive to BLT, especially in patients over 50 years of age. SLT
received transient CPAP a1one9• 103· 159- 161 (20- 80 cmH2 0) is technically easier than BLT and benefits more recipients
without mechanical or spontaneous ventilation. Miranda when donor availability is a limiting factor. The most com-
et al160 applied 30 onH20 of CPAP via a DLT to reinflate a mon indication for SLT is some form of CAO, which ac-
collapsed lung and subsequently used HFJV with 25 cmH20 counts for 77% of SLTs. 164•169- 178 Although lung ftmction
of PEEP (to the same lung after expansion) to improve gas is better after BLT, SLT substantially improves quality of
exchange. Millen et aP 61 transiently applied 60-70 cmfhO life164,176 and achieves equivalent maximum work capacity
of CPAP to individuallw1gs in two nonintubated, sponta- and maximum 0 2 consumption. l 83
neously breathing patients via a cuffed fiberoptic broncho- Over 30 reports152,159,163- 178i184- 196 plus experience from
scope with good results. Narr et al 159 required 80 cmH20 our institution provide information on 768 patients
of CPAP to reinflate an asthmatic lung that collapsed dur- receiving SLTs, 601 for CAO. ILV was required al-
ing pleurodesis and then subsequently used AILV with a most exclusively in patients who received SLT for
very low rate to the same lung to reduce its hyperinfla- CAOl63,169,171-173,177,178,184,186-189,191,193 There are few re-
tion. Plotz et al158 used HFOV (mean airway pressure of ports of patients requiring ILV after BLT for any reason,
28 onl-hO) to the atelectatic lung of a child, with CMV to nor after SLT for restrictive lung disease. In one patient,.193
the unaffected lung. There was no report of lung injury de- ILV was required for a large, unresolving BPF arising in
spite transient application of very high inflation pressures, the native lung after SLT that evenh1ally necessitated pneu-
and there were only 2 deaths in this group of 14 patients monectomy of the native lung. In another patient, 152 ILV was
with atelectasis.9,38,103,130,136,149,158-'1 60, 162 required for reperfusion edema after SLT for primary pul-
These reports demonstrate success with a range of re- monary hypertension. Use of ILV in SLT series for CAO (see
cmitment maneuvers. Application of CPAP up to 50-60 Table 26-2) varies widely: 0%164,170•174- 176 to 43%, 169 with an
cmH2 0 to both lungs for a few minutes has no prolonged overall frequency of 9%.164,169- 178
580 PART VIII VENTILATOR SUPPORT IN SPEOFIC SETTINGS
TABLE 26-2 In cid en ce of acute native lung hyperinflation (ANLH) and incidence and mortality with independent lung ventilati on
(ILV) in patients undergo ing single lung transplantation (S LT) for airflow obstru ction.
SLT FOR AIRFLOW RADIOLOGICAL SYMPTOMATIC TLV

OBSTRUCTION ANFTL ANliL TLV MORTALITY
Authors No. Pts No. Died Mortality No. % No. % No. % No. %
Kaiser et aJ 11 0 0% 1 9% 0 0%
Patterson ct a! 7 1 14% 1 1 0
Egan et aJ 4 0 0% 1 25% 0 0%
Marinelli eta! 7 1 14% 0
Low eta! 16 2 13% 0
Montoya eta! 39 1 3% 0
Yonan et aJ 27 5 19% 12 44% 12 44% 8 30% 2 25%
WeiU etal 51 0 0% 16 31% 8 16% 1 2% 0 0%
M itchell et aJ 132 34 26% 13 10% 6 46%
Hansen eta! 90 1 1% 0
Angles eta! 14 7 50% 9 64% 9 64% 6 43%
Author's 170 21 12% 78/95 82% 20 12% 20 12% 7 35%
institution
Totals 568 73 13% 116 60% 50 19% 50 9% 15 30%
From Kaiser et al 178, Patterson et al l6-l, Egan et at 177, Marinelli et at 175 , Low et at 176 , Montoya et at 174 , Yonan et al 173, Weill et al 179, Mitchell et al 171 , Hansen
et al 170, Angles et al 169 and the author's institution (unpublished).
The phenomenon leading to use of ILV has been termed lapse, hypoxia, or hypotension and without the need for
acute native lung hyperinJ1atiOir (ANHL), which is defined as ILV.164,195 This phenomenon arises because of asymme-
radiologic mediastinal shift with flattening of the ipsilateral try of lung disease following transplantation. The native
hemidiaphragm (Fig. 26-2A) associated with signs of hemo- lung with severe airflow obstruction undergoes dynamic
d ynamic instability or respiratory dysfunction. 169,172,173 hyperinflation during CMV, just as both lungs would do
Evolution of this phenomenon can be divided into three during CMV before transplantation.197 A healthy trans-
stages: planted lung with normal compliance and airflow resis-
ta nce will receive most of the blood flow and ventilation,
1. Asymptomatic ANLH. Dynamic hyperinflation of the na- thereby reducing the degree of dynamic hyperinflation
tive lung with mediastinal shift is seen commonly in that would have occurred if both lungs received the same
the postoperative period without transplant-lung col- ventilation. Nevertheless, the trans planted lung does
FIGURE 26-2 Chest x-rays of a patient with a right single-lung transplant before (A) and (B) after insertion of a right double-lumen tube
and independent lung ventilation, as sugges ted in Table 26-4.
A B
TA BLE26-3 In cid en ce of radiological and symptomatic acute native lung hyperinflation (ANLH) in left
and righ t single lung tra nsplantation (S LT) for airflow obstruction .
RADIOLOGICAL ANHL
LEFT RICHT
No. Total (Yo o. Total % P value
Weill et aJ 10 27 37 6 24 25 NS
Author's instituition 45 54 83 33 41 80 NS
TOTAL 55 81 68 39 65 60 NS
SYMPTOMATIC ANHL
LEFT RICHT
No. Total % o. Total % P value
Weill et aJ 4 27 15 4 24 17 NS
Angles et at 5 6 83 4 8 50 NS
Author's institution 14 82 17 7 88 8 NS
TOTAL 23 115 20 15 120 13 <0.05
From Weill et al 179, Angles et aJ 169 and the author's institution (unpublished)
not have a "balancing" degree of dynamic hyperinfla- 3. Mechanical ventilation response. The typical response to a
tion, and mediastinal shift occurs commonly. The occur- lung collapse with worseni11g hypoxemia and hypercap-
rence of asymptomatic ANHL is reported infrequently nia includes increasing PEEP, increasing rate, and/ or in-
(Table 26-3). Weill et al172 reported asymptomatic ANHL creasing VT. Each response increases dynamic hyperin-
in 16 of 51 patients (31%), although smaller series have flation in the native lung,197• 198 which can worsen gas
reported symptomatic ANHL in 44%173 and 64%169 of exchange, precipitate circulatory collapse, and necessi-
SLTsforCAO. In our institution, mediastinal shift (shift of ta te ILV. Although the requirement for ILV usually is
right heart border rela tive to the spine by 1 em or greater attributed to step 2 (above), the precipitant often is the
toward the transplanted lung) occurred in 78 of 95 con- fa ilure to improve (or deterioration) with mechanical
secutively evaluated SLTs (82%) for CAO (see Table 26-3) . ventila tion. Risk factors for this problem, in addition to
The asymmetry usually improves or resolves over time, injury to the transplanted lung (above), include severity
but it persists indefinitely in some patients. In some
tients it can arise weeks or months after transplant.'16
ra- of airflow obstruction in the native lung, size of the trans-
planted lung, and side of the transplant. Severity of air-
2. Transplanted lung dysfunction. Any dysfunction in the flow obstruction directly affects the degree of dynamic
transplanted lung, whether parenchymal (e.g., reperfu- hyperinflation.197•198 Yonan et af173 found tha t patients
sion edema, contusion, rejection, pneumonia, o r collapse) who developed ANHL had higher pulmonary artery
or airway (e.g., anastomos is narrowing or sputum ob- pressures, higher residual volumes, and lower forced ex-
struction), impedes ventilation in the transplanted lung piratory volumes (FEV1 ) than did patients who did not
and redistributes ventilation to the native lung, espe- develop symptomatic ANHL. Weill et al172 suspected
cially during volume-controlled ventilation. This nec- more symptomatic ANHL in patients with bullous
essarily increases dynamic hyperinflation in the native emphysema, but lung function and pulmonary artery
lung a nd increases mediastinal shift and collapse and pressure were equivalent among patients with and with-
further impairs gas exchange in the transplanted lung. out symptomatic ANHL. Angles et al169 found no pre-
A vicious cycle results, redistributing more ventilation operative predictors of ANU-I. The size of the donor
to the native lung with greater dynamic hyperinflation lung164•178• 188 is an important factor. A donor's predicted
and mediastinal shift. Progressive compromise of the vital capacity (VC) that approximates 178 or is smaller
transplanted lung can lead to refractory hypoxia and hy- than188 the recipient's predicted VC is associated w ith
percapnia, whereas dynamic hyperinflation, mediastinal the need for ILV. Donor-to-recipient predicted VC ratio of
shift, a nd pulmonary vessel compression can lead to cir- 1 .4'~ 78 or a donor-lung predicted VC exceeding recipient-
culatory compromise 'With hypotensio n (see Fig. 26-2A). lung predicted VC by 2 1iters 164 is associated with the
Primary dysfunction of the transplanted lung, 189 severe absence of mediastinal shift following SLT. Others have
postimplanta tion syndrome,188 and ARDS have been fo und no difference in donor size.172
identified as major contributors to native-lung hyperin-
flation and mediastinal shift. 177•178•186• 188• 189, 191 It usually Several reports have suggested a higher incidence of
results in hypotension, collapse of the transplanted lung ANLH with left SLTs (see Table 26-3). Weill et al172 found
w ith hypoxia, or both. This has been termed symptomatic radiographic ANLH in 37% of left SLTs and 25% of right
ANLH172•173 (see Table 26-3). Almost all such problems SLTs and no difference in symptomatic ANLH (Table
have occurred o nly during mechanical ventila tion in the 26-4). Angles et al169 did not report radiographic ANill but
immediate or early postoperative period. found symptomatic ANLH in 83% of left SLTs and 50% of
TABLE 26-4 Venti lator settings for independent ven tilation blockad e,178•186 CPAP,193 or spontaneous ventilation (SV).188
after single lung transplantation for airflow obstructi on. to the native lung. All methods are viable o ptions. The ven-
Native Lung Transplanted Lung
tilatory requirements of each lung differ so much, however,
that AILV is the metl1od of choice primarily because of dif-
Ventilator rate (b/ min) 2- 4 14- 20 ferent rate requirements of the two lungs (see Table 26-4).
Tidal volume (ml/kg) 2- 3 3- 4 AILV was the method of choice in 27 patients in tl1ree re-
Plateau pressure (em H20) <25 <30 cent series169•171 •173 and in the 20 patients at our institution
lnspiratory flow ra te 80 40- 50 who received ILV. The donor lung commonly requires PEEP
(L/ min at a sufficient level to expand collapsed regions and im-
PEEP (em H 2 0) 0 10- 17
prove oxygenation, a VT sufficiently low to avoid pressure
Recruitment maneu ver No ± 35-50*
injury to the lung, and a rate high enough for adequate C02
(em H 20)
elimination without causing flo w limitation. A recruitment
• StabiHty of the anas tomosis and the presence of air leak need to be considered maneuver may maximize the benefit from PEEP, provided
before undertaking a recru itment maneuver. l ower than normal recruitment that it is safe to undertake}54 The native lung should be
pressures may be initially chosen. ventila ted with a pattern that maximizes its contribution
to gas exchange without excessive d ynamic hy perinflation.
right SLTs. At our ins titution, mediastinal shift did not differ This necessitates low VT, high inspiratory flow rate, and a
between left and right SLTs for CAO, but ILV was required very low rate 198 (see Table 26-4). The goals of native-lung
tw ice as often w ith left SLTs (see Table 26-4). ventilation are to maintain a low plateau pressure, restore
the mediastinum to the midline (see Fig. 26-2B), and al-
Severe symptomatic ANLH commonly requires urgent
low r estoration of circulatory instability (that caused by d y-
intervention. Options include
namic h yperinfla tion). If this is not achieved, rate should be
reduced further (even to 0). The goals of SLT ventilation are
1. Permissive hypercapnin.'170 Permissive hypercapnia re- a safe plateau pressure (see Table 26-4) and restoration of
duces d ynamic h yperinflation in the native lung and may adequa te Sao, and Paco,- If this is not achieved, further re-
improve mild symptomatic ANLH but is wilikely to be cruitment maneuvers and higher PEEP should be explored.
adequate for severe ANLH. Although ILV was not used The introduction and stabilization of these different ventila-
in this study, four patients required ECMO. tor strategies to each lung gen erally necessitate sedation and
2 _ ILVY"'· t67, 16§,171-'1 73, 177,178,184, tS/i-189,191,193 Although tech-
paralysis during the early stages of ILV. If Sao, or circulation
nically complex, ILV commonly results in immedia te resis not satisfactory, ECMO may be needed.
olution o r improvement in gas exchange and circulatory Withdrawal of ILV can be initiated when function of
problems and provides the most rapidly available and the transplanted lung improves and its ventilatory require-
cl1osen solution (see Fig. 26-2). ments decrease. This can be assessed with a DLT in situ
3. ECM0. 170 ECMO is a complex and invasive solution but by ventilating both lungs with a single ventilator a nd a
provides an alternative to ILV. bifurcated ventilator circuit. Since spontaneous ventilation
4. Contrnlaterallung-reduction surgenJ.m -m This has been is difficult with a DLT, patients usually require reintuba-
reported recently. It has been undertaken concurrently tion with a single-lumen ETT for weaning before extu-
w ith SLT, during the post-operative period, and late a fter bation. Others experience recurrent dynamic hyperinfla-
SLT. It may o ffer the best long-term solution to ANLH tion w ith double-lung ventilation and must wean with
but is less readily applicable in urgent or life-threatening the DLT in situ. fLV has been required for as little as
situations. 1 day. 178 ln most instances, prolonged ILV has been re-
5. Contrnlaterallu.ng transplnn.tatiDn. 171 • 113 After primary SLT, quired; periods exceeding 1 month188, 189•191•193 have been
this offers a solution but depends on availability o f a reported with eventual resolution and good functional out-
donor lung and subjects the recipient to two major sur- come. Patients who require prolonged ILV should undergo
gical procedures and two sets of foreign antigens. a tracheostomy and receive a do uble-lumen tracheostom y
6. Retransplnntntion of the SLT.173 This has been used for early tube.''ss, 191, 199 (Fig. 26-3).
graft dysfw1ction associated with ANLH.
The choice of DLT for ILV is different following SLT. A Outcome of ANLH
left DLT normally is easier to position correctly. With a left Three series 1 69• 172•173• 1 88·"~ 91 • 199 reported a longer duration of
SLT, however, this can compromise the anastomosis and mechanical ventilation and ICU stay in patients with symp-
airway distal to the anastomosis, which has a tenuous blood tomatic ANLI-1. One series reported a higher mortality in
supply in the immediate postoperative period. Thus a DLT ANLH patients. 173 In a second series,'169 mortality was not
opposite to the side of the SLT normally is chosen in the significantly higher because of small numbers. In a third se-
early postoperative period. If ILV is required more than 2- 3 ries, no difference was noted. 172 Combining all three series
weeks after left SLT when the anastomosis is stable, a le ft plus da ta from our institution reveals differences in mortal-
DLT may be used, although a smaller size is chosen in case ity: 7% mortality in 213 SLT patients without symptomatic
the anastomosis is narrower tl1an the adjacent airway. ANLH and 37% mortality in 49 SLT patients witl1 symp-
ILV after SLT usually consists of CMV to the trans- toma ticANLH (P < .05). Yonanetal' 73 reported lowerFEV 1
planted lung and AILV,177•178, '1 88, 189 SILV, 19 '1 bronchial values and hig her residual volumes after transplantation in
affected lung, mai11tenance of gas exchange, and thoraco-
tomy d osure.159
PATIENT SELECTION FOR ILV IN UNILATERAL

LUNG DISEASE
Asymmetric lung disease usually is easy to recognize, but
criteria for ILV are not so clear. Not all patients with asym-
metric lw1g disease require ILV. Commonly used criteria are
tmila teral or clearly asymmetric lung disease, which is ev-
ident on chest x-ray or known from the patient's condition
(e.g., SLD, plus one of the following:
1. Severe hypoxemia despite 100% 0 2 and different levels

of PEEP
2. Circula tory failure/ hypotension secondary to dynamic
hyperinflation
Factors that suggest that a patient is likely to benefit from

ILV include
1. Worsening hypoxemia and/or circulatory status by in-

creasing PEEP, rate, or VT
2. Improvement in gas exchange but marked d eterioratio n
in circulatory status with increasing PEEP and the oppo-
FIGURE 26-3 A double-lumen tracheostomy tube. site when PEEP is reduced
ANLH patients, whereas Weill et al,172 in a larger series, BILATERAL SYMMETRIC LUNG DIS EASE
fmmd no differences in long-term lung fw1ction.
Acute bilaterallung injury mayappeardiffuse, uniform, and
symmetric on chest x-ray but contain significant inhom o-
Outcome of ILV geneity on CT scan. 201•202 Ma ny of these changes result from
Fifteen papers163,167,1 69,171 - 173,177,178,184,186- 189; 19 1, 193 plus
a unifo rmly injured lung collapsing in dependent zones as a
data from our institution report 63 patients with ILV result ofincreased lung weight. Because pa tients commonly
following an SLT for CAO. Overall mo rtality was 30%. are nursed on their back, collapse occurs in posterior zones
Including only recent case series in which all SLT patients and is not apparent on anteroposterior chest x-rays. In this
and ILV survival were reported,17'1 - 173 plus our data, ILV case, no PEEP is required to open alveoli in the least depen-
patients had higher mortality (15 of 42 patients, or 36% dent regions, and high PEEP may be required in the mos t
mortality) than non-ILV patients (45 of 338 patients, or 13% dependent regions. Generalized PEEP may fail to inflate
mortality). This difference is not surprising because ILV the most dependent regions and may overinflate nonde-
patients are sicker and show a higher incidence of graft pendent regions. There is now increasing evidence that the
dysftmction. injury can result from prolonged collapse203 and repetitive
In summary, SLT for airflow obstruction poses a risk of collapse/ re-expansion and overexpansion 204•205 and that
ANLH with mediastinal shift. When this is sufficient to com- lung injury may contribute to multiple-organ fa ilure and
promise gas exchange and/ or circulation, AILV is the initial death.155 •206 Considerable effort has been devoted to venti-
method of choice and may reduce the need for ECMO. lator strategies that reduce prolonged collapse, collapse/ re-
expansion, and overexpansion.155•156•207 While some strate-
UNILATERAL BRONCHOSPASM gies have been successful, all have the same problem of
In patients w ith asthma, airways respond locally to local conflicting pressure requirements within different regions
stimuli; irritants applied to one lung may create a differ- of the same lung.
ent degree of bronchospasm in the two lungs.200 During The application of ILV under these circumstances is based
mecl1anical ventilation, this can lead to different levels of on two principles:
dynamic hyperinflation and mediastinal shift, and during
thoracic surgery, this can lead to difficulty with thoracotomy 1. Differences in compliance, ventila tion-perfusion ratios,
closure and the need for ILV. Narr et al159 reported unila t- and gas exchange between the two lungs may be present
eral bronchospasm during unilateral pleurodesis. The pleu- and not be suspected from plain x-ra ys.23 •26•130•151
rodesed lung initially collapsed; following DLT insertion 2. Placing the pa tient in the lateral decubitus position
and ILV with 80 cmH20 of CPAP applied to the collapsed w ill redistribute much of the collapsed (high-PEEP-
lung, that ltmg inflated and would not deflate. Low-level requiring) lung regions to the d ependent lung and the
CPAP to the affected lung, CMV to the unaffected lung, and open Oow-PEEP-requiring) regions to the nondependent
aggressive bronchodila tor therapy allowed deflation of the lwlg.23,26,208,209
When a patient w ith normal lungs is ventilated in the

later al decubitus position, up to two-thirds of perfusion
goes to the d ependent lung, and up to two-thirds of ven-
tilation goes to the nondependent lung, 18-22 creating signif-
icant ventilation-perfusion mismatch and shunt. Applica-
tion of global PEEP improves distribution of ventilation,210
but perfusion inequa lity may be increased and cardjac out-
put reduced22 with little net benefit.
ILV with equal VT to each lung and selective PEEP to
the dependent lung proved additive in improving shtmt
fraction, arterial oxygena tion, cardiac output, and 0 2 de-
livery compared with CMV in both the supine and lat-
eral positions. 28-29 These maneuvers have been applied on
a long-term basis in bilateral lung injury with some early
success. 209 Wickerts et al 208 and Diaz-Reganon Valverde et
al211 prospectively studied 11 and 45 pa tients, respectively,
with severe bila teral ARDS who received JLV. These patients
were assessed in the supine position on global PEEP and
then rein tuba ted with a DLT and placed in the lateral decu-
bitus position. PEEP was applied to the dependent lung and
no PEEP to the nondependent lung. Both groups repor ted
improved oxygena tion, and Diaz-Reganon Valverde et al 2n FIGU RE 26-4 Flow p atterns that may occur during auscultatory
reported a good response in 83% of patients. ver ifi cation of a left D LT position (A) when D LT is ins ufficiently
inserted and the left lumen is ventilated (rig ht lumen clamped)
ILV is difficult a nd labor-intensive to apply. 208 Accord- and (B) wh en DLT is inserted too far and the right lume n is
ingly, it has not gained w idespread acceptance for symmet- ventila ted (left lume n clamped).
ric bilateral lung injury.
PVC DLTs usually are introduced with the endobronchial

curvature angled anteriorly and a rigid stylet in situ to fa-
cilita te passage of the tip through tl1e vocal cords. Once
Techniques and Problems with !LV through tl1e cords, the stylet is removed and the DLT is ro-
tated through 900 so tl1at tl1e endobronchial curvature is
LUNG SEPARATION directed toward the appropria te side. The tube then is ad-
Use of ILV must be preceded by the introduction of a DLT o r vanced until an increase in resistance is detected.
alternative device. TI1ese must be introduced, correctly po- DLT tube position and function then must be confirmed
sitioned, and then tested to demonstra te they have achieved by one or more of three techniques:
their intended purpose: isolation of lung ventilation.
The preferred DLT is the PVC type (e.g., Mallinckrodt, 1. A uscul tation . Following cuff inflation, the tracheal port
Sheridan, Rusch, Concord, Portex, and Marraro; see Fig. should be cla mped and the bronchial port ventilated.12
26-1). These DLTs are more flexible, have better internal- Bilateral or contralateral breath sounds indicate incor-
external dia meter ratios, better gas-flow characteristics, and rect placement and the need to repositio n the tubes (Fig.
easier suction and bronchoscopy access,87 allow airway seal 26-4 A), whereas breath sounds heard only on the cor-
with lower cuff pressures/12 are less irritating to respira- rect side indicate correct placement (see Fig. 26-1). Dif-
tory mucosa, have a lower risk of trauma, and are easier ficulty with ventilation should be resolved by deflating
and quicker to position 213 compared witl\ their red-rubber the bronchial cuff: Bila teral breath sounds indicate tl1at
cmmterparts.3- 5 Despite this a irway injury from PVC DLTs placement is too proximal (see Fig 26-4A), whereas breath
still may occur. 214· 21 5 sounds heard only on tl1e side of the endobronchial tube
For most indications, a left DLT (see Fig. 26-1 B) should indicate that placement is too distal (see Fig. 26-48).
be used because placement is easier and less critical than Lung auscultation a lways should include both upper
with a right DLT, which has a high risk of right upper-lobe and low er lobes to ensure correct placement of the en-
occlusion 216 A right DLT (see Fig. 26-1 A) is reqllired for tho- dobronchial port within the broncllUS, especia lly witl1 a
racic surgical procedures that include the left main bronchus right DLT, with which th e right upper lobe is occluded
(left pneumonectomy, left main bronchial lesions, stenosis, easily.
or rupture), thoracic aortic aneurysm repair, or anatomic ab- 2. Bronchoscopy. Following DLT insertion, a small fiberoptic
normalities that prevent satisfactory access to the left main bronchoscope may be passed through the tracheal lu-
bronchus 12-13•217 A right DLT is also required for ILV with a men to confirm position of the tracl1eal port and that
recent left SLT to avoid injury to the anastomosis and dis- th e endobronchial tube is in the correct position.'12, 21 8
tal a irway. To minimize airflow r esistance and maximize The endobronchial cuff should be visible just distal to the
endo bronchial access, the la rgest DLT that w ill not cause la- carina. Subsequent insertion of the bronchoscope d own
ryngeal or airway injury should be chosen (see Table 26-3 ). th e endobronchial lumen may be used to confirm tl1at
Single
Ventilator Ventilator 1 Ventilator 2
FIGURE 26-S (A) Both lumens of a double-lumen

tube connected to a single ventilator airway. (B)
A B Each lumen of a double-lumen tube connected to
separate ventilators.
endobronchial placement is not too distal and that, with lumen that allows irrigation, suction, 0 2 insufflation, CPAP,
right DLTs, the right upper-lobe bronchus is over the and high-frequency ventilation.16 The Arndt endobronchial
corresponding fenestration. Although not essential for blocker93,94,2l9 (Fig. 26-7) requires bronchoscopic guidance
DLT placement, bronchoscopy reliably confirms accurate for placement. The kit comes with an ETT adaptor that al-
placement and should be used routinely. It has an advan- lows access for mechanical ventilation, the blocker, and the
tage with anatomic variations and in detecting partial bronchoscope through separate ports (see Fig. 26-7). The
airway ocdusions. 216 bronchoscope is passed into the airway that requires block-
3. Leak test. While ventilating one lung, a connection to the ing, and the blocker is then guided into that airway via a
second a irway can be placed under water. Any bubbling snare over the bronchoscope (see Fig. 26-7 A). The broncho-
indicates air leak from the ventilated lung to the oppo- scope then is withdrawn, the balloon is inflated, and its po-
site side. Such leaks may not be detected by ausculta- sition is confirmed by bronchoscopy before withdrawal (see
tion or bronchoscopy and may be important, particularly Fig. 26-78). This has the advantage of being performed via
when one of the goals is to protect one lung against fluid the ETT in situ, thereby avoiding reintubation, provided
(whole-lung lavage, blood, or purulent secretions) from that the ETT is sufficiently large to admit both the blocker
the other lung. Bubbling may indicate the need for tube
repositioning or higher bronchial-cuff inflation.
FIGURE 26-6 The Univent tube with the balloon inflated in the
left main bronchus.
Chest x-ray may be used to visualize DLT position but is
insufficient to verify critical tube placement or functional
isolation.
DLTs may be connected to a single ventilator (e.g., for
hemoptysis or at the beginning and end of whole-lung
lavage; Fig. 26-SA) or connected to two separate ventilators
(see Fig. 26-SB).
Bronchial blocking teclmiques and selective endo-
bronchial intubation are alternatives to a DLT. The right
or left main bronchus may be blocked by placement of
a balloon-tipped catheter into that bronchus. This allows
OLV and is suitable for thoracic surgery, bleeding, or fis-
tula control. The catheter (Arndt endobronchial blocker,
Magill blocker, Cohen Flexitip Endobronchial Blocker, Fog-
arty or Foley catheter)93,94·186•219·220 may be placed outside
or within a standard cuffed ETT lumen or passed down a
specially desi?;'ed second small lun1en in the ETT (Uni-
vent tube). ts- 7 A Univent tube (Fig. 26-6) has a coude-
tipped brond1ial blocker that allows blind guidance of the
blocker into the desired bronchus with auscultatory confir-
mation of correct positioning. Bronchoscopic confirmation
of best position within the a irway, however, is still recom-
mended. In addition, the Univent's axial-blocker shaft has a
58 6 PART VIll VENTILATOR SUPPORT IN SPECIFIC SETIINGS
successful in animals, this technique holds no advantages

BronchoscopeJ
over other forms of ILV, and its use has not been reported
in humans.
Ventilator 2. A single ventilator linked to a twin circuit with devices that
create different flaws into each circuit. This may be achieved
by flow dividing: Varia ble resistances are placed in each
inspiratory line, which divide inspiratory flow from the
ventilator in a variable m anner.39•131 ·.,.,4 Since the flow
(and hence volume) that each lung receives will be de-
termined both by the resistance in the circuit and by
impedance in the lung, Vr must be measured indepen-
dently in each circuit and resistance adjusted accord-
ingly. GaUagher et aJ 133, 136 described an alternative to this
technique by placing flow controllers in both inspiratory
lines. VT delivered to each lung was simply the product
of set flow in each circuit and inspiratory time. Separate
PEEP in each circuit was achieved by expiratory flow
controllers. This method allows different VTand PEEP to
each lung but necessarily must have the same TilTE.
3. A single ventilator linked to two circuits, each with a sepa-
rate PEEP valve or other PEEP-generating device. 150. 225 This
arrangement allows different PEEP to each ltmg. The di-
vision of VT between the lungs is not controlled indepen-
dently, being determined by both the relative inherent
impedance of each lung and the effect of PEEP on that
A B impedance.
FIGURE 26-7 The Arndt endobronchial b locker shown (A) 4. A single ventilator linked to two ciraJits with 110 attempt to
during bronch oscope guidance into th e left main bronchu s and influence the distribution of ventilation ..87 This method gen-
(B) after partial bronchoscope withdrawal and balloon inflation, erally is used during selective airway protection. The di-
with the bronchoscope remaining to check balloon position. vision of VT between the two lw1gs is determined solely
by their relative impedance.
and the available bronchoscope. The Cohen Aexitip Endo- While ma ny indications for TLV are suited to having the
bronchial Blockerl2° has a flexible tip that can be guided un- same ventilator rate to each lung, there is usually no partic-
der bronchoscopy but independently of the bronchoscope. ular benefit for exact coordination of two ventilators. The
only exception may be the uncommon circumstance where
TECHNIQUES FOR ILV patient-triggered ventilation is a ttempted .
Several techniques have been reported . ASYNCHRONOUS ILV (AILV)
AILV consists of completely independent ventilator tech-
SYNCHRONIZED JLV (SILV) niques applied to each lung. It requires two separate venti-
SILV consists of synchronous initiation of inspiration into lation devices. Options include
each lung. Each lung necessarily must have the sam e r espi-
ratory rate but can have different VT, PEEP, and inspiratory 1. Controlled or intermittent mechanical ventilation to both
flow. SILV may be achieved by a variety of techniques. lungs (CMV, IMV)10,38, 40,l23- 125,128,149,157,163
2. CMV or IMV to one lung and HF]V to the other41 ,42,124,1V .160
1. Two ventilatars of the same type linked to ctjcle synchronlJUsly. 3. CMV or IMV to one lung and CPAP to the other9.40,124, 159
This may be achieved by electronicaJiy "slaving" the 4. High-frequency oscillatory ventilation to botl! lungs 147
rate control of a second ventilator to a primary ("mas -
ter") ventilator. 22,23,26,28,29, 126,145, 151,211,216 Alternatively, ATLV permits different rate, VT, inspiratory flow, and
synchronization may be achieved by the ra te of two PEEP to each lung. Lack of synchronization between the
ventila tors being electronically controlled by an external two lungs offers the greatest flexibility a nd appears to hold
device132•162 or by manually resetting the respiratory cy- no disadvantage and a number of advantages compared
cle on paired ventilators and relying on accurate internal with SILV.38•157
timing devices to maintain synchronization.143•221 This
method allows different VT, PEEP, inspiratory flow, and ONE-LUNG VENTILATION (OLV)
hence inspiratoryI expiratory time (T1/ T E) combinations. With OLV, one lung is ventilated med1anically w hile the
Another form of SILV is one in which the lungs are other is either occluded or open to atmosphere with an op-
ventilated alternately with the two ventilators synchr o- tion of spontaneous ventilation. OLV is used mainly in tho-
nized 180° out of phase with each other.222,223 Although racic surgery to keep the lung collapsed and immobile. It
CHAPTER26 INDEPENDENT LUNG VENTILATION 587
also may be u sed in BPF to prevent air leak or for selec- TABLE 26-5 Polyvinyl chloride double-lumen t\tbes:
tive airway protection if secretions from the affected lung choice of size
prevent any useful ventilation (e.g., massive haemoptysis).
Tube Size Circumference Lumen Diameter
Options include (French) (mm) (mm) Use
1. Intubation with DLT, and CMV applied to only one 28 Children <40 kg
lumen.11,13,19,25,217,226 35 38 50 Children >40 kg
2. Endotracherrl inhtbntion with a bronchial blocker inserted 37 40 55 Small adult
into one of the major bronchi. The occlusive balloon ex- 39 44 60 Medium adults,
usual female size
d udes that lung from mechanical ventilation, and the
41 45 65 Large adult, usual
blocker lumen allows deflation (and inflation) of that
lung. L'I 3.15,93,94,219 male size
3. Endobrm1.clzial intubation with n single-lumen tube (e.g., SOURCE: Adapted from Burton NA 229 •
Mackintosh-Leatherdale left endobronchial tube and
Gordon Green right endobronchial tube).'13
PVC DLTs and 130 ± 41 mmHg in Carlen s tubes. 21 2. 237 This
SPONTANEOUS VENTILATION study suggests a considerably lower risk to the airway from
PVC tubes, although the pressures required to prevent leaks
Spontaneous ventilation with a DLT and differential CPAP
stiU were well above safe limits.
applied to each lung was firs t reported by Venus et al. 227
Bronchial rupture was reported regularly229,23S- 243 and
It has been used in spontaneously breathing patients with
unilateral pulmonary contusion and atelectasis with good there is one report of broncl1ial stenosis 143 with red-rubber
results.144·227 It is not recommended becau se of increased tubes. Bronchial rupture is uncommon with PVC DLTs,
work of breathing through a long, narrow tube. although they are not free of this complication229•231 ,244
(Table 26-5).
Although lumen diameter has improved consider-
PROBLEMS WITH ILV ably with PVC tubes, difficult suction access, retained
Many of the problems with ILV are related to the DLT. The secretions, 43·125·132.148 and lumen blockage remain a prob-
technique of DLT placement and verifying its correct posi- lem and can lead to difficult ventilation, the need for reiitlar
tion is complex, time-consuming, and requires experienced bronchoscopic toilet, and the need to change the DLT. 7
personne1.12•13•213·218 These considerations can limit the use When ILV is continued for some time, several difficul-
ties related to patient care arise. Head movement, patient
of DLTs and ILV when required urgently or under adverse
movement, and routine pa tient turning all threaten DLT
circumstances, such as massive hemoptysis.88•91
Trauma of the lary nx and upper airways was a common position and can lead to loss of ltmg isolation and lobe
problem with red-rubber tubes12·.58 but is uncommon with occlusion. 43·125·148•236 Frequent bronchoscopy may be re-
PVC tubes. 213·228•229 Ra re complications have included car- quired to maintain DLT position. 148•229 Running two venti-
diovascular collapse after a DLT displaced a mediastinal lators requires additional space, 0 2, air and, suction outlets ,
tumor into the mediastinal vessels230 and exsanguination and sta ndard patient charts usually are inadequate. 125 There
following inclusion of the DLT in sutures during pneu- are significant increases in nursing time requirement and
monectomy with subsequent vessel laceration when the workload, 125·245·246 and the patient may find the DLT more
DLT was removed.231 ·232 uncomfortable and restrictive than normal intubation. 43
Placement of right DLTs is critical with respect to right
upper-lobe ventilation. Benumof et al233 estimated a right
upper-lobe occlusion ra te of 11% w ith PVC tubes. McKenna Conclusion
et al216 assessed occlusion of the right upper lobe by bron-
choscopy: Occlusion was 89% with Mallinckrodt PVC DLTs ILV h as been used in a wide range of conditions (see Ta-
and only 10% with right Robertshaw red-rubber DLTs. This ble 26-1). Although ILV is required infrequently, AILV can
has become an uncommon problem now that most DLT in- be undertaken with any ventilator and used for all indica-
sertions are assessed rou tinely by bronchoscopy. Left upper- tions. ILV has an established and occasional lifesaving role
lobe occlu sion also has been reported 234·235 with left PVC for many conditions. Users of mechanical ventilation must
DLTs from overinsertion, wedging the tip of the DLT in the be familiar with the complexities o f ILV so that it can be in-
left lower-lobe bronchus. Saito et al236 fow1d 27 ± 6 mm stigated promptly and appropriately when tl1e need arises.
movement of the tip of a left DLT, proximally with neck ex-
tension and distally with flexion, with a total potential range
of movement of up to 4.5-7 em. This range of movement is References
sufficient to either occlude the left upper-lobe bronchus or
lose lung isolation. Similar problems are more likely with a 1. Magill I. Anaesthesia in thoracic surgery, with special reference
right DLT, with which tube position is more critical. to lobectomy. Proc R Soc Med 1936; 19:643-53.
High cuff pressures are a significant problem with DLTs . 2. Moody J, Trent J, Newton G. An endobronchial balloon for
In routinely placed tubes with cuffs inflated to avoid air the control of bronchial secretions during lobectomy and pneu-
leak, broncllial cuff pressures were 56 ± 21 mmHg in left monectomy. J Thoracic Surg 1947; 16:258.
3. Carlens E. A new flexible double-lumen tube for bronchos- and central hacmodynamics. Acta Anaesthesia! Scand 1983;
pirometry. J Thorac Surg 1949; 18:742- 6. 27:270-4.
4. White G. A new double-lwnen endobronchial tube. Br JAJlaesth 27. Cohen E, Eisenkraft J, Tilys D, et al. Oxygenation and hemo-
1960; 32:232. dynamic changes during one-lung ventilation: Effects of CPAP
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through a double-lumen tube. Anaesthesiology 1980; 52: 237. Brodsky ], Adkins M, Gaba D. Bronchial cuff pressures of
74-7. double-lumen tubes. Anesth Analg 1989; 69:608-10.
228. Wagner D,GammagcG, WongM. Tracheal rupture following in- 238. jooss D, Zeiler D, Muhrcr K, Hempelmarm C. Die Bronchia1-
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229. Burton N, WatsonDC, Brodsky J, et al. Advantages of a new 40:291-3.
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Thorac Surg 1983; 36:78. usc of a double-lumen tube in a small adult. Anesthesiology
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Anesthesiology 1987; 66:422. placement in repair of ruptured bronchus. Anaesth Intensive
231. Scherer R, Reinhold P, Buchholz B. Einseitiges Lungenooem Care 1987; 15:459-62.
nach Thoraxtrauma: Eine lndikation zur seitendifferenten Beat- 241. Foster J, Lau 0 , Alimo E. Rupture of bronchus follo\o\-ing endo-
mung. Anasth Intensivther Notfa11med 1983; 18:65-7. bronchial intubation. Br J Anaesth 1983; 55:687-8.
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233. Benumof J, Partridge B, Salvatierra C, eta!. Margin of safety in 243. Guemelli N, Bragaglia R, Briccoli A, eta!. Tracheobronchial rup-
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thesiology 1987; 67:729-38. 244. Rommelscheim K. A new double-lumen tracheos tomy tube for
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thapter 27 _ _ _ __ _ _ _ __ therefore, continuous assessment of the airway is vitally im-
portant. Pulse oximetry is helpful in identifying hypoxia,
MECHANICAL although hypoxia may be a relatively late sign of ainvay
compromise. [t is therefore important to evaluate breath-
VENTILATION DURING ing pattern, level of consciousness, and shortness of breath
continuously.
RESUSCITATION When endotracheal intubation of children was added
to paramedic practice, 15 of 177 (- 8%) children either
ACHTM VON GOEDECKE were intubated esophageally or dislodgment of the endo-
VOLKER WENZEL
tracheal tube went unrecognized; 14 of these 15 children
died subsequently.6 Accordingly, invasive pediatric airway
equipment was removed from emergency medical service
units in Los Angeles County; instead, bag-valve-mask ven-
tilation was recommended. A similarly alarming experience
was seen in Orlando, Florida, when the esophagus was in-
SPECTRUM OF EMERGENCY-CARE SKILLS tubated in 18 of 108 (- 16%) patients being m<maged by the
DISTINCTION BETWEEN AIRWAY PROTECTION emergency medical services? This suggests that the skills
AND ASSISTED VENTILATION and experience of a rescuer performing basic and advanced
Cricoid Pressure/Sellick Maneuver airway management may determine if these maneuvers
ROLE IN DIFFERENT SEITINGS achieve effective oxygenation and carbon dioxide elimina-
Prehospital Care tion o r result in extremely serious complications, such as
Cardiopulmonary Resuscitation (CPR) severe neurologic impairment, or even death. 8
Trauma Endotracheal intubation is the "gold standard" for pro-
Cervical Spine Injury viding emergency ventilation. Thus every advanced emer-
Open Penetrating Chest Wounds and gency medical service provider must acquire and, es-
Tension Pneumothorax pecially, maintain intubation skills. Such a goal may be
Traumatic Brain Injury difficult to guarantee because of the large numbers of
Burns individuals who require training and/or the infrequent
Drowning performance of intubations. This experience is similar to ob-
ADJUNCTS FOR OYXGENATION, VENTILATION, servations of the emergency medical services in Houston,
AND AIRWAY CONTROL Texas, where airway device-related complications were as-
Oxygenation Devices sociated more with training with the devices than with the
Ventilation Devices devices thernselves. 9 TI1is confirms that the success rate of
Airway Control Devices airway management interventions depends on several fac-
CONCLUSION tors: (1) initial training, (2) continuous quality assurance,
and (3) actual frequency of performing the specific inter-
Before the arrival of an emergency medical service unit, ven- vention. For example, when the actual frequency of per-
tilation given by bystanders must employ techniques that forming endotracheal intubation is relatively low, as in the
do not require special equipment. Safar, Elam, and Ruben case of the Los Angeles County emergency medical ser"
first showed that obstruction of the upper airway by the vices (e.g., 2584 trained individuals performing 420 actual
tongue and soft palate occurs commonly in victims who endotracheal intubations over 33 months), it is not surpris-
lose consciousness or muscle tone and that ventilation with ing that endotracheal intubation performed by paramedics
manual techniques is markedly reduced or prevented by (who were allowed to perform bag-valve-mask ventilation)
such obstruction. 1 ·J Subsequent!y, Safar et al4•5 developed did not improve survival or neurologic outcome; instead, it
techniques that prevent obstruction by extending the neck caused some catastrophes.6 This actually may tip the scales
and jaw and applied these in conjunction with mouth-to- toward bag-valve-mask ventilation for emergency ventila-
mouth ventilation. The "gold standard" today for airway tion of patients with a respiratory or even cardiac arrest per-
maintenance during resuscitation is intubation of the tra- formed by emergency medical services personnel without
chea, whicll provides a route for ventilation with oxygen, excellent intubation skills. Thus, teaching emergency med-
allows suctioning of the upper airway, protects the airway ical services personnel a limited number or even a single
from aspiration of gastric contents, and prevents inflation airway procedure may follow the axiom "The simpler, the
of the stomach. better'' and ensure adequate oxygenation and avoid airway-
related catastrophes.
Spectrum of Emergency-Care Skills Distinction between Airway Protection

Airway management should be mastered by all properly and Assisted Ventilation
trained prehospital personnel. This involves both airway
assessment and airway control. Compromise of the airway Discussion of whether health care professionals or lay by-
may occur suddenly or slowly and progress over time; standers should or should not perform mouth-to-mouth
595
TABLE 27-1 Rescu er and Patient Variables Affecting Respiratory M echanics d uring Mouth-to-Mouth
Ventilation an d Bag-Va lue-M ask Ventilation
Rescuer Patient Conscious Anesthetized Cardiac Arrest
Chin support LESP (em H20) ~2o-25 ~20 5?

Tidal volume Crs (ml/cmH20) ~10o-150 -so ~20-50
Inflation time Raw (cmH20/liter/s) ~2-4 ~1 5 ?

Ventilator setting
Bag-valve-mask size
ABBR.E\'lATTONS: LESP, lower esophageal sphincter pressure; Crs, compliance of the respiratory system; Raw, airway resistance.
ventilation has emotional connotations. TI1e question of Many factors can change lung compliance. Pulmonary vas-
whether satisfactory lung ventilation in an unintubated car- cular congestion during cardiac arrest increases the vol-
diac arrest patient can be achieved, however, is clearly a ume of the parenchymal interstitium and reduces compli-
scientific issue. If it is possible to identify ventilation strate- ance. Chest compressions and pulmonary edema secondary
gies that are beneficial to patients and not hannful, then to left-ventricular failure also contribute to a reduction in
resuscitation outcomes may be improved. compliance.21
The distribution of ventilation volume between lungs and Chin support and backward tilt of the head are the two
stomach in a patient with an unprotected airway depends on most important maneuvers during rescue ventilation of par-
factors such as lower esophageal sphincter pressure, airway alyzed and nonparalyzed patients \<\rith an unprotected air-
resistance, and respiratory system compliance. 10 Of equal way. Moreover, a slight lateral tilt of the head may reduce
importance are specifics of techniques used for basic or ad- upper airway obstruction arising from backward relaxation
vanced airway support, such as head position, tidal volume, of the tongue and soft tissues. 22 The settings of an auto-
inflation flow rate, and duration, all of which determine matic ventilator or the technique of bag-valve-mask venti-
upper airway pressure. 11•12 The combination of these vari- lation governs inflation flow rate, inflation time, and tidal
ables determines gas distribution between the lungs and the volume, all of which affect peak inflation pressure, assum-
esophagus and, subsequently, the stomach. 13 Several funda- ing that there is no significant upper airway obstruction. 23
mental differences exist between respiratory mechanics in a The relationship between peak inflation pressure and lower
healthy, awake adult, an anesthetized supine patient, and a esophageal sphincter pressure determines gas distribution
victim of a cardiac arrest (Table 27-1). between the stomach and lungs. 24 For example, when peak
Lower esophageal sphincter pressure is the pressure that inflation pressure exceeds sphincter pressure, some air will
prevents regurgitation of stomach contents into the phar- flow into the stomach; if sphincter pressure is higher than
ynx and insufflation of air into the gastrointestinal tract peak inflation pressure, inspiratory air will flow completely
during ventilation. Sphincter pressure in a healthy adult is into the lungs. The preceding scenario, however, depends
approximately 20-25 cmH20 but may be lower in patients on the assumption that the lower esophageal sphincter pres-
with chronic esophageal reflux disease, during induction of sure acts like a mechanical valve, which may not be the case.
anesthesia, and after insertion of a laryngeal mask airway.14 For example, Safar25 stated that stomach inflation in healthy
It is unclear, however, whether these cl1anges in sphincter volunteers was self-limiting, but lower esophageal sphinc-
pressure result from induction of anesthesia. Animal inves- ter pressure was not reported. This observation implies that
tigations showed that the lower esophageal sphincter pres- the physiology of respiratory mechanics in human subjects
sure deteriorated rapidly from a baseline level of 20 to 5 may be more complex than has been considered previously.
cmH20 within 5 minutes of untreated cardiac arrest.15•16 Until a better understanding of these mechanisms is ob-
This decrease in lower esophageal sphincter pressure also tained, the goal of ventilation with an unprotected airway
was measured in human subjects following cardiac arrest.17 is to keep it permanently patent and to keep peak infla-
In a healthy adult, air flows freely from the lips to the alve- tion pressure to a minimum at all times to prevent stomach
oli, and therefore, minimal inspiratory pressure is required inflation.
to move gas during spontaneous ventilation. In a patient Stomach inflation is a com~lex problem that may
with chronic obstructive lung disease, airflow through the cause regurgitation,26 aspiration, 7 pneumonia, 28 and pos-
respiratory system may be impaired by mucus or airway sibly death. 29 Stomach inflation will increase intragastric
spasm. 18 Data from clinical studies showed an airway re- pressure,30 elevate the diaphragm, restrict lung movements,
sistance of 2-4 crnH 20/liter per second in healthy volun- and so reduce respiratory system compliance.31 A reduced
teers, 8-15 cmH20 / liter per second in patients with vary- respiratory compliance may direct even more ventilation
ing degrees of lung disease, and 17 cmH 2 0 / liter per second volume into the stomach when the airway is unrrotected, 10
with positive-pressure bag-valve-mask ventilation in a pa- thereby inducing a vicious ct;cle with each brenth3 (Fig. 27-1).
tient during induction of anesthesia.19 In a healthy awake The life-threatening complication of stomach inflation, re-
adult, 1 cmH20 of inspiratory pressure moves approxi- gurgitation, and subsequent aspiration pneumonia (in-
mately 100 m1 of air into the lungsi compliance decreases duced by gastric acid) causes a loss of alveolocapillary
to 50 ml in an anesthetized supine adult and may decrease integrity and pulmonary surfactant. As a result, fluid
to approximately 20-50 rnl in a cardiac arrest patient. 20 and proteins pass into the interstitial spaces, alveoli, and
CHAPTER 27 MECHANICAL VENTILATION DURING RESUSCITATION 597
Cranial movement of
diaphragmf
Redistribution of tidal volume
from lung to stomach t
Respiratory system
compliance J.
A
FIGURE 27-1 Vicious circle of increasing stomach inflation and
decreasin g lung ventilation durin g ventilation of an urtintubated
cardiac arrest patient. (Reprinted f rom Wenzel eta/: Resuscitntiou
38:113-8, 1998, with permission from Elsevier Science, lrdn.ud.)
bronchi, causing pulmonary edema, d ecreased pulmonary

compliance, increased lung weight, a.n d significant intra-
pulmonary shunting or ventilation-perfusion mismatching.
Consequently, alveolar gas exchange is impaired markedly.
Data from an animal model showed that aspiration of more
than 0.8 ml/kg of body weigh t resulted in 50% mortality.
Extrapolation o f these r esults to humans suggest a critical
as piration volume of 50 ml a t a pH of 1.0.33 T he resu lts from
recent studies of anesthetic practice, however, suggest that
the true morbidity from acid aspiration has been exagger-
ated greatly. 34
B
FIGURE 27-2 A. Latex tube inflated to 100 em H20 , filled with a
CRICOID PRESSURE/SELLICK MANEUVER
contrast agen t, and inserted into the esophagus. B. Manual
A maneu ver for preventing stomach irulation during venti- obstruction of the latex tube in the esophagus with cricoid
latio n with an unprotected airway is to apply cricoid pres- p ressure. Only approximately 3-5 kg of pr essure on the cricoid
sure; this is a simple, effective maneuver to prevent stom- cartilage, but not on the thyroid cartilage (Adam's apple), is
needed to obstruct the esophagus. (Repriuted, with permission,
ach infla tion35 that was first d escribed 200 years ago.36 In
from Sellick : Lancet 2:4{}4-6, 1961.)
a model of human cadavers, an intraesophageal pressure
of 75 cmH20 was required to overcome cricoid pressure,
indicating tha t the Sellick maneuver may be able to pre- tremely rare. It also should be remembered that active vom-
vent gastric distension even when ventilating with a high iting does not occur in pa tients during cardiac arrest. This
peak inflation pressure37 (Fig. 27-2). One study investigat- may tip the balance of risks during ventilation with an un-
ing the efficacy and minimum inflation pressure a t which protected airway in favor of cricoid pressure,42 a maneuver
gas entered the s tomach in pediatric patients found that proven to prevent stomach inflation,43·44 which outweighs
appropriately applied cricoid p ressure was invariably ef- the risk of esophageal n1pture.
fective in preventing gas insufflation into the stomad1 in One possible complicatio n of cricoid pressure is airway
all dllidren with and with out paralysis. The minimum obstruction. In 52 anesthetized patients, airway obstruction
infla tion pressur e at which gas entered the stomach d e- did not occur without cricoid pressure, occurred in 1 pa-
creased significantly from 31 cmrhO in nonparalyzed patient (2%) with cricoid pressure of 30 N (3 kg or - 7 lb),
tients to 24 cmH2 0 in paralyzed pa tien ts; thus neuromuscu- in 29 patients (56%) with cricoid pressure of 30 N (3 kg or
lar blockade and functional paralysis, such as cardiac arrest, "'7 !b) applied in an upward and backward direction, and
may increase the risk of stomach inflation. 38•39 The value in 18 (35%) patients with cricoid pressure of 44 N (4.4 kg or
of cricoid pressure has been questioned 40 because o f the ~10 lb). 45 This indicates that cricoid pressure needs to be
risk of esophageal rupture when vomiting occurs.4 "' Stom- applied carefully and accurately. Finally, administration of
ach infla tion, asphyxia, and aspiration a fter ventilation with both cricoid pressure and bag-mask ventilation by a single
an u nprotected airway are relatively common; however, rescuer is nearly impossible and requires a second person
esophageal rupture after applying cricoid pressure is ex- to assist.
IPreoxygenation I Bog-valve-mask ventilation I

~
11. ln1Ubotlon attempt successfi.A ?I ~
1]09-valve-mosk ventilation I
y~
r 0:=-p--:t:i.m
-""7"1z-a-:-:-
tion - o7f - ..--:-ng
positionl
~ - ., ,....[l_MA.
_ C_T
_, -LT-. P-TLA
--.j
anes1heslo, BURP
Yes ..,..111-- I 2. Intubation attempt successful? I l

Ventilation posslble ?
FIGURE 27-3 Algorithm for airway
managemcmt. ILMA, intubating
laryngeal mask airway; CT,
No! combitube; LMA, laryngeal mask
airway; LT, laryngeal tube; PTLA,
Intubation mandatory ? I No pharyngotracheallumen airway;
BURP, backward, upward,
rightward pressure maneuver,
No Petc 0 ,, end-tidal carbon dioxide;
IFibefopttc intubation. ILMA successful ? - - - - - - --+ ICricothyroldotomy I sOz. oxygen saturation.
Role in Different Settings ing, poor retention of skills and knowledge,49 and limited
motivation are the main causes of the disappointingly low
PREHOSPITAL CARE rates of bystander CPR worldwide. This situation cannot
necessarily be rectified simply by eliminating ventilation.50
Securing the airway by tracheal intubation in the prehospi- One argument that ventilation during CPR could be aban-
tal setting may be very difficult. If airway management is doned is that gasping provides sufficient gas exchange. The
difficult in a prehospital patient, maintenance of oxygena- value of gasping in human subjects has to be interpreted
tion can be in doubt d espite use of a bag-valve-mask. Def- with caution because fundamental differences in human
inite securing of the airway can be done later in the emer- and animal upper airway anatomy make it difficult to ex-
gency department with more experienced personnel and trapolate results from laboratory studies, where gasping
equipment. In acute life-threatening situations, however, a was beneficial. The human upper airway is kinked and is
standardized procedure, such as an algorithm, may be fast subject to rapid occlusion by the tongue and/ or head po-
and reliable (Fig. 27-3). sition in the supine position, whereas the upper airway in
swine, dogs, and rats is straight and may not be occluded by
the tongue or head position in the supine position.51 In addi-
CARDIOPULMONARY RESUSCITATION (CPR)
tion, animal studies were performed in fasting animals that
Outcome after CPR in adults with chest compression alone are therefore extremely unlikely to aspirate gastric contents.
was similar to that after chest compressions combined with Furthermore, it is unknown if humans gasp as frequently or
mouth-to-mouth ventilation; the authors concluded that as deeply as animals during cardiac arrest. Whether gasp-
cl1est compressions alone may be the preferred approach fo r ing in humans results in effective gas exchange has not been
bystanders inexperienced in CPR.46 It has been suggested studied, and for ethical reasons, such a study would be ex-
that more lives could be saved if only rapid chest compres- tremely difficult to perform. If a patient is gasping and the
sions are performed (producing immediate reperfusion of rescuer is unwilling or unable to perform mouth-to-mouth
vital organs but with decreased oxygen content) in contrast ventilation during basic life-support CPR, one strategy is to
to the "gold" solution of rapid chest compressions combined keep the a irway open and perform chest compressions alone
w ith ventilation, which may produce less perfusion but with until emergency medical services arrive in order to provide
higher oxygen content. Most likely, the value of ventilation a minimum of ventilation. 52 In the absence of a dedicated
increases over time because ischemia and hypoxic hyper- airway, extending the head by placing a pillow under the
carbia increase. 47 Until a prospective trial proves when and shoulder or gently tilting it laterally could reduce the acute
how ventilation should be done, assisted ventilation should pharyngeal obstruction from the tongue falling backward
be provided whenever possible.48 over the palate.
The relucta nce to perform mouth-to-mouth-ventilation Ventilation consumes time during CPR that could be de-
does not represent a problem in most cases because most voted to cl<est compressions.53 Because only rapid chest
arrests of cardiac etiology occur at home. Unreliable recom- compressions are effective, some argue that time spent for
mendations for mouth-to-mouU1-ventilation, lack of train- ventilation should be decreased and the time for chest
compressions increased. Because cardiac output during Proper ventilation and perfect intubation skills in the
CPR is at bes t approximately 25% of normal, some argue field are of utmost importance, although not possible in all
that the low cardiac output does not need to be accompa- cases. Rescue personnel must recognize the importance of
nied with a normal minute ventila tion. This argument has skill retention. Before intubation attempts, a risk-benefit as-
yet to be proven in a clinical study. Until evidence is avail- sessment is needed to prevent harm with multiple failed
able, assisted ventilation should be performed during CPR attempts. For example, if conditions are difficult (morbid
whenever possible, although the rate of chest compressions obesity or midface fractures), it may be prudent to use a
should not be decreased critically by ventilation attempts. bag-valve-mask device and subsequently intubate immedi-
ately after arrival in the emergency department. H ealth care
personnel, however, must understand that bag-valve-mask
TRAUMA
ventilation needs to be performed carefully. In laboratory
The underlying principle for care of tra uma patients is the shock models, excessive ventilation with a bag-valve-mask
ABCs (airway, breathing, circulation) of resuscitation. Ini- caused increasing positive intrathoracic pressure, inhibi-
tial priorities after tra uma are the same for the field and tion of venous rennn, decreased coronary perfusion, and
the hospital, but field providers usually have only limited thereby decreased survivaJ.63, 64
equipment and limited assistance. They also provide care
in the least controlled circumstances, such as the roadside.
CERV ICAL S PLNE I NJURY
Airway management is the highes t priority and should oc-
cur as early as possible; in severe cases, it may be necessary Cervical spine injuries occur in 2- 5% of blunt trauma
in the field. Physical examination may reveal subcutaneous patients,65 and 7- 14% of these ar e uns table. 66, 67 The most
emphysema, absent breath sounds, a nd unilateral hyperres- comm on fracture was C2, accouJl ting for 24% of fractures.
onance, identifying a tension pneumothorax, which can be Dislocations are most common at CS-6 and C6-7.68 Missed
decompressed. Progressive clouding of consciousness in- cervical spine injury can have disastrous consequences.
dicates nearly always a loss of airway protection, risking The incidence of missed or delayed diagnosis is 1-5%,
aspiration; endotracl1eal intubation is required. Oral intuba- and up to 30% of these patients develop secondary neu-
tion is the most common method because adequately sized rologic damage.69 The primary objective w hen managing
tubes can be placed under direct vision. Nasal intubation the airway of such a patient is to minimize neck movem ent
requires significant expertise, especially w hen performed w hile the airway is secured rapidly and efficiently. Flight
blind, and may exacerbate agitation; it is contraindicated in paramedics had only a 52% success rate with blind nasal
patients with midface fractures. Laryngoscopy in an awake intubation in spontaneously breathing patients in an out-of-
patient nearly always worsens agitation; in these instances, hospital setting but were successful with this procedure in
rapid-sequenceintubation (RSD is advised. RSI involves ad- 14 of 15 patients in the hospital. 70 Traumatologists working
ministration of a sedative followed by a short-acting muscle in a prehospital environment used RSI with a success rate
relaxant, typically succinylcholine. If endotracheal intuba- of 97- 99%.71 When emergency physicians were compared
tion fails, however, the patient mus t be ventilated with a with anesthesiologists using RSI in an out-of-hospital en-
bag-valve-mask device until short-term paralysis resolves. vironment, the nonanesthesiologists were twice as likely to
A retrospective analysis of trauma patients revealed that fail to intubate and needed to undertake a surgical airway. 72
RSI in the field and in hospital were equally successful During normal direct laryngoscopy and oral intubation,
(97.9% versus 98.5%) and safe.54 Other studies reported significant extension occurs between the occiput and Cl
success rates of 84-90.5% for field inhtbations, suggesting and between Cl a nd C2. 73 In an emergency department,
that trainin ~ and experience are the major determinants of the most common approach to intubating the multiple-
success.ss-s Failed intubation was associated mainly w ith injury patient w ith a potential cervical spine injury is RSI
inadequate relaxation and difficult anatomy (i.e., morbid while maintaining cricoid pressure and manual inline neck
obesity or inability to visualize the vocal cords). Although stabilization. Manual inline neck stabilization is provided
the length of hospital stay and mortality were comparable, by an assistant who holds the patient's mastoid processes
pneumonia occurred more frequent with RSI in the field firmly down, opposing the upward forces generated during
than in hospital (28% versus 6%). 54 -58 In a prospective study laryngoscopy.74 In anesthetized patients, this maneu ver re-
of severely injured trauma patients who were intubated in duced head extension bls 50% and should increase the safety
the field via RSI or immediately intubated on admission of direct laryngoscopy. 5 Axial traction must be avoided be-
to the hospital, total out-of-hospi.tal times were twice as cause excessive distraction m ay injure the spinal cord. The
high for the field group versus the hospital group (26 versus view at laryngoscopy is better with manual inline neck sta-
13 minutes).59 Patients intubated in the field versus in the bilization than with rigid-collar immobilization76; if a cer-
hospital had more ventilator, hospital, <md intensive-care- vical collar is left on during laryngoscopy, the view often
Wlit (ICU) days, higher mortality (23% versus 12.4%), and will be grade 3 or 4.77 Once manual inline neck stabilization
a 1.5-fold increased ris k of nosocomial pneumonia. 60 These has been applied, the rigid collar should be removed and
data argue against spending extra time in the field w ith then reapplied when successful placement of the tracheal
severely or even moderately injured patients (injury sever- tube has been confirmed. Direct laryngoscopy and oral in-
ity score 15-25).61 Of more than 6000 intubations in emer- tubation are the quickest method for securing the airway in
gency departments, the success rate was 98.7%, with a 1% a patient with potential cervical spine injury. Cricoid pres-
cricothyroidotomy rate.62 sure is applied during RSI; in a recent cadaver study using
600 PART Vlli VENTILATOR SUPPORI' IN SPEOFIC SETTINGS
la teral cervical spine x-rays, cricoid pressure caused neg- followed by bronchoscopy; a rigid scope m ay be useful if
ligible cervical spine movement? 8 By accepting a view of there is blood or copious secretions in the pharynx.
only the arytenoids and using a gum-elastic bougie for in-
tubation, the laryngoscopist uses less force and mininuzes
TRAUMATIC BRAIN INJURY
cervical spine movement.75•79
Many clinicians advocate awa ke intubation as the safest Outcome of traumatic brain injury depends heavily on ini-
approach in a patient w ith a cervical spine injury. It is tial and admission Glasgow Coma Scale (GCS) score and
thought that preservation of m uscle tone provides protec- age. 90 Direct trauma-related destruction of brain structures
tion, and spinal integrity can be monitored during airway (primary lesion) cannot be saved therapeutically. Secondary
manipulation. 80 Prolonged hypotension or malpos ition af- brain injury, however, defined as the damage to neurons
ter intubation is at least as likely to cause neurologic injury owing to a systemic physiologic response to the initial in-
as the intubation itself. 81 Awake techniques are particularly jury, ca n be irtfluenced . Hypotension and hypoxia are ma-
favored when the need for inhtbation is not urgent. Awake jor causes of secondary brairt injury.91 One of the first tasks
intubation is slower than RSJ. In the acute trauma patient of trauma resuscitation is airway management. Approxi-
it may increase the risk of aspiration a nd can increase in- mately 50% of traumatic brain injury patients are reported
tracranial pressure. Awake techniques, such as blind nasal, to be hypoxic in the field, a finding associa ted with in-
blind oral, and fiberoptic intubation, require considerable creased m ortality.92 Indications for intubation include an
trairting and the patient has to be cooperative. Of the awake inability to maintain and to protect the airway but also
techniques, fiberoptic intubation is best in the patient w ith may include inadequate ventilation, need to hyperventi-
a cervical spine injury. The laryngeal mask airway (LMA), late, hemodynamic instability, and need for radiographic
intubating LMA, and ProSeal LMA are useful alternatives if imaging a nd subsequent surgery. The common coexistence
tracheal irthtbation is not possible. The LMA can be inserted of cervical spine injury requires vigilance. Early orotra-
easily irt the neutral position and is an option in patients cheal intubation is recommended if GCS score 8 or less,
with cervical spirte instability. 82 The s tandard LMA and in- although retrospective studies revealed increased mortal-
tubating LMA cause temporary pressures of greater than ity with field intubation.93, 94 Intubation usually can be ac-
250 cmH2 0 against the posterior pharyngeal w all during complished without seda tion and pharmacologic para ly-
insertion in cadavers. This pressure is sufficient to induce sis. Sedation and neuromuscular blockade can be useful in
up to 2 mm of displacement of C3.83 During irtsertion, the optinlizirtg transport of the head-injured patient, but they
irttubating LMA causes some movement of the upper cer- interfere with neurologic examination a nd influence initial
vical spine, but it is less tha n that produced during direct evaluation and management.95 H emod ynamic stability sim-
laryngoscopy.84 N eck-stabilization methods make insertion ilarly is ranked as a priority before and after intubation.
of theLMA and irttubating LMA more difficult, although the These priorities should not be compromised in an attempt
effect on the intubating LMA is less.85 to prevent an increase in intracranial pressure.
Intracranial hypertension itself is not harmful unless it
causes cerebral perfusion pressure to fall below a crit-
OPEN PENETRATING CHEST WOUNDS AND
ical value. Cerebral ischemia leads to neuronal injury
TENSION PNEUMOTHORAX
and cerebral edema, which further irtcreases intracranial
An open penetra ting chest w ound is a challenging in- pressure, progressing to irreversible neurologic dama ge.
jury that is potentially associa ted with life-threatening air- Proper maintenance of gas exchange is more important than
way compromise requiring complicated emergency airway pharmacotherapy aimed at intracranial pressure control.
management. 86 Intubation is challenging because preoxy- Hyperventilation reduces intracranial pressure by caus-
gena tion may be less effective than usual; further, if mask ing cerebral vasoconstriction with a subsequent reduc-
ventilation is a ttempted, air may be forced into the subcuta- tion in cerebral blood flow. Long-term hyperventilation is
neous tissue, further distorting the anatomy. 67 In one study no longer recommended because outcome is worse than
of thoracic trauma, approximately 20% of the pa tients suf- with normocapnia96•97; initial target Pace, should be 35-
fered a pneumothorax and I or hemothorax, injuries were 40 mmHg. 98 Short-term hyperventilation, ho wever, may
penetrating in approximately 10%, and only approximately ha ve a role in reducing intracranial pressure in patients
3% required a thoracotomy.88 Dyspnea, hemoptysis, sub- who are deteriorating rapidly before other measures can
cutaneous emphysem a, pneumomediastinum, and pneu- be instituted. 99 The lowest level of positive end-expiratory
mothorax are fotmd commonly in pa tients with open pen- pressure tha t m aintains adequate oxygena tion and prevents
etrating chest wounds (secondar y to blunt trauma). Such end-expiratory a lveolar collapse should be used.92 Hemo-
a difficult airway needs to be secured; alternative airway d ynamic stability has particular importa nce in serious tra u-
techniques have been recommended as first-line approach, matic bra in injury pa tients because outcome is worse w ith
in particular fiberoptic laryngoscopy. Fiberoptic intubation systolic pressures of less than 90 mmHg 100 and cerebral per-
is the "gold standard" whenever the airw ay is expected to fusion pressures of less than 70 mmHg.10 1 Thus perfusion
be difficult; direct airway injury can be diagnosed defini- pressures should be kept higher by employing either in-
tively, and an endotracheal tube can be placed into one of travascular volume replacem ent or vasopressors. Evidence
the bronclu if there is a major injury of the opposite side.89 of elevated intracranial pressure includes progressive coma
The pa tient should breathe spontaneously for as long as and pupillary dilatation. Maneuvers tha t decrease intracra-
possible and ideally undergo a gas induction of anesthesia nial pressure include raising the head to 30°, ensurirtg
w1obstructed venous d rainage, and infusion of mannitol, acute lung injury followed by acute respiratory distress syn-
which may reduce cerebral blood flow in patients at high drome within a very short time. Because hypoxia is the ma-
risk of secondary ischemic brain injury. 10 2, l03 jor cause of death, the primary goal is to restore oxygen
delivery. Immediate rescue out of the water is critical. After
initia l resuscitation, continuing heat loss must be grevented
BURNS
by adequate insula tion against the environment. 1 8 Patients
In a burn patient, airway and respiratory complications representing awake or somnolent but with clinical signs of res-
main a common cause of morbidity and mortality. Multiple piratory distress should receive oxygen at a high concentra-
variables have an impact on resuscitation, including delay tion using a tight-fitting mask and a reservoir bag. In the case
in its initiation, inhalation injury, and the d epth and vapor- of progressive d eterioration of respira tory or neuro logic
transmission characteristics of the wound itself. Inaccurate function, RSI under crico id pressure has to be performed
volume administration causes substantial airway, respira- and ventilation with positive end-expiratory pressure
tory, and other morbidity; thus burn resuscitations must be and 100% oxygen initiated w ithout d elay. A nasogastric
guided by hourly evaluation of resuscitation endpoints.'104 tube will decompress a full stomach and aid ventilation in
Constricting circumferential or near-circumferential torso these patients. Asystole and ventricular fibrillation warrant
wounds can reduce ches t-wall compliance as soft tissues aggressive CPR because the prognosis is dismal; unfortu-
swell beneath the inelastic eschar. Improvement in venti- na tely, CPR is underused in drowning victims. 109 In a recent
latio n is common after escharotomy of the chest and ab- investigation of unwitnessed out-of-hos pital cardiac arrest,
domen. In the initia l evaluation and resuscitation phase, near-drowning was an independent predictor of survivaJ.l1°
the key point of airway management is assessment of air- The level of consciousness on h ospital admission is a
way patency and inhalation injury. The latter results from rough predictor of outcome. Patients awake or with blunted
aspiration of superheated gases, steam, or n oxious products consciousness on admission usually survive without neuro-
of incomplete combustion. Inhalation injury adversly affects logic pathology. In hemod ynamically s table but hy pother-
gas exchange and hemodynamics. It also profoundly influ- mic patients, reheating should be performed us ing warmed
ences mortality from that predicted by age and burn size.105 humidified inspiratory gases, warmed intravenous fluids,
Physical signs of particularimportance are singed nasal hair, heating bla nkets, or forced-air surface rewarming. With
facial burns, and soot ii1 the mouth and between the teeth. these methods, body temperature may increase by approx-
Stridor mandates rapid intubation. In questionable cases, di- imately 1-2°C per hour. 111 In the presence of hemodynamic
rect laryn goscopy and fiberoptic bronch oscopy can be very instability, more aggressive reheating s trategies, including
helpful; the bronchoscope can serve as a stylet for intuba- bladder irrigation, gastric or pleural lavage, peritoneal dial-
tion. Patients at risk for progressive edema should be ob- ys is, and extracorporal rewarming us ing hemofiltration,
served closely and intubated early. After securing the air- are mandatory. 108 In severely hypothermic patients with
way, the following require close attention: bronchospasm, cardiocirculatory arrest, rewarming employing cardiopul-
sm all airway obstntction, carbon monoxide poisoning, and monary bypass is the method of choice.112
respiratory failure. If massive edema is associated with bum
resuscitation, reintubation after tmplanned extubation can
be especially difficult; prevention by endotracheal tube se-
curity is the best approach, su ch as securing the endotra- Adjuncts for Oyxgenation, Ventilation,
cheal tube with an umbilical tie harness. Adjunctive tecll- and Airway Control
niques in case of difficult intubation, such as laryngeal mask
airway or a needle or open cricothyroidotomy, can be life- OXYGENATION DEVICES
saving.
During resuscitation, 100% inspired oxygen (Fr0 2 = 1.0)
should be used as soon as possible. Exhaled air contains
DROWNING approximately 17% oxygen and approximately 4% carbon
Worldwide, 3.5 deaths per 100,000 population are caused dioxide. 113•114 Small tidal volumes (500 ml) of 17% oxy-
by drowning accidents . Death by submersion is the second gen and 4% carbon dioxide in animals 115 and healthy, con-
most common cause of accidental death in children.Hl6 Vic- scious voltmteers resulted in insufficient oxygenation and
ventilation.1'1 6 Short-term therap y w ith pure oxygen is bene-
tims of drowning accidents usually show an initial phase of
panic and swimming movements. Apnea and brea th hold- ficial and not toxic. Oxygen toxicity occurs only during pro-
longed therapy with a high Fr0:1 . During bag-valve-mask
ing often are followed by swallowing of large amounts of
ventilation using room air (21% oxygen) and a normal car-
fluid with subsequent vomiting, gasping, and fluid aspira-
tion. Ultimately, severe hypoxia leads to unconsciousness, diac output, tidal volumes of 700-1000 ml (""8.5 ml/kg)
loss of airway reflexes, and further movement of water into were required to maintain adequate oxygenation.117•118
the lungs. Aspirated hypotonic or hypertonic fluids result
in bronchospasm, leading to an increase in relative shunt
and alveolar edema.1w These events cause hypoxemia, d e- VENTILATION DEVICES
creased lung compliance, and increased work of breathing. BAG-VALVE-MASK VENTILATION
Up to 70% of drowning victims aspirate foreign material A simple, portable bag-valve-mask device usually is avail-
such as mud, algae, and vomitus. Patients usually d evelop able in hospital war ds a nd in every emergency m edical
Mi n ute
~0
ventil ation (L )
Lung
Stomach
•
[]
6
4
Mask D
2
0
bag size adu lt pediatric adu lt p ediatric adul t pediatric
L ESP (em H 20) t;

FIGURE 27-4 Mask, lung, and stomach tidal volume applied with an adult and p ediatric self-inflatable bag at lower esophageal sphincter
pressure (LESP) levels of 15, 10, and 5 cmH20. Bars rep resenting lung (black colrmlils) and stomach tidal volumes (gray colrw ws ) for a
given bag size, and LESP levels are superimposed; mask tidal volumes (wlrite colum.us ) start from 0. Data are shown only as means.
(Repriut'ed, witlr. pennissio11, from Lippincott Williams & Wilkins and Weuzel et al: Crit Care Med 26:364-8, 1998.)
service. Proper bag-valve-mask ventilation is a fundamental unintubated patients, it depends on the m ode of power; that
skill of resuscitation and should receive a high priority in is, in pressure-cycled devices, because these device must
training. Unfortunately, these skills are poorly performed achieve a relatively high airway pressure (usually greater
even after retraining, and inadvertent hyperventilation is than the reported lower esophageal sphincter pressure) to
detrimental to morbidity and mortality. With an unpro- turn off the fl ow and cycle to an exhalation, they create large
tected airway, the risk of stomach inflation and aspiration amounts of stomach inflation, especially as the airway re-
is hlgh using standard bag-valve-mask resuscitators. Short sistance increases or lung compliance decreases. The guide-
inspiratory times, hlgh flow rates, and hlgh airway pres- lines for resuscitation recommend avoiding these devices.
sures, caused by squeezing the bag too hard and too fast, On the other hand, tidal volume should be restricted in
are the main causes of stomach inflation. Reduced expira- volume- and time-cycled ventilators. In an in vitro m odel of
tory times produced by inadvertent hyperventilation stacks an unprotected airway, significantly less stomach inflation
air in the lungs, creating decreasesd cardiac refill and de- was found when applying a tidal volume of approximately
creased coronary perfusion pressure. A small self-inflatable 500 ml versus approximately 1000 m1. 122 Controlling infla-
bag was advantageous over a la rge one when paramedics tion time, flow rate, and flow waveform with a mechanical
undertook bag-valve-mask ventilation with a pediatric ver- ventilator may be the best solution to control and limit peak
sus an adult-sized self-inflatable bag using an in vitro model inflation pressure for a given tidal volume, but these vari-
of ventilation with an unprotected airway. Pulmonary ven- ables are not controlled easily during manual ventilation.
tilation w as similar with both bags, but stomad1 inflation
was much less with the pediatric bag,.19•120 (Fig. 27-4).
Depending on lung compliance, different tidal volumes AIRWAY CONTROL DEVICES
caused stomach inflation in patients, but most often at a OROPHARYNGEAL AND NASOPHARYNGEAL
peak inflation pressure of greater than 20 cmH2 0. Data from AIRWAYS
an in vitro model of an unprotected ainvay confirmed that These airway adjuncts can be used in unintubated patients
longer inflation times produced increased lung ventilation requiring ventilation. The oropharyngeal airway should be
and reduced stomach inflation, especially when intrapul- inserted only in unconscious patients; otherwise, gagging
monary a irway resista nce was high. While the bag-valve and vomiting can be evoked. The nasopharyngeal airway is
mask is the simplest and most-cost effective ventilation de- better tolerated in somnolent patients. The devices should
vice available, its efficacy is diminished by lack of skill of the be inserted carefully by trained personnel; lubricants ease
user, the "incident stress" associated with treating a patient insertion.
in cardiac arrest, and the subsequent inadvertent hyperven-
tilation that these issues cause. A relatively new bag-valve- ENDOTRACHEAL TUBE
mask tedmology exists tha t assists rescuers in ventilating As early as possible during resuscitation, trained person-
correctly by responding to squeeze and release of the bag nel should intubate the trachea. Before commencing in-
and controlling the flow of gas from the bag, reducing air- tubation, the patient should be preoxygenated either by
way pressure, increasing inspiratory times, and nearly com- spontaneously breathing pure oxygen or by controUed bag-
pletely eliminating the risk of stomach insufflation.·121 valve-mask ventilation with a high inspired concentration
of oxygen. Preoxygena tion increases the a lveolar pressure
AUTOMATIC TRANSPORT VENTILATORS of oxygen; elimina tion of nitrogen increases the reservoir
In prehospital care, mechanically powered devices are as ef- of oxygen fivefold and generates a grace period of several
fective as other devices for ventilating intubated patients. In minutes before a patient becomes hypoxic (Fig. 27-5). The
100
........... .....
-..............
'\ '\
\
-......_ \p regnont l \
'
90
\
\
Modorotely II 1\ \\
\
70 kg Adult
1\
--
~
80 \ Normal
70kg
Adult
\
Obese
d'
0
(/) 70
130 kg
Adutt 1\
\\
60 \
\
0 0 1 2 3 4 5 6 7 8 9 10 FIGURE 27-5 D esaturation after preoxygenation.
Time in minutes until o xygen saturation (S ao 1 )
Time (minutes) drops during apn ea.
grace period depends on the alveolar volume, shunts, oxy- ing of the tube is just above the glo ttis, providing venti-
gen consumption, and oxygen-carrying capacity. The inter- lation and oxygenation. The main limitation of theLMA is
ruption of ventilation should be as brief as possible, and a lack of protection against aspiration, 128 although regurgi-
adequate ventilation and oxygenation must be provided if tation is less likely than with bag-valve-mask ventilation.'129
more than one intubation attempt is necessary. To facili- A recently developed ProSeal LMA has an additional lu-
tate intubation, the sniffing position and hyperextension of men to introduce a nasogastric tube to drain the stomach
the head at the atlanto-occipital joint is beneficial. A stylet, or regurgitated fluids 130 away from the respiratory tract.131
which should not extend over the distal end, can be used to The bowl of the mask is deeper than that of a standard
provide some stiffness to the tube and makes control dur- LMA, with an additional cuff on the dorsal side. Because
ing insertion easier. A second rescuer applies cricoid pres- of these modifications, the airway sealing pressures achiev-
sure during bag-valve-mask ventilation and intubation to able with the ProSeal LMA are at least 10 cmH20 higher
prevent regurgitation and subsequent aspiration. When the than with the standard LMA. As with the standard LMA, the
cuff of the tracheal tube is inflated and the airway thus se- ProSeal LMA can be inserted in the neutral position, mak-
cured, cricoid pressure can be removed. Tube placement is ing it a ttractive in potential cervical spine injury. Another
confirmed by chest excursion and auscultation; over the epi- limitation of the LMA is the relatively low leak pressure
gastrium, no stomach gurgling should be heard during in- 19-22 cml-h0,132,133 which may decrease tidal volume and
spiration. These clinical signs are not always reliable123; un- increase stomach inflation.134 The intubating LMA is a mod-
recognized misplacement of the endotracheal tube occured ified conventional LMA; once inserted, it allows passage of a
in up to 6-25% of intubated patients in the field. 6' 7 Verifi- tracheal tube, either blindly or by fiberoptic bronchoscopy.
cation by direct visualization of the tube passing through Standard insertion requires a neutral position; manipula-
the vocal cords and use of end-tidal carbon dioxide moni- tion of the head and neck is not needed.
toring also are recommended.124,125 Clinical assessment and
esophageal detector devices may be used but are not reliable COMBITUBE
in all patients. The Combitube is essentially a double-lumen tube that is in-
serted blindly through the mouth and is more likely to pass
LARYNGEAL MASK AIRWAY into the esophagus (.....,95%) than into the trachea (---5%). The
The laryngeal mask airway (LMA) now is used widely for esophageal lumen is closed distally and perforated at the
managing failed intubations or difficult airways.126,"127 It hypopharyngeallevel with several small openings; the tra-
should be considered first among the alternative airway cheal lumen is open distally. First, the proximal large pha-
devices. Placement and use of an LMA are simpler than ryngeal balloon is inflated, thereby filling the space between
tracheal intubation because laryngoscopy and visualiza- the base of the tongue and the soft palate. Second, the dis-
tion of the vocal cords are unnecessary. The LMA is intro- tal cuff is inflated. These cuffs provide a good seal of the
duced into the hypopharynx, and the cuff seals the larynx hypopharynx from the oropharynx and stability in the tra-
after inflation. While the arrow is positioned at the upper chea or esophagus, respectively. The most common reason
esophageal sphincter without sealing it, the distal open- for failure to ventilate is placing the Combitube too deeply;
604 PART Vlli VENTILATOR SUPPORT IN SPECIFIC SETTINGS
the entire perforated pharyngeal section enters the esoph- TRACHEOSTOMY AND CRICOTHYROIDOTOMY
agus. Pulling the Combitube back 3-4 em usually resolves When the airway is compromised by trauma, or when
the problem. The success of insertion and ventilation with massive oropharyngeal or hypopharyngeal pathology is
the Combitube is comparable with that of other upper air- present, emergency access may be possible only through
way devices 135 and is 100% in an urban environment where an emergency tracheostomy or cricothyroidotomy. Emer-
trauma patients receive care. 136 The Combitube, however, gency tracheostomy usually is performed via a vertical in-
is not well tolerated by patients with a persistent strong gag cision from the cricoid cartilage down in the direction of
reflex. It should be exchanged to an alternative airway as the sternal notch. A skilled operator can insert a small,
early as possible. Advantageously, the Combitube can be cuffed endotracheal tube rapidly. Emergency cricothyroido-
a routine device in emergency medicine137 and in "cannot tomy is a valid alternative for a less skilled operator. The
ventilate, cannot intubate" situations.138 The Combitube has cricothyroid membrane, palpable directly under the skin,
the same limitations as theLMA Thus it may be unsuitable is incised in its inferior third to minimize the possibility of
in patients with hypopharyngeal pathology or preexisting bleeding. The cricothyroid membrane is not always easy
esophageal pathology, such as a malignancy or esophageal to appreciate (in obese patients or those with short necks).
varices.139 Cricothyroidotomy is performed infrequently; in inexperi-
enced hands, success is only 60-70%.143 The main advan-
tage of this technique is the blunt dissection of the subcu-
LARYNGEAL TUBE taneous tiss ues all the way to the cricoid membrane. An
The recently introduced single-lumen laryngeal tube can be airway catheter is then introduced over a dilator threaded
inserted orally without additional equipment and is effec- over the guidewire. 144 This technique allows the ultimate in-
tive for ventilating and oxygenating patients who experi- sertion of an airway that is considerably larger than the ini-
ence a respiratory arrest during induction of anesthesia..140 tial needle or catl1eter. Its internal diameter often is sufficient
Thus the laryngeal tube may be used as an alternative air- to allow ventilation with conventional ventilation devices,
way device during routine or emergency airway manage- suctioning, and spontaneous ventilation. Needle cricotlly-
ment. Handling of the laryngeal tube has been simplified roidotomy is another alternative, regardless of whether it
by blocking two cuffs with one instead of two catheters; is surgical or percutaneous. Needle cricothyroidotomy al-
the first secures inflation of the oropharyngeal cuff, and the ways requires the use of a jet device to provide ventilation. It
second secures inflation of the esophageal cuff because of is associated with a high incidence of complications, such as
different resistance characteristics of the connected tubing. massive subcutaneous emphysen1a, barotrauma with pneu-
Given its design, the laryngeal tube may not be the best motllorax or tension pneumotl1orax, and air trapping with
device for spontaneously breatl1ing patients.141 The blind severe hemodynamic instability.
ending in the esophageal inlet a lso may cause esophageal
rupture in the case of vomiting.142 Accordingly, the laryn-
geal tube has been fitted with a second lumen for suction- Conclusion
ing and free stomach drainage Oaryngeal tubeS) but not for
ventilation, as with the Combitube. In contrast to the Com- The goal of ventilation strategy during resuscitation is to
bitube, the laryngeal tube S has only one adapter, which optimize oxygenation and carbon dioxide elimination. TI1is
may be connected with a ventilation device, whereas the can be achieved in an unprotected airway with techniques
remaining connector can only be connected to a suction such as mouth-to-mouth ventilation but preferably with
adapter. This may achieve additional patient safety; it pre- bag-valve-mask ventilation. Because ventilation of an un-
vents an inexperienced user from inadvertently attaching a protected airway may result in stomad1 inflation and sub-
ventilator or bag-valve-mask device to the esophageal tub- sequent severe complications, securing the airway with an
ing, which could result in stomach inflation and subsequent endotracheal tube is the "gold standard"; however, other
ventilation-related complications. airway devices are acceptable if rescuers are trained prop-
erly. Of importance, airway device complications are more
related to training than to the devices themselves. Excellent
PHARYNGOTRACHEAL LUMEN AIRWAY success in emergency ventilation depends on initial train-
The pharyngotracheal lumen airway is an improvement ing, retraining, and actual freq uency of performing a given
on the design of the esophageal obturator airway and the procedure on the job.
esophageal gastric tube airway. Both devices are double-
lumen airways that are inserted blindly, preferably into the
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131. Keller C, Brimacombe J, Kleinsasser A, Loeckinger A. Does the 138. Della Puppa A, Pittoni G, Frass M. Tracheal esophageal Corn-
ProSeal laryngeal mask airway prevent aspiration of regurgi· bitube: A useful airway for morbidly obese patients who cannot
tated fluid? Anesth Analg 2000; 91:1017- 20. intubate or ventilate. Acta Anaesthesiol Scand 2002; 46:911-3.
132. Ocker H, Wenzel V, Schmucker P, et a!. A comparison of the 139. Vezintl D, Lessard MR, Bussicres J, ct al Complications associ-
laryngeal tube with the laryngeal mask airway during routine ated with the use of tl1c esophageal-tracheal Combitubc. Can J
surgical procedures. Anesth Analg 2002; 95:1094-7. Anaestll1998; 45:76-80.
133. Asai T, Kawashima A, Hidaka I, Kawachi S. The laryngeal tube 140. Asai T, Murao K, Shingu K. Efficacy of the laryngeal tube dur-
compared with the laryngeal mask: insertion, gas leak pressure ing intermittent positive-pressure ventilation. Anaesthesia 2000;
and gastric insuffla tion. Br j Anaesth 2002; 89:729-32. 55:1099-102.
134. Devitt JH, Wenstone R, Noel AG, O'Donnell MP. The laryngeal 141. Miller OM, Youkhana I, Pearce AC. The laryngeal mas k and
mask airway and positive-pressure ventilation. Anesthesiology VBM laryngeal tube compared during spontaneous ventilation:
1994; 80:550-5. A pilot study. Eur J Anaesthesiol2001; 18:593-8.
135. Rumball Cj, MacDonald D. The PTL, Combitube, laryngeal 142. Dorges V, Ocker H, Wenzel V, Schmucker P. The laryngeal
mask, and oral airway: A randomized prehospital comparative tube: A new simple airway device. Anesth Analg 2000; 90:
study of ventilatory device effectiveness and cost-effectiveness 1220-2.
in 470 cases of cardiorespiratory arrest. Prehosp Emerg Care 143. Eisenburger P, Laczika K, List M, et al. Comparison of conven-
1997; 1:1-10. tional surgical ven.Lis Seldinger technique emergency cricotlly-
136. Blostein PA, Koestner AJ, Hoak S. Failed rapid sequence intu- rotomy performed by inexperienced clinicians. Anesthesiology
bation in trauma patients: Esophageal tracheal Combitube is a 2000; 92:687- 90.
useful adjunct. J Trauma 1998; 44:534-7. 144. Chan TC, Vilke GM, Bramwell KJ, et al. Comparison of wire-
137. Rabitsch W, Sche!Jongowski P, Staudinger T, et a!. Comparison guided cricothyrotomy versus standard surgical cricothyro-
of a conventional tracheal airway with the Combitube in an tomy technique. J Emerg Med 1999; 17:957-62.
!tJ
Chapter 28 _ _ _ _ __ _ _ __ compact, rugged equipment. Clinicians should be aware of
the physiologic effects of transport, frequency of adverse
TRANSPORT OF THE events, and methods to prevent complications.
VENTILATOR- In trahospital Transport

SUPPORTED Intrahospital transport of the ventilated patient includes
PATIENT movement between the operating room and recovery room
or ICU, a routine procedure accomplished in minutes.4
RICHARD D BRANSON Transport of critically ill patients from the ICU for diagnos-
JAY A JOHANNIGMAN
tic techniques represents a greater challenge.2. 3 Intrahospi-
tal transport from the ICU is accomplished mos t commonly
for computed tomography (CD with a mean duration of
90 minutes.5- 7 CT is ordered most frequently for evalua-
tion of head injury, identification o f bleeding, and location
and drainage of Auid collections. 4 - 14 Table28-llists investi-
INTRAHOSPITAL TRANSPORT gations of intrahospital transports, indicating the type and
INTERHOSPITAL TRANSPORT number of patien ts along with most frequent destinations.
PREPARATION AND PLANNING Magnetic resonance imaging (MRI) is an increasingly
GUIDELINES common destination for the critically ill ventilated patient.
RISK-BENEFIT OF TRANSPORT The prohibition of ferrous materials in the MRI scanner rep-
PHYSIOLOGIC EFFECTS AND COMPLICATIONS resents a significant challenge in providing mechanical ven-
OF TRANS PORT tilation.
Cardiovascular Complications
Respiratory Complications
Neurologic Complications Interhospital Transport
Other Complications
CONTRAJNDICATIONS TO TRANSPORT Tnterfacility transport has increased in recent years owing
EQUI PMENT MALFUNCTION/MISHAPS to the regionalization of specialty care and the growth of
EQUIPMENT AND MONITORING hospital systems. Neonatal intensive-care and extracorpo-
DURING TRANSPORT real membrane oxygenation centers are the classic exam-
RATIO NALE FOR USE OF A PORTABLE VENTILATOR ples of this model. More recently, specialty care in respi-
TRANSPORT VENTILATORS ratory fai lure, trauma, transplant, and cardiac disorders at
Automatic Resuscita tor tertiary-care medical faci lities has increased interhospital
Simple Transport Ventilator transports. 15• 16 TI1e g rowth of hospital systems with acute-
Sophisticated Transport Ventilator and chronic-care facilities represents another reason for in-
ATTRIBUTES COMMON TO ALL terhospital transport as patients travel back and forth based
TRANSPORT VENTILATORS on acuity.
Weight Interhospital transport can be accomplished using
Durability ground or air transport. Each method possesses unique ad-
Power Requirements vantages and new challenges. Choice of transport vehicle
Controls should include an assessment of urgency, weather, traffic,
Safety geography, and cost. Grow1d transport using a specially
Assembly and Disassembly equipped ambulance and personnel can provide "mobile
PERFORMA NCE ISSUES RELEVANT TO ALL TYPES intensive care" and is the most common mode of transport.
OF TRANS PORT VENTILATORS Ground transport is the most readily available and cost-
Delivered Tidal Volume effective while also the least influenced by weather.3
Imposed work of Breathing Air transport should be considered when d istances ex-
ANCILLARY EQUIPMENT FOR TRANSPORT ceed 50 miles or ground transport requires greater than
Oxygen Supply 2 hours. Rotor-wing o r helicopter transport is preferred
Humidification in areas where access is limited or distances are between
SUMMARY 50 and 150 miles. Helicopter transport reduces transport
time, but the environment is cramped and noisy compared
with ground transport. Additionally, rotor-wing aircraft are
Mechanical ventilation of the critically ill patient is best prac- expensive to purclutse, operate, and maintain and have a
ticed in the safe confines of the intensive-car e unit (ICU). poorer safety record. 3 Fixed-wing transport is considered
Transport of ventilated patients, however, remains a fre- when distances exceed 150 miles. While some hospitals
quent challenge. 1- 3 Successful transport requires effective maintain a fixed-wing aircraft as a consequence of geog-
communication, appropriate plaru1ing, key persoru1el, and raphy, air ambulances frequently are private corporations
609
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610 PART Vlli VENTILATOR SUPPOKI' IN SPECIFIC SETTINGS
TABLE28-1 Comparison of Stu dies Evaluating lntrahospital Tran sport of Critically Ill Pati ents
Year, Author Number of umber of Duration of

(Reference) Patients Patient Population Transports Transport Destination Transport Mean (Range)
1986, lnsel (4) 47 Adult, postoperative 47 Radiology 30%, OR 70% NR

1987, Braman (8) 36 Adult, rcu 36 Radiology 100% R
1988, lndeck (6) 56 Adult, trauma 103 Radiology 100% 81 min
1989, Weg (9) 20 Adult, ICU 20 Radiology 100% 50 min (15-80 min)
1990, Andrews (10) 27 Adult, closed head injury 35 OR 51 %, radiology 49% NR
1990, Smith (7) 127 Adult, lCU 127 OR 25%, radiology 75% 95 min
1992, Hurs t (5) 83 Adult, surgical/trauma 100 Radjology 100% 74 min (20-225 min)
1995, Szem (11) 175 Adult, surgical 203 OR 39%, radiology 61% NR
1995, Evans (12) 36 Adult, ICU 36 Radiology 100% 62 min (26-166 min)
1995, Wallen (13) 139 Pediatric 180 OR 49%, radiology 30% NR
1998, Stearly (14) 237 Adult, ICU 237 Radiology 100% NR
available for hire. When using a fixed-wing aircraft, the dis- line recommends that at least one member of the transport
tance for ground transport from the airport to the hospital team be certified in advanced cardiac life support (ACLS)
must be considered. or pediatric advanced life support (PALS). 20 The AARC also
recommends that one member be proficient in endotracheal
intubation. Several groups have suggested that a registered
Preparation and Planning nurse and a respiratory therapist accompany all ventilated
patients. 1•5•19- 21 Requiring a physician to attend transports
The key to a successful, safe transport is preparation and may increase patient safety and decrease the number of un-
planning. Before movement, goals of transport should be necessary transports but is impractical outside of academic
established and appropriate personnel and equipment as- centers.5•21
sembled . Communication with the receiving institution or
department is critical to reduce unnecessary delays.1•17 Dur-
ing intral1ospital transport to radiology, goals include ob- Risk-Benefit of Transport
taining a q uality examination while maintaining stability,
continuing care, and avoiding mishaps. Elective transports Considerable effort has been expended to ca talog the risks of
should be delayed until patient stability is achieved.16 In transport. 1•4 - 14 These are considered in detail below. Bene-
emergent situations, current care and resuscitation should fits of transport include discovery of pathology or verifying
be continued and plans to treat further deterioration agreed diagnoses that guide treatment. Several investigatiollS have
on. Uneventful transport often is attributed to planning and noted that in two-thirds of transports to radiology, the pa-
communica tion.18 tient's treatment course is unaltered.s,6, 11 Head CT is least
likely to result in a change in therapy, whereas abdominal
CT is most likely to result in new findings and guide in-
Guidelines tervention. Negative findings, however, rule out sources of
clinical deterioration and lead the physician to search for
The American College of Critical Care Medicine (ACCM)
guidelines state that "each hospital should have a formal- other etiologies.
ized plan for intra- and interhospital transport." 19 This in- Cost-benefit ratio is difficult to measure and includes not
only the cost for the procedure but also the costs of transport
cludes pretransport coordination and communication and
equipment, transport personnel, and personnel to cover the
guidelines for defining the appropriate personnel, equip-
workload of caregivers attending the patient outside the
ment, and monitoring. ACCM further suggests that these
plans should be developed by multidisciplinary teams and ICU. This additional burden to remaining ICU staff fre-
subjected to continuous q uality improvement. quently is associated with reduced staffing levels and end-
of-shift overtime.s,6
The ACCM guidelines are based on research suggesting
that protocols reduce mishaps and facilitate transport.7•21
Transport protocols should match patient acuity with the
personnel and equipment necessary to acl1ieve appropriate
Physiologic Effects and Complications
monitoring and safety. A survey of 152 ICUs, showed that of Transport
95% expressed being quite concerned or very concerned
(51 %) about the dangers of transporting critically ill pa- Transport of the ventilated patient requires exchange of ex-
tients. In the same survey, only 45% had policies defining isting monitoring and support equipment to portable equip-
personnel requirements.2'1 ment, as well as the physical movement of the patient. These
Transport policies should describe the type and level of interruptions in care and change in patient position can alter
training for personnel involved 1 •16•19· 20 The American Asso- the patient's condition. Patients typically are transported in
ciation for Respiratory Care (AARC) clinical practice guide- the supine position, which changes respiratory mechanics
CHAPTER28 TRANSPORT OF THE VENTILATOR-SUPPORTED PATIENT 611
TAB LE 28-2 Commonly Reported Complica tions during ritability, leading to dysrhytlunias. 8•25 - 28 This finding com-
Transport of the Mechani call y Ventilated Patient monly is associated with unmonitored manual ventilation
Cardiovascular
but can occur with a ventilator when minute ventilation is
Arrythmia unreliable. 28
Hypotension Hypotension during transport may result from loss of
Hypertension intravenous access, interruption of vasoactive agents, pneu-
Tachycardia mothorax, or bleeding. Alkalemia associated with hyper-
Bradycardia ventilation likewise can cause hypotension. 8·28· 29 Hyperten-
Myocardial ischemia sion can result from stress and anxiety, as well as from
Worsening heart failure patient movement that encounters "bumps" in the trans-
Cardiac arrest port path and jostling of patients that causes pain.5•6•10•22
Respiratory Cardiac arrest has been reported during transport, but pa-
Hypoventilation tient movement per se has not been directly implicated.
Hyperventialion
Hypoxemia
Barotrauma RESPIRATORY COMPLICATIONS
Neurologic
Elevated intracranial pressure
Hypoxemia may occur during transpor t as a consequence
Increased anxiety of loss of positive end-expiratory pressure (PEEP), changes
Other
in patient position, impaired secretion removal, and fail-
lncreascd risk of ventilator associated pneumonia
ure to reproduce ventilator settings adequately. 2• 5• 6- 8•29 - 31
Bleeding or hemorrhage During transport of adult patients, high inspired oxygen
Hypothermia concentrations (Fro2 ) are used commonly as a matter of
Effects of altitude on physiology" convenience. 1•32 Elevated Fie, may lead to masking of de-
Equ ipment failure/mis haps terioration in lung function and contribute to absorption
Airway obstruction atelectasis. Patients requiring PEEP of more thanlO cmHzO
Extubation have demonstrated a deterioration in oxygenation during
Intubation of right main-stem bronchus trans port that lasted for up to 24 hours.10
Gastric aspiration around endotracheal tube cuff Hyperventilation is a frequent complication associated
Loss of battery power to monitoring equipment or ventilator with manual venblation8•28•31•33 and with poor control of
Damage to equipment due to mishandling or falls
minute ventilation by portable ventilators?' Sudden res-
Loss of oxygen supply
Fai lure to reproduce lCU ventilation parameters with a portable
piratory alkalosis can result in changes in cardiovascular
ventilator or manual ventilator (loss of PEEP, failure to trigger, function. During resuscitation, hyperventilation has been
inappropriate tidal volume or frequency) shown to impair hemodynamics and contribute to the de-
Effects of altitude on equipment performa11ce• velopment of electromechancial disassociation and poor
Loss of venous access/indwelling vascular catheters outcome.34 Hyperventilation increases intrathoracic pres-
Interruption of medications- continuous and intermittent sure, produces air trapping, reduces cardiac output, shifts
Inadequate chest tube drainage the oxyhemoglobin dissociation curve to the left hinder-
ing oxygen unloading, and causes cerebral and myocardial
"Unique to air transport.
vasoconstriction. These combined effects may affect patient
outcome adversely.34
and may alter hemodynamics. Many departments where Hypoventilation is reported less frequently and gener-
procedures are done are distant from the ICU, located in fa- ally is better tolerated.4 - 14 Too small a tidal volume may
cilities never designed to house the critically ill patient. Both contribute to atelectasis and respiratory acidosis. In acute
remote location and poor physical plant may contribute to acidosis, cardiac function may be compromised. Hypoven-
tmtoward outcomes following a complication. Complica- tilation may result from the increased use of sedation and
tions of transport are frequently recalled as ''the catastro- neuromuscular blocking agents to achieve patient comfort
phe in radiology." The spectrum of complications ranges and facilitate quality examinations.
from minor changes in heart rate to cardiac arrest. A list of Loss of the artificial airway is an infrequent but catas-
common complications is given in Table 28-2. trophic complication of transport. Inability to establish an
adequate airway is associated w ith hypoxemia and poor
outcome in head-injured patients.17•35 Unintubated patients
CARDIOVASCULAR COMPLICATIONS
with marginal ainvay control may benefit from intubation
Cardiovascular events are the most frequent complication before transport. Radiologic procedures requiring the pa-
of transport and are reported in up to 50% of cases.6•8•9•11 An tient to remain supine may compromise the tenuous airway.
increase in heart rate is seen frequently as a result of anx-
iety, pain, and activity. Arrhythmias are common during
the transport of high-risk cardiac patients, a finding com- NEUROLOGIC COMPLICATIONS
plicated by the fact that routine lead II monitoring may be Increases in intracranial pressure have been reported
tmable to detect early changes. 23•24 Acute respiratory alka- during transport and are associated with s upine posi-
losis res ulting from hyperventilation alters myocardial ir- tioning, changes in ventilation, airway compromise, and
612 PART VIII VENTILATOR SUPPORT IN SPECIFIC SEITINGS
hypoxemia.10•17•35 Anxiety may contribute to hemodynamic Equipment M alfu nction/M ishaps

alterations as well as increased intracranial pressure (ICP).
Anxiety results from patient movement and uncertainty, as Mishaps range from the benign to the catastrophic. The fre-
well as adjustment from ICU to transport equipment. quency of mishaps varies v.'idely with the definition. Mishap
has been defined as "the occurrence of any unplanned event
that potentially could have a detrimental effect on patient
OTHER COMPLICATIO NS care stability."7•9 Using a broad definition of mishap, early
Hypothermia during transport occurs because hallways studies fow1d that half of patients suffered a mishap dur-
and examination areas have less precise environmental ing transport. Most of these, however, were minor (e.g.,
controls. 13 Exposure of skin surfaces for adequate radio- electrocradiograph electrode disconnection), and only 24%
logic examinations and use of skin p reparations for proce- of mishaps resulted in any change in patient physiology?
dures further contribute to temperature loss. Blood loss has Other common mishaps include loss of vascular access,
been reported during movement of patients with unstable disconnection from oxygen supply, disconnection from the
fractures. 13 A late complication of transport is ventilator- ventilator, and improper care of chest tubes. 6 - 9•22
associated pneumonia. Transport from the ICU is an in- Equipment failure rema.ll1s a common mishap during
dependent predictor for the development of pneumonia.36 transport, frequently attributed to poor planning and
Possible causes include supine positioning, aspiration carlessness.9•22 Reported failures include depletion of bat-
around artificial ainvays, contaminated manual resuscita- tery power of ventilator or monitoring equipment, exhaus-
tors, manipulation of the ventilator circuit, and inadequate tion of portable oxygen supplies, and damage to devices re-
infection control policies.37 - 39 It is also possible that the need sulting from falls to the floor. 4 - 9 Exhaustion of a compressed
for transport implies a greater severity of illness and pro- oxygen supply during use of a pneumatically powered ven-
longed ventilaton, increasing the risk of pneumonia. tilator terminates ventilation and can be a life-threatening
Air transport introduces the unique issues of physiologic mishap. Table 28-3 provides a comparison of studies evalu-
alterations at altitude. Fixed-wing aircraft employ pressur- ating complications and mishaps in intrahospital transport
ized cabins equivalent to an altitude of 8000 ft (barometric of critically ill patients.
pressure of 565 rnmHg). 40 Rotor-wing aircraft may operate
at higher altitudes during movement over rugged terrain.
The hypobaric environment can cause hypoxic hypox- Equipment and Monitoring
emia and expansion of gases in closed spaces. A change
in altitude from sea level to 8000 It is associated with hy- During Transport
poxemia in gatients with normal and abnormal pulmonary
function. 41 •4 At similar altitude changes, gas trapped in Approriate equipment and monitoring are important to
maintaining homeostasis and ensuring safety. Monitoring
dosed spaces can expand in volume by 30%. Gas trapped
during transport should emulate the ICU. Minimum re-
in the body, such as a small pneumothorax, can become
quirements include electrocardiographic (ECG) monitoring
significant at altitude. Gas in equipment is also affected, in-
(lead ID of heart rhythm and rate, invasive or noninvasive
cluding the volume and pressure inside airway cuffs and
urinary catheters, which may result in pain, discomfort, or blood pressure monitoring, and pulse oximetry. Monitoring
rupture. Ventilator performance can be adversely affected should adapt to the needs of the patient and include addi-
by changes in barometric pressure. In particular, pneumat- tional pressure monitoring if ICP or central venous pressure
ically operated devices will have alterations in tidal vol- catheters are present. Battery-powered intravenous pumps
tune, frequency, and inspiratory time as altitude increases. for medication delivery also are required.
Newer ventilators include a barometric pressure sensor Equipment for transport should be rugged, lightweight,
that automatically compensates for hypobaric effects on gas reliable, and operate from battery power for at least
density. 43 1 hour. Required equipment includes the physiologic mon-
itor, pulse oximeter, and ventilator. Additional equipment
includes a manual resuscitator with a PEEP valve, oxygen
supplies, stethoscope, and emergency airway-management
Contraindications to Transport equipment. A spirometer to monitor tidal volume during
manual resuscitation also should be available.
There are few absolute contraindications to transport. Ap- A drug box with the patient's current medications and
propriate planning, equipment, persoru1el, and monitoring agents for resuscitation should accompany the patient.
allow safe transport. Transport of the ventilated patient is Agents for sedation or paralysis and intravenous fluids
best considered as transferring the ICU with the patient, not for resuscitation and ongoing management also should be
transferring the patient from the ICU. Patients occasionally available.
are deemed too sick to transport. The specific contraindi- A dedicated transport cart or trolley may simflify trans-
cations to transport are (1) inability to maintain acceptable por t but is an inefficient use of resources. 6•23•33A •44 The ad-
hemodynamic status, (2) inability to establish an adequate vantage of the cart is immediate availability of required de-
airway, (3) inadequate personnel, (4) inability to maintain vices. The disadvantages are cumbersome size and cost. A
adequate gas exchange, and (5) inability to monitor patient dedicated trolley for transport perhaps is best suited for in-
status effectively. terhospital transport.45 Table 28-4 lists the monitoring and
TA8LE28-3 Comparison of Studies Evaluating Complications and Mishaps in l ntrahos-pital Transport of Critically Ill Patients
COJ\1PLICATIONS
Year, Author Complicntion Type o f
(Reference) R:'lt~ Cardiovascular R<$piratory Equipment Other Ventilation A tte ndants
1975, Waddell (22) 7.2% 7.2% hypotens ion, 0% 0% Blt'Cding 1.6% NR Rl'I, MD
hypertension,
tachycardia
1986, lnscl (4) 24% 24% hypotensiol'l, O"'o 0% 0% Manual RN, MD
arrhythmia
1987, Bramal\ (8) 66% 25% hypotension, 56'Yo hypocarbia, 5.5% ventilator battery failure, 0% Manual, u = 20 RN, MD, RRT
1988, lndeck <6> 68t}';,

arrythmia
6 1% tachycardia,
hypotens ion,
hyperca rbia
37% hypoxemia,
tilchypnea
,.
disconnl-'Ct:Cd oxygen supply
o·• O'fn
Ventilator, u = 16
Ventilator RN, MDIU<r
hypertension
1989, Weg (9) 15% 0% 1~~ hypoxemia 5% disconn('Cted oxygen s upply 0% Mi'nual RN, RRT
0'1 hyp01.-arbia
~ 1990, Andrews (10) 51 % 9% hypotension, 23% rise 9o/.. hypoxemia NR 0% Ventilator NR
w in ICP, 14% hypertension
1990, Smith (7) 34% NR NR 34% ECC lead d isconnected, NR Nil RN, MD, RRT
monitor battery failure,
ventila tor disconnection
1992, Hurst (5) 66% 27% tachycardia, 20% tachypnea 5% pulse oximeter failure. 0% Ventilator RN,MD,RRT
36% hypotension, 2% hypoxemia monitor bat-tery fa ilure
hypertension
1995, Szom ('11) 5.9% 1'}'Q hypotensiort, 4'fo hypoxemia NR NR Manual or MD,RRT
1.5% cardiac arrest ventilator
1995, Evans (12) 53% 5.5% arrhythmia, 17'Yo hypoxemia 11% 0% Ventilator NR
25% tachycilrdin,
39% hypotension
1995, Wallen (13) 76% 47% tachycardia, 29% tachypnea 10% monitoring battery failure, l<Yt'u hypothermia Manual RN, MD
21% hypotension 6% h ypoxemia ventilator d isconnection
1998, Stearly (14) 15.5% NR NR NR NR NR RN
AtunttrVI A1'10NS: ECC, e){'ctrocardiograph; ICP, intraCTanial ptel-.sure; MD, physician; NR. not reported; RN, regL'itl!Nd nurse; RRT. reg:istert>d respiratory therapist.
614 PART Vlli VENTILATOR SUPPORT IN SPECIFIC SEITINGS
TABLE 28-4 Monitoring an d Life-Su pport Equipment for tient with normal lungs during transport to the recovery
Transport of th e Ventilator- Dep enden t Patien t room is safe, ventilation of the patient requiring PEEP, ele-
Monitoring
vated Fr02 , and constant volume is best accomplished by a
• ECG monitoring (rate and rhythm) ventilator.
• Arterial blood pressure monitoring (invasive or noninvas ive)
• Pulse oximetry
• Additional pressure monitoring (e.g., pulmonary artery,
intracranial) Transport Ventilators
• Stethoscope
• End-tidal CD2 monitor (optional) Technically, any ventilator that operates from a battery and
• Portable spirometer either an internal gas source or a compressed gas cylin-
Support cquipme11t der could be considered a transport ventilator. Because of
• Portable ventilator capable of providing required mode, Fr02 , the demands of patient transport, however, these simple
tidal volume, and PEEP criteria are inadequate. Using performance to discriminate
• Airway maintenance (should include a difficult airway kit)
transport ventilators yields three categories: automatic re-
• Manual resuscitator and mask
suscitators, pneumatically powered transport ventilators,
• Oxygen supplies (one or two cylinders)
• Drug box (emergency drugs, patient specific drugs, sedatives, IV
and sophisticated transport ventilators.
fluids)
• Infusion pumps (ba ttery operated)
• Defibrillator (optional) AUTOMATIC RESUSCITATOR
• Portable suction (optional)
An automatic resuscita tor is a device that provides ventila-
tion at a set pressme. A few automatic resuscitators do not
have the ability to set or control frequency. These devices are
life-support equipment necessary for transport of the ven-
tilated patient. flow-limited and pressure-cycled. Frequency varies with
lung impedance: When impedance is high, tidal volume is
small and frequency rapid; when impedance is low, tidal
volume is high and frequency slow. These devices are pow-
Rationale for Use of a Portable Ventilator ered pneumatically (requiri11g no electricity), have only a
mechanical, audible high-pressure alarm, and have only
Manual ventilation his torically has been used during trans- disposable pressure manometers.
port. It is inexpensive, simple, and requires only human
power. During manual ventilation, however, the volume,
frequency, and pressure applied are unknown. Several in- INTENDED USE
vestigators have noted hyperventilation and acute respira- These devices are designed for use in a prehospital set-
tory alkalosis during manual ventilation resulting in cardio- ting by personnel with limited expertise in mechanical
vascular complications. 2•23•28•29· 31•33- 35 Aggressive manual ventilation.
ventilation can result in excessive airway pressures, causing
barotrauma or volutrauma and worsening air trapping.46 EXAMPLES OF AUTOMATIC RESUSCITATORS
Manual ventilation can be successful in the hands of Examples include the Vortran and Oxylator EM-100 (Fig.
a skilled clinician with additional volume- and pressure- 28-1). Both these devices are flo..,v-limited and pressure-
monitoring capabilities. 9•13 Monitoring end-tidal C02 also cycled. As such, rate cannot be set, and tidal volume varies
may prove helpful in preventing hyperventilation. Simple v.rith changes in patient resistance and compliance. The Vor-
reasoning, however, dictates that manual ventilation can- tran has proven unreliable when the ventilator's orientation
not replicate the tidal volume, frequency, FIOt, PEEP, and is changed, failing to cycle. 49•50 Both devices are inexpensive
mode of ventilation with the consistency and precision of a (Vortran $45 and Oxylator $600). In the presence of a leak, ii
ventilator. Maintaining constant PEEP with a manual resus- the set peak pressure cannot be reached, both devices will
citator is difficult and can lead to hypoxemia.1.2,30 Finally, remain stuck in inspiration. Successful use of the Vortran in
manual resuscitators were not meant to allow spontaneous intubated, closely monitored subjects has been reported.51
breathing, causing excessive work of breathing. 47•48 The Ambu Matic is a pneumatically power-ed automatic
Comparisons of manual ventilation wit11 a transport ven- resuscitator delivering controlled mandatory ventilation
tilator uniformly support the use of a ventilator to pre- (Fig. 28-2). ltconsistsof a patient valve and a control module
serve normal gas exchange. 8·28·3·1 A mechanical ventilator with a single-slide control for frequency and tidal volume
also allows monitoring and alarms. Recently introduced settings and a control for manually triggering a breath. An
portable ventilators provide volum.e- and pressure-control FIOt of0.6 (prolonging the duration of oxygen supply) or 1.0
ventilation along with flow triggering and pressure-support is available. There is a fixed pressure-limiting valve, set at
ventilation.32 A portable ventilator also can provide a con- 60 cmH20. Performance in the laboratory suggests that this
stant Fro 1 and maintain PEEP. device can provide set tidal volumes up to a peak pressure
Portable ventilators are more expensive than manual re- of 50 CinH20.52 A comparison of the physical and opera-
suscitators, and many require a high-pressure (50 psig) gas tional characteristics of automatice resuscitators is given in
supply. While manual ventilation of the postoperative pa- Tables 28-5 and 28-6.
CHAPTER28 TRANSPORT OF THE VENTILATOR-SUPPORTED PATIENT 615
FIGURE 28-2 The AmbuMatic automatic resuscitator.
FIGURE 28-1 Examples of automatic resuscitators, the Vortran

(left) and the Oxylator (riglrt). More complex than automatic resuscitators, these devices
offer a range of breath rate and tidal volume adjustment and
also can be used with spontaneously brea thing patients. A
SIMPLE TRANSPORT VENTILATOR comparison of the physical and operational characteristics
TI1e simplest transport ventilator is a device that supplies of automatic resuscitators is given in Tables 28-7 and 8.
mechanical ventilation at a specified rate and volume and
includes a pressure-relief valve with an audible m echani- EXAMPLES OF SfMPLE TRANSPORT VENTILATORS
cal alarm. Most simple transport ventilators are powered TI1e Auto Vent 2000 (Fig. 28-3) a11d 3000 are pneumatically
and controlled pneumatically. In some instances, a battery powered transport ventilators operating in the intermittent
allows for simple low- and high-pressure ala rms, as well as mandatory ventilation (IMV) mode. Mandatory breaths are
monitoring and display of airway pressure. time-triggered, flow- or pressure-limited, and time-cycled
at an Fro, of 1.0. A demand valve at the airway opens
INTENDED USE at - 2 cmH2 0. Spontaneous breaths are pressure-triggered,
These devices also are used primarily in prehospital settings pressure-limited, and pressure-cycled. During spontaneous
by personnel with some training in mechanical ventilation. breaths, the patient brea thes from the d em and valve at
TABLE 28-5 Physical Characteristics of Automatic Resuscitators
Dimensions Supply Operating Temperature Minimum Patient

(em) Weight (kg) Pressure (psig) (°C) Cas Consumption Weight (kg)
Ambu Matic 16 X 9 X 4 '1.2 39-94 - 18-50 0.8 liters/ cycle 15

VAR Model RT 16.8 X 8.4 X 6.4 0.074 50 - 18-50 (storage -40-60) NS 40
VAR Model RC 6.6 x 3.3x 2.5 0.074 50 - 18-50 (storage -40-60) NS 40
Oxylator EM-100 5.7 X 10.8 0.5 45-80 - 30-60 (storage -40-70) NS 10
Oxylator FR-300 4.8 x 10.0 (round) 0.18 45-80 - 30-60 (storage -40-70) NS 10
paraPAC Responder 4 X 6 X 18 1.9 (Patient 37-87 - 10-65 Max of 2 liters/min in 2.3
valve 0.08) excess of minute
volume
NS, not specified.

616 PART VIII VENTILATOR SUPPORT IN SPEOFIC SETIINGS
TABLE 28-6 Operationa l C haracteristics of Automatic Res uscitators
Cycling Rate 1idal Inspiratory Peak Row

Variables Modes (breaths/min) Volume (ml) 1ime (s) (liters/min)
Ambu Matic Pressure CMV 4 o r 20 20Q-1200 NS 40

VAR Model RT Pressure CMV,AMV Varies with 17Q-2000 0.5-3 40
impedance
VARModel RC Pressure CMV,AMV Varies with 17Q-2000 0.5-3 40
impedance
Oxylator EM-100 Pressure (2Q-50 CMV Varies with Depends on l:E 1:1 or 1:2 40
cmH20) impedance respiratory system
compliance
Oxylator FR 300 Pressure CMV Varies with Depends on 1:1.5 30
(20cmH20) impedance respiratory system
compliance
paraPAC Responder Trme CMV 11- 21 34Q-1450 0.5-2.2 40
PEEP/CPAP Demand-Row Manual

F1,12 (onH20l Alarms Monitoring Valve Breath
AmbuMatic 0.6 o r 1.0 Extemal Audible high Accessory module No (does allow Yes
PEEP/C PAP pressure available entrainment of
valve Accessory module ambient air)
available
VARModel RT 1 '1/ 10 of PIP, 2-5 Audible high Optional airway Yes No
cml-hO pressure pressure
manometer
VARModel RC 0.5 o r 1.0 1/ 10 of PIP, 2-5 Audible high Optional airway Yes No
cmH20 press ure pressure
manometer
Oxylator EM-100 1 2-4 Audible high None No (does allow Yes
pressure entrainment of
ambient air)
Oxylator FR 300 1 2-4 Audible high None o (does aUow Yes
press ure entrainment of
ambient air)
paraPAC Responder 1 No Audible high None No No
press ure
ABBREVIATIONS: CMV, continuous mandatory ventilation; AMY, assisted mandatory ''enWation; NS, not specified.
48liters/ min. If patient demand exceeds 481iters /min, am- 3000 is designed for adults and children and has three con-
bient air is drawn into the valve, diluting the Fro2 • A me- trols: breath rate, tidal volume, and inspiratory time. Both
chanical visual indicator on the patient valve tums green consist of a control module, patient valve, and connecting
during the inspiratory phase. U the 50 cmH2 0 pressure re- hoses.
lief is violated, an audible alarm caused by gas escaping can The AutoVent ventilators consume approximately 0.5
be heard. There is no monitoring. liter I min of gas to operate the logic. The higher the fre-
The AutoVent 2000 is designed for adults with a con- quency setting, the higher is the gas consumption. The in-
trol for breath rate an d one for tidal volume. The AutoVent spiratory flow is fixed at 48liters/min. If patient inspiratory
TABLE 28-7 Physical Characteris tics of S imple Trans port Ventilato rs
Dimensions Weight Supply Operating Gas Consumption Minimum Patient

(em) (kg) Pressure (psig) Temperature (°C) (Liters I min) Weight (kg)
Auto Vent 2000 15 X 9 X 4.5 0.68 4Q-90 36"C 0.5 liter/ min depending on Child
breath rate
Auto Vent 3000 15 X 9 X 4.5 0.68 4Q-90 - 34-36°C 0.5 liter/ min depending on Child
brea th rate
para PAC Medic 9.2 X 22.0 X 16.2 2.8 39- 87 - 10-65"C Delivered volume plus 10 4.5
ml/cycle
Uni-Ve11 t 706 20 X 13 X 5.5 1.45 SG-100 - 60-65°C 0 lluant
CHAPTER28 TRANSPORTOFTHE VENTILATOR-SUPPORTED PATIENT 617
TABLE 28-8 Operational Characteristics of Simple Transport Ventilators
Cycling Rate lid a! Inspiratory Peak Flow

Variables Modes (breaths/ min) Volume (ml) lime (s) (liters/ min)
AuttoVent 2000 lime CMV,lMV 8, 9, 10, 12, 14, 16, 400, 600, 800, 1000, 1200 1.5 48
20
AutoVent 3000 lime CMV, JMV Child 9, 11' 14, 17, Child 200, 300, 400, 500, Child 0.75 48
20,23, 27 600 AduJt1.5
Adul t 8, 9, 10, 12, Adult 400, 600, 800, 1000,
14, 16,20 1200
Para PAC Medic lime Synchronized 8-40 70- 1300 0.6 to 1.6 60
minimum
manda tory
ventilation
Uni-Ve.nt 706 Time CMV Child/ infant 14, 10-1250 Child 0.75 to 2.7; 90
20,30 Adult 1.5 to 3.5
Adult 12, 18
PEEP/CPAP Demand-Flow Manual

Ft 02 (cmH20) Alam1s Monitoring Valve Breath
AutoVent 2000 1 No Audible high Green light indicating Yes No

pressure inspiratory phase
AutoVent 3000 1 No Audible high Green ligh t indicating Yes No
pressure inspiratory phase
ParaPAC Medic 0.5 or 1.0 Add on PEEP valve Audible high Airway pressure Yes No
to20anH20 airway pressure
Uni-Vent 706 1 No Audible high None No Yes
airway
pressure, low
battery"
ABBREVIATIONs: CMV, C<)ntinuous mandatory ventilation; LMV, intermittent mandatory ventilation.

"Battery duration 10 hours.
flow exceeds 48 Hters/min, the patient entrains ambient tory time, and inspiratory-expiratory (I:E) ratio combina-
air, increasing the imposed work of breathing. The limited tions corresponding to those predicted to be appropriate
number of rate-tidal volume combinations that can be set for adult and pediatric ventilation. Inspiratory flow is lim-
is a limitation. ited from 0-90 liters/min, and a high-pressure limit can be
The Uni-Vent 706 (Fig. 28-4) is a pneumatically powered, set (60 or 80 cmH2 0) at the patient valve, which activates an
electronically controlled ventilator delivering an FIQ, of 1.0. audible a larm when exceeded. Indicator lamps illuminate
Controls set inspiratory flow and a series of rate, inspira- signaHng inhalation and exhalation. There is a low-battery
alarm. Prehospital use of the Uni-Vent 706 by paramedks
duri11g cardiopulmonary resuscitation of intubated victims
FIGURE 28-3 The AutoVent 2000 simple transport ventilator. has proven successful.53
SOPHISTICATED TRANSPORT VENTILATOR

A sophisticated transport ventilator is capable of perfor-
mance comparable with that of an ICU ventilator. These
devices may have built-in compressors or turbines to gen-
erate positive pressure without compressed gas and contain
an air-oxygen blender.
INTENDED USE
Sophisticated transport ventilators are intended for inter·
or intrahospital transport of critically ill patients. These de-
vices should be capable of ventilating the sickest patients.
618 PARTVill VENTTLATORSUPPORTINSPEOFICSETTINGS
only in that the latter are pressure-triggered, and the fluidic

logic prevents pressurization of the exhalation valve.
The LTV 1000 is a flow-triggered, flow- or pressure-
limited, flow- or time-cycled microprocessor-controlled de-
vice that has an integral turbine (Fig. 28-6). Oxygen can be
I::\ 4 C • DC supplied from a low-flow or compressed-gas source. The
\:.f4D4PTlA
ventilator provides SI.NfV, controlled mechanical ventila-
l[lt1
tion (CMV), pressure-support, and CPAP modes. Pressure-
IZVOG and volume-controlled breaths ar e possible. Operator con-
trols include primarily a keypad and rotating knob. Controls
• UWAl4TION include ventilation m ode, F1~, rate, tidal volume, inspira-
• tNHAl A1'10H
noAA. vat.UME tory time, peak flow, PEEP, sensitivity, pressure support,
•
•
LOW 8.4TTIIIY
CICAAGl &
* ~USf * and peak pressure. Parameters monitored and displayed
OllF
~Oft CHEST AISl include airway pressure, total breath rate, exhaled tidal vol-
elDUL T CPA I V Jl1 ume, total minute volume, I:E ratio, calculated peak flow,
e. • ADi,ILT HYPf.lh,tNT
• CW\.tl/lM ANT Clll!
CHllO( INFAIIl Vt N1
Ct<l\.0/llffA'fT HYPEI'YfNl
MAHUAl
and pa tient effort. There are indicators for electrical power
status. A full set of alarms is available. An optional color dis-
play is available that displays meas ured values in a graphic
or numerical format. The LTV 1000 offers the performance
TIIIGG.II of a critical-care ventilator at a size and weight appropriate
for a transport ventilator.
The Uni-Vent 754 is an electrically powered flow or pres-
sure controller that is triggered by pressure o r time or man-
ually; it is also time- or pressure-cycled a nd has an inter-
Automatic Retytcltator nal compressor and oxygen-air blender (Fig. 28-7). Modes
of ventilation include CMV, SIMV, and CPAP. Calibrated
dials and pushbuttons select mode of ventilation, breath
rate, inspiratory time, tidal volume, sensitivity, PEEP, sigh,
FI~, and peak inspiratory-pressure limit. Airway pressure
is displayed, as well as the a irway pressure waveform, ven-
FI GURE 28-4 The Uni-Vent 706 simple transport ventilator. tila tor breath rate, inspira tory tin1e, I:E ratio, tidal volume,
Fr~, external air on/ off, set pia teau pressure, high- and low-
pressure alarm setting, mean airway pressure, and baseline
airway pressure. A full set of alarms is present.
EXAMPLES OF SOPHISTICATED The Uni-Vent 754 has a proven track record in transport-
TRANSPORT VENTILATORS ing ventilated military casualties by U.S. Air Force critical-
The IC-2A is a flow controller that can be triggered by pres- care air-transport teams. A comparison of the phys ical and
sure or time or manually; it is also pressure- or flow-limited operational characteristics of sophis ticated transport venti-
and time-cycled (Fig. 28-5). It requires a compressed-gas lators is given in Tables 28-9 and 28-10.
source for delivery to the patient, as well as for the fluidic
logic circuit. The IC-2A delivers an F1 0 2 of 1.0. Controls in-
dude the mode of ventilation, inspiratory and expiratory
time, inspiratory flow, sensitivity, and PEEP I continuous Attributes Common to All
positive airway pressure (CPAP) level. A single control on
the rear panel adjusts the mechanical pressure limit. Mode Transport Ventilators
is selected by toggle switches and inspiratory flow; inspira-
tory and expiratory times are adjusted with calibrated dials. WEIGHT
Controls for sensitivity, PEEP /CPAP, and pressure limit are These devices must be person-portable and able to be
uncalibrated. Airway pressure is displayed on an aneroid mounted on a variety of platforms. A maximum weight of
pressure gauge. Pressure-activated indicators alert the op- 8 kg facilitates these requirements.
erator to the type of brea th delivered (mandatory or spon-
taneous).
The IC-2A is used most often for ventilation in the MRI
D URABILITY
scanner because it has no ferrous components. The excessive
gas consumption should be considered when gas supplies These devices should be compact, simple to operate,
are limited. The system for delivering gas during sponta- durable, and unaffected by extremes of heat and cold or
neous breaths is not a demand valve. If the pa tient's inspi- vibration. Proper shielding is required to limit emission of
ratory effort exceeds the sensitivity setting, the IC-2A will unacceptable levels of electromagnetic energy. Automatic
deliver gas at the set inspiratory flow and inspiratory time resuscitators in particular should function properly after
on the ventilator. Mandatory and spontaneous breaths differ prolonged storage with minimal maintenance.
CHAPTER 28 TRANSPORT OF THE VENTILATOR-SUPPORTED PATIENT 619
FIGURE 28-5 The JC-2A ventilator used for

transport of p atients to magnetic resonance imaging
(MRI).
POWER REQUIREMENTS ture with oxygen from a low-pressure source such as a con-
Automatic resuscitators ar e pneumatically powered, nega t- centrator.
ing the need for batteries. Simple and sophisticated trans-
port ventila to rs often are powered electrically and pneumat-
ically. Battery life should be sufficient for the duration of the CONTROLS
expected transport. Battery life of ventilators with a built-in Controls should be large and not easily adjusted acciden-
air source is shortened by increased lung impedance, use of tally. Any display should be viewable from an angle and in
pressure-control ventilation, and increased PEEP.53 variable ambient light.
Transport ventilators use a variety of battery supplies.
Sealed lead-acid (SLA) batteries have a low energy den-
sity but are durable and inexpensive. SLA batteries hold a
SAFETY
charge even when stored for long periods of time. Nickel-
cadmium (NiCad) batteries have a higher energy density Automatic resuscitators and simple transport ventilators
but are more expensive. Nickel- metal hydride (NiMH) bat- have basic safety features, whereas sophisticated transport
teries have even a higher energy dens ity than NiCad batter- ventilators possess safety features comparable with those of
ies and are more expensive. Lithium-io n (Li-ion) ba tteries critical-care ventilators. A pressure-relief valve that vents
have the highest energy density and are the most expen- gas to the atmosphere at a preselected peak inspiratory
sive. NiCad and to a lesser extent NiMH batteries (but not pressure is essential. Violation of the high-pressure limit
SLA or Li-ion batteries) can suffer from voltage memory should be signaled by a visual or audible alarm. An antias-
and should be s tored in the d ischarged state. Both Li-ion phyxia valve that allows the patient to breathe from ambi-
and NiCad batteries will self-discharge during storage. ent air in the event of power-source failure is desirable.55
Oxygen consumption should be less than 5 liters/min, Battery-powered ventilators should be equipped w ith a
keeping in mind that oxygen consumption varies w ith ven- "low battery" alarm as the battery nears depletion. If the
tilation mode and the use of PEEP. The device should have compressed-gas source falls below operating pressure of
the capability of generating flow w ithout a compressed-gas the ventilator or is emptyI discmmected, an a udible or vi-
source and offer a means of enriching the inspired-gas mix- sual alarm should sow1d. Visual alarms are critical when
I •I
1~. ~-
() •
•
FIGURE 28-6 The LTV-1000 sophisticated transport ventilator.

FIGURE 28-7 The Impact 754 soph isticated transport ventilator.
ventilators are used in environments with high levels of work of breathing.59 In recent s tudies of new devices
ambient noise such as aircraft. there remains a wide range of capabilities among transport
ventilators. 60- 62 Transport ventilators with flow triggering
A SSEMBLY AND DISASSEMBLY
and PEEP compensation consistently offer the least imposed
work of breathing.
These devices should be designed so that incorrect circuit
installation is impossible. Typically, there is a single-limb
circuit with an external expiratory valve. Patient valves lo-
cated at the endotracheal tube should be cleared of secre- Ancillary Equipment for Transport
tions easily.
OXYGEN SUPPLY
All ventilators require a n oxygen supply source. Both
Performance Issues Relevant to All Types compressed-gas cylinders and liquid systems can fulfill this
need. lntrahospital transport usually is accomplished with
of Transport Ventilators an E cylinder or two E cylinders yoked together. These pro-
vide 630 and 1260 liters of gas, respectively. An H cylinder
DELIVERED T IDAL VOLUME contains 6900 liters and may be required for longer trans-
Several investigators have demonstrated unreliable tidal ports. The H cylinder is 152 em in height, weighs 68 kg, and
volume delivery with transport ventilators, encouraging requires its own attendant.
monitoring with a portable spirometer.21•56- 58 This includes Liquid-oxygen systems can provide 860 ft3 of gaseous
low tidal volumes in the face of low lung compliance and oxygen for every liquid cubic foot. Most liquid systems,
excessive tidal volume under normal loads. however, cannot operate at 50 psig.
IMPOSED WORK OF BREATHING H UMIDlFICATION

Transport and home-care ventilators often used for trans- A passive humidification device, or "artificial nose," is ideal
port have been shown to have an unacceptable imposed for transport. Use of an artificial nose may result in a
TABLE23-9 Physical Characteristics of Sophis ticated Transport Ventilators
Battery Duration Using Minimum Patient

Dimensions Weight S upply Operating Cas Consumption Nominnl Ventilator Weight
(em) (kg) Pressure (psig) Temp<!rature (' C) (liters/ min) Settings (h) (kgl
Avian 25.4 X 3().5 X 12.7 5 40-60 - 20-40 3.8-6.6 , NS

Crossvcnt 4 22.5 X 16.25 X 10.6 3.6 44-66 - 10-!;Q NS 15 Infa nt to adult
IC-2A 8.6 X 15.5 X 26 4.1 45-55 NS 12 No battery Pediatric to adult
JVentmt 35 X 24 X 29 11 40-60 (also us..'S low· 18-50 0 1- 2 10
0'\ pressure 02 source)
....,
N
lnternal compressor
LTV1000 7.62 X 25.4 X 30.48 5.72 40-70 (also uses l<.n.v· s-40 0 1.6 10
pressure 0 2 source)
Intern:~ I con, pressor
MVP-10 20x 23x7.4 2.3 45-55 NS 3, changes with No battery NconataJ to pediatric
breath per o\inutc
Oxylog2000 21.5 X 12 X 20.5 4.3 4!Hl7 - 18-50 0 4 7.5
pMaPAC 9.2 X 22.0 X 16.2 2.8 40- 90 - 10-65 Delivered volurne No battery 4.5
Transport plus 10 ml/ cycle
Uni-Vent750 23.9 X 11 .5 X 4.5 4.4 5()..90 - 60-60 0 12 NS
Uni-Vent 754 23 X 29 X 11 5.8 50 lntemal compr('Ssor - 60-60 0 3 (Compressor o n) Infant to adults
12 (Compressor off)
NS, not spedfi~d.

TABLE28-10 Operational Char acteristics of Sophisticated Transport Ventilators
Cycling Rate Tidal Volume Inspiratory Peak Flow

Variables Modes (breaths/min) (ml) Time (s) (liters/min)
Avian Time CMV, AMV, SlMV, (PAP 0--150 50--2000 0.1--3 100
Crossvent 4 Time, pressure CMY, SIMV/ CPAP, PSV, ~150CMV 5-2500 0.1 - 3 120
PCV 0.6-30 SIMV
TC-2A Time, pressure S!NIV, CMV / CPAP 1-666 130--2500 0.4-2 75
rventzol Time, pressure, flow YCY, PCY, AMV, STMY, 1- 50 100- 2000 0.3--3 180
CPAP, PSY
LTV 1000 TIme, pressure, flow VCY, PCY, AMV, CMV, o-so 50--2000 0.3-9.9 140
SIMV, CPAP, NPPV
MVP-10 (pedi- Time IMV,CMV 0--120 0--666 0.2- 2 25
atTic/neonatal)
Oxylog 2000 Time, p ressure CMV, SJMV, CPAP 5-40 100-1500 0.5-2 60
paraPacTransport Time Synchronized minimum 7- 60 50--3000 0.5--3 > 120
mandatory ventilation
Uni-Vent 750 Time, pressure CMV, SIMV, AMY 1- 150 10--3000 0.1 -3 100
Uni-Vent 754 Tune CMY, AMV, SIMV, CPAP 1- 150 70--1300 0.1--3 60
Operational Characteristics of Sophisticated Transport Ventilators (Continued)
PEEP/CPAP Demand-Flow
F1 02 (cmH 2 0) Valve Manual Breath
Avian 1.0 0--20 Yes Yes

Crossvent 4" 1.0 (0.5 optional) 0--35 Yes Yes
.IC-2A 1 Yes Yes Yes
1Vent201 0.21 to 1.0 0--20 Yes Yes
LTV 1000b 0.21 to 1.0 0--20 Yes Yes
MVP-10 (Pedi- 0.21 to 1 0--25 No (continuous flow) No
atTic / neonatal)
Oxylog 2000 0.6 and 1.0 0--15 Yes Yes
paraPacTransport 0.5 or 1.0 Add on, 0--20 Yes No
Uni-Yent 750 1 Add on Yes Yes
Uni-Vent 754 0.21 to 1.0 0 to20 Yes Yes
ABBREVIATIONs: VCV, volume controlled ventilation; PCV, Pressure controlled ventilation; AMV, as.~isted mandatory ventilation; CMV, controlled mandatory
ventilation; SIMV, sy nchronized intermittent mandatory ventilation; CPAP, continuous positive ain,•ay pressure; NPPV, noninvasive positive pressure ventilation.
•cv 3, Pediatric and adult; CV 2, NL>Onate, pediatric
bLTV 900, CMY, AMV, SlMV, CPAP (VCV, PCV, PSV); no~ blender, low flow 0 2 only; LTV 950 CMV, AMV, S!MV, CPAP {VCV, PSV) no 02 blender, low flow 02
only
progressive increase in breathing circuit resistance, and the prevention and treatment. The nuances of individual venti-
patient should be monitored for signs of expiratory-flow lators from battery life and oxygen consumption to imposed
restriction. Dead space should be accounted for during low- work of breathing must be appreciated.
volume ventilation. Premoistening an artificial nose is in-
advisable, does not improve efficiency, and only serves to
further increase flow resistance. References
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ill adults during intrahospital trans port. Prog Cardiovasc Nurs manual ventilation. Respir Care 2005; 50:340-4.
1994; 9:4-12. 47. Hess D, Hirsch C, Marquis-D'Amico C, Kacmarek RM. Im·
25. Freeman LJ, Nixon PGF. Are coronary ar tery spasm and progres- posed work and oxygen delivery during spontaneous breathing
sive damage to the heart associa ted with the hyperventilation with adult disposable manual ventilators. A nesthesiology 1994;
syndrome? Br Med J 1985; 291:851- 5. 81:1256-63.
26. H isano K, Matsuguchi T, Ootsbo H, et a!. Hyperventilation- 48. Mills PJ, Baptiste J, Preston J, Barnas GM. Manual resusci tators
induced variant angina with ventricular tachycardia. Am Heart and spontaneous ventilation: An evaluation. Crit Care Med 1991;
1 1984; 108:423-9. 19:1425-31.
27. Samuelson RG, Nagy G. Effects of respiratory alkalosis and aci- 49. Mellor S, Holland D, Boynton j. Effects of positioning on there-
dosis on myocardial excitation. Acta Physiol Scand 1976; 97:158- liability and clfectiveness of the Vortran A utomatic Resuscita tor
65. (abstract). Respir Care 2001; 45:A1021.
28. Gervais HW, Eberle B, Konietzke D, et al. Comparison of blood 50. Blackson T, Speakman B, Iverson ), et al. Effect of positional
gases of ventilated patients during transport. Crit Care Med 1987; changes on the performance of the Vortran Automatic Resus-
15:761- 5. citator (abstract). Respir Ca re 2004; 49:A1231.
51. Romano M, Raabe OG, Walby W, et al. The stability of arterial preset minute ventilation of portable emergency. Crit Care Med
blood gases during transport of patients during the RespirTech 1989; 29:1637-40.
PRO. Am J Emerg Med 2000; 18:273- 7. 58. Attebo L, &ngtsson M, Johnson A. Comparison of portable emer-
52. Nolan JP, Baskett PJF. Gas powered and portable ventilators: An gency ventila tors using a lung model. Br J Anaesth. 1993; 70:
evaluation of six models. Prehosp Disaster Med 1992; 7:25- 34. 372-7.
53. Johannigman JA, Branson RD, Johnson OJ, eta!. Out-of-hospital 59. Branson RD, Davis K. Work of breathing imposed by five venti·
ventilation: Bag valve devices vs transport ventilators. Acad laton; used for long term support: The effects of PEEP and patient
Emerg Med 1995; 2:719- 24. demand. Respir Care 1995; 40:1270-8.
54. Campbell RS, Austin PA, Matacia GM, ct al. Battery life of eight 60. Austin PA, Campbell RS, Johannigman JA, Branson RD. Work of
portable ventilators: Effect of control variable, PEEP, and F1o 2 • breathing during ventilator failure in portable and ICU ventila-
Respir Care 2002; 47:1173-83. tors. Respir Care 2002; 47:667- 74.
55. Austin PA, Campbell RS, johannigman JA, Branson RD. Work of 61. Nakamura T, Fujino Y, Uchiyama A, eta!. Intra hospital transport
breathing during ventilator failure in portable and ICU ventila- of critically ill patients using ventila tor with patient-triggering
tors. Respir Care 2002; 47:667- 74. function. Chest 2003; 123:159- 64.
56. McGough EK, Banner M), Melker Rj. Variations in tidal volume 62. Miyoshi E, Fujino Y, Mashimo T, Nishimura M. Performance
with portable transport ventila tors. Respir Care 1992; 37:233-9. of transport ventilator with patient-triggered ventilati()n. Chest
57. Heinrichs W, Mertzluft F, Dick W. Accuracy of delivered versus 2000; 118:1109-15.
Chapter 29 _ _ _ _ _ _ _ __ _ rapidly developing impairment of pulmonary oxygen (02 )
exchange accompanied by diffuse infiltrates and altered res-
MECHANICAL piratory system mechanics that cannot be attributed solely
to hydrostatic forces. Fueled by better characterization of
VENTILATION IN THE innate pathophysiology and of iatrogenic factors, consid-
erable progress has been made in recent years toward re-
ACUTE RESPIRATORY ducing the adverse consequences of this condition. Yet, af-
ter almost four decades, active debate continues regarding
DISTRESS SYNDROME key elements of the ventilatory prescription and appropri-
ate therapeutic targets.
JOHN J. MARINI From the outset, mechanical ventilation with positive
pressure has been essential in addressing the life-threaten-
ing gas-exchange abnormalities and otherwise unsustain-
able workloads associated with acute lung injury (ALI).
Only in the relatively recent past, however, has there been
clear documentation that the tidal pressures with which me-
GENERAL OBJECTIVES FOR VENTILATOR SUPPORT chanical ventilation is conducted can have an impact on
DEFINING THE PROBLEM morbidity and survival. 2' 3 This awareness gradually has
PATHOPHYSIOLOGIC FEATURES RELEVANT TO resulted in a conceptual shift away from attempting to
VENTILATOR SUPPORT maintain or restore normal blood-gas values at high pres-
sure and 0 2 costs and toward adopting the avoidance of
Mechanical Properties of the Injured Lung
preventable iatrogenicity ("lung protection") as the first
Atelectasis
Pulmonary Edema priority.
MECHANISMS AND CONSEQUENCES OF Many aspects of the debate concerning appropriate venti-
VENTILATOR-INDUCED LUNG INJURY lator management of this group of conditions can be traced
Pathophysiology and Prevention of VILI to the heterogeneity of the patient population, to our still
imperfect comprehension of the mechanisms of ventilator-
VENTILATING OBJECTIVES AND DECISIONS IN
associated lung injury, and to the relative imprecision of
ARDS
the criteria on which the ARDS/ ALI label is assigned. 4 De-
Therapeutic Targets
Implementing Ventilatory Support spite an incomplete and still evolving understa nding, a rich
Modes of Ventilation for ARDS experimental and clinical database-much of it collected
Adjuncts to Mechanical Ventilation over the past decade-allows for the development of a ra-
tional set of principles on which to formulate an effective
SETTING THE VENTILATOR: RECOMMENDATIONS
ventilation strategy.5 ,6 Definitive answers for many impor-
FOR PRACTICE
tant clinical questions related to this topic are not available;
Insights from Clinical Trials of Lung Protection
what is presented here reflects a pathophysiology-
General Guidelines for Ventilator Management
Suggested Sequence of Management Decisions guided approach to accomplish essential clinical objec-
tives while avoiding ventilator-induced lung injury (VILI)
FUTURE DIRECTIONS AND RESEARCH
(Table 29-1 ).
Pathogenesis and Detection of VILI
Long-tem1 Damage to Airways and Parenchyma
Relationship of VILI to Multisystem Organ
Dysfunction
General Objectives for
Ventilator-associated Pneumonia Ventilator Support
Environmental Modifications
Appropriate Levels of PEEP and Tidal Volume In the clinical setting, mechanical ventilation ensures
Recruitment Maneuvers adequate oxygenation of arterial blood, provides suffi-
Prone Positioning cient 0 2 transport to vital organs and tissues, assists in
Noninvasive Ventilation eliminating carbon dioxide (C02), relieves excessive bur-
Therapeutic Value of Hypercapnia and Tolerance of dens placed on the respiratory muscles, helps to main-
Hypoxemia tain alveolar stability, and facilitates therapeutic measures
High-frequency Ventilation where ventilatory control is required. It has become dear,
Value of Adjunctive and Pharmacologic Measures however, that despite its undeniable value, mechanical ven-
SUMMARY AND CONCLUSION tilation also has the potential to inflict adverse clinical out-
comes. The task of accomplishing ventilation safely in pa-
Few areas of critical-care medicine have been the subject of tients with injured lungs is made far more difficult by the
as much investigative attention or clinical concern as the med1anical heterogeneity of the respiratory system and the
set of problems grouped under the label acute respiratory diversity of pathophysiology encountered among different
distress S1jl1drome (ARDS). This syndrome, first formally de- patients who satisfy extisting operational criteria for this
scribed in 1967,1 continues to be recognized clinicaJJy as a condition.
625
626 PART VIII VENTILATOR SUPPORT IN SPECIFIC SETIINGS
TABLE 29-1 Conceptual Principles in ARDS Ventilation
ARDS is a heterogeneou s problem

Between patients
Over time
Between lung regions -5
Risk for VILI is proportional to trmlsalveolar pressure
Lung recruitment is essential to avoid VlLI
The chest wall influences regional lung volumes, tolerated
pressures, and recruitability
ABBREVIATION: VTLI, ventilator-induced lung injury-
Normal Stiff Chest Wall

Defining the Problem FIGURE 29-1 Influence of ches t-wall compliance on
transpulmonary pressure and lung volume. Any specified airway
1l1e terms ALI and ARDS, diagnoses based on physiologic pressure is associated with less transpulmonary pressure in the
and radiographic criteria, comprise a category of patients presence of chest wall stiffness or expiratory effort.
vvith varied pathoanatomy and mechanical characteristics.
According to the widely used American-European consen-
sus guideline,4 the primary criteria on which this diagnosis goal of minimizing tiss ue stresses, depending on the type
is based relate to pulmonary 0 2 exchange, the appearance and severity of lung injury, the compliance of the chest wall,
of the plain chest radiograph, and a clinical assessment of and the ranges for opening pressures and closing tenden-
left-ventricular function. Although such broadly inclusive cies among the multiplicity of the lung units that comprise
criteria may be useful for some purposes, they prove prob- the injured ltmg.
lematic for others. In formal definitions, for example, no
provision is made for the level of positive end-expiratory
pressure (PEEP) at which the arterial sample is obtained
or the chest radiograph is exposed. No stipulation requires Pathophysiologic Features Relevant
that the defining criteria be met under standardized condi- to Ventilator Support
tions a nd remain reproducible over time. Chest-wall prop-
erties and body weight are left unaccounted for. Yet pul- One of the major conceptual advances of the past 20 years
monary 02 exchange is influenced not only by the properties is the recognition that the lungs of patients with ARDS
of the lung but also by end-expiratory lung volume, body are mechanically heterogeneous and vary enormously in
position, mixed venous 0 2 content, pulmonary blood flow, their patterns of infiltration, their inflation and collapse
and the integrity and intensity of hypoxic pulmonary con- properties, and their regional expressions of pathology. CT
striction. The chest radiograph is interpreted subjectively, scanning has revealed densities that may be localized or
and experts often differ with respect to their assessments. 7 diffuse-with implications for response to ventilator inter-
Moreover, it is clear that the lungs of.different patients with ventions such as PEEP.11 Variation in the underlying con-
ARDS vary with regard to radiographic appearance, inher- ditions that give rise to the clinical problem described as
ent recruitability, and histopathology. Even within the same ARDS precludes categorical histologic descriptions that ap-
individual, assessed at the same moment, the pathoanatomy ply across the full range of clinical experience. A few salient
and mechanical environment vary from site to site within characteristics, however, are shared by m ost. In its earli-
the injured lung. Such regional differences ar e explained est phase, noncardiogenic (high-permeability) edema gives
in part by the properties of the surrotmding chest wall, rise to a lung w hose parenchymal airspace is partially oc-
which profoundly influence the inflation characteristics of cupied by proteinaceous edema a nd cellular infiltra te. A
the integrated respiratory system as well as their regio nal relatively la rge proportion of the lung-often exceeding
distribu tion. 8' 9 50%- is airless at end expiration, with the exact percent-
Similar clinical presentations can mas k radical differences age depending jointly on severity, disease stage, and eti-
in lung pathology, mechanical properties, and response to ology. Destruction of surfactant-producing type 2 a lveolar
ventila tor settings and maneuvers. Lungs of patients w ith cells leads to its diminished production, whereas exuded
ARDS resulting from pneumonic consolidatio n, for exam- proteins and inflammatory products compromise the via-
ple, are less likely to inflate easily than are lungs made bility of the surfactant tha t remains.13 Surfactant plays sev-
edematous by the circulating mediators of extra pulmonary eral important biologic and physiologic roles. From a purely
°
sepsis. 1 Computed tomographic (CT) patterns may reflect mechanical standpoint, the loss of functional surfactant in-
these differences.11 Moreover, inflexibility of the chest wall creases surface tension, thereby contributing to alveolar
may increase dramatically the pressures required to inflate flooding, increased tissue elastance, small-airway closure,
the respiratory system12 (Fig. 29-1). From these considera- and atelectasis-particularly at low lung volumes.
tions, it is dear that inflexible guidelines for selecting PEEP The relative proportions of airless an d aerated tissue a lso
and tidal volume that advise specific numerical values of vary with disease type and stage. Although some contro-
these settings will be variably effective in accomplishing the versy persists, CT scan es timates of gas and tissue volumes
CHAPTER 29 MECHANICAL VENTILATION IN THE ACUTE RESPIRATORY DISTRESS SYNDROME 62 7
suggest that potentially "recruitable" tissue comprises only Opening
a minority of radiographic density at functional residual Pressure
capacity (FRC) in most patients.14 Flooded and consoli-

dated lung units comprise the remainder. Although clearly
Inflated
0 0
a minority viewpoint, a plausible a rgument has been ad- 10·20 cmH,O

vanced that "reopening" of lung units by alveolar pres-
sure may occur primarily by redistributing alveolar liquid ----~Alveolar Collapse
- (Rub..,rpllon} 20-60 cmH1 0
and shifting fluid volwne from the alveolar to the intersti-
tial compartments of the lung-not by atelectasis reversal
("recruitment").15 The rapidity with which CT scan tissue
density develops and resolves, however, as changes in alve-
olar pressure are imposed, as well as direct observations by
intravital microscopy of alveoli at the lung's surface,16 cast
doubt on the primacy of the "fluid-shift hypothesis." FIGURE 29-2 Spectrum of opening pressures associated with
lung units within the injured lung. Lung units located in
dependent areas are compressed by the weight of the overlyin g
MECHANICAL PROPERTIES OF TH E I NJURED LUNG lung and mediastinum. Local transpulmonary pressures vary
considerably; some lu ng units remain fully inflated throughout
Replacement of airspaces by inflammatory debris, cells, and the tidal cycle, whereas others cannot be aerated. Less pressure is
fluid results in a lung whose aeratable capacity and compli- req uired to open small airways when the alveoli remain aerated
ance (meas ured in terms of volume accepted per unit of than when all alveolar gas has been absorbed. (Image courtesy of
pressure) is severely reduced. The compliance of the res- Luciano Gattinoni.)
piratory system Oungs and chest wall) falls during ARDS
for two reasons: First, infiltrated and surfactant-depleted
cation of nonphysiologic stretching forces, as during high
tissue is inherently more elastic than healthy tissue.
tidal volume/high-pressure tidal ventilation, is currently
Second- and more important-many functionallw1g units
believed to initiate molecular signaling of a local inflam-
operate near their elastic limit because many fewer are avail-
matory response. 21•22 Mechanical interdependence among
able to accept the tidal volume. Under normal conditions,
the lung units of a heterogeneously affected lung amplifies
surfactant-modified surface forces allow the lung to inflate
the s tresses of high pressure a t the junctions of dosed and
and deflate at similar pressures. In contrast, the injured lung
is characterized by a right-shifted pressure-volume loop,
made so by its reduced aeratable capacity and by surfactant
depletion.12•17• 18 For the same tidal volwne, therefore, the FIGURE 29-3 Mechanical characteristics of lung units in
mecl1anical work of breathing is increased dramatically. dependent (below) and nondependent (above) lung regions. As
the lung is inflated by constant flow of gas, electrical impedance
Although clinicians characterize the mechanics of the
increases in proportion to aerated volume. Although the
injured lung by airway pressttre and flow measurements relationship between volume and impedance for the total lung
made at the airway opening-the common entry and exit appears roughly linear (ceuter tracing), upper lung regions are
points for gas exchange with the environment-the me- relatively overdistend ed (upper tracing), whereas lower lung
chanical properties of the lung's individual subunits are regions are relatively underrecruited until total lung capacity is
hardly uniform, even in health. In part, this heterogene- achieved (lower tracing). (Image courtesy of Marcelo Amato.)
ity relates to regional variations of pleural (and therefore
transpulmonary) pressure that arise from interactions of CONSTA NT
the chest wall with the injured lung and from the need FLOW
0.08
for dependent tissues to support the weight of the medi-
as tinal contents and the edematous lung (Fig. 29-2). This 0.06 Upper lung
underlying mecltanical heterogeneity is implied by quan-
titative CT imaging techniques that characterize tl1e topo- C/)
w
0.04
graphic anatomy in response to changing patterns of air-
way pressure or more directly in real time by imaging of ":z:z
~
0.02
ventilation witl1 radiotracer gases or electrical impedance 0 0.00

tomography.19•20 w
0
For any specified airway pressure, there exist lung units z~ ·0.02
that are closed and t110se that are open. Among tl1e popula- Q
w ·0.04
tion of open Wlits, there exists a range of s tates of lung-unit a.
:i:
expansion depending on the local transpulmonary pres- ·0.06
sures that distend them. Even at airway pressures that gen-
·0.08
erally are considered modest, some of the open lung units
verge on overdistension, whereas others are on the com- ·0. tO
pliant po rtion of their pressure-volume relationship (Fig.
29-3). While a lveolar distension that approaches the elastic 0 30 60 90
limit stimulates surfactant production, the repetitive appli- Time (seconds)
tension stretching at the interface re mains to be resolved .

It appears, therefo re, tha t there ar e at least two critical el-
em ents tha t place the injured lung a t risk for ventila tion-
associated lung da mage: high inflating pressures and the
prevalence of collapsed lung units that interface with open
ones.
ATELECfASIS
At the microscopic level, lung-unit collapse may be thought
of in two broad categories: "Loose" atelectasis arises pri-
marily from compressive forces of the heavy lung acting to
close small airways and responds to relatively low levels of
FIGURE 29-4 Amplification of tension at the boundaries of open transpulmonary pressure, conversely, adhesive or "sticky''
and collapsing lung tissue. Nonnally distended (left), collapsing atelectasis results from gas absorption and requires very
(center), and overdistended (right) states of inflation. Because of high pressures to reverse.25 High concentrations of inspired
interdependence, the tensions applied to a collapsing alveolus are Oz encourage the latter in poorly ventilated regions, as well
amplified. A simple mathematical model predicts that the as interfere w ith surfactant kinetics. These hard-to-recruit
tensions resulting from an alveolar pressure (Pappi) produce a
units may be among the first to close as high airway pressure
ten sion comparable with an effective pressure (Peff) described by
the equation. At 30 cmH 2 0 applied pressure, the volume of an
is w ithdrawn. Loose and sticky types of atelectasis often co-
aerated alveolus (V) is approximately 10 times that of a collapsed exist, perhaps accounting for the fact that lung units open
alveolus (V 0 ). Thus the estimated pressure n ecessary to m imic the throughout the entire range of total lung capacity (TLC)2 6,27
tens ions at the interface is approximatel y 4.5 times as great as that (Fig. 29-5). In the setting of severe ARDS, pressures that
applied (140 cmH2 0). (Used, witlr permission, f rom I· Mead et al exceed 60 cmH2 0 may be needed to complete the recruit-
lAP 1970 Am I Respir Crit Care M ed 163:1609-13, 2001.) ing process. Although opening of lung units is primarily a
function of tra nsalveola r pressure, the duration with w hich
open lung units in a nonlinear fashion23 (Fig. 29-4). Such pressure is applied also contributes; that is, a lower pressure
recurring forces not only strain the lung's structura l mesh- may be sufficient if applied for an adequate period. More-
work to signal inflammation but also assist in reopening over, atelectatic lung units tend to "yield" (open) in a stut-
potentially recruitable (a telecta tic) lung units. 24 When at- tering, discontinuous fashion, v.i th high sustained pressure
electatic tissues are subjected to high pressures, amplified causing a serial snapping open of small blocks of units.28
shearing forces within these zones at high risk for damage Discontinuous lung opening during the tidal cycle may give
may be of sufficient magnitude to tear the delicate termi- rise to audible crackles, usually best heard in dependent
na l airways or alveoli themselves, creating m icrowounds regions.
that produce tissue hem orrhage and incite inflammation as
a secondar y phenomenon. Stress amplification at the mar-
PULMONARY EDEMA
gins of dissimilar tissues is at least partially a function of
their relative volumes. (A flooded, gasless alveolus of vol- The increased microvascular permeability of AU / ARDS
ume similar to its air-filled neighbors may experience forces renders it vulnerable to edema formation and impedes its
that are no more intense.) Whether injury results from the relative ra te of edema clearance. The weight of the normal
process of repetitive popping open of lung units under lung does not begin to rise significantly until pulmonary ve-
high pressure or simply is the cumulative result of high- nous pressure exceeds 20 mmHg. Unlike the healthy lung,
FIG URE 29-5 Histograms relating percentage of

50
potentially recruitable lung units to inflation (opening)
and deflation (d osing) airway pressures. Unstable
40 airways open at relatively modest pressures, whereas
Opening
........ • pressure
alveoli that have undergone absorption collapse
require much hi gher pressures to open. The spectrum
30
. . Closing
of closing pressures is shifted to the left. Note that
. some lung units b egin to collapse at relatively high
20 .. pressure airway pressures (Adapted, witlr permission, from Crotti
et al: Am I Respir Crit Care Med 164:131-40, 2001.)
Dep/ Stick y
. 5 patietlts,
10
0
0
ND/Loose ~
5
f i !
10 15 20 25 30 35 40 45 50
ALI/ARDS
Airway Pressure [cmH 2 0]

CHAPTER 29 MECHANICAL VENTILATION IN THE ACUTE RESPIRATORY DISTRESS SYNDROME 629
however, extravascular water in the injured lung bears a
strong quasi-linear dependence on hydrostatic microvascu-
lar pressure, a relationship that begins from capillary pres-
sures tha t are considered low by most clinical standards. 29
The term n.oncardiogenic pulmonary edema, therefore, does
not imply that gas excha nge cannot be improved by low-
ering the hydrostatic pressure gradient across the injured
lw1g. Because extra-alveolar microvessels as well as cap-
illaries can leak,30 numerous factors influence the vascu-
lar pressures relevant to edema formation. These include
left-ventricular filling pressure, cardiac output (which in-
creases the pressure needed to drive blood flow through
the lung with limited capillary recruiting reserve), plasma
oncotic pressure, interstitial flu id pressure, and the integrity
of the a lveolar and lymphatic lung-water clearance mecha-
nisms. Clearance mechanisms are influenced by the degree I I I
54700·38 2.0kV 10.6mm x 10.0k SE(M) 12/18100 s.ooum
of lung stretcl1. Translocation of blood from infradiaphrag-
matic vascular capacitance beds to the central vessels of the FIGURE 29·7 Stress fracture of the alveolar-capillary membrane
thorax can occur as intra-abdominal pressure rises. 31 res ulting from ventilator-induced lung injury in a previously
normal ra t lung. Similar tears also have been demonstrated to
occur in human patients with ARDS.
M echanisms and Consequences of ing or collapsed structures. Indeed, an overwhelming body

Ventilator-Induced Lung Injury of experimental work indicates the lung-protective effect
of sustained "recruitment" when high tidal inflation pres-
For more than three decades, experimental studies have sures are used. 32•35 Mechanosignaling at moderately high
shown that excessive mechanical stresses developed during airway pressures may induce the formation and release
mechanical ventilation can inflict injury on both normal and of inflammatory mediators, 21.22 initiateJrogrammed cell
acutely injured lungs and, once the lungs are injured, re- death (apoptosis), or produce necrosis. Excessive s train
tard their healing.32.33 Injury may res ult from overstretcll- may exceed cytoskeletal tolerances, causing physical tears
ing of tissues that are already open, from shear forces at the and stress fractures of endothelium, epitheliUlll, and inter-
jw1ctions of expandable and unyielding tissue, and from cellular matrix37·38 (Fig. 29-7). Experiments conducted in
repeated percussion of dosed terminal airways (Fig. 29-6). animals and in patients indicate that translocation of in-
Repeated application of transalveolar pressures exceeding flammatory mediators and bacteria into the bloodstream is
those corresponding to the inflation capacity of a healthy influenced by the ventilatory pattern.39A 0 - 42 Although brisk
lung may disrupt the alveolar epithelial barrier, especially controversy continues, such observations suggest possible
in the absence of s ufficient end-expiratory pressure to re- links between adverse patterns of ventilation and dysfwlc-
duce stress focusing by holding open mechanically unsta- tion in remote vital organs.
ble lung units. 32•34 From a theoretical standpoint, sustained
recruitment reduces the potential for damaging forces to
PATHOPHYSI O LO GY AN D PREVENTIO N OF VILI
concentrate at the boundaries of inflating lung and unyield-
From available data, VTLI appears to be a complex pro-
FIGURE 29-6 Fonns of tissue s tress that occur near the junctions cess initiated by the repetitive application of excessive
of open an d closed lung u nits. stress/ strain to the lung's fibroskeleton, microvasculature,
terminal airways, and delicate juxta-alveolar tissues. D efin-
ing the linkage between stress, strain, and diffuse alveolar
damage is currently a subject of intense investigation.36,43A4
On the strength of excellent laboratory evidence, however, it
seems undeniable that high levels of mechanical stress may
Expanding disrupt the normal functioning of cells that populate the
Airway Trau ma pulmonary microenvironment and that sufficient dimen-
Alveolus
sional strain triggers the release of inflammatory media-
tors and destructive enzymes43- 45 (Fig. 29-8). Under mod-
Collapsed erate degrees of strain, such mechanosignaling may be the
"Stretch" primary pathway to injury. When the applied mechanical
Alveolus
stress is very high, fibroelastic structural integrity may be
breached directly, with the inflammatory process a conse-
quence rather than initiator of the observed histopathology
(Fig. 29-9). These high tissue-rupturing forces are especially
"Shear" likely to be generated in dependent lung regions, where
630 PART Vill VENTILATOR SUPPORT IN SPECIFIC SEITINGS
Cytoskeletal Structure
"
IKI<
I
1
\ , ... ~
\
MA? K SAPK
\ p 38 JNK
\
\ Inhibited by
\ Dexamethasone
\ NF·IC'B
\
GENE
ISRE ! DNA
Tranlriptlon
FIGURE 29·8 Mechanosignaling pathways of inflammation under cond itions of excessive tissue strain. (Used, with permissiou, [ro111 Dos
Sautos eta./: JAppl Pllysiol 89:1645-55, 2000.)
unstable alveoli are most prevalent (Fig. 29-10). Another im- From an engineering perspective, mechanical stress is a
portant mechanism in the causation of lung-tissue damage fun ction of transstructural tension; strah1 is the dimension-
may occur at the level of the terminal airways as they open altering consequence of high transstructural pressure, con-
and reclose with each tidal cycle.34 Damaging shear forces ditioned by the elastance of the element in question. Al·
(those that run tangential to the plane of the structure) ap- though by no means the only determinant of tissue forces,
pear to rip the epithelium from its attachments. the measurable analogue of the stress across the entire lung
FIGURE 29· 9 Excised h eart-lung block from a previously normal

animal subjected to high inflation p rcssun and low levels of
PEEP. Specimen is sh own inflated at 20 cmH 2 0 airway pressure FIGURE 29-10 Mech anical behavior of capillaries embedded in
in the s upine (left paue() and prone (rigl1t pa11ell conditions. Note the wall of inflatable alveoli and of microvessels within the
the sharp demarcation of hemorrhagic edema from relatively interstitial spaces. Capillaries embedded in the alveolar walls are
normal appearing lung. Damage may progress sequentially from compressed, whereas extra-alveolar microvessels (and perhaps
dependent to non dependent regions, as indicated by the comer vessels) arc dilated by lung expansion.
sequence of arrows.
low high
lung VOIUm1! lung volume
is transpulmonary pressure--<:rudely estimated as the dif- markedly in magnitude and even in direction between
ference between s tatic airway pressure (the "plateau" pres- structures situated within microns of one another. Shearing
sure) and the average pleural pressure (often estimated by forces, one of the varied forms of mechanical stress resulting
use of an esophageal balloon). Regional transpulmonary from lung inflation, intensify at the junctions of tissues w ith
pressures vary considerably secondary to the influence of different compliance values and anchoring attachments. 23
gravity, chest-wall irregularities, intra-abdominal r ressure, Minimizing or eliminating these irregularities reduces the
mediastinal weight, and vascular-filling pressure4 (see Fig. potential for adverse "stress focusing" and tissue strain. In
29-2). Available laboratory data illustrate that pleural pres- such a microenvironment, limiting end-tidal alveolar pres-
sure, however measured, does not accurately reflect inter- sure assumes major importance for two primary reasons:
stitial pressure when the ltmg is edematous and inflamed. 47 (1) A high plateau pressure may overstretch open alveoli,
Even directional changes of pleural and interstitial pres- and (2) perhaps more important, because junctional ten-
sures may not track together in a nonuniform environment. sion rises in nonlinear proportion to airway pressure}J the
Although not directly measurable, strain correlates with aer- plateau pressure acts as a potent lever arm at stress focus
ated volume as a fraction of aeratable capacity. points.
By reducing the number of junctional interfaces and by
HOW DOF..S TIDAL VOLUME RELATE preventing the repetitive opening of terminal lung units
TO TISSUE STRESS? at high press ure, recruitment of lung tissue-defined as
Once this latter concept is understood, it becomes clear the sustained reversal of atelectasis on whatever scale it
that tissue stress is not a predictable function of tidal vol- occurs- may be lung protective. When nearly all potentially
ume but rather is influenced strongly by tidal volume in recruitable tissue is aerated, the lung is said to be "open."51 A
relation to the size (and compliance) of the compartment given transpulmonarypressure applied to a fully open lung
forced to accept it. Even this, however, is not the full story- should be associated with less stress than the same pres-
stress amplification and shearing forces at the boundaries of sure applied to a lung with closed units juxtaposed to open
tissues with differing capacities to expand must be consid- ones. Some authors argue that the injured lung should be
ered. Peak tidal transalveolar pressure interacts with end- fully "opened" in order to reduce the potential for repetitive
expiratory transalveolar pressure to determine local stress, opening and reclosure. 51 Presently, however, it is not clear
which varies markedly from site to site across the damaged that this a lways should be given highest priority; to what
lung. The alveolar pressures resulting from tidal volume extent repetitive opening and closing of small airways pro-
and PEEP, therefore, are both interactive elements in the duces injury and whether the prevention of such behavior
injury process, but even when considered together, they is the key to lw1g protection remain debatable, especially
cannot estimate tissue s tresses precisely because interstitial when peak tidal pressures are res trained; modest ain.vay
pressure is an unmeasured variable that differs throughout. pressures may not inflict shearing injury when opening oc-
Moreover, the damaging strain that results from a given curs at low pressure. In addition, because the difference be-
stress depends on tissue fragility. In the setting of ARDS, tween opening and closing pressures is often quite narrow
tissue integrity is likely to be at least normally delicate or in units that do open at higher pressure, some degree of tidal
even compromised , especially in its earliest phase. The low recruitment may be unavoidable. Therefore, how much of
compliance typically associated with ALI results primarily the ltmg should be "opened" and what pressure cost is ac-
from the reduced number of aeratable lung muts-not from ceptable are key tmresolved questions.
increased stiffness of the individual lung lliUts themselves. 48
TI1e tidal volumes pulled during exercise by a healthy ath- PATHOGENETIC COFACTORS OF VILI
lete may exceed 25- 30 ml/kg of lean body weight, whereas Experimentally, a number of cofactors apart from end-
much smaller breaths eventually would cause damage or inspiratory and end-expiratory tidal transpulmonary pres-
lung rupture in the setting of ALI. In the same individual, in- sures are important ir1 the generation or prevention of VILI
creasing tidal volume invariably will cause tissue stresses to (Table 29-2). Prone positioning confers a protective advan-
rise in some lung w1its; a raised tidal volume, however, actu- tage in both normal and preinjured animals.52•53 TI1e po-
ally may cause the stresses in other units to fall . This appar- tential role of high inspired 0 2 as a contributor to iatro-
ent paradox results from the recruiting effect of the higher genic injury has been intimated for many years but never
pressures and perhaps improved ventilation of marginally
ventilated units predisposed to absorption collapse. At any
TABLE 29-2 Clinically Modifiable Cofactors Influen ce the
clinically selected tidal volume, tissue stresses may be re- Expression of VILI
duced or accentuated by the application of PEEP, d epend-
ing on whether PEEP effectively recruits vulnerable tissue Vascular pressure
or simply raises plateau pressure. Quests for a universally High inflow or low outflow pressures
applicable predetermined tidal volume or PEEP value ap- Ventilation frequency and/ or minute ventilation
plicable to all patients would seem destined to be a fruitless Hypercapnia may be protective
exercise. Position
Body temperature
Modifying the characteristics of the chest wall (e.g., by
Inspired oxygen percentage
prone positioning49•50 ) is a potent mechanism for alter- Pharmacological interventions
ing regional differences in transpulmonary pressure. Even
within the same small region, inflationary stresses can vary ABBREVIATION: VIti, ventilator-induced lung injury.
Extreme Stress/Strain Tidal Forces Moderate Stress/Strain

(Transpulmonary and
1\'licrovascular Pr ess ures)
•••
Rupture
D Epithelial &
Endothelial Cells
D
Meclumo signaling via
Accomodate Their Surfaces
integrins. cytoskeleton, ion channels
D
inflamma/0/y cascade
CeUular Infiltration and lnOammation

+ Global stress/strain reduced by lowering TrJnspulmonary pressure
• Local stress/strain reduced if Transpulmonary pressure is more homogeneously applied (prone position)
"- Local stress/strain reduced if PEEP ..keeps open"
FIGU RE 29-11 H ypothetical relationship between tissue damage and the severity of mechan ical stress/strain during the tidal cycle.
Moderate forces applied repeatedly to junctional tissues may result in m echanosignaling of inflammation. Extreme stress/strain causes
microwounds to develop, with inflammation occurring as an epiphenomenon. (Used, w it/1 pennissim1,jrom. Marini eta/: Crit Care Med
32:25Q-5, 2004.)
documented convincingly in the clinical setting.1•35 As other as injurious forces unzip structural elements of the lung's
examples, higher precapillary54 and lower postcapillary55 fibroskeleton .
vascular p ressures intensify the injury inflicted by a fixed What level of transpulmonary pressure is likely to be
ventilatory pa ttern. As the lung expands, alveolar and extra- damaging, therefore, depends on variables other than the
alveolar rnicrovessels are compressed and dilated, respec- tidal " plateau" pressure. Moreover, when the lung is com-
tively (Fig. 29-11). At some intermediate point on the lu- prised of large numbers of recruitable units, PEEP attenu-
minal pathway that links them, the pushes and pulls are ates the tendency for hiSh plateau pressures or tidal vol-
oppositely directed, giving r ise to forces that stress the mi- umes to cause injury. 60 - It is therefore difficult to specify
crovascular endothelium. Energy dissipation across the wa- an exact level of transpulmonary pressure that serves as an
terfall created by intermittent zone 2 conditions, vascular appropriate threshold criterion for safety. From a theoretical
interdependence, and opening and closing of the microvas- standpoint, a trnnspulmo11nry pressure of 20 cmH2 0 (corre-
cular endothelium potentially could explain the damaging sponding in a patient with a normal chest wall to a plateau
influence of reduced postalveolar vascular pressure. For pressure that may be in the range of 25-35 cmH2 0) gives
identical tidal inflation and end-expiratory pressures, re- cause for concern because some higher-compliance regions
ducing respiratory frequency attenuates or delays damage, of the injured lung may approach their elastic limits at this
provided that the tidal ventilatory stresses are sufficiently pressure. It is worth noting that a trnnspulmonnn; pressure of
high.56 This observation seems logical, in that some large only 15 cmH20 subjects the norma/lung to about two-thirds
tidal breaths and sighs occur infrequently as part of an of its total capacity and is associated with a tidal volume ex-
inherent pattern of normal breathing. Sighs, for example, ceeding 2500 ml.n
are inherent to the natural breathing pattern and are not In addition to these pathogenetic cofactors, intriguing ex-
injurious. 57 Multiple high-tension tidal cycles are required perimental data suggest that lung tissues can be injured by
to signal inflammation.. Experimental evidence also demon- mechanical stretching forces more easily in the setting of
strates that effective repair of minor defects of the cell mem- other noxious influences. In other words, it takes a higher
brane may occur within seconds of reducing stress,SB,S9 and stretching force to cause injury in a previously healthy lung
reducing respiratory frequency may allow these repair pro- than in one that has been exposed previously or concur~
cesses sufficient time to run to completion. Alternatively, rently to another inflammatory stimulus, such as endotoxin,
less cwnulative damage to the lw1g may occur per unit time hyperoxia, or cytotoxic drug. 63•64 Such data have given rise
1.0 ACTIONS OF PEEP
0.9 Elevating the pressure baseline from which breaths are
0.8
taken or delivered raises mean and end-expiratory lung
*l 0.7
volumes. Doing so nearly always improves oxygenation
a: 0.6
·~ 0.5 to some extent -primarily a function of keeping the lung
t: 0.4 open. When the breaths are drawn spontaneously or with
~ 0.31/
0.2
0.1
pressure support, it is customary to call the end-expiratory
pressure contin11ous positive airway pressure (CPAP); during
breaths of predetermined leng th, the term is PEEP. Both are
0.0 'r-~-,-----.--..--.---..-~--.----.'
10 20 30 40 50 60 70 instrumental in the supportive care of patients with ARDS.
Plateau Pressure (cmH2 0)
FIGURE 29-12 Relationship between mortality rate and plateau Gas Exchange
pressure generated during the NIH-sponsored ARDS Network The potential clinical utility of PEEP in improving oxygena-
multicenter trial of high versus low tidal volumes. Note the tion was mentioned in the paper that first brought ARDS
quas i-linear relationship of mortality rate to plateau p ressure. to widespread clinical attention.1 Subsequent work demon-
(Used, witlr permission, from Brower et al: Am I Respir Crit Care strated its potential to increase ventilation dead space and
Mcd 166:1515-7, 2002.) impair cardiac output by several mechanisms, the most im-
portant of which are imped ed venous return and increased
right-ventricular afterload. 67 In patients in whom PEEP sta-
to the "two-hit hypothesis" for VJLI and underscore the po- bilizes lung units that are susceptible to collapse, the re-
tential vulnerability of the preinjured lung to imprudent sponse to increasin g PEEP is generally to improve pul-
ventilatory prescriptions. At the same time, such vulner- monary 0 2 exchange effidency. Many patients show limited
ability can be viewed as an opportunity to modulate the or negligible response, however, presumably because the re-
severity of VIU by altering nonventilatory as well as venti- cruitable population of lung tmits w1der baseline conditions
latory factors. is small. Infrequently, increasing PEEP actually can cause
A post hoc analysis of the ARDS Network tidal volume Pao, to fall presumably by redirecting pulmonary blood
trial (ARMA) indicates that observed mortality paralleled flow, by causing pulmonary arterial pressure to rise high
plateau pressur-e to very low values- cons iderably lower enough to shunt venous blood through a patent foramen
than 20 cmH 20 65 (Fig. 29-12). This correlation, which is dif- ovale, or by causing sufficient reduction in 0 2 delivery to
ficult to explain entirely by indices of disease severity, sug- force a n increase in systemic ~ extraction and desaturate
gests the possibility that for the injured lung there is no venous blood (see Chapter 37).
obvious safety threshold below which ventilator-associated The benefit of PEEP on oxygenation depends on improv-
lung damage does no t occur. Other data have shown a simi- ing FRC. When patients labor to breathe, as during hyper-
lar relationship but argue that plateau pressures of less than pnea, expiratory efforts made against PEEP may force lung
30 cmH20 have little impact on mortality once PEEP and volume to fall below its equilibrium value, effectively stor-
disease severity are accow1ted for.66 [Tidal volume must ing elastic energy to aid inspiration but interfering w ith
correlate with plateau pressure in any given individual; improvement in 02 exchange. Under these circumstances,
pres tudy tidal volume and plateau pressure data from the eliminating forceful expiratory muscle action (such as by
ARMA trial, however, showed remarkably poor correlation sedation) tends to improve 0 2 exchange efficiency.68
because compliance is the missing parameter (Fig. 29-13).]
Alteration of Tissue Stress
Because PEEP has the potential to maintain recruitment
of unstable lung units (thereby reducing "stress amplifica-
FIGURE 29-13 Scatter plot o.f tidal volume versus plateau
tion"), there has been intense interest in its role as a core ele-
pressure before randomization to the limbs of the (NIH-ARDS
ment of a 1W1g-protective ventilating stra tegy. When plateau
Network) ARMA trial. (Used, with permission, from Brower eta /:
AmJ Respir Crit Care Med .166:1515-7, 2002.) pressure is held constant, raising PEEP not only reduces
c:: the number of closed lung units but also shortens the lever
0
:;;:: 18 arm applied to the unstable lung units a t risk to open force-
<II
·~ 16 fully (Fig. 29-14). Yet, when tidal driving pressure is pre-
0
"0
c:: 14
... served, PEEP raises both mean and peak tidal pressures,
<II d istends lung units that are already open, redirects blood
a: flow, and alters cardiac loading conditions. Moreover, those
2? 10
-0
~ 10 ... ,.1
., II"" 1.)1•.. :· . - 1 .. • •
.. . .. . I .. .......
,t t.JI~: a J•tt .. • : I • ••
r· J" • I' . . , ..... .. .
• I
.•
lung units tha t continue to W1dergo repeated tidal recruit-
ment despite an increase of PEEP are subjected to any PEEP-
Cl>
E
:::>
8 0 •
. .
0 ~.· '······i •·
• • •
:
..
; • ; • • •
. . ... ·. . . .
•• • • • related elevation of end-inspira tory pressure, increasing the
0 tendency for damage to those specific units. Thus PEEP has
> 6
0 •• ' • • 0 • •
the clear potential for benefit or harm depending on the bal-
30
(ij
:2 4 ance among its multiple effects. Prone positioning tends to
1-
10 20 40 50 60 70 even the distribution of ventilation and reduce the grad i-
Plateau Pressure Before Randomization ent of transpulmonary pressure across the lung that exists
ft.••cr Units at· Rbk !.

• •
•• •••
PEEP .• •.••
........... •
Alveolar Pressure Alveolar Pressure
'
'
Alveolar Pressure
FIGU RE 29-14 Conceptual relationship between plateau pressure, PEEP, and tissue strain. In the gen eration of tissue strain, the driving
pressure for tidal volume (the difference be'tween plateau pressure and PEEP) acts as a force lever arm, whereas PEEP acts as the fulcrum.
(Upper-left) Levels of plateau pressure and PEEP produce strain within acceptable limits. (Bottom-center) Increasing plateau pressure
while keeping PEEP at a level insufficient to hold open uns table units lengthens the lever arm and produces excessive tissue strain.
(Upper-rigll t) When PEEP is increased, the same high plateau pressure that caused damage previously is b etter tolerated in that fewer lung
units are p laced at risk after recruitment, and the lever ann of driving pressure is shortened.
in the supine position.50•69 Airway and lymphatic drainage RECRUITING MANEUVERS

also te nd to improve (Fig. 29-15). This improved uniformity A major clinical challenge is to apply sufficient pressure to
facilitates the selection of a single combination of PEEP and keep the lung fully recruited vvithout either increasing the
tidal volume that achieves a protective strategy for the e11tire stress applied to tissue that remains dosed or overdistend-
organ. ing alveoli that remain patent. Certain steps can be taken to
minimize the number of unstable units by reversing those
FIGURE 29-15 CT slices o btained in supine and prone positions conditions tha t predispose to compressive and absorptive
in two patients without ARDS. In both patients, the heart and atelectasis (Table 29-3). PEEP cannot keep lung units open
mediastinal contents are supported by dependent lung tissue in that were not open at an earlier point in the respiratory cy-
the supine pos ition. In the prone position, the sternum bears the cle, and the recmiting process is not completed until pres-
compressive weight, allowing the lung to expand. Lymphatic sures are reached that considerably exceed the total capacity
d rainage also may be improved in the prone position in that the of the healthy lung (Fig. 29-16). Although most lung units
h eart resides below rather that above the midplane that divides
open at pressures less than 25 cmH20 , some refr actory units
the lung tissue into superior and inferior portions. (Modified,
w ith permission, from Albert et a/: Am J Respir Crit Care M ed
of the acutely injured lung may require much higher pres-
161:1660-5, 2000.) sures to establish patency. To reach the " yield" (operung)
pressures of refractory lung units requires the initial appli-
cation of pressures that would be hazardous during tidal
ventilation. 14•27•70 Once opened, the lung units tend to dose
at lower pressures, allo"ving ventilation with the same tidal
Supine . ··· Supine volume and PEEP to occur in the context of a more open
TABLE 29-3 How Is the In jured lung Best Recruited?
Prone position
Adequate PEEP
Adequ ate tidal volume (and/or sighs?)
Prone ·· Prone Recruiting maneuvers
Minimize edema (?)
Lowest acceptable Fi~ (?)
Spontaneous efforts (?)
"¢'
a.
100 Q
......=
0
100
,...· ..············
~
...t- 80 I:'S 80 .......

v
8. 60
~ 60 .·
a -o
..····
§
.....
40 ...= 40
I:'S
.·· ...... ..... Inflation %
e= •
4)
] Recruitment
~ 20 ... 20
·ev
0
20 30 40 50 60 ~ 0 5 10 15 20 25 30 35 40 45 50
Press ure [cm.H20) P'.tw [cmH 2 0]
FIGURE 29-16 (Left) CT slices obtained after oleic acid injury of the lung superimposed on the pressure-volume relationship of the
respiratory system. Consolidation and radiographic density are greatest in the dependent lung regions, and high pressures mus t be
applied even in this "highly recruitable" lung model to fully reverse the radiographi c evidence of colla pse. Percentages denote aerated
recruitable tissue. (Right) Recruitment and inflation p ercentages as functions of stati c airway preSS\ue. The pressure-recruitment curve
parallels th e p ressure-inflation curve when b oth are expressed as p ercentages of their maximum ranges. (Used, w ith permission, from
Pelosi eta/: Am J Respir Crit Ca re Med 164:122-30, 2001; and Crotti eta/: Am J Respir Crit Care Med 164:131-40, 2001.)
lu ng with fewer lung units at risk for opening and closure ceptions, this "stabilizing" value of PEEP is higher than the
(Fig. 29-17). initial one before recmitment.71 • 72 The effect of a recruiting
Because of viscoelastance and other time-dependent maneuver is extremely short lived if PEEP returns to its
force-distribu ting phenomena, the tendency of a previously original value.
collapsed airway to open (or "yield") is a jointly hyper- While most w1stable lung units can be kept open w ith
bolic function of transmural pressure a nd time. A number end-expiratory alveolar pressures (tota l PEEP) of approx-
of techniques known as recruiting maneuvers are designed imately 10 cmH 2 0 (assuming a normally compliant chest
to "open" the lung so that safe and effective combinations wall), some units close a t pressures considerably higher
of PEEP and tidal voltm1e can be used. Each recognizes than those that are safe to apply with each tidal breath 27
that recruitment depends not only on the magnitude of
transpulmonary pressure but also on the duration of its ap-
plication (Fig. 29-18). To consolidate benefit after a success-
fu l "recruiting maneuver," end-expiratory pressure must re- FIGURE 29-18 Time course of changes in functional residual
capacity (FRC) in respiratory failure following a step increase of
main high enough to hold open these newly recruited units
PEEP from 3-13 cmH20. Multi ple tidal cycles are required to
once safe tidal plateau pressures are resumed. With few ex- fully achieve the ultimate increase in an expiratory lung volume.
Although tidal volume would affect the time needed to
FIGURE 29-17 Effect on the tidal pressure-volume rel ati onship equilibrate, in this instance, approximately 40 seconds was
(sma ll loops) before and after a sustained-inflation (SI) recruiting required . (Usell, w itlr peml'ission, from Kat2 et al: Anesthesiology
maneuver during controlled mechanical ventilation (CMV). 54:9-16, 1981.)
Hypothetically, first opening the lung by increasing pressure to BREATH-BY-BREATH FRC CHANGE
high values (by means of a sustained-inflation recruiting AFTER INCREASE IN PEEP
maneuver) allows tidal ventilation to occur at similar or lowe.r
pressures with more lung units open at an expiration . 100
HlO
90
eo 75
70 Mean ± SEM
FRC
N. a
60 CHANGE
VOLUME
(% TLC) 50
50
40
30
20
oj~,~~~1~--3~--~s--~7--~9--~~1-1L.2-0--~-3~1.40
BREATH NUMBER
10 3cmH20 13cmH20
0
0 5 10 15 20
pressure (cmH20)
25 30 35
t - 40 SECONDS
t
63 6 PART Vill VENTILATOR SUPPORT IN SPECIFIC SETTINGS
TABLE 29-4 Determin ants of Recruitment Maneuver applied by pressur e-control ventilation. When sustained
Effectiveness pressure is applied without relief, mean and peak air-
way pressures are equivalent. This imposes extraordinary
ARDS category
Inherent potential for response backpressure to ven ous return and poses a high afterload to
ARDS stage the right ventricle for the period of its application. Both in
Responsiveness diminishes over time experimental models and the clinical setting, ARDS caused
Starting PEEP and tidal volume by pneumonia (a primary form of alveolar damage) appears
Was th e lw1g well recruited to start wi th? to be the condition with greatest risk for hypotension and
How much higher than the tidal plateau is the recruiting pressure? least responsiveness to the susta ined-inflation recruitment
How many more wlits can be opened? maneuver.77
Postrecruitment PEEP Susfllining high pressure is believed to be an important
Duration of response component of the recruiting process, whereas the length of
Aggressiveness and type of recruiting method
time required for its effect remains unsettled . Moreover, it is
Often limited by tolerance
possible that for the same maximum pressure, briefer appli-
cations more frequently m ay be as effective as fewer cycles
with a longer inspiratory time. M ean airway pressure can be
(see Fig. 29-5). It is a fallacy to consider all injured t is- reduced consid erably while mainta ining the same peak air-
sue as potential~ recruitable. Unlike most experimental way pressure value-the actual recruiting pressure-using
models of ALV ·73 only a small fraction of the lungs of a limited period of tidal ventilation with a constant driving
pneumonia-caused ("primary") ARDS, for example, can be pressure [e.g., 1-2 minutes of pressure control with a driv-
"opened ."74•75 ing pressure of 30 em H 20 and hig h PEEP (e.g., 25 cmH20) ].
Although a number of recruitment maneuvers have been Thus the pressure-control recruitment ma neuver may h old
d escribed, their efficacy depends on numerous factors (Ta- an ad vantage if pressures beyond those tolerated during
ble 29-4). Moreover, even when indicated, the best tech- the sustained high-pressure method are needed to complete
nique with which to perform a recruitment maneuver is lung opening.75•77
currently unknown and may well vary with specific cir-
cumstances, and repeated maneuvers m ay be required SPONTANEOUS VENTILATORY EFFORTS
for maximum benefit. The two most commonly used are Preservation of spontaneous breathing efforts durii1g
the sustained-inflation and the incremental-PEEPI fixed- assisted ventilation may help to improve ventila tion-
driving-pressure methods76 (Fig. 29-19). The latter is often perfusion matching by preferentially ventilating the peridi-
aphragmatic regions that receive disproportionate blood
flow?8•79 Whether this redistribution of ventilation aids sus-
tained recruitment and thus whetl'ter it reduces or augments
FIGURE 29-19 Three types of recruiting maneuvers that combine
the tendency for VILI currently remain unknown. The an-
high pressures with extended application time. Recruitment that
employs tidal ventilati on with pressure-control ventilation (PCV)
swer may well vary with the intensity of the breathing efforts
achieves the same peak pressure for the same cumulative time as and the vigor of expiratory muscle activity.
sustained inflation but at considerably lower mean airway
pressure. PCV also provides multiple recruiting cycles and
ventilates during the maneuver. (Usecl, witl1 pu missiou, from Lim Ventilating Objectives and Decision s
eta/: Crit Care M ed 32:2371- 7, 2004.)
inARDS
Sustained Inflation
The foregoing discussion suggests that a rationa l hmg-
protective ventilator strategy should include tl1e following
45 for 40 s elements: (1) avoidance of high tidal end-inspiratory alve-
olar pressures, (2) provision of adequate end-expiratory
pressure to avoid extensive end-expiratory tidal collapse,
Incremental PEEP (3) reduction of regional non uniformity of mechanical prop-
erties, and (4) to the extent possible, avoidance of cofactors
that abet the development of VILI, such as high inspired
concentrations of 0 2 and increased metabolic demands for
35 Pea k ventilation and cardiac output. Choice of the appropriate
therapeutic targets is fundamentally linked to lowering the
Pressure Controlled Ventilation risk for iatrogenic lung injury.
45/ 16 and I :2 THERAPEUTIC TARGETS

for 120 s There is little evolutionary precedent for surviving ARDS
that requires advanced levels of life support. Yet the limits
0 1 2 3 4 5 of tolerance to abnormalities of gas excha nge in this
Time (min) setting and the capacity for the pa tient to adapt to abnormal
CHAPTER 29 MECHANICAL VENTILATION IN THE ACUTE RESPIRATORY DISTRESS SYNDROME 63 7
blood gases have not been explored extensively and remain recruited to avoid hypoxemia, precluding intermittent re-
largely unknown. Tradeoffs must be made when interven- moval. For these reasons, airway intubation is virtually al-
ing to sustain life because the supports applied to main- ways required in severe cases of lung injury.
tain oxygenation and ventilation-inspired 0 2 and posi- Patterns of lung expansion differ for passive and actively
tive pressure-are both potentially injurious to the lung. 64' 80 assisted breathing. Preservation of muscular effort concep-
The discipline of intensive care evolved as an extension tually holds an advantage regarding the matching of venti-
of postoperative care. Therefore, it was natural to employ lation to perfusion-at least in the healthy lung. The same
ventilator parameters that serve well in that setting, where advantage also may hold for the acutely injured lw1g, pro-
the general aim is to hold arterial blood gases reasonably vided that breathing remains comfortable and tmlabored.
close to their preoperative values, and large tidal voltm1es Vigorous efforts, however, are undes irable for several rea-
are needed to forestall atelectasis and avert dyspnea. Three sons: increased ventilatory workload, 0 2 consumption, and
decades ago, awareness of 0 2 toxicity was well entrenched, C02 production; increased cardiac output and pulmonary
and the acutely injured lung was viewed on the basis of blood flow (which may accelerate edema formation and
plain frontal chest radiographs as mecl1anically uniform- possibly VILI); and expiratory muscle contraction that coun-
diffusely stiff and therefore tolerant of the high ventilating ters the effects of PEEP.91 Whether gentle or vigorous, it has
pressures needed to maintain normal blood gases. yet to be shown convincingly that patients who expend ef-
Over the ensuing decades these assumptions eventually fort in breathing benefit from doing so.
were challenged. Premature infants ventilated for infantile
respiratory distress syndrome (lRDS) dearly were vulnera-
MODES OF VENTILATION FOR ARDS
ble to the application of high ventilating pressure. In adults,
the h igh mortality rate of diseases with intrinsically high An extensive arra y of ventilator options is available for treat-
survivability, such as asthma, 81 the high incidence of radio- ing patients with ARDS. Each method is described in de-
graphically evident barotrauma,82 and newfound aware- tail elsewhere in this textbook. As a general statement, it is
ness of dynamic hyperinflation 83' 84 brought the wisdom of accurate to state that the cl1oice of ventilating mode is of
traditional practices and therapeutic targets into question. much less importance than how the selected mode is imple-
TI1e concept of reducing ventilatory requirements by allow- mented. When guided by the princi pies of attaining efficient
ing Paco2 to rise was first implemented successfully in the gas exchange, targeting appropriate therapeutic objectives,
care of patients with status asthmaticus. 85 Five years later, and protecting the lung against iatrogenic damage, many
the same strategy was reported to have been implemented different selections can be justified. What is presented here
successfully in patients with ARDS. 86 Subsequent research is a brief outline of some of the more important cl1aracteris-
has emphasized that acute hypercapnic acidosis occurring tics applicable to ALI.
in this setting is a complex phenomenon with diverse phys- For the past two decades, four modes have served to
iologic effects that include those with potential benefit (e.g., ventilate patients with ARDS at conventional frequencies:
inhibiting inflammation) as well as those with potentially (1) flow-controlled, time- or volume-cycled ventilation (vol-
undesirable consequences (e.g., stimulation o f ventilatory ume control), (2) pressure-targeted, time-cycled ventilation
drive and cerebral vasodilation) 87 (see Chapters 41, 44, 46, (pressure control), (3) pressure-targeted, flow-cycled ventila-
and 47). Although guidelines for selecting the most appro- tion (pressure support), and (4) combination modes in which
priate values for pH and Paco, are elusive and undoubt- a specified number of stereotyped time-limited machine cy-
edly should vary with the individual in question, it is clear cles (pressure- or volume-controlled) that are specified by
from accumulated experience that mild to moderate devia- the clinician and synchronized to be triggered by patient ef-
tions from the normal ranges of both parameters are gener- fort are delivered intermittently at evenly spaced intervals
ally well tolerated. At present, the dangers of VTLI are per- among additional breaths of variable size and depth taken
ceived to outweigh those attributable to either inspired 02 or by the patient [synchronized intennittent mechanical ventila-
hypercapnia. tion (SIMV)]. As described in detail elsewhere in this book,
flow and pressure cannot be controlled simultaneously be-
cause the energetics of ventilation require one or the other to
IMPLEMENTING VENTILATOR SUPPORT
become a dependent variable in order to satisfy the equation
Important principles gathered from laboratory experi- of motion for ventilating the respiratory system.92
ments, shared clinical experience, observational studies, Flow control ensures that the desired tidal volume will be
and randomized clinical trials have emerged regarding the delivered reliably but obligates t11e patient to that specified
application of ventilator support to lw1g-injured patients contour, independent of flow demand. Therefore, alveolar
(see Table 29-1). Noninvasive ventilation has been reported pressure, a fw1ction of delivered volume and compliance
to be successful in patients with mild to moderate sever- during passive ventilation, has the potential to ascend to
ity of injury,88 - 90 and when feasible to employ, benefit is dangerous levels. The flow profile delivered may be un-
likely to accrue from the need for less sedation and the lower changing ("square") or decelerating. Pressure control offers
incidence of infection associated with this approach.90 Al- the flexibility to satisfy flow demand and under passive con-
though the interface between ventilator and patient conditions ensures that alveolar pressure rises no higher than
tinues to improve, only limited pressure can be tolerated a known peak airway pressure. [During active breathing
for longer than brief periods, many patients cannot pro- (assisted cycles), the maximum transpulmonary pressure
tect the upper airway, and the lung must be kept well is not regulated by pressure control.] Flow is inherently
decelerating, which may improve distribution of ventila- NEWER MODES OF VENTILATION

tion mod era tely among heterogeneous Iung units com pared For patients capable of sustained ventilatory effort, it is an
with constant flow. The potentially adverse tradeoff with option to elevate the airway pressure baseline, allowing
using pressure control is that the delivered volume is a the patient to draw breaths from that higher volume level.
function of the impedance to breathing and any backpres- When airway pressure is maintained relatively constant
sure opposing inspiratory flow, so tidal volume may change throughout both phases of the breathing cycle, the condi-
abruptly with muscu lar activity, airway resis tance, lung and tion is termed CPAP.95 If the baseline shifts periodically,
chest-wall compliance, or auto-PEEP. with the patient able to draw breaths wumpeded through
In recent years, the imperative to maintain consistent ven- a valveless system at each level, ventila tor assistance is
tilation and nearly normal levels ofPaco2 has declined in rel- given to an extent governed by the difference between
ative importance. Awareness of the potential for high ven- pressure baselines and the frequency with which these
tilating pressures to inflict iatrogenic lung injury, coupled baseline shifts occur. This mode is known as biphasic ainvay
with a growing clinical experience that suggests the safety pressure (BiPAP).96 When a high CPAP baseline is released
of higher than normal Pace, values (permissive hypercap- only for a very brief period and then restored quickly to its
nia), has caused many clinicians to adopt pressure control as original level, BiPAP contracts into airway pressure-release
the default mode. In the absence of effort and provided that ventilation (APRV). 97,98 The putative advantage of each
both tidal volume and end-inspiratory pause pressure are of these modes for tl1e care of patients witl1 ARDS is that
monitored, the choice of pressure or volume control makes they encourage maintenance of an open lung with their
little practical difference to physiology or outcome. high-pressure baselines and ensure that the spontaneous
Inverse-ratio ventilation (IRV), a mode that extends in- breathing pattern is preserved. As with so many mode
spiratory time with the intent of raising mean airway pres- options, however, no definitive evidence exists to confirm
sure and capping applied airway pressure while maintain- their relative advantage over a well-adjusted traditional
ing adequate ventilation typically is applied with pressure approach (see Chapters 10 and 12).
control.93,9-' To prevent airway closure at end expiration,
however, rna y require generation of au to-PEEP that narrows High-frequency Ventilation
the inspiratory pressure difference and limits tidal volume Awareness of the tissue-damaging potential of applying
(Fig. 29-20). Although there may be rare exceptions, IRV ap- high end-inspiratory plateau pressures with insufficient
pears not to offer any notable advantage over conventional- end-expiratory pressure to keep unstable alveoli open ig-
ratio ventilation that is applied with adequate PEEP. tuted interest in using methods that apply very small tidal
During vigorous breathin~ as during the first days of se- volumes so rapidly that alveolar collapse has no time to
vere ARDS, it may be difficult to avoid patient-ventilator occur. Over the past three decades, various techniques for
dyssynchrony with either assist volume control or pressure providing high-frequency ventilation have been explored
control because both require preset inspiratory times. Pres- with entlmsiasm, tried tentatively in the clinical setting,
sure limitation and failure to deliver full tidal volumes then and then set aside reluctantly. 99 - 103 These have included
may occur. In these instances, high-level pressure-support positive-pressure ventilation with valved-circuit closure to
ventilation (PSV), a flow-cycled mode, offers response flex- separate the phases of the ventilatory cycle (as traditionally
ibility. When used alone or in combination with intermit- done) but applied at nonconventional frequencies an.d tidal
tent time-limited mandatory machine cycles (SIMV)_ PSV volumes. The technical demands of such high-frequency
may minimize the timing collisions that otherwise occur valving have limited its operating frequency range, effi-
between the cycling phases of patient and machine. In any ciency, and safety. Another form of high-frequency venti-
form of pressure-targeted or flow-regulated breathing, the lation, jet ventilation, uses a lung-directed injector of con-
ventilator's alarms should be set carefully so as to avoid ditioned gas pulsating at rapid frequencies into an open
overapplication of pressure or underventilation. circuit. Problems with gas trappin~ drying of airway se-
cretions, and limited efficacy have dampened enthusiasm
for its use in critically ill patients. At present, a third form,
FIGURE 29-20 Concept of inverse-ratio ventilation u sing !ugh-frequency oscillation, is in most widespread clinical
pressu.re-control ventilation. As airway pressure is applied and use for patients v.rith ARDS.101' 102 This "open-circuit'' tech-
released, alveolar pressure rises and falls exponentially (11eavy nique uses a rapidly reciprocating piston-like action to vi-
line). Extending the inspintory time fraction increases mean brate the air column at high amplitude, building and re-
airway pressure and leveJs of auto-PEEP without changing peak leasing small alveolar pressure excursions in the process. A
al veolar pressure. fresh-gas source allows effective gas exchange via mecha-
Paw tusrns that complement the bulk flow that accounts for ven-
' tilation at lower frequencies 103 (see Chapter 20). Although
the experimental and clinical data available amply docu-
ment the feasibility of high-frequency oscillation for the set-
' - ting of ALI in adu lts, 10"~ - 103 the prevailing opinion is that
- Auto-PEEP this unfamiliar and seemingly exotic tecl1nique seems to
1--PEEP
~0---------------------------L- offer little advantage over ventilation performed conven-
tionally with equivalent attention to the principles of lung
Time protection.
CH.APTER 29 MECHANICAL VENTILATION IN THE ACUTE RESPIRATORY DISTRESS SYNDROME 639
TABLE 29-5 T herapeuti c Adjuncts to Mechanical Ventilation ate tradeoff, however, remains a topic of active debate. The
ofARDS available clinical database, albeit difficult to reconcile, ap-
pears broadly to agree with the highly consistent scientific
Minimize D.! demands
Optimize D.! delivery body o f information that addresses ventilator use in the set-
Recruiting maneuvers ting o f ALI.
Prone positioning
Inhaled nitric oxide/ inhaled prostacydin
I NSIG HTS FROM C LIN ICAL TRIALS
Tracheal gas insufflation
Corticosteroids and (?) other drugs
OF LU NG PROTECTION
With the rise of "evidence-based practice," physicians have
sought guidance from clinical trials that have addressed the
ADJUNCTS TO MECH ANICAL VENTILATION relative me rits of different ventilation strategies.1,3,112- 115
Attention to limiting tissue stra in mandates that the pres- Studies in which the highest tidal volumes and pressures
sure driving each tidal cycle (the difference between end- were applied in the "control arm" have shown benefit from
inspiratory and end-expiratory pressures), as well as the low-tidal-volume ventiJation.2•3 Results have been particu-
larly impressive when higher PEEP was used in conjunc-
number of high-pressure cycles applied per unit time, be
t~on with small tidal volumes in a setting where empha-
~ept within acceptable bounds. These requirements limit
tidal volume and minute ventilation and stimulate interest Sl.s was pl~ce~ on establishing stable recruitment, avoiding
in m ethods that reduce the requirements for ventilation and htgh venttlatmg pressures, and managing clinical cointer-
oxygenation, reduce local tissue stresses, a11d improve the ventions consistently.2. 115
efficiency o f pulmonary gas exdtange, all without the need Only one o f the several studies that randomized selec-
for additional ventilating pressures or higher ventilating tively on tidal volume-by far the largest yet published-
frequency (Table 29-5). The majority of these "adjunctive" successfully demonstrated mortality benefit for a smaller-
tidal-volume approach. 3 In retrospect, this hardly sho uld
techniques are discussed in detail elsewhere in this book.
Here it should be emphasized that perhaps the most ef- come as a surprise because the physiologic impact of tidal
volume depends on compliance (see Fig. 29-13). Further-
fective and universally applicable means for avoiding the
need for high ventilatory pressures is to reduce the demand more, provocative examinations of the data collected in the
for them by the patient or to readjust the clinician's ther- ARDS Network ARMA study and a meta-analysis of all
apeutic targets for ventilator support. Thus avoidance of published trials addressing the selection of tidal volume
hig h fever, pain, agitation, and metabo lic acidosis reduces have suggested that " lower is not necessarily better," espe-
Chand ventilation d emands, as well as the need for cardiac cially when compliance is less severely impaired and peri-
output-an important potential cofactor for VILI in the ex- odic si.ghs or r~ruiting maneuvers are no t employed. 116,117
peri~ental setting. Optimizing 0 2 d elivery by improving
Knowmg that ttdaJ volume is only indirectly linked to tissue
cardiac performance and providing adequate hemoglobin strain, inflammation, and rupture (consider the noninjuri-
concentration a lso minimize the ventila tory requirements . ous effects o f hig h tidal volumes during exercise), it is inter-
esting to specula te that the recruiting effects of higher tidal
Using the prone position evens the distribution of
volumes actually might have a salutary effect on inflam-
transpulmonary pressure, reducing local tissue strains and
mato ry signaling if peak transpulmonary pressure were
effectively recruiting well-perhtsed dorsal parenchyma,
kept below the "overstretch" signaling threshold and an
thereby improving oxygenation in most patients.50 Meth-
ods for improving gas-exchange efficiency include those di- appropriate level of PEEP were used. Whatever the valid-
rected at oxygenation (inhaled nitric oxide104 - 106 or inhaled ity o f this controvers ial argument, the collective results of
pros tacyclin 107), and those that lessen wasted ventilation these clinical studies have focused attention on transalve-
(tracheal gas insufflation 108- 110 or reduction of apparatus olar stresses rather than on tidal volume per se. They also
de~dpace 11 ~). ~I though often considered to be a ventilatory have ~emonstrat.ed that t~e levels and effects of hypercapnia
expen enced dunng low-tidal-volume ventilation, although
adJunct of hmtted value, recruiting maneuvers are incorpo-
complex,87 118 120 generally are modest and well tolerated.
rated by many p ractitioners, including this author, as an
~e National Institutes of Health (NIH)-sponsored trial
entrenched part of clinical practice. 111 In difficult situations,
the recruiting maneuver affords a logical means of reopen- ? fhtgh ve~sus moderate PEEP failed to demonstrate a signif-
ing the atelectatic lung so that the appropriate values of Icant survtval advantage for patients allocated to the high-
PEEP and tidal volume may be selected (see below). PEEP group.121 Impo rtant considerations, however, were
(1) neither group was exposed to plateau pressures that
were dearly in a da ngerous range, (2) recruitment poten-
tial ~as not str~tified, so patients who were not likely to
Setting the Ventilator: Recommendations benefit were asstgned to both groups, and (3) no recruiting
for Practice maneuver preceded PEEP application, nor was PEEP reg-
ulated as in co nv~ntiona l clinical practice. Unfortunately,
Given the joint po tential for the ventilator to offer life sup- there also was a fatlure of the randomization process so that
port or to extend the severity and duration o f the illness, a disproportionate number of older patients were assigned
the machine settings for the ventilatory cycle are of un- to the high-PEEP limb. The importance of PEEP is likely
questioned importance. How best to adlieve the appropri- to depend on the plateau pressure adUeved. A recently
TABLE 29-6 Common Effects of Pron e Positioni ng in ther study entered its targeted number of patients. More-
Early ARDS over, because pos t hoc analyses of the large Italian trial
More homogeneous transpulmonary pressure
strongly suggested that the most seriously affected patients,
Increased and su stained traction on dorsal lung units those exposed to higher ventilating pressures, and those
Better V/Q matchi11g who demonstrate improved ventilation efficiency are most
Tendency for recntitmeut likely to benefit126•129 (Fig. 29-21 ), a foUow-up trial focused
Improved airy,ray drainage on this subset has now been initiated. This important ques-
Improved lymphatic drainage tion rema ins unsettled. Therefore, despite the lack of trial
Modestly increased functional residual capacity (FRC) evidence, there is a strong rationale to use prone position-
Reduced tidal tissue strain [Vr / FRC (and VILI?)] ing to improve oxygenation, to allow reductions in Flo, and
ventilating pressure, and for its as yet unproven potential
ABBREVIATlOliiS: V/Q, ventilation-perfusion ratio; VT, tidal volume; VILl,
to protect the lung.
ventilator-induced lung injury.
Disappointingly, clinical trials of various other adjuncts
to ventilation also have not demonstrated major outcome
completed Spanish multicenter trial appears to confirm that advantages.130- 134 From a physiologic perspective, this is
PEEP is an integral part of a lung-protective approach,115 an hardly surprising. Precise numerical guidelines for selecting
implication supported by an analysis of "real world" venti- PEEP, tidal volume, and ventilatory position that are appli-
latory practice and outcomes.66 cable to any given individual patientshouldnotbe expected
Recruitment maneuvers also have been examined in a from the results of studies conducted in a diverse sam-
clinical trials format as a substudy of the high-PEEP NIH ple population whose inclusion criteria are broadly inclu-
investigation.122 The recruiting maneuvers were applied sive and for whom management details are uncons trained.
only in the high-PEEP limb, and the peak pressure achieved In the end, the best that can be hoped for is a proof of
was limited to 35 cmH20. The small separation between principle-not a prescription for care. However internaUy
plateau pressure and PEEP, the underlying disease charac- valid such trials rna y be, they do not correspond to the "real
teristics of the study population, the relatively high level of world" environment wherein comorbidities impinge and
PEEP at baseline, and the failure to augment PEEP after the management of potentially influential variables (such as
recruiting maneuver undoubtedly biased the result against PEEP, Paco.u and fluid management) is not protocolized.
showing a significant benefit.123 What follows is an approach to care of the individual pa-
Finally, notwithstanding considerable theoretical appeal tient with ARDS based on an understanding of the physio-
(Table 29-6), oxygenation benefit, 124 and suggestive exper- logic principles that must be brought to bear in the complex
imental evidence,52,SJ,J2S three relatively large randomized clinical environment.
trials126 - 128 have failed to demonstrate a statistically signif-
icant mortality benefit for prone positioning in broad sam-
G ENERAL GUIDELINES FOR VENTILAT OR
ples of patients with ARDS. A French s tudy reported a lower
MAN AGEMEN T
incidence of ventilator-associated pneumonia in the prone
cohort,.127 but this did not translate into a survival advan- Key guiding principles include the following: First, adjust
tage for that trial limb. An Italian trial used prone position- ventilator parameters empirically rather than by formula-
ing for less than one-third of each day, and a prematurely driven rules; prioritize patient comfort and safety. Second,
truncated Spanish trial,128 in whicl1 prone positioning was assign the prevention of mechanical trauma precedence
maintained for three-quarters of the day, showed an im- over maintenance of normocapnia and avoidance of 0 2 tox-
pressive separation (25% relative risk of death) between icity. Although no exact upper limits for acceptable plateau
the supine and prone treatment arms. Unfortunately, nei- pressure or F1~ can be specified, very high settings of Fxo,
FIGURE 29-21 Effect of p rone positioning on mortality as functions of illness sever ity (/eft) and tidal volu me (rigiJt). In patients wh o were
most critically ill (highest SAP S quartile) or receiving tidal volumes that risk ventilator-ind uced lung inj ur y (highest tidal volume
quartile), prone positioni ng may offer a survival ad vantage. (Data from l tnlinu multiceuter cliuical trial of proue versus supiue positiouiug
iu ARDS.126 )
0.5 c=J S upi11e 0.5

c::::J Supi11e
- Pro11e ~
1'1 0.4 - Pro11e
• p <0.05 vs Supine ~
* p <0.05 vs Supine
c 0.3
:;
~
0 .2
0 .1
0 ·0 -'-"'>"-49 40- 49 31· 40 0 . 31 0 .0

< 8.2 8.2- 9.7 9.7- 12 > 12
Quartiles of SAPS ll Quartiles of VT/Predicted body weight
pose a risk for absorption a telectasis as well as 0 2 toxicity. accomplished wit11 carefully adjusted pressure-controlled
Therefore, F1Dl should be held to less than 0.70 w henever ventilation in a well-sedated patient.
possible. Third, consider the impact of chest-wall stiffness All patients should be assessed for severity of disease
(including abdominal contents) o n transpulmonary pres- and for recruitment potential. After deficits in intravas-
sure and gas-exchange efficiency. In questionable situations, cular volume have been addressed and hemod ynamics
determine abdominal (bladder) and/ or esophageal pres- have been optimized, recruitment potential is gauged by
sures to help estimate the transalveolar pressure. 43 Fourth, applying high-level pressure-control ventilation: PEEP of
monitor hemodynamics as well as mechanics and gas ex- 15-20 cmH20, driving pressure of 30 cmH20 , and plateau
d1ange when regulating ventilatory therapy. Wide respi- pressure of 50-60 cmH20 for 1-2 minutes, as tolerated. Even
ratory variation in the arterial pulse pressure suggests the higher pressures may be appropriate for som e severely af-
need for additional volume. 135 A surrogate for measuring fected patien ts and for patients with very stiff chest walls-
hemodynarnks directly may be to monitor the central ve- for example, bum victims with chest-wall edema or es-
nous 0 2 saturation. A value greater than 70% and a dif- char. Although sus ta ined inflation with high pressure has
ference of 25% or less between arterial and mixed-venous been used traditionally, employed widely, and selected for
saturations almost invariably is associated with an adequate most reported research,.139 it is no more effective and tends
cardiac index(> 2.5liters/ m2 / min).136 Fifth, in severe cases, to be less well tolerated hemodynamically than a recruit-
attempt to minimize ventilatory demands and thereby re.- ing method based on pressure-controlled ventilation that
duce airway pressures, high rates of gas flow, and car- achieves lower a verage pressure but similar peak pres-
diac output requirements. Sixth, incorporate the "chal- sure during its inspiratory phase.77 If oxygenation a nd lung
lenge" principle in making therapeutic decisions regarding mechanics do not improve substantia!Jy with high-level
both the intensification and the "vithdrawal of therapeutic pressure-controlled ventilation as a recruiting technique,
measures. Examples of such challenges include recmiting the patient is considered to have low recruiting potential
maneuvers to assess lung-unit instability and closely mon- in tllnt position and at that specific time. Management goals
itored d1allenges of fluid administration or removal. Sev- in the "recntitable" group emphasize the maintenance of
enth, unless otherwise contraindicated, use prone position- high-level end-expiratory pressure, whereas in poorly re-
ing when high values fo r ventilatory pressure, PEEP and cruitable patients, PEEP is maintained as low as feasible-
F10 2 are needed to maintain adequate supin e arterial 0 2 ten- generally in the range of 5-10 cmH 20. In both groups, end-
sion. Eighth, assess pulmonary interventions in the volume- inspiratory plateau pressure is kept less than 30 cmH2 0,
contr ol mode of ventilation so as to better track thoracic me- except w hen chest-wall compliance is very low. Periodic
chanics and the lung's gas-exchanging efficiency for C~. At sighs may be advisable when very low tidal volumes are in
other times, employ pressure-limited forms of ventilation use.t40,141
(e.g., pressure control, pressure support, or BiPAPI APRV)
for ongoing management. ADJUSTING PEEP (TABLE 29-7)
As a general rule, the desired goal is to use the least Patients with an extensive "recruitable" population of lung
PEEP and tidal volume needed to achieve acceptable gas units should respond to increased PEEP and recruiting ma-
exchange while avoiding tidal collapse and reopening of un- neuvers by demonstrating improved alveolar mechanics
stable lung units. Knowing that m oderate hypercapnia gen- and improved gas excha nge, reflected both by increased
erally is well tolerated, therapeutic targeting priorities are Pao, and a reduction of the ratio of minute ventilation to
directed toward lung protection and maintenance of appro- Pacor TI1ese salutary changes are accompanied by only
priate hemodynamics and 0 2 delivery. Recruiting maneu- marginal effects on hemodynamics, as judged by systemic
vers help to characterize PEEP responsiveness, to determine blood pressure and centra l venous 0 2 saturation.126 Assum-
the relative status of intravascular filling a nd response to al- ing an unchanged rate of C02 production, the latter index-
tered cardiac loading conditions, and to set the PEEP- tidal- like a dead-space calculation-reflects tl1e efficiency of C02
volume combination. Prone positioning is s trongly consid- elimination, which is expected to improve with recruitment
ered in all but the mildest cases and patients who rapidly and deteriorate witl1 overdistention. Inspiratory crackles
improve. On rare occasions, noninvasive mechanical ven-
tilation using a comfortable full face mask (or a helmet, if
TABLE 29-7 H ow Should PEEP be Adj usted? A Practical
available) may overcome short-lived deficits of 0 2 exchange
Compromis e
without the need for intubation. In practice, however, the
needs to control the airway, to reduce ventilatory require- Ensure adequate preload.
ments, to apply hlgh levels of end-expiratory pressure, and Use small to moderate V-r or driving pressure.
to sustain support for extended periods us ually preclude Recruit by increasing PEEP /PCV to plateau of "' 50-60 cmH20
the use of noninvasive ventilation. for "' 1- 2 minutes.
In the first phase of ventilatory support, pa tient comfort Reduce driving pressure to 15- 20 cmH20.
must be ensured and ventilatory effort kept to a minimum. Reduce PEEP w1til arterial 0 2 or compliance falls significantly.
Modes such as APRV, BIPAP, and high-frequency oscilla- Rerecruit and select next higher PEEP if hemodynamics are
acceptable.
tion have persuasive advocates and consider able theoretical
Ensure that plateau pressure remaius below acceptable maximum
appeal.96, 98, 137, 138 The existing database and shared personal (e.g., <30 cmH 20)
experience, however, have not provided convincing evi-
dence that they offer a great deal beyond that which can be ABBREVIATIONS: VT, tidal volume; PCV, pressure-controlled ventilation.
642 PART VIII VENTILATOR SUPPORT IN SPEOFIC SEITINGS
(rales) audible over the dependent zones of the chest suggest patients is 30° to horizontal (Fowler) with frequent (at least
that recruibnent and derecruitment are occurring with each every 2-4 hours) lateral turning. Similar rules apply in the
breath and indicate that recruitment maneuvers and higher prone position; reverse Trendelenberg at 15-300 is preferred
levels of end-expiratory pressure may be indica ted to silence to flat (0°) horizontal. Tidal volwne is adjusted to the same
°
them. 14 Crackles occurring late in inspiration are of particu- value used in the supine position. An increase in plateau
lar concern because they may originate in units opening un- pressure strongly suggests that chest-wall compliance has
der relatively high pressures. ln gauging response to PEEP, been alte red by proning. Tn these instances, a proportional
it is important to consider CDl exchange as well as oxy- increase in PEEP also may be justified. (For example, if
genation response. With rare exception (e.g., when PEEP- plateau pressure rises by 10%, PEEP would be increased
impaired cardiac output causes mixed-venous 0 2 content by 10%.)
to fall), Pao, tends to increase when PEEP is applied. This
oxygenation improvement, however, may be accounted for
either by recruitment of lung units or by reduced or redi- SUGGESTED SEQUENCE OF MANAGEMENT
rected blood flow within the injured lung. In the latter cir- D.ECISIONS (FIG. 29-22)
cumstance, Pace, al'>o may rise. When recruitment is the INITIAL PHASE OF STABILIZATION AND SUPPORT
explanation for 0 2 improvement, however, C02 exchange 1. Determine whether the patient with oxygenation im-
is not compromised and even may improve, reflecting in- pairment has ALI, and if so, determine whether it is
creased alveolar ventilation. Similar principles apply during complicated by such reversible comobidities as volume
prone positioning. overload, pleural effusion, abdominal distension, or
The prone position should be considered in patients with pneumothorax.
severe gas-exchange impairment regardless of their " re- 2. Initiate ventilation with face mask or intubate as severity
cnTiting test" result in the supine position. Patients requiring warrants.
more than 10 cmH20 of PEEP at an Fro, of 0.6 to maintain 3. Decide on controlled versus spontaneous ventilation.
0 2 saturation at 90% or greater should be considered for Use controlled or nearly controlled ventilation to sub-
prone positioning unless there is a clear contraindication or due respiratory efforts for the most severely involved
the patient is improving rapidly. TI1e prone position should patients during the early stage of support.
be considered independently of supine recruiting potential 4. Initial ventilatory settings: Fr02 0.80, PEEP 5-8 onH2 0
because prone positioning w ill help lymphatic drainage and (depending on concern regarding hemodynamic toler-
secretion removal and release the lower lobes of the lungs ance), and tidal volume 6-10 nu/ kg (depending on in-
from the need to support the weight of the heart. Although spiratory plateau pressure).
provocative experimental data have challenged the concept 5. Estimate volemic status initially from arterial blood
recent! y, 143 the preferred angle for head elevation in supine pressure, respiratory variations of pulmonary and
FIGURE 29-22 A suggested decision sequence for ventilation decisions in ARDS. (Used, with permission, fro m Mariu1 eta /: Crit Care Med
32:250-5, 2004.)
Classify ARDS Type, Severity, & Co-Morbidities I

+
High Severity or Obtunded?
Non-Invasive Ventilation v"~ Intubate and Minimize Effort

~ No •
Estimate Intravascular
Adequate ABGs & Tolerance? Volume Status
Stable and alert? j_
Yes ! Rep ail" Volume Oclicit or Excess
1\:stablish Adequa te BP
Continue Non-Invasive
Ventilation
-•-
Determine Recruitment Potential With
+ Recruililllt Maneuver & PEEP Trial
Ready for Ventilator No I Acliust PEEP -•-
and Tidal Volume I
Discontinuation?
Yes Dramatic Improvement?
~ ~__Nn_
Extubate and/or Continue Supine 45-90• Y~ I Proning Contraindicated?
Discontinue Ventilation Reposition Frequently
LINO. TGI, Flo·Lan_j .&, ! No
Prone Positionh1g for 1+-
12-20 Hours/Dlll'_
Yes
I
l No
I Signi fie ant Clinicallmprovcmcnt? I-
systemic arterial pulse pressures, central venous pres- PATHOGENESIS AND D ETECTION OF VILI
sure, urinary output, and urinary electrolytes.
Experimental data suggest that numerous intersecting vari-
6. Confirm adequacy of intravascular volume using ables can influence the severity ofVTLl. For a given combina-
ecl1ocardiography, results from a volume cl1allenge, and tion of PEEP and tidal volume, vascular pressure, brea thing
central venous and pulmonary artery catheter data (car-
frequency, and body temperature appear to be important co-
diac index, mixed-venous 0 2 saturation, and occlusion
variables in the expression of VIU. Although both mechan-
pressure), ii available.
ical and inflammatory disruptions of the air-blood interface
7. Replete any volume deficits, and support the circulation are likely to be in some part responsible, how mechanical
with vasopressors and inotropes to the extent necessary forces cause structural alterations and signal inflammation
to perform the ventilator manipulations safely. is not well elucidated. Markers for damaging patterns of
8. Determine the recruitment potential of the pa tient by ventilation are badly needed.
using a recruiting maneuver /PEEP trial.
9. Selected tidal volume should be inversely proportional
to individual thoracic compliance and may range from LONG-TERM DAMAGE TO A IRWAYS
5-8 ml/ kg of ideal bod y weight. During the PEEP trial, AND PARENCHYMA
cons ider together the oxygenation change, the Pac~
change, the alterations in mecl1anics, and the hemody- The determinants of alveolar and small airway damage oc-
namic response. Adjust the PEEP and tidal volume com- curring in patients ventila ted for ARDS are not clear-peak
bination to the lowest tolera ted values that susta in the pressure, end-expiratory pressure, or both. Future outcome
recruitment benefit. studies should target the incidence of obstructive, restric-
10. Proning is advisable in patients with no contraindica- tive, a.n d disordered gas exchange following recovery from
tions and moderate to severe disease regardless of re- ARDS.
cruiting test unless they are already improving rapidly.
If the patient does not respond to the prone position,
another recruiting maneuver is attempted while the pa- RELATIONSHIP OF VILI TO MULTISYSTEM
tient is prone. The PEEP and tidal volume combination ORGAN DYSFUNCTION
is readjusted, as before. Although laboratory studies have shown the release into
11. When proning is used, scheduled reversion to the the systemic circulation of gas, bacteria, a nd inflammatory
supine position is conducted at least once a day for mediators from injured lungs ventila ted at high pressures
cleanup, dressing changes, edema clearance, diagnos- with insufficient PEEP, the causative roleofVILiin multiple-
tic procedures, transport to imaging, and so o n. Many organ failure mus t be investigated further for the clinical
patients require almost continuous proning to maintain setting.
adequate gas exchange during the first several days of
illness. Proning can be discontinued when it no longer
makes an impressive difference to oxygenation, and VENTILATOR-ASSOCIATED PNEUMONIA
pla teau pressure can be kept in a "safe" range when
The incidence of ventilator-associated pneumonia is high
the patient is supine.
in intubated patients, especially among those with ALI.
Whether and how ventilator-related injury predisposes to
SUBSEQUENT CARE pneumonia needs to be clarilied and the measures neces-
sary to reduce its incidence identiiied.
Recovery onset is recognized by improving Pa 0 2 / FI~ and
minute-ventilation-to-Pac~ ratios, clearing radiographic
opacity, and rising compliance of the total respiratory sys- ENVIRONMENTAL MODIFICATIONS
tem. Appropriate adjustments then are made to sedation
and ventilating pressures, and spontaneous breathing is en- Multiple factors have been shown in the laboratory to be
couraged by conversion to PSV or to pressure-controlled impor tant in the expression of VILI, including elevations
ventilation with lower driving pressures as tolerated. Pron- in precapillary pressure, reduced left-atrial pressure, and
ing is d iscontinued when the alterations in Pao 2 observed elevated body temperature. Whether such factors play a
during position changes are less than 10%, status is clearly role in the clinical setting is not clear. Do such cofactors as
improved, or no obvious benefit has been achieved after a edema, Fr0z, vasoactive and anti-inflammatory drugs, and
lengthy trial (> 48 hours). Reductions in Fio2 to an accept- plasma protein concentrations determine the severity of ex-
able range are undertaken before cutbacks in PEEP. pression of VILI? Are there additive or synergistic interac-
Weaning of PEEP is initiated when Ft~is 40% or less and tions among these variables?
Pa~ is 80 mmHg or greater.
APPROPRIATE LEVELS OF PEEP

Future Directions and Research AND TIDAL VOLU ME
How to select the most lung-protective combination of PEEP
Numerous questions related to the practical application and tidal volume remains an a rea of active controversy. Al-
of mechanical ventilation remain incompletely answered. though considerable progress has been made, the debate
TI1ese include the following. needs to be settled regarding the relative importance of
644 PART VIll VENTILATOR SUPPORT' IN SPEOFIC SETIINGS
limiting peak inflation pressure, optimizing PEEP, redu c- tiona! ventilator-based lung-protective strategies. Defini-
ing driving pressure, or limiting tidal volume. Should ar- tive comparisons of high-frequency ventilation versus lung-
terial oxygenation, thoracic mechanics, or bedside imaging protective strategies using a conventional ventila tor are
(s uch as by electrical impedance tomography or acoustic needed to identify possible benefits and hazards, as well
mapping) be u sed to guide these selections? as to learn the best approach to using this teclmology in the
clinical setting .
RECRUITMENT MANEUVERS
Sustained inflation with high airway pressure is an effec- VALUE OF ADJUNCTIVE AND
tive means of opening collapsed tissue and may be integral PHARMACOLOGIC MEASURES
to selecting PEEP. The value of repeated recruiting maneu- Tested as isola ted interventions, nitric oxide, partial-
vers and the best means of doing so, however, have not been liquid ventila tion, aerosolized surfactant, corticosteroids,
studied carefully. The effectiveness of recruitment maneu- almitrine, and prone positioning have not been demon-
vers may well vary with the type or stage of AU. More- strated to influence mortality in multicentric trials.'130 The
over, the incidence of lung rupture, hemod ynamic com- physiologic ratio nale for these measures, however, is strong
promise, and other complica tions requires documentation. for certain types of patients and for certain clinical condi-
How should such maneuvers be performed? In which pa- tions. Moreover, few of these adjuncts have been tested in
tients? How often, and at what F1~? Whether sighs help combination. (Prone positioning, for example, adds to the
to maintain recruitment in patien ts with low tidal volumes oxygenation benefit of inhaled nitric oxide.) The utility of
and unstable airways should be clarified. such measures- used alone and in combination-requires
further study in populations most likely to benefit.
PRONE POSITIONlNG
The duration of proning (e.g., how long each day and
when to cease proning in each patient) remains unsettled. Summary and Conclusion
Most investigators fa vor proning for most of each day, at
least until there ar e clear improvements in mechanics and Injury to the alveolar-capillary membrane originates from
gas exchange, allowing adequate arterial oxygenation with diverse causes that initially may disrupt either the epithelial
an Fro 1 of less than 0.50-{).60 at tolerated levels of PEEP or endothelial surfaces. Managing the spectrum of condi-
in the supine position. Whether proning confers an ad- tions grouped together under the all-encompassing label of
vantage on key outcomes other than oxygenation a nd in ARDS is a challenging assignment that must take into ac-
which categories of patient are other questions that merit count the severity of illness as well as the interactions among
investigation. the ventilatory and nonventilatory variables that influence
the progress of this condition. Prevention of excessive tissue
strain during the tidal cycle entails the avoidance of intol-
NONINVASIVE VENTILATION
erable peak transalveo1ar pressw·es and repetitive opening
Noninvasive ventilation has been applied successfully to and closing of unstable lung units, as well as a ttention to
problems of acute respiratory failure, including some pa- pathogenetic cofactors that may exacerbate injury or retard
tients with ALI and ARD$. 88 - 90 Although vastly better than healing. Because of the diversity of mechanical problems
befo re, interfaces must be improved to e nsure reliability and presented by different patients, as well as the heterogene-
patient comfort. More information is needed to guide clini- ity of mechanical properties among the lung units within
cians regarding optimal selection of patients, timing, equip- the same individual, a logical approach r equir es mastery
ment, and monitoring. of key physiologic principles, awareness of the guidelines
provided by well-conducted clinical trials, and integrated
THERAPEUTIC VALUE OF HYPERCAPNIA clinical judgment a t the patient's bedside.
AND TOLERANCE OF HYPOXEMIA
Laboratory data suggest that hypercapnic intracellular aci-
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patients wi th acute lung injury: A randomized, con trolled trial. 139. Grasso S, Mascia L, Dcl Turco M, et al. Effects of recruiting
JAMA 2004; 291:1603-9. maneuvers in patients with acute respiratory ctistress syndrome
132. Dellinger RP, Zimmerman JL, Taylor RW, et al. Effects of ventilated with protective ventilatory strategy. Anestht.~'iology
inhaled nitric oxide in patients with acute respiratory distress 2002; 96:795-802.
syndrome: Results of a randomi2ed phase II trial. Inhaled Nitric 140. Pelosi P, Cadringher P, Bottino N, et al. Sigh in acu te respiratory
Oxide in ARDS Study Group. Crit Care Med 1998; 26:15- 23. ctistress syndrome. Am J Respir Crit Care Med 1999; 159:
133. Anzueto A, Baughman RP, Guntupalli KK, et al. Aerosolized 872-80.
surfactant in adults with sepsis-induced acute respira tory dis- 141. Patroniti N, Foti G, Cortinovis B, et a l. Sigh improves gas
tress syndrome. Exosurf Acute Respiratory Dish·ess Syndrome exchange and lung volume in patients with acute respiratory
Sepsis Study Group. New EnglJ Med 1996; 334:14.17- 21. distress syn drome undergoing pressure support ventilation.
134. Bernard GR. Luce JM, Sprung CL, et al. High-dose corticos- Anesthesiology 2002; 96:788-94.
teroids in patients with the adult respiratory d istress syndrome. 142. Lichtenstein D, Goldstein I, Mourgeon E, et al. Comparative di-
New Eng! J Meet 1987; 317:1565-70. agnostic per formances of auscu ltation, chest radiography, and
135. Michard F, Chemla D, Richard C, etal. Clinical use of respiratory lung ultrasonography in acute respiratory distress syndrome.
changes in arterial pulse pressure to monitor the hemodynamic Anesthesiology 2004; 100:9-15.
effects of PEEP. Am J Respir Crit Care Med '1999; 159:935-9. 143. Panigada M, Berra L, Greco G, et a!. Bacteria l coloni7..ation
136. Rivers EP, Ander DS, Powell D. Central venous oxygen satura· of the respiratory tract following tracheal intubation: Effect
tion monitori ng in the critically ill patient. Curr Opin Cri t Care of gravity. An experimental study. Crit Care Med 2003; 31:
2001; 7:204-11. 729-37.
Chapter 30 _ _ _ _ _ __ _ __ to bronchodilator therapy. 7 In addition, some hypercapnic
patients may avoid intubation through use of noninvasive
MECHANICAL ventilation8- 10 (Fig. 30-1). Inhalation of a helium-oxygen gas
mixture (heliox) also may reduce work of breathing and de-
VENTILATION FOR crease the likelilwod of intubation.n· 12
The decision to intubate a patient with status asthmati-
SEVERE ASTHMA cus is made primarily on clinical grounds. Indications for
intubation include respiratory arrest, a depressed level of
JAMES W. LEATHERMAN consciousness, marked agitation and inability to cooper-
ate with therapy, and progressive fatigue and exhaustion.
Endotracheal intubation may be performed by either the
oral or nasal route. One advantage of oral intubation is
that it allows insertion of a larger endotracheal tube tha t
facilitates suctioning and offers less airways resistance.2•13
LIFE-THREATENING ASTHMA A rapid-sequence technique is advocated by some experts,
VENTILATOR MANAGEMENT and fiberoptic guidance also has been used.13 Regardless of
Pulmonary Hyperinflation: Mechanism and the technique used, intubation should be performed by the
Assessment most skilled operator present. Repeated airway manipula-
Ventilator Settings tion and failed intubation in patients with fulmina nt asthma
may prove catastrophic.
Gas Exchange: hypercapnia
Various drugs have been used to facilitate intubation
NONVENTILATOR MANAGEMENT
Standard Therapy of patients with severe asthma. One approach uses ke-
Alternative Therapies tamine, an anesthetic that does not cause respiratory
DEATH AND COMPLICATIONS depression or hypotension, in conjunction with a benzo-
Mortality diapine to prevent emergence hallucinations. 13 Ketamine,
Complications however, may increase laryngeal reflexes and predispose to
POSTHOSPITALIZATION PROGNOSIS laryngospasm with excessive upper airway manipulation. 14
Propofol, a potent and fast-acting sedative, decreases
It is estimated that 6000-10,000 patients require mechanical
airways resistance after intubation as compared with etomi-
ventilation for acute asthma in the United States each year.1 da te or thiopental. 15 Propofol, however, may cause h ypoten-
Although often lifesaving, mechanical ventilation for severe sion, and etomidate may be a better alternative in hemo-
dynamically unstable patients.14 Although succinylcholine
asthma is associated with many complications and a fatal
outcome in some patients. An understanding of salient prin- can cause histamine release, this is likely of little clinical
significance, and this depolarizing paralytic agent is appro-
ciples regarding ventilator support of patients with severe
asthma may reduce the risk of an adverse outcome. 2 priate for rapid-sequence intubation of patients w ith severe
asthma.14 Many of the sedative drugs used to facilitate in-
tubation reduce vascular tone and, in conjunction with de-
creased venous return secondary to marked pulmonary hy-
Life-Threatening Asthma perinflation, may contribute to hemodynamic instability at
the time of intubation. 16 Postintubation hypotension should
Asthma attacks that lead to mechanical ventilation may be anticipated and managed by rapid fluid administration
have a gradual onset over one or more days or occur sud- and manual ventilation via an Arnbu bag at a slow rate to
denly over minutes to hours (Table 30-1). Onset is grad- limit the severity of hyperinflationP
ual in 80% of patients, with viral infections being the most
common identifiable trigger. 3 Slow-onset status asthmati-
cus is characterized by extensive mucus plugging with
eosinophilic infiltration and edema, a limited immediate re- Ventilator Management
sponse to bronchodilators, and slow resolution over days.4
The remaining 20% of patients have rapid-onset attacks Traditional goals of mechanical ventilation for patients w ith
that often are triggered by aeroallergens, nonsteroidal anti- acute respiratory failure are to provide adequate oxygena-
inflammatory agents, or airway irritants.3•5 These "sudden tion with nontoxic levels of inspired oxygen and suffi-
asphyxial" attacks are caused by profound bronchospasm cient minute ventilation to achieve a normal arterial carbon
w ith minimal mucus plugging, explaining the often rapid dioxide tension (Pac0 , ) and arterial pH. In status asthmati-
resolution.4 cus, however, attempts to correct respiratory acidosis by
Regardless of the mode of onset, life-threatening asthma increasing minute ventilation may lead to extreme pul-
is associated with a markedly increased airway resis- monary hyperinflation, with the attendant risks of tension
tance, pulmonary hyperinflation, and high physiologic pneumothorax and hemodynamic collapse. 18 For this rea-
dead space, which together lead to hypercapnia and risk son, controlled hypoventilation with permissive hypercap-
of respiratory arrest.6 Hypercapnia per se, however, is not nia was first proposed 20 years ago and subsequently gained
an indication for intubation because most episodes respond widespread acceptance. l9
649
650 PART Vill VENTTLATOR SUPPORT IN SPECIFIC SETTINGS
TABLE 30-1 Patterns of Neax-Fatal Asthma
Slow-Onset Rapid-Onset
Time course (onset) One or more days Minutes to hours

Triggers Virus, unknown Aeroallergen, NSAID, airway irritant,
emotional stress, unknovm
Frequency - 80% - 20%
Mechanisms of ajrflow Mucous plugging and airway Bronchospasm ("dry airways")
obstruction edema > bronchospam
Airway inflammation Eosinophils Neutrophils
Response to treatment Slow: minimal response to initial Rapid: good response to initial bronchodilators
bronchodilators
Prevention Steroids early in exacerbation Avoid triggers
Duration intubation Often several days Often < 24 hours
ABBREVIATIOn: NSAID, nonsteroid anti-inflammatory drug.
In brief, the rationale for this approach is that hyper- (Fig. 30-2). During mechanical ventilation, dynamic hyper-
capnia poses less risk than does markedly increased lung inflation is initiated when there is insufficient time during
volume. 20· 21 Although there have been no prospective, ran- expiration for complete exhalation of delivered tidal vol-
domized studies of controlled hypoventilation in asthma, ume, resulting in an increase in end-expiratory lung vol-
a retrospective analysis suggested that it is associated with ume and positive end-expiratory alveolar pressure (auto-
better outcomes than a conventional ventilator strategy.20 PEEP). With subsequent breaths, a progressive increase in
To apply controlled hypoventilation rationally, it is essen- lung volume leads to an improven1ent in expiratory gas flow
tial to understand methods for monitoring the severity of because of higher elastic recoil pressure and an increase in
pulmonary hyperinflation and how the latter is influenced airways diameter, permitting the entire tidal volume to be
by the choice of ventilator settings. 22- 24 Although anecdotal exhaled (Fig. 30-3). Therefore, dynamic hyperinflation may
experience with pressure-control or pressure-support ven- be viewed as an adaptive process that enhances expiratory
tilation has been reported, there may be some theoretical flow in the setting of airways obstruction but one that also
advantages to use of a volume-cycled mode (assist-control exposes the patient to increased risk of complications re-
or synchronized intermittent mandatory ventilation)/ and lated to alveolar overdistension.
the great prepondera nee of clinical experience has been with The severity of hyperinflation in severe asthma varies
the latter approach. 2•9' 22- 29 Subsequent discussion of venti- among patients and within individual patients over time.
lator teclmiques and monitoring will be linUted to use of Serial monitoring of dynamic hyperinflation is important
volume-cycled ventilation. to identify those patients with marked hyperinflation who
may be at increased risk of complications and to assess
PULMONARY HYPERINFLATION: MECHANISM the response to treatment and the evolution of airflow
AND ASSESSMENT obstruction.
Spontaneously breathing patients with severe asthma un- Two principal methods of monitoring the severity of air-
dergo tidal ventilation near their total lung capacity; with flow obstruction in status asthmaticus have been used : mea-
mecl1anical ventilation, lung volumes may increase further2 surement of total exhaled volume during a prolonged ap-
nea beginning at end inspiration and assessment of airway
FIGURE 30-1 Change in Pac o 1 and pH associated

1 ..g .. Pa002 --pH with the use of non invasive positive-pressure
ventilation by face mask in patients with severe
70
asthma. (Used, with permission, from Merluri et al:
... Cllest 110:767- 74, 1996.)

65
60
-
55
"\..:
50 'I... ....
....,
' ·· . . .
--····r-··-·····-···-··-·-r···-····..··············1
<2hrs 2-6 hrs &-12 hrs 12-24 hrs
CHAPTER30 MECHANICAL VENTILATION FOR SEVERE ASTHMA 651
8 Apnea Dynamic
Hyperinflalion
7
FIGURE 30-2 Lu ng volumes in severe asthma
LUNG 6 during spontaneous ventilation and with
VOLUME mechanical ventilation. Tidal breathing occurs near
(l) 5
total lung capacity (TLC) during spontaneous
4 ventilation and above TLC during mechanical
3 --------------------------· ventilation. After delivery of tidal volume (VT)

during mechanical ventilation, a prolonged apnea
permits exhalation of volume produced by dynamic
2
hyperinflation (VoH1 ); lung volume at the end of
1 apnea, however, remains well above normal
functional residual capacity (FRC) because of gas
trapped behind occluded airways (Vtrap) (Adapted,
Spontaneous Ventilation Mechanical Ventilation with permission, fro m nucen et a/. 2 )
pressures during volume-cycled ventilation. Tuxen et use of a high inspiratory flow rate commonly results in a
aJ1S.22,23 have used a prolonged a pnea to assess dynamic peak pressure above 50 cmH 20 but without increased risk
hyperinflation in pa tients with severe asthma. With this of ba rotraurna.26 In addition, a recent stud y found iliat peak
meti1od, the total amount of gas exhaled during an ap- pressure may not reflect the reduction in dynamic hyper-
nea represents the volume (above functional residual ca- inflation that follows prolongation of expiratory time, pre-
pacity) at end inspiration (V£1). The volume at end expira- sumably because of an increase in airways resistance as lung
tion (VEE) is calculated by subtracting tid aI volume from the volume decreases24 (Fig. 30-6).
VEl and represents ti1e increase in lung volume caused by Unlike peak pressure, plateau airway pressure (Pplat)
dynamic hyperinfla tion (Figs. 30-3 and 30-4). In one study, is not affected by inspiratory flow-resistive properties and
VE1 predicted ti1e development of hypotension and baro- may be a better parameter for monitoring lung hyperinfla-
trauma better than did airway pressures.18 Measurement of tion in status asthmaticus.2'26-30 Because patients with se-
VEl and VEE, however, has not gained widespread clinical vere airflow obstruction typically have near-normal respi-
acceptance for serial monitoring of d ynamic hyperinflation ratory system compliance, an increase in Pplat is usually
in part because of the need for paralysis. 2 a result of dynamic hyperinflation. At consta nt tidal vol-
A more common m ethod of monitoring patients with se- ume, changes in tile degree of dynamic hyperinflation in
vere asti1ma is assessment of airway pressures (Fig. 30-5). response to bronchodilators or manipulation of expiratory
As described initially,l9 controlled hypoventilation in sta- time can be inferred from changes in Pplat. 24 Because Pplat
tus asthmaticus limited peak airway pressure to less Ulan represents end-inspiratory elastic recoil pressure and pro-
50 cmH2 0 , a target used by others subsequently. 25 Such vides an estimate of average peak a lveolar pressure, it also
a strategy, however, may be problematic in patients with might (in theory) help to predict risk of alveolar ntpture.
asthma because peak pressure is highly dependent on in- Although the threshold Pplat that predicts increased risk
spira tory flow-resistive properties and therefore d oes not of barotra uma is not well defined in status asthmaticus, an
reliably reflect the degree of hyperinflation. 2 Indeed, the acceptable upper limit of 25-30 cmH20 has been suggested
combination of markedly increased airways resistance and mos t often2 , 26·27•29, 30 (Table 30-2).
AllwiiY obltrudlotl FIGURE 30-3 A. Dynamic hyperinflation. FRC, functional residual

ProgressiYe dynlmfe llyptrilillltlon capacity; VT, tidal volume; VEL, volume (above FRC) at end
Lung
inspiration; V0 m, volume (above FRC) caused by dynamic
Volume hyperinflation. (Used, w itlr pcrmissiou, from Tuxeu: Am J Respir Crit
Care Metl150:1722-37, 1994.) B. Measurement of VE1 and VEE
(volume above FRC at end expiration) by use of a prolonged apnea.
VEE and VoHt are equivalent. (Used, wit/1permissiou, from ntxeu
FRC et al: Am R ev Respir Dis 136:872- 9, 1987.)
Lung l1dal Ventilation

Volume
VT
FRC
B
highest end-inspiratory alveolar pressure. Regardless of the

duration of the inspiratory pause that is selected, it is impor-
...,
4.0
, ' tant to be consistent so that changes in Pplat caused solely
by varying pause duration are not misconstrued as changes
VB{~ ~~E
in the degree of hyperinflation.
ve When measured by the "static" method of end-expiratory
--
...J
~
3.0
ve
16
, "'
airway occlusion, auto-PEEP provides an estimate of the
average end-expiratory alveolar pressure. Although there
is relatively little published data regarding levels of auto-
e
-~
::1
2.0 , "'
10 PEEP in status asthmaticus, one study found an average
value of 15 cmH2 0 on the first day of mechanical ventilation
C)
when minute ventilation approximated 10 liters/min. 24 In
c:: general, changes in auto-PEEP track closely with changes
.3 in Pplat, and either (or both) may be helpful for following
1.0 the degree of dynamic hyperinflation. There are, however,
certain caveats regarding the measurement of auto-PEEP
that must be considered.
First, the duration of the end-expiratory pause influences
FRC the auto-PEEP value; a pause of a t least 2- 3 seconds should
VJ 100 70 40 100 70 40 100 70 40
be used to avoid its underestimation. (Unlike Ppla t, a higher
TE 5.4 5.1 4.5 3.2 2.9 2.3 1.7 1.5 1.1 value for auto-PEEP will be obtained with the longer pause.)
FIGURE 30-4 Effect of minute ventilation (VE) and inspiratory Ventilators whose auto-PEEP function is automated may
flow rate (Vt) on dynamic hyperinflation during mechanical terminate the pause prematurely, and this may lead to gross
ven tilation for severe asthma. VEt, volume at end inspiration; underestimation of end-expiratory alveolar pressure. Sec-
VEE, volume at end exp iration. Vr, tidal volume. (Used, witlr ond, the measured value is influenced by the circuit com-
permission, from Tttxen et al: A m Rev Resp·i r Dis 136:872-9, 1987.) pression factor; use of a highly compliant ventilator circuit
may lead to underestimation of auto-PEEP.31 Third, patien ts
with status asthmaticus who have radiographic evidence of
The end-inspira tory airway occlusion used to measure hyperinflation a nd elevated Pplat on occasion may have un-
Pplat results in an initially rapid fall in airway pressure, expectedly low values of measured auto-PEEP when venti-
followed by a slower decline until a final, stable pressure is lated at very low respiratory rates. This phenomenon arises
reached (see Fig. 30-5). The initial drop in pressure is a func- presumably because very long expiratory times may en-
tion of inspiratory flow and inspiratory airway resistance, courage airway closure that prevents accurate assessment
whereas intrapulmonary gas redistribution (pendeluft) and of end-expiratory a lveolar pressure. 32 Fourth, and perhaps
stress relaxation are responsible for the subsequent fall in most important, expiratory muscle activity may influence
pressure. The marked time-constant heterogeneity of sta- measured auto-PEEP markedly and cause gross overestima-
tus athmaticus requires several seconds for a stable pres- tion of the severity of dynamic hyperinflation, potentially
sure to be reached. A shorter (0.4-Q.S second) inspiratory leading to unnecessary restriction of minute ventilation.l3 It
pause often has been used to measur e Pplat. 2 Al though the is therefore imperative that the patient's expiratory muscles
latter overestimates average end-inspiratory alveolar pres- be relaxed during the measurement.
sure, it may reflect more closely those lung units with the
VENTILATOR SETTIN GS
FIGURE 30-5 Proximal airway pressure during an end-inspiratory In severe asthma, three key factors determine the degree to
and end-expiratory ainvay occlusion. End-inspiratory occlusion is
which Vee increases during mechanical ventilation: resis-
followed by an initial rapid fall in airway pressure, secondary to
in trinsic airways resi sta.n cc and then a more gradual fall in
tance to airflow during expiration, tidal volume that m ust
p ressure secondary to gas redis trib ution and tissue resistance. be exhaled, and time for expiration. The key ventilator set-
Ppk. peak airway pr essure; Pplat, plateau airway pressure; tings that influence the severity of hyperinflation are tidal
auto-PEEP, au to-positive end-expiratory volume, respiratory rate, and inspiratory flow rate.
MINUTE VENTILATION: TIDAL VOLUME

AND RESPIRATORY RATE
Tuxen and Lane22 examined various ventilator settings
in severe asthma and found that minute ventilation was
the most important determinant of dynamic hyperinfla-
tion (see Fig. 30-4). For a given minute ventilation, VEE
was similar regardless of tl1e specific combination of res-
piratory rate and tidal volmne. 22 VEl, however, obviously
will be greater when a given minute ventilation is achieved
CHAPTER 30 MECHANICAL VENTILATION FOR SEVERE ASTHMA 653
Ruplnilt»ry nte
80 11 .
12 0
70 eo
-~ 60
"'p<.O I
50
-
E
u
!
::J
40
I
..
r-*-1 r*-1
I
Cll
30 •
~
Q.
20
FIGURE 30-6 Peak airway pressure, plateau
1() pressure, an d auto-PEEP at respiratory rates of 18,
U, and 6 breaths per m inute during mechanical
0 ventilation for severe asthma (u = U). (Use.tl, w ith
Jlt•ak permission, from Leatherman et al: Crit Care Metl
Preuure 32:1542-5, 2004.)
thr ough use of a higher tidal volume and lower rate. In this is less certain. A recent study examined the effect of prolon-
study, the degree of hyperinflation became quite marked gation of expiratory time on dynamic hyperinflation-as as-
when minute ventilation was increased from 10 to 16 and sessed by Pplat and auto-PEEP-when the baseline minute
26 liters/min; at the highest minute ventilation, both hy- ventilation approximated 10 liters/min.24 As expected, Pplat
potension and barotrauma were noted22 (see Fig. 30-4). and auto-PEEP decreased when expiratory tin1e was pro-
This clearly demonstrates the potential risk of progres- longed, but the magnitude of this reduction was not pro-
sively increasing minute ventilation in an attempt to correct found (see Fig. 30-6). For examp le, when respiratory rate
hypercapnia. was reduced from 12 to 6 breaths per minute (adding 5 sec-
While very high levels of minute ventilation clearly pose onds to expiratory time), Ppla t and auto-PEEP fell by only 2-
a risk in the ventilated patient, the benefit of extreme limita- 3 cmH 2 0.24 The relatively modest effect on dynamic hyper-
tion of minute ventilation, as advocated by s ome authors,34 inflation is understandable given the low expiratory flow
rates after a few seconds of expiration (Fig. 30-7). Also, be-
cause expiratory flow decreases progressively throughout
TABLE 30-2 M echani cal Ventilation for Severe Asthma: expiration, the reduction in hyperinflation resulting from a
One Approach given prolongation of expiratory time depends on the base-
line respiratory rate (i.e., less benefit at a lower respiratory
Ventilator settings (in itial) rate) (see Fig. 30-7).
Mode Assist-control Another factor that limits the extent to which prolon-
VT 8-9 ml/kg gation of expiratory time can reduce lung hyperinflation
Rate 12- 14 breaths/min
is the presence of gas trapped behind occluded ain-vays.
VE 0.1-0.13 liter/ kg/min
Vt 6Q-70 liters/min
Total pulmonary hyperinflation has two components: a
Waveform Decelerating or square dynamic component that is amenable to ventilator manip-
PEEP ~5 crnH 20 ulation and a second component caused by trapped gas be-
Fto 2 Sao2 > 90% hind occluded airways, which is therefore not influenced by
prolongation of expiratory time (see Fig. 30-2). One study
Sedation/paralysis
Propofol 2-5 mg/ kg/h infusion
used a prolonged apnea to measure the dynanuc component
Fentanyl 50- 200 f.'g/h infusion
and a postapnea radiographic estimate of lu ng volume to
Vecuroniurn 0.1 mg/ kg bolus pm estimate the fixed component.23 The results of this study
suggested that trapped gas contributed a greater percent-
Therapy of airflow obstruction age of total pulmonary hyperinflation than did dynamic
Albuterol-ipratroprium MDI 6 puffs qh x 4, then q1 -2h
Methylprednisolone 1- 2 mg/ kg/day
hyperinfla tion.23
In essence, available data s uggest that while very high
Ventilator adj ustments respiratory rates (and very short expiratory times) should
Goals: Pplat < 30 crnH20 (~ 25 ideal) and pH > 7.2 be avoided, there is often little to be gained by reducing
• Ppla t > 30 cmH 2 0 ~ decrease VE. (rate) the respiratory rate below 12- 14 breaths per minute when a
• pH < 7.2 and Pplat < 25 ~ increase VE(ra te)
tidal volume of 8-9 ml/kg is used (see Table 30-2). An excep-
• pH < 7.2 and Pplat 25-30 ~ no change
(consider buffer if adverse effects of acidosis suspected clinically)
tion might be when hyperinflation is marked (e.g., Pplat >
30 crnH20) or has resulted in complications because then
ABBREVlATJONS: Vy, tidal volume; VE, minute ventilation; V1, inspiratory flow even a small reduction in hyperinflation could have a
rate; MDI, metered-dose inhaler; and Pplat, plateau airway pressure. meaningful clinical impact. Truly dramatic reductions in
654 PART Vlli VENTILATOR SUPPORT IN SPECIFIC SETIINGS
i 70
se 60 Time(sec)
- 0 1 2 3 4
50 -
~ 200-
0
u:
10
0 ..__ __
A B
FIGURE 30-7 A. End-expiratory flow rates at respiratory rates of 18, 12, an d 6 breaths per minute during mechanical ventil ation for severe
asthma (u = 7). B. Expiratory flow tra cing from an individual patient. (Used, with pennission, from L-entlrermau et nl: Crit Care Med
32:1542-5, 2004.)
hyperinflation, however, may not be easily achieved by ven- APPLIED PEEP

tilator manipulation alone and usually must await improve- External positive end-expiratory pressure (PEEP) is used of-
ment in airflow obstruction. ten during mechanical ventilation of patients with chronic
obstructive pulmonary disease (COPD) to decrease the ef-
fort required to trigger the ventilator and does not increase
INSPIRATORY FLOW RATE lung volume as long as applied PEEP is less than auto-
At any given respiratory rate, shortening of inspiratory PEEP.35•36 There is no dear-cut rationale for the use of exter-
time through the use of a high inspiratory flow rate of nal PEEP, however, when a patient is receiving controlled
necessity will lengthen expiratory time. Similarly, inspira- med1anical ventilation under the influence of deep sedation
tory time will be shorter when the inspiratory waveform or paralysis. Furthermore, the impact of applied PEEP on
is square rather than decelerating. Accordingly, it has been lung volume may be different in asthma and COPI)-35,37,38
advocated that a flow rate of approximately 100 liters/min (Fig. 30-8). One study of found that external PEEP of
and a square waveform be used in patients with status 10- 15 cmH2 0 increased the lung volumes of ventilated
asthmaticus. 2•26•27 Although this strategy will produce a patients with severe asthma, suggesting that minin1al
more favorable inspiratory-expiratory (l:E) ratio, U1e effect PEEP (~5 cmHzO) levels should be used in this setting38
on dynamic hyperinflation in patients whose minute venti- (see Table 30-2).
lation already has been restricted will be modest. 24 With
a tidal volume of 600 ml, for example, a change from a
flow rate of 60 liters/ min with a decelerating wave to a
GAS EXCHANGE: HYPERCAPNIA
flow rate of 120 liters/min with a square wave will add less
than 1 second to expiratory time. Because end-expiratory Hypercapnia is common during mechanical ventilation of
flow rates typically are 60 mVs or less at a respiratory patients with severe asthma. Two studies found average
rate of 12-14 breaths per minute (Fig. 30-7), this degree of values for PacO:! and pH of 61 mmHg and 7.2 (mean minute
prolongation will result in a negligible reduction in lung ventilation 11.4 liters/min) and 68 mmHg and 7.18 (mean
volume (Table 30-3). In brief, a high inspiratory flow rate minute ventilation 9 litershnin). 18•24 There is considerable
and square waveform offer no significant advantage over variation in the degree of respiratory acidosis, and Pac0 2
a decelerating waveform and more conventional flow rate values may range from normal to over 100 mmH g. Hy-
(- 60 liters/min) in patients with asthma whose minute ven- percapnia despite normal or increased minute ventilation
tilation already has been limited. can only result from an increase in carbon dioxide (C02)
TABLE 30-3 Effect of Inspiratory Flow Rate in Severe As thma
v, and Waveform I:E Ratio t.DHJ (ml) t.auto-PEEP (cmH 2 0)
60 lit<:rsftnin, decelerating 1.1 3.2 1:3

120 liters.knin, square 0.3 4.0 1:13 - - 50 - - 1
NOTE: Assume VT 600 ml, respiratory rate 14 breath¥nin, respiratory compliance 60 mVcmH20, and end-expiratory flow rate~
60 mlf.;.
ABBREVIATIONs:V1, inspiratory flow rate; T1, inspiratory time; T E• expiratory time; I:E ratio, inspiratory-to-expiratory ratio; and
DHI, dynamic hyperinflation.
(Auto-PEEP:10 emH20) piratory arrest before intubation. In this situation, it is best
COPO ASTHMA
PEEP 0 PEEP 8
to avoid hypercapnia, if at all possible. As mentioned ear-
PEEP 0
lier, this may not be easy to accomplish without extracorpo-
M®MW~~
Aow 0.5]
(1.) 0 real C02 removal unless the patient has rapidly reversible
bronchospasm.
ZOs tNN Hypercapnia in status asthmaticus is acute in onset and

therefore is not compensated for by increased bicarbonate.
One approach to acute hypercapnia in status asthmaticus
~ 0.6] ~-- MNV_ JNW1 _______ _ is to ignore the elevated Pac~ and administer buffering
agents to correct acidosis. Unlike metabolic acidosis, how-
ever, buffering acute respiratory acidosis with bicarbonate
is relatively inefficient. Discounting the loss of administered
bicarbonate in the urine and generation of C0 2 through
buffering of protons, even partial correction of severe res-
piratory acidosis will require a minimum of several hun-
dred milliequivalents of sodium bicarbonate in an adult. 20
One animal study did find that administration of sufficient
(.:~0) 10) vvvvv--wwlf' sodium bicarbonate (14 mEq/kg) to preserve a normal pH
during induction of acute hypercapnia (Pac~ = 80 mmHg)
A
prevented an increase in cerebral blood flow and intracra-
FIGURE 30-8 Response to 8 cmH 20 of PEEP in COPD and nial pressure.42 The effect on intracranial p ressure was less
asthma during proportional-assist ventilation. Esophageal certain, however, if a lesser amount of bicarbonate was given
pressure (Pes) indicates a similar reduction in inspiratory effort in slowly to only partially correct pH to 7.15-7.20, as is usu-
both patients. External PEEP did no t affect lung volume (V) or
ally recommended. 20, 42 Another problem with the use of
airway pressur e (Pao) in COPD, but both were increased by PEEP
in asthma. (Adapted, with penrrission, from Ra11ieri, et a.l: Clirr large amounts of bicarbonate is that with resolution of air-
C1rest M ed 17(3):381, 1996.) flow obstruction and hypercapnia, the patient is left with a
therapeutically induced metabolic alkalosis.
production or an increase in physiologic dead space. 1t is As a general rule, unless there is some compelling reason
presumed that h ypercapnia during mechanical ventilation to correct underlying respiratory acidosis (e.g., arrhythmia,
of patients with status asthmaticus is caused by marked in- hyperkalemia, or otherwise unexplained hemodynamic in-
creases in dead space that result from alveolar overdisten- stability), it is probably reasonable to forego attempts to
sion. Normally, an increase in minute ventilation will lower correct serum pH and wait for U1e Paco, to decrease as
Paco2 (doubling the rate should decrease Pac~ by 50%) . airflow obstruction improves. Fortunately, many patients
This may not by the case in patients with status asthmaticus, experience substantial improvement in their hypercapnia
however, because when minute ventilation is increased, the during the first 12 hours of intubation. 43 lf bicarbonate ther-
resulting increase in dynamic hyperinflation may further apy is given, ideally it should be administered by slow in-
increase dead space. AlU1ough the precise effect of minute fusion rather than by rapid bolus administration because
ventilation on Paco, in status asthmaticus has not been well the latter may lead to an acute increase in C02 production
documented, anecdotal experience has shown that efforts and a transient fall in intracellular pH as a consequence of
to reduce an elevated Pac~ by increasing minute ventila- rapid diffusion of C02 into cells. An alternative to sodium
tion may be relatively ineffective. In truth, the hypercap- bicarbonate is tromethamine (THAM), a buffer that does not
nia of severe asthma may not be "permissive" because one generate C02 during the buffering process.20 Even though
may not be able to normalize the Paco 2 through ventilator THAM may offer some theoretical advantages over sodium
manipulation. bicarbonate for buffering respiratory acidosis, its use may
Because the ability to correct hypercapnia may be limited lead to U1e same problem of a posthypercapnic metabolic
and fraught with potential hazards, a reasonable approach alkalosis.
may be simply to choose ventilator settings that usually
provide a safe level of dynamic hyperinflation (tidal vol-
ume of 8-9 ml/kg, respiratory rate of 12-14 breaths per
minute) and accept the resulting Paco2 (see Table 30-2) . Nonventilator M anagement
Fortunately, hypercapnia in status asthmaticus seems to be
generally well tolerated, with truly serious adverse conse- All ventilated patients with severe asthma require bron-
quences being quite uncommon.20 Perhaps the most seri- chodilators, corticosteroids, and sedation. In rare instances,
ous risk of hypercapnia is an increase in cerebral blood flow oU1er nonconventional approaches may be considered.
and intracranial p ressure in patients w ith acute neurologic
pathology. Although unlikely to occur in the setting of sta-
tus asthamticus, there are rare reports of cerebral edema or STANDARD THERAPY
subarachnoid hemorrhage attributed to hypercapnia.39-41 BRONCHODILATORS AND GLUCOCORTICOIDS
Profound hypercapnia is of greatest concem if the patient TI1ere have been no studies specifically examining the use
has experienced profound cerebral anoxia secondary to res- of inl1aled bronchodilators during mechanical ventilation of
656 PART Vlll VENTILATOR SUPPORT IN SPEOFIC SETTINGS
pa tients w ith severe asthma. Studies in patients with COPD liberally, supplemented by short-term intermittent boluses
suggest that either metered-dose inhaler or nebulization is of an NMBA if needed, very few patients with status asth-
beneficial and that the optimal dose of albuterol given by maticus will require prolonged, continuous neuromuscular
metered-dose inhaler is likely to be 4-6 puffs.~<l-46 Because paralysis.
the dose-response characteristics in ventilated patien ts with
asthma is unknow n, assessment of lung mechanics during
ALTERN ATIV E THERAPIES
incremental dosing of inhaled fh agonists may be useful in
determining the optimal number of puffs and dosing inter- The great majority of ventilated patients with severe asthma
val for individual patients using an "n = 1" trial. A similar respond to standard treatment with inhaled bronchodila-
approach might be used when assessing other agents with tors and corticosteroids. Occasionally, however, patients
bronchodilator properties, such as ipratroprium or intra- with very fulminant asthma may be considered for one
venous magnesium sulfate. of several nontraditional approaches in order to reduce
Glucocorticoids are an essential component of the treat- extreme hyperinflation a nd lessen marked hypercapnia.
ment of severe asthma, with a n effect being evident within Strategies that have been reported ancecdotally to be ben-
12 hours of administration. 47 Based on data from nonin- eficial in severe htlminant asthma include the use of a
tubated patients, an initial dose of 1-2 mg/kg per day of helium-oxygen mixture (heliox), inhalational anesthetics or
methylprednisolone or equivalent seems appropriate. 48 ketarnine, nitric oxide, mucolytic agents, bronchoscopy, and
extracorporeal support.
SEDATION AND PARALYSIS
No studies have specifically examined various sedation reg- HELlO X
imens in status asthmaticus. As w ith other causes of respi- The lower gas density of heliox reduces fri ctional resista nce
ratory failure, minimal goals in status asthmaticus would where gas flow is turbulent and, by lowering the Reynolds
include provision of amnesia, anxiolysis, and analgesia nmnber, also encourages laminar flow.12.53 One study re-
and prevention of patient-ventilator dyssynchrony. Patients ported that heliox produced a rapid fall in peak airway
with status astlunaticus present an additional challenge be- pressure and Paco2 of ventilated patients with asthma.54
cause of the need to enforce controlled hypoventilation de- The effects on Pplat and auto-PEEP, however, were notre-
spite acute respiratory acidosis that increases respiratory ported, and it is unclear whether changes in Paco2 were at
drive. 9 A combina tion of propofol or a benzodiazepine (mi- constant minute ventilation.54 A second study of heliox in
dazolam or lorazepam) with a na rcotic (fentanyl or mor- severe asthma found little change in Pac~ when tidal
phine) often proves optimal, and very large doses may be volume and r espiratory rate were held constant. 55 Two
required9 (see Table 30-2). Because most patients improve prospective studies found that a 70:30 mixture of heliox sig-
significantly within 24-48 hours,26•43 prolonged residual se- nificantly reduced auto-PEEP during mechanical ventila-
dation that delays extubation is undesirable. One advantage tion of patients with COPD56•57 (Fig. 30-9). This suggests
of propofol over benzodiazepines in severe asthma is that that heliox may have a measurable benefit in some pa-
this agent often allows deep sedation tha t reverses promptly tients and might be considered for use when conventional
on its discontinuation . A maximal propofol dose of approx-
imately 5 mg/kg per hour is recommended because pro-
longed infusion of very high doses of propofol can lead to FIGURE 30-9 Change in trapped vol ume and intrinsic PEEP in
life-threatening complications.49 response to heliox in mechan ically ventilated p atien ts with
COPD (u = 25). (Used, w itll permissiou, from Lee et al: Crit Care
Large doses of sedatives and narcotics in combination
IVIed 33:968-73, 2005.)
with marked lung hyperinflation may lead to hypotens ion
secondary to decreased venous return. When additional
muscle relaxation is needed in the face of hemodynamic
:g--
t.)
600
instability, it may be safer to administer a nondepolariz- ~ 400

ing neuromuscular blocking agent (NMBA) than increase ~ 200
the dose of sedatives and narcotics. Even when hypoten-
sion is not present, intermittent administration of one or l
~ 0
more boluses of an NMBA may help to provide a period Air-02 Heliox Air-02
of temporary muscle relaxation, during which time seda-
tive doses can be escalated gradually to achieve target lev-
els. Prolonged use of an NMBA may increase the likeli- ,......,
0,.. 20
hood of myopa thy in status asthmaticus (see below), but
::X::
short-term use does not carry significant risk. 50•51 The spe- e
cific NMBA selected is likely not important, although ve- ~
curonium perhaps should be avoided in patients with renal ~ 10
l:tl
failure.52 Intermittent bolusing is preferred to a continu- ~
.!:!
ous infusion because this permits ongoing assessment of !'!
the adequacy of sedation and lessens the likelihood that ·sc:
the patient will undergo Uimecessarily prolonged neuro-
muscular paralysis. When sedatives and narcotics are used
- 0
Air-02 Heliox Air-02
management results in an unacceptable degree of dynamic Ketamine, an intravenous dissociative anesthetic, also has
hyperinflation in patients with status asthmaticus. 2 been advocated for use in severe asthma. This drug, how-
Before using heliox, it is crucial to fully w1derstand how ever, can lead to significant increases in blood pressure,
performance of the ventilator will be affected. 58 Some ven- heart rate, and intracranial pressure. There seems little jus-
tilators become inoperable with heliox, and others require tification for the use of ketatnine in ventilated patients with
adjustments in tidal volume or inspiratory flow rates. Be- status asthmaticus.
cause the ventilator's pneumotachographs may not inter-
pret exhaled tidal volume accurately when heliox is used, MUCOLYTICS
use of a density-independent spirometer in tl1e expiratory The potential benefit of N-acetycysteine as a mucolytic is
limb of the ventilator circuit is advisable to ensure accurate unknown; in an anecdotal report, it seemed to enhance
setting of tidal volume.l2,57 bronchoscopic extraction of mucus plugs.62 Benefit from
rh-DNAse also has been reported. 63
GENERAL ANESTHETICS NITRIC OXIDE

Inhalational anesthetics have potent bronchodilating prop- Although nitric oxide is a relatively weak bronchodilator, it
erties, and several anecdotal reports have described their was reported to be of significant benefit in one small series
use in status asthmaticus.59•60 In the only study to care- of patients with very severe asthma. 64
fully assess lung mechanics, isoflurane resulted in a de-
crease in airways resistance and auto-PEEP in three patients BRONCHOSCOPY
with asthma, although only one had a marked response61 Patients with fatal asthma often have extensive mucoid
(Fig. 30-10). It is possible that unsuccessful trials of inhala- impaction.65 Removal of impacted mucus by bronchoscopy
tional anesthetics have not been reported, and the overall has been reported to lower airway pressures and im-
likelihood of benefit is unknown. Nonetheless, tl1ere are prove gas exchange in ventilated patients with severe
w1questionably individual patients with fulminant asthma asthma. 62 Although probably safe in most instances, there
who may derive benefit from general anesthetics. is a potential for worsening bronchospasm, and several
Isoflurane and sevoflurane are less arrythmogenic than large series have reported good outcomes without use of
halothane and have equal or greater bronchodilator prop- bronchoscopy.18, 26•43 Patients who fail to improve after sev-
erties. All these agents may cause hypotension secondary to eral days of mechanical ventilation might be considered for
their peripheral vascular effects, and an increase in venous diagnostic bronchoscopy to inspect the airways for mucus
capacitance may be particularly detrimental when marked plugs that might be extracted, the goal being to reduce the
dynamic hyperinflation already has compromised venous duration of ventilator s upport.
return. The adverse hemodynamic effects generally can be
mitigated through liberal administration of fluid and with EXTRACORPOREAL MEMBRANE OXYGENATION
vasoactive support if necessary. It is mandatory, of course, Extracorporeal membrane oxygenation (ECMO) has been
that personnel highly skilled in the use of anesthetic agents used in severe asthma. 66 Because severe astl1ma is fully
be responsible for their administration. Some intensive-care reversible, this approach clearly would be justified if there
mtit (ICU) ventilators (e.g., Servo 300 and 900) have a port were an imminently lethal impairment in gas exchange.
to which the anesthesia vaporizer can be attached, and Refractory hypoxemia, however, is tmusual in asthma, and
with appropriate scavenging of anesthetic gases, the gen- hypercapnia generally is well tolerated (see above). One
eral anesthetic can be administered in the ICU. scenario in which ECMO might be considered would be
combined severe impairment in gas exchange together
with extreme hyperinflation resulting in bartorauma or
FIGURE 30-10 The effect of isoflurane on auto-PEEP and change hemodynamic instability. In this situation, ECMO con-
in lung volume (..0. V) in three patients with severe asthma. ceivably could provide a period of stability during which
(Adapted, with permission, from Maltais et al: Chest 105:1401-6, bronchoscopy could be performed to extract as much
1994.) inspissated mucus as possible.
20 1.5
·~ ·~ Death and Complications

-::r:"'
0
1.0 MORTALITY
E
.£. 10
Q.
->
:l
<I
Published mortality rates for patients undergoing mechan-
ical ventilation for severe asthma have varied great! y, rang-
w ...........
w . ing from 0- 38%. A literature review of over 1220 patients
""'~• .
0.5
-
Q.
• reported an average mortality of 12.4%.2 Although the out-
0
:::s
<It
~ come seems to have improved over the last n.vo decades,
perhaps because of more widespread use of controlled
0 0.0 hypoventilation,2. 20 mortality rates as high as 15-20% have
BEFORE DURING BEFORE DURING been reported in series published during the last 5 years. 67·68
658 PART Vill VENTILATOR SUPPORT IN SPEOFTC SETTINGS
Most fataliti es result from cereb ral anoxia secondary to VEl (L)
cardiorespiratory arrest before intubation. Indeed , in a re- 2.2, - - - - - - - - ,
cent analysis of 1223 patients who underwent mechanical
••
ventilation for severe asthma, 80% of in-hospital deaths
2.0 !- 0 0
were preceded by cardiorespiratory arrest before admission
to the TCU.68 This is not to minimize the importance of con-
trolled hypoventilation. Instead, it merely emphasizes that 1.8 "' o
0 Cb
0
0
t•
ICU man agem ent ultima tely may be less important than
-~
8Cb • Hypotension
steps taken in the outpatient setting to prevent asthma de-
teriora tion and avoidance of patient delay in activating the
1.6 ,.. 0 0
0 •• • • Barotrauma
emergency transport system in response to an acute asthma
attack. 1.4 cP<¢
0 0
••
1.2 ,_ 8 8
COMPLICATIONS
0 0
Patients with severe asthma are at risk for many of the 1.0 ~
same complications affecting other ventilated patients,
including nosocomial pneumonia, sinusitis, pulmonary
o.a~
embolism, and gastrointestinal bleeding. Additional com-
plications that result from severe asthma itself or from medi- 0 0
cations used to treat a irflow obstruction and provide muscle 0.6....__ _ _ _ ___.
relaxation include ventila tor-associated hypotension, baro- Absent
trauma, myocardial injury, rhabdomyolysis, lactic acidosis,
neurologic injury, and acute myopathy (Table 30-4). Complications
FIGURE 30-11 Relationship between hypotension, barotrauma,
HYPOTENSION and lung volume at end insp iration (VEJ). (Used, with permissiou,
Hypotension during mechanical ventilatio n for s tatus as th- from Williams eta/: Am Rev Respir Dis 146:607- 15, 1992.)
ma ticus m ost often results from excessive pulmonary hyper-
inflation that impedes venous return. In o ne series, mild to extreme hyperinflation can lead to cardiac arrest with pulse-
moderate hypotension was documented at some point dur- less electrical activity.l7 When a ven tilated patient with se-
ing the course of mechanical ven tilation in 35% o f patients, vere asthma develops significant hypotension, a 1-minute
with risk being greatest in patients whose V Er exceeded apnea trial is recommended. 2 If the apnea trial and a ra pid
approximately 20 ml/kg18 (Fig. 30-11). Although unusual, infus ion of fluid do not restore blood pressure, then less
common causes of hypotension (e.g., pneumothorax, my-
TABLE 30-4 Complications of Mechanical Ventilation for ocardial d epression) mus t be considered.
Severe Asthma
BAROTRAUMA
Complications Likely Mechanism Pneumothorax a lso occurs most often in pa tients with the
Hypotension Primary: Excessive hyperinfla tion, highest end-inspiratory lung volume18 (Fig. 30-11). The in-
sedatives cidence of pneumothorax was as high as 30% in some early
Secondary: Pneumothorax, myocardial series69 but is relatively infrequent ( <10%) when a strat-
depression egy of controlled hypoventilation is used. 9•20, 25•26 •43 In a re-
Barotrauma Excessive hyperinflation cent analysis of barotrauma in various types of respiratory
Myocardial Primary: "StUJmed myocardium" failure, pneumothorax was documented in only 6% of pa-
dysfunction secondary to massive catecl1olamine tient with status asthmaticus.7° Nonetheless, a pneumotho-
release rax may be particularly dangerous in patien ts with severe
Secondary: Severe myocardial asthma because the hyperinflated lungs resist collapse and
hypoxia/acidosis
allow even a small pneumothorax to be under tension, re-
Rhabdomyolysis Primary: Extreme muscle exertion with
sulting in rapid deterioration and sometimes death.2, 67 For
or without hypoxia
Secondary: High dose propofol this reason, clinical (and radiographic) diagnosis of tension
Lactic acidosis Primary: Excessive fh. agonists pneumothorax may be particularly challenging in severe
Secondary: Extreme muscle asthma. 2 Chest tubes always should be placed by blunt dis-
exertion I hypoxia section rather than by the blind trocar method to avoid in-
CNSinjury Primary: Cerebral anoxia secondary to juring the hyperinflated lungs. 2
respiratory arrest
Secondary: Hypercapnia-related cerebral CARDIAC COMPLICATIONS
edema, subarachnoid hemorrhage
Despite the common occurrence of severe acidosis and
Acute myopathy Glucocorticoid$ plus prolonged paralysis
or deep sedation
the use of high-dose inhaled ,82-agonist therapy, cardiac
arrhythmias in status asthmaticus are u ncommon. One
CHAPTER30 MECHANICAL VENTILATION FOR SEVERE ASTHMA 659
' '
•
!I '
~
-
- "
"'1
'
:'·~- A..
-f ..i..fl f
J~f-- f- I-: • --'-
~: '- ~· I
1- _} --~- l. FIGURE 30-1.2 Electrocardiogram of a patient with
~- _._ acute reversible left-ventricular dysfunction caused
by status asthmaticus. Deep inverted T waves in
anterior precordial leads are seen commonly in this
1- ,. condition. (Used, with permission, from Levine et al:
' lL Chest 1. 07:1469-73, 1995.)
reported cardiac complication of status asthmaticus is d e- mechanical ventilation. The pathogenesis of myopathy
creased myocardial contractility with reversible segmental is incompletely understood, but it usua lly has been at-
myocardial wall-motion abnormalities and deep T-wave in- tributed to the combined effects of g lucocorticoids and
versions in the electrocardiogram, simulating myocardial prolonged neuromuscular paralysisSO,Sl (Fig. 30-14). My-
ischemia71• 72 (Fig. 30-12). The "stunned myocardium" of sta- opathy, however, also can occur in g lucocorticoid-treated
tus asthmaticus is similar to that seen after subarachnoid patients with asthma w ho have undergone prolonged.
hemorrhage, severe psychological stress, and other condi- (>5-7 days) mechanical ventilation under deep sedation
tions associated with massive endogenous sympathetic ac- without paralysis?8•79 It is possible that p rolonged near-
tivation and typically has a benign course and no long-tem1 total muscle inactivity, whether induced by neuromus-
cardiac sequelae. 72 cular paralysis or by deep sedation, may increase the
sensitivi~ of muscles to U1e myotoxic effects of cortico-
RHABDOMYOLYS£5 stero ids. 9
Rhabdomyolysis has been reported in patients with status
asthmaticus, presumably as a result of extreme muscular
exertion coupled with hypoxia. 73 Rhabdomyolysis also has
been noted in patients who had received prolonged infu- FIGURE 30-13 Subarachnoid hemorrhage in an 11-year-old boy
sions of propofol in very high doses.49 with status asthm aticus who was managed with controlled
hypoventilation and permissive hypercapnia
LACTIC ACIDOSIS (Paco 1 = 7!)-.35 mmHg). (Use of ketamine may have contributed
Mild lactic acidosis is relatively common in status to increased intracranial pressure.) (Used, with permissiou, from
asthmaticus?4 Lactic acidosis has been attributed to lactate Edmunds eta/; Pediatr Crit Care Med 4;100-3, 2003.)
production by respiratory muscles 75•76 but also can occur
as a result of excessive use of {3 2 agonists. Although more
common when the latter are given intravenously, lactic aci-
dosis also can follow high-dose inhalational therapy with
albuterol. 77 Even a moderate degree of lactic acidosis may
be problematic in patients with significant hypercapnia.
CENTRAL NERVOUS SYSTEM INJURY

As noted earlier, cerebral anoxia is the most common cause
of death in patients with status asthmaticus. 68 Hypercapnia-
induced increases in intracranial pressure potentially could
worsen brain injury following a cardiorespiratory arrest;
overall, however, hypercapnia appears to pose little risk
of long-term neurologic sequelae. 20 Nonetheless, rare in-
stances of cerebral edema or subarachnoid hemorrhage in
status asthmaticus that occurred in the absence of prior
cerebral anoxia have been attributed to hypercapnia 39o-41
(Fig. 30-13).
MYOPATHY
Acute myopathy probably is the most common cause of
morbidity affecting patients with asthma who undergo
I p< .OOt I arrest in young patients with asthma. New Eng! J Med 1991;
8 • 324:359--63.
7
6
-• 6.
7.
Molfino NA, Nannini LJ, Martelli AN, Slutsky AS. Respira·
tory arrest in near-fatal asthma. New Eng! J Med 1991; 324:285-
8.
Mountai11 RD, Sahn SA. Clinical features and outcome in patients
• with acute asthma presenting with hypercapnia. Am Rev Rcspir
5 •• 8.
Dis 1988; 138:535-9.
Meduri GU, Cook TR, Turner RE, et al. Noninvasive positive pres-
4 sure ventilation by face mask: First-line intervention in patients
3 .. ,.. 9.
with acute hypercapnic and hypoxemic respiratory failure. Chest
1996; 110:767-74.
Gehlbach B, Kress JP, Kahn J, et al. Correlates of prolonged hospi·
2 • •• talization in inner-city lCU patients receiving noninvasive and in-
1 ..•
•••••• I
- 10.
vasive positive pressure ventilation for status asthmaticus. Chest
2002; 122:1709-14.
Fernandez MM, Villagra A, Blanch L, Fernandez R. Non-invasive
oL---... mechanical ventilation in status asthmaticus. Intensive Care Med
Not weak Weak 2001 i 27:486-92.
(n=49) (n=20) 11. Kass JE, Castriotta RJ. Heliox therapy in acute severe asthma.
Chest 1995; J 07:757-60.
FIGURE 30-14 Duration of paralysis in patients with and without
weakness (defined clinically) after undergoing mechanical 12. Hess D, Chatmongkolchart S. Techniques to avoid intubation:
Noninvasive positive pressure ventilation and heliox therapy.
ventilation for severe asthma. (Used, wi tlz permissiotz, from
Int Anesthesiol Clin 2000; 38:161-87.
Leatlterma11 eta/: Am J Respir Crit Care Med 153:1686-90, 1996.)
13. Jagoda A, Shepherd SM, Spevitz A, Joseph l'viM. Refractory
asthma: 2. Ainvay interventions and management. Ann Emerg
Med 1997; 29:275-81.
Posthospitalization Prognosis 14. Marik PE, Varon J, Fromm R Jr. The management of acute severe
asthma. J Emerg Med 2002; 23:257-68.
Although in-hospital mortality of patients who receive me- 15. Eames WO, Rooke GA, Wu RS, Bishop M}. Compari.<;on of
chanical ventilation for severe asthma is relatively low, var- the effects of etomidate, pr<)pofol, and thiopental on respira-
ious studies have estimated the mortality from recurrent tory resistance after tracheal intubation. Anesthe1o'iology 1996; 84:
attacks to be between 10% and 25% over the subsequent 1307- 11.
decade. 80 Indeed, prior intubation has been identified as the 16. Franklin C, Samuel J, HuT. Life-threatening hypotension associ-
strongest risk factor for death from asthma. 1 These data em- ated with emergency intubation and the initiation of mechanical
phasize the crucial importance of outpatient management- ventilation. Am) Emerg Med 1994; 12:425-8.
including regular use of inhaled glucocorticoids, avoidance 17. Rosengarten PL, Tuxen DV, Dzulkas L, et al. Circulatory ar·
of smoking and other factors known to increase ailway re- rest induced by intermittent positive-pressure ventilation in a
patient with severe asthma. Anaesth Intensive Care 1991; 19:
sponsiveness, close supervision, and intensive education- 118-21.
following hospital discharge of patients with asthma who 18. Williams TJ, Tuxen DV, Scheinkestel CD. Risk factors for morbid·
undergo mechanical ventilation. ity in m t.'Chanically ventilated patients with acute severe asthma.
Am Rev Respir Dis 1992; 146:607-15.
19. Darioli R, Perret C. Mechanical controlled hypoventilation in sta·
tus asthmaticus. Am Rev Respir Dis 1984; 129:385-7.
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33. Lessard MR, Lofaso F, Brochard L. Expiratory muscle activity ill- 55. Schaeffer EM, Po hlman A, Morgan S, Hall JB. O xygena tion in
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~hapter 31 first-line treatment of exacerbations of COPD associated
with respiratory failure and acidosis.
MECHANICAL The decision-making process about the mode and set-
ting of ventilator support requires knowledge of the patho-
VENTILATION IN physiology of decompensated COPD, which has some pecu-
liarities compared with acute respiratory failure from other
CHRONIC OBSTRUCTIVE causes.14
PULMONARY DISEASE
SONJA KHJRANI
Pathophysiology
GUIDO POLESE
WRENZO APPENDlNI Inefficient gas exchange is a cardinal featur e of patients w ith
ANDREA ROSSI an exacerbation of COPD needing mechanical ventilation.
The associated respiratory failure is characterized by hypox-
emia (ratio of arterial oxygen tension to fractional inspired
oxygen concentration, Pa0 , /Fia,, less than 300 mmHg), of-
ten associated with hypercapnia (arterial carbon dioxide
tension, Pace>z, greater than 45 mmHg) and respiratory aci-
dosis (arterial pH < 7.36). 1•16
PATHOPH YSIOLOGY
Hypoxemia
Hypercapnia HYPOXEMIA
Respiratory Acidosis In general terms, hypoxemia results from the combina-
VENTILATOR ASSISTANCE
tion of pulmonary ventilation-perfusion NA/Q) mismatch-
Noninvasive Positive-Pressure Ventilation
ing, shunt, and reduced alveolar-capillary diffusion capacity
Pressure--Support Ventilation
Proportional-Assist Ventilation and extrapulmonary [Fie>z, minute ventilation, cardiac o ut-
Other Modes of Ventilation put, mixed venous Pe>z<PVe>z)] determinants of Pao, P Dur-
Role of PEEP ing exacerbations of COPD, both intrapulmonary and ex-
Co ntrolled Mechanical Ventilation and Monitoring trapulmonary factors contribute to the hypoxemia.
Stable COPD is characterized by an abnormal distribu-
Home Mechanical Ventilation
Failure and Success of Mechanical Ventilation tion of VA/Q ra tios.18 The abnormal distribution of pul-
Weaning monary capillary blood flow and alveolar ventilation is the
Bronchodilators result of parenchymal destntction and small airways dis-
Mortality ease, respectively. 19- 21 Figure 31-1 presents the four possi-
CONCLUSION ble patterns of VA/0. mismatching. When an exacerbation
occurs, VA/0 mismatching worsens, further impairing gas
Acute exacerbation of chronic obstructive pulmonary dis- exchange (lung failure). Using the multiple inert-gas elinU-
ease (COPD) is a common cause of respiratory failure. Many na tion technique (MIGET), hypoxemia during an exacerba-
such patients need admission to the intensive-care unit tion was found to be caused by the combination of VA/0
(ICU). The institution of mechanical ventilation should be mismatching (46%), low Pv0 2 (26%), and increased periph-
considered when hypercapnia and respiratory acidosis, of- eral oxygen (02) uptake (because of increased effort by the
ten associated with breathlessness and tachypnea, persist or inspiratory muscles to bear the increased mechanical load 14)
worsen despite aggressive and optimal medical therapy. 1- 5 (28%).16 The true shunt fraction is consistently negligible.
In some patients, ventilator assistance is instituted pri- Thus administration of Orenriched air generally is effective
marily to alleviate distressing breathlessness. On occasion, in keeping oxyhemoglobin saturation (Sao,) greater than
respiratory frequency can be abnormally low because of 90%.
extreme hyperinflation. 6 Therefore, an arterial blood-gas Pulse oximetry, although noninvasive and useful for
(ABG) sample should be obtained in Clll patients consid- monitoring oxygen saturation,22 cannot replace periodic
ered for mechanical ventilation to confirm that dyspnea is sampling of the arterial blood in patients with an exacerba-
related to respiratory acidosis and not to other causes that tion of COPD receiving ventilator assistance. 23 - 25 Indeed,
would not benefit from mechanical ventilation. oxygenation is only part of the problem. Hypercapnia a nd
In the last 20 years, use of mechanical ventilation in pa- respiratory acidosis are also major concerns.
tients with exacerbations of COPD and hypercapnic res-
piratory acidosis has undergone profound changes. The
principal d1ange has been the reevaluation of noninvasive HYPERCAPNIA
mechanical ventilation (NIMV),6•7 its rapid rise in Without supplemental 0 2 (while breathing room air), pa-
popularity,8 a nd its extensive application. 9•10 International tients with an exacerbation of COPD can develop hypercap-
guidelines for management of COPD,11 - 13 as well as for nia, which is the result of the ineffective ventilatory pattern
NIMV,1 4•15 recommend the early institution of NIMV as characterized by a rapid (high respiratory frequency) and
663
664 PART Vlli VENTILATOR SUPPORT IN SPECIFIC SEITINGS
Pattems o f Ventilation-Perfusion Distribution In COPO
Broad unimodal - 45% Low -23%

0.8
0.6
0.4
FIGURE 31·1 Characteristic patterns of
0.2 ventilation-perfusion mismatching in patients with
COPD. Ventilation ('VA; gray circles) and perfusion (Q
black circles) distributions plotted against VA/Q ratios
0.001 0.01 0 .1 1 10 100 0.001 0.01 0 .1 1 10 expressed on a logarithmic scale. (Upper left panel)
Approximately 45% of patients show abnormally
broad unimodal VA and Q distributions centered on
lung units with VA/Q ratios dose to 1. (Upper right
High · 1 ~o HigMow-14% panel) In 23% of patients, a bimodal perfusion
0.4 distributi on with blood flow diverted to lung units
with low VA/Q ratios (< 0.1) is seen. (Lower left panel)
0.3 A broad unimodal Q distribution together with a
bimodal ventilation distribution with alveolar
02 ventilation diverted to lung units with high VA/Q
ratios is observed in 18% of patients. (Lower right
0 .1 panel) Approximately 14% of patients show both
bimodal ventilation and perfusion distributions.
Perfusion to nonventilated areas (shunt) is absent in
0 .0 -;---.-11111! these patients and negligible in general. (Used, with
0.001 0.01 0 .1 1 10 100 0.001 0.01 0 .1 1 10 100
permission-from Rossi et al: Respir Care Clin North
VentJlatlon/perfusion ratio Am 8:379-404, 2002.)
shallow (low tidal volume, VT) breathing (Fig. 31-2) leading tilate the lungs14•26 and a reta rded rate of lung emptying.
to reduced alveolar ventilation. Thus the time between two inspiratory efforts is not suffi-
An exacerbation of COPD almost invariably is as sociated cient to decompress the lw1gs to the relaxation volume,27
with increased inflammation and altered mucus transport, generating d ynamic pulmonar y hyperinflation.28- 30 Con-
particularly in the small airways. Hence airway resistance sequently, p ositive end-expiratory alveolar pressure [con-
increases, leading to an augmented inspiratory effort to ven- ventionally named intrinsic positive end-expiratory pressure
(PEEP1)] is present. This pressure must be counterbalanced
by the contracting inspira tory muscles in order to produce
Bronchospasm inspiratory flow31 (Fig. 31-3).
i Airway mucus
Airway intlanm1ation A few cmH20 of PEEP1 usually are present in s table
moderate to severe COPD.32- 34 During acute exacerbations,
Diaphragm ~ PEEP1increases significantly. Consequently, the inspiratory
Air lrappmg i Raw threshold load produces increased work of breathing and
flattening
/ ~ challenges the ability of the respiratory muscles to dear car-

bon dioxide (C0 2) 33 (see Fig. 31-2). The degree of PEEP1 is
j PEEPi i Elastic
related to the severity of resting hypercapnia. 28 Compen-
Muscle / ~ I recoil
satory mechanisms exist35•36 but are inadequate. The com-
bination of increased mechanical load and reduced respi-
weakness / ""' / ""
JoyspneaJ CI'AP/ i Wo~ of ..------1 ratory muscle force may lead to respiratory muscle fatigue
- - PEEP breathmg and eventua l exhaustion oftheventila torypump? 7 Assisted
I
Respiratory
lPPV
~
ventila tion needs to be instituted promptly as a lifesaving
procedure _14
Purro et al3S showed that the mai11 characteristics of
Muscle
Failure
--~ J. VT - +-1 i Paco2j ventilator-dependent patients with extreme COPD are shal-
low breathing pattern; high (P0 _1) , airway occlusion pres-
FIGURE 31·2 General m echanism leading to an increase in Paco2
in patients with COPD and ventilatory failure. Raw, airway
sure, an index of overall neuromuscular drive39 ; high ef-
resistance; PEEPtt intrinsic positive end-expiratory pressure;
fective inspiratory impedance (P0 .JIVT/T1 ratio, where Vr
CPAP, continuous positive airway pressure; IPPV, intermittent is tidal volume, T1 is inspiratory duration, and VT/ T1 is
positive-pressure ventilation; VT, tidal volume. (Used, witll mean inspiratory flow)40; and high P / Pmax for both trans-
pemrission, from Intematiotral Conserrsus Coufuences i11 J'u tens ive diaphragmatic (Pdi) and total pleural (Ppl) pressure.41 A
Care Mcdiciue: Am J Respir Crit Care Med 163:283- 91, 2001.) P0 _,/Vr / T1 ratio greater than 10 cmF-hO/ liter/s and a
CHAPTER 31 MECHANICAL VENTILATION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE 665
0.5 Ventilator Assistance
v
LIS
in
0 ........... . ................ ........................ . ................ ······················

0.5 ex Ventilator assistance can be delivered to patients with an
exacerbation of COPD in different w ays 1: traditional or con-
Ppl
cmH,O
ventional invasive mechanical ventilation (via a n endotra-
-2: [
cheal tube) or noninvasive mechanical ventilation (NIMV)
by means of either negative (intermittent) pressure ven-
10
Pga tilation (iron lung) or noninvasive positiv~press ure ven-
cmH,O
5 tila tion (NPPV). The latter is by far the most common
mode of assistance in patients with exacerbations of COPD.
20 Negative-pressure ventilation is effective clinically46 and
Pdi
cmH,O 0
physiologically47 in the hands of a well-trained team but
has not gained wide popularity.
3s
FIGURE 31-3 Method to detcnnine dyn amic intrinsic PEEP
(PEEPt,dyn) during spontaneous unoccludcd b reathing in a
patient with COPD. (From top to bottom) Records of flow, pleural NONINVASIVE POSITIVE-PRESSURE VENTILATION
pressure (Ppl), gastric pressure (Pga), an d trans diaphragmatic Although a vailable for many years, only in the late 1980s
pressure (Pdi). The firs t vertical line indicates the point and early 1990s was N IMV reintroduced successfully in the
corresponding to th e onset of the inspiratory effort (Pdi swing).
treatment of hypercapnic respiratory failure.M8 Tt soon be-
The second vertical line indicates the p oint corresponding to the
came clear that patients with exacerbations of COPD derive
start of the inspiratory flow . The dotted h orizontal line represents
zero flow . In, insp iratory flow; ex, expiratory flow . Note that
most benefit from NlMV.7- lOA 9 - 51 N IMV can produce sig-
expiratory flow ends abrup tly before inspiration, whereas the Pdi nificant decreases in in-hospital and 1-year m orta lity, need
and Ppl s wings have already begun, and Pga remains constant of endotracheal intubation, rate of ventilator-related com-
during the inteJVal. PEEP1,dy n is measured as the negative plications, rate of ICU admission, and length of ICU and
deflection in Pp l between the onset of the Pdi swing and the hospital stay.51•52 These significant achievements were the
point of zero flow . (Used, w ith pennissiou, from Saetta eta/: Am result of a synergic effort: major advances in the knowl-
Rev Respir Dis 132:894-900, 1985.) edge of the pathophysiology of respiratory failure caus ed
by exacerba tion of COPD, improvement in the technology
of noninvasive ventilators, improvem ent in the interfaces
for the patient-ventilator connection, and the organization
Pdi/ Pdi,max of greater than 40% were associated with in-
of pros pective randomized clinical trials.
ability to sustain sponta neous breathing for more than a few
The best candidates for NIMV are patients w ith dyspnea,
minutes. 38 The ineffective compensa tory mecha nism w ith
increased breathing frequ ency, hypercapnia, and respira-
the low VT caused chronic C0 2 retention. The data of Purro
tory acidosis who ar e able to cooperate with their caregivers
et al38 were collected in a special long-term weaning unit.
and interact w ith the ventilator. The patient shares the act
Nevertheless, the results are in line with many other studies
of breathing with the ventila tor and must trigger each m e-
showing that patients with COPD develop a high respira-
chanical breath. According to international guidelines on
tory drive in trying to cope with an excessive mechanical
COPD11 - 13 and NPPV} 5 NPPV is a first-line intervention,
load.
together with optimal medical therapy and 0 2 supplemen-
tation, for the management of patients w ith hypercapnic
respiratory failure secondary to exacerba tions of COPD. In
RESPIRATORY ACIDOSIS
the firs t few hours, NPPV requires the sam e level of as-
When the lungs cannot remove all the C02 produced by sistance as conventional ventilation .53•54 In appropriate set-
the bod y, or when alveolar ventilation is decreased, respira- tings, NPPV can be as effective as conventional ventilation
tory acidosis occurs. Respiratory acidosis represen ts a Paco2 in reversing acute respiratory failure secondary to decom-
that is higher than normal (>45 mmHg), leading to an arte- pensation of COPD.ss
rial blood pH of less than 7.36. If a patient with respiratory Despite the widespread use of NPPV, many patients w ith
acidosis breathes ambient air, !He-threatening hypoxemia exacerbations of COPD and respiratory acidosis s till need
ensues. One reason for hypercapnia is inappropriately in- endotracheal intubation and conventional ventilation, 56
creased supplemental oxygen. 42 Supercabia (Pac~ > 150 which may be m ore appropriate.8 It always must be
mmHg) can occur. promptly available in any environment administering
Correction of respiratory acidosis should be performed NlMV. Controlled ventilation can be delivered only in in-
car efully.' The goal is to return
3 4
gH
toward normal limits, tubated patients, whereas assis ted ventilation can be ap-
not to return Pco2 to normal. - A Vigorous increases in plied either throu gh an endotracheal tube or noninvasi-
minute ventilation should be avoided because of the risk vely.
of dynamic hyperinfla tion. When d ynamic hyperinflation In patients receiving NPPV, intubation should be consid-
is a concern, and provided that intracranial hypertension er ed w hen NPPV seems to fail,57 - 59 as shown by worsening
and overt hemod ynamic instability do not exist, acceptance of ABGs over 1-2 hours o r lack of improvement in ABGs
of acidemia (pH > 7.2) may be reasonable. 45 after 4 hours.
In many instances, the choice of the ventilator mode d e- In patients with COPD ventilated through a tracheotomy,
pends more on local organizational considerations than on Appendini et al82 showed that 5 cmH2 0 of CPAP plus
scientific guidelines (e.g., physician preference and experi- 10 cmH2 0 of PSV were more effective in unloading the in-
ence, available types of ventilators, team training, and so spiratory muscles than 15 cmH2 0 of PSV. In other words,
on) . Recent approaches tend to give to the patient greater the same global level of pressure assistance achieved a bet-
control of the ventilator either mechanically or through res- ter physiologic result if pa rtitioned between CPAP and PSV
pira tory center drive. 60 rather than when delivered as PSV alone. This confirms the
NPPV can be considered successful w hen ABGs and pH important role of the inspiratory threshold load in COPD
improve, dyspnea is relieved, the exacerbation resolves patents .
without intubation, mechanical ventila tion can be discon- Brochard et ai78 reported differences between various d e-
tinued, and the patient is discharged from the hospital. vices for noninvasive PSV. These differences have an impact
on patient effort.83
PRESSURE-SUPPORT VENTILATION
The most popular mod e of delivering NPPV is pressure- PROPORTIONAL-ASSIST VENTILATION
support ventilation (PSV).61 It was introduced by Brochard Proportional-assist ventilation (PAV) was proposed as a
et aJ 62 as a mode of conventional ventilation. In patients means of bringing one oscillatory pump (tile ventilator) un-
with COPD, optimal PSV decreases 0 2 cost of breath- der the control of another (the patient's controller).B-l,SS With
ing, d iaphragmatic pressure-time index, 62 - 67 and work of PAV, responsibility for guiding the ventilatory pattern is
breathing.4•62•6U8.69 PSV does not worsen dynamic hyper- shifted completely from the caregiver to the patient, vvith the
inflation and PEEP1 in some patients with COPD? 0 - 72 aim of improving patient-ventilator interaction (Fig. 31 -4).
PSV was used preferentially by several groups for NPPV NPPV was considered as an application in which PAV
in patients with acute exacerbations of COPD admitted to an should display advantages over conventional modes. 86 - 89
ICU.4,7· 73- 77 PSVby face mask d ecreases respiratory muscle Nevertheless, the few clinical s tudies performed during in-
activity and workload. 61•77 - 79 The most effective m ode of vasive ventilation90 - 93 and NPPV in patients with acute or
NPPV is the combination of PSV (10-15 cmH20) and con- chronic respiratory failure94 - 97 did not find PAV to be sig-
tinuous positive airway pressure (CPAP) (4-8 cmH2 0).80 nificantly superior to PSV. £nvasive PAV, however, enabled
The only study addressing the effect of noninvasive PSV on greater VT variability than invasive PSV in the face of in-
gas exchange with the MIGET technique showed that NPPV creased ventilatory demand. 90 - 93 Both invasive a nd nonin-
does not improve VA/0 m isma tching significantly, but it invasive PAV improved ABGs and alveolar ventilation and
creases alveolar ventilation by correcting breathing pattern, tmloaded tl1e respjra tory muscles in bo th acute86,8?,98 and
which achieves more efficient clearance of arteria l C02 •81 chronic patients.88•89 Wysocki et al99 found that NPPV-PAV
20 r--------~
~ ---------~------~~--------~-------.--------,
I I I
0 I I I
£ .... .t .~~ .A: :"· .J.. ... A .. .... ~.......... ~.. ,.,.. W&llvMI IIWI lit~
E t - - - - -,- --- - - ~ - - - - - - ~- - - -- - r
-
u
O
~
0 - -- - - -
I
I PAV
I
I
I
I
I
I PSV
I
I
- - - - - -
I I I I I
-20 L-----------------------------------------------------~
15
,. "' ,. . ,.
I I I I I
~
q,
~~ nrY~rl ~ ~ ~ :~y- ~
.-'1 '
:X: I '""I
E
-
I
- - ,_ -
-
u
(/)
0 - :r
I
-1 - - - - ... - - - - - -
8
Q.
- 15
0 60
Time (s)
FIGURE 31-4 Representative tracing in a patient with COPD and chronic ven tilatory failure during proportional-assist ventilation (PAV)
(left) and pressure-s upport ventilation (PSV) (right) showing pressure at the airway opening (Pao) and esophageal pressure (Poes). With
greater assistance during PSV, the occurrence of ineffective efforts increases m mpared with PAV. (Used, witlt permission, from Ambrosino
et al: Tllorax 57:272-6, 2002.)
and NPPV-PSV achieved similar improvements in work of TABLE 31-1 Factors Determin ing Dynamic Pulmonary
breathing and ABGs. Patient comfort, however, was better Hyperinflation and ln td nsic PEEP
with PAV. 100 Patient respiratory mechanics
In conclusion, the most common ventilator setting of Pulmonary flow resistance
NPPV for patients with COPD in acute respiratory failure Expiratory flow limitation
remains a few cmH 2 0 of CPAP, to counterbalance intrinsic Total respiratory system compliance
PEEP, and PSV on top of CPAP to support the inspiratory Added flow resistance
effort and increase VT. 14·80 The role for PAV requires further Endotracheal tube
exploration. Ventilator tubings and circuits
Patient breathing pattern and ventilator setting
lidal volume
OTHER MODES OF VENTILATION Frequency
Tr/T1m
ASSIST-VOLUME CONTROL End-inspiratory pause
With assist-volume control (AVC) ventilation, VT, inspira-
tory flow rate, flow waveform, and trigger sensitivity are ABBREVIATIONS: PBEP, po:.itlvc end-expiratory pressure; Tr/T~r , fractional
set. In patients with COPD and high levels of PEEP,, AVC in:.piratory lime.
ventilation with high inspiratory flow rates is recommended souRce: Used, with pcm1is~lon, from ref. 209.
(provided that plateau pressure is not increased excessively)
because it shortens inspiratory time and increases expi- of PEEP1 is so high that without the addition of PEEP,
ratory time, potentially reducing PEEPr. 101 A VT of about the patient cannot trigger the ventilator. The resulting in-
7-9 ml/kg is pmdent in COPD. AVC ventilation was used effective efforts unduly increase the respiratory workload.
in some studies of NPPV in decompensated COPD,77•102 al- PEEP1 is caused by botl1 intrapulmonary and extrapul-
though PSV is now used mucl1 more commonly.51 monary factors32 (Table 31 -1) in patients wit~ acute r~pira
tory failure, including those with acute resprratory diStress
PRESSURE CONTROL syndrome 11S, I16 and acute severe asthma.116
With pressure-control ventilation (PCV), the maximal pr~s In the presence of expiratory flow limitation, step-
sure generated by the ventilator, the frequency, and the m- wise application of PEEP does not increase end-expirato~
spiratory time are set. VT is the primary output and de- lung volume (EELV) until a level close to PEEPt IS
pends on patient impedance, PEEP1, and ventilator settings. reached.'08 111 • 11 7 When PEEP exceeds initial PEEP,, EELV
Maximal airway and alveolar pressures are controlled. With may increase, worsening pulmonary hyperinflation. In
rapid variations in patient impedance, as in acute COPD, ventilator-dependent patients with COPD, several stud-
PCV will not deliver a consistent VT. 103 This mode basically ies showed that low levels of PEEP induced a reduc-
is restricted to conventional ventilation.
tion of the inspiratory threshold load witl1out affecting
EELv.m - 113,118- 120 Although there is still debate on "opti-
INTERMl TTENT MANDATORY VENTILATION mal PEEP'' in ventilated patients witl1 COPD, a reasonable
With intermittent mandatory ventilation (JMV), unsynchro- approach is to set a few cm H20 of PE~P and ensur~ that
nized breaths were feared to predispose patients to hyperin- the patient is comfortable and able to tngger all ventilator
flation and barotrauma. 4 Synchronized intennittentmanda- breaths. Alternatively, PEEP1 can be measured. 121 - 124 The
tory ventilation (SlMV), an evolution of IMV, was designed more accurate method requires an esophageal balloon and
to avoid dyssynchrony. It was believed that SIMV would sometimes an additional gastric balloon to assess changes in
facilita te weaning by allowing patients to assume graded abdominal an d transd rap . Iuagrna 0· c pressures. 125-127 Mea-
increases in the work of breathing. Aslanian and Brochard64 surement of changes in abdominal pressure allows correc-
considered this mode to represent "an interesting example tion of PEEP1 for expiratory muscle activity' 25· 126·128and a
of the discrepancy which can be found between the objec- more exact computation . o f P'EEP,.24'33' 129
tives of a modality of partial ventilatory support and its real During controlled mechanical ventilation (CMV), the res-
physiological effects." Two studies showed that SIMV was piratory muscles are inactive and cannot be unloaded. Nev-
the least effective weaning method, 104· 105 although another ertheless, Rossi et al 130 showed that replacement of PEEPr
study found SIMV to be useful in weaning of patients with with PEEP (of 50-100% of the measured static PEEP!) may
COPD. 106 rn the latter study, addition of PSV tended to pro-
improve, slightly but significantly, VAIQ mismatching and
duce a slight but not significantly shorter weaning time.
oxygenation without any effect on cardiac output.
In conclusion, low levels of CPAP / PEEP are recom-
ROLE OF PEEP mended in patients with COPD needjng mechanical ven-
tilation, either conventionally or by NPPV.
PEEP is one of the most successful clinical applications of
respiratory physiology. It was introduced 40 years ago in the
management of patients with acute respiratory failur~Y77
CONTROLLED MECHA NICAL VENTILATION
TI1e effect of PEEP in COPD depends on the mecharusm
AND MONITORI NG
of PEEP1 and its magnitude. 108 - 110 Several studies docu-
mented that PEEP1 is common in ventilator-dependent pa- CMV is used less commonly in the ICU than in the past be-
tients with COP0.32,38,111 - 114 In some instances, the level cause of wider use of NIMV and in1proved phannacologic
668 PARTVill VENTILATOR SUPPORT IN SPEOFIC SETTINGS
1 Flow
1
0.5 Occlusion
t 0.s
en
:::. 0 -r I
(I
r' v _occlusion
-0.5
-1
-0.5 v
A 0 5 10 15 20
I
Airway Pressure
40
q. 30
I
E 20 '-
0 11 .7
r T 5
5 10 15 20 0·~--~----~----~----~~=d
B Time (s) 0 2 4 6 8 10
Time (s)
FIGURE 31-5 Measurement of static intrinsic positive
FIGURE 31-6 Tracings of flow and pressure at the airway
end-expiratory pressure (PEEPr,s1) by the end-expiratory occlusion
opening in a ventilated patient with COPD in whom an
maneuver in a pa tient with COPD. The arrow in 8 indicates the
value of PEEP1,51 • (Used, with pennission, from Nucd eta/: JAppl end-inspiratory occlusion during constant-flow inflation has
been performed. After end-inspiratory occlusion, there was an
Plrysiol 89:985-95, 2000.)
immed iate drop in pressure from the maximum value (Pp eak) to a
lower value (P1 ) and then by a slow decay to an apparent p lateau
treatment of COPD.80 CMV, however, provides a unique op- (Pplat), whiclt is achieved after 2 seconds. (Used, with permission,
portunity to measure passive respiratory mechanics.24,129 from Rossi et a/. 133 )
Measurements can be performed using offline (i.e., ven-
tilator facilities, physiologic equipment, or interfering
maneuvers) or online (i.e., acquisition equipment, mathe- During relaxed expiration, d ynamic pulmonary hyper-
matical models, and continuous brea th-by-breath analysis) inflation, if present, can be computed from the difference
techniques. Several studies have shown that r espiratory me- in volume between the end-expira tory volume of relaxed
chanics are severely abnormal in ventilated patients w ith expiration a nd the end-expiratory volume of the preced-
COPD, particularly in the early days of ventilationl 31 and ing breatl1. Expiratory flow limitation also can be disclosed
at the end stage of the disease.38 by the lack of change in flow with alteration in pressure
The rapid airway-occlusion technique is a simple method at the airway opening (PEEP, NEP: negative expiratory
for assessing respiratory mechanics based on airway open- pressure)28· 141 or flow resistance. 121 , 14 "~
ing pressure and flow measurements.132·133When applied at The measurements just mentioned are not suitable for
the end of expiration [end-expiratory occlusion (EEO); Fig. continuous monitoring.142·143 Accordingly, new interest has
31-5], this technique provides a measure of the static PEEP1, focused on online monitoring of respiratory m echanics in
also known as auto-PEEP.132 If applied just before the end ventila ted patients33' 122·144 because it enables early detec-
of inspira tion [end-inspiratory occlusion (EIO); Fig. 31-6], it tion of changes in a patient's status, thus enabling rapid
enables meas urement of most variables of respiratory me- therapeutic intervention. The monitoring systen1S currently
chanics [static elastance (Est), interrupter resistance (Rint), used, however, are based on the assumption of a first-order
and to tal flow resistance (Rtot)].24·129 linear model of respiratory mechanics, w hereas resistance
Rint represents airway resistance. Rtot represents total and elastance are known to be dependent on volume and
respiratory system resistance after subtracting flow resis- airflow.
tance of the endotracheal tube.134- 140 In ventilated patients One algorithm to track respiratory pa rameters in real
with COPD, ~R (the d ifference between Rtot and Rint, time is the recursive least-squares (RLS) algorithm. 145 Nucci
caused by tissue-stress adapta tion and time-constant inllo- et al33, 144 have adopted a modified RLS algorithm based on
mogeneity within the lungs) amow1ts to almost 50% of Rtot; nonlinear behavior of respiratory mechanics,' 46 combined
this indicates that the periphery of the lungs contributes sig- with a classic first-order model and continuous measure-
nificantly to total flow resistance. 133 ment of airflow and airway pressure, to estimate respira-
During CMV, dynamic PEEP, (PEEP1,dyn) represents the tory mechanics in ventilated patients, including those with
lowest regional PEEP1 that has to be counterbalanced by COPD. The mean estimated values weighted on inspiration
the positive pressure of the ventilator to start inspiratory are updated on a cycle-by-cycle basis. Nucci et ai33 com-
flow (Fig. 31-7). This can be assessed by superimposing pares different methods of measuring PEEP, (Fig. 31-9). The
flow- airway pressure loops and looking at the point where varying numbers reflect different physiologic connotations
pressure tracings cross the zero flow33 (Fig. 31-8). With of the data obtained with the different techniques.
severe airflow limita tion, considerable regional variations Recently, Volta et al147 applied a different method based
in mechanical time constants exist. Thus the value of on least-squares fitting with a first-order model, keeping re-
PEEP1 may vary between different measurements and be sistance and compliance constant over th e whole breathing
tmderestimated.s cycle. They concluded that data weighted on inspiration
CHAPTER 31 MEO-iANICAL VENTILATION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE 669
were acceptable i11 patients with and without expiratory
flow limitation.
Khirani et al148 proposed a new method based on a math-
ematical model for noninvasive detection of expiratory air-
flow limitation. The model parameters were identified via
1s
a nonlinear curve-fitting method (Levenberg-Marquardt).
Expiratory airflow limitation was correlated with a sharp
increase in a parameter of the model, which represents re-
I sistance of the compressible airway. Agreement was found
Pdi 10( ] PEEP1 between flow-volume curve indications and model simula-
(em Hp)
I tions for severe expiratory a irflow limitation.
I
Future studies should focus on online monitoring when
respiratory activity is present because most modes involve
assisted ventilation.
0
Pga [
HOME MECH ANICAL VENTILATION
(em H2 0) 10 --:---------~-.......---~
Most patients treated with NIMV can be wea11ed within a
few days. If NIMV is needed for more tha11 1 week, this
suggests that long-term NIMV may be necessary, and the
patient may need to be referred to a center providing home
N1MV. Long-term domiciliary NIMV should be considered
Peso -10[ I in patients with COPDwho have had three or more episodes
(em H20) I ]PEEP1
0 I
of acute hypercapnic respiratory failure in the preceding
I
year. The role of long-term nocturnal NIMV in COPD is not
yet clearly established. 15 Chronic NPPV should not be pre-
FIGURE 31-7 Tracings of flow, transdiaphragmatic (Pdi), gastric scribed systematically in patients with COPD and chronic
(Pga), and esophageal (Pes) pressures in a representative patient ventilatory failure, although it may produce benefit in se-
with COPD during tidal breathing. Tidal volume was 0.75 liter. lected yet-to-be defined patients.149 Some patients with end-
The vertical dashed lines correspond to the start of inspiratory stage COPD undergo tracheotomy and become chronically
flow. Note that expiratory flow ends abruptly at the end of
ventilator-dependent.6
expiration ("truncated" appearance), whereas the Pdi and Pes
swings (inspiratory effort) already have begun, and Pga remains
Because home ventilation is applied long term and deteri-
constant in the interval. The difference between the onset of orations can occur quickly and out of sight, it is important to
swings in Pdi and Pes and the point of zero flow on the Pes include a monitoring strategy. 150 Peak flow, oximetry, and
tracing represents the intrinsic PEEP (dynamic), which has to be leaks can be monitored by patients themselves. Spirometry
coun terbalanced by the inspiratory muscles in order to start and muscular pressure measurements can be monitored fre-
inspiration. (Used, with pennissiou, from Rossi et nl.218 ) quently by staff visiting the home.
45 10 --- _..........._ ,_ ........ ____ _ . .,._

· ·----"'~---·
40 9 ---·"1-..........._ r __...,.. ___.,f ...- -...

; J
35 8 ...- ............!........ ---...~-- ....- ... -~-- ... -..... .

~
0
30
-
~ 7 .._ ... __. __ .,,t...
I
. •
·~· --~ -· ~--- . . .-...
I
-1-~
X"'
-;; 6 ~·- ·-·-t-·---·-- ~--·-·-
§ 25
~
"~
20
-
~
u 5
~ 4
_...,_..______
I
•:----·-+-··-·-·
---- - -o
.
,
0..
15
'"'
0.. 3 !
<
10 PEEPi.dyn
5
0 ~--~~--~----~--~
-0.1 -0.05 0 0.05 0. 1
-0.5 0 0.5 1.5 Flow (lis)
A Flow (1/s) B
FIGURE 31-8 Determination of dynamic PEEP1 (PEEP1,dyn>· A Airway pressure (Paw) versus flow diagram. Twenty-two consecutive
ventilatory cycles are s uperimposed. Inspiration is rightward. Note that the start of inspiration precedes the zero flow (dotted line). The
dashed box in panel A is magnified in B. Dynamic PEEP1 (PEEPt,dyn) is measured as the difference behveen the value of Paw at zero flow
and end-expiratory pressure. The small end-expiratory pressure reflects the resistive pressure consequent to end-expiratory Bow and is
included in the value of PEEP1,dyn· (Used, witlr permiss·iou, from Nucci et al: f Appl Pllysiol 89:985-95, 2000.)
670 PART Vill VENTrLATOR SUPPORT IN SPECIFIC SETIINGS
20 20 15
R = 0.91 R = 0.65 ... R = 0.73
/ ...
15 / 15 /
'0 ...
'0 / c 10
... ...
/
......
.~
,.
0 / >-
E
a: "• '0_
a: /
/
•......
... ... ...
10 / 10 / 0..
w / w w
w w / w .1. 1
~
u 0.. 0.. 5
0..
5 /
...... "' 5
.1.
0 0 "' "' 0
10
0 10 20 0 10 20 0 5 15
PEEPi,st PEEPi,st PEEPi,dyn
FIGURE 31-9 Identity plots comparing values of static (st), dynamic (dyn), and model (mod) PEEP, at zero end-expiratory pressure (ZEEP).
Model PEEP 1 was computed according to the RLS as suggested by Nucci et al.33 The values obtained by the three methods are
significantly correlated. Dashed line is the identity line, an d solid line is computed accord ing to regJ"ession analysis. R, coefficient of
correlation. For further explanations see text. (Used, w itlr permissiou, from Nucci et nl: TAppl Plzysiol 89:985-95, 2000.)
FAILURE AND SUCCESS OF MECHANICAL ries risks.160 Weaning failure is associated with increased
VENTILATION work of breathing and a high tension-time index.161 Dy-
Complications during mechanical ventilation in patients namic hyperinflation is a major determinants of weaning
with COPD are similar to those in other groups of failure. 116•'l4S, 162 Decreasing the breathing load and increas-
patients. 1•2•5 Dynamic hyperinflation is a major factor re- ing respiratory muscle capacity are the major strategies for
sponsible for ventilator dependency and weaning failure. 162 achieving successful weaning. Purro et a1 38 suggested that
In the presence of dynamic hyperinflation, high alveolar measurement of Po.1 and breathing pattern may help to dis-
pressures ensue and may cause pneumothorax, ventilator- cover why some patients are ventilator-dependent.
induced lung injury, or hypotension. The latter occurs most Three randomized trials sugges t a place for NPPV in
often immediately after intubation.1 weaning selected patients with COPD. 163- 165 NPPV wean-
NPPV decreases mortality from acute respiratory failing was associated with a shorter duration of invasive
ure, need for endotracheal intubation (in more than SO% of ventilation. Two other studies failed to s how a benefit of
patients when used as initial treatment151), treatment fail- NPPV.166 •167 Further studies are needed to assess the role of
ure, and complications of intubation and ventilation.152 A NPPV.168
face mask achieves more rapid correction of hypercapnia
than a nasal mask during NPPV7•74• 153· 154 and can be more
Exacerbation of COPD requiring ventilatory support
effective. 76 Use of helium-oxygen (He02) during NPPV
markedly enhances the ability of NPPV to reduce patient
Contraindications for NIPPY?
effort and improve gas exchange. 155
Factors associated with success of NPPV include younger
age, ability to cooperate, lower acuity of illness, an experi-
enced team of caregivers, and availability of resources (mon-
itoring). NPPV fails when the patient either needs intuba-
~
Weaning
tion or dies because intubation is not performed (i.e., for from lul\fV
ethical reasons or because it is not available). Adjustments IM onitoringl
of the mask and ventilator settings are essential during the If improvement of: pH. PaC0 2 - - - - .
first 30-60 minutes of NPPV; patients who show improve- clinical status?
ment in gas exchange within the first hour are more likely
to avoid intubation.8
The Italian NPPV study group recently proposed two Gradual weaning from
charts for predjcting the risk of failure with NIMV in pa- NIPPY until complete Continue Nl PPV
tients with exacerbations of COPD (at admission and after removal
2 hours of NPPV). 57 Figure 31-10 presents an example of a
flowcl1art that can be used as a simple tool.
WEANING
Most ventilated patients are weaned easily from the ventila- FIGURE 31-10 Flowchart for the use of noninvasive
tor, although some require considerable time.156• 157 Difficult- positive-pressure ventilation (NIPPV) during exacerbation of
to-wean patients have a high hospital mortality and poor COPD with acute respiratory failure. MV, mechanical ventilation;
long-term prognosis.158•159 Reintubation should be avoided l nMV, invasive MV; Paco2 , arterial carbon dioxide tension.
because it carries a 6 to 12-fold increased risk of mortality. (Modified, w itlz pennissiou, from Celli eta/: Eur Respir J
Continuation of unnecessary ventilator support also car- 23:932-46, 2004.)
Ceriana et al169 assessed the value of a decision flowchart TAB LE 31-2 Controlled Oinical Trials of Conventional
in d eciding whether to wean tracheotomized patients Therapy versus Noninvasive Mechanical Ventilation: 1-Year
Survival
receiving long-term ventilation. They removed the tra-
cheotomy cannula in about 80% of patients without major Author (Ref.) II Conventional Therapy NIMV
complication. It is important to note that " protocols (and
the weaning parameters therein) are meant to help guide Plant (184) 118/118 54% 62%
and expedite, and they never should substitute for common Bardi (52) 15/ 15 53% 87%
sense."170 Confalonieri (185) 24 / 24 50% 71 %
Vitacca (186) 27/ 30 37%" 70%
BRONCHODILATORS ABBREVIATIONS: 11, number of patients in each group, NIMV, noninvasive me-
chanical ventilation.
Guidelines80·171 recommend inhaled bronchodilators as "A ll patients were intubated in tlte conventiona l therapy group.
first-line therapy in the management of COPD and dis- souRcE: Used, with permission, from ref. 189.
courage the use of systemic corticosteroids in stable pa-
tients. Short-acting bronchodilators (,8-agonists, anticholin-
ergics, or the combination) are the key component. 172 Bach et and Plant et al 51· " 84 showed that addition of NPPV to stan-
al173 found no significant difference between ,B-agonists and dard therapy in patients with acute respiratory failure im-
anticholinergics. No substantial data demonstrate the supe- proved in-hospital survival only in the subgroup with an
riority of combination therapy over either agent alone. 174 exacerbation of COPD. 195 Ant6n et al196 found the evolution
Turner et al175 showed no difference between adminis- of ABGs, particularly pH, after 1 hour of NIMV to be the best
tration via a nebulizer versus metered-dose inhaler with predictor of outcome. Although NIMV reduces in-hospital
spacer. mortality, its effectiveness needs to be monitored.s1,55,184
Administering bronchodilators to intuba ted patients is Girou et al152 and Carlucci et af197 recently reported a
challenging.172• 176 To improve drug delivery to the airways, learning effect with the use of NIMV over an 8-year period.
a spacer device is helpful during conventional ventilation The efficacy of NIMV teclmique also d epends on the skill
or NPPV.m · 178 Several studies document that the inhaled and motivation of the care team. 78
route is at least as effective and safe as parenteral adminis- Table 31-3 presents the risk differences for hospital mor-
tration in ventilated patients. 177- l s t tality rates between NPPV and control groups in several
studies and clearly shows the benefit of NPPV. Those stud-
ies concluded that NPPV was indicated in patients with a
MORTAUTY severe acute exacerbation of COPD but not in patients with
COPD is a leading cause of death worldwide and the only mild exacerbations of COPD. Esteban et aP 98 reported that
major caus e of deaU1 still rising.80• 171 The rate of hospital- survival of ventilated patients is related to factors at baseline
ization for acute exacerbations of COPD is high, although (start of mechanical ventilation) and to the development of
knowledge about critical determinants is incomplete. complications and patient management in the ICU.
Connors et al 182 studied the outcome of patients hos- NIMV is now well established in the management
pitalized for acute exacerbations of severe COPD in five of COPD, and more patients should survive an aettte
hospitals. They found that 11% of the patients died within exacerbation.199 Because patients who receive NlMV for an
6 months of the in-hospital period and 43% after 1 year. Sen- acute exacerbation of COPD are at high risk for hospital
eff et a1183 observed a mortality of 24% after 1 year among
patients hospitalized for an acute exacerbation ofCOPD; in
TABLE 31-3 H osp ital Mortality Rates, Expressed as Risk
patients 65 years of age or older, mortality doubled at 1 year.
Difference, for Severe and Nonsevere Exacerbations of COPD
The need for mechanical ventilation on admission did not
influence short- or long-term outcomes. Study (Ref.) Risk Differ('nce
Only one study has compared the outcomes between
NPPV and conventional ventilation in an ICU environ- Severe ('Xaccrbations
ment; no difference in mortality or complications was Bott et al (210) 25
Servillo ('t at (211)
observed.55 Table 31-2 shows 1-year survival in patients 0
Brochard et a! (190) 22
with COPD receiving conventional therapy or NIMV in Angus et al (212) 45
four studies. 52•184- 186 Survival was better in the NIMV Avdeev et al (213) 20
group. Some studies showed a 1-year survival rate of 44- Celikel et aJ (214) 10
66% after invasive ventilation in patients wiU1 COPD and Plant et at (51) 12
respiratory failure. 186 -"~ 88 Plant and Elliott"' 89 found that Confalonieri et a! (58) 12
survival after invasive ventilation was worse than after Dikensoy et al (215) 8
NIMV. Nonsevere exacerbations
NPPV reduces mortality in patients with COPD in hyper- Barbe et al (216) 0
capnic acute respiratory failure .10·14·152•190- 192 Several stud- Keenan et a! (217) 2
ies support the early use of NPPV in this setting.107- 116 The
N OTE: Risk differences, with the exception of 0%, indicate an ou tcome in favor
benefit of early application of NPPV appears to be greater ofNPPV.
than in the case with invasive ventilation.193 Keenan et al194 souRCE: : Modified, w ith permission, from Keenan et al.a
readmission and death,199•200 E1liott suggested that home 4. Ambrosi110 N,Simonds AK Mechanical ventilation. In: Muir J-F,
N1MV might improve their long-term outcome. 199 Ram Ambrosino N, Simonds AK, editors. The Ew·opean Respiratory
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Chapter 32 conditions associated with respiratory impairment and
failure.
MECHANICAL
VENTILATION IN Overview of Pertinent Pathophysiology
N EUROMUSCULAR TI1e primary muscle of inspiration is the diaphragm, which
is innervated by the third through fifth cervical nerves. In
DISEASE addition, the external intercostal muscles provide stabil-
AHMET BAYDUR
ity to the rib cage and prevent its inward collapse d uring
diaphragmatic contraction. With ascending paralysis, such
as with Guillain-Barre syndrome or traumatic quadriple-
gia above the no level,4 there are reductions in vital ca-
pacity and other volume subdivisions, as well as rib-cage
distortion with inspiratory effort. These changes result in
regional ventilation-perfusion mismatching, particularly u1
OVERVIEW OF PERTINENT PATH OPHYSIOLOGY the dependent portions of the lungs. An early increase in the
VENTILATOR TARGETS IN alveolar-arterial oxygen (02) gradient can be found in some
NEUROMUSCULAR DISEASE patients with neur omuscular impairment long before hy-
EXPERIENCE WITH TRADITIONAL percapnia develops.5.6 Gas exchange worsens during sleep
MODES OF VENTILATION secondary to alveolar hypoventilation, inhibited intercos tal
ROLE FOR NEWER MODES OF VENTILATION and accessory muscle activity, a nd dead-space ventilation
ROLE FOR PEEP induced by rapid shallow breathing6- 8 (Fig. 32-1). Despite
SELECTING VENTILATOR SETTINGS muscle weakness, central drive in patients with neuromus-
VULNERABILITY TO VENTILATOR cular and chest-wall disorders often is increased.9
COMPLICATIONS With reduction in lung volume, respiratory compliance
ADJUNCTIVE THERAPY decreases, adding to the elastic load of already weakened
Glossopharyngeal Breathing (GPB) inspiratory muscles. 10 Thoracic scoliosis, often associated
Assisted Coughing with diso rders such as poliomyelitis and muscular dystro-
Mechanical Insufflation-Exsufflation Devices phy (Fig. 32-2), further reduces respiratory compliance, re-
TIMING OF TRANSFER FROM ICU sulting in an increase in inspiratory drive and altered force-
TO THE COMMUNITY length and force-velocity relationships.n· 12 The diaphragm
LONG-TERM SURVIVAL AND QUALITY OF LIFE has to carry most of thjs respiratory load and eventually
IMPORTANT UNKNOWNS AND THE FUTURE may fatigue. The fatigue threshold of the diaphragm in
SUMMARY AND CONCLUSION quadriplegic individuals is lower than in normal subjects
(0.10-0.12 versus 0.15, respectively).13
TI1e earliest application of assisted ventilation in patients Respiratory impairment in patients with neuromuscular
with neuromuscular disease was with the iron lung dur- disease generally is proportional to the number of respi-
ing the poliomyelitis epidemic in the 1940s and 1950s. ratory muscles involved. Measurement of maximal static
While cumbersome and associated with problems re- mouth pressures (Pmax) provides a guide to the degree of
lated to nursing and bronchial hygiene, this device saved respiratory muscle weakness (although not necessarily of
many lives, permitting most patients with severe respira- general muscle weakness) and is an adjunct to assessing
tory insufficiency to recover, become ventilator-free., and the need for assisted ventilation. In chronic stable neuro-
go on to lead productive lives.1 In most cases, the de- muscular disease, maximal expiratory mouth pressures are
vice was used for durations of a few weeks to up to lower in myopathy than in polyneuropathy and in proximal
2 years, with eventual recovery of ventilatory ftmction. than in distal muscle weakness.14 In healthy people, expi-
Many polio patients with disability continue to reside ratory Pmax increases hyperbolically with lung volume. In
in iron lungs in the conm\Unity after several decades.2 patients w ith neuromuscular disease, however, the lung vol-
Others have converted to tracheostomy-assisted positive.- ume is reduced by 10-20% for the corresponding predicted
pressure ventilation, achieving mobility and the ability to Pmax, a finding thought to be related to intercostal muscle
clear the airv.ray of secretions. With appropriate weaning weakness.10
techniques, some have switched to noninvasive positive- Weakened abdominal muscles reduce the ability to cough,
pressure ventilation (NIPPV),3 particularly those experi- as reflected by decreased peak expiratory flow rates. Bach
encing the late effects of poliomyelitis (postpolio syn- et af15 showed that patients with peak expiratory flows
drome). NIPPV is now the preferred means to support of less than 160 liters/ min need cough assistance to pre-
most patients with chronic neuromuscular disorders and vent accumulation of airway secretions. Cough impairment
is used increasingly to support patients with acute venti- is worsened by inspiratory muscle weakness and glottic
latory insufficiency, such as with Guillain-Barre syndrome dysfunction. Bulbar muscle involvement impairs swallow-
and myasthenia gravis. Table 32-1 lists neuromuscular ing and speech and increases risk of aspiration and upper
679
680 PART VITI VENTILATOR SUPPORT IN SPECIFIC SETIINGS
TABLE 32-1 Neu romuscular Diseases Associated with

--NORMAL
Resp iratory Impairmen t or Failure
---- COAD
·-··- NEUROMUSCU LAR DISEASE
1. Muscle diseases 0.5
a. Dystrophies (Ducchenne, fascioscapulohumcral, limb
girdle)
b. Myotonias
c. Autoimmune/inflammatory myopathies
(dermatomyo~ifu., polymyositis)
--
- ot
d. Metabolic myopathies (hypopho~phatemia, w

::E Vr
glycogen-storage disorders, disturbed lipid metabolism) ::::)
e. Endocrine myopathies (hypothyroidllim, ....J
....
··. ... ' ' ' '
•
hyperthyroidid~m) ~
f. Periodic paralysis •
2.
g. Toxic myopathies (alcohol)
Peripheral neuropathies
••
•• ''
a. Autoimmune/inflammatory (Guillan-Barre) 0 1 2 3 TIME(Sec)
b. Toxic (heavy metal, organophosphates, nitrofurantoin,
hexocarbons) Tt
·. -------=---------·
I
Te
c. Acute intermittent porphyria TroT
d. lick paralysis
FIGU RE 32-1 The res piratory cycle (spirogram) in a normal
e. Shellfish poisoning
individual, a patient with chronic obstructive airway disease
f. Hereditary (Charcot-M<lrie-Tooth)
(COAD), and a pa tient with neuromuscular dis ease. The normal
g. Endocrine (hypothyroidism, hyperthyroidism)
spirogram is divided into its components. VT, tidal volume; T 1,
3. Neuromuscular junction (myasthenia gravis, botulism)
4. Motor neuron disc<lsc d uration of inspi ration; Te, duration of expiration; TTOT• duration
a. Poliomyelitis of total respiratory cycle. Note the decreased VT, increased VTff1,
b. Amyotrophic lateral ~lero~is and decreased T1ffToT of th e patient with COAD and the
c. Spinal muscle atrophies decreased VT but normal VTff1 and T 1/TOT of the patient with
5. JCU-rclatcd weakness neuromuscular disease. (Reproduced, witl1 pennission, from
a. Critical illness polyneuropathy (sepsis, multisystem organ Baydur. Semi11 Respir Med 9:223-238, 1988.)
failure)
b. Neuromuscular blocking agent-related neuropathy
c. Status a~thmaticu~-associated ncuromyopathy (high-dose ings and key physiologic variables. The patient developing
steroid~, aminoglycosidcs, paralytic agents) progressive respiratory failure will experience dyspnea, in-
6. Spinal cord injury creased use of accessory neck muscles, paradoxical breath-
ing, tachycardia, sweating, and inability to say more than
a few words in a row. These findings, however, are non-
airway collapse. l11ese conditions can be exacerbated by the specific. Altered mental s tatus is a sign of severe hyper-
use of negative-pressure ventilators. capnia and acidosis and/or hypoxemia. Individuals with
Dysregulation of breathing in muscular dystrophy and slowly progressive respiratory impairment can tolerate se-
myotonic dystrophy has been attributed to abnormal feed- vere weakness without overt signs but may complain of
back from respiratory muscle receptors and abnormal cen- headaches or sleep disturbances or exhibit cognitive im-
tral ventilatory control, respectively. 16•17 Sleep-disordered pairment associated with daytime hypercapnia with partial
breathing can be related to many factors, including res-
piratory muscle weakness, chest-wall deformities, obesity,
craniofacial abnormalities, bulbar dysfunction, and abnor- FIGURE 32-2 Patient with Duchenne muscu lar dystrophy and
malities in control of ventilation. 18•19 Loss of rib-cage and severe scoliosis.
bulbar muscle tone, particularly during rapid-eye motion
(REM) sleep, results in hypoventilation, decreased inspira-
tory flow, fragmented sleep, and daytime symptoms, well
described in myotonic dystrophy, diaphragmatic paralysis,
and amyotrophic lateral sderosis.20- 22 Obstructive events
during sleep can occur in Duchenne muscular dystrophy
and amyotrophic lateral sclerosis.23·24
Ventilator Targets in
Neuromuscular Disease
Initiating ventilntion in a patient with progressive respira-
tory impairment depends on recognition of clinical find-
CHAPTER32 MECHANICAL VENTILATION IN NEUROMUSCULAR DISEASE 681
compensation. Those with generalized muscle weakness of- ings used in the evaluation of patients with impending res-
ten experience orthopnea because of a combination of di- piratory failure secondary to neuromuscular disease. A use-
aphragmatic fatigue, an unstable chest wall, and cephalad ful guide to diaphragmatic weakness is the comparison of
pressure exerted by abdominal contents on the diaphragm. the VC measured in the seated and supine positions. Reduc-
By contrast, patients with quadriplegia often prefer the tions in VC of 12-65% have been recorded in patients with
supine position because the diaphragm assumes a greater neuromuscular diseaseM·30- 32 (except in those with trau-
appositional area with respect to the abdominal wall, in- matic quadriplegia 4•25) on assuming the supine position.
creasing its resting length and force generation. Another Electromyography and nerve conduction studies provide
explanation has been a reduction in the residual volume diagnostic assistance with respect to a neuropathic or my-
occuring in the recumbent position.25 opathic cause of muscle weakness, particularly in acute ill-
Measurements of vital capacity (VC) and total lung capac- nesses (e.g., Guillain-Barre syndrome, myasthenia gravis,
ity (TLC) provide a guide to the progression of respiratory and critical-illness polyneuropathy or myopathy). They are
muscle weakness, although as much as a 50% reduction also of prognostic value in patients with acute and chronic
of respiratory muscle strength occurs before these values denervation, as in amyotrophic lateral sclerosis and critical-
are reduced.26 In general, patients with less than 10% of illness neuropathies and myopathies.
predicted VC have little tolerance off assisted ventilation. 2•3
Measurements of inspiratory and expiratory Pmax are non- Experience with Traditional
invasive and have established normal values for adults
and children. They are, however, influenced by posture, Modes of Ventilation
lung volume, and effort. Poor effort or air leaks around
the mouthpiece give rise to submaximal measurements. With increasing use of positive-pressure ventilators during
The maximal sniff test is easier to perform a nd better re- the 1960s, many patients with poliomyelitis supported with
flects global inspiratory muscle strength.27 Tests of respi- negative-pressure devices such as iron lungs (Fig. 32-3) and
ratory muscle strength that correlate best with the degree cuirasses (Fig. 32-4) and, subsequently, individuals with
of hypercapnia include tl1e measurement of maximal sniff
esophageal (Pes) and transdiaphragmatic pressures (Pdi) FIGURE 32-3 An iron lung (n egative-pressure) ventilator.
and Pdi after bilateral cervical magnetic stimulation of the
phrenic nerves.28 Measurements of Pdi during transcuta-
neous phrenic nerve s timulation are more reliable and re-
quire no patient effort but have the disadvantage of be-
ing dependent on chest-wall impedance. 29 Measurements
of Pes and Pdi, however, are invasive. For clinical pur-
poses, in patients with amyotrophic lateral sclerosis with-
out significant bulbar involvement, the noninvasive nasal
pressure measured during a sniff has been found to have
greater predictive power than percent predicted VC and
maximal mouth pressures in identifying the risk of ventila-
tory fa ilure.28 Table 32-2 lists physical and functional find-
TABLE 32-2 Indication s for In itiating Mechanical

Ventilation in Neu romuscular Diseases
Relati ve subjective symptoms [orthopnea, frequent arousals

from sleep, morning headaches, daytime
somnolence/ napping, impaired cognitive ftmction (memory,
concentration), fatigut'!)
Cor pulmonale
Vital capacity < 25% of predicted
Maximal im'J'iratory mouth pressure < 25 cmH20
Nasal "sniH" pressure < 25 cmH20
Ch<Ulges in gas exchange indica ting progressive respiratory
failure:
Daytime Paco, > 45 mmHg
Sustained nocturnal hemoglobin desaturation (> 5 minutes or
> 10% of total study time)
Recurrent acute respiratory failure episodes requiring
intervention
Failure to respond to continuous positive pressure alone in
patients with documented sleep apnea syndrome before
neuromuscular weakness is detected
682 PART Vill VENTTLATOR SUPPORT IN SPECIFIC SETTINGS
be over come with proper speech and bulbar training and

use of a one-way speaking valve). Airway vascular fistulas
(with fatal hemorrhage) and tracheobronchomalacia are in-
frequent but potentially devastating complications that can
occur even with uncuffed tracheostomies.33
Not all patients with poliomyelitis, however, elected to
undergo tracheostomy for ventilation. Many learned to use
oral, lip, nasal, or full-face interfaces w ith positive-pressure
ventilators. Some adopted this technique to maintain venti-
latory support v.rhen removed from negative-pressure ven-
tilation, whereas others used these devices solely for part-
or full-time ventilation (Fig. 32-6). Some individuals use a
lip seal during s leep. The use of such interfaces in other
neuromuscular disorders has been successful in avoiding
tracheostomies. They also have been used to wean patients
off tracheostomy-assisted ventilation. 3 An open mouthpiece
circuit can be used in respiratory-dependent neuromuscu-
lar patients with a portable volume ventilator. It has the
disadvantage, however, of alarming when the circuit pres-
sure drops during a system disconnection. Only volume-
cycled ventilators with negative-pressure triggering should
be used because flow-triggered volume ventilators autocy-
FIGURE 32-4 A cuiras.s (negative-pressure) ventila tor. cle when used with an open-circuit mouth-positive system.
Most ventilators can support mouth-positive ventilation in
the assist-control mode.3
other neuromuscular disorders received tracheostomies for Soon after the advent of continuous positive airway pres-
positive-pressure support (Fig. 32-5). Until the 1980s, most sure (CPAP) for the management of sleep apnea, bilevel
positive-pressure ventilators were of the volume-cycled va- positive airway pressure (BiPAP) was introduced to venti-
riety. Advantages of tracheostomies include the ability to late patients with neuromuscular disorders. In contrast with
suction tracheobronchial secretions and avoidance of up- volume-cycled ventilators, these pressure-limited machines
per airway collapse and hypercapnia encountered w ith exhibit tidal volume variability secondary to changes in res-
negative-pressure ventilation. Disadvantages include the piratory compliance or the presence of airway secretions or
necessity of teaching the patient and caregivers how to collapse. Patients with severe scoliosis or other causes of in·
maintain of the tracheostomy and complications such as creased respiratory elastance are likely to benefit m ore from
stomal in fections, airway erosions (from repeated suction- a volume-cycled ventilator than from a BiPAP machine. The
ing), and difficulty with speech and swallowing (tha t can latter device may generate an insufficient pressure "span"
FIGURE 32-5 A patient with Duchenne muscular dystrophy receiving tracheostomy positive ventilation.
CHAPTER 32 MECHANICAL VENTILATION IN NEUROMUSCULAR DISEASE 683
FIGURE 32-6 An individual with late effects of poliomyelitis receiving mouth positive ventilation through a mouth piece.
(i.e., the difference between the end-inspiratory and end- Patients who tolerate NIPPY have a significant survival
expiratory pressures) to ventilate the lungs. 3 Volume-cycled advantage compared with patients who do not tolerate it.
ventilators have the ad vantage of delivering higher volumes With a close working relationship between the patient and
and can provide air "stacking" to maximum insufflations via caregivers, macl1ine tolerance can be achieved in virtually
an oral interface.3 In general, they operate more quietly than aU patients with neuromuscular diseases, including those
pressure-cycled devices, use less electricity, and have alarm with hypercapnic amyotrophic lateral sclerosis. 35 The prog-
systems that are useful for nighttime ventilation. There is nosis in the latter group is particularly poor if they do not
a subgroup of patients with more severe chronic respira- tolerate or accept mask ventilation (death usually within
tory failure for whom pressure-controlled ventilation is also less than a year). One study found a survival disadvantage
inadequate.34 A period of 1 month is enough for judging the in patients treated early with NIPPY for Duchenne muscu-
efficacy of a specific type of noninvasive ventilation, such lar dystrophy,36 but this finding may have resulted from the
as pressure-cycled ventilation, a more comfortable and less exclusion of hypercapnic patients.
expensive mode. Ventilators can be used with a variety of Current evidence concerning the benefits of NIPPY is
nasal, oral, and full-face interfaces (Figs. 32-7 and 8). weak but consistent, suggesting relief of symptoms of hy-
poventilation in the short term and, for the most part, im-
provement in survival in a few small studies.37 Develop-
ment of a home protocol in which oxygen desaturations
FIGURE 32-7 A full-face mask used in noninvasive ventilation.
(Usetl, witlr permissio11, from Haus Rttdolph, Iuc.)
are prevented or reversed using NIPPY and manual and
mechanically assisted coughing techniques results in fewer
and shorter hospitalizations than if such a protocol were not
used.3
Role for Newer Modes of Ventilation

Although pressure-cycled ventilation is the most com-
mon mode of providing ventila tory assistance in the
long-term setting, patient-ventilation asynchrony some-
times occurs.38 Proportional-assist ventilatory mode im-
proves patient-ventilatory synchrony by providing inspi-
ratory flow and pressure in proportion to the patient's
effort.39 In patients with stable chronic respiratory failure
(most with chronic obstructive pulmonary disease), applica-
tion of daytime nasal proportional-assist ventilation results
in improvements in gas exchange and respiratory muscle
FIGURE 32-8 Nasal adaptor (" pillows") used with noninvasive ventilation. (Used, with permission, from Puritan-Beunett Corporation.)
function.40- 42 A lower level of mean airway pressure is gers better tha n with flow-cycled expiratory triggers. 44 As in
counteracted by more time needed to set the ventilato r.42 any patient with impaired left-ventricular function receiv-
In a recent crossover study of 14 patients with chronic vening high levels of PEEP, excess EPAP (and the concomitantly
tilatory insufficiency (10 with restrictive thoracic disorders) increased IPAP) can lead to a decrease in cardiac output.
comparing 5 consecutive nights of pressure-cycled with This could be a problem in muscular d ystrophy- associated
proportional-assist ventilation, both modes were shown to cardiomyopathy.
result in similar toleran ce and were equally effective in re-
ducing daytime hypercapnia and improving nocturnal sat-
uration and symptoms.43
Selecting Ventilator Settings
For most patients who prese11t with findll1gs of respira-
Role for PEEP tory impairment as shown in Table 32-2, ventilato r assis-
tance usually is begun noctumally. The choice of volume-
Positive end-expiratory pressure (PEEP) is used primarily to cycled versus pressure-cycled mode seems to be arbitrary,
improve oxygenation in patients w ith severe and refractory and there are no controlled, randomized trials demonstrat-
hypoxemia. Given that patients with acute respiratory d is- ing the advantage of one over the other. Bach,3 however,
tress syndrome have decreased functional residual capaci- recommends that most patients be started on a volume-
ties, application of PEEP maintains alveolar patency during cycled ventilator to acllieve air "stacking" for maximum
expiration and reverses the ventilation-perfusion mismatch insufflations (see below) a nd for eventual daytime use. Oc-
that results in hypoxemia. Sinularly, PEEP should have a casional pa tients will benefit more from a pressure-cycled
beneficial effect on reversing dependent alveolar collapse ventilator if they have glotticincompetence and cannot stack
in neuromuscular weakness because most patients have re- breaths. If they do use a pressure-cycled device, the pres-
duced functional residual capacities and dependent alveo- sure spans must be high enough to generate adequate vol-
lar units that fail to open during inspira tion. umes. The EPAP should be set as low as possible (e.g.,
The most practical application of PEEP is in the form 2 cmH2 0) unless the patient has underlying lung disease
of tl1e expiratory positive airway pressure (EPAP) deliv- or documented sleep apnea. The spontaneous-timed mode
ered by BiPAP. To the extent that EPAP is applied during is recommended. Mask leaks must be prevented to ensure
noninvasive ventilation, there must be a parallel increase consistent volume delivery. Patients with oral leaks can be
in the inspiratory airway pressure (IPAP) to provide ad- switched to a full-face mask o r, if this turns out to be un-
equate ventilation. While pressure-cycled ventilators can comfortable, to mouth or lip seals. Because the use of such
compensate partially for mask leaks, excessive leaks can interfaces results in an open system, and patients can take
prolong the inspiratory phase and worsen intrinsic PEEP in as much volume as they want, the set volume should be
and patient-ventilator asyncllrony. The latter problem can able to compensate for leaks (starting at 600-1000 ml, w ith
be corrected with the use of time-cycled expiratory trig- eventual increases to 800-1500 ml). 3
Ideally, the effects of NIPPY should be followed up by Ad verse effects of the interface, while not life-threatening,
noctumal monitoring with pulse oximetry and, if available, can lead to serious discomfort and the possibility of discon-
end-tidal capnography. This enables optimization of venti- tinuation. They include skin and eye irritation, drying of
lator settings. For patients who tolerate being off the ventila- mucus membranes, aerophagia, leaks around the nasal and
to r during the day, adaytimearterial blood-gas analysis will full-face interfaces, and abdominal distension with colic.54
determine the longer-term effects of NIPPY. With progres- Leaks can be prevented with the use of chin straps or
sive reductions in lung volume and compliance, the patient oral/ lip seals. 3
may need to be switched to a volume-cycled ventilator to Volume-cycled ventilation in control mode may result
ensure consistent ventilation. in a decrease in effective ventilation secondary to glottic
Noninvasive ventilation may be initiated in the hospital, a closure.ss,s6 Mechanical dysfunction a nd power o utages oc-
sleep laboratory, the outpatient office, or the patient's home cur occasionally, leaving the ventilator-dependent patient
depending on the resources available. Ideally, the procedure vulnerable to acute or progressive respiratory fail ure. In pa-
should be initiated with the patient alert, under the guidance tients with little or no tolerance off the ventilator, a backup
and supervision of experienced personnel. The goals should device is recommended. The physician may have to exert
be to familiarize and encourage the patient with the tech- influence as the patient's advocate to persuade third-party
nique and to establish initial ventila tor settings (determined payors to provide reimbursement for the spare ventilator.
by optimizing both by physiology and patient comfort). In- Other respiratory aids such as rocking beds, pneuma-
spiratory pressures are increased gradually over days or belts, diaphragmatic pacing, and negative-press ure venti-
weeks, usually during daytime hours. Once gas-exchange lators a re covered in other chapters of this book. In general,
and patient-comfort goals have been reached, transition they are not as effective as NIPPY, particularly in patients
to noctumal use is initiated . Evaluations should be con- with severe scoliosis and bulbar dysfunction. Negative-
ducted under monitored conditions, ideally using noctur- pressure ventilators and diaphragmatic pacers can promote
nal oximetry and daytime arterial gases. Polysomnography obstructive a pneas, whereas the disadvantages of diaphrag-
(and where available continuous C02 monitoring) are rec- matic pacers also include their high cost, lack of alarms, and
ommended in patients in whom sleep hypoventilation is potential to fail.
suspected. 45•46
Adjunctive Therapy
Vulnerability to Ventilator Complications GLOSSOPHARYNGEAL BREATHING(G PB)
Hyperventilation is a frequent complication in neuro- Originally taught to persons with poliomyelitis, GPB may
muscular patients receiving tracheostomy-assisted ventila- be useful in other neuromuscular diseases in maintaining
tion. Chronic ventilation at fixed tidal volumes, whether ventilation. In individuals with weak inspiratory muscles
hypocapnic or isocapnic in nature, results in loss of respi- and no tolerance off the ventilator, GPB is a non mechanical
ratory compliance and an increase in airway resistance,47 form of breathing that can be ha ndy in the case of sudden
thought to result from insufficient lung expansion to pre- ventilator failure or to augment spontaneous breathing. 57
dicted inspiratory capacities. The progressive weight loss in With each closure of the glottis (a "gulp"; 40-200 ml) can be
patients with many chronic neuromuscular disorders also inhaled and then exhaled to augment breathing. GPB can be
may result in a decrease in tidal volume requirements. In used to stack breaths (up to 1.6 liters) and promote cough.3
such patients, the delivered tidal volume is better based
on the actual rather than the ideal weight. Reducing the
ventila tion of patients who have been chronically hyper- ASSISTED COUGHING
ventilated results in immediate dyspnea and demands to As noted earlier, respiratory complications are the princi-
restore the previous ventilator settings. 48 - 50 Dyspnea prob- pal causes of morbidity and mortality in advanced neu-
ably occurs as a result of the loss of inhibition of inspiratory romuscular diseases, in particular, inability to eliminate
cell discharge through the Hering-Breuer reflex.51 In con- airway secretions because of ineffective coughing. Effective-
trast to tracheostomy-assisted ventilation, NIPPY provides ness of secretion clearance depends on the peak expiratory
an open system of ventilation with m aintenance of more op- flow rate. A peak flow of less than 160 liters/min has been
titnallevels of Pco2 , allowing restoration of the ventilatory recommended as an indication to provide manually or me-
drive. 3 The correction should be done with small (e.g., 50 ml) chanically a pplied cough assistance. 58 Baseline peak flows
decrements in tidal volume and/ or respiratory rate over a of less than 270 liters/ min are also associated with poor
period of weeks to restore serum bicarbonate concentrations secretion elimination during chest infections. These values
to sufficient buffering capacity. Sometimes mild sedation is should be used as guidelines and not as absolute cutoffs
required to tolerate this maneuver. Periodic assessments of because some patients may develop difficulty eliminating
blood gases or end-tidal or rebreathe Pco2 values 52 should secretions despite higher peak tlows.
be done to optimize ventilation. Ventilator volumes higher Assisted coughing can augment peak flows during
than those used in tracheostomy-assisted ventilation and coughing and increase airway clearance ability. Manually
the use of pressure-limited ventilation can compensate for assis ted coughi11g r equires cooperation on the part of the
leakage around the interface.53 patient and caregiver coordination. The patient achieves
686 PART VIII VENTILATOR SUPPORT IN SPECIFIC SETTINGS
a maximal inspiratory capacity, preferably with use of a Complications with MI-E devices are ra1·e and include
positive-pressure device and breath "stacking," closes his nausea, brad ycardia, tachycardia, and abdominal disten-
or her glottis, and then "le ts go" with the help of an ex- sion. The mos t common reason for intolerance of the MI-E
ternally applied upward and inward abdominal thrust. 59 device is inadequate caregiver training regarding its appli-
A mouth pressure of 60 cmH2 0 or more during relaxation cation. As with any respiratory device used for life support,
at peak insufflation against a dosed shutter usually indi- education of the patient and caregivers is important to en-
cates a recoil pressure adequate to generate a good cough sure best results.
flow.59 Clearance of secretions w ith assisted coughing can Bronchoscopy is useful only in selected cases of atelectasis
prevent respiratory failure and delay or avoid the need fo r caused by mucus plugging and should be tried after other
a tracheostomy. methods of secretion removal have failed.
Patients with quadriplegia can contract the clavicular por-
tion of the pectoralis major to compress the rib cage dur-
MECHANICAL INSUFFLATION-EXSUFFLATION ing forced expiration and cough.63 They have decreased
DEVICES ability to increase intrathoracic pressure, however, because
of paralysis of expiratory rib-cage a nd abdominal muscles.
A mechanical insufflation-exsufflation (Ml-E) device is a Elecb·ical or magnetic stimulation can increase intrathoracic
positive-pressure generator that produces a deep inspira- pressure inversely proportional to the degree of abdominal
tion followed by a powerful sucking action tha t acl1ieves muscle atrophy and may be used to augment d ynamic air-
a high expira tory flow rate. Minimum pressures of 35- way compression and clearance of airway secretions.64
40 cmH2 0 are required to expel secretions but should be
increased gradually over time according to the patient's
comfort leve1.60 Such pressures would be required to over-
come small lungs and stiff chest walls, as in scoliosis.
Timing of Transfer from ICU
Flows that exceed 160 liters/min decrease the risk for res- to the Community
piratory complications and the need for intubatio n and
bronchoscopy.15 The MI-E device can be used with tra- Patients may be hospitalized for a number of acute conse-
clleostomies (Fig. 32-9) and full-face masks, avoiding the quences of respiratory muscle weakness, including pneu-
mucosal trauma that results from suctioning. Frequency of monia, atelectasis, hypoventilation, and sleep apnea. Af-
use can range from once a day to every 4 hours depend- ter the complication has resolved, the patient must be pre-
ing on the amount of secretions produced. Many patients pared for discl1arge into the community using a multidisci-
note that they can breathe more easily after using the Ml- plinary approach incorporating potential caregivers in the
E device. These devices are useful in pa tients with most planning. This goal is best achieved in special care units
neuromuscular conditions,61 including amyotrophic lateral that may be part of the medical facility to which the pa-
sclerosis with bulbar d ysfunction.62 For optimal results, use tient was admitted or a separate facility designed for this
of the Ml-E device can be augmented with application of purpose. During this period, there should be clarification
manual cough technique and proper positioning of the pa- of the patient's advance directives, particularly with regard
tient to promote drainage of airway secretions. to interventions for long-term survival. Jf the patient is sup-
ported with NIPPY, attention must be given to maintenance
of appropriate ventilator settu1gs, the oral/ nasal interface,
FIGURE 32-9 A mechanical insufflati on-exsu ffl ation device
seating, mobility, and nutrition (including gastrostomy or
shown in usc through a trach eostomy. (Used, with pennission, jejunostomy feeding) . Caregivers must be trained in tech-
from J. H. Emerson Co.) niques of manual and mechanical cough assistance. Only
if such measures are unsuccessfu l in clearing secretions
(as in severe bulbar involvement with amyotrophic lateral
sclerosis or postpolio syndrome) should tracheostomies be
resorted to. If the patient has been on long-term
tracheostomy-assisted or negative-pressure ventilation, at-
tempts to transition to NIPPY may be appropriate.3 Many
patients have expressed a preference to NIPPY, even after
many years of having lived with tracheostomies.
Long-Term Survival and Quality of Life

While home NIPPY probab~ improves survival in amy-
otrophic lateral sclerosis35•6 •66 and Duchenne muscular
dystrophy,67 -69 its impact on quality of life in such pa-
tients is not clear. Because assisted ventilation does not pre-
vent the progression of disease, it is difficult to distinguish
dissatisfaction related to disease progression and family
CHAPTER32 MECHANICAL VENTILATION IN NEUROMUSCULAR DISEASE 687
stress related to the implementation of m echanical venti- for coping with the rigors of providing care under poten-
la tio n itself and the various methods need ed to maintain tially stressful conditions. Close involvement by third-party
the patient's airways clear of secretions. Another problem payors and private community-based and governmental
is that there is marked variability in clinical practice among agencies is also crucial to ease the cost of home care.
physicians70- 72 most likely because of a perception that me-
chanical ventilation may prolong suffering in a progressive
disease such as Duchenne muscular dystrophy, spinal mus-
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~hapter 33 Several reports indicate that ICU patients, especially
those needing mechanical ventilation for acute respiratory
CHRONIC VENTILATOR failure, have a relatively poor outcome. 4-s There is a subset
of patients who require prolonged mechanical ventilation
FACILITIES (i.e., > 14 days) because of complex cardiopulmonary dis-
ease or multisystem problems. These patients represent less
STEFANO NAVA than 10% of TCU admissions but consume a la rge amount of
MICHELE VITACCA financial resources. For example Cohen and Booth9 demon-
strated that this small group consumed about 50% of ICU
patient-days and resources. The. extent to which this rela-
tively small population cuts into hospital costs has attracted
the a ttention of experts in the field. Wagner has openly
stated that "there is some level of costs of acute care that
RATIONALE is beyond our society's economic capacity."10
ORGANIZATION OF CHRONIC More important, when these "duonicaUy ill" patients are
VENTILATOR FACILITIES discharged from the ICU because the precipitating cause of
Facilities within Acute-Care Hospitals their acute episode of respiratory failure has been reversed,
Facilities outside Acute-Care Hospitals they still have the need of mechanical ventilation. Thus they
Nursing Homes either require transfer to a long-term care or rehabilitation
CRITERIA FOR ADMISSION facility11 or need frequent ICU or hospital readmissions over
OUTCOMES AND EFFECTIVENESS the subsequent weeks. 12
Comparisons with ICUs Given the dramatically higher number of inpatient
Observational Studies critical-care days in 2000 than in 1985,3 the absolute number
PROBLEMS UNIQUE TO CHRONIC FACIUTIES of patients receiving mecl1anical ventilation has increased.
Finances It is also likely to continue to increase in the near future.
Staffing For example, it was demonstrated recently that the inci-
Size of the Problem dence of tracheostomy for prolonged mechanical ventila-
CONCLUSION tion increased by nearly 200% over the past decade in North
Carolina.n One reason for the sudden rise in tracheotomy
Chronic ventilator facilities (CVFs) are meant to be "pro- is an attempt by physicians to relieve congestion in busy
tected" environments for the treatment of patients requiring ICUs through the transfer of ventilator·dependent patients
prolonged mechanical ventilation. Rarely in medicine has toCVFs.
there been so great a confusion in terminology and wording
to define a relatively simple concept of patient care. On this
particular subject, researchers in different countries or even
in different areas within the same country are essentially Rationale
speaking in different medical tongues.
N umerous names are included under the umbrella of ICUs are not specifically focused on the care of chronicaUy ill
CVFs: long-term acute-care facilities, respiratory special patients for several reasons. First, the "dosed" environment
care units, chronic ventilator-dependent units, regional does not allow optimal comprehensive care for these pa-
weaning centers, ventilator"dependent rehabilitation hos- tients. Weaning from mechanical ventilation is a prolonged,
pitals, prolonged respiratory-care units, noninvasive time-consuming process that involves not only selecting
respiratory-care w1its, high-dependency units, and respi- the best ventilation method for a particular patient14•15 but
ratory intensive-care units. And this is without even con- also attention to aggressive physiotherapy,16 nursing care,
sidering nursing homes and hospice care. counseling, a return to normal eating habits,17 and open
Because "Language is the source of misunderstandings" visiting hours for family members and/ or caregivers. Sec-
(Le Petit Prince, Antoine de Saint-Exupery, 1900- 1944), 1 the ond, patient comfort is enhanced by a return to a more
aim of this chapter is to review the available scientific evi- physiologic circadian rhythm. The latter may be facilitated.
dence about the role of CVFs and to try to dissipate as much through lower noise and activity levels, especially during
confusion as possible in this field so that we do not get "lost night hours, than found in an ICU (Table 33-1 ). Third, the
in translation.'12 disproportionate number of days of care required by cluon-
A 16--year study showed that the number of acute-care ically ventilated patients contributes to overcrowding and
hospital beds in the United States has decreased over time, the limited availability of ICU beds. 23 Last, but not least, the
but the number of critical-care beds has increased progres- system of reimbursement by third-party carriers, even
sively in both absolute and proportional terms. Indeed, the through the diagnostic-related grour, (DRG) system, clearly
total number of non-critical-care beds decreased by 31 %, results in significant monetary loss. 4
whereas critical-care beds increased by 26%3 ; nevertheless, Recently, there has been an increase of facilities in both the
admissions to an intensive-care unit (ICU) are very strongly United States and Europe that specialize in the care of chron-
influenced by bed shortages. Most beds in an ICU are occu- ically ventilated patients. Being DRG-exempt, these facili-
pied by patients requiring mechanical ventilation. ties are reimbursed using a cost-based system. Although the
691
692 PART VIII VENTilATOR SUPPORT IN SPEOFIC SETIINGS
TABLE 33-1 Sound Intensity in D ifferent Envir onmen ts
Mean Day Noise Mean Night Noise Mean Peak Noise

Au thors (ReO Environment Level (d BA) Level (d BA) Level (dBA)
Gabor eta! (ref. 18) ICU 56±2 54±2 67 ±3

Freedman et al (ref. 19) lCU 60±6 57±5 84±5
Aaron et al (ref. 20) In termed ia te ICU many episodes 2:. 80
Balogh et a! (ref. 21) ICU 6Q-65 60-65 - 96
Ceriana and Frigerio CVF (Weaning Center) 47±5 44±2 57±6
(unpublished data)
Environmental Protection <45 <35
Agency (ref. 22)
No=: Refe~ence 22 is the recommended noise level in a hospital environment according to the Environmentll l Protection Agency.
ICU, mtenslVe-careunit; CVF, chronic ventilator facility.
quality of care in these facilities has never been explored in found that despite a 31-fold increase in the number of all
detail or demonstrated scientifically, these facilities appear adults transferred from ICUs to extended-care facilities in
to be very effective. Chronically ill patients in these facilities the Boston area between 1990 and 1996, the level of care
are treated at lower costs than in ICUs but achieve simila r of these facilities varied greatly depending mainly on the
outcomes.25 availability of skilled nurses.
There is still disagreement about the definition of a
ventilator-dependent patient. The ninth revision of the 111-
ternntionn/ Clnssificatioll of Disenses35 defines long-term ven-
Organization of Chronic tilation patients as those w ho have received 5 or more days
Ventilator Facilities of ventilation. Various authors, however; have used limits
as short as 48-72 hours and as long as 40 days.36-38 Realis-
TI1e term CVF is not necessarily synonymous with the tically, about 20% of pa tients in an rcu require mechanical
so-called intermediate-care unit or high-dependency unit, ventilation for more than 1 week, and about half of them are
which are meant for patients who do not require full ICU weaned successfully over the following few days.39 There-
care but are thought to need m ore care than usually can be fore, a limit of 2 weeks has been chosen by most authors to
offered in a general ward. 26-30 Not all patients in the latter define the threshold for ventilator dependency. The Health
units may be ventilator-dependent, but they may require Care Financing Adrninistration40 has expanded this limit to
eithe.r noninvasive monitoring or noninvasive mechanical 21 days of mechanical ventilation for at least 6 ho urs a day.
ventilation. There is no agreement about the classification A definition based only on time, however, does not consider
of facilities for patients needing prolonged mechanical ven- that for a particular patient to be regarded as ventilator de-
tilation because of geographic differences, lack of consensus pendent (and therefore eligible for trans fer to a chronic-care
regarding the a ppro priate timing of transfer from the ICU, facility), the precipitating cause of the respiratory failure
and different criteria of admission. For example, the Ameri- must have been reversed .
can College of Critical Care Medicine States in its guidelines CVFs have been described in the literature only in N orth
for admission to and discharge from adult intermediate-care America,25 Europe,41 and Asia. 42 Substantial differences ex-
units that "medically stable ventilator patients for wean- ist in their organization, location, and criteria of admission.
ing and chronic care" are the ideal candidates for these A recent editorial entitled, "The Challenge of Prolonged
environments.31 Unfortunately, these units were described Mechanical Ventilation: A Shared Global Experience,"43
only generically as "progressive-care units or single-organ stressed the need for common international consensus. Yet
subspecialty floors or chronic ventilator respiratory-care interna tional evidence-based guidelines and/ or "position
units." Details were not provided on how these units should papers" are lacking.
be organized or financially reimbursed. Given the confusion of terminology, we s ubmit that the
Ttming of discharge from the ICU is also critical. Long- most logical classification of CVFs is one based on the loca-
term ventilator patients are often old and have various un- tion of the different facilities, specifically whether the facility
derlyu1gchronic comorbidities that may complicate or exac- is inside or outside a so-called acute-care hospital. Figure
erbate their respiratory condition at any time after discharge 33-1 illustra tes the possible sites of care for patients who
from the ICU. 32•33 The 6-month ra te of readmission to an are chronically ventilator dependent. It should be borne in
acute-care hospital is close to 40%, and readmission is often mind that access to these different environments may dilier
within the first 2 months after discharge from the ICU. 12 internationally or even regionally within the same country.
Surprisingly, this rate was not influenced by the initial d is-
charge disposition. That is, it did not differ for patients dis-
FACILITIES WITHIN ACUTE-CARE HOSPITALS
charged to a nursing home, a CVF, o r their own home. These
findings indirectly suggest that not all CVFs are presently Mechanical ventilation is initiated outside the hospital in a
prepared to cope with the burden of a new "acute exac- relatively small proportion of patients; ventilation is mostly
erbation" in such patients. For example, Nasraway et al34 started and stabilized in an ICU. 44 TI1e timing of discharge of
CHAPTER 33 CHRONIC VENTILATOR FACILITIES 693
1999, the majority (58%) of the 11,890 patients admitted to

Medical or Surgical 55 RICUs received invasive mechanical ventilation. These
ICU units almost always (> 90%) were inside an acute-care hos-
pital. Unfortunately, no data were available on how many
Facilities Inside Facilit ies outside
Acute Care Hospitals Acute Care Hospitals of these patients actually were ventilator dependent. Never-
theless, an Italian survey published in 2001 57 reported that
( I>RGs payment system ) ( I>RGs grouping-exempt)
61% of patients receiving invasive mechanical ventilation
- Respiratol)' Monitoring Unit - Prolonged RespiratOI)' Care Unit
in Italian RICUs were tracheotomized and therefore were
- Non-invasive RespiratOI)' ICU - long-term Acute Care Unit considered ventilator dependent. The percentages may be
- Resplratol)' Care Floor - Respiratol)' Intermediate Care Unit similar in other European countries.
- Respiratol)' Special Care Unil - Weaning Centre Irrespective of location on either side of the Atlantic, the
- Ventilator Dependent Unit - Rehabilitation Centre organization and staffing of CVFs inside acute-care hospi-
• Resplratol)' Intermediate Care Unn - Extended Care Facilnies tals appear to be homogeneous and more similar to that
of an ICU than to that of a CVF located outside an acute-
.--------,
- Nursing Home
II' care h ospital.58,59 The majority of these CVFs provide nonin-
·Home vasive monitoring, the nurse-patient ratio is usually 1:2 to
-Hospice 1:4,41 , 47•50•54•55 and a lead respiratory therapist is assigned
permanently and present in the unit. General medical care
FIGURE 33-1 Potential sites of care for ventilator-dependent
is provided around the clock by medical house staff under
patients when discharged from an inten sive-care unit (ICU).
the direction of a an attending physician in either critical
DRG, Diagnostic-Related Grouping
care or pulmonology. The nursing staff usually is specially
trained through orientation and in-service programs to ad-
ventilator-dependent patients from the ICU is linked strictly dress the needs of this particular population of patients.
to the criteria of admission of each single CVF, which are TI1e approach to the patients is multidisciplinary, involving
described in Chapter 34. dieticians, psychologists, physical therapists, speech thera-
In the late 1980s, CVFs started to emerge in acute-care pists, social workers, and clergy as needed. Because these
hospitals as an attempt to provide an alternative thera- CVFs are located within an acute-care hospital, all the diag-
peutic environment for ICU patients requiring prolonged nostic (e.g., computed tomographic scans, nuclear magnetic
mechanical ventilation. Krieger et al45· 4Q probably were resonance imaging) and therapeutic (e.g., major surgery)
the first to establish a CVF within an acute-care hospital options are readily available. In Europe, the nurse-patient
(Central Respiratory Monitoring Unit at the Miami MOtmt ratio varies slightly according to the three levels of care of
Sinai Medical Center). They were followed shortly after by RICUs. 27•41 Because of the different education and respon-
Elpern et al 47, 48) (Noninvasive Respiratory Care Unit of St. sibilities of respiratory therapists (rarely present around
Luke's Medical Center in Chicago). TI1ese units were de- the clock), an attending physician is always present in the
voted mainly to patients requiring prolonged mechanical units f>~l. 61
ventilation. In 1990, the Mayo Clinic opened a ventilator-
dependent unit (VDU) inside Saint Mary's Hospital.49-52
FACILITIES OUTSIDE ACUTE-CARE HOSPITALS
Their mission was tocreateanenvironment conducive to the
rehabilitation of patients with respiratory failure and also to This classification consists of several CVFs going un-
lower the costs of ventilato r-dependent patients.53 Shortly der names such as regiona l weaning centers, prolonged
thereafter, new CVFs were opened . These went under differ- respiratory-care units, long-term acute-care units, and
ent names at Saint Vincent's Hospital and Medical Center in respiratory intensive-care units inside rehabilitation hospi-
New Yo r~4 (Non-Monitored Respiratory Care Floor) and tals. The need for these special facilities outside the acute-
at Cleveland Clinic Foundation55 (Respiratory Special Care care health system was recognized a long time ago in North
Unit). As discussed later (in outcome and effectiveness), the America but only recently in Europe. For example, the
overall rate of weaning success was high (>50%), with a Comprehensive Critical Care of the British Department of
mortality rate below 40%. Health62 recently stated that " the effectiveness of specialist
In Europe, the first report on this subject was published weaning and progressive care programs for long-term ven-
in 1995 by Smith and Shneerson56 from England. Rather tilation of patients has been demonstrated by research, and
than opening a special unit for patients requiring prolonged NHS Trusts should review the need for provision of such
ventilation, tl1ey described the institution of a progressive- services."
care multidisciplinary program carried out within the rcu The first experience of a CVF dedicated to the problem of
by a dedicated team of res piratory physicians and nurses. ventilator-dependent patients was reported by Indihar,63-65
As soon as patients were judged ready for discharge from who described 10 years of activity, starting in 1979, of a
the ICU, they were transferred to a respiratory unit, where unit located in Bethesda Lutheran Medical Center. In the
they continued the multidisciplinary program. The pro- late 1980s there was substantial growth o f regional wean-
gram was very successful with regard to discharge to home ing centers in the United States. Examples include the Bar-
(80% of the patients) and 1-year survival (76%). The recent low Respira tory Hospital in Los Angeles,66•67 the Medical
survey41 of the European Respiratory Society on respira- Center of Central Massachusetts, 68 and t11e Hospital for Spe-
tory intermediate-care units (RICUs) showed that during cial Care, New Britain, Connecticut.69•70 Later, there was an
impressive burgeoning of new long-term acute-care units. Above all, they provide physical and pulmonary rehabilita-
By 1997, these had a capacity of about 15,000 patients per tion, which has been shown to help in freeing patients from
year?1 These units were established either as free-standing mecl1anical ventilation and restoring them to an acceptable
hospitals, as in the case of most regional weaning centers, or level of autonomy.78
within an acute-care hospital but operating with total inde-
pendence. As such, their governance is independent of the
host hospital, and reimbursement is not based on a DRG NURSING HOMES
system. A small percentage of ventilator-dependent patients are
CVFs within a rehabilitation hospital are also popular in discharged from an IClJ1 2 directly to a nursing home.
the United States and Europe, especially in Germany and Nursing homes, however, are more likely to receive such
Italy, where about 15% of RlCUs are located inside rehabil- patients once they have left a CVF. In 1991, a surve~
itation centers. 41 ·n-74 by the American Association for Res piratory Therapists 9
UnlikeCVFs located within acute-care hospitals, CVFs lo- found that nearly 30% of ventila tor-dependent patients
cated outside appear to have a rather heterogeneous organi- remained in CVFs for nonmedical reasons, such as re-
zation and staffing. This heterogeneity occurs despite these imbursement obstacles to discharge or lack of pos tdis-
facilities espousing a program based on the common ideal charge placement options. Indeed, about 20% of patients
of providing comprehensive medical, nursing, and respi- cared for in a ventilator-dependent unit are transferred to
ratory care to ventilator-dependent patients. For example, nursing home simply because they are not ready to go
New England 34 has several"extended-care facilities" out- home.12
side acute hospitals; the skills and level of care vary dra- Nursing homes have been established all over the United
matically among different centers. Despite the personnel be- States80 either as independent units inside larger facilities
ing fully licensed health care practitioners, they may not all or as s tand-alone facilities. To the best of our knowledge,
be completely familiar with the complexities of ventilator- very few exist in Europe.81 Apparently, there is no stan-
dependent patients. Patient outcome is likely to depend on dardization of admission criteria, staffing, or organization
the different levels of care provided. of these units apart from the person needing "24-hour nurs-
In most North American centers, the nurse-patient ratio is ing care for a cognitive or a physical impairment.'182 Nurses
about 1:4 during the day and 1:8 at night and on weekends. working in this specialized area should be trained by res-
A full-time respiratory therapist66•75 usually is present. The piratory therapists to perform specific procedures such as
primary physicians are either internists or specialists in suctioning, tracheotomy care, and monitoring of ventilator
pulmonary and/ or critical-care medicine, whereas night- parameters. In some cases, for example, Lakeside Hospital
time coverage commonly is provided by junior doctors. in Wisconsin,80 weekly care rounds have been introduced;
The comprehensive-care team includes physical therapists, these are led by a pulmonary physician with the participa-
occupational therapists, speech and swallowing therapists, tion of the care team, including not only the certified nurses
and clinical psychologists. Screening for admission is per- but also respiratory therapists, dieticians, social workers,
formed either by an attending physician o r by a nurse in and when possible, family members. In the very few obser-
consultation with an attending physician75 Weaning pro- vational studies perfom1ed in this kind of facility, weaning
tocols and the selection of ventilator settings during this outcomes are very promising.83 Further studies are needed
process are implemented by respiratory therapists? 6 Dis- to define the characteristics of ventilator-dependent patients
charges are planned by nurses or social-work care man- who are most likely to benefit from admission to this envi-
agers. With the exception of a few facilities, which may have ronment.
operating rooms for minor surgery, most CVFs located out-
side acute-care hospitals cannot offer surgery or sophisti-
cated diagnostic procedures.
In Europe, CVFs outside acute-care hospitals are nm Criteria for Adntission
mainly by full-time attending physicians who are specialists
in respiratory and/ or critical-care medicine. 27•41·57 These Table 33-2 presents criteria for defining the "ideal" candi-
physicians are in charge of the admission and discharge date for a CVF. TI1e concept of ventilator dependency is
of patients and the weaning protocols. They are on duty the primary criterion for selecting admissions to a CVF.
24 hours a day. The doctor-patient ratio is at least 1:8. The Accordingly, most centers accept only tracheotomized pa-
nurse-patient ratio is usually similar to that of North Amer- tients because tracheotomy per se is assumed as evidence of
ican centers. Because of their different educational train- ventilator dependency. Indeed, the dramatic increase intra-
ing, respiratory therapists in Europe tend to be involved cheotomies performed over the last 10 years 13 suggests that
mainly in rehabilitation programs, for about 8 hours a day ICU physicians tend to perform an early tracheotomy before
(excluding Sundays and holidays), rather than in the wean- trying a complete weaning protocol. This change may reflect
ing process.77 [n common with North American facilities, attempts to decongest busy ICUs more rapidly by allowing
most European CVFs do not offer major surgery. transfer of ventilator-dependent patients to extended-care
Irrespective of their geographic location, CVFs located facilities. To avoid this problem, some units request proof
outside acute-care hospitals are intended to provide pri- that a patient has failed at least two weaning trials before
vacy, rest, and longer visiting hours for relatives and friends. being admitted.s1
TABLE 33-2 Criteria for Defining the Ideal Candidate to a TABLE 33-3 Classification of Patients Admitted to a Chronic
Chronic Ventilator Facility Ventilator Facili ty
Patients ventilated for more than 14 days, necessitating prolonged Acute lung injury
weaning Acute respiratory distress syndrome
Presence of a tracheostomy Pneumonia
Potential weaning possibility Aspiration injury
Defined diagnosis Burns
Single-organ failure Chronic lung disease
HemodynamicaUy stable (no pressor infusion) Chronic obstructive pulmonary disease
No sepsis or active infections Asthma
Absence of surgical problems Pulmonary fibrosis
No need of continuous sedation Fibrothorax
Absence of chronic renal failure necessitating hemodialysis Postoperative
Pae>:/FI(): > 200 and need for external PEEP < 10 cmH2 0 Lobectomy or pneumectomy
Need for aggressive rehabilitation program Cardiac surgery
Potential to benefit from a rehabilitation program Major abdomina l su rgery
Neuromuscular diseases
Amyotrophic lateral sclerosis
Multiple sclerosis
Postpolio syndrome
Other criteria used for selecting patients for admission to Spinal cord injuries
CVFs are clinical stability and potential to benefit from are- Kyphoscoliosis
habilitation program. 49•55 ClinicaJ stability is defined as re- Critically mpolyneuropathy
versal of the precipitating cause of respiratory failure, hemo- Guillain-Barre' syndrome
dynamic stability (not needing invasive measurements of Cardiovascular disorders
blood pressure or pulmonary artery pressure, not requiring Chronic congestive heart failure
Ischemic cardiomyopathy
vasoactive drug infusion before transfer), and absence an ar-
rhythmia requiring telemetry. Patients with multiple-organ souRer.: Adapted, with permission, from ref. 89.
failure often are not admitted. Patients receiving hemodia-
lytic support usually are accepted, particularly if the unit is
inside an acute-care hospital.
The idea of the ability to benefit from a rehabilitation or
Outcomes and Effectiveness
other comprehensive program is subjective and depends
COMPARISONS WITH ICUS
strongly on the judgement of the proposing or accepting
physician. In some facilities, the proposing physician must Commenting on the rationale for opening an intermediate-
make a written statement that he or she believes that the care unit, Vincent and Buchardi90 stated they "would recom-
patient is either capable of being weaned from the ventila- mend that instead of fragmenting ICU facilities by separat-
tor or is likely to return to the community despite receiving ing 'intensive' from 'intermediate,' with the potential risk of
ventilator assistance. 50 Other facilities specifically ask that reduced s taff morale and less adequate patient care, inten-
patients are returned to their referring hospital once they sive and intermediate care beds should be combined in one
have been weaned successfully or when it becomes clear unit." As stated earlier, intermediate-care units are not nec-
that weaning will not be possible. To ensure that all parties essarily equivalent to CVFs. Despite the lack of strong sci-
understand this policy, a letter of confirmation may be re- entific evidence, specific facilities for ventilator-dependent
quired from the referring physician, countersigned by the patients do have some clinical and financial advantages over
patient or his or her surrogate.54 A more liberal attitude is ICU care (they are not, however, "in competition").91 - 95 The
shown by other facilities, for example, the Worcester County main differences between ICUs and CVFs located inside or
Ventilator Unit, 68 where "specifically no admission decision outside acute-care hospitals are listed in Table 33-4.
is based on prognosis, weaning potential o r rehabilitation A recent retrospective review 95 of 429 ICU patients tra-
potential." Also, at the Long-Term Acute Care Unit of the cheotomized for respiratory failure and needing prolonged
University of Chicago/5 "patients are accepted regardless mechanical ventilation showed that only 57% of survivors
of the severity of their ilJness, provided they are stable for had been freed from mechanical ventilation by the time of
transfer." The latter institution theoretically accepts patients discharge from the ICU. Patients who were finally weaned
requiring positive end-expiratory pressure of more than and had their tracheostomy tubes removed had better sur-
10 cmH 20 or an Fr02 of greater tha n 60%. Finally, meth- vival than patients who did not. Improved survival, how-
ods have been proposed for identifying patients suitable ever, came at higher hospital cost and longer ICU stay. This
for admission to CVFs based on severity-of-illness scores or study illustrated the need to compare the clinical outcomes
activity of treatments. 85-88 and financial burdens of these "difficult to wean" patients
With small local differences, the classification of when treated exclusively in a traditional ICU or transferred
ventilator-dependent patients admitted to CVFs follows during hospitalization to a CVF. The study also demon-
that proposed by Gillespie et al89 in Table 33-3. strated that the emotional status of these patients at ICU
TABLE33-4 D ifferences in Services P rovid ed by This study24 leaves three major issues unresolved. First,
In tensive-Care Un it and Chronic Ventilator Facilities the "appropriate" timing of transfer has not been clearly
CVFs Inside CVFs Outside
defined because some CVFs accept sicker patients wiili
an Acuto:M:are an Acute-Care "overt" nonpulmonary dysfunction, whereas others only
ICU Hospital Hospital accept patients with the "single organ failure." Second, al-
though the authors showed that transfer to CVFs is as-
Medical-centred care ++++ ++ + sociated with a reduction of TCU uncompensated costs of
Dedicated + +++ ++ ++ care, ilie issue of best reimbursement system for CVFs was
multidisciplinary team not assessed. Third, even after patients were transferred
Nurse-patient ratio ++++ ++ ++ to a CVE ilie rate of discl1arge home was disappointingly
Invasive monitoring ++++ ++ + low; there is an urgent need to identify the best location
Diagnostic availability ++++ +++ ++ of care for these patients once they are discharged from a
Privacy + ++ +++
Family contact +I- ++ ++ ++ CVF.
Noise and artificial light ++++ ++ ++
Surgical availability ++++ +++ + O BSERVATIONAL STUDIES
Hemodialysis ++++ +++ +
Physiotherapy and + +++ ++++ Table 33-5 provides a summary of outcome indices for pa-
rehabilitation tients admitted to an acute-care setting for weaning. Al-
Costs ++++ ++ ++ though comparisons between studies is difficult, the rate of
weaning success ranged from 25- 92%. Variability of hos-
pital mortality was equally great, ranging from 10-50%. In
discharge was generally good, whereas physical function a controlled study, Gracey et aJ 51 found that mortality de-
was quite lirnited. 95 creased dramatically after the opening of a dedicated ven-
The only randomized, controlled study directly compar- tilator unit within an acute-care hospital. The percentage of
ing the outcomes of chronically ill patients, most of them patients discharged home is also extremely variable, and
ventilator dependent, managed entirely in the ICU or trans- about about 40% usually are discharged to long-term facil-
ferred when clinically stable to a special care unit (SCU), ities with skilled nursing care.
managed mainly by specialized nurses, was performed by Of patients discharged home, Dasgupta et al 55 found that
Rudy et al. 96 The SCU had a case-management approach only 10% were still ventilated; more than 40% of patients
for clinical problems, a full rehabilitation program, wean- discharged to a skilled nursi11g facility or nursing home
ing protocols, and control of resource use. A total of 220 were partially or totally ventilator dependent. Latriano
patients were assigned randomly to the SCU or to the ICU. et al 54 reported an alternative location to ease pressures on
Overall mortality rates were similar in the two groups, but the ICU: use of a nonmon.itored general medical floor to treat
the rate of readmission was lower and hospital stay shorter hemodynamically stable mechanically ventilated patients.
in the SCU group. TI1e average cost of delivering care was The strategy was associated with financial savings. To our
US$5000 less per patient in the SCU than in the ICU, and knowledge, this model has not been repeated elsewhere.
ilie cost to produce a survivor was US$19,000 less. It makes Table 33-6 provides a summary of outcome indices for pa-
sense iliat specialized care may achieve better outcomes. It is tients admitted to nonacute settings for weaning. There is
difficult to draw up standardized recommendations, how- overall agreement that a rehabilitation-based weaning unit
ever, based on a relatively small single-center study where can assist wiili weaning and maximal functional indepen-
the two groups were not fully comparable in either number dence and prepare the family for discharge of the ventilated
or baseline conditions. patient to home. 68
Using a retrospective chart review and questionnaires, Clinical outcome of patients requiring prolonged venti-
Seneff et a124 analyzed 6-monili mortality and hospital costs lation depends on the underlying disease. Weaning success
in 54 acute-care referral hospitals and 26 long-term acute- is highest in postoperative patients (58%) and patients wiili
care institutions. Hospital costs included the amount of un- acute lung injury (57%) and lowest in patients with chronic
compensated care incurred by the ICU under the Medi- obstructive pulmonary disease (COPD) or neuromuscular
care prospective payment DRG system. They compared 432 disease (22%). 68 Chronically ventilated patients with res-
patients ventilated for an average of 3 weeks who where piratory failure caused by COPD have a worse prognosis
referred but not transferred to CVFs (Vencor) with 1702 pa- than patients with respiratory failure from other causes.69
tients who where referred and transferred to CVFs. Six- This observation is consistent with the findings of Scl1onofer
month mortality was not adversely affected by transfer et al 72 that long-term survival rate was worse in patients
to a CVF. Because patients had long hospital stays and wiili severe COPD than in other patients. In a homogeneous
consumed much resources, overall cost of care was very group of42 patients wiili COPD, Na va et al 73 observed a suc-
high. Acute-care hospitals, however, theoretically can re- cessful weaning rate of 55% w hen a rehabilitation program
duce the amount of uncompensated care for tl1ese patients was continued for a long period outside the lCU.
by timely referral to an appropriate CVF. Only about 10% The possibility that patient outcomes is influenced by
of the two groups were discharged directly home; most a staff learning is suggested indirectly by several stud-
patients were transferred to a nursing home or another ies. De Vivo et al98 demonstrated iliat mortality decreased
CVF. dramatically over years secondary to the development
TABLE33·5 Outcoml':s for Ventilatot·Dependent Patients Admitted to a. Chronic Ventilatory Facility within an Acute ..Care Hospital
Author Patients Patients Patients Died Patienlt; Died Duration of M&hanical Post Discharge
(Ref) Year (11) Age(yrs) Patients Weaned(%) in Hospital (%) within 1 Year (%) Ventilation (days) Location (%)
Elpem (47) 1989 95 71.6 M i.x~d 31% 67% ? 8.1 ?

Rudy (96) 1995 145 64 ± 12 Mixed ? 44% ? ? ?
Latriano (54) 1996 224 66±17 Mixed 51 % (all pts) 50% ? 50±66 H=3"1 %;
92% (survived) CVFo=64%;
o ther = S%
0'1 Douglas (5) 1997 57 61 ± 20 Mixed ? 44% SO"k 28 H = 33%;
(0
'-J CVFo= 42%;
NH=18%;
o ther= 7%
Gracey (51) 1997 206 65±14 Mixed 74% 8% 31% ? ?
Dasgupta (55) 1999 212 68 Mixed 60'1. 18% ? 17 H =34%;
o ther=66%
Robson (91) 2003 161 69 Mixed 89o/o 14% ? s ?
Engoren (95) 2004 429 68 Mixed 57% 22% 36% 29 ?
AIUJIUNIA'rlCms : Ji, home; NH, nursing home hospital; CVFo, chro nic \'tmtilator facil ity oul<>ide an acute-care hospitaL
TABLE33-6 Outcomes for Ventilator-Dependent Patients Admitted t o a Chronic Ventilatory Facility outside an Acute-Care Hospital
Authol' Patients Patients Patients Died Patients Died Duration of Mechanic:. I Discharge
(Ref) Year (n) Agelyrs) Patient..; Weaned(%) in Hospital (%) within 1 Year (%) Ventilation (days) loca tion (%)
lndihar (65) 1991 171 60 Mixed 34% 60% ? 55 1

Freichels (97) 1993 442 ? Mixed ? 3'1.7% ? 48 H = 20%;
CVFo=35%;
other = 45%
Nava (73) 1994 42 67±9 COPD 55% 29% 35% 44 1
Schcilwrn (66) 1994 421 68±0.9 Mixed 74% 28% 72% ? H =SO%:
othcr =SO%
De Vivo (98) 1995 435 40 SCI ? ? 25% ? ?
Bagley (68) 1997 278 67 Mixed 38% 31 % ? (11-75) H =29,o;
CVFo=71%;
Schcinom (67) 1997 1123 69± 13 Mixed 56% 29% 62% 29 {1-226) ?
0'1 Escarrabil (99) 1998 10 59± 8 ALS 0'/o 10% 70'/o 90 (15-150) H = 100'/o
1.0 Votto (69) 1998 293 (45-70) Mixed ? ? 29--(,0% ? ?
Oo
Cars<)n (75) 1999 133 71 Mixed 70% 50% 77"/o ? H = 18%;
(d ischarged); CVFo=63%;
38% (total) other = '1 9%
Modowal ( 100) 2002 145 66± 16 M ixed 50% 34% ? 94 :1: 82 ?
Schonofer (721 2002 403 66 Mixed 68% 24% 51% 41 H =28%;
C VFo = 16%;
other =56%
StoUcr (J 01) 2003 162 65± 14 Mixed ? 17% 57% ? H = 28%;
CVFo=63%;
CVFi=9%
Ceriana (102) 2003 40 67:1: '12 Mixed 67% 15% ? 38 ?
lindsay (83) 2004 102 ? Mixed 67% 20% ? 46 H = 36%;
Nl-:T = 2M'..;
oU1cr= 44%
ABBREVIATIONS.: 1-1. home; NH, nursltlg home; CVFi. dlroni<: vcntfl<~ lor fadlity inside an i'lCl•te C..'\.re hospitt~ l; CVFo, chJ\)nk vcntilotor £adlit)' O\.Jtside tit\ acute--care hospita1; COPD, chronic obstructive
1>ulmonary disease; Al.S, i'lmyotrophic lnler,ll sclerosis; SCI. spinal cord injuries.
of improved methods of prevention a nd management of ventilator-dependent w1it (CVDU). They also observed t11at
respiratory complications, particularly pneumonia. Shein- all ICU daily costs (medical, neurosurgical, coronary care,
horn et al67 reported that a overall survival after discharge and cardiovascula r surgery ICUs) rose dramatically be-
improves over time probably because of the improved ex- tween 1993 and 1998; the only exception was the CVDU.
pertise and care of personnel. This lower cost of the CVDU was related mainly to the lower
Not all the authors have described the postdischarge des- salaries, decreased room charges, lower overheads, simpler,
tination of their surviving patients. Jn most cases, when usually noninvasive monitoring, and changes in the pattern
stated, it was home; alternatives include extended-care facil- of diagnostics and therapeutics. Given these findings, it has
ities or a nursing home. Ceriana et af7 highlighted the pos- been suggested that CVFs may be a cost-effective alterna-
sibility of removing the tracheotomy cannula from almost tive to ICUs. Unfortuna tely, we still lack randomized com-
80% of patients breathing autonomously among a group parisons of the real costs of care in the two environments.
of 72 patients recovering from weaning. It is often possi- The DRG-based system is used for payment in most ICUs
ble to use and adapt a tracheotomy speaking valve that round the world. The Medicare prospective payment sys-
facilitates verbal communication by ventilator-dependent tem is designed to compensate hospitals for overall cost of
subjects. This step facilitates care and greatly enhances the car e for patients who share a common diagnosis. DRG 483,
mental outlook of patients. 103 "tracheotomy except for mouth, larynx, or pharynx d isor-
Physical function is limited and reduced in most der," is the group usually applied to ventila tor-dependent
patients56•104•105 but is sometimes good or improved after patients.112 Because of large variation in time spent in an
discharge. 56•75, 100• 105 Quality of life is defined as good, quite ICU, whether a hospital renders uncompensated care in a
good, reasonable, or normal, although severe impairment given year depends on the case mix, average duration of
is reported in a minority of studies56:75 •100•105; often it is im- hospital stay, and availability of alternative locations for
proved 1 year after discharge. 106 Ambrosino et al105 con- patient care. Seneff et al24 reported tl1a t Medicare uncom-
ducted a prospective, controlled cohort study in a respi- pensated care in an ICU was an average of US$16,000 per
ratory intermediate intensive-care mut in 63 patients with ventilator~dependent patient.
COPD requiring mechanical ventilation. Perceived health To address the problem of under-reimbursement, some
status and cognitive function were worse in patients re- CVFs are now licensed as DRG-grouping-exempt52 and are
covering from acute-on-chronic respiratory failure (requir- required by the Health Care Financial Administration to
ing mechanical ventilation) than in stable patients receiv- maintain a mean length of s tay more than 25 days and
ing long-term oxygen therapy who never required ICU usu ally fewer than 90 days. In the United States, long-term
admission. After discl1arge, cognition and m obility im- acute-care facilities are reimbursed under regulations of the
proved to levels found in stable COPD patients on oxygen Tax Equity and Fiscal Responsibility Act (TEFRA)113 for care
therapy. provided to Medicare patients. Charges are reimbursed up
Chronic ventilator urlits provide settings in which an in- to the annual maximum cap for the facility, calculated dur-
terdisciplinary team develops and implements tools tha t ing a 12-month period designated as the base year. Hospi-
assist the patient and caregivers. A planned discharge gives tals incur penalties when charges for Medicare exceed the
the patient and caregivers confidence and skills before discharge target amount and receive incentives if charges
discharge107 and helps with the emotional burden caused by are reduced in subsequent years. This policy, tmfornmately,
the heavy responsibility of home caregivers. The time spent has led, as it did for rehabilitation hospitals, to substan-
in these units helps to prepare patients and tl1eir families, tial extra costs, including increases in payments to hospi-
educates them about various aspects of care after dischar~e, tals a nd doctors and numbers of hospital days for the aver-
and helps them with decisions about future placement. 108, 09 age patient. 113 In most European countries, the health care
system is funded primarily by government. Therefore, the
vast majority of public hospitals and some private hospitals
Problems Unique to Chronic Facilities receive most of their funds through a national health ser-
vice. Most beds are devoted to the treatment of acutely ill
FINANCES
patients, independent of the baseline d isease (i.e., medical or
surgical), and are reimbursed through a DRG-based system.
A major issue facing medicine today is containing costs, par- A minor share is devoted to the care of chronically ill pa-
ticularly with regard to critical-care beds. In this respect, tients. The latter beds are located inside rehabilitation wards
CVFs have a peculiar system of reimbursement that de- of acute-care hospitals or within independently s tructured
serves special a ttention.110 As shown in Table 33-7, most rehabilita tio n hospitals. For acute car e, the DRG-based re-
observational studies estimate that the daily cost of care imbursement per case is applied. For chronic care, reim-
for ventilator-dependent patients is lower in a CVF than bursement is on a per diem bas is, allowing for some increase
in an ICU. Dasgupta et al 55 reported that for 11 patients according to DRG classification. This per diem fee applies
transferred from a n ICU to a respiratory special care unit, for only a limited number of days (40-60), after which the
the difference in the mean daily costs for the first 3 days fee is curtailed drastically.
in the special unit and for the last 3 days of ICU car e was Mean duration of s tay in CVFs differs considerably, w ith
US$469. Gracey et al52 showed that over a 6-year period, an impressively high standard deviation. Nasraway et al34
more than US$4 million were saved in patient-care costs by reported the duration of hospital stay to range from 1-2125
transferring care for 964 patients from ICUs to their chronic days. Because the time spent in CVFs differs so greatly,
TABLE 33-7 Costs per Day for a Ventilator-Dependent Patient Admitted to an intensive-Care Unit (ICU) or to a
Chronic Ventilator Facility
Year of Year of Daily

Authors Publication Analysis Type of Unit eosts(US$)
Shein hom et al (ref. 66) 1994 ? we (outside acute-care H) 980

Latriano et at (ref. 54) 1996 ? ron-monitored care floor (inside acute-care H) 453
Bagley et al (ref. 68) 1997 1995 we (outside acute-care H) 630
Nava eta! (ref. 111) 1997 1995 RICU (outside acute-care H) 865
Gracey et al (ref. 52) 2000 1998 CVDU (inside acute-care H) 1084
Engoren et a I (ref. 104) 2000 ? Cardiac stepc!own unit (inside acute-care H) 439
Seneff et al (ref. 24) 2000 ? ICU 4174
Linsday et al (ref. 83) 2004 ? Nw·sing home 303
Halpern et al (ref. 3) 2004 2000 Daily cost per patient admitted to a critical-care bed 2647
NOTli: Reference 3 is the actual daily cost of a critical-care bed in year 2000 in the Unit£'<1 States. WC, weaning center; RICU, respiratory
intensive-<:are unit; CVDU, chronic ventilator-dependent unit.
it is clear that exemption from the DRG-based payment Boston area, as determined by an informalsurvey. 34 Marked
system is granted to avoid massive losses. The per diem differences exist in the care that each center provides to long-
reimbursement up to relatively small ceiling of days, how- term ventilated patients. The authors34 state that "some fa-
ever, may not achieve reasonable reimbursement. cilities may accept ventilator-dependent patients but may
not be able to provide for all their needs, especially when
serious infections or other setbacks ensue." Nurses work-
STAFFING ing in a CVF should be specifically trained not only in acute
CVFs, especially those outside acute-care hospitals, are still lifesavings procedures, such as resuscitation, but also in spe-
characterized by heterogeneous staffing. Most of the centers cific "chronic" procedures, such as bronchial toilet, preven-
share common views about the equipment to be used (i.e., tion of sores at the tracheotomy site, and positioning of the
ventilators and monitoring systems) and the overall mul- tracheal cannula.
tidisciplinary organization, aimed at improving the auton- Vitacca et al114 studied the allocation of nursing time
omy of patients, privacy, and environment. There is, how- in a respiratory unit located in a rehabilitation center. In
eve.r, considerable discrepancy concerning the training of the first two days after admission, tin1e devoted to care of
personnel, especially of nurses. Table 33-8 shows the avail- a ventilator-dependent patient consumed about 45% of a
ability of skilled nurses in extended-care facilities in the nursing shift.
Respiratory therapists should be skilled in weaning pro-
tocols that have been shown to shorten the duration of me-
TABLE 33-8 Range of Skilled Nursing Care in the chanical ventilation. The hospital team should be trained in
Extended-Care Facilities clinical tests (i.e., broncl1oscopy, fluoroscopy, assessment of
expiratory muscle function) that may help the clinicians to
Skilled ursing Care Nursu1g Hours/ Patient/ Day
decide whether or not a patient can have the tracheotomy
Subactute cnre 4.Q--5.0 removed?7 Special attention should be paid to the diagnosis
Patients technologically complex; of ICU-acquired neuromuscular abnormalities, which have
stable patients with prolonged been shown to increase the time to weaning. Diagnosis may
mechanical ventilation; potential require electro physiologic studies and needle electromyog-
for rehabilitation raphy of the limb and respiratory muscles.115,116
Acute rehabilitatio11 6.Q--7.0
Intensive rehabilitation; hospital
level of care; presence of SIZE OF THE PROBLEM
attending physici<m
The number o f " actual" ventilator-dependent patients" and
Long-term awte care 7.5--8.3
Hospital level of care with lCU and "post-ICU patients" who might benefit from an admis-
the possibility of minor surgical sion to a CVF is unknown because most published data
procedures; stable patients with are anecdotal and not derived from structured surveys or
prolonged mechanical ventilation rigorous epidemiology data. Figure 33-2 reports the es-
Ju tmsive care 14-18 timated number of ventilator-dependent patients in the
Tertiary Care; artificial Life support; United States and the theoretical need for CVF beds per
major surgery; full ancillary head of population, calculated on the available data. It
services is believed that the ideal number of CVF beds per head
Based on a random survey in several extended tare facilities in each category
of population for European countries would be equiva-
in the New England Region. lent to that in the United States. This estimate is based
souRcl!: Adapted, with permission, from ref. 34. on the observation that in the subset of patients ("'-15%)
87,400 Critical Core Beds in year 2000 Conclusion

l
58 ,000 Critical Care Bed oeeuponey In the year 2000 (ref.3)
Over the last 10 years, the availability of ICU beds, new tech-
nology, and improved levels of care have increased a new
c: Proportion of ventilator-dependent patients at day 21= -3%

(ref.9- 10)
population of patients termed survivors of Clltastrophic illness.
These patients commonly require prolonged weaning.
;:::.
Estimated number of ventilator-dependent patients at day 21
The rate of achieving complete ventilator indepen-
dence in specific, dedicated weaning units is generally
- 1 700
·c:: Length of hospital stay per ventilator- dependent patient not
admitted to a CVF= - 48 days (ref.Z4)
high. It has been demonstrated that these units are cost-
saving alternatives to an ICU for carefully selected pa-
tients. Survivors have an acceptable long-term quality of
life. Weaning success, however, does not in itself solve
- 13 000
'
4.!. of vent ilator-dependent patients per year other severe problems such as the heavy financial and
c:: Length of stay per ventilator- dependent patient admitted t o a

CVF= -55 days (ref.58, 63)
human burdens that the high level of dependency im-
pose on families, caregivers, and healtl't service organiza-
tions once these patients are discharged from a protected
;:::. environment.
In conclusion, the main benefits of chronic ventilator fa-
- 2 ,500 Estimated need for CVF beds
c:: US population In 2005= "'295 , 000, 000 (ref. l17)
cilities are (1) the possibility of relieving congestion of ICU
beds, (2) maintaining a high level of nursing assistance,
(3) responding to sudden changes in a patient's clinical
condition, (4) allowing enough time for a multidisciplinary
l
1/ 150,000- 1/ 200,000 Estimated number of CVF beds
rehabilitation approach, and (5) acting as a bridge to home-
care programs or oU1er forms of continuous chronic assis-
tance (e.g., telemedicine or dedicated long-term units).
FIGURE 33-2 Estimated need for chronic ventilator facility (CVF)
beds in the United States. The number of ventilator-dependent
patients on day 21 after intu b ation was estimated as 3%9•10 of the
ICU bed occupancy in the year 2000 in the United S tates.3 In that
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Chapter 34 _ _ _ _ _ _ __ _ _ aries and also facilitate transfer when this is needed. 5' 6 Al-
though most acute NIV services are situated in a specific
NONINVASIVE clinical area, a peripatetic model has been described and
has some advantages.7' 8
VENTILATION ON A For the purposes of this chapter, the following definitions
are used:
GENERAL WARD • Intensive care. High ratio of staff to patients, facility for
M ARK ELLIOTI invasive ventilation and sophisticated monitoring.
• lntennedia.te respiratory ICU or HDU. Continuous monitor-
ing of vital signs, with a staffing ratio intermediate be-
tween an rcu and a general ward, in a specified clinical
area. Intubated patients (unless with tracheostomy) usu-
ally are not cared for in this environment.
EVIDENCE AND RATIONALE FOR NONINVASIVE • General ward. Takes unselected emergency admission, and
VENTILATION ON A GENERAL WARD although most wards will have a particular speciality in-
Acute Noninvasive Ventilation terest, it is likely that because of the unpredictability of
Elective Ventilation For Chronic Ventilatory Failure demand, patients with a variety of conditions and de-
WHERE SHOULD NONINVASIVE VENTILATION grees of severity will be cared for in the same clinical area.
BE PERFORMED? Nurse staffing levels vary, but the intensity of nursing in-
Acute NIV: ICU or General Ward? put available in HDU and ICUs is not possible. Only basic
Elective NIV: General Ward o r Chronic-Care Facility? monitoring is available.
The Advantage of The General Ward
SELECTION OF PATIENTS FOR NTV Another important issue w hen considering NIV in dif-
IN A GENERAL WARD ferent locations is the severity and acuteness of the insult
Acute Respiratory Failure leading to ventilatory failure. Ventilatory failure can be con-
Chronic Respiratory Failure: Elective Institution of sidered acute when it occurs on a background of normal
NIV function, acute-on-chronic when there is a sudden deteri-
IMPLICATIONS FOR STAFFING AND TRAINING oration on a background of impaired function, or chronic
ECONOMIC CONSIDERATIONS when there is ventilatory failure but with no precipitating
CONCLUSION acute event. Assisted ventilation can be considered neces-
san; when without it death will ensue over a few hours
In any discussion about location of a noninvasive ventilation or desirable when the primary aim is to improve qual-
(NIV) service, it is important to note that the model of hospi- ity of life and also to improve survival over the longer
tal care differs between countries and that there may be sig- term.
nificant differences even between hospitals within the same
country. There will be variations in staffing levels; the skills
of doctors, nurses, and paramedical staff; and the sophistica- Evidence and Rationale for Noninvasive
tion of monitoring. The terms intensive-care unit (ICU), high-
dependency unit (HDU), and general ward have a different Ventilation on a General Ward
meaning to different people. Care therefore must be taken
ACUTE NONINVASIVE VENTILATION
when extrapolating experience and results obtained in one
environment to other hospitals and countries. The United CHRONIC OBSTRUCTIVE PULMONARY
Kingdom's King's Fund panel'' defines intensive care as "a DISEASE (COPD)
service for patients with potentiaUy recoverable diseases The respiratory muscle pump in patients with severe COPD
who can benefit from more detailed observation and treat- often is functioning close to the point at which it can no
ment than is generally available in the standard wards and longer maintain effective ventilation. There is an excessive
departments." The definition of HDU is less clear, with some elastic and resistive load on it because of hyperinflation
HDUs allowing invasive monitoring, whereas in others only and airways obstruction, respectively, and reduced capac-
noninvasive monitoring is performed. In some countries, ity because of the adverse effect of hyperinflation on the
specific respiratory ICUs and intermediate ICUs have been configuration of the respiratory muscles, causing them to
developed. 2' 3 Specifically, within the King's Fund defini- operate at a mechanical disadvantage. 9' 10 In addition, the
tion is the consideration of intensive care as a service rather presence of intrinsic positive end-expiratory pressure (in-
than a place; critical care is provided within a continuum trinsic PEEP) causes an inspiratory threshold load. 11 In an
of primary, secondary, and tertiary care, and patients are acute exacerbation, when the load on the respiratory mus-
categorized on the basis of their needs4 (Table 34-1). Move- cles becomes excessive, effective ventilation can no longer
ment through the different levels usually means transfer be maintained, worsening hypoxia, and hypercapnia and,
from one location to another. Critical-care outreach teams most important, acidosis ensue. Acidosis in particular is
can advise on care as patients cross organizational bound- deleterious to muscle function, 12 and the capacity of the
705
TABLE 34-1 Classification of Lndivid ual Patient Dependency no intubations nor deaths in either group. Arterial blood-
gas tensions improved equally in both the NIV group and
Level 0: Patients whose needs can be met through normal ward
the control group. The mean pH at entry, however, in each
care in an acute hospital
Levell: Patients at risk of their condition deteriorating or
group was 7.33; at this level of acidosis, significant mortal-
patients recently relocated from higher levels of care whose ity is not expected; in other words, it was unlikely that such
needs can be met in a11 acute ward with additional advice and a small study would show an improved outcome because
support from the critical-care team recovery was to be expected anyway. 26
Level 2: Patients requiring more detailed observation or Wood et al21 randomized 27 patients with acute respi-
intervention, including support for a single failing organ system ratory distress secondary to various conditions to conven-
or postoperative care, and those stepping down from higher tional treatment or NIV in the emergency department. In-
levels of care tubation rates were similar (7 of 16 versus 5 of 11), but there
Level3: Patients requiring advanced respiratory s upport alone or was a nonsignificant trend toward increased mortality in
basic respiratory support, together with the support of at least those given NTV (4 of 16 versus 0 of 11; p = .123). The au-
two organ systems. This level includes all complex patients
thors attributed the excess mortality to delay in intubation
requiring support for mu1tiorgan failure
because conventional patients requiring invasive ventila-
tion were intubated after a mean of 4.8 hours compared
with 26 hours in those on NIV (p = .055). It is difficult to
respiratory muscle pwnp is reduced further. Res piratory draw many conclusions from this study given its small size,
muscle function also may be compromised by the devel- that the numbers of patients in each group were different,
opment of muscle fatigue because of the increased load. A and that patients were not matched for etiology of respira-
vicious cycle develops, worsening acidosis causing further tory failure. It does highlight the danger of prolonging NIV
impairment of respiratory muscle fun ction, which, in tum, inappropriately.
has an adverse effect on pH and arterial blood-gas tensions. Another possible reason why the two studies in which
Early randomized, controlled trials (RCTs) comparing NIV NIV was initiated in the emergency room20, 21 failed to show
with conventional therapy in the ICU showed that success- any advantage for NIV over conventional therapy is the fact
ful NIV is possible. Most striking was a reduction in the that patients usually are admitted to an ICU when other
need for intubation,1 3•14 which in the largest study trans- therapies have failed, whereas most of those presenting to
lated into improved survival and reduced length of both the emergency room have not received any treatment. A
ICU and hospital s tays.13 Complications, particularly pneu- proportion is going to improve with medical therapy. In a
monia and other :infectious complications, were reduced 1-year-period prevalence study2'7 of patients with acute ex-
markedly. 13•15-17 It is s triking that NIV was administered acerbations of COPD, of 954 patients admitted through the
for only a relatively small proportion (mean 6 hours) of each emergency department (Leeds, England), 20% were acidotic
day 13 or at modest levels for a longer period.14 With NIV, on arrival in the department; of these, 25% had completely
paralysis and sedation are not needed, and ventilation out- corrected their pH by the time of arrival on the ward. There
side the ICU is an option. Given the considerable pressure on was a weak relationship between Pa02 on arrival at hospi-
ICU beds in some countries, the high costs, and that for some tal and the presence of acidosis, suggesting that, in at least
patients admission to ICU is a distressing experience.18 this some patients, respiratory acidosis had been precipitated by
is an attractive option. high-flow oxygen therapy administered in the ambulance
There have been seven prospective, randomized, con- on the way to hospital.
trolled studies of NIV outside the ICUY~-25 Bott et al19 Angus et al22 compared NIV and doxapram in patients
randomized 60 patients with COPD to either conventional with COPD and type IT (hypercapnic) respiratory failure in a
treatment or NIV. NIV initiation, by research staff, took small randomized trial ina general ward. NIV caused signif-
90 minutes, on average (range 15 minutes to 4 hours). NIV icant improvement in Pa~ and Pac~ at 4 hours. In contrast,
led to a more rapid correction of pH and Paco2 • On an no fall in Paco2 occurred in patients treated with doxapram,
intention-to-treat analysis, there was no significant bene- and initial improvement in Pa~ was not sustained at
fit from NIV. When patients unable to tolerate NIV were 4 hours. At both 1 and 4 hours, pH was significantly bet-
excluded, a significant survival benefit was seen (9 of 30 ter in the NIV group compared with the doxapram group.
versus 1 of 26). Generalizabilty from this study, although All the patients in the NIV group were discharged home,
performed on general wards, to routine practice is difficult although one required doxapram in addition to NIV during
because staff additional to the normal ward complement set the acute illness. Of eight patients treated w ith doxapram,
up NIV. The high mortality (30%) in the control group was three died, and another two received NIV. Currently, respi-
surprising considering that the mean pH was only 7.34. In ratory s timulants are not recommended routinely, although
addition, the low intubation rate, while probably reflecting they may have a role if there is no access to NIV. 28
British practice, has been criticized. Bardi et al 23 found no significant differences in hospital
Barbe et al 20 initiated NIV in the emergency department in outcome between NIV and conventional therapy in a study
patients presenting with an acute exacerbation ofCOPD and of 30 patients w ith COPD; most patients in both groups re-
continued it in a general ward. To ease some of the problems covered without the need for invasive ventilation. Given
of workload and compliance, NIV was administered for that mean pH in the two groups was 7.36 and 7.39 and
3 hours twice a day. In this small s tudy (11 = 24), there were that no patient in either group had a pH of less than 7.30,
CHAPTER 34 NONINVASIVE VENTILATION ON A GENERAL WARD 707
these results are not surprising (as with the study of Barbe with CPE or develop CPE in the coronary-care unit to ma ke
et al2o). staff training in NIV in these areas worthwhile and to en-
In a s tudy performed in an intermediat~care unit, sure enough throughput to maintain skills. When patients
Avdeev et al25 randomly assigned 29 patients to NIV and develop CPE outside these areas (e.g., in a surgical ward), it
29 to conventional therapy alone. The patients were well is likely to be sufficiently infrequent that it is not worth train-
matched, and pH indicated a severe exacerbation (7.28 ver- ing the staff, or if trained, staff will not have had sufficient
Sl.lS 7.26). The mean duration of NJV was 29 ± 25 hours. opportunity to use and develop their skills. This is a situa-
Three patients refused NJV, of whom two required intu- tion in which the peripatetic NfV team or critical-care out-
bation and one died. In patients receiving NIV, there was a reach service may have a role. It is important that personnel
significant rise in pH and fall in Paco, after 1 hour compared are able to recognize and treat arrythmias and myocardial
with no change or a worsening in the conventional group. ischemia.32
Fewer patients in the NJV group required intubation (12%
versus 28%; p = .18) or died (8% versus 31% ), and hospital
ELEC fiVE VE NTILATION FOR CHRONIC
stay was shorter (26 ± 7 versus 34 ± 1 0 days).
VENT ILATORY FAILURE
Plant et al 24 undertook the largest study to date (11 =
236) on general respiratory wards in 13 centers. NIV was There have been a number of sm all and two large33' 34 se-
applied, by the usual ward s taff, using a bilevel device in. ries reporting the use of NIV in the successful treatment
spontaneous mode according to a simple protocol. "Treat- of diurnal ventilatory failure by the adequate control of
ment failure," a surrogate for the need for intubation, de- noctumal hypoventilation in patients with chest-wall de-
fined by a priori criteria, was reduced from 27- 15% by NIV. formity, neuromuscular disorders, and morbid obesity. Al-
In-hospital mortality was reduced from 20- 10%. This study though there are no prospective RCTs, NIV is an accepted
suggests that with adequate staff training, NIV can be ap- treatment for chronic hypercapnic ventilatory failure. It is
plied with benefit outside the ICU by the usual ward s taff unlikely that such trials will ever be performed, with mos t
and that early introduction of NIV in a general ward results researchers considering such a study to be w1ethical. Com-
in better outcomes than providing no ventilator support for parative studies of patients with amyotrophic lateral sclero-
acidotic patients outside the ICU. sis (ALS) who are treated witl1 NJV shows a clear survival
advantage when comf:ared with patients who do not opt for
CONDITIONS OTHER THAN COPD assisted ventilation.3 ' 36 A prospective RCT of NIV in ALS
There are no RCTs of NIV outside the ICU in hypoxemic has been reported in abstract form and shows clear advan-
respiratory failure. The study of Antonelli et al16 showed tages in tem1s of both survival a nd quality of life with NIV.37
that NIV was as effective as conventional ventilation in im- There ha ve been a number of small prospective RCTs of
proving gas exchange in patients with acute hypoxic res- NIV in patients with hypercapnia secondary to COPD.38-41
piratory failure. Patients receiving NIV had significantly Only one showed any benefit from the combination of NIV
lower rates of serious complications, and those treated suc- and long-term oxygen therapy,40 with the others failing to
cessfully with NTV had shorter TCU stays. Post hoc anal- show any advantage to NTV. All can be criticized primarily
ysis of patients grouped according to the simplified acute because of small numbers and because, in mos t, the ad-
physiologic scores (SAPS) showed that NIV was superior to equacy of effective ventilator support ovemight was not
conventional mechanical ventilation in patients with SAPS confirmed. 42 There have been two longer-term studies.43' 44
< 16. In patients with a SAPS ~ 16, outcome was similar, Neither showed benefit from NIV, although, again, both can
irrespective of the type of ventilation. As with acute exac- be criticized 42 for similar reasons to those outlined earlier.
erbations of COPD, it appears that it is possible to manage There may be a role for NIV in patients who suffer recurrent
patients successfull y with NJV. Further data are needed. Yet exacerbations of sufficient severity to warrant hospitaliza-
it is reasonable for selected patients to have a trial of NIV tion and acute NJV because these patients are at high risk
in an experienced noninvasive unit outside the ICU; rapid for future hospitaliza tion and death. 45 In the study of Clini
access to intubation and m echanical ventilation must be et al,44 there was a trend toward a lesser time in hospital in
available. the NIV group compared witl't an increase in the oxygen-
Cardiogenic pulmonary edema (CPE) represents a s pe- therapy group when compared with the period before the
cial case because the onset and recovery usually are both study. ICU stay was reduced in both groups but more in
rapid. Most patients present to the emergency room, but the NIV group than in the oxygen-therapy group. In an un-
some develop CPE in the ward while an inpatient. The first controlled study, the provision of NIV reduced the need
focus is delivery of standard mectical therapy, particularly for hospitalization in the year after compared with the year
nitrates.29, 30 Continuous positive airway pressure (CPAP) before home NIV was instituted and reduced costs. 46 Fur-
probably is the noninvasive mode of choice, although NIV ther studies are needed, but at present, NIV should not be
may have a role in patients with significant hypercapnia.31 considered for most patients with COPD.
Patients usually should receive ventilator support where In summary there is no prospective RCTevidence to sup-
they are because by the time arrangements have been made port the chronic use of NJV in any patient group. Most prac-
and transfer effected, most patients will have either im- titioners, however, would consider it unethical not to offer
proved or deteriorated to the point at which intubation is NIV to pa tients with chest-wall deformity and neuromuscu-
needed . Sufficient patients will attend the emergency room lar disease, and it is unlikely that there will ever be any RCTs
of NIV in these conditions. Chronic NIV is not appropriate tory failure, a nd likelihood of success witl1 NIV (Fig. 34-1).
for most patients w ith COPD. Patients who cannot sustain ventilation for more than a few
minutes when acutely unwell require continuous observa-
tion. This level of support is more likely to be available in
the JCU than in other ward environments.
Where Should Noninvasive Ventilation Although there a re no published data, anecdotally there
may be a tendency to abandon NIV more readily in an TCU
Be Performed? because intubation is easily available, and in some ways it
is easier for staff to manage a paralyzed, sedated patient
AC UTE N IV: ICU O R GENERAL WA RD? than one who is struggling with NIV. When intubation is
There have been no direct comparisons of outcome with not immediately an option, there is a need to keep going
NIV delivered in the ICU, intermediate units, and in a gen- a little longer, and a number of patients who at first sight
eral ward. It is unlikely that there ever will be such a trial. It appear to be failing can be managed successfully with a
should be appreciated that while there is some over lap, the bit of persistence. It certainly has been the experience of
skills needed for NIV are different from those requir ed for the author that problems have been solved between the
invasive ventilation. Familiarity with and confidence inNIV time that the ICU staff has been contacted and its arrival
by all members of the multidisciplinary team is the most in the ward to intubate and/ or transfer tl1e patient (10-
important factor. Nurses, physiotherapists, or respiratory 15 minu tes). ·
therapists may be the primary caregiver; this will depend on Another important difference between the JCU and the
local availability, enthusiasm, and expertise. The outcome general ward is the complexity of monitoring and the
from NIV is likely to be better on a general ward where the types of ventilators available. Monitoring serves two roles:
staff has a lot of experience of NIV than in an ICU with high (1) safety, to warn of impending catastrophe, and (2) opti-
nurse-, therapist-, and doctor-patient ratios and a high level mization of ventilator settings. Vitacca et al47 have shOWJl
of monitoring, but little experience of NIV. The patient's that setting a ventilator on the basis of physiologically de-
perspective is also important; many find their experience of rived information resulted in more complete respiratory
JCU to be unpleasant, 18 and the less intensive atmosphere muscle unloading than when the ventilator was set by expe-
of a nonin vasive unit may not be as distressing for patients rienced operators using clinical judgement a lone. ICU ven-
and their relatives. NIV may be quite time-consuming in the tilators differ from the portable devices designed primarily
early stages, and patients may benefit from the extra atten- for home use but frequently used in general wards. The
tion from caregivers, which is possible in an ICU compared principal limitation to the use of home ventilators during
with less well staffed clinical areas. acu te respiratory failure is the lack of direct online mon-
Assuming that the skills to deliver NIV are equal in the itoring of pressure, volume, and flow provided by these
various possible locations, there are a nu mber of other fac- devices. The evaluation of patient-ventilator asynchrony is
tors to be considered. These include whether or not intuba- easier with visualization of flow and pressure waveforms. 48
tion is considered appropriate should NIV fai l, the presence This may be importan t, particularly during the initiation of
of otl1er system failure, comorbidity, severity of the respira- ventilation, when it is important to assess patient-ventilator
FIGURE 34-1 The s pectrum of provision for an acu te N IV service.
lnten.~ive Care General Ward
Lower pH Higher pH
Comorbidilics No comorbidi ties
Acute
Chronic
Need for inlensi ve monitoring
1\TJV 1echnically difficult NTV technically easier
Invasive ventilalion deemed appropriate ifNrv fails Invasive venti lation not deemed appropria1e
NIV the ceiling ofintervemion
Ad vantages Advantages
Higher nurse I patient ratio CosI saving compared with ICU
More monitoring Specific inlerest / experl ise lung disease
Ready access 10 invasive ventilation Absence of immediate easy intubation encourages
greater persistence and problem so lving
More "pleasant'' environment
Disadvantages Disadvant ages

Cost Low nW"se to patient ratio
Less pleasant environment Care needs of other patients may be neglected
Easier to abandon NlV and intubate Lack of ready access to invasi ve ventilation
CHAPTER 34 NONINVASfVE VENTILATION ON A GENERAL WARD 709
TABLE 34-2 Mon itori ng Duri ng N IV ELECTIVE N IV: GENERAL WARD OR
CHRONIC- CARE FACILITY?
Esse11tinl
• Regular clinical observation The onset of established chronk ventilatory failure usually
• Continuous pube oximetry is insidious. Patients at risk are best seen and regularly re-
• Arterial blood ga~s after 1 to 4 hours of NIV and after 1 hour of viewed in specialist centers so that the onset of significant
any change in ventilator set tin&> or Fr~. nocturnal hypoventilation and the development of diurnal
• Respiratory rate--continuous or intermittent
ventilatory failure can be anticipated. As a result, NTV usu-
Desirable ally should be instituted before the patient becomes criti-
• ECG cally ill requiring HDU or ICU admission. It is advisable to
• More detailed physiologic information such as leak, expired tidal acclimatize patients to NTV at an early stage once the devel-
volume, and measure of ventilator-patient asynchrony opment of significant ventilatory failure becomes likely. De-
compensation may occur w ith an intercurrent event, mos t
commonly respiratory tract infection. NIV is much easier
in the acute situation if the patient has experienced it pre-
interaction, respiratory mechanics, and the expired tidal viously when reasonably well. In such patients, if they are
volume.49 Further work is needed to establish which vari- clinically stable, there is no need for assisted ventilation to
ables should be monitored to optimize NIV. It should "work" immediately; indeed, it does not matter if the pa-
be appreciated that high-technology monitoring is never tient is hardly able to use the ventilato r at all initially. More
a substitute for good clinical observation.50 For safety, detailed description of the use of NIV in chronic res piratory
it is recomm ended that all patients receiving NIV for failure can be found in Chapters 19 and 32.
acute ventilatory failure should have continuous moni- There is little reason to admit these patients to the ICU,
toring of oxygen saturation (5o:) by pulse oximetry, reg- and it is questionable whether, with appropriate teams in
ular assessments of arte rial blood-gas tensions (because place, the patient even needs admission to hospital. Some
there is no accurate and reliable noninvasive measure patients, particularly tJ1ose with severe neuromuscular dis-
of Peoz or, more important, pH), and respiratory rate.51 ease, have complex nursing need s, and their home environ-
The So1 should be maintained at around 92%52 to avoid ment may be better adapted to their needs than a hospital
the twin dangers of dangerous hypoxia a nd the risk of bed. lt is more pleasant for relatives and caregivers to stay in
worsening hypercapnia secondary to altering the dead- their own home. Particular iSStles for that patient con cern-
space-to-tidal-volume ratio.53 There is no reason why this ing positioning of equipm ent, ensuring adequate access to
level of monitoring cannot be provided in a general ward electrical power, and so on can be addressed. 56 If the patient
(Table 34-2). is to be admitted to hospital, the choice may be between a
If NIV is only to be provided in the ICU, the number chronic-care faci lity and a general ward. As for acute NIV,
of patients needing ICU care will increase, a nd this m ay local staff expertise is the most important factor determin-
not be n ecessary or appropriate. The study of Plant et a! 24 ing the best location (Table 34-3). Staffing and expertise be-
has s hown that NlV is an optio n outside the ICU, but the ing equal, advantages of the general ward include access to
outcom e for patients w ith a pH of less than 7.30 was no t as the TCU if things go wrong and m ore ready access to other
good as that seen for comparable patients in the studies per- specialist team s because some of these patients have other
formed in a hig her-dependency setting. Also, for reasons of complex needs that the need to star t NIV brings into focus.
training, throu ghput, quality of service, and skill retention, Adequate control of n octurnal hypoventilation needs to be
NIV is best performed in a s ingle location.27 An interme- confirmed. For some patients, overnight oximetry may s uf-
diate unit with ready access to an ICU may provide the fice; fo r others, particularly those receiving supplemental
best compromise, but s uch units are not widely available.54 oxygen, m onitoring of Pee>: is necessary. Patients also will
They can be effective, and data from the United States s ug- need intermittent arterial blood-gas analyses. These advan-
gest that they a re cost-effective.ss A study3 of 756 con- tages, however, are generalizations; depending on the na-
secuti ve patients admitted to 26 respiratory intermediate- ture of the chronic-care facility, it may be better suited than
care units in Italy with a nurse-patient ratio ranging from a general ward for providing the care and s upport for the
1:2.5 to 1:4 per shift, availability of adequate continuous other needs of patients.
noninvasive monitoring, expertise in NlV and for intu-
bation in case of NIV failure, and physician availability TABLE 34-3 Elective Ventilation for Chronic Ventilatory
24 hours a d ay showed a better outcome than that expected Failure
on the basis of APACHE II scores. The median APACHE
II score was 18 (range 1-43). The predicted inpatient m or- There b likely to be great local variation. Factors that determine
tality was 22.1%, whereas the actual mortality was 16%. the best location:
All but 48 patients had chronic respiratory d isease, mainly • Enthusiastic and trained staff
COPD (n = 451 ). These units are different from other sim- • Possibility of colocating with acute fJV unit
ila r units in being able to care for intubated patients; this • Access to expertise in the management of nonrespiratory
aspects of care
has ma jor implications for training of medical and nurs-
• Diagnostics, e.g., sleep laboratory
ing staff and may no t be possible in many health care
• Access to ICU
systems.
THE ADVANTAGE OF THE GENERAL WARD of failure of NJV and the potential need for endotracheal
intubation is higher.68 If it has been decided that NJV is the
An acute and a chronic NIV service depends critically on
local factors, particularly the skill levels of doctors, nurses, ceiling of treatment, this is not necessary; indeed, if NJV
and therapists. The major advantage of the general ward is is failing, the patient may be allowed to die in a slightly
that it sits in the middle of the spectrum of locations for NIV less high-tech environment than that afforded by most
ICUs.
provis ion and is likely to treat the greatest number of pa-
tients. Use of skills is a key factor in developing and retain-
ing them. The s kills learned looking after patients needing HYPOXEMIC RESPIRATORY FAILURE
N1V acutely are equally relevant for patients being started These patients are bes t managed in an ICU because the risks
electively on NJV. Familiarity with the nonrespiratory needs of failure are higher and because the major problem is a fail-
of patients with complex neuromuscular or musculoskele- ure of oxygenation. Patients are more likely to need prompt
tal disorders, learned when patients are admitted electively invasive ventilation if they are deteriorating or have other
to start NJV, are transferable to the care of such patients organ failure; moreover, ventilators usually used on gen-
needing NJV acutely or for weaning. Continuity of care is eral wards are those designed primarily for home use, and
also important. Some patients start home ventilation after a high Fro 1 ca1mot be delivered. One further consideration
an acute event, and the option of dealing with both aspects was highlighted by Delclaux et al69 in a study on the use of
in the same place and with the same care team probably is noninvasive CPAP in patients with hypoxemic respiratory
advantageous to the patient and caregivers. failure; there was a trend toward more cardiorespiratory
arrests in the CPAP group. The increase was attributed to
the improvement in oxygenation and other physiologic pa-
rameters while the patients were using CPAP, which led to
Selection of Patients for NW a false sense of security; when patients take the mask off,
in a General Ward even for a short period, So1 may fall rapidly, putting them
at high risk. Any patient who desaturates within seconds
ACUTE RESPIRATORY FAILURE
of removing a mask should be monitored very carefully,
usually in an ICU, and probably this should be considered
COPD an indication for intubation. From a sh1dy performed by
The place of N1V in the management of COPD is now well Hilbert et al 70 in immunocompromised patients, it is clear
established.57•58 The pH at the time NJV is initiated is the that the institution of intemuttent NJV earlier than would
best single predictor of severity and the likelihood of suc- be the case for invasive ventilation conferred a dear sur-
cess with the noninvasive approach. 59 Moreover, changes vival benefit in patients who are known to have a very poor
in pH and respiratory rate are easily measurable and use- prognosis,11and this could be performed safely outside the
ful in predicting the likelihood of a successful outcome ICU.
from NJV. Arterial blood gases should be checked at base-
line and after 1-4 hours because a number of studies have
shown that the change in arterial blood-gas values, partic- CHRONIC RESPIRATORY FAILURE:
ularly pH, after a short period of NJV predicts a successful ELECTIVE INSTITUTION OF NIV
outcome. 13• 19• 6~ 4 Patients who have been intubated and The choice of location is usually between an institution (gen-
are likely to fail a weaning attempt adopt a pattern of rapid eral ward or chl'Onic-care facility, depending on local fac-
shallow breathing when disconnected from the ventilator,65 tors) and the home. Patients will need admission to an in-
suggesting that they are breathing against an unsustainable stitution if NJV is likely to be problematic, requires 24-hour
load. A reduction in respiratory rate with NJV has been vari- nursing support, there is a risk of significant decompensa-
ably observed in a number of studies; larger falls generally tion, there are other care needs best addressed in an insti-
are associated with a successful outcome from NJV,13•61· 62 tution, or there is no infrastructure in place to support the
although this is not always seen.66 Data from the largest patient at home. Some patients also will require more de-
study67 showed that hydrogen ion concentration at enroll- tailed inves tigation, such as polysomnography, before NIV
ment (odds ratio 1.22 per nmol/liter) and Paco2 (odds ratio is started.
1.14 per kPa) were associated with treatment failure. After
4 hours of therapy, improvement in acidosis (odds ratio
0.89 per nmol/liter) and/ or fall in respiratory rate (odds ra-
tio 0.92 per breath per minute) were associated with success.
Implications for Staffing and Training
If at least one of these two variables was improving, success- (Table 34-4)
ful NJV was likely. pH therefore is useful in determining,
first, who should receive NIV, second, in what location, and NIV has been reported to be a time-consuming proced ure72;
finally, when the patient can or should move to a more or as with any new technique, there is a learning curve, and
less intensive location. Generally speaking, the lower the the same authors subsequently published more encourag-
pH, the greater is the risk to the patient of needing invasive ing results. 73 A number of ICU studies have shown that a
ventilation if NlV is not offered or, if it is attempted, of fail- significant amount of time is required to establis h the pa-
ure. The more acidotic the patient, the greater is the need tient on NJV, but this drops off substantially in subsequent
for that patient to be managed in an ICU because the risk days.14•74·75 It is possible, therefore, that NJV may have a
TABLE 34-4 Key Training Requirements tice without any consideration of the economic implications.
Even techniques with a dear clinical advantage may not be
Understanding the rationale for assisted ventilation endorsed in the current health care climate without a favor-
Mask and headgear selection and fitting able cost-effectiveness analysis. The first step in an economic
Ventilator circuit assembly analysis is to calculate the cost of an intervention. Relevant
Theory of operation and adjusting ventilation to achieve desired costs for ventilation include equipment, supplies, capital,
outcome
Principles and practice of humidification
and overhead. More complex is the calculation of the costs of
Inhaled therapy for U1e patient receiving NIV the care for patients, including medical and paramedic time
Cleaning and general maintenance and the level of assistance, laboratory and pharmacy costs,
Undcn.tanding how to monitor progress nutrition costs, and ventilation costs. The daily cost of NIV
Ethical is!>ues relevant to the care of patients with incurable disease is similar to that of standard medical therapy 14 or invasive
Problem solving-the ability to recognize serious situations and act ventilation (calculated only on the first day of treatment).14
accordingly According to the different studies and countries, the mean
daily cost of NlV varies from about $85074 to $150014•76;
the difference results mainly from salaries of the person-
much greater impact on nursing workload outside the ICU, nel, which are much higher in the United States than in
where nurses have responsibility for a larger number of pa- Europe. The second step is to evaluate the outcome for pa-
tients. In the study of Bott et al,19 there was no difference tients. Outcomes may be calculated in terms of economic
in nttrsing workload, assessed by asking the senior nttrse to resources saved or created, efficacy of treatment in improv-
rate, on a visual analogue scale, the amount of care needed ing survival or, in the case of NTV, rate of intubatio n, or as
in the conventional and NlV groups. This, however, is an impact of a technique on quality of life.
insensitive way of measuring nursing needs; in addition, Although the findings are not consistent, some of the
some of the potential extra work associated with NIV was larger studies have shown that NIV can shorten length of
performed by supernumerary research staff. In the study ICU and/ or hospital stay compared, for example, with med-
of Plant et a1,24 NN resulted in a modest increase in nurs- ical therapy or invasive ventilation.13• 14• 16•17•70·77 In no study
ing workload, assessed using an end-of-bed log, in the first has NIV been shown to lengthen hospital stay. Although not
8 hottrs of the admission, equivalent to 26 minutes, but no the primary aim of the studies, the finding of reduced hos-
difference was identified thereafter. No data exist, however, pital, and particularly ICU, length of stay creates or saves
on the effect NlV on the care of other patients on the ward, resources and thereby indicates a cost benefit from NIV.
nor whether outcome would have been better had nurses There have been two detailed cost-effectiveness studies of
spent more time with patients receiving NIV. Most of the NIV: one in North America in the ICU the other in the United
centers that participated in the study had little or no pre- Kingdom, where NIV was delivered on general wards. In
vious experience of NIV and therefore required training the former, base care was modeled for a tertiary-care teach-
in mask fitting and application of NIV. Formal training in ing hospitaJ.78 The two alternatives considered were NIV
the first 3 months of opening a ward by a research doctor and standard medical therapy, w hereas the main outcomes
and nurse was 7.6 hours (SD 3.6). Thereafter, each center were modeled, and calculated were costs, mortality, and
received 0.9 hour per month (SD 0.82) to maintain skills. It intubation rntes. To detennine clinical effectiveness, the au-
should be appreciated that there was no need to make subtle thors used a meta-analysis of randomized trials. Then a de-
adjustments to ventilator settings, which all was done ac- cision tree was constructed, and probabilities were applied
cording to protocol. Much more training would be needed if at each chance node using research evidence and a com-
sophisticated ventilators are used. This underlines the fact, prehensive regional database. The authors concluded that
however, that NIV, in whatever location, is not just a ques- NIV was more effective than standard treatment in reduc-
tion of purchasing the necessary equipment but a lso of staff ing hospital mortality and also less expensive, with a cost
training. saving of about $2500 per patient admission.
Although considerable input is likely when a unit com- Intensive care is also expensive care. Intermediate units
mences to provide an NTV service, thereafter, as long as a may provide an alternative to the classic ICU at reduced
critical mass of nurses and therapists remains, new staff will cost.>l The daily costs of a ventilated patient may be re-
gain the necessary skills from their colleagues. Given that duced by two-thirds when IV is performed_ in a special-
NIV in the more severely ill patient may require as much ized respiratory unit rather than in a n ICU.55 These costs
input as an invasively ventilated patient,74 there usually can be reduced still further when NIV is performed on a
should be one nurse responsible for no more than three or general ward,19 although effectiveness may not be as good
fottr patients, although this will depend on the other care as in higher-dependency settings. Outcome in patients with
needs of the patients. In the less severely affected patient, a pH of less than 7.30 in the study of Plant et al24 was not
NIV can be successful with a lower level of staffing. 24 as good as the results obtained in the rcu in patients with a
similar severity of ventilatory failure, at least as evidenced
by the pH. 13• 14•77 Carlucci et a1 80 showed tha t over time, as
Economic Considerations practitioners develop the necessary skills and grow in con-
fidence with NIV, practice changes. They found that after
Economic analysis is complex. As a result, many diagnostic a few years, patients w ith more severe acidosis were ven-
and therapeutic technologies have been adopted into prac- tilated successfully with NN; more patients, usually those
with a higher pH, received NIV on general wards, with sig- 13. Brochard L, M ancebo J, Wysocki M, et al. Nonin vasive ventilation
nificant cost savings, compared with when they first started for acute exacerba tio ns of chronic obstructive pulmonary disease.
providing an acute NIV service. New Eng! J Med 1995; 333:817- 22.
14. Krame r N, Meyer TJ, Mch arg J, e t aJ. Randomized, prospective
trial of noninvasive p ositive pressure ventilation in acute respi·
rato ry failure. Am J Respir C rit Care Mcd 1995; 151:1799-806.
15. Nava S, Ambrosino N, Clini E, et al. No ninvasive mechanical
Conclusion ventilation in the weaning of patie nts with respiratory failure
due to chronic obstructive pulmona ry disease: A randomized,
Staff training and experience are more important than lo- controlled trial Ann Intern Med 1998; 128:721-8.
cation. Adequate numbers of staff, skilled in NIV, must be 16. Antonelli M, Conti G, Rocco M, N al. A comparison of noninva-
available throughout 24 hours. Because of the demands of sive positive-pressure ventilation and conventional mechanical
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skill retention, acute NJV usually is best carried out in one Med 1998; 339:429-35.
17. Antonelli M, Conti G, Bufl M, et al. oninvasive ventilation for
single-sex location with one nurse responsible for three to
treatment of acute respiratory failure in patients undergoing solid
four patients. Basic m onitoring, at least pulse oximetry and o rgan transplantatio n: A randomized trial. JAMA 2000; 283:235-
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47. Vitacca M, Nava S, Confalonicri M, et al. The appropriate set- 69. Dclclaux C, L'Her E, Alberti C, et al. Treatment of acute hypox-
ting of noninvasive pressure support ventilation in stable COPD emic nonllypcrcapnic respiratory insufficiency with continuous
patients. Chest 2000; 118:1286-93. positive airway pressure delivered by a face mask: A random-
48. Kacmarek RM. NIPPY: Patient-ventilator syncluony, the differ- ized, controlled trial. JAMA 2000; 284:2352-60.
ence between success and failure? Intensive Care Med 1999; 70. Hilbert G, Gruson D, Vargas F, et al. Noninvasive ventila-
25:645- 7. tion in immunosuppressed patients with pulmonary infiltrates,
49. Calderini E, Confalonieri M, Puccio PG, et al. Patit'nt-ventilator fever, and acute respiratory failure. New Eng! J Med. 2001; 344:
asynchrony d uring noninvasive vt'ntilation: The role of expira- 481...:7.
tory trigger. Intensive Care Med 1999; 25:662- 7. 71. Hill NS. Noninvasive vt'ntilation for immunocompromised pa-
50. Tobin MJ. Respiratory monitoring. JAlviA 1990; 264:244-5'1 . tients. New Eng! J Med 2001; 344:522-4.
72. Chevrolet JC, Jolliet P, Abajo B, et al. Nasal positive pressure 77. CclikcJ T, Sungw· M, Ceyhan B, Knrakurt S. Comparison of
ventilation in patients with acute respiratory failure. Chest 1991; noninvasive positive pressure ventilation with standard medi·
100:775-82. cal therapy in hypercapnic acute respiratory failure. Chest 1998;
73. Chevrolet JC, jolliet P. Workload on non-in vasive ventilation. 114:1636-42.
Ln: Vincent JL, editor. Year book of intensive and emergency 78. Keenan SP, Gregor J, SibbaJd WJ, ct al. Noninvasive positive
medicine. Berlin: Springer, 1997: 505- 13. pressure ventilation in the setting of severe, acute exacerbations
74. Nava S, Evangelisti l, Rampulla C, et al. Human and financial of chronic obstntctive pulmonary disease: More effective and less
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75. Hilbert C, Cruson D, Vargas F, et al. Noninvasive ventilation for ward based non-invasive ventilation for acu te exacerbations of
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Eur Respir J 2000; 16:710-6. domised, controlled trial. Br Med J 2003; 326:956-61.
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lator and the patient's system of control of breathing. Thus
PART IX physicians who deal with ventilated patients should know
the effects of mechanical ventilation on control of breathing,
PHYSIOLOGIC EFFECTS as well as their interaction. Ignorance of these issues may
prevent the ventilator from achieving its goals and also lead
OF MECHANICAL to significant patient harm.
VENTILATION
Physiology
Chapter 35 _ _ _ _ _ __ _ __ The respiratory control system consists of a motor arm,
which executes the act of breathing, a control center located
EFFECTS OF in the medulla, and a number of mechanisms that convey
information to the control center.5•6 Based on information,
MECHANICAL the control center activates spinal motor neurons that sub-
serve the respiratory muscles (inspiratory and expiratory);
VENTILATION ON the intensity and rate of activity vary substantially between
breaths and between individuals. The activity of spinal mo-
CONTROL OF tor neurons is conveyed, via peripheral nerves, to respira-
tory muscles, which contract and generate pressure (Pmus).
BREATHING According to equation of motion, Pmus a t timet during a
breath is dissipated in overcoming the resistance (Rrs) and
DThfl~SGEORCOPOULOS elastance (Ers) of the respiratory system (inertia is assumed
to be negligible) as follows:
Pmus(t) = Rrs x V(t) + Ers x 6. V(t) (1)
where 1:!. V(t) is instantaneo us volume relative to passive

PHYSIOLOGY functional residual capacity (FRC) and V(t) is instan-
EFFECTS OF MECHANICAL VENTILATION taneous flow. Equation (1) detem1ines the volume-time
ON FEEDBACK SYSTEMS profile and, depending on the frequency of respiratory
Chemical Feedback muscle activation, ventilation. Volume-rune profile affects
Response of Respiratory Motor Output to Chemical Pmus via neuromechanical feedback; inputs generated
Stimuli from other sources (cortical inputs) may modify the fw1c-
Operation of Chemical Feedback tion of control center. Ventilation, gas-exchange proper-
Neuromechanical Feedback ties of the lung, and cardiac function determine arte-
Behavioral Feedback rial blood gases, termed arterial oxygen tension (PaOz) and
INTERACTIVE EFFECTS OF PATIENT-RELATED arterial cnrbon dioxide tension CPacQ.z), which, in tum, af-
FACTORS AND VENTILATOR ON CONTROL fect the activity of control cen ter via peripheral and cen-
OF BREATHING tral chemoreceptors (chemical feedback). This system can
Mechanics of Respiratory System be influenced a t any level by diseases or therapeutic
Characteristics of the Muscle Pressure Waveform interventions.
THE FUTURE During mechanical ventilation, the pressure provided by
CONCLUSION the ventilator (Paw) is incorporated into the system. 3 Thus
the total pressure applied to respiratory system at time t
The main reasons for instituting mechanical ventilation are [ProT(t)] is the sum of Pmus(t) and Paw(t). As a result, the
to decrease the work of breathing, support gas exchange, equation of motion is modified as follows:
and buy time for other interventions to reverse the cause of
respiratory failure. 1 Mechanical ventilation can be applied PToT(t) = Pmus(t) + Paw(t) = V(t) x Rrs + 1:!. V(t) x Ers (2)
in patients who are making or not making respiratory ef-
forts, whereby assisted or controlled modes of support are The relationships of Eq. (2) determine the volume-
used, respectively. 1 In patients without respiratory efforts, time profile during mechanical ventilation, which via neu-
the respiratory system represents a passive structure, and romechanical, chemical a nd behavioral feedback systems
thus the ventilator is the only system that controls breathing. affects the Pmus waveform (Fig. 35-1). The ventilator
During assisted modes of ventilator support, the patient's pressure, by changing flow and volume, may influence
system of control of breathing is w1der the influence of the these feedback systems and thus alter either the patient's
ventilator pump. 2- 4 In the latter instance, ventilatory output control of breathing itself or its expression. In addi-
is the final expression of the interaction between the venti- tion, Pmus, depending on several factors, alters the Paw
715
716 PART IX PHYSIOLOGIC EFFECTS OF MECHANICAL VENTILATION
Response of ventilator
to Pmus
.••··················~ .••
Ventilator Factors .••
•• •
triggering } FIGURE 35·1 Sch ematic representation of
control variables ••• vari ables that determ ine th e volume-time
••
cycling off •
•
.. profile during mech a.n ical ventilation .
Pmus(t), in stan taneous respiratory
Patient Factors •
RS mechanics. • ..
~················ muscle pressure; Paw(t), airway
• . (ventilator) p ressure; V(t), instantaneous
.
Pmus waveform • Bow; A V(t), instantaneous volume
t
••
• relative to passive functional residual
capacity of respiratory system; Rrs,
.......................
'
~ Pmus
(t)
+ Paw(I) -- V'(t) ·Rrs + ~V(I)·Ers resistance of th e respiratory system; Ers,
elastance of the respiratory system; RS,
\ Response of Pmus
~ respiratory system. Neuromechanical,
ch emical, and behavioral feedb ack
Volume-time profile systems are the main determinants of
'. \to ventilator delivered Pmus. Th e functional op eration of the
~ breath
~ ventilator m ode (triggering, contr ol, and
cycling-off variab les) and patient-related
•..
••
•
Chemical, Neuro-mechanical, Behavioral
Feedback
factors (n am ely, resp iratory sys tem
mechanics and the Pmus waveform)
•• determine the response of the ventil ator to
, ... .•
•
...................................................•.•........
• ~ Pmus .
waveform (see Fig. 35-1). Thus, during assisted mechanical RESPONSE OF RESPIRATORY MOTOR O UTPUT
ventilation (i.e., Pmus =I= 0), ventilatory output is not under TO CHEMICAL STIMULI
the exclusive influence of patient's control of breathing; in-
C02 STIMULUS
stead, it represents the final expression of an interaction be- Carbon dioxide (C~) is a powerful stimulus of breathing: 7
tween ventilator-delivered pressure and patient respiratory
This stimulus, expressed by Paco,, largely depends on the
effort.
product of tidal volume (VT) and breathing frequency (f)
(i.e., minute ventilation) according to the Eq.(3):
Effects of Mechanical Ventilation

where Yeo, is C02 production, and Vo/VT is dead space to
on Feedback Systems VT ratio. Because minute ventilation is an adjustable vari-
able in ventilated patients, understanding the relationship
CHEMICAL FEEDBACK between respiratory motor output and C02 stimuli is of
Chemical feedback refers to the response of Pmus to Pao 21 fw1damental importance.
Paco1 and pH.5-7 In spontaneously breathing and mechan- Several studies have examined the respiratory motor out-
ically ventilated patients, this system is an important deter- put to C02 in ventilated conscious healthy subjects. 8, 15- 18
minant of respiratory motor output both during wakeful- Major findings include
ness and sleep.8- 13
Mechanical ventilation can influence chemical feedback 1. Manipulation of Paco2 over a wide range has no appre-
simply by altering the three variables Pa~, Pac~ , and ciable effect on respiratory rate. Despite hypocapnia, sub-
pH. Hypoxemia, hypercapnia, or acidemia may be cor- jects continue to trigger the ventilator with a rate similar
rected by mecllaJtical ventilation and thus modify activity to that of eucapnia. Respiratory rate increases slightly
of the medulary respiratory controller via peripheral and when Pac:o, approaches values well above eucapnia
central chemoreceptors.·7 The effects of mechanical venti- (Fig. 35-2).
lation on gas-exchange properties of the lung are beyond 2. The intensity of respiratory effort (respiratory drive) in-
the scope of this chapter and are discussed in Chapter creases progressively as a function of Pea,. This response
37. In this chapter, the fundamental elements of the re- is evident even in hypocapnic range. Over the range
sponse of respiratory motor output to chemical stimuli, of C~ s timuli examined, it was not possible to iden-
their rela tionship to unstable breathing, and the opera- tify a threshold below which the response of respira-
tion of chemical feedback during mecllanical ventilation are tory motor output did not exist. The response slope
reviewed. increases progressively with increasing C02 stimuli,
CHAPTER 35 EFFECTS OF MECHANICAL VENTILATION ON CONTROL OF BREATHING 717
350
300
<1>
.5 250
Q)
CJ)
ro 200
Ll
.....0 ISO
;ft. 100
50
0
20 25 30 35 40 45 50 55
FIGURE 35-2 Schematic representation of th e response of respiratory frequency (open squares) and p ressure-time product of the
inspiratory muscles per breath (an ind ex of the intensity of patient effort, closed squares), both expressed as a percen tage of values durin g
sp ontaneous eupnea (baseline), to C0 2 challenge in conscious healthy subjects venti lated with a high level of ventilator assistan ce. PETco1
is end-tidal Pc 02, and the dotted vertical line is PETco 2 during spontan eou s b reathing (eupnea). Contrast the vigorous response of
intensity of inspi ratory effort to C0 2, even in th e hypocapn ic range, with the response of respir atory frequency, which remains at eucapnic
level over a broad ran ge of C0 2 sti muli. The resp onse is based on data from refs. 8 and 15-18.
reaching its maximum in the vicinity of eucapnic values tient effort, whereas respiratory rate is affected consider~
(see Fig. 35-2). ably less:7 There is no reason to expect a different re-
3. There is no fundamental difference in the response to C02 sponse pattern during mechanical ventilation. Indeed, this
between various ventilator modes. is the case regarding the h ypoxic response in normal con-
4. Above eupnea, the slope of the response d oes not dif- scious subjects ventilated in assist-control mode during
fer significantly w ith that observed during spontaneous eucapnia. 22 Indirect data also revealed that during eu-
breathing, suggesting that mechanical ventilation per se capnia, the sensitivity of respiratory motor output to hy-
does not cons iderably modify the sensitivity of respira- poxia was not m odified by mechanical ventilation." Dur-
tory system to C02. ing mild hyp ocapnia, however, the response was attenu-
ated, whereas a t moderate hypocapnia (end-tidal Pco2 ""'
During sleep (or sedation), the response of res piratory 31 mmHg) the response was negligible. The latter observa-
motor output to c~ differs substantially from that during tions may be relevant clinicaly because ventilated patients
wakefulness, secondary to loss of the suprapontine neural d o not always keep Pacaz at eucapnic levels and can become
input to the medullary respiratory controller (loss of the hy pocapnic. 18
wakefulness drive to breathe).r1, 19 In ventilated sleeping
subjects, a d ecrease in PaCOl by a few millimeters of mercury CHEMICAL STIMULI AND UNSTABLE BREATHING
causes apnea.11 Sleep unmasks a highly Paco,-sensitive ap- The response pattern of res piratory motor outpu t to C02
neic threshold, whereby apnea is induced by small transient during sleep is relevant to the occurrence o f periodic breath-
reductions in Paco2 below eupnea. 11• 19 Respiratory rhy thm ing in mechanically ventilated patients. Unstable breathing
is not restored until Paco2 has increased significantly above in critically ill patients did not receive much attention in the
eupneic levels. The di fference between eupneic Paco, and past. Recent evidence, however, indica tes that this breathing
Paco, at apneic threshold, referred to as C02 reserve,20 d e- pattern might increase the m orbidity and mortality of crit-
pends on several factors (see below). This reserve d eter- ically ill patients because it can cause sleep fragmentation
mines the propensity of an individual to d evelop breathing and patient-ventilator d yssynchrony. 23·24 Sleep deprivation
instability during sleep; propensity increases as C02 reserve may cause serious cardiorespiratory,25•26 neurologic,27·28
decreases. Similar to wakefulness, the response of respira- immu nologic, and metabolic consequences. 29 - 32
tory motor output to C0 2 is mediated mainly by the inten- The following is a brief review of the factors that can lead
sity of respira tory effort, w hereas res piratory rate decreases to tmstable breathing. ln a closed sys tem governed mainly
abruptly to zero (apnea) when the CQz apneic tlueshold is by chemical control (such as occurs during sleep or sed a-
reached.21 tion), a transient ch ange in ventilation a t a given metabolic
rate (~\!initial ) will result in a transient change in alveolar
OTHER CHEMICAL STIMULI gas tensions. This change is sensed by peripheral and cen-
The effects of mechanical ventilation on the response of res- tral chemorecep tors, w hich, after a variable delay, exert a
piratory m otor output to stimuli other than C02 have not corrective ventilatory response (~ Vcorrective) that is in the
been studied adequately. In a stead y state during w akeful- opposite direction to the initial perturbation33- 35 (Fig. 35-3).
ness, the effects of oxygen (02) and pH on breathing pat- The ratio of~ V corrective to~ V;nltial defines the loop gain of the
tern are similar qualitatively to that observed with C02 : system, an engineering concept introduced by Khoo et al. 33
Changes in 0 2 and pH mainly alte.r the intensity of pa- Loop gain is a dimensionless index that is the mathematical
TABLE 35-1 Effects of Mech anical Ventilation on Gain Factors

Gplant
FRCi and Gain Changes
V'/0 '#-ti,
VofV1 .LHi, Gain Factors
P"C02.J.Hi, (Influence) Ventilator Effect" Gain Change
pAQ 2.J.H f,
CO.l.Hi, Lung volume t .1-Gplant
metabolic rate_ (stabilizing)
Cardiac output ,j. t Cplant. tG~dback
LlV' initial (destabilizing)
Thoracic blood volume ,j. i G rtc,lback
(destabilizing)
G feedback
Mixlng.J.Hi Paw response to Pmus t t G eontrollcr
Circulatory delay.!.+-+i (destabilizing)
DiHusion delayH Alveolar PC02 ,j. ! Gptant
(sta bilizing)
Alveolar P(h t ,j.C plant, .J. Goontrollct
(stabilizing)
Respiratory clastance ,j. t C controllcr
(destabilizing)
G controller
Chemosensitivity H ABBREVIATIONS: Pav,•, airway pressure; Pmus, respiratory muscle pressure; .J,,
Pmus .k-ti decrease; t, increase.
Ers t+-+i • Mechanical ventilation may also exert opposite effects on the various gain
Rrs .k-ti factors.
Paw i
FIGURE 35-3 Schematic representation of th e variables that
determine the propensity of an individual to develop periodic Positive-pressure breathing exerts multiple effects on
breathing in a closed system dominated by chemical feedback. loop gain by influencing almost all the factors that deter-
Loop gain is the product of three gain~ plant, feedback, and
mine plant, feedback, and controller gains. The effects are
controller. Instability occurs when A ~corrective (the final
response) is 180° out .of phase wi~ A Vinitial (the transient initial
complex and at times opposing and variable (Table 35-1; see
perturbation) and A YcorrectivciAV;nitial > 1. Mecltanical also Fig. 35-3). Nevertheless, the effect of mechanical venti-
ventilation, by affecting almost all variables of the system lation on controller gain exerts the most powerful influence
<T Increase, +-+ no change, ! decrease), may change both the on the propensity to develop breathing instability. 12. 21 • 24 The
magnitude and the dynamic component of loop gain and thus the magnitude and direction of the change in controller gain de-
propensity of an individual to develop periodic breathing. pends on the ventilator mode, the level of assistance, the me-
LG, Gplant• Gfecdback' and Goontrollcu loop, plan t, feedback, and chanics of the respiratory system, and the Pmus waveform
controller gains, respectively; APccoz and APc02 , the difference (see below).'12• 18•21•24 The disease states also may interfere
in partial pressures of C02 and Oz in mixed pulmonary capillary with the effects of mechanical ventilation on loop gain. For
blood, respectively; APchco 2 and APch02, the difference in
example, positive-pressure ventilation may increase or de-
partial pressure of COz and O z at chemoreceptors (peripheral and
<;entral), respectively; FRC, functional residual capacity; crease cardiac output, causing corresponding changes in cir-
V/Q, ventilation-perfusion ratio; CO, cardiac output; VoNT, culatory delay defending on cardiac function and intravas-
dead-space fraction, PAco1 an d PA 02, alveolar partial pressure of cular volumEf6- 3 (see Chapter 36). It has been shown that
C02 and 0 2 , respectively; Pmus, p ressure developed by nocturnal mechanical ventilation in patients with conges-
respiratory muscles; Paw, airway (ventilator) pressure; a.n d Ers tive heart failure decreases the frequency of Cheyne-Stokes
and Res, elastance and resistance of respiratory system, breathing, presumably by causing an increase in cardiac
respectively. output secondary to after load reduction. 40 - 42
In addition to C02, 0 2 and pH can play a key role in
producing unstable breathing in ventilated patients dur-
product of three types of gains: plant gain (the relationship ing sleep (or sedation). It is well known that hypoxia, act-
between the change in gas tensions in mixed pulmonary ing via peripheral chemoreceptor stimulation, decreases
capillary blood and D.v inlti3J), feedback gain (the relation- Pace,- The result Teduces the plant gain (stabilizing in-
ship between gas tensions at the chemoreceptor level and fluence); for a given change in alveolar ventilation, Paco2
those at the mixed pulmonary capillary level), and con- will change less when baseline Pace, is low than when it
troller gain (the relationship between D. Y correclive and the is high. 20 Hypoxia, however, increases the controller gain
change in gas tensions at the chemoreceptor level) (see to a much greater extent43 because the slope of ventila-
Fig. 35-3) . Loolisgain has both a magnitude and a dynamic tory response to C02 below eupnea increases/ a highly
component.33- In this system, instability occurs when the destabilizing influence.33- 35 Similar principles apply if pH
corrective response is 180° out of phase with initial distur- is considered as a cl1emical stimulus; acidemia decreases the
bance (dynamic component) and loop gain is greater than plant gain Oowers Paco2 ) and increases, to a much lesser ex-
1 (magnitude component). This instability leads to fluctu- tent, the controller gain. 20•43 During mechanical ventilation,
ation in chemical stimuli, namely, Pee,. U Pco2 reaches the the propensity to unstable breathing in the face of chang-
apneic threshold, apnea occurs. ing 0 2 and pH stimuli depends on a complex interaction
0-IAPTER 35 EFFECTS OF MECHANICAL VENTILATION ON CONTROL OF BREATHING 719
between the effects o f these stimuli and mechanical ventila-
A Met.bollc A c idosis
tion on plant, feedback, and controller gains (Fig. 35-4; see
I u uJJ J J
also Table 35-1).
VT(I) ] JI JHl UJ WJJJj'
Pm
10
(em H-,0) o1
OPERATION OF CHEMICAL FEEDBACK E M Gdl
The ventilator mode is a major determinant of driving pres- (a.u .)
sure for flow and thus arterial blood gases . Before dis- PETC02 ] mmrmnnnnrlnnco, •...,•• .7,, rnmHg
cussing the operation of chemical feedback, it is useful to (mmHg)
review briefly the functional features of three modes of as-
sisted ventilation, na mely, assist-control ventilation (ACV), 1 mon
pressure-support ventilation (PSV), and proportional-assist
B Met.bollc Alkalosis
ventilation (PAV) (for d etailed descriptions, see Chapters 7,
9, and 13). Figure 35-5 shows the response of the ventila tor to
respira tory effort in a representa tive subject ventilated w ith
each mode in the presence and absence of C02 challenge. 18
With C02 challenge, Paw decreases with ACV, it remains Pm
constant with PSV, and it increases with PAV. Pressure-time
product of ins piratory muscle pressure (PTP-Pmus1) is an
(em H 2 0) 10 • -----~·~J~·~~~J~
l ~I~
'·~·~·--~
' ' •'~~·J..
' __
accurate index of the intensity of inspiratory effort. 44 With f EMGdl
ACV, the ratio of VT to PTP-Pmus 1 per breath decreases w ith (a.u .)
increasingPmus (see Chapter 7); the ratio is largely indepen- co, roeo"'CC • •3.4 mmtiiJ
dent of inspiratory effort w ith PAV (see Chapter 13). With PI!TC02 401
PSV, VT/PTP-Pmus1 per breath may change in either direc- (mmHg) 0
tion with increasing Pmus, depending on factors such as the
1 min.
level of pressure assist and cycling-off criterion, chang e in
Pmus, and mechanics of the respiratory system (see Chapter c Hypoxia
9). With PSV, in the absence of active termination o f pressure
~I
d elivery (with expiratory muscle contraction), the ventila-
VT ( I )
tor d elivers a minimum Vr, which may be quite high, de- . ll«AIAIIIAIIII!I!JI jjiiUIIJj ll U 11 .II .U
pending on the pressure level, mechanics of the respiratory
Pm
system, and cycling-off criterion.21 ':a II_llJU I ILIJ
(e m H 2 0)
Assume that in a ventilated patient Pac~ drops because
EMGdl
of an increase in the set level of assistance or d ecrease in
metabolic rate and/or Vo/Vr ratio.14 During wakefulness, (a.u . )
co,··- •
]
·3.4 mmHg
patients will react to this drop by decreasing the inten- PET C02
sity of their ins piratory effort, whereas the breathing fre- ( mmHg)
quency will remain relatively constant (see " Response of
Respiratory Mo tor Output to Chemical Stimuli," above) .
1 min.
The extent to which a patient is able to prevent respira-
FIGURE 35·4 Tidal volume (VT), airway pressure (Pm),
tory alkalosis via operation of cl1ernical feedback depends
diaphragmatic EMG (EMGdi, arbitrary units), and partial
almost exclusively o n the relationship between the inten-
pressure of end-tidal C02 (PETco1 ) in a tracheostomized dog
sity of patient inspiratory effort and the volume delivered during non-REM sleep without and with pressure-support
by the ventilator (i.e., Vr / PTP-Pmus1) . Similarly, if Paco2 ventilation at a pressure level that caused periodic breathing.
increases (decrease in a ssistance level, increase in metabolic A. At a background of 5 hours of metabolic acidosis (pH 7.34,
rate and / or V 0 / Vr ratio), the patient will increase the HC03- 16 mEqlliter, Paco2 30 mmHg). B. At a background of
inten sity of inspiratory effort and, to much lesser extent, 1 hour of metabolic alkalosis (pH 7.51, HC03- 35 mEq/liter,
respira tory frequency. Thus Vr/PTP-Pmus1 per breath is Paco 2 44 mmHg). C. During hypoxia (Pa 02 47 mmHg, Pac~ 31
critical for the effectiveness of chemical feedback to com- mmHg). At a background of metabolic acidosis, C0 2 reserve was
pensate for clumges in chemical stimuli (Paco2 ). For given quite high; consequ ently, the pressure level that caused periodic
respiratory system mecha nics, Vr / PTP-Pmus1 is heavily de- breathing (20 em H2 0) was significantly higher than the
corresponding values (.-v10 cmH2 0) during metabolic alkalosis
pendent on the mode of support. Thus the effectiveness of
or hypoxia. Hyperventilation during spontaneous breathing was
chemical feedback in compensating for changes in chemi-
similar during metabolic acidosis and hypoxia (similar
cal stimuli should be mode-dependent. Modes of support stabilization influence via a decrease in plant gain secondary to
that permit the intensity of patient inspiratory effort to be low Paco2 ), indicating that the destabilizing influence of hypoxia
expressed on ventilator-delivered volume improve the ef- was caused by an increase in controller gain (hypoxic increase in
fectiveness of chemical feedback in regula ting Paco2 and the slope of C02 below eupnoea). (Used, w ith permission, from.
particularly in preventing respiratory alkalosis. In normal Dempsey et nl:] Physiol560:1- 11, 2004, bttsed on data from ref. 43.)
c 0 E F
20j
10
0
vV
10
0
- 10
-20 5s Ss Ss
n n n
FIGURE 35-5 End-tidal carbon dioxide tension (P ETCoz), airway pressure {Paw), flow (inspiration up), volume (inspiration up), and
es ophageal (Pes) pressure in a representative subj ect during proportional-assist ventilation (A, B), pressure-support ventilation (C, D), and
volume-control ventilation (E, F) in the absence (A, C, E) and presence (B, D, F) of C0 2 chall enge. With C02 challenge, Paw decreases wi th
assist-control ventilation (the ventilator an tagonizes patient's effort); it remains constan t with pressure-support ventilation (no
relationship between patient effort and level of assist); and it increases w ith proportional-assist ventilation (positive relationship between
effort and p ressure assist), (Used, with permiss ion from Mitrouskn et nl: Eur Respir T13:873- 82, 1999.)
conscious subjects receiving maximum assistance o n the illustrating the point. First, in conscious patients with sleep
three main ventilator modes, 18 the ability of the subject to apnea syndrome, a drop in Pace, because of brief (40 sec-
regulate Pac~ depends on the operational principles of each ond) hypoxic hyperventilation resulted, contrary to healthy
mode, specifically in terms ofVT/PTP-Pmus1 (Fig. 35-6). At subjects, in significant hypoventilation and triggering of pe-
all levels of C02 stimulation, preservation of neuroventila- riodic breathing in some patients. 47 This hypoventilation
tory coupling increased progressively from ACV to PSV to was interpreted as evidence of a defect (or reduced effective-
PAY; the ability of subjects to regulate Pac~ followed the ness) of short-term poststimulus potentiation, a brain-stem
same pattern. 18 mechanism that promotes ventilatory stability.48 In this sit-
During sleep or sedation, the tendency to develop uation, a level of assistance that causes a significant decrease
hypocapnia with ACV and PSV (see Chapter 57 for the efin Pac~ may promote unstable breathing in awake patients
fects of mechanical ventilation on sleep) may have serious with sleep apnea syndrome, a situation closely resembling
consequences because a drop of a few millimeters of mer- that observed during sleep. Second, studies in ventilated
cury in Pa c~ leads to apnea a nd periodic breathing.12, 21 critically ill patients have shown that when awake patients
Thus excessive assistance with ACV and PSV promotes un- are unable to increase VT appropriately as a result of the
stable breathing secondary to impaired neuroventilatory mode used (i.e., PSV), they increase respiratory rate in re-
coupling; controller gain remains high in the face of low sponse to a chemical challenge. Behavioral feedback, how-
inspiratory effort (Fig. 35-7). Unstable breathing, however, ever, may tmderlie this response pattern. In sedated patients
during sleep secondary to mechanical ventilation may be with acute respiratory distress syndrome (in whom behav-
prevented or attenuated with PAV that does not guarantee ioral feedback is not an issue) receiving PSV, considerable
a minimum VT.'12, 21 Modes that decrease the volume de- variation in Pacol elicited a steady-state response limited to
livered by a ventilator in response to any reduction in the the intensity of breathing effort, a response pattern similar
intensity of patient effort enhance breathing stability. Never- to that observed in nonnal subjects.10
theless, if the assist setting d uring PAVis such that controller
gain increases considerably, and tl1e inherent loop gain of
N EU ROMECHANICAL FEEDBACK
the pati~nt is relatively high, th~ ratient will be a t risk of
developmg unstable breathmg.3~A ,46 INTRINSIC PROPERTIES OF RESPIRATORY MUSCLES
These principles may be altered by disease states and ther~ For a given neural output, Pmus decreases with increas-
apeutic interventions. Although little is known about the ing lung volume and flow, as dictated by the force-
interaction between disease sta tes and mechanical ven- length and force-velocity relationships of inspiratory mus-
tilation on control of breathing, two examples help in cles, respectively.49 Therefore, for a given level of m uscle
0-IAPTER 35 EFFECTS OF MECHANICAL VENTILATION ON CONTROL OF BREATHING 721
0.8 facilitate proper interpretation of respiratory motor output

during mechanical ventilation. These authors showed that
0.6 the left shift of the EMGdi-PTPdi relationship was decreased
significantly by the addition of inspiratory flow to pressure
~¥ analysis. 50
~0 0.4
O..r
1-E •
%g 0.2 REFLEX FEEDBACK
>~
The characteristics of each breath are influenced by vari-
ous reflexes tha t are rela ted to lung volume or flow and
0 -f--1--
PAV PS AVC
mediated, after a latency of a few milliseconds, by recep-
tors located in the respiratory tract, lung, and chest wall.5•6
FIGURE 35-6 Ratio (mean ± SO) of tidal volume to pressure-time
Mecl1anical ventilation may stimulate these receptors by
product of inspir.J tory muscles (VTIPTP-Pmustl in normal
conscious subjects ventilated wiUt Uuee modes of assisted
changing flow and volume. ln addition, changes in ven-
ven tilation in Ute absence and presence of C0 2 cltallenge tilator settings, inevitably associated with changes in vol-
(inspired C02 concentration increase d in small steps unt il ume and flow, also may elicit acute Pmus responses me-
intoleran ce developed). Open and clos ed bars represent zero and diated by reflex feedback. In seda ted patients with acute
final (highest) concentration of inspired C0 21 rMpectively. PAV, respiratory distress syndrome, manipulation of ventilator
proportional-assist ventilation; PS, pressure-support ventilation; settings altered immediately (within one breath) the neu-
and AVC, assis t volume control. Asterisk indicates signific.a nt ral respiratory timing, w hereas respiratory drive remained
difference from the value without C02 cltaUen ge. Plus s ign constant.10•5" Specifically, decreases in VT and pressure sup-
indicates s ignificant difference from the corresponding value port and increases in inspiratory flow caus ed an increase in
witlt PAV. Witlt each mode, subjects were ventilated at the highest respiratory frequency. Depending on the type of alteration,
comfortable level of assistance (corresponding to SO% reduction
of patient resistance and elastance w itlt PAV, 10 cmHzO of
changes in respiratory frequency were mediated via alter-
pressure support, and 1.2-liter tidal volume with AVC). Witlt ation in neural inspiratory and expiratory time; increases in
COz challenge, VT/PTP-Pmus1 decreased significantly when inspiratory flow caused increases in respiratory frequency
the subjects were ventilated with PS and AVC, but it remained mainly by decreasing neural inspiratory time; decreases in
relatively constant with PAV. Witltout C02 challenge, VT and pressure support caused increases in respiratory fre-
VT/PTP-Pmus 1 was significan tly higher with PS and AVC than quency by decreasing neural expiratory time. This reflex re-
with PAV. This response pattern caused severe respiratory sponse was similar, at least qualitatively, to that observed in
alkalosis with PS and AVC Wtrrco2 decreased to "' 22 mmHg with healthy subjects during wakefulness and sleep.52 - 56 There
both modes) but not wi tlt PAV (PllTco 1 "' 30 mmHg). Unlike witlt was a strong dependency of neural expiratory time on the
PS an d PAV, subjects ventilated w itlt AVC could n ot tolerate high
time that mechanical inflation extended into neural expi-
values of PETco 2 (final PETco2 was ,...7, 11, and 13 mmHg higher
th an baseline eupnea, resp ectively with AVC, PS, and PAV).
ration; neural expiratory time increased proportionally to
Based on data from ref. 18. the increase in the delay between the ventilator cycling off
and the end of neural ins piratory time10,s1 (Fig. 35-8). This
finding indicates tha t expiratory asynchrony may elicit a
activation, Pmus should be smaller during mechanical ven- reflex timing response. A subsequent study in a general
tilation than during spontaneous breathing if pressure pro- ICU population confirmed the dependency of neural ex-
vided by the ventilator results in greater flow and volume. piratory time on expiratory asynchrony.57 The m ost likely
It has been shown in healthy subjects ventilated with PSV explanation for the timing response is the Herring-Breuer
that compared with spontaneous breathing, the relation- reflex.
ship between electrical activity (EMGdi) and pressure-time The fin al response may be unpredictable depending on
product of diaphragm (PTPdi) is shifted to the left; thus, a t the magnitude and type of lung volume change, tl1e level of
any given level of EMGdi, PTPdi is reduced.50 consciousness, and tl-\e relative strength of the reflexes in-
The influence and consequences of mechanical feedback volved. Nevertheless, reflex fe.e dback should be taken into
during mechanical ventilation have not been studied sat- account when ventilator s trategies are planned. A few ex-
isfactorily. It is possible that this type of feedback is of amples may help in illustrating the importance of reflex
clinical signifi cance in patients w ith dynamic hyperinfla- feedback in patient-ventilator interaction. Assume that the
tion (high end-expiratory lung volume), high ventilatory patient is r eceiving pressure support that is being decreased
requirements (requirements for high flow and volume), during weaning. This results in lower VT, w hich through re-
and/ or impaired neuromuscular capacity. flex feedback decreases neural expiratory time, causing an
The intrinsic properties of respiratory muscles must be increase in respiratory frequency. 10•51 This increase should
considered when pressure measurements are used to in- not be interpreted as patient intolera nce to the decrease in
fer changes in respiratory muscle activation; otherwise, e r- pressure support. Consider another patient with obstructive
rors in estimation of respiratory muscle activity may occur. lung disease receiving ACV. VT is decreased at a constant
These errors may be significant when ventilation is elevated inspiratory flow in order to reduce the magnitude of d y-
secondary to high volume and flow. During hypercapnic hy- namic hyperinflation (less volume is exhaled over a longer
perventilation, intrinsic properties of inspiratory muscles period). The lower VT usually results in less delay in breat11
may decrease peak Pmus by about 20%.8 Fauroux e t al50 re- termination as compared with the end of neural inspira-
ported correction factors for higher flows and volumes that tion, which tluough vagal feedback w ill decrease neural
CHINEMG
CI A,.
C/ A,
EOG(R)
A
= =::::: =~ :::::::::=: :t::::: ~= ::~ :t::~::::.
!J,:_....._"""'
1
::
B
•. -~_..~,.,.!;!f,~,)/!.~~~.I':..IY. :: " :• ·,: '

~C~--~---------
-~ :::: : ~: .:: ..,~ :

EOG(L) • " • • v "Y - - - - - - - -· - - - - - - -- - -- - -
RISCAGE
ABDOMEN
VOLUME
FLOW
PAW
RJBCAGE
ABDOMEN
W--
VOLUME
FLOW
Pf.W
30SEC
FIGURE 35-7 Polygraph tracings in a healthy subject during non-REM s leep with and without pressure-support ventilation. A.
S pontaneous breathing with CPAP. B- 0. Pressure s upport of 3, 6, and 8 cm H 20 , res pectively. Periodic breathing with central apneas
developed with p ressure support of 8 cmH20 . C3/A2 an d C4/Al, electroencephalogram chann els; EOG; electroocculogram [right (R) and
left (L)]; Paw, airway pressure; EMG, electrom yogram; PETco 2, end-tidal Pco1 • (Used, with pennissicm, from Mez a eta/: J Appl Physiol
"167:1193- 9, 2003.)
0,6 FIGURE 35-8 Relationship between the
• 0
changes in the time that mechanical
in~"Piration extended into neural expiration
0,4 0 (~Text, expiratory asynchrony) and neural
expiratory time (~Ten) in mechanically
,.-._ ventilated patients wi th AR DS. Closed circles,
0 open circles, an d open triangles represent
Q)
</)
~Text ind uced by changes in volume (at
'-"
constant flow), flow (a t constant volume), and
~ o,:t- o,3 o,-
f-4 -0,4 -0,3 0,5· pr essure support, respectively. Solid line,
<l regr ession line. Based on data from ref. 51 .
• -0,4
• -0,6
~Text (sec)
y= -0.004+0.897x, P<O.OO l
CHAPTER 35 EFFECTS OF MECHANICAL VENTILATION ON CONTROL OF BREATHING 723
expiratory time, limiting the effectiveness of this strategy The clinical relevance of neuromechanical inhibition is
for reducing dynamic hyperinflation. 51 Assume in another currently unknown. Available evidence suggests that its
patient receiving ACV that inspiratory flow is increased a t contribution to respiratory motor output in ventilated crit-
a constantVT, with the intent of reducing inflation time and ically ill patients is rather minimal. 10• 13•51 That neurome-
providing more time for expiration so as to reduced ynamic chanical inhibition is observed at relatively high tidal vol-
hyperinflation. This step causes a reflex decrease in neural umes and when ventilator frequency exceeds spontaneous
inspiratory time and an increase in respiratory frequency. respiratory ra te62 raises questions of its clinical relevance,
Mechanical expiratory time may change in either direction particularly with assisted modes of ventilation. In criti-
depending mainly on the relation between neural and me- cally ill patients ventila ted with PSV or ACV at relatively
chanical inspira tory time. In patients receiving ACV, expi- low tidal volumes, neuromechanical inhibition was not
ratory time showed a variable response to changes in flow evident.10· 51
rate; some patients actually demonstrate a reduced expira-
tory time with a higher flow,58 which cancels the desired ENTRAINMENT OF RESPIRATORY RHYTHM TO
reduction in dynamic hyperinflation. VENTILATOR RATE
Entrainment of respiratory rhythm to the ventilator rate
NEUROMECHANICAL INHIBITION implies a fixed, repetitive, temporal relationship between
Mechanical ventilation at relatively high tidal volume and the onset of respiratory muscle contraction and the onset
ventila tor frequency results in a non-chemically mediated of a mechanical breath.65 - 67 Human subjects exhibit one-
decrease in respiratory motor output.59 - 61 This decrease, to-one entrainment over a considerable range a bove and
referred to as neuramechanicnl inhibition, is manifested both below the spontaneous breathing frequency. 68 •69 This en-
in respiratory frequency and in amplitude of respiratory trainment response is affected by state (sleep or wakeful-
motor output. Neuromed1anical inhibition lasts for several ness) and is independent of mild increases in respiratory
breaths after termination of mechanical ventilation, thus drive induced by C02 stimulation. 68 Cortical influences
constituting a type of control-system inertia and resetting (learning or adaptation response) and the Hering-Breuer
of the spontaneous respiratory rhythm.62 Neuromechani- reflex are postulated as the predominant mechanisms of
cal inhibition has been observed both with controlled and entrainment. Theoretically, one-to-one entrainment should
assisted modes of ventilation- at VT considerably greater facilitate patient-ventilator synchrony, but studies of
than that during spontaneous breathing and at a ventila- the entrainment response in critically ill patients are
tor frequency of just 1 breath per minute higher than base- lacking.
line breathing.62 In sleeping subjects, controlled ventilation
is able to totally suppress respiratory motor output, and
it leads to apnea after cessation of support62 (Fig. 35-9A). BEHAVIORAL FEEDBACK
With assisted ventilation, neuromechanical inhibition is ex- The effects of behavioral feedback on control of breathing
pressed mainly in terms of the intensity of breathing effo rt62 in ventilated patients are unpredictable, depending on sev-
(see Fig. 35-9B). Although the mechanism underlying neu- eral factors related to the individual patient and surround-
romechanical inhibition is not entirely clear, the Hering- ings. Alteration in ventila tor settings, planned to adueve a
Breuer reflex is the most plausible explanation. It also particular goal, might be ineffective in awake patients be-
has been shown that repeated augmented ventilatorcycles cause of behavioral feedback. 70, 71 Inappropriate ventilator
delivered at a frequency higher than eupnea exert a cu- settings may cause breathing discomfort in awake patients.
mulative, time-dependent inhibition of respiratory motor Consequent panic reactions further aggravate the unpleas-
output. 63 ant breathing sensatio n and create a vicious cycle. Be-
Mechanical ventilation has been shown to influence the havioral feedback also may be altered considerably from
excitability of the motor cortex supplying the diaphragm. time to time secondary to changes in the level of sedation,
In healthy subjects, Sharshar et al64 assessed cortical con- sleep I awake sta te, patient status, and environmental stim-
trol of the diaphragm by measuring its electrical response, uli. The many factors involved in behavioral feedback com-
the motor evoked potential, to transcranial magnetic stim- plicate its study and the interpretation of its effects on the
ulation during spontaneous breathing and isocapnic ACV. system that controls breathing in mechanically ventilated
Mechanical ventilation was associated w ith a decrease in patients.
motor evoked potential amplitude and hyperexcitability of
intra cortical facilitatory neurons . The findings indicate that
wuoading of the res piratory muscles reduces the excitabil-
ity of cortical motor areas representing these musdes. 64 Interactive Effects of Patient-Related
It is possible that mechanoreceptor feedback accounts for Factors and Ventilator on Control
the depression of the motor evoked potential of the di-
aphragm via vagal and other proprioceptive a fferents to
of Breathing
the respiratory center. This effect of mechanical ventilation
represents neuromechanical inhibition a t the level of the MECHANICS OF RESPIRATORY SYSTEM
motor cortex, and it may contribute to a non-chemically The mechanical properties of the respiratory system may
mediated decrease in respiratory motor o utput in awake influence the pressure delivered by the ventilator indepen-
subjects. dent of patient effort and thus may modify the effects of
111 CMV:+3 tb,200% Vt --+
P •• 0 ~
(<m R,O)
-10
EEG ,., AIMV ... ...._.............

' .............. ·~·
MJL...u ., .........., .. II
- 'n!r' ~ , .... ' .. ..,...,~tUf-6,.....
... .• ~ • . ..•
w Jt•. , • .,....,. 0
. . ••"
Jltll
A IS sec
+-- - - A ssist Control MV---~
Pm 5 [
C<m 1110) oy~~'---1-'-..i....._,....._,-'---'....._,.,
0
45
ptl
C01
(llllllll,)
0
v, .75 [
(I) 0
B I S sec
FIGURE 35-9 Gastric pressure (Pga), esophageal pressure (Pes), transdiaphrag matic pressure (Pdi), mouth press ure (Pm), partial press ure
of end-tidal C02 (PETco 2 ), tidal volume (VT), and electroencephalog ram (EEG) in a subject during non-REM sleep. A. Spontaneous
breathing with continuous positive airway pressure (CPAP) followed b y controlled mechanical ventilation (CMV) at a res piratory
frequency that is three breaths per minute above spontaneous eupnea and a VT that is 200% of s pontaneous eupnea. Note the immediate
reduction in Pdi at CMV onset and the apnea that followed the cessation of CMV. lnspired C02 was added to prevent the PETco 2 from
falling w hen VT was raised with CMV. B. Spontaneous breath ing with CPAP followed by assist volume-control ventilation (ACV) at a
VT that was 1.95% of s pontaneous eupnea. Note the sudden decrease in Pdi and increase in Pes at the onset of ACV; these values were
maintained throug hout ACV and gradually re turned to normal d uring spontaneous breathing after the cessation of ACV. PETco1 was
maintained at or slig htly above than eupneic levels through the addition of inspired C02 • (Used, with pen nissio11, f rom R ice et a /: Am
J Respir Crit Care Med 168:92- 101, 2003.)
724
0-fAPTER 35 EFFECTS OF MECHANICAL VENTILATION ON CONTROL OF BREATHING 725
,.....,
(.J
.......~ I
)'
Q)
- ...._,
(J)
::::::
-- ..
'Q' ..,
Cl) ~
rn
.._
....
u •• -
~
0
.... "
-4.1 • •
.., T
--
" ...~ ... •• "' fl,'r
g
-
0 .4
a -..2
~ -u...:z
M
u.•
.. o. ei
.(,.....
Time (sec)
Time (sec)
FIGURE 35-10 Airflow (inspiration up), airway pressure (Paw), and esophageal pressure (Pes) in a patient with obstructive lung disease
ventilated with pressure supporl Note the triggering delay with every mechanical bre~th (see the magnified tracing of flow and Pes) and
the ineffective efforts (arrows). The ventilator rate was U breaths per minute, whereas the patient's respiratory frequency was 35 breaths
per minute. Extrapolation from ventilator rate to the patient's system of control of breathing is misleading.
mechanical ventilation on the various feedback loops. Ex- cant alteration in a pa tient's respiratory effort occurs sec-
cessive triggering delay and ineffective triggering are com- ondary to changes in feedback loop.
mon in patients w ith obstructive lung disease and dynamic
hyperinflation (Fig. 35-10). In the setting of airflow obstruc-
CHARACTERISTICS OF THE MUSCLE
tion, mathematical models predict that PSV can be accom-
PRESSURE WAVEFORM
panied by m arked variation in VT and intrinsic PEEP even
when pa tient e.ffort is constant.72 This d ynamic instability The characteristics of the Pmus waveform influence the
increases as the time constant of the respiratory system in- ventilator"delivered volume in a complex manner, depend-
creases and produces patient-ventilator asynchrony of vari- ing on several patient a nd ventilator factors. Extensive re-
able magnitude and type. The demonstration of increased view of these factors is beyond the scope of this chapter, but
arousals during PSV, but not during volume-cycled venti- some examples are provided.
lation, may be caused in part by d ynamic pa tient-ventilator The initial rate of increase in Pmus interacts with trigger-
asynclu ony.24 ing of the ventilator.13 A low rate of initial increase in Pmus
Ineffective triggering has been observed with all m odes occurs with a concave upwa rd shape of Pmus or a low res-
of assisted ventilation. It is particularly common with piratory drive (such as with low Paco,, sedation, sleep, or
tachypnea and when the level of assistance is relatively a high level of assistance); this increases the time delay be-
high and mechanical inflation extends well into neural tween the onset of patient inspiratory effort and ventilator
expiration.13•73 With PAV, the likelihood of ineffective ef- triggering and promotes asynchrony. In the presence of dy-
forts is reduced significantly because mechanical infla- namic hyperinflation, a prolonged triggering time, particu-
tion time is terminated d ose to the end of neural inspi- larly w hen associa ted with a relatively short neural inspi-
ration, and tidal volume in most cases remains relatively ratory time and low peak Pmus, may result in ineffective
smalt.73 efforts. Alternatively, an increase in the intensity of inspi-
The phenomenon of ineffective efforts cons iderably influ- ratory effort, such as occurs with an increase in metabolic
ences the interpretation of ventilatory output in relation to rate, high Paco2 , or decrease in the level of sedation or assis-
the control of breathing during mechanical ventilation.3.74 tance, is manifested both in the rate of rise and in the peak
In tl1e presence of ineffective efforts, ventilator frequency of Pmus. The change may cause a decrease in the time de-
does not reflect the pa tient's spontaneous respiratory rate lay, thus promoting patient-ventilator synchrony.13 If, how-
(see Fig. 35-10). Moreover, with ineffective efforts, signifi- ever, patient inspiratory effort is vigorous and longer than
1.5 promising results. New methods of triggering, through use

~
~ of the flow waveform or mechanical activity (Pdi-driven ser-
~ 1.0 voventilation) or electrical activity (neurally adjusted ven-
~ tilatory assistance) of the diaphragm as triggering signals,
'i 0.5 have been shown to improve the response of the ventila-
.2 tor to patient effort?5 - 77 Algorithms that automatically ad-
u.. 0.0
just the criterion for cyding off have been designed w ith
-0.5 a goal of reducing expira tory asynchrony? 8 Mechanicaf7
and electrical75,79 activity of the diaphragm has been used
- 1.0 experimentally to control the level and duration of inspi-
45 Paw ratory assis tance. This approach is challengit1g and further
40 / emphasizes the advantages ofPAV. With PAV, methods for
6 35 noninvasive automatic estimation of elastance and resis-
r '" 30 tance of the respiratory system have been introduced that
E 25
s 20 enable controller gain to be maintained constant in the fa ce
~ 15 -'-~ of changes in the mechanical load of respiratory system. 80,81
~ 10 By achieving tight coupling between neural output and
e 5 -r----.. ventilator-delivered pressure, the ventilator is able to serve
a. 0
as a respiratory muscle with high capabilities and operate
-5
-10 ~----~-------r------r------r------, in harmony with the system that controls breathing.
0 2 4 6 8 10 Negative-feedback methods, such as adaptive pressure-
Time (s) support servoventilation, have been designed recently w ith
FIGURE 35-11 Flow, airway p ressure (Paw), an d esophageal
a goal of reducing periodic breathing through appropriate
pressure (Pes) in a patient recovering from acute lung in jury and changes in the level of assistance and maintaining a target
venti lated on assist volume control at constant insp iratory flo w. minute ventilation in the face of waxing and w aning respi-
In the second breath, tidal volume (volume was not shown) was ratory efforts. 82 Incorporation of this approach in assisted
d ecreased at constant inspiratory flow . As a result, there was modes may decrease the propensity of high-risk individu-
premature termination of mechani cal inspir ation. Because the als to develop periodic breathing. Tt is not known whether
inspiratory muscles continue d to contract, th ey developed this mode could decr ease morbidity in critically ill patients,
sufficient p ressure to overcome elas tic recoil at en d insp iration . although it should enhance sleep efficiency.23
As a result, Paw decreased below the triggering threshol d, an d
th e ventilator deli vered a new mechanical breath. The ventilator
was triggered three times b y the two inspira tory efforts. Note the
high Paw of the th ird mechanical breath secondary to h igh lung Conclusion
volume (the volum e of the third breath was added to that of the
second). To tal breath duration of Ute second respiratory effort was Incorporating an auxiliary pressure into the system that con-
con siderably longer th an that of the first effort owing to trols breathing changes the volume-time profile of a breath.
activation of Hering-Breuer reDex by th e high volume. (Used, 1t also alters, via chemical, neuromechanical, and behavioral
witlr permission, from Kondili et al: Br TAuaestlL 91:106-19, 2003.)
feedback, the pressure developed by the respiratory mus-
cles. The latter, depending on ventilator and patient factors,
mechanical inflation time, the ventilator may be triggered may or may not modify the auxiliary pressure. The response
more than once during the san1e inspiratory effort (Fig. of pa tient effo rt to a ventilator-delivered breath and the re-
35-11). It follows that changes in the characteristics of the sponse of a ventilator to patient effort are the two essen-
Pmus waveform may influence the ventilator rate and ven- tial components of control of breathing during mechanical
tilatory output despiteno change in a patient's breathing fre- ventilation. The physician dealing with a ventilated patient
quency. Alterations in ventilatory output may seconda rily should be aware that both the basic features of control of
modify patient effort through changes in feedback loops (see breathing and its expression can be altered considerably by
Fig. 35-1). the process of mecha nical ventilation.
The Future References

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57. Am ] Respir Crit Care Med 1999; 160:950-60.
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J Respir Crit Care Med 1997; 156:304-8. waveform method of triggt:!ring and cycling on patit:!nt-vcntilator
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in sleeping hwnans. J Physiol 1999; 518:605-'18. 77. Sharshar T, Desmarais G, Louis B, et al. Transdiaphragmatic pres-
60. Leevers AM, Simon PM, Dempsey JA. Apnea after normocapnic sure control of airway press ure support in healthy subjects. Am
mechanical ventilation during NREM sleep. J Appl Physiol1994; J Respir Crit Care Med 2003; 168:760-9.
77:2079-85. 78. Du HL, Amato MB, Yamada Y. Automation of expiratory trig-
61. Manchanda S, Leevers AM, Wilson CR, et al. Frequency and vol· ger sensitivity in pressure support ventilation. Respir Care Clin
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mechanical ventilation. Respir Physiol1996; 105:1-16. 79. Spahija JBJ, de Marchie M, Comtois A, Sinderby C. Closed loop
62. Rice AJ, Nakayama HC, Haverkamp HC, et al. Controlled ver· control of respiratory drive using pressure support ventilation:
sus assisted mechanical ven tilation effects on respiratory motor Target drive ventilation. Am J Respir Crit Care Med 2005 (in
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168:92- 101. 80. Younes M, Webster K, Kun J, et al. A method for measuring pas·
63. Satoh M, Eastwood PR, Smith CA, Dempsey JA. Nonchem· sive clastance during proportional assist ventilation. Am JRespir
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ventilation in sleep. Am J Respir Crit Care Med 2001; 163: 81. You nes M, Kun J, Masiowski B, et al. A method for nonin·
1356-64. vasive determination of inspiratory resistance duri ng propor·
64. Sharshar T, Ross ET, Hopkinson NS, et al. Depression of di· tiona! assist ventilation. Am J Respir Crit Care Med 2001; 163:
aphragm motor cortex excitability duru1g mechanical ventilation. 829-39.
J Appl Physiol2004; 97:3-10. 82. Pepperell JC, Maskell NA, Jones DR, et al. A randomized, con·
65. Petrillo GA, Glass L. A theory for phase locking of respiration in trolled trial of adaptive ventilation for Cheync-Stokes brea thing
cats to a mechanical ventilator. Am J Physioll984; 246:R31l- 20. in heart failure. Am J Respir Crit Cart:! Med 2003; 168:1109-14.
Chapter 36 _ _ _ _ __ _ _ __ dysfunction, and if untreated, death. Thus, restoration and
maintenance of normalized cardiopulmonary function is an
EFFECT OF essential and primary goal in the management of critically ill
patients. Heart failure can impair gas exchange by inducing
MECHANICAL pulmonary edema a nd limiting blood flow to the respira-
tory muscles. Ventilation can alter cardiovascular function
VENTILATION ON by altering lung volume and intrathoracic pressure (ITP),
and by increasing metabolic demands. These processes will
HEART-LUNG be discussed from the perspective of the impact that venti-
lation has on the cardiovascular system.
INTERACTIONS
MICHAEL R. PI SKY
Relevance
The ventilatory apparatus and the cardiovascular system
have profound effects on each other.1.2 Acute hypoxia im-
pairs cardiac contractility and vascular smooth muscle
RELEVANCE tone, promoting cardiovascular collapse. H y perinflation in-
PHYSIOLOGY OF HEART-LUNG INTERACTIONS creases pulmonary vascular resistance which impedes right
Effect of Lung Volume ventricular (RV) ejection, and also compresses the heart in-
Effect of Intrathoracic Pressure side the cardiac fossa in a fashion analogous to tamponade.
SPONTANEOUS BREATHING VERSUS Lung cofla pse also increases pulmonary vascular resistance,
MECHANICAL VENTILATION impeding RV ejection.3 Acute RV failure, or cor pulmounle,
DETECTION AND MONITORING is not only difficult to treat, but it can induce immediate
Weaning Failure cardiovascular collapse and deatl-t.
Using Ventilation to Define Cardiovascular Mechanical ventilation technologies and numerous va-
Performance soactive drugs have been developed as means to improve
CLINICAL SCENARIOS oxygenation of arterial blood. These advances are the sub-
Initiating Mechanical Ventilation jects of other chapters in this book. The complex interac-
Comparing Different Modes of Mechanical Ventilation tions, however, between the heart, circulation, and lungs
Upper Airway Obstruction often lead to a paradoxical worsening of one organ system
Chronic Obstructive Pulmonary Disease function while the function of the other system is either
Auto-PEEP maintained or even improved by the use of these techno lo-
Acute Respiratory Distress Syndrome and Acute Lung gies and drugs. To minimize these deleterious events, and in
Injury the hope of more efficiently and effectively treating critically
Congestive Heart Failure ill patients with cardiorespiratory failure, a better knowl-
Intraoperative State edge and understanding of the integrated behavior of the
STEPS TO LIMIT OR OVERCOM E DETRIMENTAL cardiopulmonary system, during both health and critical ill-
HEART-LUNG INTERACTIONS ness, is essential. Based o n this perspective, the health care
Minimize Work of Breathing provider can more appropriately manage this complex and
Minimize Negative Swings in Intrathoracic Pressure challenging group of patients.
Prevent Hyperinflation Respiratory function alters cardiovascular function and
Fluid Resuscitation during Initiation of cardiovascular function alters respiratory function. A use-
Positive-Pressure Ventilation ful way to consider the cardiovascular effects of ventilation
Prevent Volume Overload during Weaning is to group them by tl1eir impact on the determinants of
Augment Cardiac Contractility cardiac performance. The determinants of cardiac function
IMPORTANT UNKNOWNS can be grouped into four interrelated processes: henri rnte,
THE FUTURE preload, coutrnctility, and nfterlood. P hasic changes in lung
SUMMARY AND CONCLUSION volume and TTP can simultaneously change all four of these
ACKNOWLEDGMENTS hemod ynamicdeterrninants for both ventricles. Our current
understanding of cardiovascular function also emphasizes
both the independence and interdependence of RV and left
The heart and lungs are intimately coupled by their ventricular (LV) performance on each other and to external
anatomic proximity within the thorax, and more impor- stresses. Complicating these matters further, the direction
tantly, by their responsibility to deliver the oxygen ((h) of interdependence, from right to left or left to right, can be
requirements of individual cells and organs. During criti- similar or opposite in direction, depending on the baseline
cal illness, if these two organ systems fail either alone or in cardiovascular state. It is clear, therefore, that a comprehen-
combination, the end result is an inadequate 0 2 delivery to sive understanding of the specific cardiopulmonary inter-
the body with inevitable tissue ischemia, progressive organ actions and their relative importance in defining a specific
729
730 PART IX PHYSIOLOGIC EFFECT OF MECHANICAL VENTILATION
cardiovascular state is a nearly impossible goal to achieve fibers, because it is abolished by selective vagotomy. Hex-
in most patients. By understa nding the components of this amethonium, guanethidine, and bretylium, however, also
process, however, one can come to a better realization of block this ref1ex.16, 17 These data suggest that lung infla-
its determinants, and, to a greater or lesser degree for any tion mediates its reflex cardiovascular effects by modulating
individual patient, predict the limits of these interactions, central autonomic tone. Interestingly, the almost total lack
and how the patient may respond to stresses imposed by of measurable hemodynamic effects of unilateral hyperin-
either adding or removing artificial ventilator support. flation in subjects with normal lungs receiving split-lung
ventila tion18 suggests that these autonomic cardiovascular
effects require a generalized increase in lung volume to be
Physiology of Heart-Lung Interactions realized. This is not a minor point because selective h yperin-
flation within lung units commonly occurs in subjects w ith
Both spontaneous and positive-pressure ventilation in- acute lung injury (ALI) and chronic obstructive pulmonary
crease lung volume above an end-expiratory baseline. Many disease (COPD). If localized hyperinflation were able to in-
of the hemodynamic effects of all forms of ventilation are duce cardiovascular impairment, these subjects would be
similar despite differences in the mode of ventilation. ITP, profoundly compromised.
however, decreases during spontaneous ins piration, while Humoral factors, including compounds blocked by cy-
it increases during positive-pressure ventilation. Thus, the clooxygenase inhibition,19 released from pulmonary en-
primary reasons for different hemodynamic responses seen dothelial cells d uring lung inflation, may also induce this
during spontaneous and positive-pressure breathing are re- depressor response,20 - 22 within a short (15-second) time
lated to the changes in ITP and the energy necessary to pro- fram e. These interactions, however, do not appear to grossly
duce those changes. alter cardiovascular status. 23 Ventilation also alters the more
chronic control of intravascular fluid balance via hormonal
release. The right atrium functions as the body's effec-
EFFECT OF LUNG VOLUME tive circula ting blood volume sensor. Circulating levels of
Changing lung volume phasically a lters autonomic tone a family of natriuretic peptides decrease in heart failure
and pulmo nary vascular resistance. At very high lung val- sta tes, secondary to right a trial s tretch. These hormones
tunes, the expanding lungs compress the heart in the car- promote sodium and water diuresis. The levels of these
diac fossa, limiting absolute cardiac volumes. This action hormones vary inversely with the degree of heart fail-
is analogous to cardiac tamponade, except that w ith hyper- ure. Both positive-pressure ventilation and sustained hy-
infla tion both pericardia! pressure and ITP increase by a perinflation decrease right atrial stretch, mimicking hypo-
similar amount. volemia. Plasma norepinephrine, plasma activity,24~ 25 and
plasma atrial natriure tic peptide 26 increase during pos itive-
AUTONOMIC TONE pressure ventilation. This humoral response is the pri-
Although neuro humoral processes define a few immedi- maryreason whyventilator-dependentpatientsgain weight
ate effects of ventilation on the heart, these processes prob- early in the course of respira tory failure, despite protein
ably play a primary function in all of the long-term ef- catabolism being common. Interestingly, when subjects
fects of ventilation on the cardiovascular system. Most of with congestive heart failure are given nasal continuous
the immediate effects of ventilation of the heart are due positive a irway pressure (CPAP), plasma atrial natriuretic
to changes in autonomic tone. The lungs are richly inner- peptide activity decreases in parallel with improvements
vated w ith somatic and autonomic fibers, which originate, in blood flow.27, 28 1l1is finding suggests that some of the
traverse throu gh, and end in the thorax. These networks observed benefit of CPAP therapy in heart failure is me-
media te multiple homeosta tic processes through the auto- diated in part through humora l mechanisms, owing to the
nomic nervous system, altering instantaneous cardiovascu- med1anical effects of CPAP on cardiac function.
lar function. The most commonly known of these are the
vagally-mediated heart rate d1anges during ventilation. 4' 5 PULMONARY VASCULAR RESISTANCE
Inflation of the lung to a normal tidal volume (<10 ml/kg) Changing lung volume alters pulmonary vascular
induces vagal-tone withdrawal, accelerating heart rate. This resistance.3 Marked increases in pulmonary vascular
phenomenon is known as respirntonJ sinus arrhythmia.6 It resis tance, as may occur with hyperinflation, can induce
can be used to document normal autonomic control? espe- acute cor pulmonale and cardiovascular collapse. The
cially in pa tients w ith diabetes who are at risk of peripheral reasons for these changes are multifactorial. They can
neuropathy.8 Infla tion to larger tidal volumes(> 15 ml/ kg), reflect conflicting cardiovascula r processes, and almost
however, decreases heart rate by a combination of both in- always reflect both humoral and mechanical interactions.
creased vagal tone 10 and sympathetic withd rawal. Sympa- Lung volume can only increase if its distending pressure
thetic withdrawal also creates arterial vasodilation .4' 9' 1'1, l2, t 4 increases. Lung-distending pressure, called the transpul-
TI1is inflation-vasodilation response can reduce LV contrac- monary pressure, equals the pressure difference between
tility in healthy volunteers,' 5 and in ventilator-dependent alveolar pressure (Palv) and ITP. If lung volume does not
patients with the initia tion of high-frequency ventilation 4 change, then trans pulmonary pressure does not change.
or hyperinflation. 12 This infla tion-vasodilation resp onse is Tims, occluded ins piratory efforts (Mueller maneuver) and
presumed to be the cause of the initial hypotension seen expiratory efforts (Valsalva maneuver) cause ITP to vary by
when infants are placed on mechanical ventilation. It ap- an amotmt equal to Palv, but do not change pulmonary vas-
pears to be m ediated at least partially by afferent vagal cular resistance. Although obstructive inspiratory efforts,
CHAPTER 36 EFFECT OF MECHANICAL VENTILATION ON HEART-LUNG INTERACTIONS 731
as occur during obstructive sleep apnea, are usually as- riched with 0 2, increasing PAo, 40 - 43 Second, med1anical
sociated with increased RV afterload, the increased after- breaths and positive end-expiratory pressure (PEEP) can re-
load is caused primarily by either increased vasomotor fresh hypoventilated lung units and recruit collapsed alve-
tone (hypoxic pulmonary vasoconstriction) or backward LV olar units, causing local increase in PA 0 ,,3·44 - 46 especially if
failure. 2~~ 30 small lung volumes a re returned to resting functional resid-
RV afterload is maximal RV systolic wall stress.31, 32 By ual capacity.47 Third, mechanical ventilation often reverses
Laplace's law, wall stress equals the product of the radius respiratory acidosis by increasing alveolar ventilation. 43
of curvature of a structure and its transmural pressure. Sys- Fourth, decreasing central sympathetic output, by seda-
tolic RV pressure equals transmural pulmonary artery pres- tion or decreased stress of breathing against high-input
sure. Increases in transmural pulmonary artery pressure impedance during med1anical ventilation, will also reduce
increases RV afterload, impeding RV ejection,33 decreas- vasomotor tone.-18.49 Importantly, these effects do not require
ing RV stroke volume,34 inducing RV dilation, and pas- endotracheal intubation to occur; they may occur with mere
sively causing venous return to decrease. 34 If such acute re-expansion of collapsed alveoli. 50, 51 Thus, PEEP, CPAP, re-
increases in transmural pulmonary artery pressure are not cruitment m aneuvers, and noninvasive ventilation may all
reduced, or if RV contractility is not increased by artificial reverse hypoxic pulmonary vasoconstriction and may all
means, then acute cor pulmonale rapidly develops. 35 If RV improve cardiovascular function.
dilation and RV pressure overload persist, RV free-wall is-
chemia and infarction can develop.36 These concepts are of
profound clinical relevance because rapid fluid challenges Volume-Dependent Changes in Pulmonary
in the setting of acute cor pulmonale can precipitate pro- Vascular Resistance
found cardiovascular collapse secondary to excessive RV Changes in lung volume directly alter pulmonary vaso-
dilation, RV ischemia, and compromised LV filling. Ven- motor tone by compressing the alveolar vessels. 38, 45,46 The
tilation can alter pulmonary vascular resistance by either actual mechanisms by which this occurs have not been
altering pulmonary vasomotor tone, via a process kn.own complete!y resolved, but appear to reflect vascular compres-
as hypoxic pulmo11ary vasoconstriction, or mechanically alter- sion induced by a differential extraluminal pressure gradi-
ing vessel cross-sectional area, by changing transpulmonary ent. The pulmonary circulation lives in two environments,
pressure. separated from each other by the pressure that surrounds
them. 45 The small pulmonary arterioles, venules, and alveo-
Hyp oxic Pulmonary Vasoconstriction lar capillaries sense Palv as their surrounding pressure, and
Unlike systemic vessels that dilate under hypoxic condi- are called alveolar vessels. The large pulmonary arteries and
tions, the pulmonary vasculature constricts. Once alveolar veins, as well as the heart and intrathoracic great vessels of
Po2 (PAo) decreases below 60 mmHg, or acidemia devel- the systemic circulation, sense interstitial pressure or ITP as
ops, pulmonary vasomotor tone increases.37 Hypoxic pul- their surrounding pressure, and are called extra-alveolar ves-
monary vasoconstriction is mediated, in part, by variations sels. Because the pressure difference between Palv and JTP is
in the synthesis and release of nitric oxide, by endothelial trans pulmonary pressure, increasing lung volume increases
nitric oxide synthase localized on pulmonary vascular en- this extralurninal pressure gradient. Increases in lung vol-
dothelial cells, and in part by changes in intracellular cal- ume progressively increase alveolar vessel resistance by
cium fluxes in the pulmonary vascular smooth muscle cells. increasing this pressure difference once lung volumes in-
TI1e pulmonary endothelium normally synthesizes a low crease much above functional residual capacity (FRC) 41 •52
basal amount of nitric oxide, keeping the pulmonary vas- (Fig. 36-1). Similarly, increasing lung volume, by stretching
culature actively vasodilated. Loss of nitric oxide aiJows and distending tl1e alveolar septa, may also compress alveo-
the smooth muscle to return to its normal resting vaso- lar capillaries, although this mechanism is less well substan-
motor tone. Nitric oxide synthesis is dependent on ade- tiated. Hyperinflation can create significant pulmonary hy-
quate amounts of 0! and is inhibited by both hypoxia and pertension, and may precipitate acute RV failure (acute cor
acidosis. Presumably hypoxic pulmonary vasoconstriction pulmonale)53 and RV ischemia.36 11ms, PEEP may increase
developed to minimize ventilation-perfusion mismatches pulmonary vascular resistance if it induces overdistention
caused by local alveolar hypoventilation. Generalized alve- of the lung above its normal FRC.54
olar hypoxia, however, increases global pulmonary vaso- Extra-alveolar vessels are also influenced by changes
motor tone, impeding RV ejection.33 At low lung volumes in transpulmonary pressure. Normally, radial interstitial
terminal bronchioles collapse, trapping gas in the termi- forces of the lung, whid1 keep the airways patent, only
nal alveoli. With continued blood flow, these alveoli lose make the large vessel more distended as lung volume
their 0 2 and also may coJJapse. Patients with acute hypox- increases,44, 55•56 just as increasing lung volume increases
emic respiratory failure have small lung volumes and are airway diameter. These radial forces also act upon the
prone to both alveolar hypoxia and spontaneous alveolar extra-alveolar vessels, causing them to remain dilated, in-
collapse. 38•39 This is one of the main reasons why pulmonary creasing their capacitance.57 This tethering is reversed w ith
vascular resistance is increased in patients with acute hy- lung deflation, thereby increasing extra-alveolar vascular
poxemic respiratory failw·e. resis tance. 41 , 44 Thus, at small lung volumes, pulmonary vas-
Based on the above considerations mechanical ventila- cular resistance is increased owing to the combined effect
tion may reduce pulmonary vasomotor tone by a variety of hypoxic pulmonary vasocons triction and extra-alveolar
of mechanisms. First, hypoxic pulmonary vasoconstriction vessel collapse, and at high !tmg volumes by alveolar com-
can be inhibited if the patient is ventilated with gas en- pression.
Q) Total PVR RV volume (ml)

(.)
c: 20 50 35 20 0
!!!
(/)
Alveolar ~
C)
·a; Hypoxic Compression I
Q) Pulmonary
E
a:
.... Vasoconstriction . .§,
111
a ·
...
..•' ~ 10
(/)
>
111 . ....•'
·• ' ::I
fJ)
~
' ' ... .... .... .~
........ ····· Extra-alveolar fJ)
._
Q)
....... ~-·············
Vessels-············..··· ---- · - -- - - - - - - - vessels
c:
0
Alveolar a..
E
~ 0
rr.
Residual Functional Total
Volume Residual Lung
Capacity Capacity 0 10 20 30 40
Lung volume
LV Volume (ml)
FIGURE 36-1 Schematic diagram of the relation between changes
in lung volume and pulmonary vascular res istance, where the FIGURE 36-2 Schematic diagram of the effect of increasing right
extra-alveolar and alveolar vascular components are separated. ventricular (RV) volumes on the relationship between left
Pulmonary vascular resis tance is minimal at resting lung volume ventricular (LV) diastolic pressure and volume (filling). Increases
or fu nctional residual capacity. As lung volume increases toward in RV volumes decrease LV d iastolic compliance, such that a
total lwtg capacity or decreases toward residual volume, higher filling pressure is required to generate a constant
pulmonary vascular resis tance also increases. The increase ht end-diastolic volume. (Adapted, with permission, from Taylor
resistance with hyperinflation is caused by increased alveolar et a/.58 )
vascular res istance, whereas the increase in resistance with lung
collapse is caused by increased extra-alveolar vessel tone.
MECHANICAL HEART-LUNG INTERACTIONS
SECONDARY TO LUNG VOLUME
VENTRICULAR INTERDEPENDENCE With inspiration, the expanding lungs compress the heart
Because RV output is linked to LV output serially, if RV in the carcliac fossa,62 in creasin g juxtacardiac TTP. Because
output decreases, LV o utput must eventually d ecrease. the chest wall and diaphragm can move away from the
The two ventricles, however, are also linked in parallel expanding hmgs, whereas the heart is trapped within this
through their common septum and pericardium, which cardiac fossa, juxtacardiac ITP usu ally increases more than
limits total cardiac volume. The most common manifes- these peripheral ITPs .63' 64 This effect is caused by increas-
tation of ventricular interdependence is pulsus pnradoxus. ing lung volume. It is not affected by the means whereby
Changes in RV end-diastolic volume inversely alter LV lung volume is increased. Both spontaneous65 and positive-
diastolic compliance.58 Because venous return can and pressure-induced hyperinflation65,66 induce similar com-
often d oes vary by as much as 200% b etween ins piration pressive effects on cardiac filling. If one measured only intra-
and expiration, owing to associated changes in the pressure luminal LV pressure then it would appear as if LV cliastolic
gradient for venous return (infra vide), RV filling also compliance was reduced, because the associa ted increase in
changes in parallel. Increasing RV end-diastolic volume, as pericardia! pressure and ITP would not be seen. 66 - 68 When
occurs during spontaneous inspiration and spontaneous LV function, h owever, is assessed as the relation bet\•veen
inspiratory efforts, will reduce LV clias tolic compliance, end-diastolic volume and output, no evidence for impaired
immediately decreas ing LV end-clias tolic volume. Positive- LV contractile function is seen,69,66 despite the continued
pressure ventilation may d ecrease venous return, causing application ofPEEP? 0 T hese compressive effects can be con-
RV volumes to also decrease, increasing LV diastolic sidered analogous to cardiac tamponade. 71 - 73
compliance. Except in volume overloaded LV failure s tates,
however, the impact of positive-pressure ventilation on
EFFECT OF INTRATHORACIC PRESSURE
LV end-diastolic volume is minimal. Ventricula r inter-
d ependence function s through two separate processes. The h eart lives within the thorax, a pressure chamber inside
First, increasing RV end-cliastolic volume will induce an a pressure cl1amber. Thus, changes in JTP will affect the pres-
intraventricular septal shift into the LV, thereby d ecreasing sure gradients for both systemic venou s return to the right
LV diastolic compliance59 (Fig . 36-2). Second, if pericardia! ventricle and systemic outflow from the left ventricle, inde-
restraint or absolute cardiac fossa! volume restraint limits p endent of the heart itself (Fig. 36-3). In creases in ITP, b y
absolute hi ventricula r filling, then RV dilation will increase increasing right atrial pressure (Pra) and decreasing trans-
p ericardia! pressure (Ppc) without a septal shift.60' 6'1 mural LV systolic pressure, wiJl reduce the pressure gracli-
Because spontaneous inspiration increases venous return, ents for venous return and LV ejection, decreasing intratho-
causing RV clilation, LV end-cliastolic compliance d ecreases racic blood volume. Using the same argument, d ecreases
during spo ntaneous inspiration. Because RV volumes usu- in ITP will augment ven ous return and imped e LV ejec-
ally d o n ot increase d uring positive-pressure inspiration, tion, increasing intrathoracic blood volum e. The increases
ventricular interdependence is usually less. in ITP during positive-pressure ventilation show marked
in Pra. This preload-sparing effect is especially well demon- Spontaneous inspiratory efforts usually increase venous re-
strated in patients with hypervolemia. In fact, abdominal turn because of the combined decrease in Pra60•104•86- 88 and
pressurization by diaphragmatic descent may be the ma- increas e in intra-abdominal pressure.95•96 For Prato remain
jor mechanism by which the decrease in venous return very low, however, RV diastolic compliance must be high
is minimized during positive-pressure ventilation. 97- l0l and RV output must equal venous return. Otherwise, sus-
In fact, Van den Berg et a1102 documented that up to tained increases in venous blood flow would distend the
20 cmH20 CPAP did not significantly decrease cardiac out- RV and increase Pra. During normal spontaneous inspira-
put, as measured 30 seconds into an inspiratory-hold mation, although venous return increases, ITP decreases at the
neuver, in fluid-resuscitated, postoperative cardiac surgery same time, minimizing any potential increase in Pra, which
patients. Although CPAP induced an increase in Pra, intra- might otherwise occur if ITP were not to decrease. 81 Aid-
abdominal pressure also increased, preventing a significant ing in this process of minimizing RV workload, the pul-
change in RV volumes (Fig. 36-5). Interest in inverse-ratio monary arterial inflow circuit is highly compliant and can
ventilation has raised questions as to its hemodynamic ef- accept large increases in RV stroke volume without chang-
fect, because its use constitutes a large component of hyper- ing pressure.34• 105 Thus, increases in venous return propor-
inflation. Mang et al,103 however, demonstrated in an animal tionally increase pulmonary arterial inflow without signifi-
model of ALI that if total PEEP (intrinsic PEEP plus addi- cant changes in RV filling or ejection pressures. Accordingly,
tional extrinsic PEEP) was similar, no hemodynamic dif- this compensatory system fails if RV dias tolic compliance
ference beh.veen conventional ventilation and inverse-ratio decreases or if Pra increases independent of changes in RV
ventilation was seen. end-diastolic volume. These differential effects of negative
(spontaneous inspiration) and positive (positive-pressure
inspiration) swings in ITP on dynamic RV and LV perfor-
Relevance of Intrathoracic Pressure on Venous Return mance are illustrated in Fig. 36-6.
It is axiomatic that the heart can only pump out that amount Note further in Fig. 36-6 that not only does RV stroke vol-
of blood that it receives and no more. Thus, venous return is ume increase with spontaneous inspiration and decrease
the primary determinant of cardiac output.80 Because Pra is with positive-pressure inspiration, but also that LV stroke
the backpressure to venous return, venous return is main- volume decreases only during spontaneous inspiration
tained near maximal levels at rest,l2•79 because RV filling (ventricular interdependence); during positive-pressure in-
occurs with minimal changes in fil ling pressure? 3 Venous spiration, however, any cl1ange in LV stroke volume occurs
blood flow is maximal if Pra is kept near zero or Iess?9•86 late, as tl1e decrease in RV output finally reaches the left
FIGURE 36-5 Effect of increasing levels of continuous positive airway pressure (CPAP) on the relations between increasing airway
pressure (Paw) and right atrial pressure (Pra) (left graplz), Paw and intra-abdominal pressure (Pabd) (center graph), and Paw and chan ges in
right ventricular end-diastolic volume (RVEOV) (right graplz) in 43 postoperative fluid-resuscitated car diac surgery patients. (Data tierived,
witlz permission, from Van den Berget aL.1112)
1.0 0.9 0.9
0.9 0.8
0.4-
• •
• •
0.7
0.6
••••
•••
0.2
• •••••
•••
••••
6P13 6Pabct 6RVEDV •••
0.5 •• 0 ••
•••••
6Paw RVEOV
6Paw
0.4 •• ••••
•••
• • 6Paw ••
•
•
•• (%em H20) -2
0.3
••
•• •
I
•••• ••
:t••• 0.2 •••
0.1
•
••
•••
• 0.1
......
••
••
-4
••
0 0 0
POSITIVE
SPONTANEOUS PRESSURE
VENTILATION VENTILATION
._,
I I
17 -
~
SVAv
ml
o- uuuul
~ 1 aec -1
17 -
SVLv
ml
0-
180-
n
PAo
mmHg
ao -
10 -
p,.tlll
mmHo
o-
25 -
P.,.,.
IIIIIIHI
a-
10-
p,.,lll
mmHg
o-
a-
Paw
mmHg
o-
p.,,
mmHg
-a-
5-
'
I
p,.
mmH'g
o-
FIGURE 36·6 Strip chart recording of right and left ventricular s troke volumes (SVrv and SVlv, respectively), aortic pressure (PAol, left
atrial, pulmonary arterial, and right atrial transmural pressures (Platm, Ppaun, and Prat1n, respectively), airway pressure (Paw), pleural
pressure (Ppl), and right atrial pressure (Pra) during spontaneous ventilation (left) and similar tidal volume positive-pressure ventilation
(riglrt) in an anestllctized, intact canine model. (Reproducetl, witlz permissiou, from Piusky et n/. 123)
ventricle. RV diastolic compliance can acutely decrease in During a Valsalva maneuver, airway pressure (Paw) and
the setting of acute RV dilation or cor pulmonale (pul- ITP increase equally, and pulmonary vascular resistance re-
monary embolism, hyperinflation, and RV infarction). Im- mains constant. During the first phase of the Valsalva ma-
portantly, acute RV dilation and acute cor pulmonale can neuver, RV filling decreases first with no change in LV fill-
not only induce rapid cardiovascular collapse, but they are ing, LV stroke volume, or arterial pulse pressure because
singularly not responsive to fluid resuscitation. Because venous return decreases. Although LV stroke volume does
spontaneous inspiration and inspiratory efforts cause both not change, LV peak ejection pressure increases equal to the
ITP and Pra to decrease, RV dilation may occur in subjects amount of the increase in ITP.liS As the strain is sustained,
with occult heart failure. Accordingly, some patients who both LV filling and cardiac output decrease owing to the
were previously stable and ventilator dependent can de- decrease in venous return,62•119 which results in the second
velop acute RV failure during weaning trials. phase. During this second phase of the Valsalva maneuver,
Finally, with exaggerated negative swings in ITP, as occur both RV and LV output are decreased; arterial pulse pres-
with obstructed inspiratory efforts, venous return behaves sure is reduced, but peak systolic pressure is sustained at
as if abdominal pressure is additive to mean systemic pres- an elevated level owing to the sustained increase in ITP.
sure in augmenting venous blood flow. 106- 109 These find- This phase delay in LV output decrease compared to RV
ings have led some investigators to suggest tha t obstruc- output decrease is also seen during positive-pressure ven-
tive breathing may be a therapeutic strategy in sustaining tilation; it is exaggerated if tidal volumes increase or if the
cardiac output in patients in hemorrhagic shock.110 Inter- pressure gradient for venous return was already low, as is
estingly, negative-pressure ventilation, by augmenting ve- the case in hypovolemia. 1 ~ 66 -68,90· 113, 120- 126 With release of
nous return, increases cardiac output by 39% in children the strain in phase three of the Valsalva maneuver, arte-
following repair of tetralogy of Fallot.111 It this condition, rial pressure abruptly declines because the low LV stroke
impaired RV filling secondary to RV hypertrophy and re- volume cannot sustain an adequate ejection pressure on its
duced RV chamber size are the primary factors limiting own. Furthermore, with the release of the increased ITP, ve-
cardiac output. This augmentation of venous return, how- nous return increases, increasing RV volume, and, through
ever, is limited, 107' 108 because as ITP decreases below atmo- the process of ventricular interdependence, decreases LV di-
spheric pressure, venous return becomes flow-limited be- astolic compliance, making LV end-diastolic volume even
cause the large systemic veins collapse as they enter the less. Conceptually, then ventricular interdependence usu-
thorax.79 This vascular flow limitation is a safety valve ally becomes apparent with sudden increases in RV volume
for the heart, because ITP can decrease greatly w ith ob- from apneic baseline, as would occur during spontaneous
structive inspiratory efforts,u and if not flow-limited, the inspira tion, but less so when RV volumes decrease below
RV could become overdistended and fail. 13,112 Finally, hav- these volumes. As described above, because RV volumes
ing subjects breathe through an airway that selectively im- are usually decreased during pos itive-pressure ventilation,
pedes inspiration will result in exaggerated negative swings ventricular interdependence is not a prominent feature of
in both fTP and Pra, and associated greater increases in this form of breathing58,124- 127 (see Fig. 36-6). Although
intra-abdominal pressure secondary to recruitment of ac- PEEP results in some degree of right-to-left intraventricu-
cessory muscles of respiration (to sustain a normal tidal lar septal shift, echocardiographic studies demonstrate that
volume).no the shift is s mall. 69· 120 It follows that positive-pressure ven-
Positive-pressure ventilation tends to create the opposite tilation decreases intrathoracic blood volume86 and PEEP
effects: increase in ITP increases Pra, thus decreasing ve- decreases it even more129 without altering LV diastolic or
nous return, RV volumes, and ultimately, LV output. The contractile function. 128' 130 During s pontaneous inspiration,
detrimental effect of positive-pressure ventilation on cardiac however, RV volumes increase transiently shifting the in-
output can be minimized by either fluid resuscitation, to intraventricular septum into the LV,59 decreasing LV diastolic
crease mean systemic pressure,n ,SJ,'I 02,106 or by keeping both compliance and LV end-diastolic volume. 47•131,127 This tran-
mean ITP and swings in lung volume as low as possible. sient RV dilation-induced septal shift is the primary cause of
Accordingly, prolonging expiratory time, decreasing tidal inspiration-associated decreases in arterial pulse pressure,
volume, and avoiding PEEP all minimize this decrease in which, if greater than 10 mmHg or 10% of the mean pulse
systemic venous return to the right ventricle.LSU!S- 89,113;114 pressure, is referred to as pulsus paradoxus60,7S (see Fig. 36-6).
Increases in lung volume during positive-pressure ventila-
tion primarily compress the two ventricles into each other, LEFf VENTRICULAR PRELOAD AND VENTRICULAR
decreasing hi-ventricular volumes.115 The decrease in car- INTERDEPENDENCE
diac output commonly seen during PEEP is caused by a Strictly speaking, issues of ventricular inte rdependence are
decrease in LV end-diastolic volume, because both LV end- not part of the effects of ITP on venous return and LV ejec-
diastolic volume and cardiac output are restored by fluid tion. But the associated rapid changes in RV filling induced
resuscitation 116· ~'~ 7 without any measurable change in LV di- by phasic changes in ITP cause marked changes in LV out-
astolic compliance.66 put, which are a hallmark of ventilation-induced hemody-
A common respiratory maneuver, called the Valsalva ma- namic changes. The fundamental interactions defining ven-
neuver, which is forced expiration against an occluded air· tricular interdependence were described above.
way (such as w hile straining a t stool), displays most of
the hemodynamic effects commonly seen in various d is- LEFT VENTRICULAR AFTERLOAD
ease s tates and with different types of positive-press ure LV afterload is defined as the maximal LV systolic wall ten-
ventilation. sion, which equals the maximal product of LV volume and
CHAPTER 36 EFFECT OF MECHANICAL VENTILATION ON HEART-LUNG INTERACTIONS 73 7
transmural LV pressure. Under normal conditions, maximal component, 136•113•72 but also increases MV02. Profound de-
LV wall tension occurs at the end of isometric contraction, creases in ITP commonly occur during spontaneous inspira-
with the opening of the aortic valve. During LV ejection, as tory efforts with bronchospasm, obstructive breathing, and
LV volumes rapidly decrease, LV afterload also decreases acute hypoxemic respiratory failure. Under these disease
despite a n associated increase in ejection pressure. Impor- conditions, the cardiovascular burden can be great and may
tantly, when LV dilation exists, as in CHF, maximal LV wall induce acute heart failure and pulmonary edema. 13•29 Be-
stress occurs during LV ejection because the maximal prod- cause weaning from positive-pressure ventilation to spon-
uct of pressure and volume occurs at that time. LV ejection taneous ventilation may induce drama tic changes in ITP
pressure is the transmural LV systolic pressure. This is the swings, from positive to negative, independent of the en-
main reason why patients with dilated cardiomyopathies ergy requirements of the respiratory muscles, weaning is a
are very sensitive to changes in ejection pressure, whereas selective LV stress test. 132•137•138 Similarly, improved LV sys-
patients with primarily diastolic dysfunction are not. Nor- tolic function is observed in patients with severe LV failure
mal baroreceptor mechanisms, located in the extra thoracic placed on mechanical venti1ation.138 Very negative swings
carotid body, fu nction to maintain arterial pressure constant in ITP, as seen with vigorous inspiratory efforts in the setting
with respect to atmosphere. Accordingly, if arterial pres- of airway obstruction (asthma, upper airway obstruction, or
sure were to remain constant as ITP increased, then trans- vocal cord paralysis) or stiff lungs (interstitial lung disease,
mural LV pressure would decrease. Similarly, if transmural pulmonary edema, or ALI), selectively increase LV after-
arterial pressure were to remain consta nt as ITP increased, load, and may be the cause of LV failure and pulmonary
then LV wall tension would decrease.132 Thus, increases in edema,'13•29,30, l39 especially if LV systolic function is already
ITP decrease LV after load, a nd decreases in ITP increase LV compromised.'140• 141
afterload.118•133 These two opposing effects of changes in ITP Pulsu s paradoxus seen during spontane01.1s inspiration
on LV afterload have important clinical implications. tmder conditions of marked pericardia! restraint reflects
The concept that increases in ITP decrease both LV primarily ventricular interdependence.142- 146 The negative
preload and LV afterload can be clearly illustrated w ith swings in ITP, however, also increase LV ejection pressure,
the use of high-frequency jet ventilation (HFJV), w hich can increasing LV end-systolic volume.118 Other sys temic fac-
increase ITP but does not result in large swings in lung tors may influence LV systolic function during loaded in-
volume. 123 When HFJV is delivered in synchrony with the spiratory efforts. These associated factors also contribute
cardiac cycle, such that heart rate and ventilatory frequency to a greater or lesser degree to the inhibition of nor-
are identical, one can dissect out the effects of ITP on preload mal LV systolic function, including increase in aortic in-
and afterload. Under hypovolemic and normovolemic con- put impedance,1 47 altered synchrony of contraction of the
ditions with intact cardiovascular reserve, positive-pressure global LV myocardium, 148 and hypoxemia-induced de-
ventilation usually decreases s teady-sta te cardiac output by creased global myocardial contractility.149 Hypoxia also
decreasing the pressure gradient for venous return. When directly reduces LV diastolic compliance.150 Experimental
one compares the hemodyt1amic effects of HFJV synchro- repetitive periodic airway obstructions induce pulmonary
nized to occur during diastole when ventricular filling edema in normal animals. 29•30 Furthermore, removing the
occurs, cardiac output decreases to levels seen during end- negative swings in ITP by applying nasal CPAP results in
inspira tion for normal large-tidal-volume (10 ml/ kg) ven- improved global LV performance in patients with combined
tilation. In the same subject, however, if the increases in obstructive sleep apnea and CI-IF. 150
ITP occur during systole, the detrimental effects of the same
mean Paw, mean ITP, and tidal volume do not impede ve- Effects of Intrathoracic Pressure on Left
nous return 134• 135 (Fig. 36-7). Furthermore, in heart failure Ventricular Afterload
states, positive-pressure ventilation does not impede car- If arterial pressure remains constant, then increases in ITP
diac output because the same decreases in venous rettm1 decrease transmural LV ejection pressure, decreasing LV
do not alter LV preload. If these increases in ITP, how- afterload. These points are easily demonstrated in a sub-
ever, reduce LV afterload, then cardiac output will also inject with an indwelling arterial pressure catheter during
crease. These points are illus tra ted in Fig. 36-8, wherein cough or Valsalva maneuvers. During a cough, ITP in-
synchronous HFJV is delivered either during pre-ejection creases rapidly without changes in intrathoracic blood vol-
systole (presystolic) or ejection (systolic). The only differ- ume. Arterial pressure also increases by a similar amount,
ence between the two ventilatory states is that a rterial pulse as described above for phase 1 of the Valsalva maneu-
pressure does not change despite increases in LV stroke ver. Thus, transmural LV pressure (LV pressure relative to
volume with presystolic increases in Paw, consistent with ITP)118•151•152 and aortic blood flow62 would remain con-
a decreased LV afterload, whereas with systolic increases stant. Sustained increases in ITP, however, must eventu-
in Paw, arterial pulse pressure increases, and peak arterial ally decrease aortic blood flow and arterial pressure sec-
pressure increases by an amount equal to the increase in ondary to the associated decrease in venous return.'118 If
ITP, consistent with mechanically augmented LV ejection . ITP increased a.rterial pressure w ithout changing transmu-
ral arterial pressure, then baroreceptor-mediated vasodila-
Relevan ce of Intrathoracic Pressure on Myocardial tion would induce a rterial vasodilation to keep extratho-
Oxygen Cosumption racic arterial pressure-flow relations constant .122 Because
Decreases in ITP increase both LV afterload and m yocardial coronary perfusion pressure reflects the ITP gradient for
0 2 consumption (MV0 2) . Accordingly, spontaneous venti- blood flow, and is not increased by ITP-induced increases in
lation increases not only global 0 2 demand by its exercise arterial pressure, such sustained increases in ITP can cause
COMPARISON OF SYNCHRONOUS HFV TO

IPPB IN THE CONTROL (NORMAL) STATE
,_
sv,,
mflkg
0-
ayatollc d laalollc:
sv...
mllltO
o- 1 /l J
150 -
,.
60 -
10 - •
o-
20 -
P I)a,m
mmHo
6-
o-
20 -
P ew
mmHg
0·
j
FIGU RE 36-7 Strip chart recording of right and left ve ntricular stroke volumes (SVrv and SVlv, respectively), aortic pressure (PAo), left
atrial, pulmonary arterial, and rig ht atrial transmural pressures (Pla1.n, Ppa1m, and Pra1m, respectively), airw a y pressure (Paw), and pleural
pressure (Ppl) during apnea (1£/t), and both systolic (StjStole) and dias tolic (d iasto le) high-.f requency jet ventilation (HFV) (midd l e), and
intermittent positive-pressure ventilation (IPPV) with similar mean Paw (right) in an anesthetized, intact canine model with n ormal
cardiovascular function. Note that the cardiac cycle-specific increases in Paw created by systole HFV minimally impede cardiac o utput,
whereas diastole HFV markedly decreases venous return (SVrv decreases first, then S Vlv decreases). The rapid strip chart s peed sh own on
the left is to illustrate the exact timing of synchro nous HFV. (Reproduced, w i t l! pennission, from Pinsky et a l.U4 )
decreased coronary perfusion pressure and induce myocar- end-expiratory lung volume can be artificially increased by
dial ischemia.153- 155 the addition of end-expiratory aitway pressure. Thus, the
primary hemodynamic differences between spontaneous
ventila tion and positive-pressure ventilation are caused by
the changes in ITP and the muscular contraction needed to
Spontaneous Breathing versus create these changes. Importantly, even if a patient is re-
Mechanical Ventilation ceiving mechanical ventilation support, spontaneous respi-
ratory efforts can persist and may result in marked increases
Both spontaneous and mechanical ventilation increase lung in metabolic load, and contribute to sustained respiratory
volume above resting end-expiratory lung volume (FRC). muscle fatigue. 156 Still, one of the primary reasons for in-
During both spontaneous and positive-pressure ventilation, stituting mechanical ventilation is to remove the work of
COMPARISON OF SYNCHRONOUS HFV TO

IPPB IN ACUTE VENTRICULAR F AlLURE
,_
SVrv
mil kg
0-
1150 -
PAo
mm Hg
150-
25 -
p ,.,,.
mmHo
5-
Paw
mmHg
20-
I
o-
16 -
FIGURE 36-8 Continuous strip chart recording of right and left ventricular stroke volumes (SVrv and SVIv, respectively), aortic pressure
(PAo l, left atrial, pulmonary arterial, and right atrial transmural pressures (Platm, Ppatm, and Pratm, respectively), airway pressure (Paw),
pleural pressure (Ppl), and right atrial pressure (Pra) during intermittent positive-pressure ventilation (VT 10 mUkg) (IPPV), apnea (left),
and then both pre-ejection systole (presystolic) and LV ejection (systolic) syn chronous high-frequency jet ventilation (HFV) (middle), and
then IPPV again (righ t) in an anesthetized, intact canine model with fluid-resuscitated acute ventricular failure. Note that the cardiac
cycle-specific increases in Paw created by both presystoli c and systolic HFV increase steady-state SVrv and SVIv (i.e., cardiac output), but
affect P Ao differently. Presystolic HFV does not change P Ao pulse pressure despite an increase in SVIv (reduced afterload), whereas
systolic HFV increases P Ao pulse pressure for a similar increase in SVIv. (Reproduced, with permissio11, fi·om Pinsky et aU34 )
breathing. Normal spontaneous ventilation augments ve- acute respiratory muscle fatigue, causing acute res piratory
nous return and vigorous inspiratory efforts account for failure or failure to wean from mechanical ventilation, and
most of the increased blood flow seen in exercise. Con- overtax the ability of the circulation to deliver 0 2 to the rest
versely, positive-pressure ventilation may impair ventric- of the body.
ular filling and induce hypovolemic cardiac dysfunction Fundamental to this concept is the realization tha t spon-
in normal or hypovolemic subjects while augmenting LV taneous ventilation is exercise. Spontaneous ventila tory ef-
function in patients with heart failure. 92 Finally, heart fail- forts are induced by contraction of the respiratory mus-
ure, whether primary or induced by ventilation, may induce cles, of which the diaphragm and intercostal muscles
comprise the bulk. 136 Although ventilation normally report, by either intubation and ventilation168 or noninvasive
quires less than 5% of total 0 2 delivery to meet its demand.136 continuous positive airway pressure,169 can reverse myocar-
(and is difficult to measure at tl1e bedside even with cali- dial ischemia. Importantly, the increased work of breathing
brated metabolic measuring devices), in lung disease states may come from endotracheal tube flow resistance. 170 Thus,
in which the work of breathing is increased (such as pul- some subjects who fail a spontaneous breathing trial may
monary edema or bronchospasm), the metabolic demand actually be able to breathe on their own if extubated.
for 0 2 can increase to 30% of total 0 2 delivery.12-l13,t36, 157 It follows, that if spontaneous ventilation is exercise, then
With marked hyperpnea, muscles of the abdominal wall weaning failure patients should display signs of circula-
and shoulder girdle function as accessory respiratory mus- tory insufficiency during a trial of spontaneous breathing.
cles. Blood flow to these muscles is derived from several Patients with chronic obstructive pulmonary disease who
arterial circuits, whose absolute flow exceeds the highest fail to wean often develop gut hypoperfusion, as assessed
metabolic demand of maximally exercising skeletal mus- by gastric tonometry, during weaning trials. 166 Similarly,
cle under normal conditions.158•159•136 Thus, blood flow is weaning failure patients d isplay an increase in arteriove-
usually not the limiting factor determining maximal venti- nous 0 2 content difference, a commonly used method of
latory effort. In severe heart failure states, however, blood assessing cardiovascular stress.167 Much of the increased
flow constraints may limit ventilation because blood flow work ofbreatl1ing can be caused by the endotrachealtube.170
to other organs and to the respiratory muscles may be com- Tims, some patients who fail spontaneous breathing trials
promised, inducing both tissue hypoperfusion and lactic can be extubated successfully, but there is no known method
acidosis. 158, I59 Aubier et al demonstrated that if cardiac out- of identifying this subgroup.
put is severely limited by the artificial induction of tampon-
ade in a canine model that respiratory muscle failure devel-
ops despite high central neuronal drive.159 Tile animals die
USING VENTILATION TO D EFINE
a respiratory death before cardiovascular standstill.159 The
CARDIOVASCULAR PERFO RMANCE
institution of mechanical ventilation for ventilatory and hy-
poxemic respirator y failure may reduce metabolic demand Because the cardiovascular response to positive-pressure
on the stressed cardiovascular system, increasing mixed ve- breathing is determined by the baseline cardiovascular
nous oxygen saturation (Sv 02 ) for a consta nt cardiac out- sta te, these responses can be used to define such cardio-
put and arterial oxygen content (Ca~ ). 160 Intubation and vascular sta tes. Sustained increases in airway pressure will
mecl1anical ventilation, when ad justed to the metabolic de- reduce venous return, allowing one to assess LV ejection
mands of the patient, may dramatically decrease the work over a range of end-diastolic volumes. If echocardiographic
of breathing, resulting in increased 0 2 delivery to other vital measures of LV volumes are simultaneously made, tl1en one
organs and decreased serum lactic add levels. Under condi- can use an inspiratory-hold maneuver to measure cardiac
tions in which fixed right-to-left shunts exist, the obligatory contractility, as defined by the end-systolic pressure-volume
increase in Svo2 will result in an increase in the Pa~ , despite relationship (ESPVR), 171 which is similar to tha t created by
no change in the ratio of shunt blood flow to cardiac output. transient inferior vena caval occlusion.172• 173 Furthermore,
these measures can be made during tl1e respira tory cycle to
define dynamic interactions.173
Patients with relative hypervolemia, a condition often as-
Detection and Monitoring sociated with CHF, are at less risk of developing impaired
venous return during initiation of mechanical ventilation,
WEANING FAI LURE
whereas hypovolemic patients are at increased risk. If pos-
Ventilator-dependent patients who fail to wean often have itive airway pressure augments LV ejection in heart fail-
impaired baseline cardiovas cular performance that is read- ure states by reducing LV afterload, then systolic arterial
ily apparent,141 but commonly patients develop overt pressure should not decrease, but actually increase, during
signs of heart failure during weaning, sucl1 as pulmonary inspiration, so-called reverse pulsus paradoxus. TI1is was
edema,1 41 • 161 myocardial ischemia,'162 - 165 tachycardia, and what Abel et al' 74 saw in 10 post-cardiac surgery patients.
gut ischemia.166 Pulmonary artery occlusion pressure may Perel et al175,t76,l77 suggested that the relation between res-
rise rapidly to nonphysiologic levels witlUn 5 minutes piratory efforts and systolic arterial pressure may be used to
of instituting weaning. 141 Although all patients increase identify which patients may benefit from cardiac-assist ma-
their cardiac output in response to a ,.,reaning trial, those neuvers. Patients who increase their systolic arterial pres-
that subsequently fail to wean demonstrate a reduction in sure during ventilation, relative to an apneic baseline, tend
mixed venous 0 2 saturation, consistent with a failing car- to have a g reater degree of volume overload 176 and heart
diovascular response to an increased metabolic demand. 167 failure,1 77 whereas patients who decrease systolic arterial
Weaning from mechanical ventilation can be considered a pressure tend to be volume responsive. Perhaps more rel-
cardiovascular stress test. Again, investigators have doc- evant to usual clinical practice is the identification of sub-
umented weaning-associated ECG and thallium cardiac jects w hose card iac output will increase if given a volume
blood flow scan-rela ted signs of ischemia in both patients challenge. Identification of preload-responsiveness is im-
with known coronary artery disease162 and in otherwise nor- portant because only half of the hemodynamically unsta-
mal patients. 164·165 Using tl1is same logic, placing patients ble patients studied in several clinical series were actually
with severe heart failure a nd/ or ischemia on ventilator sup- preload responsive.178 Thus, nonspecific fluid loading will
not only be ineffective at restoring cardiovascular stability more, the degree of pressure or flow variation will be pro-
in half the subjects, it will also both delay definitive ther- portional to tidal volume, with greater tidal volumes induc-
apy and may promote cor pulmonale or pulmonary edema. ing greater changes for the same cardiovascular s tate.188•1&3
Finally, Michard et al179 found, in a series of ventilator- Thus, the means by which cyclic changes in lung volwne
dependent septic patients, that the greater the degree of and ITP are induced will affect the magnitude of arterial
arterial pulse-pressure variation during positive-pressure pressure and flow var iations. Fourth, although the primary
ventilation, the greater the subsequent increase in cardiac determinant of arterial pulse pressure variation over a sin-
output in response to volume-expansion therapy. The re- gle breath is LV stroke volume variation, because changes
cent literature has documented that both arterial pulse in aortic impedance and arterial tone cannot change that
pressure180 and LV stroke volume variations181 •182 induced rapidly190 over time, this limitation no longer applies. As
by positive-pressure ventilation are sensitive and specific arterial tone decreases, for example, then for the same aor-
markers of preload responsiveness. The greater the degree tic flow and stroke volume both mean arterial pressure and
of flow or pressure variation over the course of the res- pulse pressure will be less. Accordingly, flow variation be-
piratory cycle for a fixed tidal volume, the more likely a comes more sensitive than pulse pressure variation as hem-
subject is to increase cardiac output in response to a vol- orrhage progresses. 182
ume challenge, and the greater that increase. The overarch-
ing principles of this clinical tool have not been previously
described. There are several important caveats and limita-
tions to this approach, which need to be considered before
Clinical Scenarios
the clinician proceeds to monitoring arterial pulse pressure
INITIATI NG MECHANICAL VENTILATION
or stroke volume variation during ventilation as a routine
means for predicting preload responsiveness. NORMO- AND HYPOVOLEMIC PATIENTS
First, and perhaps most importantly, being preload re- The process of initiating mechanical ventilation is a complex
sponsive does not mean that the subject should be given physiologic process for a variety of reasons. First, pharma-
volume. Otherwise normal subjects under general anesthe- cologic factors needed to allow for endotracheal intubation
sia without evidence of cardiovascular insufficiency are also also blunt sympathetic responses, exaggerating the hemo-
preload responsive, but do not need a vo.Iume challenge. dynamic effects induced by increasing airway pressure and
The presence of positive-pressure-induced changes in aor- defining tidal volume and respiratory frequency. This point
tic flow or arterial pulse pressure does not itself define ther- is clearly demonstrated by comparing the relatively benign
apy. Independent documentation of cardiovascular insuf- impact of re-instituting ventilator s upport in a patient w ith
ficiency needs to be sought before the clinician attempts a pre-existent trad1eotomy, with the impact of the initial in-
fluid resuscitation based on these measures. Second, these tubation and ventilation of the same patient a few days or
indices, which quantify the variation in aortic flow, stroke weeks earlier. As noted above, positive-pressure ventilation
volume, and arterial systolic and pulse pressures, have rou- increases ITP, which mus t a lter venous return. If a patient
tinely been demonstrated to outperform more traditional has reduced vasomotor tone, as commonly exists during in-
measures of LV preload, such as pulmonary occlusion pres- duction of anesthesia, the associated increase in Pra will in-
sure, Pra, total thoracic blood volume, RV end-diastolic duce a propor tional decrease in venous return, pulmonary
volume, and LV end-diastolic area. 180•181 There appears to blood flow, and subsequently cardiac output.34•81.1 91 If the
be little relation beh.veen ventricular preload and preload associated tidal volumes are excessive for the duration of ex-
responsiveness. Ventricular filling pressures poorly reflect piratory time available for passive deflation, then dynamic
ventricular volumes,183 a nd measures of absolute ventricu- hyperinflation will occur, increasing pulmonary vascular
lar volumes do not define diastolic compliance. 184 Patients resis tance and compressing the heart in the cardiac fossa,
with small LV volumes that are also stiff, as may occur with further decreasing hi-ventricular volumes. 115 If one were
acute cor pulmonale, tamponade, LV hypertrophy, and my- to examine the dynamic effects of ventilation on the LV
ocardial fibrosis, will show poor volume res ponsiveness. pressure-volume relation over the course of a single breath,
Conversely, patients with large LV volumes, as often occurs one would see a more complex effect, characterized by al-
with CHF and afterload reduction, rna y be quite volume re- terations in LV diastolic compliance, end-diastolic volume,
sponsive. Thus, preload does not equal preload responsive- stroke volume, and LV afterload (as exemplified by the left-
ness. Third, all the reported studies used positive-pressure ward shift of the end-systolic pressure-volume relations)
ventilation to vary venous return. For such d1anges in ve- (Fig. 36-9). Importantly, the impact of ventilation on LV per-
nous return, however, to induce LV output changes, the formance, as described in the first part of this chapter, is
changes in venous return must be of sufficient magnitude overly simplified by this assumption that breathing alters
to cause measurable changes in preload.185 If the increase only LV preload. Clearly, other factors aLc;o function simulta-
in lung volume with each tidal breath is either not great neously. The preload-reducing effects of tidal volume, how-
enough to induce changes in pulmonary venous flow, 186 ever, are best described during hypovolemic states, as illus-
or if the positive-pressure breath is associated with sponta- trated in the right hand panel of Fig. 36-10. Note that in-
neous inspiratory efforts that minimize the d1anges in ve- creasing tidal volumes limit ventricular filling, decreasing
nous return, 81 tl1en the cyclic perturbations to cardiac filling LV s troke volume under both normovolemic (left) and hy-
may not be s ufficient to induce the cyclic variations in LV povolemic (right) conditions (see Fig. 36-10), but this effect
filling needed to identify preload responsiveness. Further- is markedly exaggerated by hypovolemia.
.-t o ooo
IPPV 10 ml/kg
150
..,
> I
.Arrway pressure ......
130
8
110
I ,
LV presslure
'
I
I I ~
90
0>
:X:
E
-:z 23
-•Hg
'"'
-
E
~
70 c
"'"'
~
Q.
>
50
·--------
-------------- -
~
--'-
30
LV volume
' I
I 10 A
' I
LV ~04
- 10
22 27 32
LV volume (ml)
FIGURE 36-9 Dynamic effect of p ositive-pressure ventilation on the LV pressure-volume relation from end-expiration through a
ventilatory cycle. Note that during the breath, as airway pre~ssure rises and then fal.l~ (left panel) LV dias tolic compliance (right panel)
d ecreases minimally (the slope of the LV pressure-volume relation as LV volume increases during filling; lower l1orizontalline), while LV
preload markedly decreases (arrow A), and LV end-systolic pressure-volume domains do not decrease but shift to the left (arrow B),
associated with a decrease in LV stroke volume (a.rrow Q. Thus, all four processes occur during a single positive-pressure breath. Refer to
Fig. 36-10 to see how changes in tidal volume and intravascu lar volume alter tltese changes diffe.rently.
FIGURE 36-10 Effect of increasing tidal volume on Ute LV pressure-volume relation during nomtovolemic (left) and hypovolemic (right)
conditions in an intact anestltetiz.ed canine model. Under normovolemic conditions, Ute preload-reducing effects of positive-pressure
inspiration become more pronounced at end-inspiration as tidal volume increases. Under hypovolemic conditions, similar increases in
tidal volume also tend to decreas e Ute overall size and performance of the heart along lines consistent witlt pure reductions in LV preload
(end-diastolic volume); tltat is, steady-state LV end-diastolic and end-systolic volumes decrease, end-systolic pressure decreases, and
stroke volume decreases with increasing tidal volumes and airway pressures.
Effect of Varying Vt during Hypovolemia Effect of Varyin g Vt during Normovolemia
200 200
- IPPV 5 mllkg
- IPPV 5 mllkg
180 180 - IPPV 10 mllkg
- IPPV 10 mlil<g
- IPPV 15 mllkg
160 - IPPV 15 mVkg 160
~ ~ IPPV 20 mllkg
!PPV 20 mllkg 0>
~ 140 :z:: 140
E E
-
E 120
~ 100
-E
Q)
~
120
100
"'
(/)
(/) "'
(/)
(/)
80
e
Q.
80
e
Q.
60 60
>
..J
>
..J
40 40
20 20
0 0
0 10 20 30 40 50 0 10 20 30 40 50
LV volume (ml) LV volume (ml)

HYPERVOLEMIC AND HEART FAILURE PATIENTS ratory by having the subject inspire against an occluded air-
Initiating mechanical ventilation in hypervolem.ic patients way while connected to a manometer; the negative swings
has far less effect on cardiac output than that seen during in Paw can be controlled by the subject. Based on the above
normovolem.ic or hypovolemic conditions, because the im- physiologic discussion, it is clear that a Mueller maneuver
pact of ventilation on venous return is much less (right hand will result in an increase in both venous return and LV af-
panel of Fig. 36-6). Moreover, if such patients also have a terload. The hemodynamic effects, however, of positive and
component of acute RV volume overload, one may actu- negative swings in JTP may not be mirror opposites of each
ally see LV diastolic compliance increase and LV output other; the interactions are nonlinear. As ITP becomes more
markedly improve. It is not clear, however, if these often- negative, venous return becomes flow limited as the veins
seen improvements in LV performance and cardiac output collapse because their transmural pressure becomes neg-
in hypervolemic conditions represents improved LV filling, ative. LV afterload, however, increases progressively and
reduced metabolic demands, or improved LV contraction. linearly. 118 These nonlinear effects are illustrated in Fig. 36-4.
Regrettably, no clinical trials have examined the mecha- Changes in ITP will appear to shift the LV Frank-Starling
nisms by which such improvement occurs. curve to the left or right, with Pra on the x axis, equal to
the cl1ange in ITP, because the heart is in the chest and acted
upon by ITP, whereas venous return is from the body, which
COMPARING DIFFERENT MODES OF MECHANICAL
is outside of this pressure chamber. Accordingly, large nega-
VE NTILATION
tive swings in ITP will selectively increase LV ejection pres-
Any hemodynamic differences between different m odes of sure without greatly increasing RV preload or LV diastolic
mechanical ventilation at a constant airway pressure and compliance. This concept is important. Removing large neg-
PEEP are caused by differential effects on lung volume and ative swings in ITP, withoutinducingpositive swings in ITP,
ITP.134 When two different modes of total or partial ven- as would occur by endotrad1eal intubation or tracheotomy
tilatory support have similar changes in ITP and respira- to bypass a ny upper airway obstruction, should selectively
tory effort, their hemodynamic effects are also similar de- redu ce LV ejection pressure (LV afterload) and not reduce
spite markedly different airway waveforms. Partial venti- venous return (LV preload).
lator support, with

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CONTR1ll lfi'ORS xi 8. Intermittent Mandatory Ven tilation 201

3. Basic Principles of Ventilator Machinery 53 13. Proportional-Assist Ventilation 335

4. Equipment Required for Home 14. Closed-Loop Ventilation 365

PART IV NONINVASIVE METHODS OF

45 Oxygen Toxicity 965 57 Sleep in th e Ventilated Patien t 1173

ADJUNCTIVE THERAPY 1239

48 Imaging of the Mechanically Ventilated Patient 62 Diaphragmatic Pacing 1263

55 Addressing Respiratory Discomfort in the 70 Long-Term Outcomes After Mechanical

56 Ventilator-Supported Speech 1163

Charles G. Alex, MD Robert Bartlett, MD, FACS

Jason H.T. Bates, PhD, DSc

Richard D. Branson, MS, RRT Gerard J. Criner, MD

Laurent Brochard, MD Xizhong Cui, MD, PhD

Peter Q. Eichack er, MD D imitris Georgopoulos, MD, PhD

Mark Elliott, MD, FRCP Achim von Goedecke, MD

James B. Fink, MS, RRT, FAARC

Nicholas S. Hill, MD Brian P. Kavanagh, MB BSc MRCP(I) FRCP(C)

Ronald B. Hirschi, MD Sonia Khirani

Jeannette D. Hoit, PhD, CCC-SLP Theodor Kolobow, MD

Jay A. Johannigman, MD, Col USAFR Franco Lagbi, MD

Robert M. Kacmarek, PhD, RRT

Klaus Lewandowski, Prof. Dr. med. Ubaldo Martin, MD

Qin Lu, MD, PhD Daniele Mascheroni, MD

Antonio Pesenti, MD An drea Rossi, MD

Catherine S.H. Sassoon, MD

David V. Tuxen, MB, BS, FRACP, D ip OHM, MD, Michele Vitacca, MD

around 1670. Enclosing a mouse in a bell jar resulted even-

Boyle was stimulated by Harvey's work on circulation to ask

ing was nonphlogiston.1A Remarkably, both men described

FIGURE 1-3 The ice calorimeter, desig,ed by Lavoisier

FIGURE 1-4 Regnault and Reiset

animals. (Used, with penuissiou,

FIGURE 1-6 This relatively simple device enabled Haldan e and

lung did not rely on active processes for transporting oxy-

The concept of blood acid-base activity was just beginning

mtus constructed a heavy bell that, even though full of

diving in 1906. Haldane understood that minute ventilation

FIGURE l-12 A typical device

question of how air could be drawn into the heart. Unfortu-

an abdominal cuirass shell.84 An important advantage of

FIGURE 1-22 A. Eisenmenger's earlier version of his

in which cuffed tubes were used to ventilate isolated por-

I N THE OPERATING ROOM

FIGURE 1-25 The Drinker-Shaw iron lung developed

FIGURE 1-28 The volume-cycled ventilator us ed in the Harvard

practically through the tube itself. MacEwen's original work ·.. .. ~

on translaryngeal intubation for upper-airway obstruction ;.;·=~·:, '~,:,f: ::'~ ~

FIGURE 1-32 A larger version of the differential-pressure cabinet

" .~,_\. ' u ¥!

FIGURE 1-34 A positive-press ure mask us ed by Bunnell in 19U.

FIGURE 1-35 A sophis ti cated and complex ventilator built by

s-,r ( " _ _.,

described in 1928.131 Bronchoscopy and intratracheal sue-

FOR THE NONOPERATIVE PATIENT

respirator attachment for the sta ndard tank respirator d ur-

PR£SSUII( l U8[ lO (I" W.l\1(

~""'!- a.OH lfOU"< a-