Case Based Anes

15259_FM.
qxd 3/19/09 12:35 AM Page i
CLINICAL LEARNING GUIDES
CASE-BASED ANESTHESIA
15259_FM.qxd 3/18/09 12:07 PM Page ii
15259_FM.qxd 3/19/09 12:37 AM Page iii
CLINICAL LEARNING GUIDES
CASE-BASED ANESTHESIA
GEORGE SHORTEN
Professor of Anaesthesia and Intensive Care Medicine
Department of Anaesthesia
University College of Cork
Consultant Anaesthetist
Cork University Hospital
Cork, Ireland
STEPHEN F. DIERDORF, MD
Professor and Vice Chairman
Department of Anesthesia
Indiana University School of Medicine
Indianapolis, Indiana
GABRIELLA IOHOM, MD, PhD

Consultant Anaesthetist/Senior Lecturer
University College Cork
Cork, Ireland
CHRISTOPHER J. O’CONNOR, MD
Professor of Anesthesiology
Rush University Medical Center
Chicago, Illinois
CHARLES W. HOGUE, JR., MD

Associate Professor
Department of Anesthesiology and Critical Care Medicine
The Johns Hopkins Medical Institutions and The Johns Hopkins Hospital
Baltimore, Maryland
15259_FM.qxd 3/18/09 12:07 PM Page iv
Acquisitions Editor: Frances DeStefano

Product Manager: Nicole Dernoski
Marketing Manager: Angela Panetta
Production Editor: Julie Montalbano
Design Coordinator: Terry Mallon
Compositor: Maryland Composition/ASI
Copyright © 2009 Lippincott Williams & Wilkins, a Wolters Kluwer business.
351 West Camden Street

Baltimore, MD 21201
530 Walnut Street

Philadelphia, PA 19106
Printed in China.
All rights reserved. This book is protected by copyright. No part of this book may be reproduced or transmitted in
any form or by any means, including as photocopies or scanned-in or other electronic copies, or utilized by any in-
formation storage and retrieval system without written permission from the copyright owner, except for brief quo-
tations embodied in critical articles and reviews. Materials appearing in this book prepared by individuals as part of
their official duties as U.S. government employees are not covered by the above-mentioned copyright. To request
permission, please contact Lippincott Williams & Wilkins at 530 Walnut Street, Philadelphia, PA 19106, via email
at permissions@lww.com, or via website at lww.com (products and services).
9 8 7 6 5 4 3 2 1
Library of Congress Cataloging-in-Publication Data
Case-based anesthesia : clinical learning guides / [edited by] George Shorten.

p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-7817-8955-4
1. Anesthesia—Case studies. I. Shorten, George.
[DNLM: 1. Anesthesia—Case Reports. 2. Anesthesia—Problems and Exercises. 3. Anesthesiology—
methods—Case Reports. 4. Anesthesiology—methods—Problems and Exercises. 5. Anesthetics—Case Reports.
6. Anesthetics—Problems and Exercises. 7. Perioperative Care—methods—Case Reports. 8. Perioperative
Care—methods—Problems and Exercises.
WO 218.2 C337 2009]
RD82.45.C37 2009
617.9’6—dc22
2008052575
DISCLAIMER
Care has been taken to confirm the accuracy of the information present and to describe generally accepted
practices. However, the authors, editors, and publisher are not responsible for errors or omissions or for any conse-
quences from application of the information in this book and make no warranty, expressed or implied, with respect
to the currency, completeness, or accuracy of the contents of the publication. Application of this information in a
particular situation remains the professional responsibility of the practitioner; the clinical treatments described and
recommended may not be considered absolute and universal recommendations.
The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set
forth in this text are in accordance with the current recommendations and practice at the time of publication.
However, in view of ongoing research, changes in government regulations, and the constant flow of information
relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any
change in indications and dosage and for added warnings and precautions. This is particularly important when the
recommended agent is a new or infrequently employed drug.
Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA)
clearance for limited use in restricted research settings. It is the responsibility of the health care provider to ascer-
tain the FDA status of each drug or device planned for use in their clinical practice.
To purchase additional copies of this book, call our customer service department at (800) 638-3030 or fax orders to
(301) 223-2320. International customers should call (301) 223-2300.
Visit Lippincott Williams & Wilkins on the Internet: http://www.lww.com. Lippincott Williams & Wilkins cus-
tomer service representatives are available from 8:30 am to 6:00 pm, EST.
15259_FM.qxd 3/18/09 12:07 PM Page v
Dedicated to the memory of Gerard McDonnell.

Dr. Shorten wishes to thank Ms. Renee Mooney
for her incomparable efficiency and hard work.
15259_FM.qxd 3/18/09 12:07 PM Page vi
15259_FM.qxd 3/18/09 12:07 PM Page vii
FOREWORD
The discovery and application of anesthesia is the most im- So in this setting, where does Case-Based Anesthesia: Clinical
portant contribution of American medicine to mankind. Its Learning Guides edited by Drs. Shorten, Dierdorf, O’Connor,
impact exceeds even the elucidation of the human genome. Iohom, and Hogue fit in? In other words, do we need yet an-
Without visionary discoveries by pioneers in anesthesiology, other anesthesiology text? The answer, in this case, is a re-
the explosive growth in type, complexity, and safety of surgi- sounding yes! Why? First starting with the title, Clinical
cal procedures would not have occurred. More importantly, Learning Guides, the editors have chosen to emphasize learn-
anesthesiology is considered to be the lead specialty in patient ing in the broader sense, not just Board exam preparation and
safety. re-certification, but acquisition of knowledge as part of the
The core principle that drives these advances is training process of responsibility and accountability for one’s education
and continuing education. It is interesting to note that, in the and lifelong learning. By viewing education through this lens,
19th century, anesthesiology was considered a “technique” the practioner can apply information gained from this text
with little scientific merit. It was not until 100 years later into a variety of clinical and examination settings. The Editors
that the specialty developed a rigorous scientific foundation accomplish their goal through the innovative approach of
with postgraduate training programs. Even more astound- using two formats for case-based learning: “Step-by Step” or
ing is the fact that, into the late 20th century, there was a “Reflection.” This is a unique approach for a textbook.
paucity of books authored by North Americans. Textbooks Importantly, it recognizes different learning styles to help re-
supporting resident education, preparation for board exam- inforce important clinical concepts. This is the first time such
inations, and reference for clinical care were predominantly diverse information has been organized on these educationally
British in origin. sound principles in a clinical textbook. The editors have cou-
In the 1980s the educational scene changed dramatically. pled this with the use of “hot topics” where new evidence can
Residents and fellows were recruited from the upper tier of be applied to clinical conundrums as well as to responses to ex-
medical school graduates. In addition to publication of core amination questions. This is accomplished by a list of all-star
and specialty textbooks and journals, application of electronic contributors, each an authority in his/her own area of expert-
media, such as the Internet, has revolutionized the specialty ise. It is as if the reader is being taken through a clinically chal-
of anesthesiology. The American Board of Anesthesiology lenge case with an expert at their side.
has stated, “The ability to independently acquire and process As Thomas L. Friedman implies in his best-selling book
information in a timely manner is central to assure individual The World is Flat (Picador 2007), anesthesiologists worldwide
responsibility for all aspects of patient care.” Although use of are truly interconnected, as globalization brings us into wide-
the Internet and other electronic media assist in rapidly an- reaching contact with our peers and new opportunities arise.
swering questions related to patient care, most residents, fel- Thus, Case-Based Anesthesia: Clinical Learning Guides is tar-
lows, and experienced clinicians still use the printed word to geted at an international array of inquisitive trainees and clini-
comprehensively learn about a new topic, prepare for board cians whose basic goal is safe and unsurpassed clinical care of
examination and recertification, and even organize a clinical our patients.
management plan for the patient with a complex array of co-
existing diseases. Paul G. Barash, MD
Professor, Department of Anesthesiology
Yale University School of Medicine
Attending Anesthesiologist
Yale-New Haven Hospital
New Haven, Connecticut
vii
15259_FM.qxd 3/18/09 12:07 PM Page viii
15259_FM.qxd 3/20/09 8:30 PM Page ix
CONTRIBUTORS
Hassan M. Ahmad, MD John Dowling, BDS, MB, BCh, BAO(Hons),

The Johns Hopkins School of Medicine BMedSc(NUI)
The Johns Hopkins Hospital Specialist Registrar in Anaesthesia
Baltimore, Maryland Cork University Hospital
Cork, Ireland
Ioanna Apostolidou, MD
Associate Professor of Anesthesiology Craig Dunlop, MBBS, FCARCSI
School of Medicine Specialist Registrar in Anaesthesia
University of Minnesota Cork University Hospital
Minneapolis, Minnesota Cork, Ireland
Ashit Bardhan, MBBS, FCARCSI Amanda A. Fox

Specialist Registrar Staff Anesthesiologist
Cork University Hospital Brigham & Women’s Hospital
Cork, Ireland Harvard Medical School
Boston, Massachusetts
Dorothy Breen, FCARCSI, FJFICM
Specialist Registrar in Anaesthesia Kelly Grogan, MD
Cork University Hospital Assistant Professor of Anesthesiology and Critical Care Medicine
Cork, Ireland The Johns Hopkins School of Medicine
The Johns Hopkins Hospital
Siun Burke, FCARCSI Baltimore, Maryland
Research Fellow
Cork University Hospital Anthony Hennessy, FCARCSI
Cork, Ireland Specialist Registrar in Anaesthesia
Asokumar Buvanendran, MD Cork, Ireland
Associate Professor of Anesthesiology
Rush University Medical Center Charles W. Hogue, Jr., MD
Chicago, Illinois Associate Professor
Charles D. Collard The Johns Hopkins Medical Institutions and The Johns Hopkins Hospital
Professor and Vice-Chairman Baltimore, Maryland
Department of Anesthesiology
Baylor College of Medicine Michelle Isac, MD
Houston, Texas Assistant Clinical Professor of Anesthesia
McMaster University
W. Christopher Croley, MD, FCCP Hamilton, Ontario, Canada
Assistant Professor of Anesthesiology and Critical Care Medicine
Rush University Medical Center Jason S. Johnson, MD
Chicago, Illinois Associate Professor of Anesthesiology
School of Medicine
Stephen F. Dierdorf, MD University of Minnesota
Professor and Vice Chairman Minneapolis, Minnesota
Department of Anesthesia
Indiana University School of Medicine
Indianapolis, Indiana
ix
15259_FM.qxd 3/20/09 8:30 PM Page x
x CONTRIBUTORS
Roy Kan, MBBS(Singapore), MMed (Anesth) James O’Driscoll, FCARCSI

Department of Anesthesiology and Critical Care Medicine Specialist Registrar in Anaesthesia
The Johns Hopkins School of Medicine Cork University Hospital
The Johns Hopkins Hospital Cork, Ireland
Baltimore, Maryland
Owen O’Sullivan, MB, BCh, BAO
Justin Lane, FCARCSI Specialist Registrar in Anaesthesia
Specialist Registrar in Anaesthesia Cork University Hospital
Cork University Hospital Cork, Ireland
Cork, Ireland
Richard J. Pollard, MD
Peter John Lee, MB, BCh, BAO, FCARCSI Southeast Anesthesia Consultants
Specialist Registrar in Anaesthesia Charlotte, North Carolina
Cork, Ireland David M. Rothenberg, MD, FCCM
The Max S. Sadove, MD Professor of Anesthesiology
Audrey R. Leverich, MD Associate Dean, Academic Affiliations
Fellow in Cardiothoracic Anesthesiology Rush University Medical Center
Department of Anesthesiology Chicago, Illinois
Weill Cornell Medical College
New York-Presbyterian Hospital Leon Serfontein, MBChB, FANZCA
New York, New York Consultant Anaesthetist
Jay K. Levin, MD Cork, Ireland
The Johns Hopkins School of Medicine Mansoor A. Siddiqui, MBBS, FCPS, FCARCSI
The Johns Hopkins Hospital Specialist Registrar in Anaesthesia
Baltimore, Maryland Cork University Hospital
Cork, Ireland
Bryan V. May, MD
Southeast Anesthesiology Consultants Nikolaos J. Skubas, MD
Charlotte, North Carolina Associate Professor of Anesthesiology
Weill Cornell Medical College
Nanhi Mitter, MD Department of Anesthesiology
Assistant Professor New York, New York
Department of Anesthesiology
Rush University Medical Center Joshua D. Stearns, MD
Chicago, Illinois Assistant Professor of Anesthesiology and Critical Care Medicine
The Johns Hopkins School of Medicine
Laurel E. Moore, M.D. The Johns Hopkins Hospital
Department of Anesthesiology Baltimore, Maryland
The University of Michigan
Ann Arbor, Michigan Jason Van der Velde, BAA, MBChB, EMDM-A
Trauma Research Registrar
Mohan Mugawar, FCARCSI Cork University Hospital
Specialist Registrar in Anaesthesia Cork, Ireland
Cork University Hospital John Vullo, MD
Cork, Ireland Southeast Anesthesiology Consultants
Charlotte, North Carolina
Christopher J. O’Connor, MD
Professor of Anesthesiology Adrienne Wells, MD
Rush University Medical Center Assistant Professor of Anesthesiology
Chicago, Illinois Rush University Medical Center
Chicago, Illinois
Brian D. O’Donnell, MB, FCARCSI, MSc
Clinical Lecturer in Anaesthesia
Cork, Ireland
15259_FM.qxd 3/18/09 10:30 PM Page xi
CONTENTS
Foreword vii
List of Contributors ix
1. Statins and Perioperative Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

AMANDA A. FOX AND CHARLES D. COLLARD
2. Perioperative ␤-Blockade . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
STEPHEN F. DIERDORF
3. Perioperative Glycemic Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

KELLY GROGAN
4. Neuraxial Analgesic Techniques for Cardiac Anesthesia . . . . . . . . . . . . . . . . . . 14

HASSAN M. AHMAD
5. Off-Pump Coronary Artery Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

AUDREY R. LEVERICH AND NIKOLAOS J. SKUBAS
6. Aprotinin and Antifibrinolytics in Cardiac Surgery . . . . . . . . . . . . . . . . . . . . . . 22

MICHELLE ISAC
7. The Use of Recombinant Factor VIIa in Cardiac Surgery . . . . . . . . . . . . . . . . . 25

JAY K. LEVIN
8. Postoperative Neuropathy After Cardiac Surgery . . . . . . . . . . . . . . . . . . . . . . . . 27

IOANNA APOSTOLIDOU AND JASON S. JOHNSON
9. Postoperative Visual Loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

LAUREL E. MOORE
10. Postoperative Cognitive Dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

CHARLES W. HOGUE
11. Perioperative Myocardial Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

JOSHUA D. STEARNS
12. Heparin-Induced Thrombocytopenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

ROY KAN
13. Hypertonic Saline Resuscitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

DAVID M. ROTHENBERG
14. Preoperative Liver Function Test Abnormalities . . . . . . . . . . . . . . . . . . . . . . . . 51

DAVID M. ROTHENBERG
15. Perioperative Use of Albumin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

W. CHRISTOPHER CROLEY
xi
15259_FM.qxd 3/18/09 12:07 PM Page xii
xii CONTENTS
16. Neurologic Complications of Peripheral Nerve Blockade . . . . . . . . . . . . . . . . . 58

CHRISTOPHER J. O’CONNOR
17. Peripheral Nerve Block Versus Epidural Analgesia for

Total Knee Arthroplasty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
ASOKUMAR BUVANENDRAN
18. Paravertebral Nerve Blockade for Thoracic Surgery . . . . . . . . . . . . . . . . . . . . . 66

ADRIENNE WELLS
19. Carotid Artery Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

20. Postpneumonectomy Pulmonary Edema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74

NANHI MITTER
21. Perioperative Antiplatelet Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77

NANHI MITTER
22. Intraoperative Blood Conservation Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

W. CHRISTOPHER CROLEY
23. Transfusion Thresholds and Intraoperative Coagulopathy . . . . . . . . . . . . . . . . 83

ANTHONY HENNESSY
24. Anesthesia for Bariatric Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

25. Vasopressin and Resuscitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91

STEPHEN F. DIERDORF
26. Anesthesia and Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

STEPHEN F. DIERDORF
27. Pharmacologic Myocardial Preconditioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99

JOHN VULLO
28. Predicting Difficult Mask Ventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

STEPHEN F. DIERDORF
29. Awake Tracheal Intubation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106

STEPHEN F. DIERDORF
30. Is There a Future for Succinylcholine? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110

STEPHEN F. DIERDORF
31. Cuffed Tracheal Tubes for Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113

STEPHEN F. DIERDORF
32. Role of Intraoperative BIS Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116

STEPHEN F. DIERDORF
33. Duchenne Muscular Dystrophy and Volatile Anesthetics . . . . . . . . . . . . . . . . 119

STEPHEN F. DIERDORF
34. Anesthesia for Magnetic Resonance Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . 123

STEPHEN F. DIERDORF
35. Evidence-Based Prevention of Postoperative Nausea and Vomiting . . . . . . . 127

RICHARD J. POLLARD
36. Ultrasound Guidance for Central Venous Cannulation . . . . . . . . . . . . . . . . . . 131

BRYAN V. MAY
15259_FM.qxd 3/18/09 12:07 PM Page xiii
CONTENTS xiii
37. Regional Anesthesia Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136

JUSTIN LANE AND BRIAN D. O’DONNELL
38. Ultrasound Guidance for Peripheral Nerve Blockade . . . . . . . . . . . . . . . . . . . 140

BRIAN D. O’DONNELL
39. Continuous Ambulatory Regional Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . 145

JASON VAN DER VELDE
40. Postoperative Analgesia in a Trauma Patient With

Opioid Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
BRIAN D. O’DONNELL
41. Alzheimer’s Disease and Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153

OWEN O’SULLIVAN
42. Sickle Cell Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157

SIUN BURKE
43. Anaphylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162

MANSOOR A. SIDDIQUI
44. Persistent Postsurgical Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166

PETER JOHN LEE
45. Opioid-Induced Hyperalgesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169

JAMES O’DRISCOLL
46. Transurethral Resection of Prostate Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . 171

JOHN DOWLING
47. Anesthesia and Sleep-Disordered Breathing . . . . . . . . . . . . . . . . . . . . . . . . . . . 175

LEON SERFONTEIN
48. Herbal Medicine and Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179

ASHIT BARDHAN AND CRAIG DUNLOP
49. Levosimendan and Acute Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182

DOROTHY BREEN
50. Antiplatelet Agents, Low-Molecular-Weight Heparin,

and Neuraxial Blockade . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186
LEON SERFONTEIN
51. Neuroprotection During Cerebral Aneurysm Surgery . . . . . . . . . . . . . . . . . . . 189

PETER JOHN LEE
52. Anesthesia for Cerebral Aneurysm Coiling . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193

ASHIT BARDHAN
53. Emergency Reversal of Rocuronium-Induced Neuromuscular

Blockade Using Sugammadex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .198
MOHAN MUGAWAR
54. Awareness During Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200

JUSTIN LANE
55. Mitochondrial Disease and Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203

DOROTHY BREEN
56. Emergence Agitation in Pediatric Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207

MANSOOR A. SADDIQUI
15259_FM.qxd 3/18/09 12:07 PM Page xiv
xiv CONTENTS
57. The Acute Pain Team Role in Management of a Patient With

Traumatic Upper Limb Amputation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212
OWEN O’SULLIVAN
58. Occupational Exposure to Anesthetic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . 216

JASON VAN DER VELDE
59. Fetal Oxygen Saturation and Caesarean Section . . . . . . . . . . . . . . . . . . . . . . . . 220

SIUN BURKE
60. Vasoconstrictors for Hypotension During Caesarean Section . . . . . . . . . . . . . 224

JAMES O’DRISCOLL
Index 227
15259_Ch01.qxd 3/14/09 2:27 PM Page 1
CHAPTER 1
Statins and Perioperative Risk
Amanda A. Fox and Charles D. Collard
CASE FORMAT: REFLECTION CASE DISCUSSION
A 75-year-old, 50-kg, Caucasian female presented for Pharmacologic Mechanisms

left heart cardiac catheterization after having a positive of Statins
finding on a dobutamine stress echocardiogram. She had
a history of exertional chest pain, hypertension, dyslipi-
3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors,
demia, and a 45 pack-year history of cigarette smoking.
commonly known as statins, are frequently prescribed choles-
The patient’s history was also significant for peripheral vas-
terol-lowering medications that decrease circulating plasma
cular disease, with bilateral lower extremity claudication.
low-density lipoprotein (LDL) cholesterol. Statins are not only
A right carotid endarterectomy (CEA) was performed in
associated with reduced atherosclerotic plaque formation, but
2002. The patient’s serum creatinine level was 1.3 mg/dL,
there is mounting evidence that statins may help prevent ather-
with an estimated creatinine clearance of 30 mL/min. She
osclerotic plaque rupture.1 Atherosclerotic plaques that are vul-
was receiving the following medications: intravenous nitro-
nerable to rupture have a prothrombotic, lipid-rich core that is
glycerin and heparin infusions, atenolol 25 mg orally once
infiltrated with active macrophages and is covered by a thin fi-
per day, and aspirin 81 mg orally once per day.
brous cap. Surgical insults such as trauma to tissues, vascular
Cardiac catheterization revealed significant three-
cross clamping, extracorporeal circulation, or blood transfusion
vessel coronary artery disease (90% proximal left main
can trigger profound systemic proinflammatory responses that
coronary artery, 90% proximal right coronary artery, 60%
may prompt vulnerable plaque rupture resulting in arterial oc-
first obtuse marginal) and a left ventricular ejection fraction
clusion and end-organ ischemia (e.g., myocardial infarction
of 60%. Carotid ultrasound showed no significant stenosis
[MI], stroke, renal and gastrointestinal infarction). Potential
of the right carotid artery, but there was 85% to 90% steno-
mechanisms by which statins may stabilize vulnerable plaques,
sis of the left proximal internal carotid artery. Thus, the pa-
as well as reduce the impact of plaque rupture include:
tient was scheduled for combined left CEA and coronary 1. Increasing the collagen content of the lipid-rich plaque
artery bypass graft (CABG) surgery. core.2
On the day of surgery, a right radial arterial line was 2. Decreasing plaque macrophage content2 and T-cell
placed preinduction with midazolam sedation and local activity.2,3
anesthesia. The patient then underwent intravenous induc- 3. Inhibition of cellular matrix metalloproteinases involved
tion of anesthesia with 8 mg of midazolam, 100 mg of with erosion of the fibrous plaque cap.2,4
thiopental, 200 ␮g of fentanyl, and 10 mg of pancuronium. 4. Inhibition of cellular transcription factors that modify
Anesthesia was maintained with 0.6% to 0.8% end-tidal G proteins involved in regulating endothelial, leukocyte,
isoflurane. A right internal jugular central line was placed. and platelet function.4
Electroencephalogram monitoring was conducted through- 5. Decreasing inflammatory mediators such as interleukin-
out the CEA without evidence of complications. Three-vessel 6, C-reactive protein, tumor necrosis factor-␣, and serum
CABG surgery was performed (left internal mammary arte- amyloid A.3,5
rial conduit to the left main artery and saphenous vein grafts
to the right coronary artery and first obtuse marginal artery),
Thus, the benefits of statin therapy are not limited to cho-
and the patient was separated uneventfully from cardiopul-
lesterol alone, and statin therapy in the perioperative setting
monary bypass. After heparin reversal with protamine and
may be particularly beneficial because of antiatherosclerotic,
chest closure, the surgeons closed the left CEA neck incision.
anti-inflammatory, and antithrombotic properties. However,
The patient was extubated 3 hours after surgery and had an
the precise underlying mechanisms by which statins prevent
uneventful postoperative course. She was monitored for 24
or reduce adverse postoperative outcomes, such as mortality or
hours in the intensive care unit and was then transferred to
postoperative atrial fibrillation, are not yet clearly defined.6
the hospital ward. The patient’s postoperative serum creati- Perioperative Statins: The Evidence
nine peaked at 1.6 mg/dL and returned to her preoperative
value of 1.3 mg/dL before discharge. The patient was dis-
in Cardiac and Vascular Surgery
charged to home on postoperative day 7, at which time in A recent meta-analysis of 223,010 patients undergoing cardio-
addition to her previous preoperative medications, she was vascular surgery found that preoperative statin therapy was
started on rosuvastatin 5 mg orally per day. associated with 38% and 59% reductions in the risk of 30-day
1
15259_Ch01.qxd 3/14/09 2:27 PM Page 2
2 CHAPTER 1 • STATINS AND PERIOPERATIVE RISK
mortality after cardiac (1.9% vs. 3.1%; p ⫽ 0.0001) and cantly decreased incidence of adverse cardiovascular events.16
vascular (1.7% vs. 6.1%; p ⫽ 0.0001) surgery, respectively.7 If statin therapy was discontinued after the MI occurred, how-
Additionally, a retrospective, case-control study of more than ever, the incidence of 30-day death and nonfatal MI was
2600 primary, elective CABG surgery patients found that pre- significantly increased compared with patients receiving con-
operative statin therapy was independently associated with a tinuous statin therapy (OR, 2.93; 95% CI, 1.64–6.27).16 This
reduced risk of in-hospital cardiovascular death (adjusted finding may explain in part why studies of the benefits of pre-
odds ratio [OR], 0.25; 95% confidence interval [CI], 0.07–0.87) operative statin therapy have reported mixed results regarding
but not nonfatal postoperative MI.8 Thus, perioperative statin postoperative nonfatal MI outcomes, as many of these surgical
therapy has been shown to be associated with a reduced inci- studies did not assess whether statins were continued in the
dence of acute, in-hospital adverse outcomes. postoperative period. Supporting this hypothesis is a recent
However, the benefits of perioperative statin therapy extend multicenter study of 2666 CABG surgical patients in which
beyond the acute perioperative period. For example, a study of preoperative statin therapy was independently associated with
post-CABG surgery patients with moderately elevated LDL a significant reduction (adjusted OR, 0.25; 95% CI, 0.07–0.87)
cholesterol levels who were placed on aggressive, long-term lo- in the risk of cardiac death within the first 3 days following
vastatin therapy (goal LDL concentration ⬍100 mg/dL) primary, elective CABG surgery (0.3 vs. 1.4%; p ⬍0.03) but
showed that during the 4-year follow-up period after starting was not associated with a reduced risk of postoperative nonfa-
statin therapy, patients on aggressive therapy experienced sig- tal, in-hospital MI (7.9% vs. 6.2%; p ⫽ NS). In this same study,
nificantly reduced saphenous vein graft occlusion and need for however, discontinuation of statin therapy after surgery was
revascularization as compared with patients on lower-dose independently associated with a significant increase in late
statin therapy.9 This clinical observation is also supported by in (postoperative day 4 though hospital discharge) all-cause mor-
vitro evidence that statins prolong arterial bypass graft pa- tality (adjusted OR, 2.64; 95% CI, 1.32–5.26) as compared with
tency.10 Finally, at least one retrospective study suggests that patients in whom statin therapy was continued (2.64 vs. 0.60%;
statin therapy may slow the progression of bioprosthetic aortic p ⬍0.01). This was true even after controlling for the postop-
valve degeneration after surgical implantation.11 erative discontinuation of aspirin, ␤-blockers, or angiotensin-
Cardiovascular morbidity and mortality after vascular sur- converting enzyme inhibitor therapy. Discontinuation of
gery is also relatively frequent, with mortality and nonfatal MI statin therapy after surgery was also independently associated
occurring in up to 5% to 6% and 30% of patients, respectively.1 with a significant increase in late, in-hospital cardiac mortality
Retrospective studies of preoperative statin therapy in patients (adjusted OR, 2.95; 95% CI, 1.31–6.66) compared with patients
undergoing major vascular surgery have shown that statins are in whom statin therapy was continued (1.91% vs. 0.45%;
associated with a reduced risk in both in-hospital and long- p ⬍0.01).8
term, all-cause cardiovascular mortality.12,13 Additionally, a re- Despite guidelines by the American College of Cardiology
cent prospective randomized study of vascular surgery patients and American Heart Association recommending statin therapy
found that preoperative atorvastatin therapy significantly re- for CABG patients with LDL concentrations ⬎100 mg/dL,17
duced adverse cardiovascular events up to 6 months after sur- two thirds of such patients may not be receiving statin therapy
gery.14 Based on these data, it seems reasonable that the patient when discharged from the hospital after their CABG surger-
who underwent combined major cardiac and vascular surgery ies.18 Reasons for not initiating or reinitiating statin therapy
in the case presentation might have benefited from statin ther- after CABG surgery may include patients’ decreased tolerance
apy initiated preoperatively. of oral medications secondary to postoperative nausea and
vomiting, transient renal dysfunction, concerns pertaining to
Perioperative Statins: The Evidence hepatic toxicity or myositis, or failure of the responsible physi-
in Noncardiovascular Surgery cian to reimplement preoperative medications. Thus, it may be
warranted to educate physicians about the potential benefits of
Although the present case involves both major cardiac and
perioperative statin therapy that continue in the postoperative
vascular surgery, cardiovascular complications after noncar-
period. In the present case, although the patient was discharged
diac surgery are also an important cause of morbidity and
on rosuvastatin, not only was she not receiving preoperative
mortality. A recent retrospective cohort study investigated the
statin therapy, but there was also failure to initiate a statin in
association between perioperative statin therapy and in-
the immediate preoperative period. Both are measures that
hospital postoperative mortality in 780,591 patients undergo-
might have decreased her risk for both in-hospital and long-
ing major noncardiac surgery at 329 hospitals in the United
term adverse cardiovascular outcomes.
States. Moreover, this study only assessed patients whose pre-
operative statin therapy was reinitiated within 2 days after sur-
gery, and it found that perioperative statin therapy was associ- 2007 American College of
ated with a significant reduction in all-cause mortality Cardiology and American Heart
(adjusted OR, 0.62; 95% CI, 0.58–0.67).15 Not only do these Association Guidelines on
data further suggest the usefulness of preoperative statin ther-
apy, but they also suggest the importance of continuing statins
Perioperative Cardiovascular
throughout the postoperative period. Evaluation and Care for
Noncardiac Surgery
Effect of Statin Withdrawal In light of the previously mentioned evidence, the American
In a study of ambulatory patients, statin therapy initiated be- College of Cardiology and the American Heart Association
fore the occurrence of acute MI was associated with a signifi- recently published perioperative guidelines that for the first
15259_Ch01.qxd 3/14/09 2:27 PM Page 3
CHAPTER 1 • STATINS AND PERIOPERATIVE RISK 3
time specifically address the role of perioperative statin phosphokinase concentrations in a large group of major vas-
therapy.19 Specifically, these new guidelines state that: cular surgical patients.23 After correcting for cardiac risk fac-
tors and clinical risk factors for myopathy, length of surgery
1. For patients currently taking statins and scheduled for remained the only independent predictor for myopathy.23
noncardiac surgery, statins should be continued.19 No case of rhabdomyolysis was observed, and there was no
2. For patients undergoing vascular surgery with or without difference in creatine phosphokinase levels between patients
clinical risk factors, statin use is reasonable.19 on long-term preoperative statin therapy and patients who
3. For patients with at least one clinical risk factor who are started statin therapy shortly before surgery.23
undergoing intermediate-risk procedures, statins may be
considered.19
Need for Future Studies
Thus, based on these guidelines, it would have been Presently available data and guidelines suggest that perioper-
reasonable to initiate and maintain statin therapy through- ative statin therapy is both appropriate and beneficial, but fur-
out the perioperative period for the patient in the case ther studies are needed to determine optimal statin duration
presentation. and dosage. For example, although a recent meta-analysis of
more than 300,000 patients with an acute MI suggests that ini-
Safety of Statin Therapy tiating statin therapy within 24 hours of MI onset reduces
Severe hepatotoxicity or myopathy associated with statin use mortality, it is not clear if this holds true for cardiovascular
has been reported but is rare.20 This is true for all available surgical patients with acute coronary syndromes, if they re-
statins, although the risk profile for atorvastatin might be the quire longer periods of statin administration.24 There thus
most favorable.20 Although mild, dose-related elevations in remains a need for further randomized controlled trials con-
serum aspartate aminotransferase and alanine aminotrans- ducted in specific cardiac and noncardiac surgical populations
ferase occur in about 1% of patients on statins, and acute liver to identify patients who will benefit most from perioperative
injury has been isolated to a few cases.21 Although statins are statin therapy and to determine the optimal duration of peri-
considered contraindicated in patients with chronic liver operative statin therapy.
disease, a recent multicenter, randomized, double-blind,
placebo-controlled trial of pravastatin therapy in hyperlipi-
demic patients with chronic, compensated liver disease KEY MESSAGES
showed no increase in statin-associated hepatotoxicity in these
patients.21 Caution should be exercised in initiating statin 1. Statin administration is associated with decreased
therapy in patients with chronic liver disease, however, and atherosclerotic plaque formation and may contribute
should probably only be done in conference with such pa- to prevention of atherosclerotic plaque rupture.
tients’ gastroenterologists. 2. A recent meta-analysis demonstrated that preoperative
The most serious potential statin side effect is rhabdomy- statin therapy was associated with a 38% and 59%
olysis. Across a spectrum of ambulatory trials, rhabdomy- reduction in the risk of 30-day mortality after cardiac
olysis was reported to occur in ⱕ0.7% of patients receiving (1.9% vs. 3.1%; p ⫽ 0.0001) and vascular (1.7% vs.
a broad range of statins and doses.22 Cerivastatin, which is 6.1%; p ⫽ 0.0001) surgery, respectively.
no longer on the market, is known to have the greatest
associated rhabdomyolysis risk (3.16 per million prescrip- 3. Perioperative statin therapy is associated with a
tions).20 In contrast, the risk of statin-related rhabdomy- reduced incidence of acute, in-hospital adverse
olysis is only in the range of 0 to 0.19 per million prescrip- outcomes.
tions for other commonly used statins.20 The risk for
4. Preoperative atorvastatin therapy significantly reduces
rhabdomyolysis is associated with factors that increase serum
adverse cardiovascular events up to 6 months after
statin concentrations, such as small body size, advanced age,
vascular surgery.
renal or hepatic dysfunction, diabetes, hypothyroidism, and
drugs that interfere with statin metabolism, such as cy- 5. Following noncardiac surgery, perioperative statin
closporin, antifungal agents, calcium-channel blockers, and therapy is associated with a significant reduction in
amiodarone.20 Because these characteristics are prevalent all-cause mortality.
in surgical populations, it is advisable to monitor for
6. American College of Cardiology/American Heart
statin side effects in patients on perioperative statin therapy,
Association guidelines state:
particularly in those with muscle disease, or hepatic or renal
dysfunction. The present case involving a small, elderly a. For patients currently taking statins and scheduled
patient with renal insufficiency should have been closely for noncardiac surgery, statins should be
monitored in the acute perioperative period for evidence of continued.
acidosis, muscle pain or weakness, or a rise in creatinine ki-
nase level. b. For patients undergoing vascular surgery with or
Although statin-related rhabdomyolysis is extremely rare, without clinical risk factors, statin use is reasonable.
early recognition and treatment are important to avoid seri- c. For patients with at least one clinical risk factor who
ous morbidity. In a recent study by Schouten et al., perioper- are undergoing intermediate-risk procedures, statins
ative statin use was not associated with an increased risk of may be considered.
perioperative myopathy or increased postoperative creatine
15259_Ch01.qxd 3/14/09 2:27 PM Page 4
4 CHAPTER 1 • STATINS AND PERIOPERATIVE RISK
QUESTIONS in saphenous-vein coronary-artery bypass grafts. N Engl J Med

1997;336:153–162.
10. Nakamura K, Al-Ruzzeh S, Chester AH, et al. Effects of
1. What is the mechanism by which statins lower circu- cerivastatin on vascular function of human radial and left
lating LDL cholesterol? internal thoracic arteries. Ann Thorac Surg 2002;73:1860–1865;
Answer: They act as inhibitors of 3-hydroxy-3-methyl- discussion 5.
glutaryl coenzyme A reductase. 11. Antonini-Canterin F, Zuppiroli A, Popescu BA, et al. Effect of
statins on the progression of bioprosthetic aortic valve degenera-
2. How do statins stabilize atheromatous plaques or limit tion. Am J Cardiol 2003;92:1479–1482.
the adverse effects of rupture? 12. Poldermans D, Bax JJ, Kertai MD, et al. Statins are associated
with a reduced incidence of perioperative mortality in patients
Answer: Suggested mechanisms include: undergoing major noncardiac vascular surgery. Circulation
Increasing the collagen content of the lipid-rich 2003;107:1848–1851.
plaque core. 13. Kertai MD, Boersma E, Westerhout CM, et al. Association be-
Decreasing plaque macrophage content2 and T-cell tween long-term statin use and mortality after successful abdom-
activity. inal aortic aneurysm surgery. Am J Med 2004;116:96–103.
Inhibition of cellular matrix metalloproteinases involved 14. Durazzo AE, Machado FS, Ikeoka DT, et al. Reduction in car-
with erosion of the fibrous plaque cap. diovascular events after vascular surgery with atorvastatin: a
Inhibition of cellular transcription factors that modify randomized trial. J Vasc Surg 2004;39:967–975; discussion 75–76.
15. Lindenauer PK, Pekow P, Wang K, et al. Lipid-lowering ther-
G proteins involved in regulating endothelial, leukocyte,
apy and in-hospital mortality following major noncardiac sur-
and platelet function. gery. JAMA 2004;291:2092–2099.
Decreasing inflammatory mediators such as interleukin-6, 16. Heeschen C, Hamm CW, Laufs U, et al. Withdrawal of statins
C-reactive protein, tumor necrosis factor-␣, and serum increases event rates in patients with acute coronary syndromes.
amyloid A. Circulation 2002;105:1446–1452.
17. Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA Guidelines
3. What adverse effects are associated with statin for Coronary Artery Bypass Graft Surgery: a Report of the
administration? American College of Cardiology/American Heart Association
Answer: The most serious potential statin side effect is Task Force on Practice Guidelines (Committee to Revise the
rhabdomyolysis. Mild, dose-related elevations in serum 1991 Guidelines for Coronary Artery Bypass Graft Surgery).
aspartate aminotransferase and alanine aminotransferase American College of Cardiology/American Heart Association. J
Am Coll Cardiol 1999;34:1262–1347.
occur in about 1% of patients on statins; acute liver injury
18. Khanderia U, Faulkner TV, Townsend KA, Streetman DS.
has been observed in a few cases. Severe hepatotoxicity or Lipid-lowering therapy at hospital discharge after coronary ar-
myopathy is rare. tery bypass grafting. Am J Health Syst Pharm 2002;59:548–551.
19. Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007
guidelines on perioperative cardiovascular evaluation and care
References for noncardiac surgery: a report of the American College of
1. Hindler K, Eltzschig HK, Fox AA, et al. Influence of statins on Cardiology/American Heart Association Task Force on Practice
perioperative outcomes. J Cardiothorac Vasc Anesth 2006;20: Guidelines (Writing Committee to Revise the 2002 Guidelines
251–258. on Perioperative Cardiovascular Evaluation for Noncardiac
2. Crisby M, Nordin-Fredriksson G, Shah PK, et al. Pravastatin Surgery) developed in collaboration with the American Society
treatment increases collagen content and decreases lipid content, of Echocardiography, American Society of Nuclear Cardiology,
inflammation, metalloproteinases, and cell death in human Heart Rhythm Society, Society of Cardiovascular Anesthesio-
carotid plaques: implications for plaque stabilization. Circulation logists, Society for Cardiovascular Angiography and
2001;103:926–933. Interventions, Society for Vascular Medicine and Biology, and
3. Crisby M. Modulation of the inflammatory process by statins. Society for Vascular Surgery. J Am Coll Cardiol 2007;50:
Drugs Today (Barc) 2003;39:137–143. e159–241.
4. Kinlay S, Ganz P. Early statin therapy in acute coronary syn- 20. Lazar HL. Should all patients receive statins before cardiac sur-
dromes. Semin Vasc Med 2003;3:419–424. gery: are more data necessary? J Thorac Cardiovasc Surg 2006;
5. Kinlay S, Schwartz GG, Olsson AG, et al. High-dose atorvastatin 131:520–522.
enhances the decline in inflammatory markers in patients with 21. Lewis JH, Mortensen ME, Zweig S, et al. Efficacy and safety of
acute coronary syndromes in the MIRACL study. Circulation high-dose pravastatin in hypercholesterolemic patients with
2003;108:1560–1566. well-compensated chronic liver disease: results of a prospective,
6. Blanchard L, Collard CD. Non-antiarrhythmic agents for pre- randomized, double-blind, placebo-controlled, multicenter trial.
vention of postoperative atrial fibrillation: role of statins. Curr Hepatology 2007;46:1453–1463.
Opin Anaesthesiol 2007;20:53–56. 22. Davidson MH, Robinson JG. Safety of aggressive lipid manage-
7. Hindler K, Shaw AD, Samuels J, et al. Improved postoperative ment. J Am Coll Cardiol 2007;49:1753–1762.
outcomes associated with preoperative statin therapy. 23. Schouten O, Poldermans D, Visser L, et al. Fluvastatin and biso-
Anesthesiology 2006;105:1260–1272. prolol for the reduction of perioperative cardiac mortality and
8. Collard CD, Body SC, Shernan SK, et al. Preoperative statin morbidity in high-risk patients undergoing non-cardiac surgery:
therapy is associated with reduced cardiac mortality after coro- rationale and design of the DECREASE-IV study. Am Heart J
nary artery bypass graft surgery. J Thorac Cardiovasc Surg 2004;148:1047–1052.
2006;132:392–400. 24. Fonarow GC, Wright RS, Spencer FA, et al. Effect of statin use
9. The Post Coronary Artery Bypass Graft Trial Investigators. The within the first 24 hours of admission for acute myocardial in-
effect of aggressive lowering of low-density lipoprotein choles- farction on early morbidity and mortality. Am J Cardiol
terol levels and low-dose anticoagulation on obstructive changes 2005;96:611–616.
15259_Ch02.qxd 3/14/09 2:49 PM Page 5
CHAPTER 2
Perioperative ␤-Blockade
Stephen F. Dierdorf
CASE FORMAT: STEP BY STEP and allows more time for coronary artery filling. ␤-Blockers
also act at the cellular level to improve the balance between
A 67-year-old male was scheduled for an exploratory oxygen supply and demand by protecting myocardial mito-
laparotomy and probable colectomy for colon cancer. chondria by means of antioxidation. All of these effects can
The patient had first noticed blood in his stool 4 months reduce the incidence of perioperative myocardial ischemia
before the scheduled surgery, but he had only sought and cardiac dysrhythmias.
medical attention 2 weeks prior to surgery. Colonoscopy Although the initial report of the efficacy of ␤-blockers
performed at that time revealed a mass in the descending to reduce perioperative cardiac events was published in
colon, and a biopsy result was positive for adenocarci- 1987, two studies from the 1990s sparked widespread in-
noma. He was scheduled for surgery at the first avail- terest in perioperative ␤-blockers.1–3 By 2002, the indica-
able date. The patient had a 24-year history of hyper- tions for the administration of perioperative ␤-blockers had
tension treated with lisinopril and a 12-year history of been expanded.4,5
non–insulin-dependent diabetes treated with diet and an The patient’s internist recommended the oral adminis-
oral hypoglycemic agent. He denied chest pain or exer- tration of long-acting metoprolol for 72 hours before sur-
tional dyspnea. The patient, a retired accountant with a gery. Intravenous metoprolol was to be administered if the
sedentary lifestyle, underwent a lumbar laminectomy and patient’s heart rate was greater than 65 beats per minute
spinal fusion at age 53. immediately before surgery. In the preoperative holding
The patient’s vital signs were as follows: heart rate, area, the patient’s heart rate was 76 beats per minute, and
86 beats per minute; blood pressure, 152/95 mm Hg; and his blood pressure was 138/80 mm Hg. After intravenous
respiratory rate, 16 breaths per minute. His height was metoprolol (5 mg), his heart rate was 63 beats per minute,
70 inches (1.8 meters), and his weight was 225 pounds and his blood pressure was 124/68 mm Hg.
(102 kg). Laboratory studies indicated that his resting elec-
trocardiogram reading was normal; hematocrit level, 41%;
sodium, 137 mmol/L; potassium, 4.1 mmol/L; creatinine,
1.2 mg/dL; blood urea nitrogen, 13 mg/dL; and glucose, Are there differences in the pharmacologic
130 mg/dL. effects of different ␤-blockers?
The patient’s internist recommended perioperative Although differences in the effects of different ␤-blockers
metoprolol. Would this reduce the patient’s perioperative have been demonstrated in basic research and animal studies,
risk of an adverse cardiac event? there have been no compelling reports of clinically significant
Ischemic heart disease is the major cause of morbidity differences. ␤-1 and ␤-2 receptors are found in cardiac muscle;
and mortality in developed countries throughout the world. however, ␤-1 receptors are dominant. ␤-2 Receptors are the
Approximately 100 million adults undergo noncardiac sur- primary ␤-receptors in bronchi.
gery per year, and 500,000 to 1 million will suffer a peri- Propranolol, a first-generation ␤-blocker, is a nonselective
operative cardiac complication. The efficacy of ␤-blockers antagonist with equal antagonistic effects on ␤-1 and ␤-2
for the treatment of ischemic heart disease is well docu- receptors. Second-generation ␤-blockers such as atenolol,
mented, and it is only logical that ␤-blocker therapy should metoprolol, and bisoprolol have much greater selectivity for
be applied to patients with coronary artery disease under- blockade of ␤-1 receptors. Third-generation ␤-blockers such
going noncardiac surgery. as labetalol, carvedilol, and nebivolol have varying ␤- adrener-
Surgery produces an increase in stress hormones and gic blocking effects (␤-1 and ␤-2) and vasodilating capabilities.
catecholamine levels and a hypercoagulable state. Effects Labetalol is a nonselective ␤-blocker with strong ␤-1 receptor
of these increases include tachycardia, hypertension, en- blocking effects thereby causing vasodilation. Carvedilol
hanced myocardial contractility, and increased myocardial blocks ␤-1 and ␤-2 receptors. Nebivolol is a highly selective
oxygen demand. In susceptible patients, adverse cardiac antagonist of ␤-1 receptors and causes vasodilation by activa-
events such as myocardial ischemia and dysrhythmias can tion of L-arginine and nitric oxide (Table 2.1). For diabetic
occur. ␤-Adrenergic blockers reduce myocardial oxygen patients, carvedilol increases insulin sensitivity, whereas
demand by reducing heart rate, cardiac contractility, and atenolol and metoprolol decrease insulin sensitivity.6 The lack
blood pressure. Slowing of the heart rate increases diastole of ␤-selectivity of propranolol and labetalol explains the in-
creased incidence of bronchoconstriction with both drugs.
5
15259_Ch02.qxd 3/14/09 2:49 PM Page 6
6 CHAPTER 2 • PERIOPERATIVE ␤-BLOCKADE
anesthesiologist. Advisory and regulatory groups have been

T A B L E 2 . 1 ␤-Adrenergic Antagonists
quick to advocate routine ␤-blocker therapy for a large num-
First-generation ␤-blockers
ber of patients. Unfortunately, data have been accumulating
faster than these groups can revise guidelines.
Propranolol
Second-generation ␤-blockers Can the differences in outcome from these
Metoprolol studies be resolved to formulate a logical plan
Atenolol for perioperative ␤-blocker therapy that has
the highest benefit potential?
Bisoprolol
Resolving three questions concerning perioperative ␤-blockade
Third-generation ␤-blockers would provide much-needed information.
Labetalol 1. Do current ␤-blocker regimens provide maximal cardio-
Bucindolol protection?
Carvedilol Administration of ␤-blockers for 7 to 10 days before surgery
Nebivolol may be required for optimal effect at the cellular level. This pe-
riod of time may also be important for patients with hyperten-
sion to normalize cerebral autoregulation. Cooperative efforts
among internists, surgeons, and anesthesiologists would be re-
quired to achieve this goal.
Bisoprolol, metoprolol, and carvedilol have been shown to
2. Is more precise perioperative hemodynamic control
significantly reduce mortality in patients with heart failure.
required?
No clinical studies have been performed that demonstrate
the superiority of one ␤-blocker over the others with respect There is evidence that ␤-blockade and tight heart rate con-
to reducing perioperative risk. Limited evidence suggests that trol are associated with a lower incidence of myocardial is-
␤-blockers with vasodilating properties may be better for pa- chemia and better long-term outcome.10
tients after myocardial infarction and for patients with chronic
3. Are there differences in individual patients that explain
ischemic heart disease.
the inconsistencies in the results from published studies?
Induction of anesthesia was performed with propofol (1.5
mg/kg), and rocuronium (0.6 mg/kg) was administered to facil- Polymorphism in adrenergic receptors may affect a patient’s
itate tracheal intubation. Oxygen in sevoflurane was adminis- response to ␤-blockers and have a significant effect on ultimate
tered by face mask until adequate muscle relaxation was outcome. It is known that patients with hypertension have a
achieved for tracheal intubation. Direct laryngoscopy and tra- variable response to ␤-blockers based on genetic variations in
cheal intubation were performed without difficulty. The adrenergic receptors. Ser49Gly and Arg389Gly are two single
patient’s vital signs immediately after tracheal intubation were: nucleotide polymorphisms of ␤1-adrenergic receptor genes.
heart rate 68 beats per minute and blood pressure 80/45 Patients with hypertension and Arg389Arg receptors have a
mm Hg. Two 5-mg doses of ephedrine did not significantly af- greater decrease in systolic and diastolic blood pressure when
fect the heart rate or blood pressure. Phenylephrine (100 ␮g) in- treated with metoprolol.11 A study of patients undergoing sur-
creased the blood pressure to 100/60 mm Hg and decreased the gery with spinal anesthesia found that the polymorphism of the
heart rate to 58 beats per minute. Maintenance of anesthesia ␤-adrenergic receptor was more predictive of outcome than the
was done with desflurane in an air-oxygen mixture. The oper- influence of ␤-blockers.12 Because no previous perioperative
ative course was marked by blood pressure lability that studies evaluated genetic variations, differences in genetic pat-
required a phenylephrine infusion and repeated boluses of in- terns might explain variable responses to ␤-blockers. Further
travenous fluids to maintain a satisfactory blood pressure. study of the relationship between perioperative outcome and
Emergence was slower than expected, but the patient was extu- genetic variations in adrenergic receptors is clearly warranted.
bated in the operating room without difficulty. He was con-
fused for the first 48 hours after surgery. At the time of This patient had no adverse perioperative
discharge from the hospital, his wife felt that he had returned cardiac events but did have significant blood
to his normal mental status. pressure lability and possible central nervous
system morbidity (delayed emergence and
postoperative confusion). Was he, in fact, a
Are there risks to perioperative
suitable candidate for perioperative ␤-blockers?
␤-adrenergic blockade?
Aggressive ␤-blockade can cause bradycardia as well as hy- Recommendations for treatment can be divided into three
potension and may increase the risk of stroke and death. The classes based on risk-to-benefit ratio and degree of evidence.
enthusiasm for widespread perioperative ␤-blocker adminis- Class I: benefit ⬎⬎⬎ risk. Treatment should be administered.
tration has been dampened by reports concerning the lack of Class IIa: benefit ⬎⬎ risk. It is reasonable to administer
effect of ␤-blockers in some studies and an increased risk of treatment.
adverse effects reported in others.7–9 Studies such as these that Class IIb: benefit ⱖ risk. Treatment may be considered.
report conflicting results present a dilemma for the clinical Class III: risk ⱖ benefit. Treatment should not be administered.
15259_Ch02.qxd 3/14/09 2:49 PM Page 7
CHAPTER 2 • PERIOPERATIVE ␤-BLOCKADE 7
for evaluation and management of the patient with some risk

T A B L E 2 . 2 Risk for Noncardiac Surgery
factors but no overt evidence of cardiac disease have not been
Low-risk surgery sufficiently elucidated to provide the anesthesiologist with
clear and unambiguous guidelines. It is difficult for advisory
Ambulatory surgery and regulatory groups to revise recommendations as rapidly as
Breast surgery new information accumulates. Although ␤-blockers can cer-
Cataract surgery tainly reduce the incidence of perioperative cardiac events,
there are potential risks, and accurate patient stratification is
Endoscopy (gastrointestinal and gastric ulcers) necessary to obtain maximum benefit with the least risk.14 The
Intermediate risk surgery effect of the perioperative use of statins and ␣-2 adrenergic ag-
onists on outcome needs to be more thoroughly evaluated. The
Intraperitoneal surgery
judicious use of these drugs in combination with ␤-blockers
Intrathoracic surgery may achieve an even greater perioperative risk reduction
Carotid endarterectomy (Table 2.3).15
Head and neck surgery
Orthopedic surgery
KEY MESSAGES
High-risk surgery
Aortic surgery 1. ␤-Adrenergic blockers produce pharmacologic effects
that can reduce the incidence of perioperative
Peripheral vascular surgery
myocardial ischemia and cardiac dysrhythmias. These
effects include decreasing myocardial oxygen demand
by reducing heart rate, cardiac contractility, and
Patients require stratification regarding preoperative med- blood pressure; slowing of the heart rate to prolong
ical condition and degree of risk of the surgery (Table 2.1). diastole during which coronary artery flow occurs;
Patients receiving preoperative ␤-blockers for cardiac disease and protection of myocardial mitochondria by means
should have ␤-blockers continued regardless of the risk of of antioxidation.
surgery (class I). High-risk patients undergoing vascular
2. No clinical studies have been performed that
surgery should also receive perioperative ␤-blockers (class I).13
demonstrate the superiority of one ␤-blocker over the
There are several risk factors for adverse perioperative out-
others with respect to reducing perioperative risk.
comes (Table 2.2). Patients with active cardiac diseases such as
unstable angina, recent myocardial infarction, heart failure, sig- 3. Administration of ␤-blockers for 7 to 10 days before
nificant dysrhythmias (high-grade atrioventricular block), and surgery may be required for optimal effect at the
severe valvular disease require evaluation and treatment prior cellular level.
to noncardiac surgery. Provocative testing for myocardial is-
chemia need only be performed if testing will alter management
(e.g., revascularization). Patients with only one or two risk fac-
tors undergoing intermediate risk surgery do not require stress QUESTIONS
testing but may benefit from perioperative ␤-blockers.
1. By what mechanism do ␤-adrenergic blockers reduce
the risk of myocardial ischemia?
The patient had two preoperative risk factors:
hypertension and diabetes mellitus and was Answer: ␤-blockers reduce myocardial oxygen
undergoing intermediate-risk surgery. The consumption by reducing heart reate, myocardial
indication for perioperative ␤-blockers was contractility, blood pressure, and protecting mitochon-
weak and intraoperative hemodynamic dria by antioxidation. The reduction in heart rate
instability did develop. increases diastole and provides more time for coronary
perfusion.
Patients with risk factors for cardiac disease present many
challenges for perioperative management. Recommendations 2. What does class IIB recommendation imply?
Answer: Treatment recommendations are based on
strength of evidence supporting a treatment. A class IIB
T A B L E 2 . 3 Cardiac Risk Factors
recommendation suggests that enough evidence exists
Ischemic heart disease that a treatment should be considered.
Compensated heart failure 3. What are the risks of perioperative ␤-adrenergic
blockade?
Cerebrovascular disease
Answer: Although perioperative ␤-adrenergic blockade
Diabetes mellitus
can reduce the incidence of myocardial ischemia, the
Renal insufficiency risk of intraoperative hypotension, stroke, and death
are increased.
15259_Ch02.qxd 3/14/09 2:49 PM Page 8
8 CHAPTER 2 • PERIOPERATIVE ␤-BLOCKADE
References (MaVS) study, a randomized controlled trial. Am Heart J 2006;

152:983–990.
1. Pasternack PF, Imperato AM, Baumann FG, et al. The hemody- 9. POISE Study Group. Effects of extended-release metopro-
namics of beta-blockade in patients undergoing abdominal aortic lol succinate in patients undergoing non-cardiac surgery
aneurysm repair. Circulation 1987;76:III 1–7. (POISE trial): a randomized controlled trial. Lancet 2008;371:
2. Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on 1839–1847.
mortality and cardiovascular morbidity after noncardiac surgery. 10. Feringa HHH, Bax JJ, Boersma E, et al. High dose ␤-blockers
N Engl J Med 1996;335:1713–1720. and tight heart rate control reduce myocardial ischemia and tro-
3. Poldermans D, Boersma E, Bax JJ, et al. The effect of bisoprolol ponin T release in vascular surgery patients. Circulation 2006;114
on perioperative mortality and myocardial infarction in high-risk (Suppl I):I-344-I-49.
patients undergoing vascular surgery. N Engl J Med 1999;341: 11. Shin J, Johnson JA. Pharmacogenetics of ␤-blockers.
1789–1794. Pharmacotherapy 2007;27:874–887.
4. Auerbach AD, Goldman L. ␤-blockers and reduction of cardiac 12. Zaugg M, Bestmann L, Wacker J, et al. Adrenergic receptor
events in noncardiac surgery. JAMA 2002;287:1445–1447. genotype but not perioperative bisoprolol therapy may determine
5. Fleisher LA, Eagle KA. Lowering cardiac risk in noncardiac cardiovascular outcome in at-risk patients undergoing surgery
surgery. N Engl J Med 2001;345:1677–1682. with spinal block. Anesthesiology 2007;107:33–44.
6. Weber MA. The role of new ␤-blockers in treating cardiovascular 13. Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007
disease. Am J Hypertens 2005;18:169S–176S. guidelines on perioperative cardiovascular evaluation and care
7. POBBLE Trial Investigators. Perioperative ␤-blockade (POB- for noncardiac surgery: executive summary. Anesth Analg 2007;
BLE) for patients undergoing infrarenal vascular surgery: results 106:685–712.
of a randomized double-blind controlled trial. J Vasc Surg 2005; 14. Fleisher LA, Poldermans D. Perioperative ␤ blockade: where do
41:602–609. we go from here? Lancet 2008;371:1813–1814.
8. Yang H, Raymer K, Butler R, et al. The effects of perioperative 15. London MJ. Beta blockers and alpha-2 agonists for cardioprotec-
␤-blockade: results of the metoprolol after vascular surgery tion. Best Pract Res Clin Anaesth 2008;22:95–110.
15259_Ch03.qxd 3/14/09 2:50 PM Page 9
CHAPTER 3
Perioperative Glycemic Control
Kelly Grogan
CASE FORMAT: REFLECTION What is (are) the relationship(s) between the

mechanisms underlying hyperglycemia and
A 72-year-old male with a history of type 2 diabetes mel-
poor patient outcome?
litus, hypertension, and remote tobacco use presented for The mechanisms of harm from hyperglycemia center on the
coronary artery bypass graft surgery. His medications in- immune system, mediators of inflammation, vascular per-
cluded aspirin daily, metoprolol 50 mg daily, metformin turbations, altered hemodynamics, and enhanced neuronal
500 mg twice daily, omeprazole 20 mg daily, and ator- damage following brain ischemia. The association of hy-
vastatin 10 mg daily. He had no known drug allergies. perglycemia and infection appears to primarily result from
Preoperatively, an echocardiogram showed mild mitral phagocyte dysfunction involving impaired neutrophil and
regurgitation, nonsignificant aortic sclerosis, and a left monocyte adherence, chemotaxis, phagocytosis, and bacterial
ventricular ejection fraction of 40% with mild inferior killing.2 Classic microvascular complications of diabetes are
hypokinesis. Laboratory test results included a fasting caused by alterations in the aldose reductase pathway, ad-
serum glucose level of 165 mg/dL; HgbA1C, 7.6%; vanced glycation end-product pathway, enhanced reactive
hematocrit, 36%; and creatinine, 1.3 mg/dL. On the oxygen species production, and the protein kinase C path-
morning of surgery, the patient’s serum glucose level was way. Several of these pathways may contribute to immune
134 mg/dL. He had received metoprolol the morning of dysfunction.3
surgery, and was fasting since 10:00 PM on the previous Acute hyperglycemia also has numerous effects on the
evening. cardiovascular system. Hyperglycemia impairs myocardial
After induction of general anesthesia and tracheal in- ischemic preconditioning that might contribute to larger
tubation, central venous access was obtained, and a myocardial infarct size in diabetics compared with nondia-
transesophageal echocardiography probe was placed. betics.4 Hyperglycemia is associated with reduced coronary
The patient’s initial serum glucose level was 155 mg/dL. collateral blood flow5 and increased cardiac myocyte death
An intravenous insulin infusion was started at 2 units per through apoptosis6 or by exaggerating ischemia-reperfusion
hour. Serum glucose testing was repeated every hour dur- cellular injury.7 Multiple studies have identified a variety of
ing the procedure, and the insulin dosage was adjusted hyperglycemia-related abnormalities in hemostasis that
based on the institutional intraoperative insulin protocol favor thrombosis.8,9
(Table 3.1). Acute hyperglycemia is associated with enhanced neuronal
damage following induced brain ischemia.2 This enhanced
injury is mostly in the ischemic penumbra thus contributing
to stroke expansion.10–13 Elevated glucose concentrations
have been associated with enhanced cerebral ischemic damage
What is the epidemiology of diabetes mellitus? secondary to increased tissue acidosis and lactate levels.
From 1980 through 2004, the number of Americans with dia- Lactate has been associated with damage to neurons, astro-
betes mellitus increased from 5.8 to 14.7 million. Diabetes cytes, and endothelial cells.14
now affects nearly 21 million Americans, or 7% of the U.S.
population; more than 6 million of the affected do not know
they have diabetes. Compelling evidence continues to accu- Other than glycemic regulation, how does
mulate suggesting that poorly controlled glucose levels are as- insulin influence metabolic regulation?
sociated with increased morbidity and mortality rates, as well There may be beneficial effects of insulin therapy that are
as higher health care costs. Further, long-term strict glycemic separate from mere glycemic control. First, insulin inhibits
control reduces the frequency of diabetes complications, par- lipolysis, reducing free fatty acid levels that are believed to
ticularly microvascular complications and renal dysfunction. contribute to cardiac arrhythmias. Next, insulin stimulates en-
The United States spends approximately $132 billion each dothelial nitric oxide synthase enhancing nitric oxide secretion,
year on diabetes—$92 billion in direct medical costs and resulting in arterial vasodilation in addition to a variety of other
another $40 billion in indirect costs because of missed work- beneficial effects on oxidation and inflammation. Finally, in-
days or other losses in productivity.1 sulin, in the environment of euglycemia or near-euglycemia,
9
15259_Ch03.qxd 3/14/09 2:50 PM Page 10
10 CHAPTER 3 • PERIOPERATIVE GLYCEMIC CONTROL
T A B L E 3 . 1 A Insulin Loading Dose and Initial Infusion Rate
Recommended Action
Glucose (mg/dL) Intravenous Loading Bolus Infusion Rate
⬎300 12 units 8–10 U/h
261–300 9 units 7–8 U/h
231–260 7 units 6–7 U/h
201–230 3 units 5–6 U/h
171–200 2 units 3–5 U/h
141–170 0 units 2–3 U/h
120–140 0 units 1–2 U/h
100–119 0 units 0.5 U/h
appears to inhibit proinflammatory cytokines, adhesion mole- significant correlation between average postoperative glucose
cules, and chemokines, in addition to acute-phase proteins.15 level and mortality with the lowest mortality rates found in
patients with postoperative glucose levels ⬍150 mg/dL. In
patients undergoing general surgery, a single blood glucose
Is in-hospital hyperglycemia associated with level ⬎220 mg/dL is associated with a nearly threefold
adverse patient outcomes? greater risk for infection compared with blood glucose levels
Data from observational studies have linked hyperglycemia ⬍220 mg/dL.20 Multiple other retrospective studies have
with poor outcome in acutely ill patients. In cardiac surgical linked hyperglycemia with worse outcomes in patients with
patients, hyperglycemia is associated with a greater risk for acute myocardial infarction.21,22 Hyperglycemia is further
sternal wound infections.16,17 More aggressive treatment of associated with more severe brain damage and mortality after
hyperglycemia with intravenous insulin targeting serum ischemic but not hemorrhagic stroke.23,24
glucose levels of 100 to 150 mg/dL reduced the risk of deep Until recently, data linking hyperglycemia with poor
sternal wound infections by 57% compared with historical outcomes in hospitalized patients were retrospective. In a
controls in which the goal was to maintain glucose levels landmark series of prospectively randomized, double-
between 150 to 200 mg/dL.18,19 In those analyses, there was a blinded studies, Van den Berghe et al.25 reported that criti-
T A B L E 3 . 1 B Insulin Dose for Infusion Titration Based on Hourly Glucose Checks
Glucose (mg/dL) Rising Glucose Falling Glucose

Re-Bolus Increase Rate Hold Infusion Decrease Rate
⬎350 12 units 5–6 U/h — 0%
301–350 9 units 4–5 U/h — 0%
251–300 7 units 3–4 U/h — 0%
201–250 5 units 2–3 U/h — 0%–10%
161–200 3 units 1–2 U/h — 0%–10%
121–160 0 units No change 0–30 min 0%–25%
40–60 Stop infusion; ensure 30–60 min Do not restart
adequate glucose infusion until glucose
administration is ⬎120 mg/dL
⬍40 Stop infusion; Until adequate Do not restart
administer one-half rebound in glucose infusion until
amp D50 and check is ensured glucose is
glucose in 30–60 min ⬎120 mg/dL
15259_Ch03.qxd 3/14/09 2:50 PM Page 11
CHAPTER 3 • PERIOPERATIVE GLYCEMIC CONTROL 11
cally ill patients in a mixed medical surgical intensive care What are the principles of perioperative
unit (ICU) had improved outcomes with intensive insulin management of the diabetic patient?
therapy targeted to serum glucose levels of 80 to 110 mg/dL Insulin resistance and insulin secretory capacity in hospi-
compared with standard treatment. Patients in the intensive talized patients is influenced by numerous factors, including
insulin treatment group had a 34% reduction in mortality, a severity of illness, medications (e.g., glucocorticoids and cate-
46% lower incidence of sepsis, a 41% reduction in the rate of cholamines), procedures, and diet that is often interrupted.
renal failure requiring dialysis, a 50% reduction in the fre- The ability to control glucose in diabetic patients will, in part,
quency of blood transfusion, and a 44% reduction in the rate depend on the quality of their control before admission. This
of critical illness polyneuropathy compared with the control can be assessed by measuring hemoglobin A1C value (a value
group. These benefits, however, were restricted to patients ⬎6% indicates poor control).
hospitalized in the ICU for 3 to 5 days. When the data were Hospitalized patients are usually not managed with oral
limited to medical ICU patients, intensive insulin treatment hypoglycemic agents because of their long half-life, potential
was associated with worse outcomes, in fact, for patients for side effects caused by an acute illness, and the inability to
with a shorter duration of ICU admission. A meta-analysis rapidly titrate the dose. Nonetheless, continuing oral hypo-
of 35 clinical trials evaluating the effect of insulin therapy on glycemic agents taken before hospitalization is considered for
mortality rates in hospitalized patients with critical illness non–critically ill patients who had good pre-hospital glucose
found that insulin therapy decreased short-term mortality control and who are expected to eat a normal diet. Important
by 15% in a variety of clinical settings.26 These studies, how- considerations for the use of oral hypoglycemic agents in hos-
ever, did not investigate the risk versus benefits of intraoper- pitalized patients include:
ative intensive insulin management. In fact, Gandhi et al.27
found a higher mortality rate for patients randomized to • Sulfonylureas have a long duration of action (that varies
receiving intensive insulin therapy (targeted glucose levels from patient to patient) predisposing to hypoglycemia espe-
of 80 to 110 mg/dL) during cardiac surgery compared with cially in patients who are not eating (nothing by mouth
controls. [NPO]). These agents do not allow rapid dose adjustment
to meet the changing needs of acutely ill patients. Further,
sulfonylureas block ATP-sensitive potassium channels that
What glucose level should be targeted?
mediate in part myocardial ischemic preconditioning.
Based on the available data, recommendations have been Patients at risk for myocardial ischemia, thus, might expe-
advanced as to what serum glucose level to target with in- rience greater myocardial damage if given sulfonylureas
sulin therapy for patients in critical care settings. The targets (e.g., during cardiac surgery or when a perioperative
for non–intensive care patients including those during myocardial infarction occurs).
surgery are less well defined and are somewhat controver- • Metformin may lead to potentially fatal lactic acidosis par-
sial. Regardless, guidelines from the American Diabetes ticularly during the stress associated with surgery or acute
Association and the American College of Endocrinology illness. Risk factors for this side effect include cardiac
recommend intensive insulin management for both ICU and disease, heart failure, hypoperfusion, renal insufficiency,
non-ICU patients (Table 3.2).15,28 Guidelines for the man- old age, and chronic pulmonary disease. Nonetheless, pre-
agement of patients with acute stroke from the American dicting individual susceptibility is limited, and most data
Heart Association, however, acknowledge that the exact regarding this condition are from case series in which other
glucose level that should be targeted with insulin therapy factors might have confounded the findings. Regardless,
for patients with stroke are not known and are probably metformin is typically stopped the morning of surgery or at
⬍140 mg/dL.29 least 8 hours before surgery.
• Thiazolidinediones have few side effects, but these drugs do
increase intravascular volume that might predispose to con-
T A B L E 3 . 2 Recommended Targets for Serum gestive heart failure. Their use is associated with abnormal
liver function tests, and they should not be given to patients
Glucose Levels in Hospitalized
with liver dysfunction.
Patients from the ADA and the ACE
Previously diagnosed and newly diagnosed diabetics will
ADA (28) ACE (15) likely require insulin management perioperatively or during
Intensive care As close to 110 ⬍110 mg/dL an acute illness. The commonly used “sliding scale insulin
unit mg/dL as possible therapy” with regular insulin is generally inappropriate as a
sole insulin management strategy. A key component to pro-
Non–critical As close to 90–130 ⬍110 mg/dL
viding effective insulin therapy is determining whether a
care units mg/dL as possible; preprandial; patient has the ability to produce endogenous insulin.
maximal ⬍180 mg/dL maximal Patients with type 1 diabetes are by definition insulin defi-
⬍180 mg/dL cient. Patients with prior pancreatectomy or with pancreatic
To convert mg/dL of glucose to mmol/L, divide by 18 or multiply by dysfunction, those who have received insulin for greater than
0.055. 5 years, and patients with wide fluctuations in serum glucose
ACE, American College of Endocrinology; ADA, American Diabetes levels may all have a significant degree of insulin deficiency.
Association. Patients determined to be insulin deficient require basal in-
sulin replacement at all times to prevent iatrogenic diabetic
15259_Ch03.qxd 3/14/09 2:50 PM Page 12
12 CHAPTER 3 • PERIOPERATIVE GLYCEMIC CONTROL
ketoacidosis. A subcutaneous insulin regimen consists of

KEY MESSAGES
three elements:
• Basal insulin requirement provided in the form of interme- 1. Diabetes now affects nearly 21 million Americans, or
diate or long-acting analogs such as lente insulin. Some 7% of the U.S. population.
non–insulin-deficient patients may not require basal insulin
2. The mechanisms of harm from hyperglycemia center
if they are to take nothing by mouth. However, withhold-
on the immune system, mediators of inflammation,
ing basal insulin in insulin-deficient patients may result in
vascular perturbations, altered hemodynamics, and
ketoacidosis.
enhanced neuronal damage following brain ischemia.
• Prandial insulin is given before meals. The rapid-acting in-
sulin analogs, insulin lispro and aspart, are excellent prandial 3. Van den Berghe et al. reported that critically ill pa-
insulins. Some patients do receive their prandial coverage tients in a mixed medical surgical ICU had improved
immediately after eating, and the dose is based on carbohy- outcomes with intensive insulin therapy targeted to
drate counting. serum glucose levels of 80 to 110 mg/dL compared
• Correction-dose or supplemental insulin is given to treat with standard treatment.
hyperglycemia. This should not be confused with “sliding
scale insulin,” which usually refers to a set amount of in- 4. Intravenous insulin is the most reliable means for
sulin administered for hyperglycemia without regard to the achieving glycemic control, particularly in critically ill
timing of food, the presence or absence of pre-existing patients.
insulin administration, or individualization of the patient’s
sensitivity to insulin. Correctional-dose insulin can be used
to accommodate the increased insulin requirements that
accompany acute illness and insulin resistance secondary to QUESTIONS
counterregulatory responses to stress and/or illness.
1. By what mechanism(s) does diabetes mellitus result in
By far, intravenous insulin is the most reliable means for microvascular complications?
achieving glycemic control particularly in critically ill patients
who may have severe or rapidly changing insulin requirements, Answer: These mechanisms are alterations in the aldose
generalized edema, impaired perfusion of subcutaneous sites reductase pathway, advanced glycation end-product
and extremities, and those who are receiving total parenteral pathway, enhanced reactive oxygen species production,
nutrition and/or sympathomimetic drugs. Most institutions and the protein kinase C pathway.
now have standardized algorithms. The most effective are those 2. What is the most important adverse effect associated
that use dynamic scales, incorporating the rate of change in glu- with metformin administration?
cose into dose adjustments. Frequent glucose level monitoring is
imperative to ensure good control and minimize hypoglycemic Answer: Metformin may lead to potentially fatal lactic
events. As a patient’s clinical status improves, he or she can be acidosis, particularly during the stress associated with
transitioned to subcutaneous insulin. This step requires using surgery or acute illness.
the most recent infusion rate to approximate the overall daily re- 3. What factors may contribute to hypoglycemia in acutely
quirement, dividing this into basal and prandial components. It ill patients?
is often necessary to overlap the intravenous and subcutaneous
insulin to ensure a proper conversion. Answer: Decreased nutritional intake (decreased oral
intake, vomiting, procedures that require the patient
to take nothing by mouth, unexpected interruptions
PREVENTION AND MANAGEMENT of enteral feedings or parenteral nutrition, altered
level of consciousness), liver and kidney dysfunction,
OF HYPOGLYCEMIA infection, malignancy, and sepsis may be contributing
factors.
Hypoglycemia, if unrecognized and prolonged, can have severe
and permanent negative outcomes. Hospitalized patients are at
an increased risk of developing hypoglycemia because of al- References
tered nutritional state, liver and kidney dysfunction, infection, 1. Centers for Disease Control and Prevention. National diabetes
malignancy, and sepsis. Changes in medications (particularly surveillance system: prevalence of diabetes number (in millions)
steroids and catecholamines), decreased oral intake, vomiting, of persons with diagnosed diabetes, United States, 1980–2004.
procedures that require the patient to take nothing by mouth, Available at: http://www.sds.gov/diabetes/statistics/prev/national/
unexpected interruptions of enteral feedings or parenteral nu- figpersons.htm. Accessed March 3, 2009.
trition, and patients’ mental status all contribute to the com- 2. Clement S, Braithwaite SS, Magee MF, et al. Management of di-
plexity of glucose management. Patients that are sedated or abetes and hyperglycemia in hospitals. Diabetes Care 2004;
27:553–591.
under general anesthesia, having delirium, or are hospitalized
3. Sheetz M, King G. Molecular understanding of hyperglycemia’s
for neurologic events will be unable to communicate the typical adverse effects for diabetic complications. JAMA 2002;288:2579–
signs and symptoms of hypoglycemia. Decreased levels of con- 2588.
sciousness, confusion, or diaphoresis may be the only signs. 4. Kersten J, Schmeling T, Orth K, et al. Acute hyperglycemia
Acute hypoglycemia is treated by administering 25 to 50 g of abolishes ischemic preconditioning in vivo. Am J Physiol 1998;
glucose intravenously. 275:H721–725.
15259_Ch03.qxd 3/14/09 2:50 PM Page 13
CHAPTER 3 • PERIOPERATIVE GLYCEMIC CONTROL 13
5. Kersten J, Toller W, Tessmer J, et al. Hyperglycemia reduces 18. Furnary AP, Zerr K, Grunkemeier G, Starr A. Continuous in-
coronary collateral blood flow through a nitric oxide-mediated travenous insulin infusion reduces the incidence of deep sternal
mechanism. Am J Physiol 2001;281:H2097–2104. would infection in diabetic patients after cardiac surgical proce-
6. Ceriello A, Quagliaro L, D’Amico M, et al. Acute hyperglycemia dures. Ann Thorac Surg 1999;67:352–362.
induces nitrotyrosine formation and apoptosis in perfused heart 19. Furnary AP, Gao G, Grunkemeier GL, et al. Continuous insulin
from rat. Diabetes 2002;51:1076–1082. infusion reduces mortality in patients with diabetes undergoing
7. Verma S, Mailand A, Weisel R, et al. Hyperglycemia exaggerates coronary artery bypass grafting. J Thorac Cardiovasc Surg 2003;
ischemia-reperfusion-induces cardiomyocyte injury: reversal 125:1007–1021.
with endothelin antagonism. J Thorac Cardiovasc Surg 2002;123: 20. Pomposelli J, Baxter J, Babineau T, et al. Early postoperative
1120–1124. glucose control predicts nosocomial infection rate in diabetic
8. Davi G, Catalano I, Averna M, et al. Thromboxane biosynthesis patients. J Parenter Enter Nutr 1998;22:77–81.
and platelet function in type II diabetes mellitus. N Engl J Med 21. Kasiobrod M, Rathore SS, Inzucchi S, et al. Admission glucose
1990;322:1769–1774. and mortality in elderly patients hospitalized with acute myocar-
9. Knobler H, Sanion N, Shenkman B, et al. Shear-induced platelet dial infarction: implications for patients with and without recog-
adhesion and aggregation on subendothelium are increased in nized diabetes. Circulation 2005;111:3078.
diabetic patients. Throm Res 1998;80:181–190. 22. Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress hyper-
10. Prado R, Ginsberg MD, Dietrich WD, et al. Hyperglycemia in- glycemia and increased risk of death after myocardial infarction
creases infarct size in collaterally perfused but not end-arterial in patients with and without diabetes: a systematic overview.
vascular territories. J Cereb Blood Flow Metab 1988;8:186–192. Lancet 2000;355:773–778.
11. Ginsberg MD, Prado R, Dietrich WD, et al. Hyperglycemia re- 23. Capes S, Hunt D, Malmberg K, et al. Stress hyperglycemia and
duces the extent of cerebral infarction in rats. Stroke 1987;18: prognosis of stroke in nondiabetic and diabetic patients: a sys-
570–574. tematic overview. Stroke 2001;32:2426–2432.
12. Venables GS, Miller SA, Gibson G, et al. The effects of hyper- 24. Kiers I, Davis SM, Larkins R, et al. Stroke topography and out-
glycemia on changes during reperfusion following focal cerebral come in relation to hyperglycemia and diabetes. J Neurol
ischemia in the cat. J Neurol Neurosurg Psychiatry 1985;48: Neurosurg Psychiatry 1992;55:263–270.
663–669. 25. Van den Berghe G, Wouters P, Weekers F, et al. Intensive in-
13. Anderson RE, Tan WK, Martin HS, Meyer FB. Effects of glu- sulin therapy in critically ill patients. N Engl J Med 2001;345:
cose and PaO2 modulation on cortical intracellular acidosis, 1359–1367.
NADH redox state, and infarction in the ischemic penumbra. 26. Pittas AG, Siegel RD, Lau J. Insulin therapy for critically ill hos-
Stroke 1999;30:160–170. pitalized patients: a meta-analysis of randomized, control trial.
14. Petito CK, Kraig RP, Pulsinelli WA. Light and electron micro- Arch Inter Med 2004;164:2005–2011.
scopic evaluation of hydrogen ion-induced brain necrosis. 27. Gandhi GY, Nuttall GA, Adel MD, et al. Intensive intraopera-
J Cereb Blood Flow Metab 1987;7:625–632. tive insulin therapy versus conventional glucose management
15. Garber AJ, Moghissi ES, Bransome ED, et al. American college during cardiac surgery. Ann Intern Med 2007;146:233–243.
of endocrinology position statement on inpatient diabetes and 28. American Diabetes Association. Standards of medical care in
metabolic control. Endocr Pract 2004:10:77–82. diabetes. Diabetes Care 2005;28:S4–36.
16. Golden S, Peart-Vigilence C, Kao W, Brancati F. Perioperative 29. Adams HP, del Zoppo G, Alberts MJ, et al. Guidelines for the early
glycemic control and the risk of infectious complications in a co- management of adults with ischemic stroke. A guideline from the
hort of adults with diabetes. Diabetes Care 1999;22:1408–1414. American Heart Association/American Stroke Association Stroke
17. Latham R, Lancaster AD, Covington JF, et al. The association of Council, Clinical Cardiology Council, Cardiovascular Radiology
diabetes and glucose control with surgical site infection among and Intervention Council, and the Atherosclerotic Peripheral
cardiothoracic surgery patients. Infec Control Hosp Epidemiol Vascular Disease and Quality of Care Outcomes in Research
2001;22:607–612. Interdisciplinary Working Groups. Stroke 2007;38:1655–1711.
15259_Ch04.qxd 3/14/09 5:05 PM Page 14
CHAPTER 4
Neuraxial Analgesic Techniques

for Cardiac Anesthesia
Hassan M. Ahmad
The more theoretical benefits of epidural anesthesia/

CASE FORMAT: STEP BY STEP
analgesia for cardiac surgery are related to sympathetic
blockade. Decreased heart rate and coronary vasodilation re-
A 62-year-old, 85-kg man with a history of cigarette smok-
sult in improved subendocardial blood flow, which might be
ing, hypertension, and hyperlipidemia was referred by his
beneficial for patients undergoing CABG surgery. Atten-
primary care physician for a routine exercise stress test.
uation of stress reactions and attenuation of postoperative pain
Electrocardiogram changes occurred in the anterior leads
are other proposed benefits. Several (although not all) investi-
when his heart rate was 50% of the maximal predicted
gations have suggested that postoperative sympathetic block-
rate, although the patient remained asymptomatic. He was
ade decreases the incidence of atrial fibrillation typically on
then referred for diagnostic and possible interventional car-
postoperative day 2 or 3 in greater than one third of patients.
diac catheterization. Angiography confirmed the presence
Overall, potential theoretical benefits of thoracic epidural
of a 90% distal stenosis of the left anterior descending
anesthesia/analgesia for CABG surgery have not been shown
coronary artery and a 75% stenosis of the circumflex coro-
to lead to clinically important patient benefit.8,9,10
nary artery. Because the former lesion was not amenable
On the morning of surgery, the patient was transported to
to percutaneous intervention, he was referred for coronary
the preoperative area, where the anesthesiologist inserted a
artery bypass graft surgery (CABG).
thoracic epidural at the T5-6 level. A 17-gauge Tuohy needle
During the preoperative interview, the cardiac anes-
was used to the access the epidural space, utilizing a loss-of-
thesiologist learned that the patient had an active lifestyle
resistance technique. An epidural catheter was inserted 4 cm
with frequent exercise and a past medical history of hyper-
into the epidural space, and a 3-mL test dose of 1.5% lidocaine
tension. His current medications were hydrochlorothiazide,
with 1:200,000 epinephrine was administered with no evi-
atorvastatin, and aspirin. He had no known allergies and
dence of intravascular or intrathecal injection.
had undergone an appendectomy 20 years previously.
The patient had been smoking one pack of cigarettes per
day for approximately 40 years, and his family history was What are the potential risks and complications
positive for coronary artery disease (both parents having of using epidurals in cardiac surgery?
suffered “heart attacks” in their late 50s). Physical exami- Placing an epidural before surgery requiring subsequent
nation revealed faint wheezing in both lung fields. Blood anticoagulation has been shown to be quite safe in several
pressure was 142/67 mm Hg; heart rate, 72 beats per different settings. In general, the possibility of infection,
minute; room air oxygen saturation, 96%; and tempera- bleeding, and nerve injury should be clearly disclosed to pa-
ture, 36.7°C. All baseline investigations (hematology, che- tients before placing an epidural catheter.2
mistries, and coagulation studies) were normal. The greatest concern in inserting an epidural prior to cardiac
The surgical plan was perform a median sternotomy surgery is the potential risk of epidural hematoma secondary
and “off-pump” CABG surgery with the left internal mam- to anticoagulation. Large series indicate that epidural catheter
mary artery to the left anterior descending artery and saphe- placement before anticoagulation with unfractionated or low-
nous vein graft to the circumflex coronary artery. After a molecular-weight heparin can be performed with a minimal
discussion with the patient, the anesthetic plan was com- risk for epidural hematoma if certain precautions are taken.
bined general and thoracic epidural anesthesia. Other complications from epidural anesthesia include hy-
potension resulting from sympathectomy and systemic toxic
effects of opioids and local anesthetics.
Are there benefits to epidural anesthesia
and analgesia for cardiac surgery? What are the guidelines for the use of epidurals
Several studies have compared general with combined in the setting of anticoagulation with heparin?
general/epidural anesthesia for cardiac surgery. There is some It is not uncommon for patients undergoing cardiac surgery to
evidence to indicate that the use of epidural analgesia facili- have been on a heparin infusion before surgery. The American
tates early tracheal extubation postoperatively. Other out- Society of Regional Anesthesia has issued guidelines that may
comes, including duration of hospital stay and overall cost are reduce the risk of epidural hematoma related to epidurals in
similar when the two techniques are compared.6,7 anticoagulated patients. Typically, heparin infusion should be
14
15259_Ch04.qxd 3/14/09 5:05 PM Page 15
CHAPTER 4 • NEURAXIAL ANALGESIC TECHNIQUES FOR CARDIAC ANESTHESIA 15
discontinued 4 hours before epidural placement, and the inter- Are there any other regional techniques
val between epidural placement and complete anti-coagulation that can favorably influence the
for bypass should exceed 60 minutes. Also, epidural catheters postoperative course?
should be removed only when normal coagulation has been Parasternal block entails the surgeon injecting local anes-
restored; if a heparin infusion is required in the postoperative thetic along the sternal border to anesthetize the intercostal
period, the infusion should be discontinued 2 to 4 hours prior nerves and their branches. Using this technique has been
to catheter removal. In general, epidurals should be avoided in shown to significantly decrease the dose of morphine re-
patients with known coagulopathy. It is unclear whether a quired in the immediate postoperative period and was
traumatic epidural placement necessitates canceling cardiac associated with better oxygenation at the time of tracheal
surgery, but the consensus is to delay the operation for at least extubation (although not an earlier time of extubation).
24 hours, should a “bloody tap” occur.5 Nonetheless, it is a relatively safe and easy procedure that
can provide excellent analgesia.3
Can intrathecal opioids be used
for cardiac surgery?
It has been shown that inadequate analgesia in the postopera- KEY MESSAGES
tive period leads to increased likelihood of myocardial is-
chemia associated with the stress response to pain. Adverse 1. Epidural analgesia and anesthesia is an option in
changes in hemodynamics, metabolic activity, immune func- cardiac surgery and has the potential for earlier
tion, and hemostasis can be attenuated with better pain control. extubation and improved pain control in the
Several studies have evaluated the potential benefit of immediate postoperative period.
intrathecal opioids as a method of providing postoperative 2. The complete systemic anticoagulation associated with
analgesia. Most investigations have studied the use of intrathe- cardiopulmonary bypass is a concern with placement
cal morphine and its effect on time to tracheal extubation, use of epidural catheters, particularly the risk of
of additional intravenous opioids, and duration of hospital developing an epidural hematoma.
stay. Generally, the long-acting effect of intrathecal morphine
provided better analgesia compared to placebo. No clear ben- 3. A combination of local anesthetics and opioids can be
efit has been demonstrated regarding tracheal extubation and administered via epidural, and there are several
overall outcomes, however, in part because of the adverse res- potential effects related to the attenuated stress
piratory effects. The combined use of intrathecal morphine response that may be beneficial to cardiac surgical
and intrathecal clonidine provides better postoperative analge- patients.
sia and facilitates earlier tracheal extubation.1
What dosing regimen should be used? QUESTIONS

The goals for an epidural technique in cardiac surgery are es-
tablishing surgical anesthesia, thereby minimizing systemic 1. What spinal levels are associated with sympathetic
opioid use and to create a significant sympathectomy. This nervous supply to the heart?
means a block level as high as T1. Answer: T1-T5.
The dosing should begin with a test dose of 1.5% lidocaine
with epinephrine 1:200,000 to detect an unwanted intrathecal 2. What are the early clinical signs of epidural
or intravascular catheter. Then, a loading dose of preserva- hematoma?
tive-free morphine 20 ␮g/kg is given, followed by 0.5% bupi- Answer: Back pain, lower extremity weakness and dimin-
vacaine given in 5-mg increments to a total of 25 to 35 mg. ished sensation, and loss of bowel and bladder control.
A continuous infusion of 0.5% bupivacaine with morphine
25 ␮g/mL is started at 4 mL per hour and adjusted to achieve 3. What long-acting local anesthetic has been shown to
adequate analgesia. have less cardiovascular toxicity than bupivacaine?
Answer: Ropivacaine
Is the use of a total spinal technique justified?
Much of the proposed benefit of regional anesthesia in cardiac References
surgical patients is based on the sympathetic blockade, which 1. Chaney MA. Intrathecal and epidural anesthesia and analgesia
cannot be reliably achieved with intrathecal opioids alone. for cardiac surgery. Anesth Analg 2006;102:45–64.
Administration of large doses of intrathecal local anesthetics to 2. Chaney MA, Labovsky JK. Thoracic epidural anesthesia and
achieve this goal has been studied. Typically, the Trende- cardiac surgery: balancing postoperative risks associated
lenburg position is used to achieve an adequate cephalad with hematoma formation and thromboembolic phenomenon.
J Cardiothorac Vasc Anesth 2005;19:768–771.
spread to above T1, resulting in a “total spinal.” Although the 3. McDonald SB, Jacobsohn E, Kopacz DJ, et al. Parasternal block
subsequent sympathectomy is observed by serum markers and and local anesthetic infiltration with levobupivacaine after
hemodynamics, no significant clinical benefit results. More- cardiac surgery with desflurane: the effect on postoperative pain,
over, the resultant hypotension and bradycardia may make pulmonary function, and tracheal extubation times. Anesth
this technique inappropriate for cardiac surgical patients.4 Analg 2005;100:25–32.
15259_Ch04.qxd 3/14/09 5:05 PM Page 16
16 CHAPTER 4 • NEURAXIAL ANALGESIC TECHNIQUES FOR CARDIAC ANESTHESIA
4. Lee TW, Grocott HP, Schwinn D, et al. Winnipeg High-Spinal and length of hospital stay. Anesth Analg 2002;94:275–282, table
Anesthesia Group. High spinal anesthesia for cardiac surgery: of contents.
effects on beta-adrenergic receptor function, stress response, and 8. Fillinger MP, Yeager MP, Dodds TM, et al. Epidural anes-
hemodynamics. Anesthesiology 2003;98:499–510. thesia and analgesia: effects on recovery from cardiac surgery.
5. Horlocker TT, Wedel DJ, Benzon H, et al. Regional Anesthesia J Cardiothorac Vasc Anesth 2002;16:15–20.
in the Anticoagulated Patient: Defining the Risks (The Second 9. Hansdottir V, Philip J, Olsen MF, et al. Thoracic epidural versus
ASRA Consensus Conference on Neuraxial Anesthesia and intravenous patient-controlled analgesia after cardiac surgery: a
Anticoagulation) Regional Anesthesia and Pain Medicine, Vol randomized controlled trial on length of hospital stay and
28, No. 3 (May–June), 2003: 172–197. patient-perceived quality of recovery. Anesthesiology 2006;104:
6. Karagoz HY, Kurtoglu M, Bakkaloglu B, et al. Coronary artery 142–151.
bypass grafting in the awake patient: three years’ experience in 10. Barrington MJ, Kluger R, Watson R, et al. Epidural anesthesia
137 patients. J Thorac Cardiovasc Surg 2003;125:1401–1404. for coronary artery bypass surgery compared with general anes-
7. Priestley MC, Cope L, Halliwell R, et al. Thoracic epidural anesthesia alone does not reduce biochemical markers of myocardial
thesia for cardiac surgery: the effects on tracheal intubation time damage. Anesth Analg 2005;100:921–928.
15259_Ch05.qxd 3/14/09 5:07 PM Page 17
CHAPTER 5
Off-Pump Coronary Artery Surgery
Audrey R. Leverich and Nikolaos J. Skubas
incision, through which the left internal mammary artery

(LIMA) is anastomosed to the target vessel (usually the LAD);
and (b) the typical OPCAB in which multiple coronary artery
A 62-year-old man with triple-vessel coronary artery dis-
bypass grafts are constructed via a median sternotomy incision.
ease presented for off-pump coronary artery bypass graft
Exposure of the target coronary vessels is achieved with dis-
surgery (OPCAB). His past medical history included hyper-
placement of the heart.2 The LAD, diagonal branches, and
tension and hyperlipidemia. A coronary angiogram re-
proximal RCA can be adequately exposed with a suction stabi-
vealed a 95% obstruction of the left anterior descending
lizer device and sponges in the pericardial sac (Fig. 5.1), and
artery (LAD), 60% stenosis of the circumflex artery (CX),
the displacement is minimal. Targets in the posterior (distal
and 70% narrowing of the right coronary artery (RCA). Left
RCA) and lateral (CX) surface of the heart, however, require
ventricular (LV) ejection fraction was preserved (⬎50%);
rotating the heart out of the thoracic cavity with anterior dis-
there was mild mitral regurgitation, and LV pressures were
placement (“verticalization”). This is typically achieved with
135/12 mm Hg. Carotid ultrasound revealed 80% obstruc-
an aspirating device placed on the cardiac apex. In either case,
tion of the right carotid artery. Physical examination, vital
stabilizing the epicardium is necessary to carry out coronary
signs, and laboratory work were within normal limits,
arteriotomy and graft anastomosis. Stabilizer devices use a
except for a bruit audible over the right side of the patient’s
combination of pressure and suction to immobilize the
neck. His medication list included an antihypertensive, a
planned anastomotic site (Fig. 5.2). Transient interruption of
␤-blocker, aspirin, and a statin.
coronary flow is achieved with elasticized sutures placed
around the proximal and distal target vessel. Anastomoses are
then performed on a relatively bloodless, motionless field.
How does OPCAB differ from CABG?
Standard coronary revascularization procedures in the past re- Does the patient’s history affect the anesthesia
lied on the use of extracorporeal circulation (cardiopulmonary
plan?
bypass [CPB]). The use of CPB during CABG surgery, how-
ever, is associated with undesirable effects including coagulation This patient has extensive coronary artery disease, but his LV
abnormalities, activation of the inflammatory response, and the function is preserved, and there are no significant valvular
potential for multiple organ system dysfunction. OPCAB in- lesions. The presence and degree of collateral coronary blood
volves performing coronary revascularization on a beating supply should dictate the sequence of distal anastomoses. The
heart.1 High-risk patients such as those who have cerebral, renal, presence of a carotid bruit at the site of a documented carotid
or pulmonary dysfunction as well as the elderly (⬎80 years), stenosis raises concerns regarding preservation of cerebral
might likely benefit the most from OPCAB by avoiding the blood flow to the brain perioperatively. For these reasons,
deleterious consequences of CPB. Patients with severe athero- hypotension may not be tolerated in this patient. This patient
sclerosis of the ascending aortas might further benefit from might further have atherosclerosis of the ascending aorta or
OPCAB because aortic cross clamping is not necessary. of other arteries such as the renal and splanchnic arteries
Contraindications to OPCAB are mostly limited to technical (Fig. 5.3). Blood flow to the latter might be sensitive to reduce
considerations such as an intramyocardial coronary artery that is blood pressure during cardiac manipulations while OPCAB
difficult to dissect, intracavitary thrombus that can be dislodged is being performed .
during heart manipulation, and combined surgical procedures
that include open-chamber valve replacement surgery. Patients
with a history of malignant ventricular arrhythmias, as well as Which monitors should be used during the
patients who would not tolerate periods of myocardial ischemia, intraoperative period?
are not optimal candidates for OPCAB procedures (Table 5.1). Conventional five-lead electrocardiogram (ECG), pulse oxime-
try, and intra-arterial blood pressure monitoring should be per-
formed in all patients undergoing an OPCAB procedure. In
What are the surgical approaches to OPCAB? addition, a pulmonary artery catheter can be considered de-
There are two surgical approaches to OPCAB: (a) the mini- pending on ventricular function, pulmonary arterial hyperten-
mally invasive direct access coronary artery bypass graft (MID- sion, or other complicating factors. External defibrillator/pacing
CAB) procedure, which involves a small left thoracotomy pads should be placed particularly for MIDCAB where
17
15259_Ch05.qxd 3/14/09 5:07 PM Page 18
18 CHAPTER 5 • OFF-PUMP CORONARY ARTERY SURGERY
T A B L E 5 . 1 Differences Between Traditional CABG and OPCAB
CABG OPCAB
Incision Sternotomy Sternotomy or Thoracotomy
Heparinization Full: ACT ⬎480 s Partial: ACT ⬃250–300 s
Cannulation Aortic, venous Neither
Aortic cross clamp Yes No
Cardioplegia Yes No
Partial aortic cross clamp for construction Yes Yes, if ⬎ two vessels No, if all arterial grafts
of proximal anastomosis on a “Y” or “T” anastomosis to LITA
ACT, activated clotting time; CABG, coronary artery bypass graft; LIMA, left internal mammary artery; OPCAB, off-pump coronary artery bypass
graft surgery.
Figure 5.2 • The stabilizer device pushes on the left ventricular

(LV ) wall, restricts local motion, and decreases LV dimensions;
their contribution to SV is predominant. Compression of the ante-
rior and lateral walls has more serious hemodynamic consequences
Figure 5.1 • A Stabilizer Device Used for Off-Pump than compression of the inferior (posterior) wall. The most pro-
Coronary Revascularization. A combination of suction found disturbances are observed during lateral wall exposure for
(applied to the cardiac apex) and stabilization (applied at the anas- anastomosis on the left circumflex coronary artery (CX). LAD, left
tomotic site; here at the lateral wall of the heart) provides an im- anterior descending coronary artery; MR, mitral regurgitation;
mobile and bloodless field. MV, mitral valve; RCA, right coronary artery; RV, right ventricle;
RVOT, right ventricular outflow obstruction; TC, tricuspid valve.
Figure 5.3 • Upper esophageal short axis view of the aortic

arch demonstrating a protruding atheroma (grade V) at 7 o’clock.
15259_Ch05.qxd 3/14/09 5:07 PM Page 19
CHAPTER 5 • OFF-PUMP CORONARY ARTERY SURGERY 19
exposure of the heart is necessary for internal defibrillation or suture and then allowing the myocardium to be reperfused.
when cardioversion is limited.1 For this particular patient, intra- This step is believed to induce ischemic preconditioning, in
operative transesophageal echocardiography (TEE) would which the myocardium may build up a tolerance to subsequent
allow not only monitoring of volume status and evaluation of ischemia. Additionally, the use of volatile anesthetic agents 30
cardiac performance, but also examination of the aorta for the minutes before vessel occlusion may protect the myocardium
presence of atheromas. When interpreting hemodynamic data, against ischemia via anesthetic preconditioning. Early clinical
the position of the heart must be taken into account. Surgical data in patients undergoing CABG surgery, however, suggest
manipulation of the heart changes its relationship to the ECG that high concentrations (2 MAC) of volatile anesthetics are
electrodes, making it difficult to interpret the ST segments. needed to significantly reduce troponin I release.4 While the
Similarly, surgical maneuvers affect pulmonary artery catheter coronary artery is occluded, a favorable myocardial oxygen
readings. Distortion of the heart, particularly verticalization, balance is essential. ␤-Blockers and calcium-channel antago-
causes elevations in right atrial and pulmonary wedge pres- nists are used to decrease heart rate and myocardial contractil-
sures8. The vertical position of the heart, along with the interpo- ity, thereby decreasing myocardial oxygen consumption.
sition of air between the heart and esophagus, reduces the qual- Vasopressors, such as phenylephrine and norepinephrine, are
ity of TEE images during OPCAB procedures. However, most used to maintain oxygen supply by increasing coronary perfu-
TEE images remain interpretable and are extremely valuable in sion pressure. In most patients, a mean arterial pressure of 70
the diagnosis of new regional wall motion abnormalities, ven- mm Hg or higher is adequate to preserve coronary flow. It is
tricular function, and volume status. important to remember that, once the target vessel is opened,
the surgical anastomosis must be completed despite any hemo-
dynamic derangements. The surgeon might consider placing a
What is the best anesthetic plan for this temporary coronary artery shunt.
patient?
Most commonly, a conventional general anesthetic technique is What hemodynamic changes should the
used during OPCAB procedures.1 Because the postoperative
course is accelerated in the majority of OPCAB patients, the anesthesiologist be prepared to treat/prevent?
anesthetic technique should be tailored to facilitate early tra- During coronary artery bypass graft anastomosis, the anes-
cheal extubation. The agents’ duration of action should be con- thesiologist must manage the hemodynamic changes caused
sidered when choosing opioids, neuromuscular blockers, and by distortion of the heart. During vertical displacement, the
hypnotics. Additionally, every effort should be made to avoid ventricles become positioned above the atria; TEE may reveal
hypothermia. Room temperature should be maintained around an increase in atrial size and a decrease in ventricular size
24°C, fluids should be warmed, and a heat-moisture exchanger (Fig. 5.4). Because blood must now flow against gravity and
should be included in the ventilator circuit. New generations of resistance, atrial filling pressures must be maintained at a
circulating water warming mattresses might minimize heat higher level to preserve ventricular filling. In addition, the
loss. Forced air warmers can be used when saphenous vein har-
vest is not performed (or after completion). In some centers,
thoracic epidural anesthesia/analgesia is used as an adjunct to
general anesthesia. Epidural anesthesia reduces myocardial
oxygen demand and increases supply by dilating epicardial ves-
sels and improving collateral blood flow. The routine use of an-
tifibrinolytics is not recommended during OPCAB, because of
the potential trend toward a hypercoagulable state. “Full he-
parinization,” with an activated clotting time (ACT) above 400
seconds, is not required during OPCAB procedures because pa-
tients are not exposed to the foreign surface of the bypass circuit.
However, the patient’s coagulation system will be activated by
local vascular endothelial injury.6 Therefore, some degree of an-
ticoagulation is required. Heparin in a dose of 100 to 200 units
per kilogram is given before dissection of the LIMA targeting
an ACT of 250 to 300 seconds.
Can anesthetic management affect patient

outcome after OPCAB? Figure 5.4 • Cardiac chamber compression with application
After the LIMA is harvested, the target coronary arteries are of a stabilizer device (STABILIZER ON) for off-pump coronary
prepared for distal anastomoses. The risk of myocardial is- artery bypass. (A) In the midesophageal four-chamber (ME 4C)
chemia is greatest during anastomosis of the least collateralized view, application of the stabilizer device results in compression of
vessel, whereas highly collateralized vessels are less at risk.5 the left ventricular (LV) cavity and elongation of the left atrium
The most stenotic artery is therefore usually the first vessel to (LA). (B) The right ventricle (RV) is compressed during applica-
be revascularized. Before performing the anastomosis, the sur- tion of the stabilizer for construction of the right coronary arterial
geon may induce a short period of myocardial ischemia by bypass graft. Notice the near elimination of the RV cavity at end-
temporarily occluding the target vessel with an elasticized diastole (arrows). RA, right atrium.
15259_Ch05.qxd 3/14/09 5:07 PM Page 20
20 CHAPTER 5 • OFF-PUMP CORONARY ARTERY SURGERY
heart may be compressed within the chest during vertical and after OPCAB might increase the risk for early bypass graft
lateral displacement. The right ventricle may become wedged thrombosis. Most centers, however, use protamine to reduce
between the left ventricle and the right pericardium, and com- the risk of postoperative bleeding and transfusions.
plete right ventricular outflow obstruction may occur. Volume
loading and Trendelenburg positioning serve to increase pre-
load. The surgeon may release the right pericardium to allow Are patient outcomes affected by undergoing
adequate space for the right ventricle during this maneuver. OPCAB versus on-pump CABG procedures?
Manipulating the heart’s position may cause mitral regurgita- In the immediate postoperative period, OPCAB patients expe-
tion. Rotation and verticalization of the heart distorts the mi- rience a slightly accelerated recovery. They generally have less
tral valve annulus, causing it to twist and fold over on itself .3 postoperative bleeding and receive fewer blood transfusions.10
TEE evaluation may reveal new (or more severe) regurgita- Preserving pulsatile blood flow, as well as avoiding hypother-
tion. Large “V” waves may appear on the pulmonary artery mia during OPCAB procedures might further contribute to
catheter tracing. Abnormal mitral valves are more prone to accelerated recovery. The duration of hospitalization in the in-
distortion and are more likely to become functionally stenotic tensive care unit, as well as the overall hospital length of stay,
during cardiac manipulations for OPCAB. This phenomenon is shortened with OPCAB surgery compared with traditional
is also seen with distortion of the tricuspid valve and less often CABG surgery.9,11 Hospital costs are therefore lower in the
with the aortic valve. Stabilizing the epicardium during coro- OPCAB patients. At 1 year, coronary angiography has
nary artery anastomosis causes local distortion of the ventricle. demonstrated similar graft patency rates in OPCAB and on-
The immobilizing device pushes on the myocardium and re- pump CABG patients when experienced surgeons perform
stricts wall motion. Because the anterior and lateral walls sup- the surgery.9,11 Five years postoperatively, rates of myocardial
ply a major portion of stroke volume, their compression causes infarction, repeat coronary revascularization, stroke, and mor-
more severe reduction in cardiac output than when other por- tality are similar in both groups.13 In low-risk patients, rates of
tions of the ventricle are compressed. The most extreme he- neurocognitive dysfunction are similar in both OPCAB and
modynamic compromise occurs during CX anastomosis, in on-pump patients. However, patients at high risk for poor
which the heart is significantly elevated and perfusion of the neurologic outcome may benefit from OPCAB procedures.7
lateral wall is compromised. Bradycardia is common during
surgical manipulation, particularly during RCA anastomosis.
Complete atrioventricular block can occur. The surgeon
should consider placing temporary pacemaker wires before oc- KEY MESSAGES
cluding the RCA. Additionally, a defibrillator/cardioverter
should be available for the treatment of malignant arrhythmias. 1. Patients with severe atherosclerosis of the ascending
aorta benefit from OPCAB because aortic cross
clamping is not necessary.
What are the indications for conversion to CPB? 2. During OPCAB, “full” heparinization (ACT ⬎400
Even with aggressive management, up to 5% of patients can- seconds) is not required because patients are not
not tolerate the hemodynamic alterations caused by OPCAB. exposed to the foreign surface of the CPB circuit.
A cardiac index ⬍1.5 liters/minute per m2, mean arterial pres- However, the patient’s coagulation system will be
sure ⬍50 mm Hg, or a mixed venous saturation ⬍60% may activated by local vascular endothelial injury.
not be tolerated for more than 15 minutes. Persistent ST ele- Therefore, some degree of anticoagulation is
vations ⬎2 mm or malignant ventricular arrhythmias also in- required. Heparin in a dose of 100 to 200 units
dicate the need for conversion from an OPCAB to surgery per kilogram is given before dissecting the LIMA
using CPB.12 A “dry” CPB machine, as well as a perfusion targeting an ACT of 250 to 300 seconds.
team, should be available during all OPCAB procedures.
3. Following OPCAB, persistent regional wall motion
abnormalities are predictive of poor postoperative
What hemodynamic abnormalities occur after outcome.
reperfusion of the bypassed vessel? 4. Five years postoperatively, rates of myocardial
Reperfusion injury may produce significant ECG changes, infarction, repeat coronary revascularization, stroke,
such as T-wave inversions or arrhythmias, during the first 30 and mortality are similar among patients who
minutes after coronary revascularization. Ventricular function undergo CABG on or off bypass.
should be evaluated after reperfusion with TEE. Persistent re-
gional wall motion abnormalities predict poor postoperative
outcome. Signs of continuing regional ischemia or poor flow
through the bypass graft should prompt surgical intervention. QUESTIONS
1. What surgical approaches are used to perform
Should heparin be reversed at the end of the OPCAB?
case? Answer: There are two: (a) the MIDCAB approach in-
Because patients are not fully heparinized during OPCAB volves a small left thoracotomy incision, through which
procedures, protamine reversal is not always required. Some the LIMA is anastomosed to the target vessel (usually the
institutions believe that the risk of a hypercoagulable state LAD) and (b) the typical OPCAB in which multiple
15259_Ch05.qxd 3/14/09 5:07 PM Page 21
CHAPTER 5 • OFF-PUMP CORONARY ARTERY SURGERY 21
CABGs are constructed is performed via a median placebo-controlled, multicenter study. Anesthesiology 2003;98:
sternotomy. 1415–1427.
5. Koh TW, Carr-White GS, DeSouza C, et al. Effect of coronary
2. What is the role of antifibrinolytic therapy in OPCAB? occlusion on left ventricular function with and without collateral
supply during beating heart coronary artery surgery. Heart
Answer: The routine use of antifibrinolytics is not rec-
1999;81:285–291.
ommended during OPCAB, because of the potential 6. Mariani MA, Gu J, Boonstra PW, et al. Procoagulant activity
trend toward a hypercoagulable state. after off-pump coronary operation: is the current anticoagulation
adequate? Ann Thorac Surg 1999;67:1370–1375.
3. How does OPCAB compare with CABG with CPB in 7. Mark DB, Newman MF. Protecting the brain in coronary artery
terms of graft patency? bypass graft surgery. JAMA 2002;287:1448–1450.
Answer: At 1 year, coronary angiography has demon- 8. Mishra M, Malhotra R, Mishra A, et al. Hemodynamic changes
strated similar graft patency rates in OPCAB and during displacement of the beating heart using epicardial stabi-
on-pump CABG patients when surgery is performed lization for off-pump coronary artery bypass graft surgery. J
by experienced surgeons. Cardiothorac Vasc Anesth 2002;16:685–690.
9. Nathoe HM, van Dijk D, Jansen EWL, et al. A comparison of
on-pump and off-pump coronary bypass surgery in low-risk pa-
tients. NEJM 2003;348:394–402.
References 10. Nuttall GA, Erchul DT, Haight TJ, et al. A comparison of
1. Chassot PG, van der Linden P, Zaugg M, et al. Off-pump coro- bleeding and transfusion in patients who undergo coronary ar-
nary artery bypass surgery: physiology and anaesthetic manage- tery bypass grafting via sternotomy with and without cardiopul-
ment. Br J Anaesth 2004; 92:400–413. monary bypass. J Cardiothorac Vasc Anesth 2003;17:447–451.
2. Gayes JM. The minimally invasive cardiac surgery voyage. J 11. Puskas JD, Williams WH, Duke PG, et al. Off-pump vs con-
Cardiothorac Vasc Anesth 1999;13:119–122. ventional coronary artery bypass grafting: early and 1-year graft
3. George SJ, Al-Ruzzeh S, Amrani M, et al. Mitral annulus patency, cost and quality-of-life outcomes. JAMA 2004;291:
distortion during beating heart surgery: a potential cause for 1841–1849.
hemodynamic disturbance—a three-dimensional echocardio- 12. Raja SG, Dreyfus GD. Off-pump coronary artery bypass sur-
graphy reconstruction study. Ann Thorac Surg 2002;73: gery: to do or not to do? Current best available evidence. J
1424–1430. Cardiothorac Vasc Anesth 2004;18:486–505.
4. Julier K, da Silva R, Garcia C, et al. Preconditioning by sevoflurane 13. Van Dijk D, Spoor M Hijman R, et al. Cognitive and cardiac
decreases biochemical markers for myocardial and renal dysfunc- outcomes 5 years after off-pump vs on-pump coronary artery
tion in coronary artery bypass graft surgery: a double-blinded, bypass graft surgery. JAMA 2007;297:701–708.
15259_Ch06.qxd 3/14/09 5:08 PM Page 22
CHAPTER 6
Aprotinin and Antifibrinolytics

in Cardiac Surgery
Michelle Isac
establish risk factors associated with nonsurgical bleeding

after cardiac surgery to stratify patients and anticipate adverse
outcomes. Identified risk factors include advanced age, female
A 79-year-old, 62-kg (body mass index, 22) female pre-
gender, nonelective cases, reoperation, complex surgeries, and
sented to the emergency department with severe chest pain
smaller body mass index. Prolonged duration of CPB and sur-
and new ST-segment elevation in the inferior leads. She
gery as well as persistent postoperative hypothermia are fur-
was referred for urgent cardiac catheterization. Angiogra-
ther key risk factors.
phy confirmed complete occlusion of the right coronary ar-
tery (RCA) as well as significant disease of the circumflex Before beginning the procedure, the cardiac surgeon,
artery. The culprit RCA lesion was not amenable to percu- cardiac anesthesiologist, and perfusionist discuss their plans
taneous coronary intervention (PCI), and the patient was re- and concerns for this patient. They all agree that this pa-
ferred for urgent coronary artery bypass grafting (CABG). tient is at high risk for perioperative bleeding and that
Two years before this admission, the patient had un- there is a high likelihood that she will need transfusion of
dergone a PCI of the left anterior descending (LAD) artery platelets after CPB because of her recent use of antiplatelet
with a drug-eluting stent. Her other medical history includes drugs. The blood bank is alerted to ensure that an adequate
hypertension and hyperlipidemia for which she was receiv- supply of packed red blood cells, fresh frozen plasma, and
ing metoprolol and simvastatin. She is also receiving clopi- platelets is available.
dogrel and aspirin since her PCI 2 years ago. Her tempera-
ture is 36.9°C; blood pressure, 135/76 mm Hg; heart rate, Why is prevention of bleeding important in
65 beats per minute;and her respiratory rate, 18 breaths per
cardiac surgery?
minute. The patient’s preoperative hemoglobin is 12.6 g/dL,
platelet count, 253,000; international normalized ratio, Perioperative bleeding results in risk for blood transfusion and
1.1; and prothrombin time, 29 seconds. Electrolytes, blood re-exploration of the mediastinum because of continued
urea nitrogen, and creatinine are normal. bleeding or tamponade. Perioperative bleeding further results
in transfusion of packed red blood cells and hemostatic factors.
Blood transfusion is associated with infectious and nonin-
fectious complications. The risk for viral transmission from
Why is cardiac surgery associated with massive transfusion has markedly decreased as a result of im-
bleeding? proved screening methods, although the risk for transmission
Surgery involving cardiopulmonary bypass (CPB) is associated of infectious agents persists (particularly, hepatitis C).
with complex alterations to the hemostatic system resulting Transmission of bacterial pathogens from packed red blood
from hypothermia, hemodilution of hemostatic factors, con- cells, and particularly platelet transfusion, is a higher risk than
sumption of coagulation factors caused by ongoing thrombin viral transmission. Other pertinent risks associated with blood
generation, fibrinolysis, platelet consumption and dysfunction, transfusion include transfusion-related acute lung injury, vol-
inadequate reversal of heparin, and heparin rebound after its ume overload, and hemolytic and nonhemolytic transfusion
reversal with protamine. In addition, the increasing use of reactions. Further, limited supply of blood products necessi-
newer anticoagulants such as low-molecular-weight heparins, tates that strategies be implemented to minimize transfusions.
direct thrombin inhibitors (e.g., hirudin, bivalirudin) and an-
tiplatelet drugs (e.g., glycoprotein IIa/IIIb antagonist, clopido- What is the incidence of reoperation in cardiac
grel) in patients presenting for cardiac surgery contributes to
surgical bleeding. surgery, and what are its associated risks?
Resternotomy for postoperative bleeding is required in ap-
proximately 3% to 6% of cardiac surgical patients. The need
Is this patient at high risk for perioperative
for emergency mediastinal re-exploration is associated with
bleeding? increased length of intensive care unit stay, increased require-
This patient’s history suggests that she is at risk for periopera- ments for intra-aortic balloon counterpulsation, and increased
tive bleeding. The continued use of clopidogrel is associated mortality. Not surprisingly, many of the risk factors for rester-
with higher rates of bleeding compared with patients not notomy following cardiac surgery are the same as the risk fac-
receiving antiplatelet drugs. Several studies have tried to tors identified for increased bleeding.
22
15259_Ch06.qxd 3/14/09 5:08 PM Page 23
CHAPTER 6 • APROTININ AND ANTIFIBRINOLYTICS IN CARDIAC SURGERY 23
The surgical team has discussed blood conservation was associated with a relative 35% reduction in the need for al-
strategies for this patient, including the use of antifibri- logeneic blood transfusion. The use of EACA resulted in a blood
nolytic agents. loss reduction of approximately 230 mL (intraoperatively) and
200 mL (postoperatively). Studies directly comparing EACA to
TXA showed little difference between the two agents in terms
What pharmacologic approaches can be of volume of blood transfused or reoperation for bleeding.
employed to reduce bleeding and transfusion
The cardiac anesthesiologist expressed concern about
requirements? the safety of antifibrinolytics but agreed that the benefits in
Fibrinolysis is an important contributor to nonsurgical bleed- this high-risk patient likely outweighed the risks.
ing after cardiac surgery leading to not only breakdown of
thrombus but also further consumption of hemostatic factors. What are the risks associated with
The main pharmacologic treatment for preventing excessive
antifibrinolytics in cardiac surgery?
bleeding during cardiac surgery is antifibrinolytic drugs such
as tranexamic acid (TXA), epsilon-aminocaproic acid Although the efficacy of aprotinin and the lysine analogs have
(EACA), and aprotinin. EACA and TXA are synthetic deriv- been established, the safety of these agents in high-risk patients
atives of the amino acid lysine. Lysine analogs inhibit the is more controversial. The safety of aprotinin, in particular, has
process of fibrinolysis by adhering to the lysine-binding site on been the focus of debate. Prospectively randomized, placebo-
plasminogen. Binding by lysine is required for the conversion controlled studies have supported this agent’s safety. These data,
of plasminogen to plasmin. Therefore, binding by these lysine in fact, suggest aprotinin use was associated with a lowered risk
analogs inhibits the formation of plasmin. Normally, plasmin for perioperative stroke compared with placebo. Aprotinin use
causes fibrinolysis (lysis of clot) by degrading fibrin and is associated with a transient increase in serum creatinine that
fibrinogen. Not only is less plasmin generated, but existing might reflect its effect on the proximal renal tubules. Because it
plasmin is also inactivated. In contrast, aprotinin is a serione is a bovine protein, allergic reactions to aprotinin are an estab-
protease inhibitor which inhibits several important enzymes lished risk including fatal anaphylactic reactions. This risk has
including plasmin and kallikrein. The exact mechanisms of led to the use of a test dose, which can also trigger a severe re-
aprotinin’s action, however, are not completely understood. sponse. Recent exposure (less than 1 year) is known to increase
the likelihood of suffering from hypersensitivity reactions. For
this reason, it is recommended that aprotinin should be used in
What is the evidence for the efficacy of settings where CPB can be established quickly.
antifibrinolytic drugs? Considering the mechanism of action of antifibrinolytic
Several prospectively randomized, double-blind, placebo- agents, it seems logical to expect they may increase the risk of
controlled trials have been performed evaluating the efficacy thrombotic complications of surgery. The meta-analysis by the
of antifibrinolytics in cardiac surgery to reduce bleeding and Cochrane Collaboration (which analyzed 211 randomized
blood transfusion. Many studies have been small, particularly controlled trials) did not show increased risk of mortality,
those evaluating lysine analogs and those performing head- stroke, myocardial infarction, or deep vein thrombosis with
to-head comparisons of all three agents. Aprotinin has been aprotinin, TXA, or EACA. There was an increased trend to-
the most well-studied agent. Several adequately powered, ward renal dysfunction in the group receiving aprotinin, but
multicenter studies have established the efficacy of aprotinin this was not statistically significant.
to reduce bleeding, blood transfusion, and mediastinal re- The use of drugs during the well-controlled setting of a
exploration for bleeding after cardiac surgery compared with clinical trial might not adequately represent their safety profile
placebo, particularly for complex cardiac surgeries or reoper- compared with their widespread clinical use after approval. Of
ations. These studies supported approval of aprotinin by the particular concern is attention to anticoagulation. Aprotinin
U.S. Food and Drug Administration for the indication of prolongs the celite activated clotting time (ACT) regardless of
reducing bleeding during cardiac surgery. the appropriate heparinization level. The use of a kaolin-based
Similar robust data are not present for TXA or EACA. ACT, thus, is necessary when aprotinin is used and/or target-
Nonetheless, multiple studies have reported the efficacy of these ing higher levels of the ACT during surgery (⬎750 s).
agents to reduce bleeding complications of cardiac surgery. Moreover, in the “real world,” other hemostatic agents might
These data have been subjected to meta-analysis to enhance the be coadministered with aprotinin in bleeding patients. The
power of the multiple small studies. A recent Cochrane review combined use of lysine analogs with aprotinin can result in in-
of antifibrinolytic drugs evaluated 51 trials showing that apro- tense inhibition of fibrinolysis. Further, the use of recombinant
tinin use led to less chest tube drainage, fewer blood transfu- factor VIIa with aprotinin might promote prothrombotic com-
sions, and less need for reoperation for bleeding compared with plications. The safety of aprotinin was recently questioned in a
placebo. Studies comparing TXA with placebo have also shown recent retrospective analysis of data obtained in a multicenter
decreased requirement for blood product administration and study. This analysis suggested that patients receiving aprotinin
mediastinal drainage but not mediastinal reexploration for during cardiac surgery had a higher risk for myocardial infarc-
bleeding. These results suggest that TXA results in savings of tion, stroke, renal dysfunction, and death compared with lysine
approximately one unit of allogeneic blood from being trans- analog antifibrinolytics. The retrospective study design cannot
fused compared with placebo. The amount of blood loss was exclude treatment bias whereby patients given aprotinin were
reduced by approximately 300 mL with TXA use. Risk for re- at a higher risk for adverse outcomes regardless of antifibri-
operation was not affected by TXA. The small number of stud- nolytic treatment. Further, analysis of other large mostly
ies examining EACA in cardiac surgery has shown that its use single-center databases has not confirmed these findings.
15259_Ch06.qxd 3/14/09 5:08 PM Page 24
24 CHAPTER 6 • APROTININ AND ANTIFIBRINOLYTICS IN CARDIAC SURGERY
At this time, a large prospectively randomized, double- QUESTIONS

blinded multicenter trial comparing aprotinin, TXA, and
EACA in patients undergoing cardiac surgery was halted be- 1. What is the incidence of reoperation in cardiac
cause of higher rates of adverse events in the aprotinin group. surgery?
The details of this trial are pending. Nonetheless, in light of these
recent developments and on the basis of other data reported Answer: Resternotomy for postoperative bleeding is
from analysis of outcomes from a large administrative database, required in approximately 3% to 6% of cardiac surgical
the U.S. Food and Drug Administration has requested a mar- patients.
keting suspension of aprotinin until the data can be reviewed.
2. What is the principal mechanism of action of EACA?
After discussing all the options, the surgical team de-
cided that TXA would be used for this procedure. The pa- Answer: EACA is a synthetic derivative of the amino
tient had an otherwise uneventful procedure receiving two acid lysine. Lysine analogs inhibit the process of
saphenous vein bypass grafts to the circumflex and right fibrinolysis by adhering to the lysine binding site on
coronary arteries. The duration of CPB was 36 minutes, plasminogen.
and aortic cross-clamp time was 58 minutes. Heparin was
3. Is aprotinin nephrotoxic?
adequately reversed with protamine with a final ACT of
121 seconds. After ample surgical hemostasis was achieved, Answer: Aprotinin use is associated with transient
the sternum was closed, and the patient was brought to the increase in serum creatinine levels that might reflect its
cardiac surgical intensive care unit. Chest tube output was effect on the proximal renal tubules.
closely monitored for 24 hours with only minimal drainage.
The patient was discharged home on postoperative day 5
following an uncomplicated recovery.
References
1. Henry DA, Charles PA, Moxey AJ, et al. Anti-fibrinolytic use
KEY MESSAGES for minimizing perioperative allogeneic blood transfusion.
Cochrane Database Syst Rev 2007(4):CD001886.
1. The main pharmacologic treatment for preventing 2. Karthik S, Grayson AD, McCarron EE, et al. Re-exploration for
excessive bleeding during cardiac surgery is antifibri- bleeding after coronary artery bypass surgery: risk factors, out-
nolytic drugs such as TXA, EACA, and aprotinin. comes, and the effect of time delay. Ann Thorac Surg
2004;78:527–534.
2. Lysine analogs inhibit the process of fibrinolysis by 3. Mangano DT, Tudor IC, Dietzel C. The risk associated with
adhering to the lysine-binding site on plasminogen. aprotinin in cardiac surgery. N Engl J Med 2006;354:353–365.
4. Mannucci PM, Levi M. Prevention and treatment of major blood
3. Aprotinin is a serine protease inhibitor inhibiting several loss. N Engl J Med 2007; 356:2301–2311.
important enzymes including plasmin and kallikrein. 5. Dietrich W, Busley R, Boulesteix A. Effects of aprotinin dosage
on renal function. Anesthesiology 2008;108:189–198.
4. The safety of aprotinin was recently questioned in a re- 6. Hogue CW, London MJ. Aprotinin use during cardiac surgery:
cent retrospective data analysis obtained in a multicen- a new or continuing controversy? Anesth Analg 2006;103:
ter study. This analysis suggested that patients receiving 1067–1070.
aprotinin during cardiac surgery had a higher risk for 7. Despotis GJ, Hogue CW Jr. Pathophysiology, prevention and
myocardial infarction, stroke, renal dysfunction, and treatment of bleeding after cardiac surgery: a primer for cardiol-
death compared with lysine analog antifibrinolytics. ogist and an update for the cardiothoracic team. Am J Cardiol
1999;83:15B–30B.
15259_Ch07.qxd 3/14/09 5:09 PM Page 25
CHAPTER 7
The Use of Recombinant Factor VIIa in

Cardiac Surgery
Jay K. Levin
CASE FORMAT: REFLECTION Mechanism of Action of rFVIIa

In 1988, rFVIIa was administered to a patient with hemophilia
A 73-year-old female presented for aortic and mitral valve A undergoing synovectomy.2 Patients with hemophilia exposed
replacement surgery. Over the previous 6 months, she to allogenic blood factors often have inhibitory antibodies to co-
had noticed increasing dyspnea with activity and occa- agulation factors VIII and IX, limiting their effectiveness in the
sional chest pain. Preoperative echocardiography demon- treatment of acute hemorrhage. FVIIa combines with tissue fac-
strated severe aortic stenosis and moderate-to-severe mitral tor released by injured cells and initiates fibrin formation by ac-
regurgitation. Ten years previously, she had undergone un- tivating factors IX and X.3 When administered in doses that
complicated coronary bypass grafting. Recent coronary achieve supraphysiologic concentrations, rFVIIa can increase
angiography demonstrated that her bypass grafts were thrombin synthesis directly, and the resulting products are par-
patent and that no new significant coronary artery stenosis ticularly resistant to degradation by plasmin.4
had developed. After an otherwise uncomplicated opera-
tion and separation from cardiopulmonary bypass (CPB), What are the Indications for rFVIIa?
significant bleeding occurred despite having achieved her The current approved indications for administering rFVIIa
baseline-activated clotting time by protamine administra- include the treatment of bleeding in hemophiliac patients with
tion. No obvious cause of surgical bleeding was evident. inhibitors to factor VIII, congenital factor VII deficiency, and
Although the patient remained hemodynamically stable, Glanzmann’s thrombasthenia. rFVIIa has been used off-label
blood drained continuously from the chest tube even after for excessive nonsurgical bleeding after trauma, liver resection
administering four units of fresh frozen plasma. The anes- and transplant, prostatectomy, intra-abdominal hemorrhage,
thesiologist considered administration of recombinant fac- intracerebral hemorrhage, and cardiac surgery.
tor VIIa (rFVIIa).
Off-label administration of rFVIIa to cardiac

surgical patients?
DISCUSSION The widespread administration of rFVIIa to patients under-
going cardiac surgery5–10 is based on early case reports show-
Often multifactorial, postbypass coagulopathy presents a chal- ing remarkable reduction in bleeding after CPB following
lenge in managing cardiac surgical patients especially after complicated coronary artery bypass grafting, ventricular assist
“re-do surgery” (with repeat sternotomy) or prolonged CPB.1 device placement, and repeat sternotomy. One case report de-
Causative factors include preoperative antiplatelet therapy, scribed the use of rFVIIa to reverse lepirudin anticoagulation
residual heparin effect, hypothermia, a relative and absolute following CPB for a patient with a history of heparin-induced
decrease in platelet number and function, fibrinolysis, and a thrombocytopenia. Another case report described administra-
decrease in coagulation factors and function. tion of rFVIIa following CPB in a patient with a history of
anaphylactic reaction to protamine. Several retrospective stud-
ies have shown rFVIIa to be efficacious in managing refrac-
What is the initial management of post-CPB tory bleeding post-CPB, decreasing blood loss, normalizing
bleeding? coagulation factors, and decreasing the need for further blood
Management of excessive bleeding after CPB requires an eval- product administration. One case series showed an immediate
uation of the cause(s) including those of surgical origin. decrease in postoperative bleeding but no change in the vol-
Immediate responses include management of hypothermia ume of allogenic blood transfused during the first 24 hours
and/or administration of additional protamine as indicated (by postoperatively.
temperature and activated clotting time measurement, respec- The currently available prospective, randomized, placebo-
tively). Estimation of platelet count and performing coagulation controlled trials of rFVIIa after cardiac surgery are limited by
studies are indicated. On-site coagulation testing such as throm- small numbers of patients studied. In a study of 10 patients un-
boelastography provides a relatively fast and reliable, but non- dergoing complex cardiac surgery with CPB, the use of
specific, assessment of coagulation status including coagulation rFVIIa was shown to decrease transfusion of allogenic blood
factor deficiency, platelet dysfunction, and fibrinolysis. products and a tendency toward reduced blood loss. Aprotinin
25
15259_Ch07.qxd 3/14/09 5:09 PM Page 26
26 CHAPTER 7 • THE USE OF RECOMBINANT FACTOR VIIa IN CARDIAC SURGERY
was administered to both groups of patients. In a study evalu- QUESTIONS

ating pediatric cardiac surgical patients, rFVIIa failed to de-
crease blood loss or transfusion requirements. Thus, a large 1. What is the physiologic role of FVII in coagulation?
prospective, randomized, placebo-controlled trial examining
the efficacy of rFVIIa to decrease bleeding and blood transfu- Answer: In its activated form, FVIIa combines with tis-
sion after cardiac surgery is needed. sue factor released by injured cells and initiates fibrin for-
The optimal dose of rFVIIa to decrease bleeding while not mation by activating factors IX and X.
increasing the risk of adverse events is yet to be elucidated. 2. What are the currently approved indications for admin-
Reported doses range from 25 to 195 ␮g/kg (90 ␮g/kg is used istration of FVIIa?
most commonly). rFVIIa, 40 ␮g/kg, was successful in stabi-
lizing uncontrolled bleeding after cardiac surgery.8 A dose- Answer: Currently approved indications for rFVIIa in-
finding study for rFVIIa in this setting is also required. clude the treatment of bleeding in hemophiliac patients
with inhibitors to factor VIII, congenital factor VII
Risk of Thromboembolic Events deficiency, and Glanzmann’s thrombasthenia.
Prothrombotic adverse effects are the major concern with the 3. What dose of FVIIa might be administered to a patient
use of rFVIIa. In low concentrations, rFVIIa activates thrombin bleeding excessively after cardiac surgery?
formation at sites of tissue factor exposure. At greater concen-
trations, generated thrombin can diffuse from the sites of vas- Answer: Reported doses range from 25 to 195 ␮g/kg;
cular injury and could initiate intravascular thrombosis. doses of 90 ␮g/kg have been used most commonly.
Normally, naturally occurring anticoagulant proteins such as
antithrombin III inactivate excessive thrombin formation. After References
acute illness or surgery with CPB, however, antithrombin III
1. Marietta M, Facchini L, Pedrazzi P, et al. Pathophysiology of
concentrations are decreased, predisposing to intravascular bleeding in surgery. Transplantation Proceedings 2006;38:
thrombosis. 812–814.
Several of the retrospective studies and prospective, ran- 2. Hedner U, Glazer S, Pingel K, et al. Successful use of recombi-
domized, blinded, placebo-controlled studies that reported on nant factor VIIa in a patient with severe hemophilia A during
the efficacy of rFVIIa for excessive bleeding after cardiac sur- synovectomy. Lancet 1988;2:1193.
gery reported safety end points, showing no increase in throm- 3. Despotis GJ, Avidan MS, Hogue CW Jr. Mechanisms and atten-
boembolic events. Two case reports (patients with hemophilia uation of hemostatic activation during extracorporeal circula-
after lung transplantation) describe likely thrombotic events in tion. Ann Thorac Surg 2001;72(5):1821–1831.
patients receiving rFVIIa. Thus the safety of rFVIIa when 4. Weiskopf RB. Recombinant-activated coagulation factor VIIa
(NovoSeven®): current development. Vox Sanguinis 2007;92:
used in the setting of perioperative bleeding has not been
281–288.
established. 5. Filsoufi F, Castillo JG, Rahmanian PB, et al. Effective manage-
ment of refractory postcardiotomy bleeding with the use of recom-
binant activated factor VII. Ann Thorac Surg 2006;82:1779–1783.
KEY MESSAGES 6. Raivio P, Suojaranta-Ylinen R, Kuitunen AH. Recombinant
factor VIIa in the treatment of postoperative hemorrhage after
1. Nonsurgical bleeding after cardiac surgery is usually cardiac surgery. Ann Thoracic Surg 2005;80:66–71.
multifactorial in origin. 7. Heise D, Braeuer A, Quintel M. Recombinant activated factor VII
(NovoSeven®) in patients with ventricular assist devices: case re-
2. When administered in doses that achieve supraphysio- port and review of the literature. J Cardiothorac Surg2007;2:47.
logical concentrations, rFVIIa increases thrombin 8. van de Garde EMW, Bras LJ, Heijmen RH, et al. Low-dose
synthesis directly. recombinant factor VIIa in the management of uncontrolled
postoperative hemorrhage in cardiac surgery patients. J Carthor
3. Currently approved indications for rFVIIa include the Vasc Anes 2006;20:573–575.
treatment of bleeding in patients with hemophilia with 9. von Heymann C, Redlich U, Jain U, et al. Recombinant activated
inhibitors to factor VIII, congenital factor VII deficiency, factor VII for refractory bleeding after cardiac surgery—a retro-
and Glanzmann’s thrombasthenia. spective analysis of safety and efficacy. Crit Care Med
2005;33:2241–2246.
4. The safety of rFVIIa in the setting of perioperative 10. Bishop CV, Renwick WEP, Hogan C, et al. Recombinant acti-
bleeding has not been established. vated factor VII: treating postoperative hemorrhage in cardiac
surgery. Ann Thorac Surg 2006;81:875–879.
15259_Ch08.qxd 3/14/09 5:10 PM Page 27
CHAPTER 8
Postoperative Neuropathy
After Cardiac Surgery
Ioanna Apostolidou and Jason S. Johnson
CASE FORMAT: REFLECTION minute, while mechanical ventilation was maintained. No

intraoperative complications were noted, and the patient’s
A 56-year-old, 112-kg, 170-cm male with three-vessel coro- trachea was extubated 4 hours after admission to the inten-
nary artery disease, hypertension, and type 2 diabetes mel- sive care unit.
litus presented for coronary artery bypass grafting surgery. On the first postoperative day, the patient complained
The patient’s symptoms included chest pain with exertion of right-hand numbness and grip strength weakness. Upon
that was relieved with rest. His current medications were further evaluation, sensory loss was detected at the ulnar
metformin, lisinopril, and metoprolol. He was a nonsmoker, side of the wrist as well as the dorsal and palmar surfaces
used alcohol socially, and was employed as a data analyst. of the fifth and medial half of the fourth finger. The patient’s
The patient’s vital signs were as follows: tempera- hand had a claw-shaped appearance at rest. Tests of
ture, 37.2°C; blood pressure, 142/86 mm Hg; heart rate, motor function showed weakness of flexion of the second
64 beats per minute; and respiratory rate, 14 breaths per to fifth fingers. The appearance of the elbow was normal.
minute. Physical examination showed an obese male with An ulnar neuropathy was diagnosed. A physical therapist
clear bilateral breath sounds and a regular heart rate with was consulted to evaluate the patient. By the third postop-
no murmur. There was no carotid bruit. erative day, the patient had approximately 50% return of
Preoperative laboratory findings revealed normal chem- strength to the hand but continued to have numbness.
istry, cholesterol, and blood cell counts. Preoperative electro- On the fifth postoperative day, the patient was re-
cardiogram readings showed left ventricular hypertrophy but ferred to the neurology service for further evaluation.
was otherwise normal. At stress exercise testing, significant Electromyography (EMG) was performed and showed a
ST depression occurred in the lateral leads, and subsequent pattern consistent with long-standing carpal tunnel com-
coronary angiogram readings demonstrated 80% stenosis in pression. On further questioning, the patient recalled oc-
the left anterior descending artery and 90% stenosis in the casional numbness in his hands after working long hours
circumflex artery and right coronary artery. Ventricular func- at the computer. Over the course of 3 months, the pa-
tion was normal as were valve anatomy and function. tient’s symptoms returned to their preoperative level, with
After induction of anesthesia using etomidate, fentanyl, full recovery of hand motor function; he was referred to a
midazolam, and rocuronium, the patient’s airway was se- hand specialist for treatment of his carpal tunnel disease.
cured with an endotracheal tube. A 20-gauge left radial ar-
terial catheter was inserted. A pulmonary artery catheter
was advanced in the pulmonary artery via a 9-F introducer
sheath (multiaccess catheter) inserted in the right internal CASE DISCUSSION
jugular vein under ultrasound guidance. The patient’s arms
were placed at his side in a neutral forearm position, and Perioperative Peripheral
elbows, forearms, and hands were padded with foam Nerve Injury
pads. A balanced anesthesia technique was used for anes-
thesia maintenance with isoflurane, fentanyl, rocuronium, Although peripheral nerve injury (PNI) is not a life-threatening
and midazolam. complication, it can bring significant distress to the patient and
The surgical technique entailed a median sternotomy anesthesia provider and can result in short-term, or rarely in
with sternal retractors placed to facilitate left internal mam- long-term, disability. Consequently, PNI poses a major risk for
mary artery dissection. Saphenous vein grafts were used medical practice liability. Perioperative nerve damage was the
for the remaining grafts. Total cardiopulmonary bypass second major injury (16%) from the ASA Closed Claims Data-
time was 2 hours. The patient’s heart function was restored base following death (32%). Ulnar neuropathy is the most fre-
without inotropic support, and separation from cardiopul- quent nerve injury (28%) followed by brachial plexus (20%),
monary bypass was accomplished without difficulty. Intra- lumbosacral (16%), and spinal cord (13%) neuropathies.1,2
operative fluids consisted of one liter 5% albumin and three The mechanism of perioperative neuropathies is incom-
liters of Lactated Ringer’s solution. The total operative time pletely understood. Although improper patient positioning
was 6 hours. The patient was brought to the intensive care causing nerve compression, stretching, and ischemia, direct
unit and received a nitroglycerin infusion of 0.5 ␮g/kg per trauma or metabolic derangements can lead to nerve injuries,
in the majority of the reported cases, patient positioning is
27
15259_Ch08.qxd 3/14/09 5:10 PM Page 28
28 CHAPTER 8 • POSTOPERATIVE NEUROPATHY AFTER CARDIAC SURGERY
unrelated to the injury, and an explicit mechanism was not

identified.3–5
PNI can present with sensory, motor, or mixed deficits of the
area supplied by the affected nerve. Isolated sensory deficits are
usually transient and typically resolve in days or weeks without
any intervention. Motor deficits are more serious and the patient
should be referred to a neurology department for further evalu-
ation and management. Persistent sensory deficits lasting more
than 5 days should also be referred to neurology.
Nerve conduction studies and EMG can help in defining
the type of nerve injury (axonal, demyelination, or mixed), its
distribution (proximal, distal, symmetric, asymmetric), and
the severity and degree of motor or sensory involvement.6
Peripheral Nerve Injuries Following
Cardiac Surgery
Various PNIs can be a complication of cardiac surgery.7,8
Brachial plexus neuropathies, phrenic nerve injuries, saphe-
nous neuropathy, recurrent laryngeal nerve injuries, sympa-
thetic chain disturbance with resultant Horner’s syndrome,
and optic neuropathy have been described.
BRACHIAL PLEXUS Figure 8.1 • (A) Normal course of the brachial plexus as it
The frequency of brachial plexus injury is estimated at 2% to passes over the first rib. (B) Opening the sternum widely causes
18%. It is usually caused by stretching or trauma of the lower superior rotation of the first rib that pushes the clavicles into the
roots (C8-T1) resulting in ulnar neuropathy.9 Excessive sternal retroclavicular space leading to stretching of the brachial plexus.
opening and cephalad placement of the sternal retractor during (Reproduced with permission from Graham JG, Pye IF,
sternotomy as well as asymmetric retraction during internal McQueen IN. Brachial plexus injury after median sternotomy.
mammary artery dissection along with first rib fracture can Ann Thorac Surg 1971;4:315–319.)
cause compression and stretching of the brachial plexus (Fig. 8.1).
More commonly, the plexus becomes stretched between a fixed
position within its fascial plane and proximally fixed origins.
Prolonged stretching of the plexus interferes with axonal trans- patients unable to be weaned from mechanical ventilation
port and leads to transient neuropraxia. Somatosensory-evoked after cardiac surgery. Similarly, recurrent laryngeal nerve in-
potential studies of the plexus demonstrated greater than 50% jury may result in postoperative respiratory failure from vocal
amplitude reduction after placement of sternal retractors.10 Risk cord dysfunction. Radiography, ultrasonography, and EMG
factors that may worsen the injury or lead to permanent symp- are currently used diagnostic techniques.
toms include pre-existing neurologic injury such as cubital or
carpal tunnel entrapment and advanced age. This scenario was SAPHENOUS NERVE
described as the “double-crush” phenomenon in which two in- Saphenous neuralgia can result from harvesting the saphenous
juries to any single nerve will present with significant symptoms, vein.13 Endoscopic vein harvesting techniques may reduce
whereas either injury by itself would be asymptomatic. Smoking, incisional pain, but the benefits on saphenous neuralgia need
diabetes mellitus, height, and weight do not correlate well with to be further explored.
risk. Male patients seem to be at a slightly greater risk than fe-
males to have permanent symptoms.7,8 Symptoms vary with the OPTIC NERVE
location and severity of injury. Ischemia of the optic nerve resulting in visual deficits is an
infrequent but serious complication of cardiac surgery.
PHRENIC NERVE AND RECURRENT Prolonged hypotension, emboli, hemorrhage, and anemia can
LARYNGEAL NERVE decrease perfusion to any component of the optical pathway
Injury of the phrenic nerve and recurrent laryngeal nerve, res- from the retina to the occipital lobe.2
pectively, are two well-known potential complications of car- Central Venous Catheterization
diac surgery.11,12 Topical hypothermia with ice slush and/or
cardioplegia has been implicated as the principal cause. Sternal and Nerve Injury
retraction, internal mammary artery harvesting, and central Nerve injury is an infrequent complication of central venous
venous catheterization have been also related to nerve dys- cannulation (⬍1%). It is caused by direct nerve puncture or
function. Unsuccessful attempts of transesophageal echo- compression by a hematoma. Several cases of brachial plexus
cardiography probe placement have also been implicated in palsy, phrenic nerve, and recurrent laryngeal nerve injury
recurrent laryngeal nerve dysfunction. Phrenic neuropathy have been reported after multiple attempts of internal jugular
causing diaphragmatic dysfunction should be considered in vein or subclavian vein catheterization. The use of ultrasound
15259_Ch08.qxd 3/14/09 5:10 PM Page 29
CHAPTER 8 • POSTOPERATIVE NEUROPATHY AFTER CARDIAC SURGERY 29
to facilitate central venous cannulation may reduce the fre-

KEY MESSAGES
quency of nerve injury by decreasing the number of venipunc-
ture attempts. The clinical benefits of ultrasound-guided
1. Brachial plexus injuries commonly occur during cardio-
cannulation are greater success rate, fewer attempts, and a
vascular surgery.
lower rate of complications (primarily arterial punctures)
when compared with the landmark method.14 Ultrasound use 2. All PNIs should be followed closely and referred for
should be considered in difficult cases such as in patients with further evaluation as appropriate.
distorted anatomy, obesity, and scars at the cannulation site.
3. The majority of PNIs have a good overall prognosis
Ulnar Neuropathy in Noncardiac with complete resolution of symptoms within weeks or
Surgery months of the injury.
Ulnar neuropathy (UN) is the most frequent nerve injury 4. EMG can identify pre-existing neuropathies if performed
reported in the ASA Closed Claims Database.1 Compression early in the evaluation of a perioperative injury.
injuries of the ulnar nerve result in immediate symptomatol-
ogy; however, delayed onset of UN, usually 24 hours after
surgery, supports a mechanism other than direct nerve com-
pression as a primary cause in these cases.5,15 The most com- QUESTIONS
mon sites of injury are either at the elbow or higher in the
brachial plexus course. UN can occur despite careful padding 1. Which neuropathies are most commonly encountered
of the upper extremity. Risk factors associated with UN are during the perioperative period?
male gender, body mass index extremes, and hospital stay Answer: UN is the most frequently encountered nerve
duration. Symptoms of UN include sensory deficits in the injury (28%) followed by brachial plexus (20%),
ulnar and palmar aspect of the fifth and the medial half of the lumbosacral (16%), and spinal cord (13%) neuropathies.1,2
fourth digit, handgrip weakness, and fourth and fifth finger
clawing from hand muscle imbalance. Pre-existing latent neu- 2. Which PNIs are associated with cardiac surgery?
ropathy conditions may predispose patients to a perioperative Answer: Brachial plexus neuropathies, phrenic nerve
UN. This finding is supported by abnormal nerve conduction injuries, saphenous neuropathy, recurrent laryngeal
studies not only of the affected site but also of the contralateral nerve injuries, sympathetic chain disturbance with
site in a significant proportion of patients. resultant Horner’s syndrome, and optic neuropathy have
been described following cardiac surgery.
Prognosis of Peripheral
Neuropathies After Cardiac Surgery 3. Which peripheral neuropathies are associated with
central venous catheterization?
The outcome of peripheral neuropathies depends on the type
and severity of injury. Most common deficits are transient Answer: Cases of brachial plexus palsy, phrenic nerve,
with complete recovery within 6 to 8 weeks. Rarely, symptoms and recurrent laryngeal nerve injury have been reported
persist for more than 4 months with slow improvement over after multiple attempts at internal jugular vein or
time.7,8,16 subclavian vein catheterization.
Prevention Strategies and References

Management of Perioperative 1. Cheney FW, Domino KB, Caplan RA, Posner KL. Nerve injury
Neuropathies associated with anesthesia: a closed claims analysis. Anesthesiology
Preventing perioperative neuropathies is a very important part 1999;90:1062–1069.
of perioperative care of all surgical patients. Proper patient posi- 2. Miller’s Anesthesia. 6th Ed. New York: Churchill Livingstone, 2005.
3. Winfree CJ, Kline DG. Intraoperative positioning nerve injuries.
tioning and padding to avoid direct compression or stretching of Surg Neurol 2005;63:5–18; discussion 18. Review.
the peripheral nerve is of paramount importance especially for 4. Warner MA. Perioperative neuropathies. Mayo Clin Proc 1998;
prolonged duration procedures. For the upper extremities, 73:567–574.
avoid pressure over the ulnar groove at the elbow and spiral 5. Warner MA, Warner ME, Martin JT. Ulnar neuropathy. Inci-
groove of the humerus and avoid arm abduction greater than dence, outcome, and risk factors in sedated or anesthetized
90 degrees in a supine position. For the lower extremities, avoid patients. Anesthesiology 1994;81:1332–1340.
overextension of the hamstring muscle and avoid pressure of 6. Gooch CL, Weimer LH. The electrodiagnosis of neuropathy:
the peroneal nerve at the fibula head. Place protective padding basic principles and common pitfalls. Neurol Clin 2007;25:1–28.
at the pressure nerve sites and use a chest roll in patients in 7. Sharma AD, Parmley CL, Sreeram G, et al. Peripheral nerve in-
the lateral decubitus position.17 Peripheral nerve injuries identi- juries during cardiac surgery: risk factors, diagnosis, prognosis,
and prevention. Anesth Analg 2000; 91:1358–1369.
fied in the postoperative period require prompt and thorough 8. Grocott HP, Clark JA, Homi HM, et al. “Other” neurologic
evaluation, complete documentation, and close monitoring. complications after cardiac surgery. Semin Cardiothorac Vasc
If symptoms are severe or persist beyond 1 week postopera- Anesth 2004;8:213–226.
tively, a neurologist should evaluate the patient. EMG studies 9. Unlu Y, Velioglu Y, Kocak H, et al. Brachial plexus injury fol-
may help to define the type and location of the nerve injury or lowing median sternotomy. Interact Cardiovasc Thorac Surg
may reveal a pre-existing condition. 2007;6:235–237.
15259_Ch08.qxd 3/14/09 5:10 PM Page 30
30 CHAPTER 8 • POSTOPERATIVE NEUROPATHY AFTER CARDIAC SURGERY
10. Hickey C, Gugino LD, Aglio LS, et al. Intraoperative somato- 14. Randolph AG, Cook DJ, Gonzales CA. Ultrasound guidance for
sensory evoked potential monitoring predicts peripheral nerve placement of central venous catheters: a meta-analysis of the lit-
injury during cardiac surgery. Anesthesiology 1993;78:29–35. erature. Crit Care Med 1996;24:2053–2058.
11. DeVita MA, Robinson LR, Rehder J, et al. Incidence and natural 15. Prielipp RC, Morell RC, Butterworth J. Ulnar nerve injury and
history of phrenic neuropathy occurring during open heart sur- perioperative arm positioning. Anesthesiol Clin North Am
gery. Chest 1993;103:850–856. 2002;20:589–603.
12. Dimopoulou I, Daganou M, Dafni U, et al. Phrenic nerve dys- 16. Ben-David B, Stahl S. Prognosis of intraoperative brachial plexus
function after cardiac operations: electrophysiologic evaluation injury: a review of 22 cases. Br J Anaesth 1997;79:440–445.
of risk factors. Chest 1998;113:8–14. 17. Practice advisory for the prevention of perioperative periph-
13. Mountney J, Wilkinson GA. Saphenous neuralgia after coro- eral neuropathies: a report by the American Society of
nary artery bypass grafting. Eur J Cardiothorac Surg 1999; Anesthesiologists Task Force on Prevention of Perioperative
16:440–443. Peripheral Neuropathies. Anesthesiology 2000;92:1168–1182.
15259_Ch09.qxd 3/14/09 5:11 PM Page 31
CHAPTER 9
Postoperative Visual Loss
Laurel E. Moore
lesser sphenoid wing); (b) the intracanalicular segment (within

CASE FORMAT: REFLECTION
the optic canal); (c) the posterior or intraorbital segment (optic
foramen to the lamina cribrosa); and (d) the anterior or in-
A 57-year-old male with a history of prior lumbar fusion pre-
traocular segment (from the lamina cribrosa to the optic disc).
sented for spinal fusion from T12-L4. The patient’s past med-
The lamina cribrosa is a perforated membrane overlying the
ical history was significant for moderate obesity (body mass
posterior scleral foramen through which the optic nerve and
index, 30 kg m2), type 2 diabetes, and well-controlled
central retinal artery and vein enter the eye.
hypertension. The patient’s physical activity was markedly
The retina receives its blood supply from branches of the
limited by back pain, but recent cardiac testing revealed
ophthalmic artery, which is the first branch of the intracranial
good left ventricular function and no evidence of myocar-
internal carotid artery. Once the ophthalmic artery passes
dial ischemia. Preoperative laboratory data were within
through the optic foramen, it branches into several vessels in-
normal limits including a hematocrit level of 45%. The pa-
cluding the central retinal artery and a series of posterior ciliary
tient’s preoperative vital signs included a blood pressure of
arteries.4 Both arterial systems are necessary for retinal function
150/90 mm Hg, heart rate of 75 beats per minute, and
and as end vessels, there is the potential for watershed regions at
oxygen saturation of 96% on room air.
risk for ischemia.5 The intraorbital optic nerve is supplied by a
The surgery was prolonged (8 hours) but without signif-
pial plexus, which in turn, is supplied by branches of the central
icant complications. Mean arterial pressure was maintained
retinal artery and posterior ciliary arteries.6 The most anterior
within 20% of baseline with the exception of one brief (10-
portion of the optic nerve is supplied primarily by short poste-
minute) episode of hypotension (mean pressure ⬍60 mm Hg)
rior ciliary arteries and not the central retinal artery.5 It is not
associated with significant bleeding. The patient’s estimated
clear that the blood supply to the optic nerve is autoregulated
blood loss was 3000 mL. The least recorded hematocrit level
during episodes of increased intraocular pressure.7
was 24%. Replacement fluids included four units packed red
blood cells, 6000 mL crystalloid, and 500 mL hydroxyethyl Mechanism of Injury
starch. Shortly after extubation in the postanesthesia care
unit, the patient complained that he could not see. The causes of POVL are multiple and include cerebral corti-
cal infarction, pituitary apoplexy, direct injuries to the eye and
visual tracts, and ischemic injuries to the optic nerve and/or
retina. The most common of these are ischemic injuries to the
CASE DISCUSSION visual tracts, which fall into two primary categories: central
retinal artery occlusion (CRAO) and ischemic optic neuropa-
thy (ION). ION can be further subdivided into posterior is-
Visual Loss After Spine Surgery chemic retinopathy (PION: optic nerve injury posterior to the
Postoperative visual loss (POVL) has historically been associ- lamina cribrosa) and anterior ischemic retinopathy (AION:
ated with cardiac surgery and more specifically, with cardiopul- optic nerve injury anterior to the lamina cribrosa). Because of
monary bypass. The occurrence of POVL, although fortunately the increasing incidence of blindness following spine surgery,
rare, appears to be increasing, particularly in patients under- POVL and more specifically, PION have drawn the attention
going spine surgery.1 Although temporary postoperative visual of treating physicians, researchers, and the lay public. CRAO
changes can occur as a result of corneal abrasions or transient and ION will be discussed separately.
corneal edema from the prone position, true POVL in spine-
injured patients has an incidence of 0.1% to 0.2%.1,2 In 2006, CRAO
the American Society of Anesthesiologists (ASA) published the CRAO generally presents with painless monocular visual loss
findings from its POVL registry of 93 spine-injured patients1 as following emergence from anesthesia. CRAO may be an impor-
well as a practice advisory for POVL for patients undergoing tant mechanism of POVL after cardiac surgery because of the
spine surgery.3 risk of emboli to the central retinal artery (incidence as high as
4.5%8), although ION is also clearly a mechanism of POVL in
Relevant Anatomy of the Optic this setting. It is less common than ION after spine surgery. On
Nerve and Retina fundoscopic examination, patients classically demonstrate reti-
The optic nerve can be described in four segments: (a) the in- nal pallor with a cherry-red spot at the macula. The pupillary
tracranial segment (optic chiasm to the optic canal within the light reflex is reduced or absent in the affected eye.
31
15259_Ch09.qxd 3/14/09 5:11 PM Page 32
32 CHAPTER 9 • POSTOPERATIVE VISUAL LOSS
In terms of mechanism, CRAO can be embolic or effec- increased venous pressure (prone position) or potentially
tively produced by increased intraocular pressure limiting per- large-volume crystalloid infusion causing tissue edema. This
fusion pressure to the retina. Intraocular pressure has been then causes the nerve to be compressed within its sheath or as
shown to increase in patients in the prone position.9,10 it enters the orbital fossa or the eye itself.
Perfusion pressure may be further reduced if the patient’s Limited evidence indicates an association between sildenafil
orbit is compressed against a head holder (classically a horse- and ION, most commonly in males13 but also in children.14 One
shoe head holder) or some other object, the so-called head rest reference recommends the cessation of sildenafil at least 1 week
syndrome. Patients may present with marked orbital edema preoperatively.15
and limited extraocular movements (to complete ophthalmo-
plegia), as perfusion to the entire orbit including surrounding Risk Factors for POVL
tissues and extraocular muscles may be compromised. Although risk factors for atherosclerotic disease such as hyper-
In the ASA visual loss registry,1 10 of 93 POVL patients tension, diabetes, and smoking have been put forth as risk factors
undergoing spine surgery were determined to have CRAO. In for POVL (and this certainly seems intuitive), the evidence is less
contrast to the 83 patients with ION, the patients with CRAO clear. As stated previously, there are clearly certain individuals
were less likely to have been pinned using a Mayfield head who for whatever reason are at risk for POVL, but preoperative
holder (all were on head rests), procedures were shorter, and identification of these individuals is currently not possible.
there was less blood loss. Furthermore, no patients with Although intraoperative hypotension and anemia would also
CRAO had bilateral injuries unlike 66% of ION patients. appear to place patients at risk for POVL, and these two factors
Whereas visual loss from CRAO is generally felt to have a bet- are reported in multiple case reports, they are not necessarily
ter chance of visual recovery than ION, in the ASA registry, supported by larger samplings. There are reports, however, of
there was no difference in outcome between patients with POVL improving postoperatively with blood transfusion in the
CRAO and ION. case of anemia16 and with increased blood pressure.17
The two factors that are consistently supported as risk fac-
ION tors for POVL in spine-injured patients include prolonged
Of the 131 reported cases of visual loss in the ASA POVL reg- surgical procedures and large blood loss. In the ASA registry,
istry between 1999 and 2004, 93 (72%) were associated with these are defined as procedures lasting greater than 6 hours
spine surgery, and 83 (89% of all spine cases) were caused by and a predicted blood loss of greater than 1 liter.1 Of the 93
ION.1 Clearly, this number is increasing, but whether this is spine-injured patients with POVL, 94% of the procedures
related to more complex surgical procedures, patient factors, lasted 6 hours or longer. Similarly, 82% of POVL patients had
or better recognition of POVL is unclear. In any case, ION is an estimated blood loss of 1 liter or greater. It is interesting
a devastating complication without clear etiology, making that despite the fact that women undergo more spinal proce-
prevention a challenge for surgeons and anesthesiologists. dures than men, 72% of cases in the registry were men.
Patients with ION present with painless binocular or
monocular visual loss, and the severity can range from a field Avoidance of POVL
cut to complete loss of light perception. The problem is gener- As the etiologies of POVL are poorly understood, it is impos-
ally recognized upon emergence from anesthesia but may be sible to avoid this complication. However, there are a few clear
delayed for hours. Like CRAO, patients have a reduced or ab- preventive measures that may be taken. First, check the eyes of
sent pupillary light reflex. External evidence of eye injury is prone patients on a regular basis, at least every 15 minutes, to
generally absent. In patients with AION, the initial fundo- ensure that they are clear of pressure of any kind. Particularly
scopic examination reveals an edematous disc, whereas with for patients on head rests (as opposed to pins), proper initial
PION, the initial fundoscopic examination findings are gener- positioning does not guarantee against subsequent head move-
ally normal. Over time, patients with both AION and PION ment during surgery, causing the orbit to come into contact
will develop fundoscopic evidence of disc degeneration, and with the head holder. Furthermore, to optimize retinal or
the likelihood of significant visual recovery is poor. optic nerve perfusion pressure, whenever possible, the head
Although it appears easy to explain ION on the basis of position should be neutral and at or slightly above the level of
vascular disease and reduced oxygen delivery to the optic the heart. In some patients with severe kyphoscoliosis, this op-
nerve, the etiology is more complicated. There are reports of timal positioning may be impossible because of the fixed posi-
ION occurring in patients with normal intraoperative hemat- tion of the head on the thorax.
ocrit levels and perfusion pressures.11 There are also rare re- The ASA practice advisory3 was developed by a small task
ports of children developing ION,12 which would imply that force of anesthesiologists, spine surgeons (both orthopedic and
there is a population of patients who may be at increased risk neurosurgical), and neuro-ophthalmologists who evaluated cur-
for ION based on the anatomy of the blood supply to the optic rent data and surveyed practicing anesthesiologists and spine
nerve or lack of autoregulation for this blood supply. In the surgeons. The advisory was published to aid in clinical decision
ASA registry,1 66% of patients with ION had bilateral symp- making and was not intended to be a formal guideline or stan-
toms suggesting that the defect, whatever it is, is global in na- dard of practice. Despite this, their review of the subject was
ture. Certainly, patients have suffered ION without evidence comprehensive, and suggestions for care of spine-injured pa-
of ischemic injury to other vascular beds (kidney, heart), im- tients were thoughtful. A summary of their suggestions is as
plying that the visual system may be particularly sensitive to follows:
changes in oxygen delivery.
A possible mechanism of ION is an orbital compartment 1. Although there are preoperative medical conditions such
syndrome in which the optic nerve is swollen as a result of as anemia, atherosclerotic disease, and obesity, which may
15259_Ch09.qxd 3/14/09 5:11 PM Page 33
CHAPTER 9 • POSTOPERATIVE VISUAL LOSS 33
be associated with POVL, at present, these cannot be con- incidence of CRAO may be reduced with close attention to the
sidered predisposing conditions. orbit intraoperatively, but ION is more sinister in its etiology
2. Factors that place patients as high risk for POVL include and thus more difficult to prevent. Information available to us
prolonged procedures (greater than 6.5 hours) and proce- is limited because of the very rare incidence of this complica-
dures involving large blood loss (average 45% of esti- tion, and single-institution prospective studies are essentially
mated blood volume). impossible. Furthermore, there is currently no animal model
3. Although there was agreement among consultants and for POVL. Until more data on the mechanisms of POVL are
subspecialty physicians that deliberate hypotension available, staged procedures, obsessive attention to the eyes of
should be avoided in high-risk patients (with or without prone patients, and frequent consideration of oxygen delivery
well-controlled hypertension), there was a split opinion to the optic nerve and retina are the best preventive measures
whether induced hypotension should be used in patients available.
without chronic hypertension. In the end, there were in-
adequate data to recommend against the use of deliberate
hypotension. The advisory does recommend continuous
blood pressure measurement in high-risk patients. KEY MESSAGES
4. Regarding minimal acceptable hemoglobin levels, again,
there was significant variation in the opinions of consult- 1. The most common causes of POVL are ischemic in-
ants and subspecialty physicians. The average minimal juries to the visual tracts, which fall into two primary
acceptable hemoglobin level as stated by those surveyed categories: CRAO and ION.
was 9.4 g/dL. The task force could determine no lower 2. In patients undergoing spine surgery, prolonged surgi-
limit for hemoglobin concentration that has clearly been cal procedures and large blood loss are risk factors
associated with the development of POVL. for POVL.
5. In patients with significant blood loss, it was advised that
colloids should be used in conjunction with crystalloids. 3. Although the incidence of CRAO can be decreased with
6. Although there was a consensus among neuroanesthesiol- close attention to the orbit intraoperatively, ION is more
ogists that the prolonged use of ␣-agonists may reduce sinister in its etiology and thus more difficult to prevent.
perfusion pressure to the optic nerve, there were inade-
quate data to formulate an advisory on this topic.
7. Staged surgical procedures should be considered in high-
risk patients.
8. With regard to postoperative management of the patient
QUESTIONS
with POVL, although all groups agree that there is no
proven treatment for ION, they also agree that anemia 1. What is the incidence of POVL in patients who have
should be treated, blood pressure increased, and oxygen undergone spine surgery?
administered. In patients suspected of having POVL, ur- Answer: True POVL in spine-injured patients has an in-
gent ophthalmologic consultation should be obtained, and cidence of 0.1% to 0.2%.
magnetic resonance imaging should be considered to rule
out intracranial causes of blindness. 2. What are the anatomic segments of the optic nerve?
9. Preoperative discussion of POVL should be considered Answer:
for patients at high risk (prolonged procedure, anticipated a. The intracranial segment (optic chiasm to the optic
large blood loss). canal within the lesser sphenoid wing)
b. The intracanalicular segment (within the optic canal)
Management of POVL c. The posterior or intraorbital segment (optic foramen to
The patient presented in this case had at least two risk factors the lamina cribrosa)
for POVL: he underwent an 8-hour procedure in the prone d. The anterior or intraocular segment (from the lamina
position and lost approximately 50% of his blood volume. cribrosa to the optic disc)
Whether his history of hypertension or diabetes contributed to
3. What are the likely mechanisms underlying POVL?
his risk is unclear. There were also episodes of reduced blood
pressure intraoperatively, but this association with POVL is Answer: These include cerebral cortical infarction, pitu-
unclear. itary apoplexy, direct injuries to the eye and visual tracts,
There is no proven treatment for POVL. However, several and ischemic injuries to the optic nerve and/or retina.
steps should be taken urgently for this patient including rap-
idly increasing his blood pressure to at least his baseline value References
and ensuring that his hemoglobin level is within a reasonable
range (9.0 g/dL or greater). Ophthalmologic consultation 1. Lee L, Roth S, Posner K, et al. The American Society of
Anesthesiologists Postoperative Visual Loss Registry.
should be obtained immediately, and a fundoscopic examina-
Anesthesiology 2006;105:652–659.
tion should be performed in an effort to evaluate what type of 2. Myers MA, Hamilton SR, Bogosian AJ, et al. Visual loss as a
injury may be present. Magnetic resonance imaging scans complication of spine surgery: a review of 37 cases. Spine 1997;22:
should be obtained. 1325–1329.
In conclusion, POVL is a devastating complication follow- 3. Practice Advisory for Perioperative Visual Loss Associated
ing spine surgery with an outcome that is generally poor. The with Spine Surgery: a Report by the American Society of
15259_Ch09.qxd 3/14/09 5:11 PM Page 34
34 CHAPTER 9 • POSTOPERATIVE VISUAL LOSS
Anesthesiologists Task Force on Perioperative Blindness. 11. Ho VT, Newman N, Song S, et al. Ischemic optic neuropathy
Anesthesiology 2006;104:1319–1328. following spine surgery. J Neurosurg Anesthesiol 2005;17:38–44.
4. Hyman C. The concept of end arteries and flow diversion. Invest 12. Chutorian AM, Winterkorn JM, Geffner M. Anterior ischemic
Ophthalmol 1965;4:1000–1003. optic neuropathy in children: case reports and review of the liter-
5. Williams EL, Hart WM, Tempelhoff R. Postoperative ischemic ature. Pediatr Neurol 2002;26:358–364.
optic neuropathy. Anesth Analg 1995;80:1018–1029. 13. Danish-Meyer HV, Levin LA. Erectile dysfunction drugs and
6. Steele EJ, Blunt MJ. The blood supply of the optic nerve and chi- risk of anterior ischaemic optic neuropathy: casual or causal asso-
asma in man. JANA 1956;90:486–493. ciation? Br J Opthalmol 2007;91:1551–1555.
7. Pillunat LE, Anderson DR, Knighton RW, et al. Autoregulation 14. Sivaswamy L, Vanstavern GP. Ischemic optic neuropathy in a
of human optic nerve head circulation in response to increased child. Pediatr Neurol 2007;37:371–372.
intraocular pressure. Exp Eye Res 1997;64:737–744. 15. Fodale V, DiPietro R, Santamaria S. Viagra, surgery and anes-
8. Shaw PJ, Bates D, Cartlidge NE, et al. Neuro-ophthalmological thesia: a dangerous cocktail with a risk of blindness. Medical
complications of coronary artery bypass graft surgery. Acta Hypotheses 2007;68:880–882.
Neurol Scand 1987;76:1–7. 16. Kawasaki A, Purvin V. Recovery of postoperative visual loss fol-
9. Walick KS, Kragh J, Ward J, Crawford J. Changes in intraocular lowing treatment of severe anemia. Clin Experiment Ophthalmol
pressure due to surgical positioning. Spine 2007;32:2591–2595. 2006;34:497–499.
10. Cheng MA, Todorov A, Tempelhoff R, et al. The effect of prone 17. Connolly SE, Gordon KB, Horton JC. Salvage of vision after hy-
positioning on intraocular pressure in anesthetized patients. potension-induced ischemic optic neuropathy. Am J Opthalmol
Anesthesiology 2001;95;1351–1355. 1994;117:235–242.
15259_Ch10.qxd 3/14/09 5:11 PM Page 35
CHAPTER 10
Postoperative Cognitive Dysfunction
Charles W. Hogue
of clinical surveillance. Contemporary studies using sensitive

brain magnetic resonance imaging with diffusion-weighted
imaging report that as many as 45% of patients who have un-
A 75-year-old male had undergone an otherwise success-
dergone cardiac surgery have new ischemic brain lesions that
ful coronary artery bypass graft (CABG) surgery with aor-
are often clinically undetected. Hemorrhagic stroke is unusual
tic valve replacement 1 month prior to attendance at his
as a primary cause of cerebral injury after cardiac surgery.
postoperative clinic. His medical history included hyperten-
sion, non–insulin-dependent diabetes mellitus, and several Postoperative Cognitive Dysfunction
episodes of congestive heart failure in the month before his After Cardiac Surgery
surgery. He was married, had retired as a factory worker,
and was physically active until the onset of his current ill- Postoperative cognitive dysfunction is another manifestation
ness. His recent cardiac operation included 140 minutes of of brain injury from cardiac surgery that may be less clinically
cardiopulmonary bypass (CPB), transfusion of two units of obvious yet more frequent, affecting 20% to 30% of patients
packed red blood cells, 18 hours of hospitalization in the 1 month after surgery.1–3 This form of brain injury is detected
intensive care unit, and 7 days of total postoperative hos- by administering a battery of psychometric tests typically be-
pitalization. The patient had a 1-day episode of atrial fib- fore and after surgery. These tests evaluate a broad range of
rillation on postoperative day 2 that converted to sinus brain areas subserving attention, short- and long-term mem-
rhythm with intravenous amiodarone. During his clinic visit, ory, visuomotor function, and other cognitive domains. In
his wife and daughter were concerned that he seemed for- some instances, cognitive dysfunction may be noticed by fam-
getful since surgery and his ability to concentrate, such as ily members who detect mild changes in the patient’s person-
for reading the newspaper, had noticeably declined. ality, attention, memory, or even the perceptions that their
His vital signs were as follows: temperature, 36.9oC; family member “is not the same after surgery.”
blood pressure, 155/70 mm Hg; heart rate, 68 beats per
minute; and respiratory rate, 20 breaths per minute. The MECHANISMS
patient’s physical examination was unremarkable, and It is generally believed that all forms of brain injury from
his medications included aspirin, warfarin, amiodarone, cardiac surgery (i.e., stroke, delirium, and neurocognitive dys-
and atorvastatin. Twelve-lead electrocardiogram readings function) arise from a similar mechanism and that the ultimate
showed sinus rhythm, and laboratory results were accept- manifestation depends on the extent and location of brain injury
able. Physical examination, including a comprehensive (e.g., global vs. regional, motor cortex vs. areas subserving cog-
neurologic exam, was normal. The patient was oriented to nition). This theory, however, is based on indirect data and has
person, place, and time. He could repeat 7 numbers after not been conclusively proven. In general, perioperative brain in-
a delay of 5 minutes with mild difficulty. His sensorium ap- jury results from cerebral embolism or cerebral hypoperfusion
peared normal, but he did admit that he had not felt “him- that is exacerbated by inflammatory processes induced by CPB
self” since surgery. The plan was to discontinue warfarin and/or ischemia-reperfusion injury. Abnormal endothelial
and amiodarone. functions resulting from ischemic damage and inflammatory
processes leading to impaired microcirculatory flow likely con-
tribute to subsequent injury. Cerebral emboli are often arbitrar-
ily classified as macro- and microembolism. Examples of the
CASE DISCUSSION former include atheroembolism arising from an atherosclerotic
ascending aorta. The important role of atherosclerosis of the as-
cending aorta in brain injury has led to the practice of epiaortic
Cerebral Complications ultrasound scanning before surgical manipulations of the aorta.1
of Cardiac Surgery This method is more sensitive than palpation and trans-
Clinically, perioperative cerebral injury has a range of mani- esophageal echocardiography for identifying aortic atheroma
festations that includes its most notable form, ischemic stroke. allowing the surgeon to choose alternate sites for cannulations
Perioperative stroke occurs in 1.5% to 5.2% of patients after and cross clamping. When atherosclerosis is severe, alternate
cardiac surgery.1,2 The range in reported incidences depends surgical plans (e.g., different site of cannulation, off-pump
on the patient populations (e.g., patient age and risk status, surgery, etc.) may be necessary. There are many sources of
types of procedures), diagnostic definitions, and the intensity microemboli including air entrained into the circulation or the
35
15259_Ch10.qxd 3/14/09 5:11 PM Page 36
36 CHAPTER 10 • POSTOPERATIVE COGNITIVE DYSFUNCTION
CPB circuit, particulate material arising from the operative surgery such that they are incapable of further decrements of a
field, microthrombus, and lipid emboli. The latter are believed magnitude necessary to show a standard deviation decline.
to arise from pericardial fat that is aspirated with cardiotomy This “basement effect” might overlook cognitive decrements
suction during CABG surgery and then returned to the CPB that have profound importance to an elderly patient already
reservoir unfiltered. Some centers advocate first processing shed functioning at a low cognitive level. At the same time, factors
pericardial blood with a cell saver before returning the blood to other than brain injury per se might lead to a false-positive di-
the CPB reservoir. The latter method was found to reduce the agnosis of neurocognitive dysfunction. Depression, pain, and
frequency of postoperative neurocognitive dysfunction in one chronic illness might all lead to low psychometric test results in
study but not confirmed in another. the absence of cerebral injury during surgery.7
RISK FACTORS ASSOCIATED OUTCOMES

Some risk factors for stroke and postoperative neurocognitive Perioperative cerebral complications are an important source of
dysfunction overlap, yet others are distinct. Patient age, athero- patient morbidity and mortality. The chance of operative death
sclerosis of the ascending aorta, prior stroke, diabetes, hyperten- for patients suffering a new stroke is greater than 10-fold higher
sion, peripheral vascular disease, duration of CPB, and postop- than for patients who have not suffered a stroke (⬎20% vs. ⬃1%
erative atrial fibrillation are common risk factors for stroke and to 2%).1–3 Stroke, after cardiac surgery is, in fact, the second
postoperative neurocognitive dysfunction.1–3 The patient’s level most common cause of operative death after left ventricular fail-
of education is inversely related to risk for cognitive dysfunction. ure. Cerebral complications are further linked to high hospital
An explanation for this relationship is not clear, but higher costs, admission to a secondary health care facility after surgery,
levels of education might identify individuals who are more pro- high hospital readmission rates, and impaired quality of life.
ficient at taking psychometric tests or those with more cerebral The prognosis for patients with postoperative neurocogni-
reserve and are thus capable of tolerating an acute insult to the tive dysfunction has now been examined in several longitudinal
brain. Genetic susceptibility has been further identified to be studies. In a seminal investigation, investigators from Duke
associated with cerebral complications from cardiac surgery, but University found that neurocognitive dysfunction after CABG
genotypes associated with stroke and neurocognitive dysfunc- surgery predicted further cognitive decrement over a 5-year
tion appear distinct.1 Candidate genes include those associated period.3 Subsequent study by a team from Johns Hopkins
with inflammatory cytokines and neuronal reparative pathways. University compared long-term cognitive function in patients
It is hypothesized that abnormal secretion of inflammatory me- recovering from CABG surgery with that of control subjects
diators during and after surgery or defective neuronal reparative with coronary artery disease who were medically managed
processes might promote susceptibility to brain injury. Several (plus/minus percutaneous coronary artery intervention).6 These
prospectively randomized trials have reported that there is no investigators found that the rates of long-term cognitive decline
difference in the frequency of cerebral outcomes between were no different in CABG surgical patients than controls over
patients undergoing CABG surgery with or without CPB (off- a 3-year period. These investigators are now reporting similar
pump surgery).1 Other factors found to be associated with cere- results after a 6-year follow-up period. The emerging data sug-
bral injury include cerebral hyperthermia caused by excessive gest that many patients with neurocognitive dysfunction after
rewarming after hypothermic CPB and low nadir hematocrit CABG surgery recover after 3 to 6 months. Further cognitive
during CPB (⬍21% to 24%). Although hyperglycemia is impli- decline appears more related to the natural progression of cere-
cated as worsening cerebral injury, there is no evidence to date brovascular disease than the cardiac surgical procedure.
that aggressive insulin treatment during surgery leads to a lower
rate of stroke, encephalopathy, or neurocognitive dysfunction. DELIRIUM
Methodologic limitations to psychometric testing include Postoperative delirium (as distinguished from emergence
test-retest or practice effect whereby individuals undergoing delirium) is a disturbance of consciousness or awareness of the
psychometric testing score higher on repeated testing because environment accompanied by a decreased ability to focus, sus-
of familiarization with testing methodology.4,5 The statistical tain, or shift attention. Other features may include decrement in
approach for defining cognitive decline varies between stud- cognition (disorientation, reduced memory) or a perceptual
ies, and the approach chosen affects the ultimate frequency of disturbance (delusions or hallucinations) that is not caused by
the complications. There is no accepted standard for defining pre-existing dementia. Delirium is acute in onset developing
neurocognitive dysfunction. The often-used definition of a over hours to days, and the course may fluctuate throughout the
20% decline in two or more psychometric tests after surgery day. Delirium can be categorized into hypoactive, hyperactive,
from baseline has been challenged on the basis that there is or mixed forms. Hypoactive delirium might be mistaken for
often correlation between the results of many psychometric depression or dementia. The frequency of delirium depends on
tests. Thus, if two test results are correlated, decrements on the definitions, patient population, and type of surgery.
these tests might identify the same cognitive defect rather than Reported incidences after cardiac surgery range from 20% to
distinct areas of dysfunction. Principal component analysis in 65% of patients and after hip surgery, 16% to 65%, particularly
which tests that correlate are grouped into general domains, elderly patients and those undergoing CPB.8 Delirium may be
and cognitive decline defined as a standard deviation decline transient, or it may be associated with longer-term decrements
from baseline overcomes this limitation. in cognition, long-term disability, mortality, loss of independ-
Perhaps a larger limitation of psychometric testing as a ence, admission to a nursing home, and high health resource
means for detecting brain injury from cardiac surgery is its utilization. The etiology of delirium is unknown, but it may
insensitivity and nonspecificity in an aging surgical population.4 involve similar factors as those leading to postoperative
Many patients might have pre-existing cognitive deficits before neurocognitive dysfunction. Other factors implicated to be asso-
15259_Ch10.qxd 3/14/09 5:11 PM Page 37
CHAPTER 10 • POSTOPERATIVE COGNITIVE DYSFUNCTION 37
ciated with the condition include perioperative stress responses QUESTIONS

including systemic inflammatory response to surgery, abnor-
malities of brain cholinergic or norepinephrine neurotransmit- 1. What is the incidence of POCD after noncardiac
ter pathways, metabolic abnormalities, electrolyte abnormality, surgery?
cerebral edema, hypoxia, or infections. Pre-existing patient fac-
tors, pain, and medications (e.g., benzodiazepines, drugs with Answer: After noncardiac surgery, the incidence of
central anticholinergic effects, corticosteroids, and some antibi- POCD in the immediate postoperative period may be
otics) are suggested to increase susceptibility to postoperative as high as 25%, but this rate declines to roughly 10% by
delirium.8 Acute or chronic substance abuse is further impli- 3 months postoperatively.
cated. Data derived mostly from observational studies suggest a 2. What is delirium?
link between meperidine use in elderly patients and delirium.
Although the data are presently insufficient, there currently Answer: Delirium (as distinguished from emergence
does not appear to be an association among other analgesics and delirium) is a disturbance of consciousness or aware-
risk for delirium. Interventions that may improve or prevent ness of the environment accompanied by a decreased
delirium include frequently providing the patient with orienta- ability to focus, sustain, or shift attention. Other fea-
tion cues such as a clock, calendar, and list of hospital staff. tures may include decrement in cognition (disorienta-
Physical exercise, visual aids, cognitive stimulation, regular tion, reduced memory) or a perceptual disturbance
daily routines, and sleep cycles are further measures. (delusions or hallucinations) that is not caused by pre-
existing dementia.
Postoperative Cognitive Dysfunction 3. How can postoperative cognitive function be formally
After Noncardiac Surgery assessed?
Cognitive dysfunction has been reported after noncardiac sur- Answer: It can be assessed by administering a battery
gery mostly in elderly patients. Overall, the incidence in the of psychometric tests typically before and after
immediate postoperative period might be as high as 25%, but surgery. These tests evaluate a broad range of brain
this rate declines to roughly 10% by 3 months postoperatively.8,9 areas subserving attention, short- and long-term
The available evidence suggests that by 1 year, cognitive per- memory, visuomotor function, and other cognitive
formance in most patients has returned to that expected for a domains.
matched control group not undergoing surgery. As with cardiac
surgery, the detection of cognitive dysfunction after noncardiac
surgery depends on baseline cognitive state and thus requires References
paired administration of a psychometric testing battery. 1. Hogue CW, Palin CA, Arrowsmith JE. Cardiopulmonary
Generalized cognitive tests such as the Mini-Mental Exam are bypass management and neurologic outcomes: an evidence-
mostly insensitive for detecting cognitive dysfunction. There is based appraisal of current practices. Anesth Analg 2006;103:
no signal test for this purpose, as a comprehensive battery is nec- 21–37.
essary to fully assess the broad range of cognitive domains that 2. Roach GW, Kanchuger M, Mora-Mangano C, et al. Adverse
cerebral outcomes after coronary bypass surgery. N Engl J Med
might be affected by surgery. Of note, the type of anesthesia, re-
1996;335:1857–1863.
gional versus general, does not seem to influence the incidence 3. Newman MF, Kirchner JL, Phillips-Bute B, et al. Longitudinal
of postoperative neurocognitive dysfunction. assessment of neurocognitive function after coronary artery by-
pass surgery. N Engl J Med 2001;344:395–402.
4. Selnes OA, Pham L, Zeger S, McKhann GM. Defining cognitive
KEY MESSAGES change after CABG: decline versus normal variability. Ann
Thorac Surg 2006;82:388–390.
1. Perioperative stroke occurs in 1.5% to 5.2% of pa- 5. Van Dijk D, Keizer AM, Diephuis, JC, et al. Neurocognitive
tients after cardiac surgery. dysfunction after coronary artery bypass surgery: a systematic
review. J Thorac Cardiovasc Surg 2000;120:632–639.
2. Postoperative cognitive dysfunction affects 20% to 6. Selnes OA, Grega MA, Borowicz LM, et al. Cognitive changes
30% of patients 1 month after cardiac surgery. with coronary artery disease: a prospective study of coronary ar-
tery bypass graft patients and nonsurgical controls. Ann Thorac
3. Patient age, atherosclerosis of the ascending aorta, Surg 2003;75:1377–1386.
prior stroke, diabetes, hypertension, peripheral vascular 7. Fong HK, Sands LP, Leung JM. The role of postoperative anal-
disease, duration of CPB, and postoperative atrial fibril- gesia in delirium and cognitive decline in elderly patients: a
lation, are common risk factors for stroke and postoper- systematic review. Anesth Analg 2006;102:1255–1266.
ative neurocognitive dysfunction after cardiac surgery. 8. Newman S, Stygall J, Hirani S, et al. Postoperative cognitive
dysfunction after noncardiac surgery. A systematic review.
4. Operative death for patients suffering a new stroke is Anesthesiology 2007;106:572–590.
greater than 10-fold higher than for patients who have 9. Silverstein JH, Timberger M, Reich DL, Uysal S. Central nerv-
not suffered a stroke (⬎20% vs. ⬃1% to 2%). ous system dysfunction after noncardiac surgery and anesthesia
in the elderly. Anesthesiology 2007;106:622–628.
15259_Ch11.qxd 3/14/09 6:37 PM Page 38
CHAPTER 11
Perioperative Myocardial Infarction
Joshua D. Stearns
amount of blood loss, it was likely that the patient would need
a transfusion of packed red blood cells. If these initial measures
did not lead to an increase in blood pressure, a reduction in
A 74-year-old female presented for a right femoral-
heart rate, and resolution of the ST-segment changes, the pa-
popliteal arterial bypass. Her medical history was signifi-
tient may have been experiencing left ventricular dysfunction
cant for hypertension, peripheral vascular disease, an 80
or cardiogenic shock secondary to myocardial ischemia.
pack-year history of tobacco use, and recently diagnosed
diabetes mellitus. The patient had undergone a cholecys-
tectomy 20 years previously under general anesthesia with- What mechanism of myocardial ischemia was
out incident. Her current medications included lisinopril, most likely in this patient?
glyburide, oxycodone and acetaminophen, and daily as- The etiology of perioperative myocardial ischemia is often mul-
pirin. Preoperative electrocardiogram (ECG) readings re- tifactorial. In this patient’s situation, the presence of tachycardia,
vealed normal sinus rhythm at 72 beats per minute and left blood loss, and likely reduced hemoglobin concentration, sug-
ventricular hypertrophy by voltage criteria. The patient’s gests that the underlying mechanism for myocardial ischemia
preoperative hemoglobin level was 12.5 mg/dL, and her was myocardial O2 supply/demand mismatch. Hypovolemia
serum creatinine level was 1.3 mg/dL. The planned anes- leads to reflex tachycardia increasing myocardial O2 demand.
thetic technique was general endotracheal anesthesia with At the same time, lessened blood O2 carrying capacity from re-
propofol induction and maintenance with fentanyl, nitrous duced hemoglobin compromises myocardial O2 supply. Hypo-
oxide, and isoflurane along with vecuronium for muscle re- tension in this case might have resulted from reduced cardiac
laxation. Invasive arterial monitoring was utilized. preload or reduced stroke volume from myocardial ischemia.
Initially, the patient tolerated the procedure well with-
out evidence of myocardial ischemia by ECG monitoring What other mechanisms are implicated in
(leads II and V5 and ST-segment analysis). An hour and a perioperative myocardial ischemia/infarction?
half into the procedure, however, and following approxi-
mately 800 mL of blood loss, the patient’s heart rate in- Many episodes of myocardial ischemia occur despite a normal
creased to 110 beats per minute and there was evidence heart rate and blood pressure. The latter episodes result from
of ST-segment elevation in ECG lead II. Multiple lead reduced coronary artery blood flow often caused by a ruptured
analysis showed ST-segment elevation in leads II, III, and atherosclerotic plaque leading to platelet activation and release
aVF. The patient’s blood pressure slowly decreased from of vasoactive substances, thrombus formation, and partial or
135/85 mm Hg to 90/60 mm Hg over several minutes. complete arterial obstruction. Atherosclerotic plaque disrup-
tion can occur in patients with only modest angiographic
evidence for coronary artery stenosis. Furthermore, a stable
What measures should be have been taken coronary artery plaque can acutely transform to a plaque that
at this point to limit myocardial ischemia? is vulnerable to fissuring or frank rupture caused by localized
inflammation or shear stresses resulting from sympathetic ac-
The treatment of myocardial ischemia is aimed at improving
tivation or rheologic factors. Patients with extant coronary
the balance between myocardial oxygen (O2) supply versus de-
plaque may be at additional risk for acute coronary syndromes
mand. Nitrous oxide should have been discontinued, and the
as a result of the multiple stresses associated with surgery.1
patient should have been administered 100% O2. Her blood
pressure should have been increased by intravascular volume
replacement and by administering a vasoconstricting agent What is the definition of myocardial infarction?
such as phenylephrine. Avoiding drugs with ␤-adrenergic ef- The World Health Organization uses the following criteria for
fects (e.g., ephedrine, epinephrine, or norepinephrine) is advis- diagnosis of a myocardial infarction (MI). Two of the following
able to prevent further tachycardia and increased myocardial must be present: (a) typical ischemic chest pain; (b) elevated
O2 demand. A short-acting ␤-blocker (e.g., esmolol) should serum creatine kinase (CK-MB enzyme); and/or (c) typical
have been considered to lessen the patient’s heart rate. The tar- ECG findings including the development or presence of patho-
get heart rate should be close to the patient’s baseline or the low- logic Q waves.1
est rate that is hemodynamically tolerated. The patient’s arterial In 2000, however, the European Society of Cardiology and
blood gas, hemoglobin, and electrolytes should have been meas- the American College of Cardiology (ACC) revised the formal
ured. In light of the preoperative hemoglobin level and the definition of an MI incorporating the use of increasingly
38
15259_Ch11.qxd 3/14/09 6:37 PM Page 39
CHAPTER 11 • PERIOPERATIVE MYOCARDIAL INFARCTION 39
sensitive biochemical assays such as troponin I and T for the chemia that does not necessarily lead to actual myocyte necrosis.
diagnosis (information to follow).2 There is much debate, therefore, as to the specific cut-off values
that can be used to define an MI in the perioperative setting.
Several studies suggest that even small elevations of cardiac tro-
Do perioperative MIs present in a fashion ponins in the perioperative period identify some myocardial
consistent with the World Health injury.4 These elevations and the accompanying myocardial
Organization’s definition of MI? injury may be implications for both short- and long-term
Most often, perioperative MI is not accompanied by typical mortality. Over time, the threshold values have decreased sug-
chest pain caused by residual anesthetics, analgesic drugs, or gesting that there is an association between small troponin ele-
sedation, especially in the setting of patients who remain in- vations and cardiac outcome. Laboratory cut-offs for diagnoses
tubated postoperatively. In addition, perioperative MI often differ from institution to institution. An increase in CK-MB
manifests few of the classic ECG findings such as ST-segment ⬎10% (upper limit of normal ⫽ 170 IU), cTn-I ⬎1.5 ng/mL,
elevation or Q waves.1 As a result, the use of biochemical mark- or cTn-T ⬎0.1 ng/mL have been shown to be independent pre-
ers of myocardial injury often provides the most definitive di- dictors of mortality from cardiac events at 1-year and 5-year
agnosis of perioperative MI. According to one study, 12% of follow-up for patients undergoing vascular surgery.4
patients developed elevated cardiac troponin T (cTnT) levels,
while only 3% exhibited characteristics that confirmed periop-
erative MI by the World Health Organization definition.3 What are the pharmacologic treatment options
for patients diagnosed with a perioperative MI?
Medical therapy for perioperative MI is directed based toward
Which biochemical markers are commonly used rectifying myocardial O2 demand/supply mismatch. Myocar-
in the diagnosis of perioperative MI? dial O2 demand is reduced by the judicious use of ␤-blockers
Biochemical markers for detecting myocardial injury include while ensuring myocardial perfusion pressure. Certainly, the
serum creatine kinase (CK-MB) and cTnT or troponin I (cTnI) most well-studied and used pharmacologic preventive treat-
assays. Cardiac troponins are both specific and sensitive for ment for perioperative myocardial ischemia or perioperative
detecting myocardial injury and appear to provide improved MI is ␤-blocker therapy. Several studies have shown reduced
detection of MI as compared to CK-MB levels. adverse cardiac events for patients in the perioperative setting,
especially in patients considered at high risk for coronary heart
disease. Patients considered high risk include those with risk
What threshold levels of CK-MB and cardiac factors such as diabetes mellitus and hypertension as well as
troponins are diagnostic of perioperative MI? patients who have been shown to exhibit “inducible” myocar-
CK-MB is not specific for cardiac tissue; thus, interpreting dial ischemia by exercise or pharmacologic stress testing.
elevations in this isoenzyme is confounded perioperatively by (Table 11.1). Furthermore, the initiation of ␤-blockers days or
other sources (e.g., muscle injury). Cardiac troponins are specific weeks in advance of surgery appears to provide greater bene-
for the heart, but they are also released because of myocardial is- fit (a target heart rate of ⬍65 beats per minute is optimal).
T A B L E 1 1 . 1 ACC/AHA Recommendations for Perioperative Use of ␤-Blockers Based on Published

Randomized Clinical Trials
Surgery No clinical risk factors One or more clinical Coronary heart disease Patients currently taking
risk factors or high cardiac risk ␤-blockers
Vascular Class IIb, level of Class IIa, level of Patients found to have Class I, level of
evidence ⫽ B evidence ⫽ B myocardial ischemia evidence ⫽ B
on preoperative testing:
class I, level of evidence
⫽ B; patients without
ischemia or not previous
test: class IIa, level of
evidence ⫽ B
Intermediate Insufficient data Class IIb, level of Class IIa, level of Class I, level of
risk evidence ⫽ C evidence ⫽ B evidence ⫽ C
Low risk Insufficient data Insufficient data Insufficient data Class I, level of
evidence ⫽ C
ACC, American College of Cardiology; AHA, American Heart Institute.
Adapted from Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac
surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the
2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Circulation 2007;116:e418–499.
15259_Ch11.qxd 3/14/09 6:37 PM Page 40
40 CHAPTER 11 • PERIOPERATIVE MYOCARDIAL INFARCTION
Aspirin has been shown to be beneficial in the setting of

T A B L E 1 1 . 2 Cardiac Conditions That Should
acute MI. Both its anti-inflammatory effects and antiplatelet
aggregation effects appear to play a role in the reduction of Have Further Evaluation in
thrombotic activity characteristic of the plaque rupture mecha- Advance of Surgical Procedure
nism for MI. The benefits of aspirin may be increased in the pe-
rioperative setting because of the accompanying inflammatory 1. Unstable coronary syndrome—unstable or severe
response to surgery. A meta-analysis of perioperative use of angina
aspirin identified an almost 50% reduction of postoperative 2. Decompensated congestive heart failure—NY class IV
acute MI when administered with a dose of 325 mg or less.5 The 3. Malignant arrhythmias including
relative benefits of aspirin (given via a gastric tube or rectally) for i) High-grade atrioventricular block
secondary prevention of myocardial injury will outweigh the a) Mobitz type II AV block
minimal risk of enhanced bleeding for most surgical procedures. b) Third-degree AV block
Heparin has been a mainstay for the treatment of acute MI; ii) Supraventricular tachycardia
however, in the postoperative setting, the advantages of un- c) Atrial fibrillation with rapid ventricular response
fractionated heparin, other anticoagulants (such as low-
d) Symptomatic bradycardia
molecular-weight heparin or direct thrombin inhibitors such
as bivalirudin), and antiplatelet drugs must be considered in e) Symptomatic ventricular arrhythmias
reference to the risks of bleeding from the surgical wound. iii) New-onset ventricular tachycardia
Antiplatelet drugs commonly used include clopidogrel and 4. Severe valvular disease
glycoprotein IIb/IIIa inhibitors.6 The use of anticoagulants i) Severe aortic stenosis
and/or antiplatelet drugs should be initiated with the consul- ii) Severe mitral stenosis
tation of a cardiologist. This consultation should address other Adapted from Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA
potential therapies such as angiotensin-converting enzyme in- 2007 guidelines on perioperative cardiovascular evaluation and care for
hibitors might be further considered particularly for anterior noncardiac surgery: a report of the American College of Cardiology/
MI or in the setting of left ventricular dysfunction. Increasing American Heart Association Task Force on Practice Guidelines
interest has been placed on the use of statins (3-hydroxy-3- (Writing Committee to Revise the 2002 Guidelines on Perioperative
methylglutaryl coenzyme A reductase inhibitors) in the preven- Cardiovascular Evaluation for Noncardiac Surgery). Circulation 2007;
tion of MI. Their use in the acute setting of an MI is unclear, 116:e418–499.
although initial data suggest that statins confer benefits when
administered in the acute setting.
␣-2 Adrenoceptor agonists such as clonidine and dexme- preoperative cardiac evaluation based on three components.
detomidine may have benefits if used prior to surgery; however, First, active evidence of cardiac disease and/or of clinical risk
the slow onset of effect of ␣-2 adrenoceptor agonists may limit factors helps determine proper cardiac evaluation (Tables
their value in the treatment of an identified MI. Nitroglycerin 11.2 and 11.3). Patients demonstrating existing cardiac
use for coronary dilatation may be of benefit if hemodynamics disease (major risk factors) should have further cardiac
are stable and if there is ongoing evidence by ECG of ischemia.7 evaluation before surgery, whereas those presenting with
clinical risk factors may or may not require further testing.
What potential interventions should be Previous guidelines stratified clinical risk factors into mild-,
considered as treatment for ongoing ischemia intermediate-, and high-risk; however, the most recent
or infarction? ACC/AHA guidelines have replaced that stratification with
Placement of an intra-aortic balloon pump should be consid- a list of clinical risk factors (Table 11.3). Second, an evalua-
ered for refractory or recalcitrant myocardial ischemia. The tion of a patient’s functional capacity is considered. Third,
definitive treatment of an acute MI is coronary artery reperfu- the type of surgery is factored into the algorithm with high-
sion. Thrombolytic therapy is contraindicated because of the (e.g., vascular), intermediate-, and low-risk being assigned to
recent surgical incision and may be less effective than percuta- each surgery (Table 11.4). According to the latest update, the
neous coronary artery interventions (PCI). Early consultation presented patient had one clinical risk factor (diabetes melli-
with an invasive cardiologist is mandatory when there is an tus) and was undergoing a high-risk procedure (vascular sur-
acute MI. Prompt transfer of the patient to the coronary gery). The case described does not, however, describe the
catheterization laboratory for coronary angiography and pos- patient’s functional capacity. Nevertheless, the algorithm of-
sible coronary artery angioplasty with or without stent place- fers the practitioner the option of considering further cardiac
ment may rescue compromised myocardium.7 evaluation or proceeding with the case using perioperative
␤-blockers.8
According to the ACC/American Heart
Association Guidelines for Perioperative What role does preoperative coronary
Cardiovascular Evaluation for Noncardiac revascularization play in the reduction of
Surgery, what would be an appropriate perioperative MI?
preoperative strategy for evaluating cardiovas-
cular risk in the patient presented in this case? PCI
The ACC/American Heart Association (AHA) Guidelines PCI includes both coronary angioplasty with or without the
stratify perioperative cardiac risk and specify the appropriate use of intraluminal stents. The routine use of these interven-
15259_Ch11.qxd 3/14/09 6:37 PM Page 41
placement is currently under debate. However, a widely used

T A B L E 1 1 . 3 Clinical Risk Factors for
antithrombotic strategy should include the use of clopidogrel
Perioperative Cardiac Events for 6 weeks with concomitant aspirin that should be continued
for life. Stent manufacturers recommend that clopidogrel
1. History of ischemic cardiac disease
should be continued for at least 3 months with sirolimus-
2. History of compensated or previous heart failure eluting stents and 6 months with paclitaxel-eluting stents.12
3. History of cerebrovascular disease Despite these recommendations, more recent experience sug-
4. Diabetes mellitus gests that dual antiplatelet therapy is needed for longer than 1
5. Renal insufficiency year after insertion of a drug-eluting stent. Elective surgery
Adapted from Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA should be delayed if the patient has not received an adequate
2007 guidelines on perioperative cardiovascular evaluation and care for duration of dual antiplatelet drug therapy. The optimum
noncardiac surgery: a report of the American College of Cardiology/ management of patients requiring surgery during the window
American Heart Association Task Force on Practice Guidelines of mandatory dual antiplatelet drug therapy is not known.
(Writing Committee to Revise the 2002 Guidelines on Perioperative Consultation with a cardiologist should be made, and consider
Cardiovascular Evaluation for Noncardiac Surgery). Circulation 2007; glycoprotein IIb/IIIa drug use while clopidogrel is stopped.
116:e418–499. Because of this management dilemma, the prophylactic use of
PCI with stents as a strategy to reduce cardiac risk in the
perioperative period is not well supported by the literature. If
tions in advance of an elective surgery is heavily debated. To PCI with stenting has taken place in advance of surgery, an
date, no randomized trials to evaluate the efficacy of preoper- interval of at least 6 weeks should take place before surgery. In
ative percutaneous transluminal coronary angioplasty for re- the case of drug-eluting stents, a minimum of 12 months
ducing perioperative MI have been conducted. Several retro- should be considered8 (Fig. 11.1).
spective cohort studies have examined patient populations
who underwent percutaneous transluminal coronary angio- Surgical Coronary Revascularization
plasty in an effort to ameliorate symptomatic angina and/or to Revascularization by coronary artery bypass grafting has been
reduce perioperative risk of myocardial ischemia. Overall, the proposed and used as a means to reduce cardiovascular risk in
three studies reported a low incidence of perioperative MI high-risk patients undergoing noncardiac surgery. However,
and/or perioperative cardiac death.9–11 Unfortunately, no the Coronary Artery Revascularization Prophylaxis trial
comparison groups were analyzed. demonstrated that coronary artery revascularization prior to
The placement of coronary artery stents, either bare metal elective vascular surgery conferred no long-term outcome
or drug eluting, prior to surgery introduces the need for benefits.13 As such, the decision to use coronary revasculariza-
antiplatelet drug therapy with aspirin and clopidogrel to avoid tion before elective surgery should be based on the same crite-
intrastent thrombosis. The optimum duration of dual an- ria for the use of coronary artery bypass grafting in patients
tiplatelet drug therapy after PCI with intracoronary stent not scheduled to undergo noncardiac surgery.
T A B L E 1 1 . 4 Cardiac Risk Stratification Based on Type of Surgery
Risk Stratification (Risk of Cardiac Events) Types of Procedures

Vascular (⬎5%) Aortic and other major vascular surgery
Peripheral vascular surgery
Intermediate risk (1% to 5%) Intraperitoneal and intrathoracic surgery
Carotid endarterectomy
Head and neck surgery
Orthopedic surgery
Prostate surgery
Low risk (⬍1%) Endoscopic procedures
Superficial procedures
Cataract surgery
Breast surgery
Ambulatory surgery
Adapted from Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular eval-
uation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation
for Noncardiac Surgery). Circulation 2007; 116:e418–499.
15259_Ch11.qxd 3/14/09 6:37 PM Page 42
42 CHAPTER 11 • PERIOPERATIVE MYOCARDIAL INFARCTION
Previous PCI
Balloon Bare-metal Drug-eluting

angioplasty stent stent
<365 days
Time since PCI <14 days >14 days >30-45 days <30-45 days >365 days
Delay for elective or Proceed to the Delay for elective or Proceed to the
nonurgent surgery operation room nonurgent surgery operating room
with aspirin with aspirin
Figure 11.1 • ACC/AHA Proposed Guidelines, Based on Expert Opinion, for Management of
Patients with Recent Percutaneous Coronary Interventions Requiring Noncardiac Surgery.
(Reproduced with permission from Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 guidelines on
perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines [Writing Committee to Revise the
2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery]. Circulation
2007;116:e418–499.)
KEY MESSAGES QUESTIONS
1. Perioperative MI leads to significant morbidity and 1. Which biochemical markers are commonly used in the
mortality and costs the health care system billions of diagnosis of perioperative MI?
dollars each year. Answer: Biochemical markers for detecting myocardial
2. Perioperative MI is proposed to have two basic yet
injury include CK-MBand cTnT or troponin I (cTnI)
often overlapping mechanisms: (a) myocardial O2
assays. Cardiac troponins are both specific and sensitive
supply/demand mismatch and (b) ruptured coronary
for detecting myocardial injury and appear to provide
plaque or associated thrombus leading to coronary
improved detection of MI as compared to CK-MB levels.
occlusion. 2. What limitations apply to interpreting elevations in bio-
3. Perioperative MI is most commonly diagnosed by the markers of myocardial injury?
presence of elevated cardiac enzymes because the Answer: CK-MB is not specific for cardiac tissue;
usual cardiac symptoms are typically masked by anes- thus, interpreting elevations in this isoenzyme is con-
thetic and analgesic drugs and also because it fre- founded perioperatively by other sources (e.g., muscle
quently occurs with few or none of the classic ECG injury). Cardiac troponins are specific for the heart,
findings. but they are also released because of myocardial ischemia
that does not necessarily lead to actual myocyte necrosis.
4. Perioperative ␤-blocker use has been shown to be the
most effective medical therapy for reducing periopera- 3. Why is aspirin administration indicated in the setting of
tive MI—especially in high-risk patients, including acute MI?
those undergoing vascular surgery.
Answer: Both its anti-inflammatory effects and
5. Perioperative use of aspirin and statin drugs may also antiplatelet aggregation effects appear to play a role in
reduce the risk of PMI. the reduction of thrombotic activity characteristic of the
plaque rupture mechanism for MI.
15259_Ch11.qxd 3/14/09 6:37 PM Page 43
References 8. Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007
guidelines on perioperative cardiovascular evaluation and care
1. Priebe HJ. Perioperative myocardial infarction—aetiology and for noncardiac surgery: a report of the American College of
prevention. Br J Anaesth 2005;95:3–19. Cardiology/American Heart Association Task Force on Practice
2. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarc- Guidelines (Writing Committee to Revise the 2002 Guidelines
tion redefined—a consensus document of The Joint European on Perioperative Cardiovascular Evaluation for Noncardiac
Society of Cardiology/American College of Cardiology Committee Surgery). Circulation 2007;116:e418–499.
for the redefinition of myocardial infarction. J Am Coll Cardiol 9. Allen JR, Helling TS, Hartzler GO. Operative procedures not
2000;36:959–969. involving the heart after percutaneous transluminal coronary
3. Kim LJ, Martinez EA, Faraday N, et al. Cardiac troponin I pre- angioplasty. Surg Gynecol Obstet 1991;173:285.
dicts short-term mortality in vascular surgery patients. 10. Elmore JR, Hallett JW Jr, Gibbons RJ, et al. Myocardial revascu-
Circulation 2002;106:2366–2371. larization before abdominal aortic aneurysmorrhaphy: effect of
4. Landesberg G, Mosseri M, Zahger D, et al. Association of cardiac coronary angioplasty. Mayo Clin Proc 1993;68:637.
troponin, CK-MB, and postoperative myocardial ischemia with 11. Gottlieb A, Banoub M, Sprung J, et al. Perioperative cardiovas-
long-term survival after major vascular surgery. J Am Coll cular morbidity in patients with coronary artery disease under-
Cardiol 2003;42:1547–1554. going vascular surgery after percutaneous transluminal coronary
5. Robless P, Mikhailidis DP, Stansby G. Systematic review of angioplasty. J Cardiothorac Vasc Anesth 1998;12:501.
antiplatelet therapy for the prevention of myocardial infarction, 12. Howard-Alpe GM, de Bono J, Hudsmith L, et al. Coronary ar-
stroke or vascular death in patients with peripheral vascular tery stents and non-cardiac surgery. Br J Anaesthesia 2007;98:
disease. Br J Surg 2001;88:787. 560–574.
6. Ramanath VS, Eagle KA. Evidence-based medical therapy of 13. McFalls EO, Ward HB, Moritz TE, et al. Coronary-artery revas-
patients with acute coronary syndromes. Am J Cardiovasc Drugs cularization before elective major vascular surgery. N Engl J
2007;7:95–116. Med 2004;351:2795–2804.
7. Hogue CW Jr, Stamos T, Winters KJ, et al. Acute myocardial
infarction during lung volume reduction surgery Anesth Analg
1999;88:332–334.
15259_Ch12.qxd 3/14/09 6:37 PM Page 44
CHAPTER 12
Heparin-Induced Thrombocytopenia
Roy Kan
ical onset time of 4 days after heparin exposure, a platelet

nadir of 100,000 to 150,000/␮L, and a recovery time of 1 to
3 days with minimal complications. It has an estimated inci-
A 56-year-old woman with hypertension and hyperlipidemia
dence of 5% to 30%. HIT type I is caused by platelet mi-
presented to the emergency department with congestive
croaggregation and subsequent sequestration in the spleen. It
heart failure. A cardiology evaluation revealed triple-vessel
is not associated with heparin-dependent antibodies.
coronary artery disease with marked global left ventricular
Heparin administration should be continued despite the low
hypokinesia (left ventricular ejection fraction, 15%). The
platelet count.
patient underwent urgent coronary artery bypass surgery
HIT type II is an immune-mediated syndrome caused by
during which intravenous (IV) heparin 30,000 U was ad-
an antibody to the heparin-PF4 complex. It is a disorder ini-
ministered for cardiopulmonary bypass (CPB). Her platelet
tiated by an immunologic response to heparin exposure and is
count prior to surgery was 180,000/␮L.
characterized by an absolute or relative thrombocytopenia that
The patient continued to do poorly after coronary revas-
paradoxically increases the risk of thrombosis, leading to life-
cularization with low cardiac output despite large doses of
threatening complications.
dobutamine and milrinone. The patient underwent place-
An estimated 600,000 new cases of HIT type II occur in the
ment of a biventricular assist device on the next day, during
United States every year with thromboembolic complications
which IV heparin was administered again. There was a pro-
occurring in approximately 300,000 patients and death in
gressive decline in platelet count from 98/␮L prior to the
approximately 90,000 patients. Health care costs from HIT
biventricular assist device placement to 36/␮L 3 days later.
type II complications in cardiac surgery alone are estimated to
be approximately $300 million USD.
What causes thrombocytopenia? What is the pathophysiology of type II HIT?

In general, the etiology of thrombocytopenia includes hemod- The pathogenesis of HIT has been thoroughly reviewed.
ilution from infusion of fluids or blood products, increased The administration of heparin in susceptible patients leads to
platelet destruction, or reduced platelet production by the heparin binding to PF4 on the platelet membrane. The
bone marrow. Increased platelet destruction may result from formation of heparin-PF4 complexes changes the conforma-
nonimmune causes (e.g., sepsis, disseminated intravascular co- tion of PF4 exposing epitopes that allow its recognition and
agulation, or thrombotic thrombocytopenic purpura) or from binding by immunoglobulin G (IgG). The platelets, in turn,
immune causes (e.g., posttransfusion purpura or idiopathic are activated by the Fc domain of the IgG. A positive feed-
thrombocytopenic purpura). Drugs that can lead to immune- back loop is created whereby activated platelets release mi-
mediated thrombocytopenia include heparin, quinine, quini- croparticles that promote thrombin formation, which, in
dine, sulfa drugs, vancomycin, and others. Platelet production turn, fuels further platelet activation. Activated platelets also
by the marrow may be affected by disease conditions (e.g., release PF4, which leads to immune complex production.
aplastic anemia, leukemia, myelodysplasia) or drugs (e.g., cyto- The resultant thrombocytopenia and thrombin generation
toxic agents, alcohol). produces a prothrombotic state, which is exacerbated by
Given the association with heparin use in this case, the di- the antibody-mediated endothelial injury and tissue factor
agnosis of heparin-induced thrombocytopenia (HIT) must be production.
actively excluded. The Iceberg Model of HIT proposed by Warkentin sug-
Heparin therapy was discontinued and replaced with lep- gests that thrombocytopenia and associated thrombosis only
irudin. Laboratory testing for heparin platelet factor 4 (PF4) occurs in a small subset of patients with platelet-activating
complex antibodies was positive for HIT. antiheparin/PF4 antibodies. It has been estimated that about
7% to 50% of heparin-treated patients generate heparin-PF4
HIT antibodies.2 HIT antibodies circulate only temporarily,
What is HIT? with a median half-life of 85 days by antigenic assay. These
HIT is classified into two types. HIT type I is also known as antibodies may be clinically significant because the presence
nonimmune heparin-associated thrombocytopenia. It is the and concentration, regardless of thrombocytopenia, are associ-
more benign of the two forms of HIT characterized by a typ- ated with increased morbidity or mortality in various clinical
44
15259_Ch12.qxd 3/14/09 6:37 PM Page 45
CHAPTER 12 • HEPARIN-INDUCED THROMBOCYTOPENIA 45
settings, such as acute coronary syndromes, hemodialysis, and 2. Arterial thrombosis (15% to 30%)
cardiovascular or orthopedic surgery. a. Limb artery thrombosis
Both unfractionated and low-molecular-weight heparin b. Stroke
can cause type II HIT, but the risk is higher with the former, c. Myocardial infarction
particularly when given intravenously or in high doses. The 3. Skin lesions at heparin injection site (10%)
use of both porcine and bovine can result in type II HIT, but a. Skin necrosis
the risk is higher with the latter. b. Erythematous plaques
High-risk groups for type II HIT include orthopedic pa- 4. Acute reaction after IV bolus of heparin (10%)
tients given postoperative heparin as well as cardiac transplant 5. Disseminated intravascular coagulation (10%)
and neurosurgery patients (11% and 15%, respectively). Other
risk factors for HIT include high-titer, IgG HIT antibodies
How is HIT diagnosed?
and female gender.
HIT should be suspected whenever the platelet count decreases
by 50%, or when new thrombosis occurs 5 to 14 days after the
What are the clinical manifestations start of heparin therapy. Routine platelet count monitoring,
and complications of type II HIT? including a pre-heparin value, is recommended for most he-
Type II HIT has three clinical presentations: (a) latent phase parin-treated patients. For patients with suspected HIT, labora-
in which antibodies are present without thrombocytopenia, tory testing is recommended, but because of its high thrombotic
(b) HIT whereby antibodies are present with thrombocytope- risk, treatment for such patients should not be withheld while
nia, and (c) heparin-induced thrombocytopenia-thrombosis waiting for laboratory results. Clinical scoring systems may be
(HITT) in which antibodies are present with thrombocytope- used to estimate the probability of HIT. An example of such a
nia and thrombosis. scoring system is the “Four Ts” (for timing, thrombocytopenia,
Of the patients who develop latent type II HIT with thrombosis, and oTher sequelae). A score of 0, 1, or 2 is assigned
IgG seroconversion, 30% to 50% will develop thrombocy- depending on the onset time and severity of thrombocytopenia,
topenia. Of these patients, 30% to 80% will demonstrate the presence of thrombotic manifestations, as well as the absence
isolated thrombotic events, of which 0.01% to 0.1% will ex- of other causes of thrombocytopenia. An overall score greater
perience multiple thromboses or white clot syndrome. than 6 is highly suggestive for HIT.
Bleeding is rare despite the severity of the thrombocytopenia. Laboratory testing for HIT antibodies may be divided into
Approximately 10% of patients with HIT and thrombosis antigenic and functional testing. Antigenic tests include
require a limb amputation. The mortality rate is approxi- enzyme-linked immunosorbent assay and rapid particle gel
mately 20% to 30%. immunoassay that detect antibodies to heparin-PF4 complexes
Platelet counts of 20,000 to 150,000/␮L are seen typically or complexes of PF4 and other polyanions. Commercial en-
5 to 10 days after exposure to heparin. A fall in platelet count zyme-linked immunosorbent assay, which detect IgG, IgM,
of more than 50% is considered to be diagnostic. In patients and IgA, are sensitive for detecting antibodies but are not spe-
with elevated baseline platelet counts, a 50% or greater de- cific for HIT. Measurement of only IgG antibodies enhances
crease without falling below a normal platelet level may be clinical specificity, whereas antibody titer based on the optical
observed. The platelet counts usually return to normal levels density can be more informative. Higher-titer antibodies are as-
in 5 to 10 days after heparin is stopped. sociated with increased thrombotic risk. Antibody titers by gel
Rapid-onset HIT leads to reduced platelet counts within particle immunoassay correlate with clinical likelihood scores in
minutes to hours of heparin exposure. This tends to occur in pa- suspected HIT.
tients with preformed heparin-PF4 antibodies from a previous Functional tests include the 14C-serotonin release assay and
heparin exposure within the prior 3 months. The platelet count the platelet aggregation test. The platelet aggregation test
should be determined immediately for comparison with a pre- measures platelet aggregation resulting from IgG in the serum
bolus count. or plasma of an HIT patient given heparin. It has a high spe-
HIT can sometimes present days to weeks after heparin has cificity of 90%, is simple to perform, and is widely available.
been stopped. This scenario, known as delayed-onset HIT, is However, the sensitivity of this test is poor, although this can
less common than the more rapid presentations of HIT but be improved by using washed platelets. The serotonin release
should be considered if a recently hospitalized, heparin- assay measures serotonin released from aggregated platelets
treated patient presents with thrombosis. from HIT. Although this test has high sensitivity and speci-
Up to 50% of patients with isolated HIT (thrombocytope- ficity, it requires the use of radioactive reagents and is techni-
nia with no evidence of thrombosis) develop clinical evidence cally demanding and time consuming to perform.
of thrombosis despite cessation of heparin within the first
week if no alternative anticoagulant is started. Clinical throm- What is the treatment for HIT?
bosis may manifest as:
When HIT is suspected, all forms of heparins should be imme-
1. Venous thrombosis (30% to 70%) diately stopped while awaiting laboratory confirmation of the
a. Deep vein thrombosis diagnosis. Avoid using “flush” solutions containing heparin in-
b. Pulmonary embolism cluding dialysate fluid and central venous or pulmonary
c. Adrenal vein thrombosis, leading to adrenal necrosis catheters with heparin coatings. Low-molecular-weight he-
d. Cerebral sinus venous thrombosis parins should be avoided because of possible cross-reaction with
e. Venous limb gangrene heparin-PF4 antibodies to exacerbate HIT.
15259_Ch12.qxd 3/14/09 6:37 PM Page 46
46 CHAPTER 12 • HEPARIN-INDUCED THROMBOCYTOPENIA
Serial monitoring of platelet counts is mandatory as is that has been used safely and effectively in critically ill pa-
vigilant monitoring for thrombotic manifestations of HIT. tients with HIT. Fondaparinux is a novel anticoagulant that
Prophylactic platelet transfusion is not recommended, as it is modeled after the antithrombin-binding pentasaccharide
may increase the risk of thrombosis. region of heparin. It has anti-Xa and anti-IXa activity that
Heparin should be avoided, if possible, for as long as he- does not cross-react with HIT antibodies. Although it is
parin-PF4 antibody testing is positive, although a longer he- approved in the United States and elsewhere for prophylaxis
parin-free period is often preferred because of the availability and treatment of venous thromboembolism, the usefulness of
of safe, effective alternative anticoagulants and uncertainty re- fondaparinux for the treatment of type II HIT has not been
garding the risk of recurrence on heparin re-exposure. The established.
British Committee for Standards in Hematology recommends The usefulness of antiplatelet agents has not been estab-
the use of nonheparin anticoagulation for most patients lished. Aspirin has only marginal therapeutic benefit because
requiring anticoagulation with previous HIT. of its variable inhibition of platelet activation by HIT anti-
Alternative anticoagulant coverage is used to prevent throm- bodies. Although the prostacyclin analog, iloprost, has been
botic complications. However, warfarin should not be used as used to treat patients with type II HIT undergoing CPB
the initial, sole anticoagulant therapy because of its slow onset of surgery in combination with heparin, its use has been limited
action. In addition, the protein C and protein S deficiency by severe hypotension. The role of ADP inhibitors such as
induced by warfarin can cause microvascular thrombosis result- ticlopidine and clopidogrel in the treatment of HIT has not
ing in coumarin-induced venous limb gangrene. If warfarin has been evaluated.
already been started when HIT is recognized, vitamin K should
be given to reverse the effects of warfarin and to minimize the
risk of warfarin-induced limb gangrene or skin necrosis. An emergency heart transplant was arranged
Warfarin may be introduced at a later stage when platelet levels for this patient. What are the drugs available
have normalized and when overlapping alternative anticoagu- for anticoagulation during cardiac transplant?
lants are at therapeutic levels. Parenteral and oral anticoagulants For patients with current or previous HIT who require
should overlap for at least 5 days, with a therapeutic interna- cardiac surgery, the surgery should be delayed, if possible,
tional normalized ratio achieved for at least 2 days before the until heparin-PF4 antibodies are negative. In patients with
parenteral anticoagulant is stopped. acute HIT undergoing cardiac surgery, direct thrombin inhi-
Given the time course for thrombotic risk in HIT, non- bition is preferred over heparin or danaparoid. Of the direct
heparin anticoagulation should be maintained for at least thrombin inhibitors available, bivalirudin is preferred over
1 month with a longer duration warranted if HIT-associated lepirudin, as the former is least organ dependent for its
thrombosis occurred. Available agents include direct throm- metabolism and is not associated with anaphylaxis from
bin inhibitors such as lepirudin, bivalirudin, or argatroban. lepirudin re-exposure. Appropriate dosing of the direct
Consideration is given to the pharmacokinetic profile and thrombin inhibitors during cardiac surgery has not been
route of elimination of each agent (Table 12.1). There are no established, however, and no direct thrombin inhibitor is
agents currently available to reverse the anticoagulant effects approved for use in this setting.
of direct thrombin inhibitors. The most appropriate method for anticoagulation monitor-
An alternative to the direct thrombin inhibitors is dana- ing during CPB when direct thrombin inhibitors are used is not
paroid, a glycosaminoglycan derived from porcine intestine clear. The activated clotting time is affected by many variables
T A B L E 1 2 . 1 Drugs for Nonheparin Anticoagulation
Lepirudin Argatroban Bivalirudin Danaparoid Fondaparinux

Drug type DTI DTI DTI Heparinoid FXa inhibitor
Clearance Renal Hepatic Renal, Enzymic Renal Renal
Half-life 80 min 40 min 36 min 7h 15 h
Cross-reactivity No No No Minimal Negligible
with HIT
antibodies
Monitoring ECT or aPTT ACT or aPTT ACT or aPTT Anti-FXa Not required
Target aPTT 1.5–2.5 baseline 1.5–3 baseline 1.5–2.5 baseline NA NA
Effect on INR Yes Yes Yes No No
Approved in HIT Yes Yes Yes (for PCI) Yes (no in USA) No
ACT, activated clotting time; aPTT, activated partial thromboplastin time; DTI, direct thrombin inhibitors; ECT, ecarin clotting time; INR, international
normalized ratio; NA, not applicable; PCI, percutaneous coronary intervention.
15259_Ch12.qxd 3/14/09 6:37 PM Page 47
CHAPTER 12 • HEPARIN-INDUCED THROMBOCYTOPENIA 47
in addition to thrombin inhibition, including hemodilution, QUESTIONS

thrombocytopenia, and hypothermia. The activated clotting
time, thus, is a poor monitor of thrombin inhibition or the ef- 1. How is HIT classified?
fectiveness of anticoagulation. Thromboelastography has been
used to monitor both clot initiation and clot strength during Answer: HIT is classified into two types. Type I HIT,
cardiac surgery with direct thrombin inhibition. The ecarin also known as nonimmune heparin-associated thrombocytope-
clotting time has been used for monitoring lepirudin and bi- nia is caused by platelet microaggregation and subsequent
valirudin during cardiac surgery, but this is not a commer- sequestration in the spleen. Type II HIT is an immune-
cially available test in the United States. mediated syndrome caused by an antibody to the heparin-
Cardiotomy suction blood should be processed in a cell PF4 complex.
saver that uses citrate and not heparin for anticoagulation. 2. What are the clinical manifestations and complications
Care must be taken to administer additional bivalirudin into of type II HIT?
the CPB reservoir after separation from bypass to ensure anti-
Answer: Type II HIT has three clinical presentations:
coagulation while the blood is recirculated.
(a) latent phase in which antibodies are present without
thrombocytopenia, (b) HIT whereby antibodies are present
with thrombocytopenia, and (c) HITT in which antibodies
are present with thrombocytopenia and thrombosis.
KEY MESSAGES
3. How is HIT antibody detected?
1. An estimated 600,000 new cases of type II HIT Answer: Laboratory testing for HIT antibody is classified
occur in the United States every year with thromboem- as antigenic or functional testing. Antigenic tests include
bolic complications occurring in approximately enzyme-linked immunosorbent assay and rapid particle
300,000 patients, and death in approximately gel immunoassay that detect antibodies to heparin-PF4
90,000 patients. complexes or complexes of PF4 and other polyanions.
2. The administration of heparin in susceptible patients
Functional tests include the 14C-serotonin release assay
leads to heparin binding to PF4 on the platelet mem-
and the platelet aggregation test.
brane. The formation of heparin-PF4 complexes
changes the conformation of PF4 exposing epitopes References
that allow its recognition and binding by IgG. 1. Keeling D, Davidson S, Watson S, the Haemostasis and
Thrombosis Task Force of the British Committee for Standards
3. Type II HIT has three clinical presentations: (a) latent in Haematology (2006). The management of heparin-induced
phase in which antibodies are present without throm- thrombocytopenia. Br J Haematol 2007;133:259–269.
bocytopenia, (b) HIT whereby antibodies are present 2. Warkentin TE. Heparin-induced thrombocytopenia. Hematol
with thrombocytopenia, and (c) HITT in which anti- Oncol Clin North Am 2007;21:589–607.
bodies are present with thrombocytopenia and 3. Levy JH, Tanaka KA, Hursting MJ. Reducing thrombotic com-
thrombosis. plications in the perioperative setting: an update on heparin-
induced thrombocytopenia. Anesth Analg 2007;105:570–582.
4. When alternative anticoagulant coverage is used to 4. Keeling D, Davidson S, Watson H. The management of heparin-
prevent thrombotic complications, warfarin should not induced thrombocytopenia. Br J Haematol 2006;133:259–269.
be administered as the initial, sole anticoagulant ther- 5. Warkentin TE, Greinacher A. Heparin-induced thrombocy-
apy because of its slow onset of action. topenia: recognition, treatment, and prevention. Chest 2004;126:
S311–S337.
15259_Ch13.qxd 3/14/09 6:38 PM Page 48
CHAPTER 13
Hypertonic Saline Resuscitation
David M. Rothenberg
only in terms of targeted hemodynamic end points but also in

terms of quantity and nature of fluid administration. Given
that the extracellular space is four to five times larger than the
A 33-year-old male presented to the emergency department
plasma volume, large volume, isotonic crystalloid resuscitation
having sustained a closed head injury and blunt abdominal
is often required for trauma or burn patients to re-establish
trauma following a motor vehicle collision. He had suffered
circulatory stability. Trauma, burns, or major surgery lead in-
loss of consciousness at the scene but was now awake
variably to an obligatory loss of fluid into the intracellular or
and complaining of neck and abdominal pain. His past
so-called third space compartment and an increase in the ratio
medical and surgical histories were unremarkable. He was
of extracellular to plasma volume. Progressive brain swelling,
taking no medications and had no known allergies. He de-
increases in lung water, intra-abdominal hypertension, as well
nied alcohol, tobacco, or drug use. The patient’s vital signs
as immunologic and microcirculatory dysfunction can de-
were as follows: blood pressure, 90/60 mm Hg; heart rate,
velop. The use of low-volume, hypertonic solutions may de-
110 beats per minute; respiratory rate, 24 breaths per
crease the risk of these adverse events by restoring circulation
minute; and his temperature was 36.5°C.
and decreasing third space fluid sequestration, while prevent-
On physical examination, the patient was oriented to
ing or minimizing the incidence of cerebral and pulmonary
person only, and a left sixth cranial nerve palsy was demon-
edema and abdominal compartment syndrome.
strated. Posterior neck tenderness was elicited, the lungs
were clear to auscultation, his abdomen was distended, Traumatic Brain Injury
rebound tenderness was present, and bowel sounds were
diminished.
Cerebral edema and intracranial hypertension often develop
Following administration of 3 liters of normal saline
from traumatic brain injury (TBI) and are associated with
(at the scene and in the emergency department), labora-
poor outcome. Osmotherapy with mannitol remains the most
tory results were as follows: hemoglobin, 9.6 gm dL⫺1;
widely recommended mode of treatment. However, experi-
white blood cell count, 13,000/mm3; Na⫹, 145 mEq/L;
mental data indicate that hypertonic saline (HTS) (3%, 7.5%,
K⫹, 3.6 mEq/L; HCO3⫺, 18 mEq/L; Cl⫺, 110 mEq/L; cre-
23.4%) can be as effective in reducing intracranial pressure
atinine, 1.4 mg%; and blood urea nitrogen, 31 mg%.
and may have a longer duration of action. Prospective, ran-
Abdominal paracentesis was positive for blood. A chest ra-
domized human trials assessing the use of HTS in patients
diograph revealed possible free air under the diaphragm.
with TBI, however, are limited. Vailet et al. evaluated 7.5%
The patient’s computerized tomography (CT) scan of the
HTS versus mannitol in 20 patients with TBI and intracranial
head and neck demonstrated bilateral frontal lobe contu-
hypertension refractory to conventional therapy and found
sions with a moderate-sized right frontal parietal subdural
HTS to be more effective.1 Cooper et al. compared a prehos-
hematoma (Fig. 13.1) but a normal cervical spine. A per-
pital bolus of 250 mL of 7.5% HTS versus Lactated Ringer’s
forated cecum was seen on abdominal CT.
solution in victims of traumatic brain injury.2 Although there
The patient underwent exploratory laparotomy,
were no outcome differences between groups, patients in the
drainage of the subdural hematoma, and insertion of an ex-
HTS group had a prolonged period of sustained elevation in
ternal ventricular drain and intracranial pressure monitor.
cerebral perfusion pressure, consistent with the aforemen-
He received a total of 6 liters of intravenous normal saline,
tioned experimental studies. Although experimental and clin-
500 mL of human albumin, and 2 units of packed red blood
ical data validate the effectiveness of HTS in reducing ICP,
cells. Forty-eight hours later, he remained comatose, and the
data proving improved outcomes are lacking.3 A significant
CT scan of his head revealed diffuse cerebral edema. On
confounding variable is that the majority of patients studied
the third postoperative day, he developed oliguria and was
also suffered from polytrauma, thus making it more difficult
noted to have intra-abdominal pressures of 35 mm Hg.
to differentiate the etiologies of morbidity and mortality.
Acute Lung Injury/Adult Respiratory
Syndrome/Immunomodulation
CASE DISCUSSION Acute lung injury and adult respiratory distress syndrome occur
in as many as 40% of patients suffering from polytraumatic in-
Intravascular volume resuscitation in the setting of traumatic juries. A cascade of inflammatory mediators released following
head injury, polytrauma, and severe burns is controversial not the sequestration of activated polymorphonuclear neutrophils
48
15259_Ch13.qxd 3/14/09 6:38 PM Page 49
CHAPTER 13 • HYPERTONIC SALINE RESUSCITATION 49
decrease cardiac output by diminishing preload and increasing

systemic vascular resistance. Unintended intra-abdominal hy-
pertension can also impair respiratory, renal, gastrointestinal,
and hepatic function and lead to multiorgan system failure.
Aggressive crystalloid fluid resuscitation in an attempt to
counter these pathophysiologic changes often contributes to
the development of abdominal compartment syndrome and
has been termed “futile crystalloid preloading.” Some studies
have suggested that more than 6 liters of crystalloid fluids
within the first 24 hours of resuscitation of critically ill patients
may result in a higher incidence of abdominal compartment
Figure 13.1 • A right-sided frontoparietal subdural hematoma syndrome and multiorgan system failure.6 In this regard, it
with ventricular compression and evidence of increased intracra- has been suggested that the use of HTS may be advantageous
nial pressure. in minimizing intra-abdominal hypertension. Oda et al. com-
pared the administration of hypertonic lactated saline versus
standard Lactated Ringer’s solution in patients who sustained
within the microcirculation of the lung is purported to be an burn injuries of greater than 40% of their body surface areas
important mechanism by which secondary injury occurs in the and found a significant decrease in the incidence of intra-
setting of trauma and hemorrhagic shock. Experimental studies abdominal hypertension and secondary abdominal compart-
have shown HTS-mediated immunomodulation, which sug- ment syndrome.7 Improvements in oxygenation were also
gests a role in mitigating the inflammatory process. Junger and noted. Despite these preliminary findings, further random-
colleagues found HTS (7.5% sodium chloride, 4 mL/kg) en- ized controlled studies are necessary before definitive recom-
hanced T-cell function in vitro and cell-mediated immune mendations can be made regarding the use of HTS to prevent
function in vivo in a murine model of hemorrhagic shock.4 secondary abdominal compartment syndrome.
HTS also protected animals by improving survival from sepsis.
Rizoli et al. noted a beneficial effect of HTS (4 mL/kg of Types and Methods of Hypertonic
7.5% sodium chloride) in significantly reduced transpulmonary Saline Administration
albumin leak, bronchioalveolar lavage fluid neutrophil counts, HTS tends to mobilize intracellular water, reduced cellular
and the degree of histopathologic lung injury, when compared edema, and reduced overall volume requirements during re-
to Lactated Ringer’s solution resuscitation in a rodent model of suscitation. Plasma volume is expanded, cardiac output is in-
hemorrhagic shock.5 creased, and overall oxygen delivery is improved all relatively
rapidly when compared with isotonic saline resuscitation. The
Secondary Abdominal Compartment most often used formulation of hypertonic solution is a combi-
Syndrome nation of 7.5% sodium chloride (2400 mOsm/L saline) and
Abdominal compartment syndrome is defined as the presence 6% dextran 70, a colloid solution that exerts two to three times
of sustained intra-abdominal pressure elevation ⱖ20 mm Hg the colloid osmotic pressure of an equal concentration of
with or without abdominal perfusion pressure ⬍50 mm Hg human albumin. An infusion of 4 to 6 mL/kg over several
and associated with new-onset single or multiorgan system hours appears to be safe and effective. Bolus doses of 250 mL of
failure. Abdominal compartment syndrome can occur as a re- 7.5% sodium chloride over 10 to 15 minutes also appear to be
sult of primary abdominal trauma or surgery or secondary to well tolerated in clinical studies.8 Table 13.1 details the charac-
massive fluid resuscitation-induced visceral edema in non- teristics of the most commonly administered HTS solutions.
trauma or burn patients, particularly in the setting of shock.
The gut is prone to ischemia-reperfusion injury, and the sub- Complications of HTS Administration
sequent increase in microvascular permeability leads to large HTS resuscitation can be associated with hyperosmolarity
quantities of free intraperitoneal fluid and subsequent intra- and hypernatremia. Serum osmolarity levels greater than
abdominal hypertension. Intra-abdominal hypertension and 320 mOsm/L have been associated with acute renal failure
secondary abdominal compartment syndrome significantly during the use of mannitol; data are lacking regarding HTS
T A B L E 1 3 . 1 HTS Characteristics
HTS (%) Na1/Clⴚ (mEq/L) Osmolality (mOsm/L) Maximum Infusion Rate

3 513 1030 100 mL/hr
5 855 1710 100 mL/hr
7.5 1282 2400 250 mL (bolus)
23.4 4000 8000 NA
HTS, hypertonic saline solution.
15259_Ch13.qxd 3/14/09 6:38 PM Page 50
50 CHAPTER 13 • HYPERTONIC SALINE RESUSCITATION
and these complications. Central pontine myelinolysis is a C. Urine output

complication of the rapid correction of extracellular serum D. Cardiac output
sodium levels in the setting of hypotonic hyponatremia.
Retrospective studies, however, have failed to demonstrate E. Gastric pH
central pontine myelinolysis either by magnetic resonance Answer: A
imaging or at postmortem examination. Other concerns with
HTS administration include rebound intracranial hyperten- 3. Which of the following serum electrolyte abnormalities
sion and hyperchloremic metabolic acidosis.9 is more likely to occur when large volume fluid resusci-
In conclusion, the use of HTS may offer a novel approach tation is performed with Lactated Ringer’s solution
in caring for patients with traumatic brain injury, polytrauma, rather than with small volume hypertonic saline?
or burn injuries; however, its use must be tempered by the lack A. Hypomagnesemia
of clinically relevant outcome data. Current randomized, B. Hypocalcemia
controlled trials may offer further insight into this type of
C. Hypokalemia
therapy.10
D. Hyponatremia
E. Hypochloremia
KEY MESSAGES Answer: D
1. HTS can be of benefit in the management of traumatic

brain injury by decreasing intracranial pressure. References
1. Vialet R, Albanese J, Thomachot L, et al. Isovolume hypertonic
2. Massive crystalloid resuscitation may result in a sec- solutes (sodium chloride or mannitol) in the treatment of refrac-
ondary abdominal compartment syndrome that can be tory posttraumatic intracranial hypertension: 2 mL/kg 7.5%
mitigated by the use of HTS solutions. saline is more effective than 2 mL/kg 20% mannitol. Crit Care
Med 2003;31:1683–1687.
3. Complications of HTS administration may include hy-
2. Cooper DJ, Myles PS, McDermott FT, et al. Prehospital hyper-
perchloremic metabolic acidosis, hyperosmolarity, and tonic saline resuscitation of patients with hypotension and severe
rebound intracranial hypertension. traumatic brain injury: a randomized controlled trial. JAMA
2004;291:1350–1357.
3. White H, Cook D, Venkatesh B. The use of hypertonic saline for
treating intracranial hypertension after traumatic brain injury.
QUESTIONS Anesth Anal 2006;102:1836–1846.
4. Junger WG, Coimbra R, Liu FC, et al. Hypertonic saline resus-
1. Hypertonic saline resuscitation for a patient with trau- citation: a tool to modulate immune function in trauma patients?
matic brain injury may result in which of the following Shock 1997;8:235–241.
5. Rizoli SB, Kapus A, Fan J, et al. Immunomodulatory effects of
complications?
hypertonic resuscitation on the development of lung inflamma-
A. Central pontine myelinolysis tion following hemorrhagic shock. J Immunol 1998;161:
B. Cerebral edema 6288–6296.
6. Kirkpatrick AW, Balogh Z, Ball CG, et al. The secondary ab-
C. Cerebral artery vasospasm dominal compartment syndrome: iatrogenic or unavoidable? J
D. Rebound intracranial hypertension Am Coll Surg 2006;202:668–679.
7. Oda J, Ueyama M, Yamashita K, et al. Hypertonic lactated saline
E. Diabetes insipidus resuscitation reduces the risk of abdominal compartment syn-
Answer: D drome in severely burned patients. J Trauma 2006;60:64–71.
8. Kramer GC. Hypertonic resuscitation: physiologic mechanisms
2. A 33-year-old male receives hypertonic saline resusci- and recommendations for trauma care. J Trauma 2003;54:
tation following a 50% body surface area thermal in- S89–S99.
jury. Which of the following physiologic parameters 9. Bunn F, Roberts I, Tasker R. Hypertonic versus isotonic crystal-
may be expected to decrease when compared to stan- loid for fluid resuscitation in critically ill patients. Cochrane
dard therapy with isotonic crystalloid solutions? Database Syst Rev 2008.
10. Brasel KJ, Bulger E, Cook AJ, et al. Hypertonic resuscitation: de-
A. Intra-abdominal pressure sign and implementation of a prehospital intervention trial. J Am
B. PaO2/fiO2 ratio Coll Surg 2008;206:222–232.
15259_Ch14.qxd 3/14/09 6:39 PM Page 51
CHAPTER 14
Preoperative Liver Function Test

Abnormalities
David M. Rothenberg
phosphatase are present in a small proportion of the general

population1 and in as many as 36% of patients with psychiatric
illnesses (in whom alcohol and illicit drug use may be a contrib-
A 39-year-old, 6-ft, 80-kg man presented for repair of his left
utory factor).2 The overall prevalence of clinically significant
anterior cruciate ligament following a skiing injury. The pa-
liver dysfunction in asymptomatic patients, however, is less
tient’s past medical history was significant only for hyperten-
than 1%.3 Therefore, the decision to pursue further costly diag-
sion treated with hydrochlorothiazide. His past surgical his-
nostic workup is rarely indicated on the basis of laboratory re-
tory included a right inguinal hernia repair performed under
sults alone. Rather, the most logical approach to such a patient
inhalational general anesthesia 1 year prior to this admis-
begins with a targeted history and physical examination elicit-
sion. His social history included occasional alcohol use but
ing signs and symptoms of active hepatobiliary disease. This in-
no history of recreational drug use. The patient’s vital signs
cludes findings such as right upper quadrant pain or tenderness
were as follows: blood pressure, 140/90 mm Hg; heart
and history of scleral icterus, pruritus, fatigue, anorexia, nau-
rate, 88 beats per minute; respiratory rate, 12 breaths per
sea, or vomiting. Stigmata of cirrhosis are often self-evident;
minute; and his temperature was normal. The remainder of
however, the patient should also be queried regarding a history
his physical examination was unremarkable.
consistent with chronic hepatitis, Wilson’s disease, hemochro-
The orthopaedic surgeon had ordered an array of lab-
matosis, diabetes, as well as a history of previous blood product
oratory tests including complete blood count, coagulation
transfusion. All medications, vitamins, and herbal remedies
profile, serum electrolytes, and liver function tests (LFTs). The
should be reviewed for potential hepatotoxic adverse effects,
results of the laboratory tests were within normal limits with
and the patient should be further questioned regarding the fre-
the exception of serum aspartate aminotransferase (AST), 65
quency and pattern of alcohol usage. Finally, a targeted history
IU/L (normal range, 10–34 IU/L) and alanine aminotrans-
should also make reference to include illicit drug use, presence
ferase (ALT), 55 IU/L (normal range, 8–37 IU/L). Total biliru-
of tattoos, consumption of raw seafood, and sexual activity. If a
bin and alkaline phosphatase levels were within normal lim-
detailed history and physical examination fail to suggest an eti-
its as was the internationalized normalized ratio (INR).
ology of the abnormal LFTs, it is reasonable to assume that the
At the outpatient surgery center, the anesthesiologist
initial abnormalities were false positives and the tests should be
was reluctant to perform an anesthetic because of the ele-
repeated. Slight elevation in LFTs (less than twice normal
vation in LFTs and recommended further workup of the pa-
values) do not warrant further testing before anesthesia or/and
tient’s abnormal transaminase results.
surgery. Greater elevation in LFTs requires a more detailed
analysis of each specific abnormality. Abnormal LFTs in oth-
erwise healthy patients can also reflect either a subclinical acute
DISCUSSION process, such as viral or toxin-mediated hepatitis or a chronic
disorder such as chronic hepatitis.
Patients with asymptomatic elevation in preoperative LFTs Abnormalities of ALT and AST in combination tend to
pose a dilemma for anesthesiologists in assessing perioperative indicate hepatocellular injury.4,5 An elevation in ALT greater
hepatic risk, as prospective studies addressing this concern are than AST favors a diagnosis of viral hepatitis; an increase in
lacking. The preoperative evaluation of risk for the develop- AST greater than ALT tends to suggest alcohol-mediated
ment of postoperative hepatic dysfunction requires not only hepatic injury. Increases in alkaline phosphatase and serum ␥-
consideration of the magnitude of LFT abnormalities and glutamyltransferase indicate hepatobiliary disease, specifically
whether or not active inflammatory or cholestatic disease exists, extrahepatic bile duct obstruction or intrahepatic cholestasis.
but also the nature of the surgical procedure planned. Further assessment of LFT abnormalities should include assess-
The first question that must be asked regarding patients ment of synthetic function. These tests entail measurement of
with asymptomatic elevation in LFTs is why the tests were ini- serum bilirubin, albumin, and prothrombin time (as expressed
tially ordered. Indiscriminate laboratory testing that reveals an by the INR); the latter being a sensitive index of hepatic synthetic
increase in LFTs in an otherwise asymptomatic patient often function, often changing within 24 hours of hepatobiliary injury
leads to a delay in surgery based on the concern that adminis- because of impaired synthesis of essential coagulation factors.
tering an anesthetic may predispose the patient to postoperative At this time, no prospective, randomized controlled trials
hepatic dysfunction and subsequent morbidity or mortality. have been performed to evaluate the perioperative risk of
Abnormalities in LFTs including ALT, AST, and alkaline anesthesia or surgery in otherwise asymptomatic patients with
51
15259_Ch14.qxd 3/14/09 6:39 PM Page 52
52 CHAPTER 14 • PREOPERATIVE LIVER FUNCTION TEST ABNORMALITIES
ALT/ AST
< 2x Normal > 2x Normal
Hx – (R/O drug/ETOH use)
normal: >2x NL Repeat Test < 2x NL proceed with

alkaline phosphatase surgery
bilirubin
prothrombin Verify ratio
ALT>AST Viral
hepatitis delay surgery
screening for formal
assessment
AST>ALT Assess for (e.g. ultrasound,
proceed with surgery ETOH & abuse computed assisted
tomography, liver
biopsy)
ALT/ AST and abnormal INR hepatobiliary dysfunction delay surgery for
formal assessment
Alkaline Phosphatase
< 2x Normal >2x Normal

Abnormal GGT/Bilirubin
Repeat Test biliary disease
Assess GGT – normal proceed delay surgery for

bilirubin - normal with formal assessment
surgery
Figure 14.1 • Asymptomatic Patient with Abnormal Liver Test Results for Surgery. (From O’Connor CJ,
Rothenberg D, Tumank KJ. Anesthesia and the hepatobiliary system. In Miller’s Anesthesia, 6th Ed. New York: Elsevier, 2005.)
elevated LFTs. A suggested approach to such patients is delin- surgery in cirrhotic patients with an elevated INR, hypoalbu-
eated in Figure 14.1. minemia, or preoperative infection or encephalopathy.
The preponderance of medical literature regarding periop- The actual surgical procedure itself, however, may be the
erative morbidity and mortality in patients with acute hepati- most important risk factor for the development of postopera-
tis of any etiology suggests that elective surgery should be tive hepatic dysfunction.6 Abdominal surgery per se appears to
delayed until resolution of hepatic dysfunction. Patients with significantly decrease total hepatic blood flow, particularly in
steatosis or steatohepatitis should also probably be considered patients with cirrhosis undergoing hepatic resection for hepa-
to be at risk for developing postoperative liver failure, espe- tocellular carcinoma.7,8 Cardiothoracic surgery is also associ-
cially if they are to undergo major abdominal surgery. ated with a high mortality rate in patients with pre-existing
Additionally, patients with chronic hepatitis should be evalu- liver dysfunction.9 Cardiopulmonary bypass may exacerbate
ated before elective surgery for any evidence of hepatic syn- pre-existing hepatic dysfunction by a multitude of mechanisms,
thetic dysfunction. When surgery cannot be delayed or including hepatic artery and portal venous hypoperfusion, low
avoided, care must be taken during all phases of surgery to cardiac output syndrome, micro- or macroembolism, cytokine
maintain hepatic vascular perfusion and to avoid factors that or oxygen free radical formation, and the influence of vasoac-
may precipitate liver failure, hepatic encephalopathy, or both. tive and anesthetic drugs.
Finally, patients with abnormal LFTs and a clinical con- In assessing the patient described in this case, it is important
stellation that is consistent with cirrhosis may be at particular to recognize that the peripheral nature of anterior cruciate liga-
risk for developing postoperative hepatic failure depending on ment surgery imparts a minimal risk for this patient to develop
the stage of cirrhosis as well as the type of surgery. postoperative liver failure, despite the slight elevation in this pa-
Preoperative risk in patients with cirrhosis is often assessed by tient’s LFTs. The magnitude of LFT elevation also indicates
using the Child-Turcotte-Pugh scoring system (Table 14.1) minimal risk of developing postoperative liver dysfunction and
and occasionally in conjunction with the model for end-stage most likely represents either an effect of alcohol use or, less
liver disease scores (Table 14.2). Elective surgery should be likely, that this is related to a cholestatic effect of hydrochloroth-
considered contraindicated in patients with Child-Turcotte- iazide. Repeating the LFTs is indicated primarily to rule out
Pugh classification C. Additionally, it is best to avoid elective further increases indicative of ongoing or progressive pathology.
15259_Ch14.qxd 3/14/09 6:39 PM Page 53
CHAPTER 14 • PREOPERATIVE LIVER FUNCTION TEST ABNORMALITIES 53
T A B L E 1 4 . 1 Modified Child-Turcotte-Pugh Scoring System
Modified Child-Turcotte-Pugh Score*

Parameters 1 2 3
Albumin (g/dL) ⬎3.5 1.8–3.5 ⬍2.8
Prothrombin time
Seconds prolonged ⬍4 4–6 ⬎6
International normalized ratio ⬍1.7 1.7–2.3 ⬎2.3
Bilirubin (mg/dL)† ⬍2 2–3 ⬎3
Ascites Absent Slight–moderate Tense
Encephalopathy None Grade I–II Grade III–IV
*Class A, ⫽ 5 to 6 points; B, ⫽ 7 to 9 points; and C, ⫽ 10 to 15 points.
†For cholestatic diseases (e.g., primarily biliary cirrhosis), the bilirubin level is disproportionate to the impairment in hepatic function, and an allowance
should be made. For these conditions, assign 1 point for a bilirubin level less than 4 mg/dL, 2 points for a bilirubin level of 4 to 10 mg/dL, and 3 points for
a bilirubin level greater than 10 mg/dL. Reproduced with permission from Pugh RNH, Murray-Lyon IM, Dawson JL, et al. Transection of oesophagus for
bleeding of oesophageal varices. Br J Surg 1973;60:646–649.
KEY MESSAGES QUESTIONS
1. Asymptomatic elevation in LFTs may or may not pose 1. Which of the following serum levels may be associated
a significant perioperative risk for the patient undergo- with increased perioperative morbidity?
ing anesthesia. A. ALT 55 IU/L
2. Specific LFT abnormalities can indicate the influence of B. Bilirubin 3.6 mg%
preoperative medications, alcohol use, or active in- C. INR 1.6
flammatory disease. D. AST 90 IU/L
3. Preoperative LFTs should only be considered on pa- E. Alkaline phosphatase 42 mg%
tients who present with a history or physical evidence Answer: D
of hepatic dysfunction.
4. The decision to perform surgery and administer anes-
2. A patient presenting for total hip replacement is noted
thesia to patients with abnormal LFTs should be predi-
to have clinical stigmata of cirrhosis including mild
cated on the nature of the surgery and the magnitude
ascites. Preoperative laboratory values include a serum
of changes on the LFTs.
albumin level of 2.7 gm%, INR of 2.8, and a serum
bilirubin level of 4 mg%. The most appropriate next
step in this patient’s care should be:
A. Therapeutic paracentesis
B. Preoperative plasma transfusion
T A B L E 1 4 . 2 MELD Score Calculation C. Delay of surgery
D. Administration of 5% albumin
MELD ⫽ 3.78 [Ln serum bilirubin (mg/dL)] ⫹
E. Avoidance of inhalational general anesthesia
11.2 [Ln INR] ⫹ 9.57 [Ln serum creatinine
(mg/dL)] ⫹ 6.43 Answer: C
In addition, the following are modifications of the 3. Which of the following surgeries is associated with an
MELD score: increase in postoperative hepatic dysfunction in a
• The maximum score given is 40. All values higher patient with a preoperative history of chronic active
hepatitis?
than 40 are given a score of 40.
A. Pneumonectomy
• If the patient has been dialyzed twice within the last
7 days, the serum creatinine level used should be 4. B. Partial colectomy
C. Bilateral total knee replacement
• Any value less than 1 is given a value of 1.
D. Carotid endarterectomy
INR, internationalized normalized ratio; MELD, end-stage liver
disease. E. Total thyroidectomy
Answer: B
15259_Ch14.qxd 3/14/09 6:39 PM Page 54
54 CHAPTER 14 • PREOPERATIVE LIVER FUNCTION TEST ABNORMALITIES
References moderate degree in asymptomatic patients. Hepatology

1989;9:193–197.
1. Kamath PS. Clinical approach to the patient with abnormal liver
test results. Mayo Clin Proc 1996;71:1089–1095. 6. Friedman LS. The risk of surgery in patients with liver disease.
2. Farrell RL, DeColli JA, Chappelka AR. Significance of abnor- Hepatology 1999;29:1617–1623.
mal liver function studies in psychiatric admissions to military 7. Mansour A, Watson W, Shayani V, Pickelman J. Abdominal op-
hospitals. Mil Med 1975;140:101–103. erations in patients with cirrhosis: still a major surgical challenge.
3. Pratt DS, Kaplan MM. Primary care: evaluation of abnormal Surgery 1997;22:730–736.
liver-enzyme results in asymptomatic patients. N Engl J Med 8. Ziser A, Plevak DJ, Wiesner RH, et al. Morbidity and mortality
342:2000;1266–1271. in cirrhotic patients undergoing anesthesia and surgery.
4. Cohn JA, Kaplan MM. The SGOT/SGPT ratio—an indicator of Anesthesiology 1999;90:42–53.
alcoholic liver disease. Dig Dis Sci 1979;24:835–838. 9. Filsoufi F, Slazberg SP, Rahmanian PB, et al. Early and late out-
5. Hay JE, Czaja AJ, Rakela J, Ludwig J. The nature of un- comes of cardiac surgery in patients with liver cirrhosis. Liver
explained chronic aminotransferase elevations of a mild to Transpl 2007;13:990–995.
15259_Ch15.qxd 3/14/09 6:40 PM Page 55
CHAPTER 15
Perioperative Use of Albumin
W. Christopher Croley
CASE FORMAT: REFLECTION home on the seventh postoperative day. On discharge

from the hospital, his hemoglobin level was 9 gm/dL, and
A 68-year-old, 60-kg male with a history of hypertension, his creatinine and other laboratory measures were at their
hypercholesterolemia, and non–insulin-dependent diabetes baseline values.
presented for a left hemicolectomy. The patient was cur-
rently taking metoprolol, metformin, and simvastatin. He
completed a bowel preparation consisting of clear liquids,
a Fleet enema, and 4 liters of GoLYTELY on the day before
his procedure. The patient reported a recent history of nau- CASE DISCUSSION
sea, vomiting, fatigue, and a 5-kg weight loss. His preoper-
ative assessment revealed the following normal vital signs: The debate on crystalloid versus colloid fluid resuscitation
blood glucose, 108 mg/dL and hemoglobin, 13 gm/dL. continues to elicit strong opinions from clinicians who are
Electrocardiogram readings showed normal sinus rhythm forced to deal with volume resuscitation of patients on a daily
with possible left ventricular hypertrophy. On physical ex- basis. Although human albumin has been used for more than
amination, the patient had clear lung fields, normal heart 60 years, semi-synthetic colloid fluids have only been intro-
sounds, a Mallampati I airway, and was edentulous. duced relatively recently. Albumin and semi-synthetic solu-
Preoperatively, the patient had two 16-gauge intra- tions are available in various concentrations. Although human
venous (IV) cannulae and a right radial arterial line in- albumin has been used for many years, there are insufficient
serted. Once inside the operating suite, standard monitors data from large clinical trials to demonstrate improvement in
were applied and general anesthesia was induced with morbidity or mortality rates when using human albumin as a
180 mg of sodium thiopental, 250 ␮g of fentanyl, and resuscitation fluid.
muscle relaxation was achieved with vecuronium 6 mg. Human albumin preparations contain more than 95% albu-
The patient’s trachea was easily intubated with a 7.5-mm min with a uniform molecular size (Table 15.1). The capillary
endotracheal tube. Anesthesia was maintained with fen- membrane is fairly permeable to small ions (i.e., Na⫹ and Cl⫺)
tanyl (3 ␮g/kg per hour), sevoflurane (inspired but is relatively impermeable to larger molecules such as albu-
1%–1.5%), and further increments of vecuronium were admin. Therefore, it is postulated that colloids will remain in the
ministered as required. After induction of anesthesia, a intravascular space for a longer period of time than crystal-
right internal jugular triple-lumen catheter was inserted loids. The duration that a colloid will affect plasma volume ex-
under ultrasound guidance for central venous pressure pansion is a function of the rate of colloid molecule loss from
(CVP) monitoring. His initial CVP was 2 mm Hg. His vital the circulation and by metabolism. Proponents of colloid fluid
signs remained stable throughout the procedure with resuscitation argue that the increased duration of plasma vol-
mean arterial blood pressures (MAPs) between 60 to ume expansion and decreased leaking of colloid molecules
75 mm Hg and CVP values ranging from 1 to 15 mm Hg. from the capillary membrane ultimately lead to less tissue
Estimated blood loss for the 4-hour procedure was 900 edema, which may (in theory at least) benefit patient outcome.
mL. The patient received 4000 mL of Lactated Ringer’s so- Human albumin has several disadvantages not associated
lution and 750 mL of 5% human albumin. His trachea was with synthetic colloid products because it is a human-derived
extubated at the end of the procedure, and he was trans- product (Table 15.2). Some of these disadvantages include
ferred to the surgical intensive care unit for further moni- expense, risk of transmission of infectious agents, and possible
toring. On arrival to the surgical intensive care unit, his allergic reactions.
vital signs were as follows: heart rate, 105 beats per The Saline versus Albumin Fluid Evaluation trial is a ran-
minute; blood pressure, 85/40 mm Hg with a MAP of domized controlled trial of approximately 7000 patients that
55 mm Hg; respiratory rate, 24 breaths per minute; and compared albumin and saline as resuscitation fluids and
CVP, 2 mm Hg. He received an additional 500 mL of 5% showed no difference in outcome between the two groups. This
human albumin, which increased his CVP to 10 mm Hg landmark trial is consistent with results of several other trials
and MAP to 70 mm Hg. The patient was monitored in the that have evaluated colloid versus crystalloid for fluid resuscita-
surgical intensive care unit for 1 day and was then trans- tion and failed to demonstrate a significant mortality benefit.
ferred to the general surgical floor. He was discharged Despite a lack of evidence demonstrating a clear benefit of
colloid over crystalloid, some clinicians continue to use albumin
55
15259_Ch15.qxd 3/14/09 6:40 PM Page 56
56 CHAPTER 15 • PERIOPERATIVE USE OF ALBUMIN
T A B L E 1 5 . 1 Composition of Commonly Used Crystalloid Fluids
Solution Osmolarity (mOsm/L) Na⫹ (mmol/L) Cl⫺ (mmol/L) K⫹ (mmol/L) Ca⫹⫹ (mmol/L)
0.9% Sodium chloride 308 154 154 -0- -0-
Lactated Ringer’s solution 309 147 156 4.0 2.2
Normasol 280 140 98 5 0
as a preferred resuscitation fluid. It is proposed that large vol- and has a weak radial pulse. The patient has one
umes of crystalloid dilute plasma proteins, as well as plasma on- 22-gauge IV in her left forearm, and four units of blood
cotic pressure, resulting in tissue and pulmonary edema. are on hold in the blood bank. The most appropriate
Clinically, the decrease in oncotic pressure and increase in tissue initial fluid given the following options would be:
edema has not been proven to be detrimental in terms of patient
mortality (Fig. 15.1). A. 250 mL of 0.9 normal saline
For patients with limited IV access, albumin or other col- B. 500 mL of dextran
loid fluids will expand plasma volume more rapidly than crys- C. 250 mL of 5% human albumin
talloid and at a lower volume of total fluid infused. Outside of
this particular indication, albumin should not be routinely D. 100 mL of 3% hypertonic saline
used as a preferred resuscitation fluid because of lack of evi- Answer: C. This patient has one small-bore IV line and
dence of improved mortality, increased cost, and possible ad- will need rapid volume expansion while blood is or-
verse events associated with administration. Future studies dered from the blood bank and additional IV access is
should aim to compare crystalloid versus colloid in terms of established; 5% albumin will provide greater plasma
meaningful patient outcomes other than mortality. It will re- volume expansion in a shorter period of time than crys-
quire careful systematic evaluation to identify specific clinical talloid. Dextran may have deleterious effects on platelets
scenarios in which one or another type of fluid resuscitation and worsen bleeding. Hypertonic saline is not indicated
will benefit the patient. for rapid volume expansion during hypovolemic shock.
2. All of the following affect duration of albumin for

KEY MESSAGES plasma volume expansion except:
1. No mortality differences have been shown between

A. Continued resuscitation with 0.9% normal saline
patients who receive crystalloid versus colloid fluid for B. Hypoalbuminemia
resuscitation in the perioperative period. C. Rate of loss from circulation
2. Human albumin is one of several colloid fluids avail- D. Metabolism of administered albumin
able for volume resuscitation. E. None of the above
3. Limitations of albumin administration include acquisition
cost, possible allergic reactions, and infectious risks.
QUESTIONS
1. You are preparing to transport a 69-year-old female to
the endoscopy suite from the intensive care unit for an
upper endoscopy when she begins to vomit bright red
blood, becomes tachycardic to 140 beats per minute,
Figure 15.1 • (A) Mean complications per patient and percent-

T A B L E 1 5 . 2 Concerns with Human Albumin age of patients, p value ⬍0.008. Graph (B) depicts the percentage
Administration of patients with septicemia, p value ⬍0.04. Graph (C) depicts pa-
tients with pneumonia, p value ⬍0.05. These were each random-
• Relatively expensive ized controlled trials comparing albumin versus no albumin in pa-
• Possible transmission of infectious agents tients with hypoalbuminemia that required total parenteral
nutrition. Gray, albumin; white, no albumin. (Adapted from
• Allergic reactions
Haynes GR, Navickis RJ, Wilkes MM. Albumin administration—
• Limited supply what is the evidence of clinical benefit? A systematic review of ran-
domized controlled trial. Eur J Anest 2003;20:771–793.)
15259_Ch15.qxd 3/14/09 6:40 PM Page 57
CHAPTER 15 • PERIOPERATIVE USE OF ALBUMIN 57
Answer: B. Continued resuscitation with 0.9% References

normal saline will dilute the plasma oncotic pressure
and decrease the amount of time that the albumin 1. Miller RD. Miller’s Anesthesia, 6th Ed. Philadelphia: Elsevier, 2005.
2. Boldt J, Schölhorn T, Mayer J, et al. The value of an albumin-
has an effect on plasma volume expansion; hypoal- based intravascular volume replacement strategy in elderly
buminemia has no correlation with how long the al- patients undergoing major abdominal surgery. Anesth Analg
bumin is administered, as resuscitation fluid will re- 2006;103:191–199.
main intravascular. 3. The SAFE Study Investigators. A Comparison of albumin and
saline for fluid resuscitation in the intensive care unit. NEJM
3. Problems associated with albumin include all of the 2004;350:2247–2256.
4. Vincent JL, Sakr Y, Reinhart K, et al. Is albumin administration
following except:
in the acutely ill associated with increased mortality? Results of
A. Increased cost the SOAP study. Critical Care 2005;9:R745–R754.
5. Haynes GR, Navickis RJ, Wilkes MM. Albumin administration—
B. Limited availability of product what is the evidence of clinical benefit? A systematic review of ran-
C. Potential allergic reactions domized controlled trials. Eur J Anesth 2003; 20:771–793.
6. Russell JA, Navickis RJ, Wilkes MM. Albumin versus crystalloid
D. Potential transmission of infectious organisms for pump priming in cardiac surgery: meta-analysis of controlled
E. Difficulty cross-matching blood after its trials. JCVA 2004;18:429–437.
administration 7. Fuhong S, Zhen W, Ying C, et al. Fluid resuscitation in severe
sepsis and septic shock: albumin, hydroxyethyl starch, gelatin, or
Answer: E. All answers listed are problems associated Ringer’s Lactate—does it really make a difference? Shock
with albumin administration. 2007;27:520–526.
15259_Ch16.qxd 3/14/09 6:40 PM Page 58
CHAPTER 16
Neurologic Complications of Peripheral

Nerve Blockade
Christopher J. O’Connor
CASE FORMAT: REFLECTION ing resolved immediately, and within 15 minutes, the pa-
tient was once more responsive and oriented. Sensory and
A 55-year-old, 90-kg man with a history of hypertension, motor testing of the right arm and shoulder revealed dense
non–insulin-dependent diabetes mellitus, and shoulder anesthesia.
pain presented for right total shoulder arthroplasty. He The patient underwent uncomplicated total shoulder
had previously undergone inguinal hernia repair and an arthroplasty and recovery. Five days later, however, he re-
appendectomy without anesthetic complications. His ported a sensory paresthesiae in the median nerve distribu-
regular medications included metoprolol, valsartan, met- tion of his right arm. Nerve conduction studies demon-
formin, and naproxen. The preoperative evaluation strated mild conduction disturbance of his right median
identified left ventricular hypertrophy on his electrocardio- nerve that resolved completely over 3 weeks. His recovery
gram, his nonfasting serum glucose level was 170 was otherwise uneventful.
mg/dL, and hemoglobin concentration was 12.9 mg/dL.
Initially, the patient’s vital signs were as follows: blood
pressure, 136/80 mm Hg; heart rate, 65 beats per
minute; arterial oxygen saturation, 98%; and respiratory
rate, 18 breaths per minute. Neurologic function of the DISCUSSION
operative arm was normal.
The anesthetic plan comprised an interscalene block Central Nervous System Toxicity
(to be inserted preoperatively) and a continuous intersca-
lene catheter for postoperative analgesia, in conjunction Central nervous system (CNS) toxicity follows vascular ab-
with general anesthesia and tracheal intubation. sorption or intravascular injection of LA and manifests as a
An intravenous catheter was placed in the contralat- change in the patient’s sensorium or mental status, the pa-
eral arm, and standard monitors were applied. Oxygen tient’s perception of a metallic taste, tinnitus, or as an overt
was administered at 3 L per minute by nasal cannulae, grand mal seizure. CNS toxicity tends to precede cardiovascu-
and incremental doses of midazolam (0.5 mg) and fen- lar toxicity and is typically short lived. Appropriate manage-
tanyl (25 mcg) were administered according to the anes- ment entails administration of small doses of midazolam or
thesiologist’s clinical judgment. A nerve stimulator was pre- sodium thiopental and support of ventilation and oxygenation
pared by attaching the grounding lead to a surface during the (usually) brief duration of the seizure or altered
electrode, the patient’s chest, and a 17-gauge insulated mental status. If the patient’s mental status returns to baseline
Tuohy needle was primed with local anesthetic. The right promptly, and if no injuries are sustained during the event, it
side of the patient’s neck was prepared using sterile pre- is reasonable to proceed with surgery.
cautions. Local anesthetic (LA) (lidocaine 2%, 2 mL) was in-
jected subcutaneously at the interscalene groove, and the
Peripheral Nerve Injury
Tuohy needle was advanced until the characteristic muscu- Nerve injury following peripheral nerve blockade (PNB) is
locutaneous nerve response (biceps muscle contraction) gratifyingly uncommon. Published investigations of the inci-
was achieved. Following negative aspiration of the needle dence of this complication are limited by study design and in-
for blood, 35 mL of 0.5% ropivacaine with epinephrine consistent neurodiagnostic follow-up. Moreover, it is often
(1/10,000) was incrementally injected with serial aspira- difficult to determine the precise etiology of postoperative
tions after each 3-mL injection. No change in heart rate or neurologic deficits (PNB-related vs. surgical). Despite these
sensorium was noted. Following completion of the LA injec- limitations, certain conclusions can be drawn. The mechanism
tion and as the interscalene catheter was inserted through of nerve injury after surgery accompanied by PNB can be
the Tuohy needle, the patient’s left hand and arm began to related to several factors, including block-related events
twitch, and he became unresponsive to verbal command. (e.g., needle trauma, intraneural injection [INI],1,2 and LA
The needle was immediately withdrawn, and midazolam neurotoxicity), surgical factors (e.g., surgical trauma, stretch
(3 mg) was administered, while oxygen (100%) was given injuries, and the impact of tourniquets, hematomata, compres-
using positive-pressure bag/mask ventilation. The twitch- sive dressings, and positioning), and the impact of pre-existing
conditions (e.g., bony deformities and peripheral neuropathy).
58
15259_Ch16.qxd 3/14/09 6:40 PM Page 59
CHAPTER 16 • NEUROLOGIC COMPLICATIONS OF PERIPHERAL NERVE BLOCKADE 59
Needle trauma is probably uncommon, whereas INI appears knee arthroplasty, are additional mechanisms that can result
to be the likely mechanism of block-related nerve injury in in postoperative neurologic deficit unrelated to PNB. In fact,
most patients. High injection pressures2 and severe pain on Horlocker et al.7 noted that 89% of neurologic deficits after
injection indicate INI and subsequent fascicle disruption. The 1614 axillary blocks were related to the surgical procedure it-
peripheral nerve is a complex structure bounded by the self, a finding consistent with other clinical reports. In addi-
epineurium that encases multiple nerve fascicles surrounded tion, 4% of patients undergoing shoulder arthroplasty sustain
by a perineural layer. Each fascicle contains myelinated neu- brachial plexus injuries in the absence of PNB, again suggest-
rons that can be damaged by intrafascicular injection of LA. ing surgical nerve injury.8 Candido et al. observed that of the
This appears to produce neurologic injury by inducing 4.4% of 684 patients experiencing paresthesia after intersca-
swelling and edema of the fascicle with subsequent neurovas- lene block for shoulder surgery, 45% were located at the site of
cular compromise and possibly by direct LA toxicity.3,4 the block, and 23% were in the distribution of the greater au-
Interestingly, Bigeleisen demonstrated that 81% of patients ricular nerve; more serious distal sensorimotor neuropathies
undergoing ultrasound (US)-guided axillary block had evi- were thus infrequent.9 Finally, although preoperative neu-
dence of INI in at least one nerve, with no subsequent evi- ropathy and nerve localization techniques can be associated
dence of neurologic injury,3 suggesting that small-volume INI with postoperative nerve injury, well-designed prospective
does not produce clinical nerve injury and occurs commonly studies have failed to show any consistent relationship be-
without a clinically detectable adverse outcome. This finding tween diabetes, pre-existing neuropathy, or the use of nerve
is borne out by clinicians experienced with US-guided PNB. localization techniques and the incidence of neurologic deficit
Although US may facilitate accurate LA deposition around after PNB.
rather than within the nerve, there are no clinical data to vali- Most postoperative neurologic complaints manifest within
date that assumption. Bigeleisen’s findings also imply that in- the first 48 hours after surgery. They are typically sensory
jection beneath the perineurium is the probable site of injury deficits and usually resolve within 2 to 4 weeks, although
from INI. rarely, deficits can require up to 9 months for complete recov-
In addition to block-related injury, surgical factors appear ery. Nerve conduction studies (NCS) and electromyography
to be especially important in producing neurologic deficits. (EMG) typically reveal conduction delays consistent with
Experimental data, as well as electrophysiologic studies in pa- neuropraxia, a temporary injury pattern associated with func-
tients have shown the compressive and neuronal ischemic ef- tional recovery. Assessment of neurologic deficits should in-
fects of excessive tourniquet duration and inflation pressure clude a careful neurologic examination, and, in most cases,
on peripheral nerves. Horlocker et al.5 and Fanelli et al.6 NCS and EMG. Repeat studies are commonly performed at 4
demonstrated that duration of tourniquet inflation and pres- to 6 weeks, after which clinical assessment appears to suffice in
sures ⬎400 mm Hg, respectively, were associated with an in- the absence of severe motor deficits.
creased incidence of postoperative neurologic deficit after limb Determining the incidence of block-related nerve injury is
surgery. Retractor injury to the femoral nerve during hip difficult (Tables 16.1 to 16.3). However, prospective analyses
arthroplasty, stretch injury of the brachial plexus during of more than 70,000 patients have indicated an incidence of
shoulder arthroplasty, and peroneal nerve injury related to 0.02%. This is likely to be an underestimate caused by self-
preoperative valgus deformities and flexion contractures after reporting. Other prospective and retrospective analyses have
T A B L E 1 6 . 1 Incidence of Neurologic Injury After Peripheral Nerve Blockade: Single-Injection Nerve Block
Study Incidence Block Type

Author Patient No. Design (F/U Time) UE LE Recovery (at mos)
Auroy, 2002 50,223 Pro 0.02% (NS) All All 42% (6 mo)
Auroy, 1997 21,278 Pro 0.02% (48 h) All All 100%
Fanelli, 1999 3996 Pro 1.7% (1 mo) ISB, Ax F-SB 99% (3 mo)
Stan, 1995 1995 Pro 0.2% (? 1 wk) Ax — 100% (2 mo)
Klein, 2002 2382 Pro 0.25% (7 d) All, ISB F-SB 100% (3 mo)
Horlocker, 1999 1614 Retro 8.4% (2 wk) Ax — 100% (5 mo)
Candido, 2006 693 Pro 8.5% (2 d–1 mo) ISB — 97% (4 mo)
Bishop, 2005 568 Retro 2.3% (2 wk) ISB 91% (6 mo)
Giaufre, 1996 1995 Pro 0% All All —
Ax, axillary; F-SB, femoral-sciatic block; F/U, follow-up; ISB, interscalene block; LE, lower extremity; NS, not significant; pro, prospective; retro,
retrospective; UE, upper extremity.
15259_Ch16.qxd 3/14/09 6:40 PM Page 60
60 CHAPTER 16 • NEUROLOGIC COMPLICATIONS OF PERIPHERAL NERVE BLOCKADE
T A B L E 1 6 . 2 Incidence of Neurologic Injury After Peripheral Nerve Blockade: Continuous Catheters
Patient Study Incidence Block Type Recovery

Author No. Design (%) UE LE (at mos) Comments
Capdevila, 2005 1416 Pro 0.2% (24 h) All All 100% (3 mo)
Borgeat, 2003 700 Pro 8% (10 d) ISC — 100% (7 mo)
Borgeat, 2001 530 Pro 14% (10 d) ISC — 99% (9 mo) No difference
(SS⫹CC) SS and CC
Swenson, 2006 620 Pro 0.3% (1 wk) ISC FIC, SC 100% (2 mo)
Bergman, 2003 405 Retro 1% (postop) AxC — 100%
Sada, 1983 597 Pro 0.5% (?) AxC — ?
Grant, 2001 228 Pro 0% (1, 7 d) ISC ? —
Singelyn, 1999 446 Pro 0.1% (?) — FC ?
Cuvillon, 2001 211 Pro 0.4% (6 wk) — FC 99% (12 mo)
FC, femoral catheter; FIC, fascia iliaca catheter; F/U, follow-up; ISB, interscalene block; ISC, interscalene catheter; LE, lower extremity; NS, not signifi-
cant; sc, sciatic catheter; UE, upper extremity.
shown greater complication rates of 0% to 8% after single- It may result from INI, a complication that can be minimized
injection upper extremity blockade and rates ⬍0.5% for lower by discontinuing injection when either high injection pres-
extremity blocks. Studies of continuous catheter (CC) tech- sures or pain are encountered, and it appears unrelated to the
niques have similarly revealed low neurologic injury rates. type of nerve localization technique employed. Whether US
Capdevilla et al.10 demonstrated a 0.21% incidence of nerve in- guidance will decrease the already low incidence of these com-
juries after 1416 upper and lower extremity CC techniques as plications has yet to be determined. It certainly holds promise
did Swenson et al.11 in a similar analysis of 620 CC techniques. for visual, real-time assessment of needle placement and LA
In conclusion, nerve injury can occur after PNB but is in- deposition. Ultimately, as long as needles, nerves, and local
frequent, is typically a transient sensory neuropraxia, and may anesthetics are in close proximity, the potential for nerve in-
be related to surgical (rather than block-related) mechanisms. jury will exist.
T A B L E 1 6 . 3 Pattern and Causality of Nerve Lesions: Single Injection
Block Type
Author Injury Pattern/Nerve Involvement UE LE Anesthesia vs Surgery Cause
Auroy, 2002 Per neuropathy All All Not specified
Auroy, 1997 Not specified All All Not specified
Fanelli, 1999 Not specified ISB, Ax F-SB Not specified
Stan, 1995 1 ulnar/MC paresthesia Ax — 0.2% because of block
Klein, 2002 ISB-RN injury All, ISB F-SB 50% clearly surgical
SCB-UN Injury
Horlocker, 1999 Pain/numbness: UN (4), RN, MN Ax — 88% because of surgery
Candido, 2006 Paresthesia: ISB Site, aur ner, thumb ISB — 54% because of block
Bishop, 2005 Sensory neuropathy ulnar 5/10 ISB — Not specified
Schroeder, 1996 Not specified All — 72% because of surgery
aur ner, auricular nerve; Ax, axillary; blk, block; F-SB, femoral-sciatic block; ISB, interscalene block; LE, lower extremity; MC, musculocutaneous;
MN, median nerve; Per, peripheral; RN, radial nerve; UE, upper extremity; UN, ulnar nerve.
15259_Ch16.qxd 3/14/09 6:40 PM Page 61
CHAPTER 16 • NEUROLOGIC COMPLICATIONS OF PERIPHERAL NERVE BLOCKADE 61
KEY MESSAGES 3. The mechanism of peripheral nerve injury after PNB

and orthopaedic surgery most likely results from:
1. Seizures are unpredictable but not uncommon compli- A. The use of paresthesia-seeking techniques
cations of PNB. They are typically brief in duration, B. Needle trauma
have few sequelae, and are easily managed with con-
C. The compressive effects of dressings
servative therapy, including sedative/hypnotics in small
doses, supplemental oxygen, and airway support. D. Local anesthetic toxicity
E. Surgical factors
2. Serious nerve injury after PNBs is rare and is typically
sensory in nature. Such injury may be related to the Answer: E
nerve block itself (i.e., primarily intraneural injection,
rarely needle trauma), direct surgical injury, or tourni-
quet-related nerve ischemia. It usually resolves in 3 to References
6 weeks, although rarely sensorimotor lesions can last 1. Hadzic A, Dilberovic F, Shah S, et al. Combination of intraneural
as long as 9 months. injection and high injection pressure leads to fascicular injury and
neurologic deficits in dogs. Reg Anesth Pain Med 2004;29:417–423.
3. Evaluation of persistent nerve injury after extremity sur- 2. Kaufman B, Nystrom E, Nath S, et al. Debilitating chronic pain
gery using PNB entails careful clinical assessment syndromes after presumed intraneural injection. Pain 2000;85:
within 48 hours of surgery, NCS, EMG, and clinical 283–286.
evaluation at 2 and 6 weeks postoperatively. NCS 3. Bigeleisen P. Nerve puncture and apparent intraneural injection
and EMG help to estimate the severity and location of during ultrasound-guided axillary block does not invariably re-
the lesion and the time course and likelihood of recov- sult in neurologic injury. Anesthesiology 2006;105:779–783.
ery but may not reveal its etiology (e.g., surgery vs. 4. Borgeat A. Regional anesthesia, intraneural injection, and nerve
block-related nerve injury). injury. Anesthesiology 2006;105:647–648.
5. Horlocker T, Hebl JR, Gali B, et al. Anesthetic, patient, and sur-
gical risk factors for neurologic complications after prolonged
total tourniquet time during total knee arthroplasty. Anesth
Analg 2006;102:950–955.
QUESTIONS 6. Fanelli G, Casati A, Garancini P, et al. Nerve stimulator and
multiple injection technique for upper and lower limb blockade:
1. The most appropriate evaluation of persistent paresthe- failure rate, patient acceptance, neurologic complications. Anesth
sia after surgery involving PNB includes: Analg 1999;88:847–852.
A. MRI of the involved extremity 7. Horlocker T, Kufner RP, Bishop AT, et al. The risk of persist-
ent paresthesia is not increased with repeated axillary block.
B. Careful observation for 4 weeks Anesth Analg 1999;88:382–387.
C. Somatosensory-evoked potential measurements 8. Lynch N, Cofield RH, Silbert PL, et al. Neurologic complica-
tions after total shoulder arthroplasty. J Shoulder Elbow Surg
D. EMG and NCS 1996;5:53–61.
E. Surgical re-exploration of the involved limb 9. Candido K, Sukhani R, Doty R Jr, et al. Neurologic sequelae
Answer: D. after interscalene brachial plexus block for shoulder/upper arm
surgery: the association of patient, anesthetic, and surgical factors
to the incidence and clinical course. Anesth Analg 2005;100:
2. Most postoperative neurologic complaints after PNB
1489–1495.
and orthopaedic surgery: 10. Capdevila X, Pirat P, Bringuier S, et al. Continuous peripheral
A. Manifest 96 hours after surgery nerve blocks in hospital wards after orthopedic surgery: a multi-
B. Resolve within 1 week center prospective analysis of the quality of postoperative analge-
sia and complications in 1,416 patients. Anesthesiology 2005;103:
C. Are usually motor deficits 921–923.
D. Represent neuropraxia of the involved nerves 11. Swenson JD, Bay N, Loose E, et al. Outpatient management of
continuous peripheral nerve catheters placed using ultrasound
E. Are secondary to the nerve block guidance: an experience in 620 patients. Anesth Analg
Answer: D 2006;103:1436–1443.
15259_Ch17.qxd 3/14/09 6:41 PM Page 62
CHAPTER 17
Peripheral Nerve Block Versus Epidural

Analgesia for Total Knee Arthroplasty
Asokumar Buvanendran
CASE FORMAT: REFLECTION Neuraxial Anesthesia and Analgesia

Although general anesthesia is still practiced in many hospitals
A 62-year-old, 5⬘10⬙ male weighing 122 kg presented to for joint replacement, this trend is gradually decreasing as clin-
the anesthesia preoperative clinic 2 weeks before scheduled ical studies have shown a greater incidence of adverse effects
right total knee arthroplasty (TKA) for osteoarthritis. He ex- associated with general anesthesia and intravenous opioids com-
pressed major concerns regarding postoperative pain con- pared with regional anesthesia/analgesia.3 TKA is associated
trol and recollected severe postoperative pain from his pre- with severe postoperative pain, which interferes with early mo-
vious left TKA with poor range of motion currently in bility and physical therapy, thereby affecting both short- and
addition to chronic pain of his left knee. The patient’s past long-term patient outcomes. With the widespread use of re-
medical history was significant only for hypertension and gional anesthetic techniques, combined spinal epidural anes-
sleep apnea. His medications included metoprolol and non- thesia followed by continuous and patient-controlled epidural
steroidal anti-inflammatory drugs (NSAIDs); the latter had analgesia has become a common anesthetic/analgesic procedure
been discontinued 1 week before his visit to the preanesthe- for joint replacement surgeries. Epidural analgesia has been
sia clinic because of concerns regarding perioperative shown to reduce postoperative blood loss, provide superior pain
bleeding. He had a continuous positive airway pressure control, and improve postoperative functional outcome in
(CPAP) machine, which he used most nights. The remaining comparison with intravenous patient-controlled analgesia.4
history, physical examination, and diagnostic workup did Epidural analgesic solutions that are commonly used include
not indicate cardiac disease. Physical examination revealed opioids such as fentanyl, local anesthetics such as bupivacaine
an obese, cooperative patient with a Mallampati class III air- (many hospitals currently use ropivacaine because of its prefer-
way and normal vital signs. ential sensory blockade properties and cardiovascular safety), or
The patient was very concerned about stopping the a combination of the two. Common adverse effects associated
NSAID, as it was the only drug providing him with pain re- with epidural analgesia include hypotension, urinary retention,
lief for his right knee arthritis. He was willing to discuss any pruritus, nausea, vomiting, and headache. Significant intraoper-
option that would provide him with adequate pain relief ative hypotension can lead to postoperative nausea and vomiting
and also a better functional outcome than that following his and can also be associated with decreased postoperative cogni-
previous TKR. tive function. This may be detrimental to initiation of early
physical therapy, which is crucial for improved knee range of
motion. Serious adverse effects such as epidural hematoma and
the associated nerve damage, respiratory depression, and infec-
CASE DISCUSSION tion have also been reported.
If the patient in the case presented consents to neuraxial
TKA is a very effective treatment modality for severe chronic anesthesia, a reasonable approach would be to perform com-
osteoarthritis of the knee. This procedure has become increas- bined spinal epidural using bupivacaine (10–15 mg) and fen-
ingly common over the past 2 decades.1 In 2002 alone, more tanyl 25 ␮g for the spinal anesthetic because of their synergis-
than 350,000 primary unilateral TKAs were performed.1 This tic analgesia. Given this patient’s history of sleep apnea,
number has escalated to about 441,000 in 2004 and is expected caution is advisable as administration of opioids intrathecally
to increase to 3.5 million by 2030.1 This dramatic rise in the can trigger respiratory depression. Administration of a short-
utilization rate for TKA can be attributed to an increasing eld- acting opioid intrathecally can be safe but requires appropriate
erly population and increased usage because of advances in monitoring postoperatively. In addition, this patient should re-
surgical, anesthetic, and analgesic techniques. These advances ceive an appropriate multimodal regimen (Table 17.1).
have collectively contributed to decreased blood loss, less post- Postoperative analgesia can be maintained with a local anes-
operative pain, a shorter duration of hospital stay, and im- thetic alone or in combination with clonidine (␣2-agonist at
proved functional outcome. The duration of hospital stay after low doses) as an adjuvant, thereby avoiding narcotics as the ad-
TKA has decreased from an average of 7 to 10 days in the ditive in the epidural mixture because of his history of sleep
early 1990s to an average of 2 to 4 days currently.2 The remain- apnea. The patient should be monitored while using CPAP for
der of this discussion addresses the anesthetic management of respiratory parameters. As the patient undergoes rehabilita-
this challenging patient. tion, the epidural solution can be titrated to provide analgesia.
62
15259_Ch17.qxd 3/14/09 6:41 PM Page 63
CHAPTER 17 • PERIPHERAL NERVE BLOCK VERSUS EPIDURAL ANALGESIA 63
T A B L E 1 7 . 1 Recommended Multimodal Drugs
Preoperative
Drug and Intraoperative Postoperative
Acetaminophen 1000 mg 500–1000 mg three times daily
COX-2 inhibitor: celecoxib 400 mg 2 hours before surgery 200 mg twice per day
Ketamine 20–70 mg IV
Gabapentin or pregabalin 600 mg or 100 mg respectively 300 or 75 twice per day
Clonidine 100 ␮g PNB
Clonidine 10 ␮g via epidural
IV, intravenous; PNB, peripheral nerve blockade.
The epidural catheter can be removed on the third postopera- cluded that the analgesic efficacy of epidural and PNB tech-
tive day or earlier depending on his achievement of discharge niques was similar but that the incidence of adverse effects
criteria set by the physiotherapist. The subject of deep vein (hypotension, urinary retention, and nerve injury) was less for
thrombosis (DVT) prophylaxis for joint arthroplasty is contro- PNB.5 Nerve injuries associated with PNB present much less
versial with some authorities advocating aspirin alone, espe- patient morbidity than a neuraxial injury. The review also
cially for patients undergoing minimally invasive joint evaluated the potential benefit of combining a sciatic block
replacement. with a femoral block and concluded that there was no addi-
The risk of developing a hematoma in the epidural space is tional benefit.5 Although the lumbar plexus block has greater
greater in patients who receive low-molecular-weight heparin consistency with regard to blocking the obturator nerve com-
(LMWH) postoperatively for DVT prophylaxis, especially pared to the infrainguinal femoral block (three-in-one), it is
after surgery involving the lower limbs.9,10 The dramatic in- unclear as to whether there is any benefit in adding the obtu-
crease in the use of LMWH in the early 2000s for DVT pro- rator block.6 The incidence of quadriceps weakness with
phylaxis influenced the movement toward peripheral nerve PNBs is greater and can therefore interfere with early mobi-
blockade (PNB) (and use of continuous catheter techniques) lization of the patient, but there appears to be no difference in
for pain after orthopaedic procedures. Thus, the use of rehabilitative outcomes for the two groups at the time of dis-
LMWH and other anticoagulants has been an important de- charge.6 Only limited evidence exists on whether continuous
terminant of how postoperative analgesia is provided after femoral nerve block is more effective than a single-shot
total joint replacement. femoral block. In one randomized trial by Salinas et al., con-
tinuous femoral block (vs. single shot) lessened pain scores and
PNB increased opioid consumption significantly; however, the du-
PNB of the major nerves supplying the lower extremities has ration of hospital stay and functional outcome did not differ
emerged as a good alternative technique to an epidural for between the two groups.7 Although the mechanism is not
providing postoperative analgesia following procedures on the clear,8 the addition of clonidine 100 ␮g to PNB leads to pro-
lower limb, especially in view of the current anticoagulation longation of analgesic effect.
guidelines. PNB can be achieved by “single-shot” blockade or In the case presented herein, a reasonable alternative ap-
by continuous infusion. For lower limb surgeries, a femoral proach would be to insert femoral nerve and sciatic nerve
nerve block, a sciatic nerve block, an obturator nerve block, or catheters preoperatively. This combination could be used to
a “three-in-one” block can be performed. Femoral nerve provide adequate anesthesia for TKA either alone or with a
blocks are most commonly used for knee arthroplasties, either mini-dose single-dose of spinal anesthetic. The local anes-
alone or in combination with a sciatic nerve block. After com- thetic concentration in the two peripheral catheters should
pletion of the femoral nerve block, the patient is turned later- be low so that patients can participate actively in their phys-
ally for placement of a sciatic perineural catheter using a iotherapy. It is also important to administer neuronal block-
gluteal approach. Anatomically, an obturator nerve block in ade as one element of a multimodal regimen that is adjusted
combination with a femoral nerve block provides superior in response to patient recovery throughout the perioperative
analgesia compared with femoral plus sciatic nerve block. period.
Performing an effective obturator nerve block is challenging. Opioids and Obstructive
A “three-in-one” block is intended to block the lateral femoral
cutaneous, the femoral, and the obturator nerves using a sin- Sleep Apnea
gle injection. A known or presumptive diagnosis of obstructive sleep apnea
Several studies have compared the analgesic efficacy and (OSA) in a patient scheduled for surgery can influence the
incidence of adverse effects of PNBs (femoral alone or femoral choice of anesthetic as well as postoperative analgesic man-
plus sciatic) versus epidural analgesia. In a systematic review agement. In every obese adult patient, preoperative assess-
of studies that compared the two techniques, Fowler et al. con- ment should include questions on nocturnal snoring, and/or
15259_Ch17.qxd 3/14/09 6:41 PM Page 64
64 CHAPTER 17 • PERIPHERAL NERVE BLOCK VERSUS EPIDURAL ANALGESIA
mary analgesia. Nevertheless, they are valuable elements of a

T A B L E 1 7 . 2 Screening Questions for
multimodal approach to postoperative pain management. In
Sleep Apnea addition, the use of pregabalin or gabapentin may decrease the
incidence of chronic pain developing after knee surgery1 (as in
• Do you snore excessively? the case described). Patients who already have chronic pain
• Is your sleep refreshing? from a previous surgery and are undergoing another surgical
• Do you have periods when you stop breathing procedure are at a greater risk of developing an adverse out-
come. Therefore, the perioperative physician should make
while sleeping?
every attempt to attenuate the surgical response, both humeral
and neuronal, so that the patient can have an improved out-
come. Other agents that could be used in the perioperative pe-
riod for this patient include a round-the-clock regimen of
snorting and/or apnea, and daytime sleepiness (Table 17.2). acetaminophen (not exceeding 4 g/day), magnesium (N-
Patients with OSA are particularly sensitive to the depressant methyl-D-aspartate antagonist), and vitamin C (antioxidant).
effects of opioids, sedatives, and tranquilizers.11,12 Opioids
have been shown to increase the effects of sleep and decrease
arousal mechanisms. In a patient without OSA, the ensuing SUMMARY
hypoxemia and hypercarbia after the use of opioids and other
sedatives trigger carotid and brainstem chemoreceptors to in- Patients undergoing TKA should be offered a COX-2 in-
crease respiratory drive. In individuals with OSA, however, hibitor until the day of surgery to relieve pain from osteoarthri-
this physiologic response is vulnerable to the effects of opioids tis. A multimodal analgesic regimen should be applied and
and other sedatives. In these patients, it is recommended that adjusted during the perioperative period.16 Postoperative
opioid analgesia should be avoided, and a multimodal anal- management should include either a femoral nerve catheter
gesic regimen, which includes regional analgesia, should be or an epidural to optimize analgesia, so that patients can un-
used during the postoperative period.13 It is important that dergo aggressive physical therapy for an improved functional
such patients (as in the case described) continue their CPAP outcome.
settings during the perioperative period, and oxygen satura-
tion should be monitored continuously. Given the severity of
postoperative pain associated with TKA, judicious adminis- KEY MESSAGES
tration of opioids may be necessary even in the presence of a
functioning PNB.
1. Postoperative analgesia for patients undergoing TKA is
Multimodal Analgesia for TKA vital for improved long-term outcome. Either PNB or an
epidural can safely be instituted.
Tissue inflammation resulting from surgery triggers the pro-
duction of prostaglandins (PG). Prostaglandins, particularly 2. Patients with OSA present a significant challenge to
PGE2, mediate pain by sensitizing the peripheral nociceptors anesthesiologists, and caution needs to be exercised
to mechanical and chemical mediators of pain. Prostaglandins in administering opioids and sedatives.
have also been shown to play a role in central sensitization.
3. Acute postoperative pain is associated with an in-
One isoenzyme of cyclooxygenase (COX-2) is primarily re-
creased likelihood of developing chronic pain. It is
sponsible for the production of PGE2. Selective COX-2 in-
likely that an effective multimodal analgesic regimen
hibitors decrease postoperative inflammation and pain and
including neuraxial or PNB decreases the incidence of
improve the overall functional outcome in patients after
persistent postsurgical pain.
TKA.14,15 Unlike other NSAIDs, selective COX-2 inhibitors
such as celecoxib, do not compromise hemostasis; therefore,
patients can continue to take celecoxib until the day of surgery
and continue this regimen into the postoperative period. This
presents one solution to the concerns expressed by the patient
in this case. Discontinuing NSAIDs before surgery can lead to
QUESTIONS
increased preoperative pain (osteoarthritis flare-up), and in
turn, to increased postoperative pain scores. Patients who dis- 1. Which of the following statements is true?
continue NSAIDs should be started on COX-2 inhibitors be- A. Poor postoperative pain control surgery will lead to
fore surgery and for 10 to 14 days (for suggested doses, see good outcome.
Table 17.1) postoperatively until the inflammatory response to B. Opioids can be safely administered in patients with
surgery has resolved. Pregabalin is an ␣2-␦ ligand that can act sleep apnea.
in synergy with COX-2 inhibitors to decrease postoperative C. Excellent postoperative pain control has been associ-
hyperalgesia. Randomized controlled trials conducted in the ated with improved functional outcomes.
perioperative setting in orthopaedic populations, both with
gabapentin and pregabalin, have demonstrated an opioid- D. PNBs should not be performed in orthopaedic
sparing effect (10%–20%). However, neither of these drugs patients.
alone or in combination can completely replace opioids for pri- Answer: C
15259_Ch17.qxd 3/14/09 6:41 PM Page 65
CHAPTER 17 • PERIPHERAL NERVE BLOCK VERSUS EPIDURAL ANALGESIA 65
2. Pregabalin acts at which receptor? gery: a systematic review and meta-analysis of randomized trials.
Br J Anaesth 2008;100:154–164.
A. N-methyl-D-aspartate receptor 6. Campbell A, McCormick M, McKinlay K, Scott NB. Epidural
B. Aminobutyric acid receptor vs. lumbar plexus infusions following total knee arthroplasty:
C. ␣2–␦ subunit of calcium channel randomized controlled trial. Eur J Anesthesiol 2008;1–6.
7. Salinas FV, Liu SS, Mulroy MF. The effect of single-injection
D. Inhibits prostaglandins femoral nerve block versus continuous femoral nerve block after
E. Acts at the ␣2 channel total knee arthroplasty on hospital length of stay and long-term
functional recovery within an established clinical pathway.
Answer: C Anesth Analg 2006;102:1234–1239.
8. Kroin JS, Buvanendran A, Beck DR, et al. Clonidine prolonga-
3. Obese patients need to be asked the following
tion of lidocaine analgesia after sciatic nerve block in rats is me-
questions except: diated via the hyperpolarization activated cation current, not by
A. History of snoring alpha-adrenoreceptors. Anesthesiology 2004;101:488–494.
B. History of waking up in the night 9. Checketts MR, Wildsmith JAW. Central nerve block and
thromboprophylaxis—is there a problem? Br J Anaesth 1999;82:
C. History of lethargy early in the morning and falling 164–167.
sleep during the day 10. Horlocker TT, Wedel DJ, Benzon H, et al. Regional anesthesia
D. Do not bring the CPAP machine they use at home to in the anticoagulated patient: defining the risks. Reg Anesth Pain
the hospital Med 2003;28:172–197.
11. Harrison MK, Childs A, Carson PE. Incidence of undiagnosed
Answer: D sleep apnea in patients scheduled for elective total joint arthro-
plasty. J Arthroplast 2003;18:1044–1047.
12. Practice Guidelines for the perioperative management of pa-
References tients with obstructive sleep apnea. Anesthesiology 2006;104:
1. Mahomed NN, Barrett J, Katz JN, et al. Epidemiology of total 1081–1093.
knee replacement in the United States Medicare population. 13. Benumof JL. Obstructive sleep apnea in the adult obese patient:
JBJS 2005;87:1222–1228. implications for airway management. Anesthesiol Clin N Amer
2. National Hospital Discharge Survey, 1991–2004. The U.S. 2002;20:789–811.
Department of Health and Human Services. 14. Buvanendran A, Kroin JS, Berger RA, et al. Up-regulation of
3. Chu CPW, Yap JCCM, Chen PP. Postoperative outcome in prostaglandin E2 and interleukins in the central nervous system
Chinese patients having primary total knee arthroplasty under and peripheral tissue during and after surgery in humans.
general anesthesia/intravenous patient controlled analgesia com- Anesthesiology 2006;104: 403–410.
pared to spinal-epidural anesthesia/analgesia. Hong Kong Med J 15. Buvanendran A, Kroin JS, Tuman KJ, et al. Effects of perioper-
2006;12:442–447. ative administration of a selective cyclooxygenase 2 inhibitor on
4. Choi PT, Bhandari M, Scott J, Douketis J. Epidural analgesia for pain management and recovery of function after knee replace-
pain relief following hip or knee replacement. Cochrane ment: a randomized controlled trial. JAMA 2003;290:2411–2418.
Database Systematic Review. 2003;(3):CD003071. 16. Reuben SS, Buvanendran A. Preventing the development of
5. Fowler SJ, Symons J, Sabato S, Myles PS. Epidural analgesia chronic pain after orthopedic surgery with preventive multi-
compared with peripheral nerve blockade after major knee sur- modal analgesic techniques. JBJS 2007;89:1343–1358.
15259_Ch18.qxd 3/14/09 6:42 PM Page 66
CHAPTER 18
Paravertebral Nerve Blockade for

Thoracic Surgery
Adrienne Wells
CASE FORMAT: REFLECTION CASE DISCUSSION
A 72-year-old, 65-kg female with a history of dyspnea, Changes in Respiratory Function

productive cough, and fatigue presented for a left lower After Thoracotomy
lobectomy for lung cancer. Her medical history was signif-
icant for a 90 pack-year smoking history, coronary artery
Following thoracic surgery, characteristic respiratory abnor-
stent placement following an acute myocardial infarction
malities include a restrictive defect with severely reduced
3 months previously, and obstructive lung disease. Her
vital capacity and functional residual capacity. This de-
medications included metoprolol, salmeterol/fluticasone
creased inspiratory capacity, limits the patient’s ability to
inhaler, lovastatin, aspirin, and clopidogrel.
cough effectively, and increases the risk of atelectasis. Full re-
Preoperative evaluation revealed a frail elderly woman
turn to preoperative values may not be seen for several weeks
who was sitting up in bed, receiving oxygen by nasal can-
after surgery. Patients, such as the one presented in this case,
nulae. She was slightly dyspneic but able to complete
who have pre-existing respiratory dysfunction and a long
sentences and carry on a conversation. Her airway exami-
smoking history, are at greatest risk for postoperative pul-
nation was normal, but lung auscultation revealed coarse
monary complications.
breath sounds throughout and decreased breath sounds at
Both thoracic epidural analgesia (TEA) and PVB have
the left base. The patient’s heart sounds were normal, and
been shown to preserve postoperative lung function. Some
the results of her laboratory tests were within normal limits,
evidence suggests that the protective effect of PVB outweighs
except for hemoglobin concentration (16 gm/dL) and car-
that of TEA. Figure 18.1 compares the proportionate preser-
bon dioxide content of 34 mEq/dL. Her echocardiogram
vation of lung function with different analgesic options.
showed evidence of an old inferior myocardial infarction. Postthoracotomy Pain
Her pulmonary function tests demonstrated significant ob-
structive disease, and SpO2 on 4 liters of oxygen via nasal Postthoracotomy pain is mediated by nociceptive output via
cannula was 97%. The decision was made to include a three different nerve pathways: the intercostal, phrenic, and
regional technique as part of her plan for postoperative vagus nerves. Elevated catecholamine levels are observed,
analgesia. Because she may have had impaired hemostatic and the sympathetic nervous system is also activated.
function caused by concomitant aspirin and clopidogrel ther- Effective pain control without respiratory depression is the
apy, it was decided to provide continuous paravertebral major goal postoperatively and can be accomplished using ei-
blockade (PVB) with a local anesthetic/opioid combination. ther TEA or PVB.1–3 It has been suggested that PVB may be
The patient arrived in the operating room with a large- unique because it can modulate the neuroendocrine stress re-
bore intravenous cannula and an arterial cannula in place. sponse and abolish evoked potentials to thoracic dermatomal
After application of standard monitors, she was then placed stimulation.
in a sitting position, and the paravertebral space at T8–T9
was identified. A loss-of-resistance technique was used, and
TEA
the paravertebral space was found at a depth of 3.5 cm from Long considered the gold standard for the treatment of post-
the skin. An epidural catheter was advanced easily, and the thoracotomy pain and still practiced exclusively in many
test dose was negative. Fifteen milliliters of a 0.25% ropiva- institutions, TEA is an effective means of pain control in this
caine solution was administered via the catheter, and an in- setting. Unfortunately, TEA results in a bilateral sympathec-
fusion 0.2% of ropivacaine was started at 5 mL per hour. tomy, which can produce hypotension. In turn, this can re-
A double-lumen endobronchial tube was placed, and quire a reduction in the rate of the epidural infusion of local
the patient’s left lung was deflated to facilitate surgical ac- anesthetics and result in inadequate analgesia. Urinary reten-
cess and one-lung ventilation. Her SpO2 decreased despite tion can also occur. TEA has several limitations, with active
administration of 100% oxygen. Positive end-expiratory anticoagulation considered an absolute rather than a relative
pressure was administered to the dependent lung, and con- contraindication. Because this patient had been treated with
tinuous positive airway pressure was applied to the nonde- clopidogrel 3 days before surgery, she was still considered to
pendent lung, resulting in improvement in SpO2 (to 96%). A have a potential impairment in hemostasis. The clinically
left lower lobectomy and mediastinal node dissection were accepted time for cessation of clopidogrel therapy before
performed uneventfully. using a central neuraxial technique is 5 to 7 days, although
66
15259_Ch18.qxd 3/14/09 6:42 PM Page 67
CHAPTER 18 • PARAVERTEBRAL NERVE BLOCKADE FOR THORACIC SURGERY 67
Interpleural
Epidural Opioid
Epidural Local Anesthetic + Opioid
Epidural Local Anesthetic
Intercostal Blocks
Paravertebral Blocks
0 20 40 60 80
Percent Preservation
of Lung Function (%)
Figure 18.1 • Comparison of Paravertebral Blockade and Thoracic Epidural

Analgesia for the Treatment of Postthoracotomy Pain. This figure demonstrates better
efficacy of paravertebral blockade in preserving lung function after thoracotomy compared with a
variety of other analgesia modalities. (Data from Richardson J, Sabanathan S, Shah R. Post-thoracotomy
spirometric lung function: the effect of analgesia. A review. J Cardiovasc Surg 1999:40:445–456.)
this recommendation is largely empiric and based on the time the catheter tip advances along the course of an intercostal
required for full return of normal platelet function. nerve root. Test dosing is the same as for thoracic epidural
placement.
PVB
First described in 1905, PVB remains underutilized. The par- CONCLUSION
avertebral space is defined anterolaterally by the parietal
pleura, posteriorly by the superior costotransverse ligaments,
In summary, postthoracotomy pain is an important and often
medially by the vertebrae, and superiorly and inferiorly by the
difficult problem to manage. TEA and PVB are both useful
heads of the ribs. The paravertebral space, like the epidural
techniques for providing postoperative analgesia. The lesser
space, communicates both superiorly and inferiorly. Local
incidence of hypotension, decreased stress response, unilat-
anesthetic injected here will produce a unilateral somatic and
eral blockade, and potentially better preserved pulmonary
sympathetic block.1,4 Because this block is unilateral, paraver-
function than with TEA, make continuous PVB an attractive
tebral catheters generally produce less hypotension than TEA.
option, especially for patients with abnormal hemostatic
Limited data suggest that PVB is more effective than TEA in
function.
preserving lung function after thoracotomy5 (Fig. 18.2).
Although the absolute contraindications for PVB are similar to
those for TEA, anticoagulation is a relative contraindication.
There are few vessels in the paravertebral space, and a paraver- KEY MESSAGES
tebral hematoma has fewer potential neurologic complications
than a thoracic epidural hematoma. 1. Preoperative respiratory dysfunction may be associ-
ated with significant impairment of postoperative pul-
Technique for PVB monary function after thoracotomy and lung resection.
Paravertebral catheter placement involves a loss-of-resistance 2. The etiology of postthoracotomy pain is multifactorial
technique, similar to that of thoracic epidural catheter place- and involves both nociceptive and neuropathic
ment. With the patient in the sitting position, the desired pathways.
thoracic level is identified. A mark should be made 2.5 cm lat-
eral to the midpoint of the spinous process, and a 17-gauge 3. TEA or PVB can decrease respiratory depression asso-
Tuohy needle is advanced slowly until the transverse process ciated with opioid use and can improve postoperative
is contacted (Fig. 18.3). The needle should then be redirected respiratory function.
in a caudad fashion until a loss of resistance is felt, typically at 4. Paravertebral catheter placement is technically straight-
1 cm beyond the transverse process. The catheter should be forward and produces unilateral anesthesia and anal-
threaded no more than 4 cm into the space for an adult and gesia, compared with the bilateral effects of TEA.
2 to 3 cm for a child. This decreases the likelihood that
15259_Ch18.qxd 3/14/09 6:42 PM Page 68
68 CHAPTER 18 • PARAVERTEBRAL NERVE BLOCKADE FOR THORACIC SURGERY
A
5.0 Paravertebral
Epidural
4.0
Plasma cortisol
3.0
2.0
1.0
0 10 20 30 40 50
Time after operation (h)
Mean plasma concentrations of cortisol as a fraction of preincisional

control values, with 95% confidence intervals. The area under the curve
was significantly lower in the paravertebral group (P<0.004).
B C
Paravertebral 100 Paravertebral
1.1 Epidural Epidural
Oxygen saturation (%)

1.0 98
Postoperative PEFR
0.9
96
0.8
94
0.7
0.6 92
0.5 90
12 24 36 48 0 4 8 12 16 20 24 28 32 36 40 44 48
Time after operation (h) Time after operation (h)
Postoperative mean peak expiratory flow rate (PEFR) as a fraction Mean oxygen saturation with 95% confidence intervals. The
of preoperative control values. Error bars represent 95% confidence intervals. paravertebral group had significantly higher saturations after
Pulmonary function in the paravertebral group was significantly better. operation (P=0.0001).
Figure 18.2 • Graph A Shows the Lower Cortisol Levels Seen with Paravertebral Blockade Compared with
Thoracic Epidural Analgesia After Thoracotomy. Graphs B and C show the improvement in spirometric values and oxygen
saturation levels in patients treated with paravertebral blockade. (Reproduced with permission from Richardson J, Sabanathan S,
Jones J, et al. A prospective, randomized comparison of preoperative and continuous balanced epidural or paravertebral bupivacaine
on post-thoracotomy pain, pulmonary function and stress responses. Br J Anaesth 1999;83:387–392.)
15259_Ch18.qxd 3/14/09 6:42 PM Page 69
CHAPTER 18 • PARAVERTEBRAL NERVE BLOCKADE FOR THORACIC SURGERY 69
A B
Figure 18.3 • Technique of Thoracic Paravertebral Blockade. (From Hadzic A, Vloka JD.
Peripheral nerve blocks: principles and practice New York: McGrawHill, 2004.)
QUESTIONS B. Palpation of the ipsilateral transverse process

C. Needle insertion 2.5 cm lateral to the spinous
1. Thoracic PVB: process
A. Produces a bilateral thoracic sympathectomy D. Performance in the lateral position
B. Produces more hypotension than thoracic epidural E. Needle advancement 3 cm beyond the transverse
blockade process
C. Is associated with improved postthoracotomy Answer: C
analgesia
D. Is inferior to intercostal blocks for postthoracotomy
analgesia
E. Involves a noncontinuous space at the thoracic level References
Answer: C 1. Richardson J, Lonqvist PA. Thoracic paravertebral block. Br J
Anaesth 1998;81:230–238.
2. Which of the following is the most important property 2. Richardson J, Sabanathan S, Shah R. Post-thoracotomy spiro-
of TEA? metric lung function: the effect of analgesia. J Cardiovasc Surg
A. Effective postoperative analgesia 1999:40:445–456.
3. Craig D. Postoperative recovery of pulmonary function. Anesth
B. Absence of urinary retention Analg 1981;60:46–51.
C. Bilateral sympathectomy 4. Saito T, Den S, Cheema SPS, et al. A single injection, multi-
D. Motor blockade segmental paravertebral block extension of somatosensory and
sympathetic block in volunteers. Acta Anaesthesiol Scand 2001;
E. Alteration of cortisol levels
45:30–33.
Answer: A 5. Richardson J, Sabanathan S, Jones J, et al. A prospective, ran-
domized comparison of preoperative and continuous balanced
3. Ideal performance of thoracic PVB includes: epidural or paravertebral bupivacaine on post-thoracotomy pain,
A. Passage of catheters 6 cm into the paravertebral pulmonary function and stress responses. Br J Anaesth 1999;
space in adults 83:387–392.
15259_Ch19.qxd 3/14/09 6:43 PM Page 70
CHAPTER 19
Carotid Artery Stenosis
CASE FORMAT: REFLECTION of ⬍3% for asymptomatic patients, ⬍5% for symptomatic pa-
tients, and ⬍7% for those with a prior stroke. CAS and trans-
An 82-year-old woman presented for carotid artery stenting luminal balloon angioplasty of the carotid artery was intro-
(CAS) because of several recent transient ischemic attacks duced as a minimally invasive approach to carotid stenosis
and a 70% restenosis of the left internal carotid artery. She that would avoid the risks associated with surgery and gen-
had undergone a left carotid endarterectomy (CEA) 4 years eral anesthesia in high-risk patients. CAS avoids a neck inci-
previously. Her history was remarkable for hypertension, sion that can lead to cranial nerve injuries or postoperative
hypercholesterolemia, and coronary artery disease with wound infections. However, the efficacy of CAS versus CEA
prior stenting of her left anterior descending and circumflex in decreasing subsequent neurologic morbidity had not been
coronary arteries 2 years ago. Her medications included determined when CAS was introduced. Several recent stud-
metoprolol, lisinopril, simvastatin, clopidogrel, and aspirin. ies and meta-analyses4–7 indicate that CEA can be performed
Her previous CEA had been performed under general anes- safely with a lesser risk (compared with CAS) of stroke or
thesia maintained using a remifentanil infusion, nitrous death at 3 and 6 months postoperatively. Many surgeons con-
oxide, and low concentrations of sevoflurane. She had re- sider CEA to be the “gold standard” for the treatment of
cently presented with several episodes of amaurosis fugax. carotid stenosis in both low- and high-risk patients.
Carotid ultrasound and digital subtraction angiography
studies confirmed a 70% restenosis of her left carotid ar- CEA
tery. CAS was selected as the operative procedure to dilate
CEA entails a longitudinal arteriotomy of the involved vessel
and stent the stenotic vessel. Using intravenous (IV) sedation
after cross clamping of the internal carotid artery. The plaque
and infiltration with local anesthetic to expose her right
is removed by cephalad extension of the endarterectomy plane
femoral artery, carotid angioplasty and stenting were per-
until all of the plaque has been removed. To decrease the inci-
formed using a cerebral protection device to minimize dis-
dence of restenosis, many surgeons perform CEA (and several
tal embolization of atherosclerotic debris. After successful
have shown superior results) with patch angioplasty. Either a
completion of CAS, the patient was transferred to the inten-
piece of autologous vein or synthetic material is used to close
sive care unit for monitoring with stable vital signs. Two
the arteriotomy. Patch angioplasty significantly decreases the
hours after the procedure, she abruptly developed right-
risk of perioperative stroke or death, the risk of perioperative
sided leg and arm weakness. A heparin infusion was
restenosis, and the long-term risk of restenosis.
started and continued for 48 hours; oral aspirin and clopi-
Anesthetic goals during CEA are to prevent stroke and pe-
dogrel therapy was maintained. Three days postopera-
rioperative myocardial infarction (MI) by optimizing intraop-
tively, she underwent right groin exploration for drainage of
erative cerebral and myocardial perfusion. Although adequate
a femoral hematoma and also required transfusion of two
cerebral perfusion can be maintained during the period of
units of packed red blood cells. The patient was eventually
carotid clamping from the contralateral carotid artery via the
discharged from the hospital to a nursing facility 10 days
Circle of Willis, 10% to 15% of the time, clamping will lead to
after CAS.
symptomatic hemispheric ischemia.
The optimal anesthetic for CEA has yet to be determined
(Table 19.1). The use of regional anesthesia—comprising deep
or superficial cervical plexus block, local anesthetic infiltration,
CASE DISCUSSION or a combination of these—has been advocated to decrease the
incidence of perioperative MI, maintain intraoperative hemo-
CEA is a well-validated procedure for managing sympto- dynamic stability, reduce the duration of hospitalization, and
matic and asymptomatic carotid artery stenosis. Several stud- reduce costs. However, none of these contentions has ever been
ies have shown that CEA is superior to medical treatment for firmly established in large-scale, randomized trials. It has been
symptomatic patients with a stenosis of ⬎60%, provided that suggested that the response of the awake patient during
centers performing CEA do so with a low rate of morbidity carotid clamping represents the “gold standard” for neurologic
and mortality.1–3 The Joint Committee of the Society for monitoring in that patients can reliably display signs of cere-
Vascular Surgery has determined that institutions perform- bral ischemia during the period of carotid clamping. Although
ing this surgery should have a combined stroke mortality rate this may be true, it has yet to be borne out by any evidence base
70
15259_Ch19.qxd 3/14/09 6:43 PM Page 71
CHAPTER 19 • CAROTID ARTERY STENOSIS 71
T A B L E 1 9 . 1 A Comparison of the Advantages and Disadvantages of Regional Versus

General Anesthesia for Carotid Endarterectomy
Technique Advantages Disadvantages

Regional Less intraoperative hypotension More intraoperative hypertension
Simple nerve block Unfamiliarity for surgical team
Intubation not required Challenging airway control if GA
needed
Sensitive neurologic monitor Sedation may obscure neurologic
monitoring
Avoids postoperative somnolence Patient discomfort if cerebral
of GA ischemia develops
Shorter hospitalization, lower cost, Sedation-induced hypoxemia may
fewer CV complications increase cerebral ischemia
Provides postoperative analgesia Need to convert to GA
General Reliable airway control Intubation required
Secure control of PaCO2, PaO2 More intraoperative hemodynamic
changes
Possible neuroprotective effects of Delayed emergence may obscure
anesthetics diagnosis of new cerebral event
CV, cardiovascular; GA, general anesthesia.
data. In addition, technical factors may limit the use of regional

anesthesia. These include the presence of a short, obese neck;
a high carotid bifurcation or tortuous arteries; and patients
who are anxious or agitated. In the United States, more than
90% of CEAs are performed on patients under general anes-
thesia. It is likely that until the superiority of one technique
over another has been established, most clinicians will continue
to choose general anesthesia for CEA.
A variety of monitors/methods have been used to assess the
adequacy of cerebral perfusion during CEA. These include
electroencephalography or somatosensory-evoked potentials,
transcranial Doppler, and stump pressure measurement.
None of these methods is infallible, and they cannot reliably
detect intraoperative cerebral ischemia or predict postopera-
tive stroke. Stump pressure measurements and cerebral
oximetry yield low rates of sensitivity and specificity for the
detection of cerebral ischemia. Transcranial Doppler monitor-
ing is technically more demanding (e.g., maintenance of angle
of insonation) and inconsistent in acquiring blood flow signals.
However, 16-lead electroencephalography monitoring is a re-
liable and valid neurologic monitor during CEA. Ultimately,
the choice of intraoperative monitor may be less critical than
surgical factors, because cerebral ischemia during the period of
carotid clamping is an uncommon cause of perioperative
stroke. Most neurologic injuries occur secondary to periopera-
tive thromboembolic events (as in the case described).
CAS
CAS (Fig. 19.1) was originally introduced as a minimally inva- Figure 19.1 • The Technique of Carotid Artery
sive approach to managing carotid stenosis that would avoid Angioplasty and Stenting.
15259_Ch19.qxd 3/14/09 6:43 PM Page 72
72 CHAPTER 19 • CAROTID ARTERY STENOSIS
the risks of surgery and general anesthesia in high-risk pa- stenting should only be performed in high-volume, specialized
tients. CAS is currently approved only for patients in clinical centers with experience in CAS, where stenting and angio-
trials evaluating the efficacy of CAS. It was advocated for the plasty can be used in selected individuals with specific lesions
high-risk patient with clinically significant cardiac (severe is- amenable only to nonoperative treatment. One advantage of
chemic disease or significant congestive heart failure) or pul- CAS compared with CEA is the lesser incidence of cranial
monary disease, very advanced patient age (⬎80 years), or nerve injuries (although local complications such as groin
those with certain anatomic factors that make CEA more dif- hematomas are more common with CAS).
ficult. However, current evidence indicates that CAS has a Anesthesia for CAS is usually performed with local anes-
greater 30-day death or stroke rate and greater 1-year stroke thetic infiltration, with or without monitored anesthesia care
and death rates compared with CEA (Fig. 19.2). In addition, and sedation. Bradycardia can occur at balloon dilation of the
CAS appears superior only in the setting of conditions that carotid artery; this can typically be managed with balloon de-
render surgery technically difficult, such as restenosis after flation and administration of IV anticholinergic agents. The
prior CEA (as in the patient in this case), prior radical neck use of cerebral protection devices—either umbrellas or bal-
surgery, previous neck radiation, and in selected patients with loon devices to trap embolic material—has lessened the inci-
severe concurrent cardiopulmonary disease. Currently, carotid dence of procedural-related cerebral ischemic events.
30
25 *
20 *
Patient #
CEA
15
CAS
*
10 *
0
Stroke Stroke/Death MI Brady/Hypotension CN Injury
Figure 19.2 • Data Comparing Outcomes Between CAS and CEA. It is apparent that the incidence of stroke or combined
stroke and death are lower in patients undergoing CEA compared with CAS. It is also clear that the incidence of myocardial infarc-
tion—expected to be lower with the less-invasive approach of CAS—was no different between the two groups. In contrast, hypotension
and bradycardia were higher in the CAS group. Cranial nerve injuries were higher in the CEA group, as expected. CAS, carotid artery
stenting; CEA, carotid endarterectomy; CN, cranial nerve; MI, myocardial infarction. * p ⬍0.05. (Data from Mas JL, Chatellier G,
Beyssen B, et al. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med 2006;355:
1660–1671.)
15259_Ch19.qxd 3/14/09 6:43 PM Page 73
CHAPTER 19 • CAROTID ARTERY STENOSIS 73
KEY MESSAGES C. Is best achieved with a superficial cervical plexus

block
1. Overall, CEA appears to be associated with a lesser D. Has a high conversion rate to general anesthesia
risk of stroke, MI, and death when compared with E. Allows for communication with the patient during
CAS. carotid occlusion
2. Based on currently available evidence, CAS should be Answer: E
reserved for high-risk patients with severe concomitant
cardiac disease or anatomic conditions that render 3. Which of the following is most likely to detect cerebral
surgery technically difficult, such as restenosis after ischemia during carotid occlusion?
prior CEA, prior radical neck surgery, or previous A. Stump pressure measurement
radiation to the neck. B. Cerebral oximetry
3. CEA is commonly performed on patients with general C. Sixteen-lead electroencephalography analysis
anesthesia, although many patients can be managed D. Transjugular venous oxygen saturation
safely with IV sedation and combined superficial/deep
E. Motor-evoked potentials
cervical plexus blocks. In contrast, CAS is primarily
performed on patients who receive IV sedation and Answer: C
local infiltration with a local anesthetic.
References
1. Abbruzzese TA, Cambria RP. Contemporary management of
QUESTIONS carotid stenosis: carotid endarterectomy is here to stay. Perspect
Vasc Surg Endovasc Ther 2007;248–256.
2. Biggs KL, Moore WS. Current trends in managing carotid
1. As compared with CEA, CAS is most often associated artery disease. Surg Clin North Am 2007;995–1016.
with: 3. Flanigan DP, Flanigan ME, Dorne AL, et al. Long-term results
A. Lower incidence of local complications of 442 consecutive, standardized carotid endarterectomy proce-
dure in standard-risk and high-risk patients. J Vasc Surg
B. More frequent nonfatal strokes 2007;46:876–882.
C. Intraoperative hypotension 4. Luebke T, Aleksic M, Brunkwall J. Meta-analysis of random-
D. Lower rates of perioperative MI ized trials comparing carotid endarterectomy and endovascular
treatment. Eur J Vasc Endovas Surg 2007;34:470–479.
E. Fewer cranial nerve injuries 5. Mas JL, Chatellier G, Beyssen B, et al. Endarterectomy versus
Answer: B stenting in patients with symptomatic severe carotid stenosis. N
Engl J Med 2006;355:1660–1671.
2. Regional anesthesia for CEA: 6. Naylor AR. What is the current status of angioplasty vs. en-
A. Is associated with higher hospital costs than general darterectomy in patients with asymptomatic carotid artery dis-
ease? J Cardiovasc Surg 2007;48:161–180.
anesthesia 7. Rothwell PM. Current status of carotid endarterectomy and
B. Results in lower perioperative stroke rates than stenting for symptomatic carotid stenosis. Cerebrovasc Dis
general anesthesia 2007;24(suppl 1):116–125.
15259_Ch20.qxd 3/14/09 6:44 PM Page 74
CHAPTER 20
Postpneumonectomy Pulmonary Edema
Nanhi Mitter
CASE FORMAT: STEP BY STEP What is the appropriate initial response to the
decrease in SpO2?
A 72-year-old, 5⬘8⬙, 60-kg man with a history of hyper- Possible etiologies of hypoxemia during OLV include malpo-
tension, benign prostatic hypertrophy, and hyperlipi- sition of the DLT, bronchospasm, low FiO2, dependent lung
demia presented with progressive dyspnea, cough, and atelectasis, and secretions. The anesthesiologist should con-
recent (2-month) weight loss of 7 kg. Bronchoscopy and firm the patient is receiving an FiO2 of 1.0 and establish that
mediastinoscopy confirmed the diagnosis of non-small the DLT is correctly positioned. It would be reasonable to
cell carcinoma, and he was scheduled to undergo a right apply suction to the ventilated lung and administer a bron-
pneumonectomy. chodilator such as albuterol. CPAD to the non-ventilated lung
The patient was currently smoking two packs of ciga- would be the next step to improve oxygenation.
rettes per day and had an 80-pack year smoking history. Following these maneuvers, the patient’s SpO2 increased to
His pulmonary function tests revealed a decreased forced 96%. Surgery proceeded, and while the surgeon was dissecting
expiratory volume/forced vital capacity (60% predicted) the pulmonary artery, severe hemorrhage ensued, and an acute
and a reversible component to his bronchospasm. His blood loss of 2 liters (over 5 minutes) was observed. Two units
medications included fluticasone/salmeterol, aspirin, sim- of packed red blood cells were administered, and the arterial
vastatin, metoprolol, and amlodipine. He was not using blood gas revealed a metabolic acidosis (pH ⫽ 7.30) with a he-
home oxygen therapy. moglobin level of 7 g/dL. The patient’s central venous pressure
On preoperative evaluation, the patient seemed com- was 5 mm Hg, blood pressure was 100/50 mm Hg, and his
fortable with a normal airway examination and dimin- heart rate measured 110 beats per minute.
ished breath sounds over the right lung field. His vital
signs were as follows: blood pressure, 150/84 mm Hg;
heart rate, 70 beats per minute; respiratory rate, 20 Are patients undergoing pneumonectomy at
breaths per minute; and SpO2, 90% to 94% on room air. risk of “fluid overload”?
His room air blood gas revealed pH, 7.34; pCO2, 56 Excess intraoperative fluids may play a role in the develop-
mm Hg, and pO2, 98 mm Hg. The patient’s preoperative ment of post-pneumonectomy pulmonary edema. In the face
cardiac evaluation revealed left ventricular hypertrophy of global hypoperfusion, however, as evidenced by metabolic
on electrocardiogram and normal left ventricular ejection acidosis and the observed hemodynamic instability, fluid re-
fraction on echocardiography. He had not experienced suscitation takes priority.
chest pain but described fatigue and shortness of breath The anesthesiologist administered another two units of
on minimal exertion, which he attributed to his lung dis- packed red blood cells. The surgeon controlled the bleeding,
ease. Preoperative investigations revealed a hemoglobin and 2 hours later, the right lung was resected, and the patient’s
concentration of 17 g/dL (all other parameters were chest was closed. The total blood loss was estimated to be 3 liters
normal). and the results of the patient’s blood gas analysis and hemoglo-
After a 16-gauge intravenous and an arterial bin concentration had normalized. He had received a total of 4
catheter were inserted, the patient was taken to the oper- units of packed red blood cells and 1 liter of crystalloid; his vital
ating room where an epidural catheter was introduced signs were also normal. Upon auscultation of his left lung, mild
at the T8 level. After a test dose was administered via expiratory wheeze was audible.
the epidural catheter, two 5-mL increments of 2% lido- After complete reversal of neuromuscular blockade and
caine with epinephrine (1:200,000) were administered. administration of albuterol (by metered dose inhaler with ex-
An infusion of bupivacaine (0.125%) and fentanyl tension), the patient’s trachea was extubated, and 40% oxygen
(10 mcg/mL) was commenced and continued throughout was administered by Venturi face mask. The patient was ad-
the case. The patient’s trachea was intubated using a left- mitted to the ICU postoperatively; his chest radiograph
sided 37 F double-lumen tube (DLT). A central venous (CXR) upon arrival revealed mild pulmonary congestion in
catheter was inserted into the right internal jugular vein. his left lung field and an absent right lung.
Upon institution of one-lung ventilation (OLV), the patient’s The patient’s ICU course was uneventful. On the second
oxygen saturation decreased from 99% to 92% over postoperative day, he was transferred to the ward but experi-
15 minutes. enced mild dyspnea 1 day later. He continued to complain of
progressive dyspnea, and his SpO2 gradually decreased from
74
15259_Ch20.qxd 3/14/09 6:44 PM Page 75
CHAPTER 20 • POSTPNEUMONECTOMY PULMONARY EDEMA 75
KEY MESSAGES
1. Patients undergoing pneumonectomy are at risk for

postoperative pulmonary dysfunction from interstitial
edema, atelectasis, and restrictive respiratory patterns
caused by inadequate analgesia.
2. Risk factors for postpneumonectomy pulmonary edema
include excess intraoperative fluid administration, prior
chest irradiation, right pneumonectomy, and possibly
preoperative alcohol use and high intraoperative venti-
latory pressures.
3. The management of postpneumonectomy pulmonary
Figure 20.1 • In the patient’s postoperative day 3 chest x-ray, edema is largely supportive, including supplementary
note the pulmonary edema pattern in the left lung and the normal oxygen, mechanical ventilatory support if necessary,
cardiac silhouette, suggesting an acute lung injury pattern. diuresis, and aggressive pulmonary toilet.
97% on a 50% oxygen face mask to 90% over the course of his
third postoperative day. A CXR revealed pulmonary edema in
QUESTIONS
the left lung field (Fig. 20.1). Blood gas analysis revealed PaO2
1. Which of the following statements are true?
to be 60 mm Hg.
A. Patients undergoing a right pneumonectomy have no
added risk for postoperative pulmonary edema.
What are the risk factors for postoperative B. All patients undergoing a pneumonectomy should
pulmonary edema? have pulmonary function tests completed
The risk factors for postpneumonectomy pulmonary edema preoperatively.
are listed in Table 20.1.1–6 C. Hypoxic pulmonary vasoconstriction should be maxi-
mized in the dependent lung.
What are the options for ventilatory D. All patients should be ventilated with high lung vol-
management of this patient? umes (10–12 mL/kg). This is the only way to ensure
that atelectasis will not develop.
At this point, the options for ventilatory management in-
clude noninvasive ventilation, transfer to the ICU for closer E. None of the above
monitoring, or immediate tracheal intubation and transfer to Answer: B
the ICU. 2. Which of the following statements is false regarding
In light of the pneumonectomy, fluid administration, CXR, management of hypoxemia during OLV?
and arterial blood gas results, it was decided to reintubate the
A. The bronchial cuff of the DLT when visualized with a
patient’s trachea and transfer him to the ICU. This decision
fiberoptic bronchoscope should be about 1 cm
was made to avoid further hypoxemia given that the clinical
above the carina.
picture was consistent with hydrostatic pulmonary edema or
acute lung injury. Over the next few hours, the patient’s oxy- B. During OLV, positive end-expiratory pressure to the
genation improved, and he was successfully weaned from the dependent, ventilated lung may worsen the shunt.
ventilator on postoperative day 5. The remainder of his postop- C. During OLV, constant positive airway pressure to
erative course was uneventful. the nondependent, nonventilated lung may improve
oxygenation.
D. High tidal volumes may injure alveoli in the venti-
T A B L E 2 0 . 1 Predictors of Postpneumonectomy lated lung.
Pulmonary Complications E. An FiO2 of 1.0 should be used.
Answer: A
1. Right pneumonectomy
3. Which of the following are risk factors for the develop-
2. Excessive perioperative fluid administration ment of postpneumonectomy pulmonary edema?
3. Increased intraoperative ventilation pressures A. Right pneumonectomy
4. Preoperative alcohol abuse B. A history of breast cancer
5. Decreased postoperative predicted DLCO C. Large volumes of intraoperative fluid
(diffusing capacity of the lung) D. A and C
6. Radiation therapy E. None of the above
Answer: D
15259_Ch20.qxd 3/14/09 6:44 PM Page 76
76 CHAPTER 20 • POSTPNEUMONECTOMY PULMONARY EDEMA
4. Dulu A, Pastores SM, Park B, et al. Prevalence and mortality of

References acute lung injury and ARDS after lung resection. Chest 2006;
1. Alam N, Park BJ, Wilton A, et al. Incidence and risk factors for 130:73–78.
lung injury after lung cancer resection. Ann Thorac Surg 2007; 5. Leo F, Scanagatta P, Baglio P, et al. The risk of pneumonectomy
84:1085–1091. over the age of 70: a case-control study. Eur J Cardiothorac Surg
2. Bapoje SR, Whitaker JF, Schulz T, et al. Preoperative evaluation 2007;31:779–782.
of the patient with pulmonary disease Chest 2007;132:1637–1645. 6. Dancewica M, Kowalewski J, Peplinski J. Factors associated
3. Licker M, de Perrot M, Spiliopoulos A, et al. Risk factors for with perioperative complications after pneumonectomy for pri-
acute lung injury after thoracic surgery for lung cancer. Anesth mary carcinoma of the lung. Interact Cardio Vasc Thorac Surg
Analg 2003;97:1558–1565. 2006;5:97–100.
15259_Ch21.qxd 3/14/09 6:45 PM Page 77
CHAPTER 21
Perioperative Antiplatelet Therapy
Nanhi Mitter
CASE FORMAT: REFLECTION packed red blood cells and 50 mL of 8.4% sodium bicarbon-
ate were administered rapidly, and hyperventilation was in-
A 62-year-old female with a history of coronary artery dis- stituted. Despite aggressive fluid resuscitation, the patient re-
ease, hyperlipidemia, and hypertension presented with mained hypotensive (mean arterial pressure 40–45 mm Hg)
vaginal bleeding and was scheduled for a total abdomi- with a CVP of 3 mm Hg. A transesophageal echocardio-
nal hysterectomy and bilateral salpingo-oophorectomy. graphic probe was inserted and revealed no regional wall
Unfortunately, 3 days before she was due to undergo this motion abnormalities. After transfusion of two further units of
operation, she experienced substernal chest pain radiat- packed red blood cells, the patient’s hemodynamic parame-
ing to her jaw. She was taken to the emergency depart- ters normalized. The surgery continued without further inci-
ment where her electrocardiogram readings (Fig. 21.1) dent. At the end of the procedure, her CVP was 11 mm Hg.
and cardiac enzymes were consistent with an ST-segment A repeat arterial blood gas analysis revealed a normal pH
elevation myocardial infarction (MI). She underwent emer- and a hemoglobin level of 11g/dL. The patient’s trachea
gency coronary angiography, which revealed 99% oc- was extubated, and she was transferred to the ICU where a
clusion of the left circumflex artery. An angioplasty was cardiac evaluation was normal.
performed, a bare metal stent (BMS) was placed across
the lesion, and normal flow was re-established. She was
admitted to the coronary care unit, and after an unevent-
ful recovery was discharged home 5 days later. CASE DISCUSSION
The patient’s total abdominal hysterectomy and bilat-
eral salpingo-oophorectomy had been canceled and was Percutaneous coronary interventions (PCI) generally should not
rescheduled for 4 weeks after her ST-segment elevation MI. be performed as a preoperative step to prevent adverse cardio-
On preoperative evaluation for the re-scheduled procedure, vascular events for patients undergoing noncardiac surgery un-
she was noted to be taking metoprolol, hydrochlorothiazide, less they present with an acute coronary syndrome. Patients
simvastatin, and aspirin. She had stopped taking clopido- who present with an acute coronary syndrome and who require
grel 7 days previously but had continued to take aspirin. subsequent noncardiac surgery require special evaluation and
She had stopped smoking 3 years previously, and her alco- manipulation of their medical therapy.1 The type of interven-
hol consumption was minimal. With the exception of hemo- tion—percutaneous transcoronary angioplasty versus coronary
globin concentration 8.9 g/dL, all of her laboratory values artery stenting—should be planned considering the choice of
were within normal limits. Since her ST-segment elevation dual-antiplatelet therapy (DAT), risk of bleeding, and the na-
MI, she had been asymptomatic and had been able to walk ture and timing of surgery.
on a treadmill without difficulty. She appeared nervous but Using the guidelines outlined in Table 21.1 will help with
otherwise healthy. The patient’s vital signs were as follows: planning for surgery.
temperature, 37.0°C; blood pressure, 120/71 mm Hg; Current recommendations regarding DAT include the
heart rate, 62 beats per minute; respiratory rate, 18 beats use of aspirin and a thienopyridine agent. DAT is initiated
per minute; and room air oxygen saturation, 99%. Her phys- because upon balloon inflation or stent deployment, the en-
ical examination was unremarkable, and the upper airway dothelium of the coronary artery is denuded. Normally, the
was evaluated as normal. endothelium functions to inhibit platelet aggregation along
After standard ASA monitors were applied and the ar- the vessel wall. Without the endothelium present, pharmaco-
terial and venous cannulae were inserted, anesthesia was in- logic agents such as aspirin and a thienopyridine agent must
duced, and the patient’s trachea was intubated uneventfully. provide for the platelet inhibitory function until the endothe-
A triple-lumen catheter was inserted in her right internal jugu- lium resumes this role.
lar vein, and her central venous pressure (CVP) was moni- In the setting of balloon angioplasty (BA) and BMS, the
tored continuously. Two hours into the procedure, blood loss endothelium develops after 4 to 6 weeks; hence DAT is no
was estimated to be 1 liter, the patient became tachycardic longer necessary and is subsequently discontinued.2 After a
and hypotensive, and her CVP was 3 mm Hg. Arterial blood period of time, however, late stent restenosis of the BMS can
gas analysis revealed metabolic acidosis, and the patient’s lead to MI or even death, and therefore, drug-eluting stents
hemoglobin concentration was 6.6 g/dL. Two units of (DES) have become widely used. There are two types of
DES—the sirolimus-eluting stent and the paclitaxel-eluting
77
15259_Ch21.qxd 3/14/09 6:45 PM Page 78
78 CHAPTER 21 • PERIOPERATIVE ANTIPLATELET THERAPY
perform surgery in patients with BMS, the risk of acute stent

thrombosis (albeit rare, ⬍0.1% in most case series) and rein-
farction is present.1,5
Invasive monitoring such as a transesophageal echocar-
diogram can be helpful in these patients to differentiate
between intrinsic cardiac etiology (i.e., in-stent restenosis
manifesting as regional wall motion abnormalities) versus
Figure 21.1 • The patient’s electrocardiogram reading reveals extrinsic factors that may lead to hemodynamic instability
an ST-segment elevation myocardial infarction. (i.e., hypovolemia secondary to acute blood loss or to bowel
preparation). High-risk patients can be managed by optimiz-
ing the myocardial oxygen supply/demand ratio. Methods to
stent. These stents are impregnated with chemotactic achieve this goal include but are not limited to avoiding
agents that help to prevent re-endothelialization that leads tachycardia, providing adequate analgesia in the preopera-
to late stent restenosis. Because these stents prevent re- tive setting, optimizing oxygenation and ventilation, avoid-
endothelialization, DAT is mandated to prevent acute ing alkalosis and acidosis, avoiding anemia, aggressive fluid
thrombosis of the stent for longer periods of time compared resuscitation, perioperative ␤-blockade, and statin use.
with BMS or balloon angioplasty. Finally, postoperative management may include ICU admis-
In patients who have undergone balloon angioplasty, per- sion and close follow-up.
forming noncardiac surgery within the first 2 weeks may be
unsafe because of residual injury from recent vessel manipula-
tion. Performing surgery between 2 to 4 weeks is ideal because
of theoretical vessel healing and the low risk of restenosis at
the site, which is most common after 8 weeks. Patients should KEY MESSAGES
be treated with DAT for 4 to 6 weeks.2–4
In patients undergoing stenting with BMS, the risk of 1. Preoperative management of a patient who has had a
acute thrombosis is greatest in the first 2 weeks, and the risk recent acute MI but needs urgent noncardiac surgery
for restenosis is greatest ⬎12 weeks. Therefore, the ideal time requires special consideration with respect to antico-
for noncardiac surgery after BMS is 4 to 6 weeks, as it is rare agulation and the type of revascularization procedure
for thrombosis to occur during this interval because of at least to be performed.
partial endothelialization of the BMS. DAT should be contin- 2. Antiplatelet therapy is necessary in patients undergo-
ued for 1 month when BMS are used and in some cases ing PCI because of denuding of the endothelium from
longer.4 balloon deployment or the device used. The American
In patients undergoing stenting with DES, the current rec- College of Cardiology and the American Heart
ommendation is to delay elective surgery until the patient has Association recommend varying durations for DAT
completed the appropriate course of DAT. In the event of ur- depending on the type of coronary intervention.
gent or emergent surgery when the thienopyridine therapy
must be discontinued, then, if at all possible, the aspirin should 3. For patients who have had a DES placed, continuation
be continued perioperatively, and the thienopyridine therapy of both clopidogrel and aspirin in the perioperative
should be restarted as soon as possible. period is recommended. If clopidogrel needs to be
In this case, the patient had a BMS placed and underwent stopped, aspirin should be continued throughout the
surgery after 4 weeks. Although this is the ideal time to perioperative period.
T A B L E 2 1 . 1 Recommendations Regarding Time Frame for Surgical Intervention

After Revascularization
Mode of
Revascularization Unsafe Safe Period Unsafe
BA ⬍2 weeks ⬎2 weeks
BMS ⬍4–6 weeks 4–6 weeks ⬎12 weeks
DES ⬍1 year After 1 year
This table demonstrates “safe” and “unsafe” time periods for patients undergoing elective noncardiac surgery after a revascu-
larization procedure. The decision regarding timing of surgery should be ultimately made by the anesthesiologist, surgeon,
cardiologist, internist, and patient involved. Data based on the American College of Cardiology/American Heart Association
2007 guidelines.
BA, balloon angioplasty; BMS, bare metal stent; DES, drug-eluting stent.
15259_Ch21.qxd 3/14/09 6:45 PM Page 79
CHAPTER 21 • PERIOPERATIVE ANTIPLATELET THERAPY 79
QUESTIONS B. It is recommended to wait 4 to 6 weeks after pa-

tients have had a BMS placed before proceeding
1. Which of the following drug combinations are used as with surgery.
DAT for patients undergoing PCI? C. Only 6 weeks of DAT are necessary for patients who
A. Aspirin and clopidogrel have had placement of a DES.
B. Lovenox and clopidogrel D. Elective surgery can be performed without incident in
patients after BA within the first 2 weeks of the PCI.
C. Coumadin and clopidogrel
Answer: B
D. Coumadin and aspirin
Answer: A
References
2. Which of the following is a true statement regarding 1. Fleisher LA, Beckman JA, Brown KA, Calkins H, et al.
antiplatelet therapy (AT) in patients who have under- ACC/AHA 2007 Guidelines on Perioperative Cardiovascular
gone PCI? Evaluation and Care for Noncardiac Surgery: Executive
A. The patients are placed on AT because they are at Summary. A Report of the ACC/AHA Task Force on Practice
risk for stroke after PCI. Guidelines. Circulation 2007;116: 1971–1996.
2. Brilakis ES, Orford JL, Fasseas P, et al. Outcome of patients
B. In patients undergoing PCI with DES, only 3 months undergoing balloon angioplasty in the two months prior to non-
of aspirin are necessary for AT. cardiac surgery. Am J Cardiol 2005;96:512–514.
C. Patients need AT after PCI because in the process 3. Leibowitz D, Cohen M, Planer D, et al. Comparison of cardio-
of balloon or stent deployment, the endothelium is vascular risk of noncardiac surgery following coronary angio-
plasty with versus without stenting. Am J Cardiol 2006;97:
denuded—the normal endothelium is necessary to
1188–1191.
prevent platelet aggregation. 4. King SB, Smith SC, Hirshfeld JW, Morrison DA, et al. 2007
D. Patients only need AT if they are having a stent Focused Update of the ACC/AHA/SCAI 2005 Guideline
placed. Update for Percutaneous Coronary Intervention. A Report of the
ACC/AHA Task Force on Practice Guidelines: 2007 Writing
Answer: C
Group to Review New Evidence and Update the ACC/AHA/
3. Which of the following statements is/are correct? SCAI 2005 Guideline for Percutaneous Coronary Intervention,
Writing on Behalf of the 2005 Writing Committee. Circulation
A. All patients who have symptomatic coronary artery 2008;117:261–295.
disease should undergo revascularization just so that 5. Chen MS, John JM, Chew DP, et al. Bare metal stent restenosis
they can have their elective surgery. is not a benign clinical entity. Am Heart J 2006;151:1260–1264.
15259_Ch22.qxd 3/14/09 6:46 PM Page 80
CHAPTER 22
Intraoperative Blood Conservation

Strategies
W. Christopher Croley
CASE FORMAT: REFLECTION was discharged home on the third postoperative day, at
which time her hemoglobin concentration was 9 g/dL. The
A 14-year-old, 50-kg female presented for spine surgery. patient and her family were very happy that she did not re-
She was an otherwise healthy teenager who had undergone quire allogeneic blood during her hospitalization.
previous back surgery for scoliosis. She reported taking
ibuprofen “occasionally” for back pain. Physical examina-
tion was unremarkable except for severe thoracic scoliosis.
Her preoperative hemoglobin concentration was 13 g/dL, Infectious risks, immunosuppression, limited availability, and
and all other laboratory values were within normal limits. acquisition costs are legitimate concerns of clinicians responsible
The patient was scheduled to undergo an estimated for transfusion of blood products. These concerns cause those re-
6-hour procedure in the prone position. Her parents were sponsible for perioperative care to continually evaluate and im-
present in the preoperative holding area and expressed plement therapies to reduce perioperative blood loss and thereby
their concern with her preoperative hemoglobin concentra- minimize the need for allogeneic blood transfusion. Numerous
tion and the possible need for a blood transfusion periop- mechanical, pharmacologic, and physiologic strategies have
eratively. Several strategies were discussed with the patient been identified to decrease blood transfusion.1–5 Several of these
and her parents. strategies can be used in combination in a single case.
A decision was made jointly to use acute normo- Preoperative autologous blood donation (ABD) is one tech-
volemic hemodilution before starting the case, cell saver nique that can be used.6,7 This procedure entails patients do-
intraoperatively, and blood transfusion only if signs of de- nating their own blood, which is then stored for transfusion at
creased oxygen carrying capacity were demonstrated. a later date. This process must be initiated several weeks in
Two 16-gauge peripheral intravenous catheters were advance of anticipated need to allow time for restoration of
inserted while the patient was in the holding area. In the op- intravascular volume as well as preparation of the donated
erating room, standard ASA monitors were placed, and blood. Patients can donate every 72 hours, and the last dona-
general anesthesia was induced with sufentanil (1 mcg/kg), tion should be at least 72 hours before a scheduled procedure.
propofol (2 mg/kg), and rocuronium (0.6 mg/kg). After in- ABD is contraindicated in patients with anemia (hemoglobin
duction of general anesthesia, tracheal intubation was read- ⬍11 g/dL or hematocrit levels ⬍33% before each donation).
ily accomplished with a 7.0-mm oral endotracheal tube. An Problems associated with this technique include mislabeling
18-gauge right radial arterial line was inserted for blood blood products, bacterial contamination of stored units, and
pressure monitoring, blood sampling, and to facilitate nor- the costs associated with collection and administration. Costs
movolemic hemodilution. Anesthesia was maintained with a associated with preoperative ABD can be 50% to 70% greater
sufentanil infusion at 0.3 mcg/kg per hour, sevoflurane than similar techniques of acute normovolemic hemodilution
(inspired concentration 1.5%–2%), and a 50:50 mixture of and cell salvage (Table 22.1).
nitrous oxide/oxygen. Motor-evoked potentials were moni- Acute normovolemic hemodilution (ANH) is the process of
tored; therefore, no additional neuromuscular blocking removing whole blood while simultaneously infusing crystalloid
agent was used. or colloid fluid to maintain intravascular volume. This is an
Utilizing strict aseptic technique, 500 mL of blood was effective, low-cost means of intraoperative blood conservation
collected using the arterial cannula in a citrate-phosphate- that is underutilized. Blood is collected in citrate-phosphate-
dextrose containing bag. Simultaneously, 500 mL of 6% dextrose-containing bags at the beginning of the procedure and
hetastarch was administered intravenously. The patient stored in the operating room, at room temperature, for up to
was hemodynamically stable throughout the procedure. 8 hours. Collection bags are numbered by the order in which
Approximately 4.5 hours into the surgery, the estimated they were collected and are then transfused in the reverse order.
blood loss was 900 mL, and the surgeon was starting to This means the first bag collected, which (theoretically at least)
close. Using the products of cell salvage collected intra- has a greater red blood cell mass and greater concentration of
operatively, 300 mL was administered. The patient’s trachea clotting factors, is transfused last. Because this product is not
was extubated at the end of the procedure, and she was collected and stored off-site, risks of clerical errors and process-
transferred to the recovery room with stable vital signs. Her ing of the blood are greatly reduced. ANH is also a more
postoperative hemoglobin concentration was 10 g/dL. She cost-effective method of decreasing perioperative blood trans-
fusion requirements. Platelets and clotting factors are usually
80
15259_Ch22.qxd 3/14/09 6:46 PM Page 81
CHAPTER 22 • INTRAOPERATIVE BLOOD CONSERVATION STRATEGIES 81
T A B L E 2 2 . 1 Contraindications to Autologous T A B L E 2 2 . 2 Overview of Pharmacologic

Blood Donation Agents
• Anemia (hemoglobin ⬍11 g/dL) Antifibrinolytic Agents Aminocaproic acid

• Infection or risk of bacteremia Tranexamic acid
• Angina Topical Agents Thrombin
• Recent myocardial infarction Gelatin sponges
• Uncontrolled seizure disorders Fibrin
Procoagulant Drugs Desmopressin
Adapted from Porte RJ, Leebeek FWG. Pharmacological strategies to
well preserved with this method because the blood is stored at decrease transfusion requirements in patients undergoing surgery.
room temperature and then transfused within a relatively short Drugs 2002;62:2193–2211.
time. Relatively few studies have examined the practice of
ANH. A small number of prospective, randomized studies have
been completed and represent ANH as equivalent to preopera- thopaedic patients undergoing hip or knee arthroplasty have
tive autologous donation in reducing the need for allogeneic shown a decreased requirement for perioperative blood transfu-
blood transfusions. sion when erythropoietin has been administered several weeks
Cell salvage and reinfusion is another commonly used before surgery. Some studies have shown generation of sub-
method for autologous blood procurement and can be done stantial (up to 1102 mL) red blood cell production, when exoge-
intraoperatively or postoperatively. Cell salvage techniques in- nous erythropoietin has been administered. Antifibrinolytic
volve devices that collect blood as it is lost and facilitate its sub- agents should be considered when there is an imbalance be-
sequent retransfusion. Red blood cells collected in this manner tween coagulation and fibrinolysis. Other pharmacologic aids
are commonly filtered through a microaggregate filter before that help control perioperative blood loss include topical agents
transfusion to remove tissue debris and blood clots. The function (e.g., thrombin) and procoagulant drugs such as desmopressin
of red blood cells from salvage techniques appears to be similar (Table 22.2).
to that of allogeneic red blood cells. This technique cannot be There are numerous methods (some outlined previously)
used if topical procoagulants (e.g., topical thrombin) are present for minimizing intraoperative blood loss and decreasing peri-
in the surgical field from which the blood is being recovered. operative allogeneic blood transfusion requirements. To date,
Salvaged blood often undergoes a washing procedure using none of these methods has been shown to decrease the duration
saline solutions to remove some inflammatory mediators (e.g., of hospital stay. In view of the multiplicity of methods avail-
cytokines). Unwashed salvaged blood has a greater incidence of able, it is important for institutions to establish and implement
hypotension, hyperthermia, and pulmonary edema when rein- transfusion guidelines with appropriate transfusion thresholds
fused than washed blood. Other risks associated with cell salvage and individualized to each patient (Table 22.3). The tech-
include air emboli, infection, and coagulation derangements. niques discussed in this case can be used alone or in combina-
Induced hypotension is an anesthetic technique that can be tion and should be tailored to meet the needs of each patient.
used to minimize intraoperative blood loss.8 This technique has
been well described, primarily in the orthopaedic literature,
where it has been shown that blood loss can be reduced by 30% T A B L E 2 2 . 3 Examples of Blood Transfusion
to 50% when using a hypotensive or regional (spinal or epidural) Indications
technique. Induced hypotension involves lowering the mean ar-
terial pressure to 50–55 mm Hg, using either sympathectomy Patient with acute blood loss ⬎20% of blood volume:
associated with neuraxial anesthesia or vasoactive agents (e.g., Transfuse
esmolol, nicardipine, nitroprusside). Hypoperfusion is the obvi- Hemoglobin/hematocrit ⬍10 g/dL or 30%, ask:
ous concern when deliberately lessening the patient’s blood
• History of coronary artery disease
pressure. This technique should be used cautiously in patients
with altered autoregulatory mechanisms (e.g., hypertension) • History of stroke
and those susceptible to ischemic complications (e.g., coronary • History of valvular heart disease
artery disease, renal insufficiency, diabetes). It should also be
noted that induced hypotension and ANH are sometimes used • Syncope
If yes to any Consider
in combination. Using this combination increases the risk of • Tachycardia
transfusion
decreased oxygen delivery. • Angina
Pharmacologic methods that can decrease the need for
perioperative blood transfusion (but not necessarily intraopera- • Hypoxemia
tive blood loss) include preoperative administration of • Mental status changes
erythropoietin and/or intraoperative administration of antifibri- • Electrocardiogram changes
nolytic agents such as aprotinin, ⑀-aminocaproic acid, or tranex-
amic acid.9 Erythropoietin is a glycoprotein hormone that • Decreased mixed venous oxygenation
stimulates red blood cell production. Numerous studies of or-
15259_Ch22.qxd 3/14/09 6:46 PM Page 82
82 CHAPTER 22 • INTRAOPERATIVE BLOOD CONSERVATION STRATEGIES
KEY MESSAGES C. Induced hypotension

D. Intraoperative antifibrinolytic drug use
1. Blood transfusion risks can often be minimized if strate- E. Lowered transfusion thresholds
gies are used to avoid allogeneic blood transfusion.
Answer: E
2. Perioperative blood conservation requires collabora-
tion and planning by members of the surgical and 3. Which of the following patient conditions is most likely
anesthesia teams. to contradict the use of autologous blood donation?
A. A history of congestive heart failure
3. Multiple techniques may need to be combined to mini-
mize perioperative blood loss and decrease the need B. Preoperative anemia
for allogeneic blood transfusion. Examples of blood C. Insulin-dependent diabetes mellitus
conservation techniques include acute normovolemic D. Moderate aortic stenosis
hemodilution, controlled hypotension, ABD, and cell
E. A history of a prior stroke
salvage/reinfusion.
Answer: B
4. ABD as well as donor-directed blood donation can still
pose some risks that are associated with banked
blood from anonymous donors. References
1. Bridgens JP, Evans CR, Dobson PMS, et al. Intraoperative red
blood-cell salvage in revision hip surgery. A case-matched study.
J Bone Joint Surg Am2007;89:270–275.
2. Carless P, Moxey A, O’Connell D, et al. Autologous transfusion
QUESTIONS techniques: a systematic review of their efficacy. Transfusion
Medicine 2004;14:123–144.
1. When comparing ABD toANH as blood conservation 3. Dutton RP. Controlled hypotension for spinal surgery. Eur
Spine J 2004;13:S66–S71.
strategies, ABD: 4. Goodnough LT. Blood and blood conservation: a national per-
A. Is more cost-effective than ANH spective. J Cardiothor Vasc Anes 2004;4:6s–11s.
B. Is more efficacious than ANH 5. Goodnough LT. Rationale for blood conservation. Surgical
Infections 2005;6:3s–8s.
C. Produces better preservation of platelet function 6. Keating EM, Callaghan JJ, Ranawat AS, et al. A randomized,
than ANH parallel-group, open-label trial of recombinant human erythro-
D. Is less likely to be associated with clinical errors poietin vs. preoperative autologous donation in primary total
than ANH joint arthroplasty. J Arthroplasty 2007;22:325–333.
7. Park JO, Gonen M, D’Angelica MI, et al. Autologous versus al-
E. Results in bacterial contamination of blood more logeneic transfusions: no difference in perioperative outcome
often than ANH after partial hepatectomy. J Gastrointest Surg 2007;11:1286–1293.
Answer: E 8. Lim YJ, Kim CS, Bahk JH, et al. Clinical trial of esmolol-
induced controlled hypotension with or without acute normov-
2. The most efficacious of the following techniques to re- olemic hemodilution in spinal surgery. Acta Anaesthesiol Scand
duce perioperative blood transfusion is: 2003;47:74–78.
9. Porte RJ, Leebeek FWG. Pharmacological strategies to decrease
A. Acute normovolemic hemodilution transfusion requirements in patients undergoing surgery. Drugs
B. Autologous blood donation 2002;62:2193–2211.
15259_Ch23.qxd 3/14/09 6:47 PM Page 83
CHAPTER 23
Transfusion Thresholds and Intraoperative

Coagulopathy
Anthony Hennessy
CASE FORMAT: REFLECTION An extended incision was required, as surgical access

was difficult. Despite careful surgical technique, the patient
A 69-year old, 70-kg man was admitted to hospital on the bled at a steady rate, losing 600 mL of blood during the first
day before planned revision hip arthroplasty. He had un- hour. Ephedrine 6 mg ⫻ 2 was administered to maintain
dergone an ipsilateral total hip replacement 6 years previ- MAP ⬎70 mm Hg during that time. Removing the old pros-
ously. This hip had caused him severe pain and disability thesis and cement with exposure of cancellous acetabular
for the preceding 4 months. Four years previously, he had and femoral bone led to ongoing hemorrhage despite pack-
suffered “a small heart attack” for which he spent 5 days in ing of the femur.
a distant hospital. He had not experienced angina since After 2 hours of surgery, the patient’s estimated blood
then and described good exercise tolerance, playing a loss was 1300 mL. He had received 2 L of Hartmann’s so-
round of golf 3 days a week up to 4 months previously lution with 500 mL of colloid and five aliquots of ephedrine
when his mobility had deteriorated. He was taking aspirin (each 6 mg) to maintain MAP ⬎70 mm Hg and urine out-
75 mg a day, which he had discontinued 7 days previously put ⬎50 mL per hour. An epidural bolus of bupivacaine
as per his surgeon’s request. The patient was also taking 0.5% 5 mL had been administered to maintain adequate
bisoprolol 10 mg daily and pravastatin 20 mg daily. sensory block. The patient’s SpO2 was 97%, his heart rate
The patient’s clinical examination was unremarkable: was 82 BPM, and ECG ST monitoring was unchanged. His
blood pressure, 135/81 mm Hg (mean arterial pressure, core temperature was 35.9oC. Arterial blood gas analysis
[MAP] 95 mm Hg); electrocardiogram (ECG) showed sinus demonstrated the patient’s Hb level was 9.1 g/dL, and his
bradycardia at 58 beats per minute (BPM) with no other ab- serum lactate level was 3.1 mmol/L. Having decided that
normality; chest radiograph was normal; hemoglobin (Hb) a transfusion threshold of 8.0 g/dL was reasonable, the
level,12.1 g/dL; and other laboratory results were within anesthetist requested two units of PRBCs and decided to
normal limits. The blood bank made four units of cross- recheck the Hb in 1 hour. Surgeons described the patient
matched packed red blood cells (PRBC) available on request. as “oozy” and murmured about the aspirin effect. A coag-
A 20-gauge radial arterial cannula, a 14-gauge intra- ulation screen was dispatched to the laboratory.
venous cannula, and a triple-lumen central venous catheter The patient required aliquots of ephedrine with greater
were inserted, and administration of Hartmann’s solution frequency over the following 30 minutes to maintain MAP
(1 L) was started preoperatively. A combined spinal ⬎70 mm Hg, and the anesthetist decided to transfuse the
epidural was placed at L3 to L4 using an 18-gauge Tuohy two units of PRBC, as there was ongoing hemorrhage.
needle and a 27-gauge pencil point spinal needle. Isobaric After reconstruction of the acetabular cup using bone
bupivacaine 0.5% (2 mL) was injected intrathecally fol- graft, wires, and an acetabular cage, reaming com-
lowed by bupivacaine 0.5% (5 mL) epidurally producing a menced on the femur with a visible increase in blood loss.
satisfactory sensory block to T10. Midazolam 2 mg was ad- The patient’s MAP decreased to 55 mm Hg, his heart
ministered; oxygen (O2) at 28% via face mask was ap- rate increased to 88 BPM, and his core temperature de-
plied, a temperature-monitoring urinary catheter was increased to 35.3oC. The anesthetist administered 100 ␮g
serted, and the patient was draped and prepared for aliquots of phenylephrine to maintain the patient’s MAP
surgery. Surgery commenced with O2 saturations of 97%, ⬎60 mm Hg.
heart rate 68 BPM, and the patient’s MAP was 71 mm Hg. Repeat analysis showed that the patient’s Hb concen-
The anesthetist calculated a maximal allowable blood tration was 7.7 g/dL, and his serum lactate levels were
loss (MABL) to a minimum Hb of 8 g/dL based on the pa- 5.8 mmol/L. The anesthetist requested and transfused two
tient’s stable ischemic heart disease using the formula: further units of PRBC and ordered four more (he was in-
⎡ (initial Hb ⫺ minimum ⎤ formed that those would be available in 1 hour). The results
MABL ⫽
⎢ allowable Hb) ⎥ ⫻ (weight in kg) of the coagulation screen were telephoned to the operating
⎣ initial Hb ⎦ room: the international normalized ratio was 1.7, and the
activated partial thromboplastin time was 41 seconds.
⫻ (mL of blood per kg body weight). Two units of fresh frozen plasma were transfused. The
⎛ 12.1 ⫺ 8.0 ⎞ femoral shaft required bone graft before insertion of the
⎝ 12.1 ⎠ ⫻ 70 ⫻ 72 ⫽ MABL of 1708 mL. femoral prosthesis, which was eventually accomplished after
83
15259_Ch23.qxd 3/14/09 6:47 PM Page 84
84 CHAPTER 23 • TRANSFUSION THRESHOLDS AND INTRAOPERATIVE COAGULOPATHY
rinolysis, and thrombin generation, resulting in less allogeneic

3 hours. The surgery continued with measurement and fitting blood transfusion and less bleeding. For revision or bilateral
of the femoral component requiring one change followed by hip arthroplasty, blood loss is decreased through the adminis-
closure. The total blood loss was estimated to be 2110 mL. tration of aprotinin by 25% to 50% in various studies.8 There
The patient was transferred to the postanesthetic care are concerns about adverse thrombogenic and renal effects of
unit. His vital signs were stable as follows: MAP, 61 mm Hg; aprotinin.9 A recent prospective randomized controlled trial
SpO2, 97%; heart rate, 91 BPM; and a temperature of in patients undergoing high-risk cardiac surgery has shown
35.1oC. He complained of feeling cold and was shivering. an excess mortality rate in patients who received aprotinin
One hour postoperatively, Hb concentration was 8.7 g/dL, compared with those who received tranexamic acid or
international normalized ratio was 1.9, and activated par- aminocaproic acid.10 The excess mortality occurred despite a
tial thromboplastin time was 44 seconds. There was ongo- greater decrease in blood loss in the aprotinin group.
ing loss in the drains. One unit of PRBC was transfused, and Tranexamic acid inhibits fibrinolysis by blocking the lysine
two additional units of fresh frozen plasma and one unit of binding sites of plasminogen to fibrin. Studies have shown a
cryoprecipitate were administered. reduction in blood loss of 43% to 54% in patients undergoing
The patient developed chest pain with ST depression on knee surgery.11 Conclusive evaluation of potential prothrom-
ECG during the night and required transfer to the coronary botic adverse effects and demonstration of beneficial effects on
care unit. He remained there for 3 days during which T-wave reducing blood loss in orthopaedic surgery are required before
inversion on ECG and an increase in serum troponin levels the routine use of tranexamic acid can be recommended for
were diagnostic of a subendocardial myocardial infarct. hip revision arthroplasty.
Intraoperative Blood Salvage
CASE DISCUSSION Perioperative red cell salvage and filtration, combined with
appropriate washing of red blood cells and retransfusion is an
Revision hip arthroplasty is performed commonly, as primary appropriate therapy to decrease allogenic transfusion pro-
hip arthroplasty is associated with a 10% failure rate by 10 vided that infection and malignancy have been excluded. The
years. Reasons for failure include aseptic loosening, instability, available evidence supports its use when the expected blood
and infection. Removing the implanted prosthesis and expos- loss is ⬎1500 mL. Adverse effects include transmission of in-
ing cancellous bone of both the acetabulum and femur leads to fection and possibly worsening of coagulopathy.12 Use of a
prolonged exposure of, and bleeding from the medullary vas- blood salvage system in the case discussed would have de-
culature. The associated blood loss is substantial, as the mean creased the patient’s exposure to allogenic transfusion and the
intraoperative blood loss was 2249 mL (range, 900–5600 mL) risks of associated adverse effects.
by one estimate.1
The World Health Organization defines anemia as a Hb Transfusion Thresholds/Maximal
level ⬍13 g/dL.2 In general, for patients undergoing noncar- Allowable Blood Loss with
diac surgery, preoperative anemia is associated with a poor Coexisting Ischemic Heart Disease
postoperative outcome. A large recent retrospective study Calculating a maximal allowable blood loss for an individual
showed a 1.6% increase in 30-day postoperative mortality for patient is useful and is usually based on a formula first popu-
each percentage-point increase or decrease in the hematocrit larized by Gross.13 Selecting the initial Hb as the denominator
value from normal.3 Mild degrees of anemia have been associ- results in a conservative estimate of MABL. Variations using
ated with worse outcomes in patients with ischemic heart dis- mathematical modeling with different hemoglobin or hemat-
ease.4 Early preoperative screening for elective surgery and in- ocrit values and incorporating ongoing hemodilution and cell
tervention to investigate anemia and optimize Hb levels would salvage have been reported.14
reduce transfusion and improve outcome. Thirty days before The Transfusion Requirement in Critical Care trial has pro-
surgery is an appropriate time for screening to allow for opti- duced excellent prospective data on transfusion requirements in
mization.5 A combination of appropriate investigations and chronic stable critical care patients.15 The trial excluded pa-
therapy using iron, folate, vitamin B12, and erythropoietin can tients with active hemorrhage and other acute hemodynamic
be used. Commonly used erythropoietin regimens include6 600 insults. The outcome was no worse in the group for whom a
units/kg weekly ⫻ four doses 300 units/kg for 15 days. transfusion threshold was 7.0 g/dL as compared with that for
Preoperative autologous blood donation is useful in de- whom the threshold was 9.0 g/dL. The only patient subgroup
creasing allogenic transfusion exposure but requires rigorous with evidence of poorer outcome in the lower threshold arm
organization and planning to be of value.7 There is a risk of was patients with known ischemic heart disease.
adverse reactions to and infections from blood storage. It is These data cannot be extrapolated to calculate MABL in the
probably not the optimal management for a patient with is- hemorrhaging patient. Similarly, the use of these hemoglobin
chemic heart disease such as in the case discussed. This type of values to rigidly define transfusion thresholds intraoperatively
treatment would not outweigh the benefits of Hb optimiza- would not be appropriate. O2 consumption and utilization are
tion with erythropoietin. markedly different in patients with intraoperative hemody-
namic stress and hemorrhage compared with recovering stable
Antifibrinolytic Therapy critical care patients.
Aprotinin has been used with success in decreasing blood loss The poorer outcome of patients with unstable ischemic
in orthopaedic surgery including spine, hip, and knee surgery. heart disease in the lower threshold group in the Transfusion
Aprotinin decreases the systemic inflammatory response, fib- Requirement in Critical Care trial may be relevant to the
15259_Ch23.qxd 3/14/09 6:47 PM Page 85
CHAPTER 23 • TRANSFUSION THRESHOLDS AND INTRAOPERATIVE COAGULOPATHY 85
management of the patient described in this case. It is difficult 2. Fresh frozen plasma should be administered when the
to define the point at which O2 consumption/extraction by international normalized ratio or activated partial throm-
myocardial tissue is maximal and can only be improved by boplastin time is elevated.
augmenting the O2 carrying capacity. 3. Cryoprecipitate should be administered when fibrinogen
The best evidence currently available supports the following: concentrations are ⬍80 mg/dL (2.3 umol/L).
• Hb ⬎10 g/dL: Transfusion is unlikely to be useful. These guidelines also indicate that recombinant activated
• Hb ⬍7 g/dL: Transfusion is likely to be useful. factor VII is an appropriate rescue drug when traditional,
well-tested options have been exhausted.20
Between these levels, the decision to transfuse should be
Development of coagulopathy in the case described herein
based on the rate of blood loss and ongoing loss supported
was multifactorial. Observation of the surgical field and com-
by laboratory and clinical evidence of inadequate tissue
munication with the surgical team would have led to earlier
oxygenation.
awareness of the need for intervention.
Maximal allowable blood loss and Hb thresholds are very
useful for guidance at the outset but are difficult to apply sat-
isfactorily in patients with ongoing substantial hemorrhage. KEY MESSAGES
The rate of early blood loss, the identified risk of periopera-
tive acute coronary syndrome, and the known complexity and 1. Anemia requires investigation and treatment before
duration of this surgery should have prompted an earlier major elective surgery.
intervention to optimize O2 carrying capacity.
2. Estimates of transfusion thresholds, maximum allow-
Intraoperative Hypothermia able blood loss, and rates of ongoing blood loss
Mild perioperative hypothermia (⬍1°C) increases blood loss should be used to guide transfusion.
by approximately 16% (4%–26%) and increases the relative 3. Intraoperative red cell salvage can reduce allogenic
risk for transfusion by approximately 22% (3%–37%).16 transfusion.
Maintaining perioperative normothermia decreases blood loss
and transfusion requirement by clinically important 4. Preoperative consideration should be given to aggres-
amounts.16 Shivering will increase O2 consumption contribut- sive maintenance of intraoperative normothermia.
ing further to tissue hypoxia and critical organ ischemia. 5. In the operative setting, abnormal excessive bleeding or
Aggressive intraoperative warming reduces blood loss during “ooze” can provide early evidence of coagulopathy.
hip arthroplasty.17 Perioperative hypothermia also adversely
affects wound healing.18 In the case discussed, development of
intraoperative hypothermia was the most preventable factor
that contributed to the adverse patient outcome.
QUESTIONS
Perioperative Coagulopathy
Coagulopathy can develop in patients with substantial hemor- 1. What is the result of choosing “initial Hg” as the
rhage as a result of hemodilution, hypothermia, administration denominator when calculating MABL?
of fractionated blood products, and disseminated intravascular Answer: A conservative (small) estimate of MABL
coagulation. results.
The decision when and if to discontinue antiplatelet med-
ication or other anticoagulants is important and difficult. This 2. At what level of anticipated blood loss in intraoperative
case highlights these difficulties, as discontinuing antiplatelet cell salvage viable?
medication increases the risk of postoperative myocardial in- Answer: 1500 mL
farction by a factor of three, and continuation will increase
hemorrhage volume by a factor of 1.5. In the elective setting, 3. What is the effect of mild intraoperative hypothermia
multidisciplinary assessment of the risk/benefit ratio for each (⬍1°C) on blood loss?
individual patient will be necessary to optimize outcome and Answer: It substantially increases intraoperative blood
minimize risk in the perioperative period.19 loss (approximately 16%).
Intraoperative and postoperative management of potential
or actual coagulopathy includes (a) visual assessment of the sur- References
gical field for microvascular bleeding and laboratory monitor- 1. Blackley HR, Davis AM, Hutchison CR, et al. Proximal femoral
ing for coagulopathy, (b) transfusion of platelets, (c) transfusion allografts for reconstruction of bone stock in revision arthro-
of fresh frozen plasma, (d) transfusion of cryoprecipitate, plasty of the hip. JBJS Am 2001;83:346–54.
(e) administration of drugs to treat excessive bleeding (e.g., 2. DeMaeyer E, Adiels-Yagman M. The prevalence of anaemia in
desmopressin, topical hemostatics), and (f) recombinant acti- the world. World Health Stat Q 1985;38:302–316.
vated factor VII. 3. Wu WC, Schifftner TL, Henderson WG, et al. Preoperative
The American Society of Anesthesiologists guidelines state hematocrit levels and postoperative outcomes in older patients
that, in a patient with ongoing bleeding: undergoing noncardiac surgery. JAMA 2007;297: 2481–2488.
4. Lee PC, Kini AS, Ahsan C, et al. Anemia is an independent pre-
1. Platelets should be administered when the count is dictor of mortality after percutaneous coronary intervention. J
⬍50,000 cells/mm3. Am Coll Cardiol 2004;44:541–546.
15259_Ch23.qxd 3/14/09 6:47 PM Page 86
86 CHAPTER 23 • TRANSFUSION THRESHOLDS AND INTRAOPERATIVE COAGULOPATHY
5. Goodnough LT, Shander A, Spivak JL, et al. Detection, evalua- Available at: http://www.sign.ac.uk/guidelines. Accessed
tion and management of anemia in the elective surgical patient. March 5, 2009.
Anesth Analg 2005;101:1858–1861. 13. Gross JB. Estimating allowable blood loss: corrected for dilution.
6. Feagan BG, Wong CJ, Kirkley A, et al. Erythropoietin with iron Anesthesiology. 1983;58:277–280.
supplementation to prevent allogeneic blood transfusion in total 14. Waters JH, Lee JS, Karafa MT. A mathematical model of cell
hip joint arthroplasty: a randomized controlled trial. Ann Intern salvage efficiency. Anesth Analg 2002;95:1312–1317.
Med 2000;133:845–854. 15. Hébert PC, Wells G, Blajchman MA, et al. A multicenter, ran-
7. Forgie MA, Wells PS, Laupacis A, et al. Preoperative autologous domized, controlled clinical trial of transfusion requirements in
donation decreases allogeneic transfusion but increases exposure critical care. N Engl J Med 1999;340:409–417.
to all red blood cell transfusion: results of a meta-analysis. 16. Rajagopalan S, Mascha E, Na J, et al. The effects of mild periop-
International Study of Perioperative Transfusion (ISPOT) erative hypothermia on blood loss and transfusion requirement.
Investigators. Arch Intern Med 1998;158:610–616. Anesthesiology 2008;108:71–77.
8. Murkin JM, Shannon NA, Bourne RB, et al. Aprotinin decreases 17. Winkler M, Akça O, Birkenberg B, et al. Aggressive warming
blood loss in patients undergoing revision or bilateral total hip reduces blood loss during hip arthroplasty. Anesth Analg 2000;9:
arthroplasty. Anesth Analg 1995;80:343–348. 978–984.
9. Mangano DT, Tudor IC, Dietzel C, et al. The risk associated 18. Kurz A, Sessler DI, Lenhardt R, et al. Perioperative normother-
with aprotinin in cardiac surgery. N Engl J Med 2006;354: mia to reduce the incidence of surgical-wound infection and
353–365. shorten hospitalization. N Engl J Med 1996;334:1209–1215.
10. Fergusson DA, Hebert PC, Mazer CD, et al. A comparison of 19. Chassot PG, Delabays A, Spahn DR. Perioperative antiplatelet
aprotinin and lysine analogues in high-risk cardiac surgery. N therapy: the case for continuing therapy in patients at risk of
Engl J Med 2008;358:2319–2331. myocardial infarction Br J Anaesth 2007;99:316–328.
11. Jansen AJ, Andreica S, Claeys M, et al. Use of tranexamic acid 20. Practice Guidelines for Perioperative Blood Transfusion and
for an effective blood conservation strategy after total knee Adjuvant Therapies: An Updated Report by the American
arthroplasty. Br J Anaesth 1999;83:596–601. Society of Anaesthesiologists Task Force on Perioperative Blood
12. Scottish Intercollegiate Guidelines Network. Perioperative Transfusion and Adjuvant Therapies. October 2005. Available
blood transfusion for elective surgery. Blood sparing strategies. at: www.asahq.org. Accessed March 5, 2009.
15259_Ch24.qxd 3/14/09 6:48 PM Page 87
CHAPTER 24
Anesthesia for Bariatric Surgery
CASE FORMAT: REFLECTION unit with a non-rebreather oxygen face mask in place. He
remained in the surgical intensive care unit for 24 hours for
A 44-year-old, 5⬘ 11⬙, 170-kg man (body mass index cardiopulmonary monitoring, glycemic control, and to facil-
[BMI], 52) with a history of hypertension, obstructive sleep itate the use of CPAP. The patient was discharged home
apnea (OSA), and non–insulin-dependent diabetes mellitus after 5 days but returned after 2 weeks with a suspected pul-
presented for laparoscopic gastric bypass surgery. His monary embolus. This was treated with intravenous heparin
medications included metoprolol, pioglitazone, and hy- and subsequently with subcutaneous low-molecular-weight
drochlorothiazide. He had a continuous positive airway heparin before being discharged home for the second time.
pressure (CPAP) machine at home but rarely used it. His
preoperative assessment was remarkable for a serum glu-
cose level of 200 mg/dL, an electrocardiogram showing
left ventricular hypertrophy and right heart strain, and an CASE DISCUSSION
echocardiogram revealing moderate tricuspid regurgita-
tion, right ventricular hypertrophy, and estimated peak sys- Bariatric surgery has been shown to be more efficacious than
tolic pulmonary artery pressure of 45 mm Hg. The patient’s any other method of weight reduction, and several studies
left ventricular function was normal. Physical examination have shown consistent reductions in weight and the incidence
revealed a morbidly obese man with clear lungs, normal of related comorbidities, as well as overall mortality.1,9,11,13
heart tones, and a Mallampati grade III airway with a There is a significant reduction in the incidence of hyperlipi-
“thick neck” and limited cervical extension. It was noted demia, hypertension, type 2 diabetes, and OSA accompanying
that venous access would be difficult to secure. Baseline the weight loss induced by bariatric surgery.3 Classification of
room air arterial oxygen saturation was 94%. obesity is shown in Table 24.1.
The patient was scheduled to undergo a laparoscopic Bariatric surgery encompasses several types of procedures,
gastric bypass procedure. A 22 guage intravenous line was broadly classified as either restrictive (gastric banding, vertical-
placed with difficulty, and famotidine 20 mg and metoclo- banded gastroplasty, malabsorptive [biliopancreatic diver-
pramide 20 mg were administered intravenously, with 30 mL sion]), or combined procedures (gastric bypass) (Fig. 24.1).
of sodium citrate. Midazolam 2 mg was administered in- Restrictive procedures cause weight loss by limiting the stom-
travenously before insertion of a radial arterial catheter. In ach’s capacity to accommodate food, whereas malabsorptive
the operating room, standard monitoring was commenced, surgery involves bypass or resection of the stomach and bypass
and topical anesthesia was applied to the patient’s of long segments of the small intestine to reduce the area for
oropharynx. A transtracheal injection of 4% lidocaine was nutrient absorption. Gastric bypass is a combined procedure
performed, as was an awake fiberoptic intubation. A pul- that involves dividing the stomach into a small, proximal
monary artery catheter was inserted via the right internal pouch and a separate, large, distal nonfunctional remnant.
jugular vein using ultrasound guidance. After anesthesia in- The upper pouch is then attached to the jejunum through a
duction, intermittent positive pressure was instituted using a small gastrojejunal anastomosis. The proximally divided je-
tidal volume of 8 mL/kg, respiratory rate of 14 breaths per junum is then reattached to the jejunum 75 to 150 cm below
minutes, 60% inspired oxygen, and 7 cm H2O positive the gastrojejunal anastomosis, thus creating a Roux-en-Y
end-expiratory pressure. Peak airway pressures of 36 cm limb.5 Malabsorptive surgery is effective but causes more se-
H2O were observed. The patient’s anesthetic consisted of a vere postoperative metabolic complications, whereas purely
neuromuscular blockade with vecuronium, a remifentanil in- restrictive procedures produce less durable weight loss than
fusion at 0.5 mcg/kg per minute, and 1% to 1.5% inspired gastric bypass. Laparoscopic gastric bypass appears to be the
sevoflurane. The procedure was completed in 3 hours, with most efficacious of all bariatric procedures.
blood loss of 250 mL, and 4.2 liters of Lactated Ringer’s so-
lution was used as a fluid replacement. An insulin infusion
Airway Management
was used to maintain normoglycemia. At the end of sur- Morbid obesity and OSA, a common comorbid condition, can
gery, 60 mg of ketorolac and 4 mg of ondansetron were make mask ventilation difficult. Proper positioning of the
administered. The patient’s trachea was successfully extu- obese patient with blankets to elevate the head and shoulders
bated, and he was transferred to the surgical intensive care (“ramped” position) has been shown to improve laryngeal
exposure. Although some evidence suggests more difficult
87
15259_Ch24.qxd 3/14/09 6:48 PM Page 88
88 CHAPTER 24 • ANESTHESIA FOR BARIATRIC SURGERY
suggesting that remifentanil and fentanyl dosing should be

T A B L E 2 4 . 1 Classification of Obesity
based on ideal body weight, whereas sufentanil dosing can be
Classification Body Mass Index accurately predicted using total body weight. Neuromuscular
blocking drug dosing is more predictable because of the hy-
Overweight 25 kg/m2 drophilic nature of nondepolarizing agents. Both vecuronium
Obese 30 kg/m2 and rocuronium should be dosed based on ideal body weight to
Morbidly obese 40 kg/m2 avoid prolonged neuromuscular blockade. Although all volatile
agents can be safely used in morbidly obese patients, desflurane
Super obese 50 kg/m2 and sevoflurane are associated with more rapid emergence than
isoflurane. Dexmedetomidine—a selective ␣2-adrenergic ago-
nist—may reduce intraoperative opioid requirements, while
intubation in morbidly obese patients, a study of 100 morbidly also improving intraoperative hemodynamics.2,4 Epidural anal-
obese patients found that neither obesity nor BMI predicted gesia, although technically more difficult to administer in the
difficult intubation, but rather large neck circumference (a morbidly obese, improves postoperative analgesia, as does the
marker of OSA) and a greater Mallampati score were predic- use of incisional local anesthetic infiltration.12
tive. Obese patients, however, desaturate O2 more quickly Ultimately, no one anesthetic technique has been shown to
than nonobese individuals after the induction of apnea and be superior to another for morbidly obese patients undergoing
general anesthesia; as a result, thorough preoxygenation is es- bariatric surgery, but the presence of OSA and common sense
sential. Moreover, if there is any question about the potential suggest that anesthetic techniques that employ shorter-acting
difficulty of tracheal intubation, an awake intubation tech- agents may allow a more prompt recovery, less postoperative
nique should be strongly considered. respiratory depression, and a more rapid return to baseline
Just as the approach to tracheal intubation should be ap- respiratory function.
proached with caution, the timing and decision regarding
extubation should also be managed conservatively. Many clini- Intraoperative Monitoring
cians choose postoperative mechanical ventilation in the super There is little evidence that morbidly obese patients require
obese or for patients undergoing open, rather than laparo- more intense cardiovascular monitoring during bariatric sur-
scopic, procedures. gery than nonobese patients.6 The presence of significant co-
morbidities should guide the use of more invasive monitors.
Anesthetic Management Patients with pulmonary hypertension, however, such as those
Drug pharmacokinetics differ in morbidly obese patients. with OSA or super obesity, may require the use of a pul-
Propofol dosing can be determined using total body weight, monary artery catheter. Difficulties with peripheral venous
rather than ideal or lean body weight.16 Because of their access and blood sampling are facilitated by inserting a central
lipophilicity, thiopental and benzodiazepines may need to be venous catheter, often using ultrasound guidance. Finally, it
administered in greater doses to obese than to nonobese patients. may be necessary to place intra-arterial catheters because of
Opioid pharmacokinetics are more complex, with limited data technical difficulties associated with blood pressure cuffs.
A Esophagus B C Resected
Gastric pouch stomach
tissue
Band
Gall bladder Ileum
Pancreas
Duodenum
and jejunum
Ascending colon
Figure 24.1 • (A) Adjustable gastric banding. An inflatable silicone band around the upper stomach partitions it into a
⬃30-mL proximal pouch and a large, distal remnant, connected through a narrow, nondistensible adjustable constriction.
(B) Gastric bypass divides the stomach into a small, proximal pouch measuring ⬃30 mL and a separate, large, distal defunc-
tionalized remnant. The upper pouch is joined to the jejunum through a narrow distensible gastrojejunal anastomosis. The
proximally divided jejunum is reattached to the jejunum 75 to 150 cm below the gastrojejunal anastomosis creating a Roux-
en-Y limb. (C) Biliopancreatic diversion, with or without a pylorus-sparing “duodenal switch” causes malabsorption as
pancreatic and biliary secretions are diverted to the distal small intestine approximately 50 cm from the ileocecal valve.
Absorption is thus limited to the distal ileum. A “sleeve” gastrectomy is depicted. (From Kral JG, Näslund E. Surgical treat-
ment of obesity. Nature Clinical Practice Endocrinology & Metabolism 2007;3:574–583.)
15259_Ch24.qxd 3/14/09 6:48 PM Page 89
CHAPTER 24 • ANESTHESIA FOR BARIATRIC SURGERY 89
T A B L E 2 4 . 2 Risk Factors for Postoperative QUESTIONS

Complications
1. The incidence of which of the following conditions is
• Age ⬎45 least reduced by bariatric surgery?
• Male gender A. Hypertension
• Super obesity (body mass index ⬎50 kg/m2) B. Coronary artery disease
• Pulmonary hypertension C. Diabetes mellitus
• Obstructive sleep apnea D. Hyperlipidemia
E. Sleep apnea
Answer: B
Patient Outcome 2. Which of the following medications should dosing be
The overall rates of mortality and morbidity associated with based on total body weight?
bariatric surgery are less than 1% and 15%, respectively, al- A. Fentanyl
though rates may be greater for open versus laparoscopic pro-
cedures and for patients with multiple comorbidities. A variety B. Rocuronium
of risk factors have been identified by multivariate analyses and C. Propofol
risk models as predictive of mortality. These include male gen-
D. Remifentanil
der, age ⬎45 years, BMI ⬎50 kg/m2, and the presence of
OSA/pulmonary hypertension (Table 24.2).7,8 Postoperative E. Vecuronium
mortality appears to be secondary to pulmonary embolism/deep Answer: C
venous thrombosis, intra-abdominal leaks/sepsis, and myocar-
dial infarction. Other nonfatal complications include wound 3. Which of the following patient characteristics increases
infection, pneumonia, ventral hernias, nutritional deficiencies, morbidity and mortality after bariatric surgery?
and surgical events related to a given procedure (e.g., pouch en-
A. ⬎ Female gender
largement, band slippage).
B. BMI ⬎40 kg/m2
C. Age ⬎40 years
CONCLUSION
D. OSA
For morbidly obese patients, bariatric surgery is an effective E. Presence of diabetes mellitus
method of weight reduction that decreases the incidence of co-
morbidities as well as long-term mortality. Answer: D
References
KEY MESSAGES
1. Adfams TD, Gress RE, Smith SC, et. Al. Long-term mortality
after gastric bypass surgery. NEJM 2007;357:753–761.
1. Morbidly obese patients have a high incidence of co-
2. Bakhamees HS, El-Halafawy YM, El-Kerdawy HM, et al.
morbidities, including diabetes mellitus, hypertension, Effects of dexmedetomidine in morbidly obese patients undergo-
OSA, gastroesophageal reflux disease, and pul- ing laparoscopic gastric bypass. Middle East J Anesthesiol 2007;
monary hypertension/right heart dysfunction. 19:537–551.
3. Dixon JB, O’Brien PE, Playfair J, et al. Adjustable gastric band-
2. Important anesthetic considerations include selective
ing and conventional therapy for type II diabetes. JAMA
use of special monitors (often intra-arterial and central 2008;299:316–323.
venous catheters), conservative airway management, 4. Hofer RE, Sprung J, Sarr MG, et al. Anesthesia for a patient with
insulin therapy to maintain normoglycemia, and the morbid obesity using dexmedetomidine without narcotics. Can J
use of short-acting anesthetic agents. Anesth 2005;52:176–180.
5. Kral JG, Näslund E. Surgical treatment of obesity. Nature
3. Intraoperative ventilatory management should employ Clinical Practice Endocrinology & Metabolism 2007;3:574–583.
high-inspired oxygen concentrations and 5 to 10 cm 6. Kurubsa R, Koche LS, and Murr MM. Preoperative assessment
H2O-positive end-expiratory pressure. Postoperative and perioperative care of patients undergoing bariatric surgery.
care should include aggressive cardiopulmonary moni- Med Clin N Am 2007;90:339–351.
toring for select patients with significant comorbidities 7. Levi D, Goodman ER, Patel M, et al. Critical care of the obese
and the use of CPAP for patients with OSA. and bariatric surgical patient. Crit Care Clin 2003;19:11–31.
8. Leykin Y, Pellis T, Del Mestro E, et al. Anesthetic management
4. Perioperative management and postoperative morbidity of morbidly obese and super-morbidly obese patients undergoing
and mortality are related to several risk factors, as well bariatric operations: hospital course and outcomes. Obesity
as the preoperative BMI, and super-obese patients Surgery 2006;16:1563–1569.
(BMI ⬎60) have the greatest incidence of complications. 9. Livingston EH. Obesity, mortality, and bariatric surgery rates.
JAMA 2007;298:2406–2408.
15259_Ch24.qxd 3/14/09 6:48 PM Page 90
90 CHAPTER 24 • ANESTHESIA FOR BARIATRIC SURGERY
10. Passannante A, Rock P. Anesthetic management of patients with 12. Schumann R, Shikora S, Weiss JM, et al. A comparison of mul-
obesity and sleep apnea. Anesthesiol Clin North Am 2005;23: timodal perioperative analgesia to epidural pain management
479–491. after gastric bypass surgery. Anesth Analg 2003;96:469–474.
11. Omalu BI, Ives DG, Buhari AM, et al. Death rates and causes of 13. Sjöström L, Narbro K, Sjöström CD, et al. Effects of bariatric
death after bariatric surgery for Pennsylvania residents, 1995 to surgery on mortality in Swedish obese subjects. NEJM
2004. JAMA 2007;142:923–928. 2007;357:741–752.
15259_Ch25.qxd 3/14/09 6:53 PM Page 91
CHAPTER 25
Vasopressin and Resuscitation
Stephen F. Dierdorf
CASE FORMAT: REFLECTION DC countershock was unsuccessful and asystole devel-

oped. Forty units of intravenously administered vasopressin
A 75-year-old, 95-kg male patient with a 4-day history of resulted in spontaneous cardiac activity and an increase in
worsening abdominal pain presented for an emergency la- blood pressure to 60/30 mm Hg. During the next 5 min-
parotomy for a suspected perforated duodenal ulcer. His utes, 500 mL of 5% albumin was administered, and a con-
coexisting medical conditions included hypertension tinuous vasopressin infusion at 0.2 units per minute was ini-
treated with daily losartan 100 mg and coronary artery tiated. The patient’s heart rate and blood pressure
disease. He underwent coronary artery bypass grafting at stabilized at 90 BPM and 100/50 mm Hg, respectively.
age 72 and has been free of cardiac symptoms since.
The preoperative assessment performed in the emer-
gency department showed a patient in obvious discomfort
with a blood pressure of 100/60 mm Hg, heart rate of CASE DISCUSSION
110 beats per minute, and a respiratory rate of 28 breaths
per minute. His temperature was 39°C. The patient was re- This case is representative of the course of anesthesia for an eld-
ceiving supplemental oxygen via nasal cannula at 4 liters erly patient with significant preoperative physiologic derange-
per minute, and arterial saturation by pulse oximetry was ment. The cause of clinically significant hypotension during
96%. There had been no urine output since arrival at anesthesia is not always clear, and there are many treatment
the hospital. Laboratory results obtained upon admission options. Ideally, a definitive cause for the hypotension can be
to the emergency department were as follows: hemoglo- elucidated, and specific therapy can then be instituted. The
bin, 15 g/dL; hematocrit level, 45%; serum potassium, goal of resuscitation is restoring vital organ perfusion and func-
4.3 mEq/L; sodium, 140 mEq/L; bicarbonate, 18; blood tion. In some cases, the presumptive diagnosis is accurate, but
urea nitrogen, 35; and creatinine, 1.0. The echocardio- therapy is controversial. The controversy surrounding resusci-
gram readings showed first-degree atrioventricular block tation concerns the role of vasopressors and volume expansion:
with normal QRS morphology. The patient was taken to the Is one better than the other, or is combination therapy better?
operating room for exploratory laparotomy, and standard Clinical studies of cardiac arrest are difficult because of the
monitors were applied. After preoxygenation and pretreat- large number of variables and the lack of a matched control
ment with 2 mg cis-atracurium, anesthesia was induced group. Animal models of cardiac arrest and shock have been
with propofol 100 mg. Succinylcholine 160 mg was ad- developed, but the ability to translate those findings to real-
ministered to facilitate tracheal intubation, which was world patients is unknown. The vasopressors most frequently
performed without difficulty with an 8-mm inner diameter used for resuscitation from cardiac arrest have been epineph-
tracheal tube. Soon after induction, the patient’s blood rine and norepinephrine. Although the vasoconstrictive effects
pressure decreased to 60/20 mm Hg, and his heart rate of vasopressin have been known for more than 100 years, it was
increased to 140 beats per minute (BPM). ST depression not until the mid-1990s that vasopressin garnered much scien-
appeared in the inferior leads on the surface echocardio- tific attention for resuscitation.
gram. Immediate treatment consisted of the intravenous in- Vasopressin, an antidiuretic hormone, is a naturally oc-
fusion of norepinephrine at 5 ␮g per minute, increasing to curring nonapeptide synthesized in the hypothalamus and
30 ␮g per minute, the administration of 1500 mL of stored and secreted by the posterior pituitary. Vasopressin
Lactated Ringer’s solution, and 500 mL of 5% albumin. release is triggered by increased plasma osmolarity, de-
Despite this treatment, the patient’s blood pressure contin- creased blood pressure, and decreased cardiac filling (hypo-
ued to decline, his blood pressure became unmeasurable, volemia). Three vasopressin receptors have been identified:
and his heart rate decreased to 55 beats per minute. V1 mediates vasoconstriction, V2 acts on the renal collecting
Epinephrine 1 mg was administered intravenously. The pa- tubules and causes water retention, and V3 mediates corti-
tient’s heart rate increased to 120 BPM, and his blood cotrophin release in the central nervous system. Stimulation
pressure increased to 30/15 mm Hg. A second dose of ep- of V1 receptors on vascular smooth muscle cells mobilizes in-
inephrine 1 mg increased his heart rate to 160 BPM and tracellular calcium and increases extracellular calcium influx,
produced frequent premature ventricular contractions lead- thereby causing vasoconstriction (Table 25.1).1,2 The meta-
ing to ventricular tachycardia and ventricular fibrillation. bolic effects of vasopressin are mediated via V2 and V3 recep-
tors and can influence a large number of physiologic systems.
91
15259_Ch25.qxd 3/14/09 6:53 PM Page 92
92 CHAPTER 25 • VASOPRESSIN AND RESUSCITATION
with asystole, and a combination of epinephrine (1 mg) and

T A B L E 2 5 . 1 Vasopressin Receptors and Effects
vasopressin (40 units) may be better than either drug alone.
Current recommendations are that vasopressin (40 units) may
Receptor Effector Site Effect be substituted for the first or second dose of epinephrine
V1 Vascular smooth Vasoconstriction (1 mg) during cardiac arrest. The outcome from out-of-hospi-
muscle tal cardiac arrest is very poor, and survival rates worldwide
average 6%. Survival rates from out-of-hospital witnessed
Platelets Aggregation ventricular fibrillation have, however, been reported to be as
Brain Baroreflex mediation high as 74%. This success is predicated on laypersons trained
V2 Renal collecting Antidiuresis in cardiopulmonary resuscitation and the immediate availabil-
duct cells ity of defibrillators. Patients in the operating room are well
monitored, and adverse events can be detected early and man-
V3 Anterior pituitary ACTH secretion aged with highly controlled interventions.
ACTH, adrenocorticotropic hormone.
Septic Shock The cornerstones of therapy for vasodilatory or
septic shock have been antibiotics, volume resuscitation, and
catecholamines. The key to improved survival in patients with
septic shock is rapid intervention. Current recommendations
The metabolic effects of vasopressin in critically ill humans, for the treatment of septic shock include administration of
however, have not been extensively studied. Current knowl- antibiotics and volume resuscitation to maintain a central ve-
edge suggests that vasopressin does not alter glucose, lactate, nous pressure of 8 to 12 mm Hg and a mean arterial blood
or electrolyte levels; may reduce oxygen demand; and pre- pressure of 65 mm Hg or greater. If volume administration
serves pulmonary arterial endothelial function.3 The plasma does not produce the desired hemodynamic responses, norep-
half-life of vasopressin is 4 to 20 minutes. Terlipressin is a inephrine and dopamine are the vasoactive drugs of choice.10
synthetic analog of vasopressin with a half-life of 6 hours. In cases of septic shock refractory to catecholamines or at doses
Vasopressin contributes little to blood pressure control dur- that cause side effects such as tachydysrhythmia, vasopressin
ing normal physiologic conditions. When other compensa- increases blood pressure and permits a reduction in cate-
tory mechanisms are not effective, vasopressin becomes an cholamine doses. Vasopressin in high doses can cause mesen-
important mechanism for normalizing hemodynamics. teric vasoconstriction to the point of intestinal ischemia. In low
Metabolic acidosis attenuates the effects of catecholamines. doses, vasopressin appears to improve gastrointestinal perfu-
The vasoactive effects of vasopressin, however, are unaf- sion. A continuous vasopressin infusion may be preferable to
fected by acidosis. Vasopressin may be more effective than intermittent bolus doses of the longer-acting terlipressin to
catecholamines if acidosis is present or when catecholamines reduce the likelihood of mesenteric vasoconstriction and gas-
become ineffective. Low-dose vasopressin may produce trointestinal ischemia.
vasodilation in the coronary and cerebral arterial beds and
increase myocardial blood flow (Table 25.2).4 Anaphylactic Shock Recommended therapy for anaphylactic
There are five different scenarios for which vasopressin shock is fluid administration and epinephrine. Vasopressin
may be efficacious: (a) cardiac arrest, (b) vasodilatory shock, has been shown to completely reverse histamine-induced va-
(c) anaphylactic shock, (d) hemorrhagic shock, and (e) during sodilation, whereas epinephrine results in only partial reversal.
liver transplantation. Until further definitive evidence exists, vasopressin is a rea-
sonable choice when epinephrine fails to produce hemody-
Cardiac Arrest Despite early reports of success in a small namic stability.11
number of patients suffering cardiac arrest in 1996, subse-
quent human and animal research has not fully clarified the Hemorrhagic Shock The goals of resuscitation from hemor-
role of vasopressin for resuscitation.5–9 Epinephrine has been rhagic shock have been to restore circulating blood volume to
the mainstay of pharmacologic therapy for cardiac arrest for preserve or improve vital organ perfusion and function.
decades. Vasopressin may offer some advantages in patients There is increasing evidence in animal models that volume
resuscitation alone produces a worse outcome than limited
volume resuscitation in combination with vasopressin or nor-
epinephrine.12 The precise mechanism of improved outcome
with vasopressin remains to be elucidated. Proposed mecha-
T A B L E 2 5 . 2 Vasopressin Doses nisms include vasopressin-induced vasoconstriction shifting
blood from the wound site and an increase in circulating va-
Condition Dose sopressin levels from depleted endogenous stores. Successful
Vasopressin Cardiac arrest 0.5 units/kg (bolus) resuscitation with vasopressin may be dose dependent. Low-
Hypotension 0.00002–0.002 units/kg dose vasopressin may improve hemodynamics while avoiding
the deleterious effects of organ ischemia from high doses of
per minute
vasopressin.
Terlipressin Hypotension 1 mg intravenously
(repeat every 4–6 hours) Liver Transplantation Patients with liver failure have multi-
system disease, and the development of hepatorenal syndrome
15259_Ch25.qxd 3/14/09 6:53 PM Page 93
CHAPTER 25 • VASOPRESSIN AND RESUSCITATION 93
is a poor prognostic indicator. Low-dose vasopressin infusions

KEY MESSAGES
may increase renal blood flow and have been used with some
success in treating hypotension immediately after liver trans-
1. There are multiple causes of intraoperative hypoten-
plant. At present, research data are insufficient to determine
sion and shock.
the role of vasopressin in patients with liver failure.
2. Vasopressin is effective for managing intraoperative
Intraoperative Hypotension Patients receiving long-term hypotension caused by several factors.
therapy with angiotensin-converting enzyme inhibitors or
angiotensin receptor blockers are more likely to develop hy- 3. Vasopressin complements epinephrine for resuscitation
potension during anesthesia. This hypotension may be resist- following cardiac arrest.
ant to treatment with catecholamines and volume expansion. 4. Successful resuscitation depends on early multimodal
The vasoconstrictive effect of vasopressin is independent of treatment.
catecholamine and angiotensin receptors. Vasopressin has
been shown to be effective for the treatment of hypotension in
patients receiving those drugs.13
The use of vasopressin for patients with severe hypotension
and shock is controversial. In milieu of the shock state, vascu- QUESTIONS
lar smooth muscle may be less sensitive to, and even refractory
to the effects of catecholamine. For patients who respond 1. By what mechanism does vasopressin cause
poorly to catecholamines, vasopressin provides another thera- vasoconstriction?
peutic option. Continued research should better define the role Answer: Vasopressin stimulates vasopressin-1 receptors.
of vasopressin. Activation of these receptors increases calcium movement
into vascular smooth muscle and results in vasoconstriction.
SUMMARY 2. How does the effect of vasopressin differ from the effect
of epinephrine when used for the treatment of cardiac
Hypovolemia and sepsis contributed to the intraoperative arrest?
shock that occurred with the patient described in this case. Answer: Vasopressin is effective in an acidotic milieu;
Volume resuscitation does not always correct the hemody- whereas, the effect of epinephrine is attenuated by acido-
namic instability caused by septic or hemorrhagic shock. sis. Vasopressin does not cause tachycardia.
Excessive fluid administration may, in fact, worsen the out-
come. It is not always possible to know the patient’s balance 3. Does treatment with vasopressin produce a better
between endogenous substances and intravascular volume outcome from cardiac arrest than treatment with
that results in hemodynamic stability. Choices to be made in epinephrine?
this situation include how much and what type of fluid to Answer: Despite initial reports of the efficacy of vaso-
administer and which, if any, vasoactive drugs should be pressin for treatment of cardiac arrest, other studies have
given. Norepinephrine and epinephrine have been used for not confirmed the superiority of vasopressin.
decades to treat hypotension and shock. Patients unrespon- Nonetheless, vasopressin may be effective when
sive to these drugs may develop side effects that offset the epinephrine fails.
benefits as the dosages are increased. Vasopressin is a natu-
rally occurring vasoactive substance that may be deficient in
some patients and may require replacement therapy. References
Vasopressin in combination with catecholamines may im- 1. Treschan TA, Peters J. The vasopressin system. Anesthesiology
prove the hemodynamic profile and permit a dose reduction 2006;105:599–612.
of the catecholamines. The initial enthusiasm regarding va- 2. Barrett LK, Singer M, Clapp LH. Vasopressin: mechanisms of
action on the vasculature in health and in septic shock. Crit Care
sopressin for resuscitation has been tempered by subsequent
Med 2007;35:33–40.
research. Vasopressin has a different mechanism of action at 3. Dunser MW, Westphal M. Arginine vasopressin in vasodilatory
the cellular level than catecholamines, and the two different shock: effects on metabolism and beyond. Curr Opin Anesthesiol
drugs may be complementary. If epinephrine administration 2008;21:122–127.
fails to achieve the desired effect, vasopressin is the next best 4. Jochberger S, Wenzel V, Dunser MW. Arginine vasopressin as a
choice. Although the advantages of vasopressin as compared rescue vasopressor agent in the operating room. Curr Opin
with other vasopressors for the treatment of shock are not yet Anaesthesiol 2005;18:396–404.
clear, the timing of intervention may be critical.14,15 The 5. Lindner KH, Prengel AW, Brinkmann A, et al. Vasopressin in
anesthesiologist can potentially intervene with effective refractory cardiac arrest. Ann Intern Med 1996;124:1061–1064.
treatment at the very early stages of shock, thus increasing 6. Wyer PC, Perera P, Jin Z, et al. Vasopressin or epinephrine
for out-of-hospital cardiac arrest. Ann Emerg Med 2006;48:
the likelihood of a successful outcome. More selective uses of
86–97.
vasopressin in the operating room include treatment for ana- 7. Aung K, Htay T. Vasopressin for cardiac arrest. Arch Intern
phylactic shock, vasodilatory shock after cardiopulmonary Med 2005;165:17–24.
bypass, and refractory hypotension in patients receiving 8. Ali B, Zafari AM. Narrative review: cardiopulmonary resuscita-
angiotensin-converting enzyme inhibitors or angiotensin tion and emergency cardiovascular care: review of the current
receptor blockers. guidelines. Ann Intern Med 2007;147:171–179.
15259_Ch25.qxd 3/14/09 6:53 PM Page 94
94 CHAPTER 25 • VASOPRESSIN AND RESUSCITATION
9. Hazinski MF, Nadkarni VM, Hickey RO, et al. Major changes liver trauma model with uncontrolled and otherwise lethal hem-
in the 2005 AHA guidelines for CPR and ECC: reaching the orrhagic shock in pigs. Anesthesiology 2003;98:699–704.
tipping point for change. Circulation 2005;112:IV206–211. 13. Wheeler AD, Turchiano K, Tobias JD. A case of refractory in-
10. Dellinger RP, Levy MM, Carlet JM, et al. Surviving sepsis traoperative hypotension treated with vasopressin infusion. J
campaign: international guidelines for management of severe sep- Clin Anesth 2008;20:139–142.
sis and septic shock: 2008. Crit Care Med 2008;36:296–227. 14. Bellomo R, Wan L, May C. Vasoactive drugs and acute liver
11. Levy JH, Adkinson NF. Anaphylaxis during cardiac surgery: injury. Crit Care Med 2008;36(Suppl):S179–S186.
implications for clinicians. Anesth Analg 2008;106:392–403. 15. Patel BM, Chittock DR, Russell JA, Walley KR. Beneficial
12. Stadlbauer KH, Wagner-Berger HG, Raedler C, et al. effects of short-term vasopressin infusion during severe septic
Vasopressin, but not fluid resuscitation, enhances survival in a shock. Anesthesiology 2002;96:576–582.
15259_Ch26.qxd 3/14/09 6:54 PM Page 95
CHAPTER 26
Anesthesia and Hypertension
Stephen F. Dierdorf
Although there are well-known specific causes of hyper-

tension such as pheochromocytoma, primary aldosteronism,
renovascular disease, and coarctation of the aorta, the specific
A 56-year-old, 5⬘6⬙, 127-kg male presented for resection
cause of hypertension in most patients is unknown (essential
of a right upper lung lobe mass via a right thoracotomy.
hypertension). There are several mechanisms by which renal
The patient had a 3-month history of a dry cough. A chest
dysfunction causes hypertension: (a) reduced glomerular fil-
radiograph and subsequent chest computed tomography
tration rate that limits sodium excretion, (b) humoral disor-
scan revealed a 4-cm mass in the upper lobe of the right
ders that increase sodium reabsorption, and (c) renal ischemia.
lung. Past surgical history included a right inguinal hernia
Recently, it has been suggested that prolonged ingestion of
repair at 18 years and a laparoscopic cholecystectomy at
fructose increases uric acid production, which in turn, acti-
46 years. The patient was diagnosed with hypertension at
vates the renin-angiotensin system, thereby increasing blood
47 years of age, and treatment at the time of surgery in-
pressure.1 More research will be required to fully delineate the
cluded an angiotensin receptor blocker (losartan) and an
different mechanisms that cause hypertension with the hope
angiotensin-converting enzyme (ACE) inhibitor (lisinopril).
of developing specific treatment plans.
During the past 4 years, his blood pressure had been la-
The traditional definition of hypertension is blood pressure
bile and difficult to control. At times, a ␤-adrenergic
greater than 140/90 mm Hg. The correlation between blood
blocker (metoprolol) was added to the treatment regimen.
pressure and the incidence of myocardial ischemia and stroke is
He had not taken metoprolol during the 3 months prior to
so strong that the definition of hypertension has been modified,
surgery. The patient had a 5-year history of sleep apnea
and individuals with blood pressure greater that 120/80 but less
and used a continuous positive airway pressure machine at
than 140/90 mm Hg are considered to have pre-hypertension.
night. Physical examination revealed an obese male with no
Treatment of prehypertensive patients decreases the likelihood
evidence of respiratory distress. The patient’s blood pressure
of ischemic heart disease.2
was 165/105 mm Hg, and his heart rate was 82 beats per
As more data have accumulated regarding the effects
minute. His laboratory testing values were as follows: he-
of different antihypertensive drugs on patient outcome, im-
moglobin level, 14.5; hematocrit, 43; sodium, 141 mEq/L;
proved recommendations for treatment have developed. The
potassium, 4.3 mEq/L; fasting glucose, 83 mg/dL; creati-
ACE inhibitors and angiotensin receptor blockers (ARB) have
nine, 1.0 mg/dL; and blood urea nitrogen, 10. The preop-
been shown to be effective for a wide range of patients.
erative room air arterial blood gas was PaO2, 82; PaCO2
Thiazide diuretics and calcium channel blockers are generally
41; pH, 7.39, and base excess, 0. The patient’s resting
indicated for the initial treatment of uncomplicated hyperten-
echocardiogram reading was normal. A preoperative
sion. ␤-Adrenergic blockers are no longer considered to be a
transthoracic echocardiogram showed concentric left ven-
first line antihypertensive but are indicated for patients with
tricular hypertrophy, an enlarged left atrium, and grade I di-
ischemic heart disease and heart failure.3,4 Therapy may also
astolic dysfunction (impaired relaxation).
be guided by monitoring the effects of antihypertensives on
secondary cardiac effects such as left ventricular hypertrophy
with echocardiography.5 Patients with hypertension are a very
What is the pathogenesis and treatment heterogeneous group, and therapy directed at reducing the
of hypertension? impact of hypertension on end-organ function in an individ-
Hypertension is one of the most common disorders in the ual patient would be desirable (Tables 26.1 and 26.2).
adult population of developed countries, and the incidence is
30% in some parts of the world. The increase in the incidence
of hypertension in the last 50 years has been dramatic. The Should the patient’s surgery be postponed
precise cause of this increase is not known parallels the in- because of elevated blood pressure?
crease in the incidence of obesity. Obesity causes physiologic The risks of anesthesia and surgery in a patient with hyperten-
derangements such as sympathetic nervous system activation, sion include myocardial ischemia, stroke, renal dysfunction,
insulin resistance, endothelial dysfunction, and increased al- and intraoperative blood pressure lability. Blood flow to most
dosterone levels, all of which promote hypertension. Whether critical organs is autoregulated across a wide range of blood
the two conditions are causally related or coincidentally re- pressures. Chronically hypertensive patients can have altered
lated remains to be determined. autoregulatory responses, but it is difficult in an individual
95
15259_Ch26.qxd 3/14/09 6:54 PM Page 96
96 CHAPTER 26 • ANESTHESIA AND HYPERTENSION
T A B L E 2 6 . 1 Types of Hypertension T A B L E 2 6 . 2 Treatment Recommendations

for Hypertension
Type Blood Pressure (mm Hg)
Normal 120/80 ⬍55 years of age ACEI
Prehypertension 130/85 ARBs
Mild hypertension 140/90 If additional therapy required, add CCB or diuretics
Moderate hypertension 160/100 ⬎55 years of age CCBs
Severe hypertension 180/110 (African descent, any age) Diuretics (thiazide)
Very severe 210/120 If additional therapy is required, add an ACEI or ARB.
hypertension ␤-adrenergic blockers may be required for patients with ischemic
heart disease or heart failure. Other antihypertensive drugs that may
Isolated systolic Systolic blood pressure be required for treatment of resistant hypertension are spironolactone,
hypertension ⬎140 mm Hg, diastolic vasodilators (hydralazine), and ␣-2 adrenergic agonists (clonidine).
blood pressure ⬍90 mm Hg ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin re-
ceptor blocker; CCB, calcium channel blocker.
Pulse pressure Pulse pressure ⬎65 mm Hg
hypertension
patient to precisely define those altered autoregulatory re- decreased to 135/85 mm Hg. A thoracic epidural catheter was
sponses. As anesthetics typically reduce blood pressure, the placed without difficulty at T5.
concern in hypertensive patients is whether the decrease in
blood pressure reduces vital organ perfusion.
Studies performed in the 1960s and 1970s indicated that What are the goals for perioperative
there was a significant perioperative risk of cardiac dysrhyth- management of the patient with hypertension?
mias and myocardial ischemia in hypertensive patients. Many An accurate assessment of preoperative blood pressure is re-
of these patients, however, were not receiving any antihyper- quired so that perioperative blood pressure targets can be estab-
tensive therapy. Most hypertensive patients today are receiving lished. Anxiety (white coat hypertension) causes an elevation in
treatment, and the perioperative risks may not be as prevalent. blood pressure that does not accurately reflect the patient’s
The addition of many parenteral antihypertensive drugs for steady state blood pressure. A review of serial blood pressure
perioperative use has increased the anesthesiologist’s ability to measurements from the medical records of the patient’s pri-
control blood pressure intraoperatively. mary care physician will provide a better blood pressure base-
Current guidelines state that elective surgery in a patient line. Blood pressure can be reduced with preoperative sedation
with a blood pressure of 180/110 mm Hg or greater should and alleviation of anxiety. After the patient’s “normal” blood
have surgery postponed until better blood pressure control has pressure has been established, the goal during the perioperative
been instituted. If urgent or emergent surgery is required, period is to maintain blood pressure within 20% of normal.
control can be instituted with rapid-acting antihypertensives.6 Postoperative analgesia with regional anesthesia may improve
These recommendations are based on the review of a number outcome after major surgery in hypertensive patients.8 For the
of studies that could not show a significant correlation be- patient described in this case, a continuous thoracic epidural
tween hypertension and adverse perioperative cardiac events. was selected as the technique of choice for postoperative anal-
Despite liberalization of blood pressure values for surgery, gesia. After establishing that the patient’s normal blood pres-
patients with hypertension-induced end-organ damage such sure was 135/85 mm Hg (mean, 100 mm Hg), a target goal with
as ischemic heart disease, heart failure, renal disease, and a mean blood pressure of 80 to 100 mm Hg would be desirable.
cerebrovascular disease have an increased risk of adverse peri- Anesthesia was induced with propofol 1.5 mg/kg and
operative events.7 Appropriate preoperative evaluation and rocuronium 0.8 mg/kg followed by positive pressure ventila-
perioperative management of these disorders is subsequently tion by mask with oxygen in sevoflurane followed by tracheal
required. intubation with a 41-F left-sided double-lumen tube. After
As the patient’s blood pressure was less than 180/110 laryngoscopy and intubation, the patient’s blood pressure was
mm Hg, and the evidence of end-organ damage was mild (di- 210/120 mm Hg, and his heart rate was 94 beats per minute.
astolic dysfunction, left ventricular hypertrophy), it was de-
cided to proceed with the surgery. The fact that the lung mass
was most likely malignant conveyed some urgency for the sur- Do patients with hypertension have
gery. The patient agreed to the insertion of a thoracic epidural intraoperative cardiovascular lability?
catheter before induction for postoperative pain management. Hypertensive patients have a more active response to laryn-
Sedation for epidural catheter insertion was achieved with goscopy and frequently demonstrate marked increases in blood
the intravenous administration of 2 mg of midazolam and pressure. The hypertensive response is more pronounced with
50 mcg of fentanyl. After sedation, the patient’s blood pressure prolonged laryngoscopy times. This response may be attenuated
15259_Ch26.qxd 3/14/09 6:54 PM Page 97
CHAPTER 26 • ANESTHESIA AND HYPERTENSION 97
with a number of different drugs such as ␤-blockers, opioids, patients with ISH, however, can be challenging and must be
dexmedetomidine, and vasodilators. Aggressive treatment may, done with caution. An aggressive reduction of blood pressure
however, result in hypotension. Whether blood pressure and can cause myocardial ischemia or cerebrovascular insufficiency.
heart rate lability influence outcome and whether outcome is Younger patients may exhibit systolic hypertension and an
worse in hypertensive patients is a complex issue. There is some increased pulse pressure that has been termed pulse pressure
evidence that tachycardia and hypertension are associated with hypertension (PPH). Although the causative mechanisms for
adverse outcomes in patients undergoing prolonged surgery.9 PPH may be different from ISH, there is an increased risk of
Whether better intraoperative control would have improved adverse postoperative cerebral and renal outcomes in patients
outcome is unknown. Today’s anesthesiologist is much better with PPH.13 Whether elective surgery should be postponed in
equipped with a variety of drugs to control intraoperative he- patients with PPH or ISH remains to be determined.14
modynamics than the anesthesiologist of 30 years ago.
Intravenous metoprolol was administered in incremental
dosages of 1 mg (total dosage, 3 mg) to reduce the patient’s KEY MESSAGES
heart rate, which declined to 71 beats per minute. His blood
pressure decreased to 180/100 mm Hg. Intravenous nicardip- 1. Elective surgery in a patient with a blood pressure
ine was administered in 1-mg increments (total dosage, 2 mg), of 180/110 mm Hg or greater should have surgery
and his blood pressure decreased to 125/75 mm Hg. Fifteen postponed.
minutes after induction, the patient’s blood pressure decreased
to 80/50 mm Hg, and he did not respond well to ephedrine 2. Intraoperative control of hemodynamics in hypertensive
and phenylephrine. patients may be challenging.15
3. Postinduction hypotension is more likely to occur in
Does treatment of hypertension with ACE hypertensive patients treated with angiotensin receptor
inhibitors and ARBs increase the likelihood blockers compared with hypertensive patients treated
of intraoperative hypotension? with ␤-adrenergic blockers or calcium channel blockers.
Postinduction hypotension is more likely to occur in hyperten- 4. Aggressive treatment of post-laryngoscopy hyperten-
sive patients treated with angiotensin receptor blockers as sion may result in hypotension once the stimulant effect
compared with hypertensive patients treated with ␤-adrener- of laryngoscopy has dissipated.
gic blockers or calcium channel blockers. Hypotension in this
group of patients typically responds poorly to ephedrine and
phenylephrine and is more responsive to vasopressin or terli-
pressin.10 Whether angiotensin II antagonists and ACE in-
hibitors should be discontinued 24 hours before surgery is QUESTIONS
controversial.11 This choice may be impractical and may lead
to other unanticipated side effects. Such a recommendation is 1. What are the risks of anesthesia and surgery for
reminiscent of the recommendation for the discontinuation of patients with poorly controlled hypertension?
␤-adrenergic blockers preoperatively in the 1970s. A more ra- Answer: Risks include myocardial infarction, stroke,
tional approach may be to administer vasopressin initially or as cardiac dysrhythmias, renal dysfunction, and periopera-
soon as ephedrine and phenylephrine have proved ineffective. tive blood pressure lability.
A typical scenario in patients with hypertension is a signifi-
cant increase in blood pressure with laryngoscopy that is treated 2. Why are ␤-adrenergic blockers no longer considered
with ␤-adrenergic blockers, vasodilators, or an increased in- to be first line anti-hypertensive drugs?
haled concentration of volatile anesthetic. Aggressive treatment Answer: Angiotensin receptor blockers (ARB) have been
of post-laryngoscopy hypertension may result in hypotension shown to be effective anti-hypertensives without the side
once the stimulant effect of laryngoscopy has dissipated. The effects of ␤-blockers, such as bradycardia, exercise and
risk of hypotension may be reduced by the use of short-acting cold intolerance, and peripheral vasoconstriction.
antihypertensives and somewhat less aggressive treatment.
3. What is the most effective treatment of intraoperative
refractory hypotension in patients receiving preopera-
Although this patient did not exhibit tive angiotensin receptor blockers (ARB) and/or
isolated systolic hypertension, do elderly angiotensin converting enzyme (ACE) inhibitors?
patients with this condition have an increased Answer: Some patients receiving ARBs or ACE
perioperative risk? inhibitors can develop significant intraoperative hypoten-
The aging process produces changes in the walls of large arter- sion. Vasopressin is more effective than ephedrine and/or
ies that increase the stiffness and rigidity of the blood vessels. phenyephrine.
The loss of elasticity in the aorta causes an increase in systolic
pressure, a decrease in diastolic pressure, and a subsequent in-
crease in pulse pressure. Although the treatment of isolated sys- References
tolic hypertension (ISH) was controversial, it is now accepted 1. Johnson RJ, Feig DI, Nakagawa T, et al. Pathogenesis of essen-
that there is an increased risk of morbidity and mortality from tial hypertension: historical paradigms and modern insights.
ISH and that treatment is indicated.12 Treatment of elderly J Hypertens 2008;26:381–391.
15259_Ch26.qxd 3/14/09 6:54 PM Page 98
98 CHAPTER 26 • ANESTHESIA AND HYPERTENSION
2. Rosendorff C, Black HR, Cannon CP, et al. Treatment of hyper- 9. Reich DL, Bennett-Guerrero E, Bodian CA, et al. Intraoperative
tension in the prevention and management of ischemic heart tachycardia and hypertension are independently associated with
disease. Circulation 2007;115:2761–2788. adverse outcome in noncardiac surgery of long duration. Anesth
3. Higgins B, Williams B. Pharmacological management of hyper- Analg 2002;95:273–277.
tension. Clin Med 2007:7:612–616. 10. Brabant SM, Bertrand M, Eyraud D, et al. The hemodynamic
4. Trewet CLB, Ernst ME. Resistant hypertension: identifying effects of anesthetic induction in vascular surgical patients chron-
causes and optimizing treatment regimens: South Med J 2008; ically treated with angiotensin II receptor antagonists. Anesth
101:166–173. Analg 1999;1388–1392.
5. Davila DF, Donis JH, Odreman R, et al. Patterns of left ventric- 11. Bertrand M, Godet G, Meersschaert K, et al. Should angiotensin
ular hypertrophy in essential hypertension: should echocardiog- II antagonists be discontinued before surgery? Anesth Analg
raphy guide the pharmacological treatment? Int J Cardiol 2008; 2001;92:26–30.
124:134–138. 12. Duprez DA. Systolic hypertension in the elderly: addressing an
6. Eagle KA, Berger PB, Calkins H, et al. ACC/AHA guideline unmet need. Am J Med 2008;121:179–184.
update for perioperative cardiovascular evaluation for noncar- 13. Aronson S, Fontes ML. Hypertension: a new look at an old prob-
diac surgery—executive summary. Anesth Analg 2002;94: lem. Curr Opin Anaesthesiol 2006;19:59–64.
1052–1064. 14. Prys-Roberts C. Isolated systolic hypertension: pressure on the
7. Hanada S, Kawakami H, Goto T, Morita S. Hypertension and anaesthetist? (editorial) Anaesthesia 2001;56:505–510.
anesthesia. Curr Opin Anaesthesiol 2006;19:315–319. 15. Howell SJ, Sear JW, Foex P. Hypertension, hypertensive heart
8. Tziavrangos E, Schug SA. Regional anaesthesia and periopera- disease and perioperative cardiac risk. Br J Anaesth 2004;92:
tive outcome. Curr Opin Anaesthesiol 2006;19:521–525. 570–583.
15259_Ch27.qxd 3/14/09 6:57 PM Page 99
CHAPTER 27
Pharmacologic Myocardial Preconditioning
John Vullo
oxygen supply. Two other important causes of decreased coro-

nary blood flow are coronary artery stenosis and coronary
artery spasm. Myocardial oxygen demand is dependent on
A 73-year-old, 86-kg female presented for three-vessel off-
heart rate, left ventricular contractility, and myocardial wall
pump coronary artery bypass grafting. She had been ex-
stress, as determined by afterload. The heart requires a 50%
periencing exertional angina and dyspnea increasing in
increase in blood flow for a doubling of any of these factors.
severity for the 3 months before scheduled surgery. Co-
ronary angiography revealed 90% occlusion of the right
coronary artery and 70% occlusion of the left anterior de- What medications can be used to improve the
scending and circumflex arteries. Her electrocardiogram balance between myocardial oxygen supply
demonstrated nonspecific ST-T waves changes and first- and demand?
degree atrioventricular block (PR interval, 0.24). Trans- Treatment of coronary artery disease must be individualized
thoracic echocardiography showed inferior wall hypokine- for each patient to provide medical and revascularization
sis, impaired left ventricular relaxation, an enlarged left treatments that optimize myocardial oxygen supply and
atrium, mild mitral regurgitation, and an ejection fraction of demand while preserving left ventricular function.1–3
45%. The patient had long-standing hypertension treated There are several medications that can favorably influence
with daily valsartan and hydrochlorothiazide. Other med- myocardial oxygen supply and demand. Nitrosovasodilators
ications included atenolol, simvastatin, and an over-the can decrease left ventricular pressures, decrease left ventricu-
counter-medication for heartburn. lar afterload by decreasing systolic pressure, and increase coro-
The patient’s past surgical history included a cholecys- nary circulation through direct coronary artery and arteriolar
tectomy at 32 years of age and an abdominal hysterectomy dilation or reversal of spasm. ␤-Adrenergic blockers directly
at 68 years of age without known anesthetic complications. reduce myocardial oxygen consumption and improve coro-
The physical examination, including airway evaluation, nary blood flow by prolonging the diastolic filling time.
was not remarkable. The patient’s vital signs were as fol- Calcium channel blockers decrease myocardial contractility
lows: blood pressure, 152/84 mm Hg; heart rate, 76 beats and reverse coronary artery spasm. Ranolazine, a late sodium
per minute; and respiratory rate, 16 breaths per minute. channel blocker, reduces diastolic wall stress, and antithrom-
Room air arterial oxygen saturation by pulse oximetry was botic agents maintain coronary artery patency by platelet inhi-
95%. The laboratory testing values were as follows: hema- bition. Statin drugs, generally used to reduce lipid levels, have
tocrit level, 38; hemoglobin level, 12.7 g/dL; creatinine, also been found to reduce inflammation and oxidative stress.4
1.0; potassium, 4.2; and sodium, 138. There are several clinical studies suggesting the efficacy of
The patient asked if anything could be done before different medications that may reduce perioperative cardiac
her surgery to improve her cardiac outcome. risk. Many of these studies lack the power to justify broad
recommendations for the entire surgical population. The
anesthesiologist must carefully evaluate each patient and indi-
vidualize the anesthetic for each patient.
What are the primary determinants of The enthusiasm for perioperative ␤-adrenergic blocker
myocardial oxygen supply and demand? therapy has been tempered by the outcomes of the recently
Myocardial oxygen supply is determined by coronary blood published results of the PeriOperative ISchemic Evaluation
flow and arterial oxygen content. Oxygen content is regulated trial, which showed a decrease in the perioperative myocardial
by arterial oxygen saturation, oxygen tension, and hemoglobin infarction rate but an increased risk of death and stroke in
as defined by the equation: patients receiving long-acting metoprolol.5
CaO2 ⫽ 1.34 ⫻ hemoglobin ⫻ O2 saturation ⫹ 0.0031 ⫻ PaO2
How did the patient’s preoperative medical
Coronary blood flow occurs as a result of the pressure dif- problems influence the selection of
ferential between aortic diastolic pressure and left ventricular perioperative monitors?
end-diastolic pressure. An increase in left ventricular end-
diastolic pressure or a decrease in aortic diastolic pressure can The patient had significant coronary artery disease and long-
significantly decrease coronary blood flow and myocardial standing hypertension with less-than-optimal control. The
99
15259_Ch27.qxd 3/14/09 6:57 PM Page 100
100 CHAPTER 27 • PHARMACOLOGIC MYOCARDIAL PRECONDITIONING
standard intraoperative monitors used included a five-lead develop and lasts for 3 to 4 days. The late phase has the unique
continuous electrocardiogram, capnography, and pulse oxime- property of reducing myocardial stunning following reperfu-
try. An indwelling radial artery catheter, central venous sion as well as reducing infarct size. Preconditioning leads to
catheter, and a transesophageal echocardiograph (TEE) were the release of cellular substances including adenosine,
also used. A pulmonary artery catheter was not inserted, as the bradykinin, and endorphins, which activate G protein-
TEE would provide more information about ventricular func- coupled receptors. Multistep processes activate signaling ki-
tion, segmental wall motion, and ventricular filling. nases, which maintain mitochondrial adenosine triphosphate
(ATP) generation and inhibit apoptosis.7
Patients who have had anginal episodes preceding an in-
What induction drugs should be selected for farct have better outcomes than those without antecedent
this patient? angina. Repeated coronary occlusions during cardiac catheter-
The goals of anesthesia for this patient are to reduce myocar- ization can decrease subsequent ischemic events for as long as
dial oxygen demand, provide adequate coronary filling pres- 1 year. Intermittent cross-clamping of the aorta during cardiac
sure, and preserve left ventricular function. Concerns during surgery before cardiopulmonary bypass seems to provide some
induction include the potential for hypotension in a patient cardioprotection.
with mildly depressed left ventricular function and probable
hypovolemia from chronic diuretic therapy. Induction of anes-
thesia should be performed in a slow, controlled manner by
slow intravenous (IV) bolus injection or IV infusion. A BIS- Can anesthetics precondition the heart?
guided IV infusion of propofol would accomplish those goals. Many in vitro studies have shown the cardioprotective effects
Etomidate is a suitable alternative to propofol, although adre- of volatile, inhaled anesthetics including halothane, enflurane,
nal suppression continues to cause concern about the use of isoflurane, desflurane, and sevoflurane. Isoflurane and
etomidate. Perhaps more important than the actual induction sevoflurane have been shown to reduce infarct size even when
drug is the rapidity with which induction is performed. the volatile agent is discontinued prior to coronary artery oc-
Upon arrival in the operating room, a noninvasive blood clusion. Proposed mechanisms for anesthetic-induced IPC in-
pressure cuff, electrocardiogram, pulse oximeter, and BIS clude preservation of ATP, attenuation of inflammation, and
monitors were applied. Prior to the induction of anesthesia, IV reduced calcium loading. At the intracellular level, volatile
sedation with midazolam (30 ␮g/kg) and fentanyl (1 ␮g/kg) anesthetics open mitochondrial ATP-sensitive K⫹ (KATP)
was performed. A right radial arterial catheter was inserted channels and in turn, decrease mitochondrial energy con-
with local anesthesia. Induction of anesthesia commenced sumption during ischemia (Table 27.1). Volatile anesthetics
with a propofol infusion at 600 ␮g/kg per minute and have also been shown to inhibit platelet aggregation, reduce
remifentanil 025 ␮g/kg per minute until loss of consciousness myocardial damage, and decrease the likelihood of apoptosis
was confirmed with loss of eyelash reflex and the BIS was 46. during reperfusion after ischemia. The release of reactive oxy-
Rocuronium (0.8 mg/kg) was administered, and positive gen species (ROS) during reperfusion depresses myocardial
pressure was ventilation provided. The patient’s trachea was contractility. Volatile anesthetics reduce the release of ROS
intubated without difficulty with a 7.0-mm inner diameter and attenuate or abolish neutrophil-induced myocardial de-
orotracheal tube. After the tracheal intubation, her blood pres- pression.8 Opioid agonists such as morphine and remifentanil
sure was 115/75 mm Hg, and her heart rate was 68 beats seem to enhance the protection of the myocardium achieved
per minute. The propofol infusion rate was decreased to by anesthetic preconditioning. Studies of propofol and keta-
100 ␮g/kg per minute, and the remifentanil infusion rate was mine have produced conflicting results regarding myocardial
decreased to 0.15 ␮g/kg per minute. preconditioning. Midazolam and etomidate do not affect
Another anesthesiologist suggested that

volatile, inhaled anesthetics produce T A B L E 2 7 . 1 Proposed Mechanisms of
myocardial ischemic preconditioning. What is
Anesthetic Myocardial
ischemic preconditioning?
Preconditioning
Myocardial preconditioning is a phenomenon that increases
the heart’s resistance to a period of ischemia. This protection Anti-inflammation
persists after the intervention has taken place and has been re-
moved. Methods relying on direct cardioprotection cease to Reduced calcium loading
provide protection once therapy is withdrawn. Ischemic pre- ROS
conditioning (IPC) was first described by Murry et al. in 1986.6 Decreased platelet adhesion
IPC is elicited by exposing the heart to a brief episode or
episodes of sublethal ischemia. A preconditioned heart that Improved ATP synthesis
undergoes a subsequent period of prolonged ischemia will de- Decreased neutrophil adhesion
velop a much smaller infarct when compared with a noncon-
Opening of KATP channels (mitochondria)
ditioned heart. There are two phases to IPC, early and late.
The early phase develops within minutes of ischemic exposure ATP, adenosine triphosphate; KATP, ATP-sensitive K⫹; ROS, decreased
and lasts for 2 to 4 hours and is very effective for reducing reactive oxygen species.
lethal ischemia or infarct size. The late phase takes 24 hours to
15259_Ch27.qxd 3/14/09 6:57 PM Page 101
CHAPTER 27 • PHARMACOLOGIC MYOCARDIAL PRECONDITIONING 101
T A B L E 2 7 . 2 Drugs That Affect Anesthetic

pressure was 108/86 mm Hg, and her heart rate was 72 beats per
minute. Brief periods of hypotension occurring during the
Preconditioning grafting process were treated with intermittent doses of
phenylephrine (1–2 ␮g/kg). After completion of the grafts,
Produce APC TEE showed no regional wall abnormalities and a left ventric-
Halothane ular ejection fraction of 50% (Simpson’s method). Postoperative
sedation was provided with dexmedetomidine 0.5 ␮g/kg per
Isoflurane
hour. The patient’s trachea was extubated 3 hours after surgery.
Enflurane There are many concerns for patients with coronary artery
Sevoflurane disease undergoing cardiac or noncardiac surgery. Optimal pre-
Desflurane operative medical management of patients with ischemic dis-
ease has not yet been determined. Patients consequently present
Opioids for surgery with a variety of drug regimens and recommenda-
Flumazenil tions from cardiologists. The results of new studies have con-
Reduce APC
founded the attempts of large medical organizations to develop
firm guidelines for the testing of patients with coronary artery
Sulfonylureas disease undergoing noncardiac surgery. Frequent revisions of
Glitazones guidelines are required as the results of new studies appear.15
Appropriate monitoring of intraoperative cardiac function
Cyclooxygenase-2 inhibitors
has been controversial for many years. The wealth of informa-
No Effect on APC tion provided by TEE exceeds what is possible with a pul-
Midazolam monary artery catheter. The TEE is relatively noninvasive,
and the development of less expensive and more mobile echo
Etomidate units has increased convenience of use. Ischemic myocardial
Conflicting Evidence preconditioning of volatile anesthetics has produced a more
Propofol balanced approach to anesthesia that uses volatile anesthetics
in combination with opioids. The anesthesiologist must con-
Ketamine tinue to develop perioperative management plans tailored to
APC, anesthetic preconditioning. the individual’s medical conditions.
KEY MESSAGES
KATP channels and do not produce anesthetic preconditioning
(APC) (Table 27.2). 1. The PeriOperative ISchemic Evaluation trial demon-
Hyperglycemia and diabetes may block the effects of IPC strated a decrease in the perioperative myocardial
and APC. Sulfonylureas may also reduce the effectiveness of infarction rate but an increased risk of death and
IPC and APC. stroke in patients receiving metoprolol in the
perioperative period.
Is APC clinically relevant? 2. Volatile anesthetics open mitochondrial KATP channels

and decrease mitochondrial energy consumption
Clinical studies of APC are difficult because of the many con- during ischemia of the myocardium.
founding variables such as altered hemodynamics, coexisting
diseases, concomitant drug administration, and multi-drug 3. Anesthetic preconditioning is likely to be clinically
anesthetic techniques. Several clinical studies, however, have significant.9,10
produced compelling evidence that APC is clinically signifi-
cant.9,10 Clinical markers of improved outcome after coronary
artery bypass grafting include reductions in the release of cre-
atine kinase MB and troponins I and T, reduced incidence of QUESTIONS
dysrhythmias, and improved myocardial function.11,12 It also
appears that administration of volatile anesthetics is preferable 1. What are the mechanisms by which anesthetics pro-
throughout the intraoperative period rather than selected duce myocardial ischemic preconditioning (IPC)?
periods before and after ischemia.13 In patients undergoing Answer: The mechanisms include anti-inflammation,
single-vessel off-pump coronary artery bypass grafting, both reduced calcium loading, reduction of reactive oxygen
enflurane and a 5-minute period of ischemia/reperfusion pre- species (ROS), decreased platelet adhesion, and enhanced
served myocardial function and reduced free radical forma- ATP synthesis.
tion compared with a control group.14
After induction of anesthesia, the propofol was discontinued, 2. What anesthetics have been shown to produce myocar-
and maintenance anesthesia was provided with remifentanil dial IPC?
(0.1 ␮g/kg per minute) and a sevoflurane-oxygen mixture. Answer: Anesthetics that produce myocardial IPC in-
During the maintenance phase of anesthesia, the patient’s blood clude isoflurane, sevoflurane, desflurane, and opioids.
15259_Ch27.qxd 3/14/09 6:57 PM Page 102
102 CHAPTER 27 • PHARMACOLOGIC MYOCARDIAL PRECONDITIONING
3. Are there drugs that inhibit or reduce myocardial IPC? 8. Tanaka K, Ludwig LM, Kersten JR, et al. Mechanisms of cardio-
protection by volatile anesthetics. Anesthesiology 2004;100:
Answer: Anti-diabetic drugs such as sulfonylureas and 707–721.
glitazones inhibit myocardial IPC. 9. DeHert SG, Turani F, Mathur S, et al. Cardioprotection with
volatile anesthetics: mechanisms and clinical implications.
Anesth Analg 2005;100:1584–1593.
References 10. Bienengraeber MW, Weihrauch D, Kersten JR, et al. Cardio-
1. Daemen J, Serruys PW. Optimal revascularization strategies for protection by volatile anesthetics. Vasc Pharmacol 2005;42:
multivessel coronary artery disease. Curr Opin Cardiol 2006;21: 243–252.
595–601. 11. Bein B, Renner J, Caliebe D, et al. Sevoflurane but not propofol
2. Banerjee P, Card D. Preserving left ventricular function during preserves myocardial function during minimally invasive direct
percutaneous coronary intervention. J Invasive Cardiol 2007;19: coronary artery bypass surgery. Anesth Analg 2005;100:610–616.
440–443. 12. Cromheecke S, Pepermans V, Hendrickx E, et al. Cardio-
3. Chambers TA, Bagai A, Ivascu N. Current trends in coronary protective properties of sevoflurane in patients undergoing aortic
artery disease in women. Curr Opin Anaesth 2007;20:75–82. valve replacement with cardiopulmonary bypass. Anesth Analg
4. Feringa HHH, Bax JJ, Poldermans D. Perioperative medical 2006;103:289–296.
management of ischemic heart disease in patients undergoing 13. De Hert SG, Van den Linden PJ, Cromheecke S, et al.
noncardiac surgery. Curr Opin Anaesth 2007;20:254–260. Cardioprotective properties of sevoflurane in patients undergo-
5. POISE Study group. Effects of extended-release metoprolol suc- ing coronary artery surgery with cardiopulmonary bypass are
cinate in patients undergoing non-cardiac-surgery (POISE trial): related to the modalities of its administration. Anesthesiology
a randomized controlled trial. Lancet 2008;371: 1839–1847. 2004;101:299–310.
6. Murry CE, Jennings RB, Reimer KA. Preconditioning with is- 14. Drenger B, Gilon D, Chevion M, et al. Myocardial metabolism al-
chemia: a delay of lethal cell injury in ischemic myocardium. tered by ischemic preconditioning and enflurane in off-pump coro-
Circulation 1986;74:1124–1136. nary artery surgery. J Cardiothor Vasc Anesth 2008;22:369–376.
7. Shim YH, Kersten JR. Preconditioning, anesthetics, and peri- 15. Gregoratos G, Brett AS. Are the current perioperative risk man-
operative medication. Best Pract Res Clin Anaesth 2008;22: agement strategies for myocardial infarction flawed? Circulation
151–165. 2008;117:3134–3151.
15259_Ch28.qxd 3/14/09 6:57 PM Page 103
CHAPTER 28
Predicting Difficult Mask Ventilation
Stephen F. Dierdorf
CASE FORMAT: REFLECTION exhaled carbon dioxide was detected. Oxygen saturation
increased to 99%. After 5 minutes of assisted ventilation,
A 71-year-old, 5⬘ 10⬙, 106-kg male presented for a left the patient awakened, and the LMA was removed.
carotid endarterectomy for carotid stenosis. Fifteen years
before this procedure, he underwent successful coronary
artery bypass surgery and has been free of cardiac symp- DISCUSSION
toms since. He had a history of snoring at night and had
intermittently used a continuous positive airway pressure This case illustrates several important features of airway man-
machine. He had smoked one pack of cigarettes per day agement. The preoperative airway examination must evaluate
for 52 years. The patient’s medications included meto- several variables, as no single airway examination technique is
prolol 50 mg daily and aspirin. His preoperative electro- reliable. Based on the findings for this patient, some difficulty in
cardiogram reading showed nonspecific ST-T waves mask ventilation should have been anticipated. After induction
changes and sinus rhythm. The patient’s blood pressure of anesthesia, mask ventilation was difficult, but insertion of an
was 152/84 mm Hg, and his heart rate was 55 beats oropharyngeal airway allowed satisfactory mask ventilation.
per minute. His airway examination showed Mallampati Direct laryngoscopy proved to be difficult, and an alternative
grade II, slightly decreased cervical extension, full beard intubation technique using flexible fiberoptic laryngoscopy was
present, and thyromental distance, 5 cm. required. The rapidity and ease with which the anesthesiologist
Monitors applied prior to induction included an elec- changes from the primary technique to an alternative technique
trocardiogram, a pulse oximeter, noninvasive blood pres- reduces the likelihood of an adverse airway event. At the con-
sure, and a 12-lead electroencephalogram. Anesthesia clusion of the case, extubation was premature, and mask venti-
induction was achieved with midazolam 2 mg, fentanyl lation was impossible until an intubating LMA was inserted.
100 ␮g, and propofol 100 mg. Rocuronium 70 mg was The importance of the airway during the emergence phase of
administered for muscle relaxation to facilitate tracheal anesthesia is often overlooked even in patients with known air-
intubation. After induction, mask ventilation was difficult but way difficulty. There is often a desire to extubate patients at
improved considerably after insertion of an oropharyngeal a deeper plane of anesthesia after head and neck surgery to
airway. Rigid direct laryngoscopy was attempted with a no. avoid bleeding and excessive coughing. Depth of anesthesia is
3.5 Macintosh blade; only the tip of the epiglottis could be difficult to predict, and deep extubation requires careful plan-
visualized. The oropharyngeal airway was replaced and ning to avoid serious consequences. If extubation is performed
mask ventilation continued. Two more attempts at rigid di- when the patient is not fully awake, there is a risk of laryn-
rect laryngoscopy were unsuccessful. Tracheal intubation gospasm and upper airway obstruction, especially in patients
was successful with a flexible fiberoptic scope and a 7.5- with sleep apnea.
mm inner diameter tracheal tube. The surgical procedure Airway management is the single most important task for
was uneventful. At the conclusion of surgery, neuromuscular the anesthesiologist. It is also the greatest source of adverse
blockade was reversed with neostigmine 4 mg and 0.6 mg outcomes in the practice of anesthesia.1 Considerable research
glycopyrrolate. Sustained tetanus was demonstrated with a and development of new airway devices and techniques has
peripheral nerve stimulator. The patient began to cough occurred in the past 15 years. Difficult airway management
during emergence, and his trachea was extubated to avoid is usually equated to tracheal intubation. Three notable pub-
further increases in blood pressure. Arterial oxygen satura- lications that focused on the broad area of the difficult air-
tion at the time of extubation was 100%. The patient did not way reported the incidence of difficult mask ventilation to be
resume spontaneous ventilation after extubation, and posi- 0.07% to 1.4%.2–4 Research specifically related to difficult
tive pressure ventilation was not possible. An oropharyn- mask ventilation, however, has been sparse. The importance
geal airway was inserted, but there was no appreciable of mask ventilation cannot be overemphasized, as it is the
ventilation as evidenced by the lack of exhaled carbon first technique used for ventilation after induction of anes-
dioxide and no chest movement. Arterial oxygen saturation thesia; it is a technique that has changed little in the past
decreased to 92%. An intubating laryngeal mask airway decades. A careful analysis of difficult airway management
(LMA) was inserted, chest excursion was observed, and should separate mask ventilation and tracheal intubation, as
the alternative techniques used for each are different.
103
15259_Ch28.qxd 3/14/09 6:57 PM Page 104
104 CHAPTER 28 • PREDICTING DIFFICULT MASK VENTILATION
The objective of the preoperative airway examination

T A B L E 2 8 . 2 Grading Scale for Mask
should be evaluation and assessment of the patient for both
mask ventilation and tracheal intubation. Two studies pre- Ventilation
dicted difficulty with mask ventilation in 1.56% to 5% of pa-
Grade 0: Mask ventilation not attempted
tients. Impossible mask ventilation occurred with a frequency
of 1 in 600 to 1 in 1500 patients.5,6 Predictive factors for diffi- Grade 1: Ventilation by mask
cult ventilation common to both studies were (a) history of Grade 2: Mask ventilation with pharyngeal
snoring (? sleep apnea), (b) presence of a beard, (c) age greater airway
than 55 to 57 years, and (d) a body mass index ⬎26 to
30 kg/m2. Other factors reported in the studies but not com- Grade 3: Difficult mask ventilation (inadequate,
mon to both or measured by both were (a) limited mandibu- unstable, two-person)
lar protrusion, (b) lack of teeth, and (c) a thyromental distance Grade 4: Unable to mask ventilate
less than 6 cm. Differences in findings among studies may be
Data from Han R, Tremper KK, Kheterpal S, et al. Grading scale for
secondary to variations in the definition of difficult mask ven-
mask ventilation. Anesthesiology 2004;101:267.
tilation. The American Society of Anesthesiologists Practice
Guidelines for Management of the Difficult Airway defines
difficult mask ventilation as:
1. It is not possible for the unassisted anesthesiologist when difficult mask ventilation by increasing the lower limit of
using 100% oxygen to maintain the arterial oxygen satura- arterial oxygen saturation (92%) and developing a grading
tion greater than 90% in a patient whose arterial oxygen sat- system for mask ventilation. The clinical benefit of a stricter
uration was greater than 90% before induction of anesthesia. definition of difficult mask ventilation is earlier intervention
2. It is not possible for the unassisted anesthesiologist to pre- with an alternative technique, thereby reducing the risk of an
vent or reverse signs of inadequate ventilation during adverse outcome (Table 28.2).
positive pressure ventilation. Signs of inadequate ventila- Mask ventilation is only one part of airway management.
tion include cyanosis, absence of exhaled carbon dioxide, Mask ventilation is, however, of considerable importance, as it
absence of breath sounds and chest movement, and hemo- is the first technique used after a patient loses consciousness. If
dynamic changes associated with hypoxemia and hyperventilation with a face mask is adequate, even if tracheal intu-
carbia7 (Table 28.1). bation is difficult, there is time to initiate alternative airway
management techniques. Inadequate ventilation resulting in
The Difficult Airway Society Guidelines from the United hypoxemia reduces the amount of time available for use of al-
Kingdom focus on unanticipated difficult intubation and have ternative techniques. Airway evaluation predictive of difficult
little information concerning mask ventilation.8 Since the ini- mask ventilation, consequently, is important to permit accessi-
tial publication of the American Society of Anesthesiologists bility to other devices and techniques.
difficult airway guidelines in 1993, subsequent studies of dif- The supralaryngeal airways, most notably the LMA, have
ficult mask ventilation have used more liberal definitions of led to change in how difficult ventilation is defined. Because
supralaryngeal airways are extremely effective for ventilation
in difficult situations, the definition of difficult ventilation is de-
T A B L E 2 8 . 1 Preoperative Airway Evaluation termined by the inability to establish ventilation with a suprala-
ryngeal airway rather than by face mask. Anesthesiologists
History
must be highly skilled in the use of the LMA, and anesthesia
Preoperative respiratory conditions training programs have a responsibility is ensure that each
Smoking trainee is thoroughly versed in the use of the LMA. There are
two learning phases for the LMA. The first phase requires 50
Snoring to 75 uses and allows the user to learn the rudiments of the
Obstructive sleep apnea LMA and establish ventilation in healthy patients. The second
Age phase requires several hundred uses to develop skills for reli-
ably managing patients with difficult airways.
Physical Examination
Mallampati classification
SUMMARY
Cervical range of motion
Mouth opening Airway management is the most important task that an anes-
Condition of teeth and bite thesiologist performs. At the conclusion of formal training,
anesthesiologists are experts at airway management of healthy
Thyromental distance patients. True expertise for managing the difficult airway
Presence or absence of a beard requires considerable experience and skill development. A
complete preoperative airway examination is a poor predictor
Body mass index
of airway outcome. Preoperative airway evaluation, however,
Neck circumference does provide the anesthesiologist with an indicator of what
alternative techniques may be required for a specific patient.
15259_Ch28.qxd 3/14/09 6:57 PM Page 105
CHAPTER 28 • PREDICTING DIFFICULT MASK VENTILATION 105
The anesthesiologist must be skilled with several alternative 3. What is the most appropriate procedure for impossible
techniques and should be able to smoothly and quickly move mask ventilation of a morbidly obese patient?
from one technique to another when the clinical situation Answer: Insertion of a supraglottic airway (e.g., LMA)
arises. Unless there is a specific contraindication, extubation would be the most appropriate method for ventilation
with the patient fully awake can avoid several potential airway of a morbidly obese patient should mask ventilation
problems in patients with a history of obstructive sleep apnea.10 fail.
KEY MESSAGES
References
1. The airway examination is a multivariate exercise with 1. Cheney FW, Posner KL, Lee LA, et al. Trends in anesthesia-
poor predictive power. related death and brain damage. Anesthesiology 2006;105:
2. Difficult mask ventilation and difficult intubation are 1081–1086.
2. Rose DK, Cohen MM. The airway: problems and predictions in
different entities.
18,500 patients. Can J Anaesth 1994;41:372–383.
3. The anesthesiologist must be skilled in alternative air- 3. El-Ganzouri AR, McCarthy RJ, Tuman KJ, et al. Preoperative
way techniques. risk assessment: predictive value of a multivariate risk index.
Anesth Analg 1996;82:1197–1204.
4. Tracheal extubation has risks similar to those associ- 4. Asai T, Koga K, Vaughan RS. Respiratory complications associ-
ated with intubation. ated with tracheal intubation and extubation. Br J Anaesth 1998;
80:767–773.
5. Langeron O, Masso E, Huraux C, et al. Prediction of difficult
mask ventilation. Anesthesiology 2000;92:1229–1236.
QUESTIONS 6. Kheterpal S, Han R, Tremper KK, et al. Incidence and predic-
tors of difficult and impossible mask ventilation. Anesthesiology
1. Complications with what organ system contribute to the 2006;105:885–891.
7. Task Force on Guidelines for Management of the Difficult
greatest likelihood of adverse outcomes related to the
Airway. Practice guidelines for management of the difficult air-
practice of anesthesia? way. Anesthesiology 1993;78:597–602.
Answer: Respiratory system complications produce the 8. Henderson JJ, Popat MT, Latto IP, Pearce AC. Difficult Airway
highest incidence of adverse outcomes during the course Society guidelines for management of the unanticipated difficult
of anesthesia. intubation. Anaesthesia 2004;59:675–694.
9. Han R, Tremper KK, Kheterpal S, O’Reilly M. Grading scale
2. What are the predictive factors for difficult mask for mask ventilation. Anesthesiology 2004;101:267.
ventilation? 10. American Society of Anesthesiologists Task Force on
Perioperative Management of Patients with Obstructive Sleep
Answer: Predictive factors for difficult mask ventilation Apnea: practice guidelines for the perioperative management of
include a history of snoring, presence of a beard, body patients with obstructive sleep apnea. Anesthesiology 2006;104:
mass index of ⬎30, and age greater than 55 years. 1081–1093.
15259_Ch29.qxd 3/14/09 6:59 PM Page 106
CHAPTER 29
Awake Tracheal Intubation
Stephen F. Dierdorf
patient when integrated with the American Society of

Anesthesiologists guidelines for management of the difficult
airway leads to the logical recommendation for awake, tra-
A 64-year-old, 74-kg male with laryngeal cancer pre-
cheal intubation.1
sented for laryngectomy and right radical neck dissection.
The patient complained of hoarseness, dysphagia, and
dyspnea when supine that had increased in severity over How should the patient be prepared for
the previous 3 months. He had declined surgery 6 months awake, tracheal intubation?
before the current scheduled surgery. The patient had
Patient preparation begins with a thorough explanation re-
smoked 2 packs of cigarettes per day for 44 years. The
garding the importance of performing intubation while
ear, nose, and throat surgeon’s consultation noted that
awake. A frank discussion of the potentially dire consequences
there was a large mass originating from the right false
of the lost airway after anesthesia induction and the necessity
vocal cord, and the cross-sectional area of the glottic inlet
of an awake intubation will do much to convince the patient of
was reduced by 65%. The mass extended into the anterior
the merits of awake intubation. The patient must also be as-
tracheal wall, and there was a significant reduction of
sured that his comfort during the procedure is of paramount
epiglottic mobility.
importance, and a variety of methods including parenteral
The patient’s past medical history included an inferior
sedation and topical and/or regional anesthesia will be used to
wall myocardial infarct followed by off-pump three-vessel
make him comfortable.
coronary artery bypass grafting at 61 years of age. Since
The innervation of the upper airway is extensive and is
the coronary artery bypass grafting, he had been free of
provided by several nerves. Branches of the trigeminal nerve
chest pain; however, dyspnea from the laryngeal cancer
supply the nasal cavity, and the glossopharyngeal nerve pro-
had restricted his physical activity. An open cholecystec-
vides sensation to much of the pharynx, while the vagus nerves
tomy had been performed at age 44 without known anes-
provide sensory innervation to the larynx via the superior la-
thetic complications. He has had a long-standing history of
ryngeal nerves. The gag reflex is controlled by the vagus
hypertension treated with angiotensin-converting enzyme
nerves.2 A single nerve block that provides complete upper
inhibitors. The patient’s vital signs were as follows: blood
airway anesthesia is, consequently, not possible. Techniques
pressure, 145/85 mm Hg; heart rate, 84 beats per minute;
for regional anesthesia include glossopharyngeal nerve block
respiratory rate, 22 breaths per minute; and the room air
(oropharynx), superior laryngeal nerve block (larynx above the
oxygen saturation was 91%. The preoperative airway
vocal cords), and transtracheal block (larynx below the vocal
examination showed decreased cervical range of motion
cords). Regional nerve blocks may be technically challenging
and decreased mouth opening. There was a hard 8-cm
and less reliable in patients with distorted anatomy secondary
fixed mass in the right neck, and there was stridor with
to tumor growth and tissue infiltration.
forced inspiration.
Either the nasal or oral route can be selected for fiberoptic
intubation. Unless the procedure specifically requires nasotra-
cheal intubation, the oral route is preferred. Nasal intubation
is associated with a higher likelihood of complications such as
How should the patient’s airway be managed epistaxis, sinusitis, and bacteremia. Passage of a tracheal tube
for anesthesia induction? through the nasal passage is more uncomfortable for the
The patient had several airway abnormalities such as de- patient because the pressure sensation as the tracheal tube
creased cervical range of motion, poor mouth opening, and an compresses the soft tissue of the nasal passage against bony
obstructive laryngeal mass that make awake, tracheal intuba- structures is difficult to attenuate.
tion the best option. Induction of general anesthesia before After the patient arrived in the preoperative holding area,
intubation increases the risk of further airway obstruction in the anesthesiologist provided a thorough explanation of the
a patient that may be difficult to ventilate and perform rigid, plan for awake, tracheal intubation. Glycopyrrolate (0.1 mg
direct laryngoscopy for tracheal intubation. Insertion of a intravenous [IV]) was administered. The patient was in-
supraglottic airway after induction of anesthesia does not structed to slowly and deeply inhale 4% lidocaine via a nebu-
guarantee a patent airway in a patient with significant laryn- lizer. After inhaling the lidocaine, the patient was transferred
geal pathology. The overall clinical presentation of this to the operating room.
106
15259_Ch29.qxd 3/14/09 6:59 PM Page 107
CHAPTER 29 • AWAKE TRACHEAL INTUBATION 107
Pharyngeal secretions retard diffusion of the local anesthet-

T A B L E 2 9 . 1 Patient Preparation for Awake,
ics across the membranes of the upper airway. An antisialo-
gogue will dry mucous membranes and improve the quality of Tracheal Intubation
topical anesthesia. In comparison to atropine, glycopyrrolate
produces comparable drying of secretions with less risk of Thorough explanation of the purpose
tachycardia or central nervous system side effects. Inhalation of Explanation of the process
topical anesthetic will disperse the medication throughout the Administration of an antisialogogue
upper airway. This initial phase of upper airway anesthesia can
be done in the holding area without parenteral sedation. Inhalation of local anesthetic
After transfer to the operating room, parenteral sedation Parenteral sedation
was initiated with midazolam (30 ␮g/kg) and fentanyl
Direct application of topical anesthetic
(1 ␮g/kg). An IV infusion of dexmedetomidine (0.7 ␮g /kg per
hour) was begun. Before sedation, the patient’s heart rate was Insertion of an intubating oral airway
86 beats per minute, and his blood pressure was 150/85 mm Fiberscope insertion
Hg. After sedation, his heart rate was 71 beats per minute, and
his blood pressure was 120/75 mm Hg. Fiberscope navigation
The level of sedation must be closely monitored to avoid Passage of tracheal tube
oversedation that increases the likelihood of airway obstruc-
tion and apnea. Low-dose midazolam produces amnesia with-
out excessive sedation. Fentanyl provides additional sedation
and suppresses the cough reflex. Dexmedetomidine, a short- flexible fiberscope allows the anesthesiologist to visualize the
acting ␣-2 adrenergic agonist provides sedation without signif- larynx without altering the position of the mass with little risk
icant respiratory depression.3,4 Dexmedetomidine can be of trauma. The working channel of the fiberscope provides
administered as a continuous infusion (0.7 ␮g/kg per hour) or a route for instillation of additional local anesthetic to the la-
as a loading dose (1 ␮g/kg, ideal body weight). Rapid infusion ryngeal inlet and the trachea.6
of dexmedetomidine can cause bradycardia and hypotension. Satisfactory sedation and topical anesthesia of the orophar-
Although sedation techniques have been described for each of ynx was achieved. An Ovassapian intubating airway was
these drugs independently, the higher doses of a single drug slowly inserted into the oropharynx with minimal discomfort
increase the likelihood of complications. Combining the drugs to the patient. A 5.2-mm video bronchoscope with a pre-
in lower doses produces a comfortable patient without respira- loaded 6.0-mm inner diameter tracheal tube was passed
tory depression. To obtain an optimal level of sedation, proper through the patient’s airway and into the hypopharynx.
timing of sedative administration and adequate time to Oxygen at 4 L/min was insufflated via the working channel.
achieve effect are required. At the level of the epiglottis, 2 mL of 4% lidocaine was in-
After a satisfactory level of sedation has developed, addi- jected through the working channel. Instillation of the lido-
tional topical anesthetic can be applied to the tongue, orophar- caine provoked mild coughing; no further advance of the
ynx, and hypopharynx. Many different methods can be used fiberscope was attempted until the coughing subsided. After
that employ commercially available products and dispensing the patient’s coughing ceased, the fiberscope was advanced
devices.5 Lidocaine ointment can be applied to the under sur- under the epiglottis and into the glottic inlet where 2 mL of
face (tongue contact side) of an intubating airway. The airway 4% lidocaine was instilled through the working channel.
is slowly advanced over the patient’s tongue and into the phar- Slight coughing developed that quickly subsided, the fiber-
ynx; as the ointment is warmed, it liquefies and coats the mu- scope was advanced into the subglottic region, and another
cous membranes of the oropharynx and hypopharynx. Once 2 mL of 4% lidocaine was administered via the working chan-
the airway has been inserted to maximal depth and the patient nel. No coughing occurred with the final lidocaine instilla-
is comfortable, a flexible fiberscope can be passed through the tion, and the fiberscope was advanced into the midtrachea.
airway, and additional topical anesthetic is instilled through After confirmation of the fiberscope position in the midtra-
the working channel of the fiberscope (Table 29.1). chea, the well-lubricated tracheal tube was advanced over the
fiberscope and into the trachea. The tracheal tube cuff was
gently inflated, and tracheal intubation was confirmed by
Which device or technique should be used capnograph. General anesthesia was induced with IV propo-
for intubation? fol and inhaled sevoflurane.
Every technique for tracheal intubation has been used for There are two basic types of flexible fiberscopes in clinical
awake intubation. The development of new devices and tech- use. The older optical type fiberscopes contain an imaging
niques for intubation in the past 15 years has increased the bundle of optical fibers through which the endoscopist views
anesthesiologist’s options for intubation of the patient with a the airway. Optical fiberscopes are limited in resolution, mag-
difficult airway. Technique selection depends on the type of nification, and field of view by the number of fibers in the im-
airway abnormality and the likelihood of success without aging bundle and are subject to some optical aberration. A
complications. For this patient with a laryngeal mass, it is camera can be attached for image display on a monitor. The
valuable to inspect the relationship of the mass to the laryngeal camera, however, does not alter the resolution or field of view.
inlet without undue trauma. Blind insertion of any device The second and more modern type of fiberscope, the flexible
incurs the risk of trauma to the tumor and displacement of videoscope, has a charged-coupled device (CCD) chip at the end
the mass into a more obstructive position. A high-resolution of the scope that transmits a digital signal to a microprocessor
15259_Ch29.qxd 3/14/09 6:59 PM Page 108
108 CHAPTER 29 • AWAKE TRACHEAL INTUBATION
that constructs an image on a monitor. Videoscopes provide Does the availability of supraglottic airways
high-resolution, wide-angle images that are superior to the eliminate the need for awake, tracheal
images of an optical fiberscope. Videoscopes are preferred for intubation?
use in patients with upper airway tumors or when there is There is little doubt that the invention and development of
blood in the airway. The wide-angle field of view displays the supraglottic airways has reduced the need for awake, tracheal
laryngeal tumor in relationship to the entire hypopharynx. intubation.8,9 This is especially true for situations in which
Proper fiberscope selection to meet the requirements of the external abnormalities (e.g., cervical spine abnormalities) limit
clinical situation improves the efficiency and success rate for airway access or in children with congenital airway abnormal-
awake, tracheal intubation. ities (e.g., Pierre-Robin, Treacher-Collins, Klippel-Feil syn-
If the endoscopist is patient and recognizes anatomical dromes). For patients with immediate supralaryngeal or
landmarks before advancing the fiberscope, this will permit intralaryngeal pathology (e.g., tumors, direct trauma), direct
methodic manipulation of the scope and navigation through visualization of the lesion provides important information
the airway. Instillation of local anesthetic through the work- concerning airway management. The need for awake, tra-
ing channel of the fiberscope at the levels of the epiglottis, cheal intubation is still present for the anesthesiologist, as there
laryngeal inlet, subglottis, and midtrachea enhances patient are still situations in which awake, tracheal intubation may
comfort and cooperation. If the local anesthetic provokes prevent significant morbidity and mortality.10,11
coughing, the scope should not be advanced until the local
anesthetic has taken effect and the coughing has ceased.
Oxygen insufflated through the working channel blows secre-
tions away from the end of the fiberscope and reduces lens KEY MESSAGES
fogging. Direct observation of the airway pathology provides
important diagnostic information that may alter the plan for 1. Patient preparation for awake, tracheal intubation
airway management. begins with a thorough explanation of the importance
and need for the procedure.
What are the potential complications from 2. Regional nerve blocks performed to facilitate awake,
awake, fiberoptic tracheal intubation? fiberoptic intubation may be technically challenging
and less reliable in patients with distorted anatomy
The complication rate for awake, fiberoptic tracheal intuba- secondary to tumor growth and tissue infiltration.
tion is extremely low.7 There are sporadic case reports of
infrequent complications that may be a result of the endo- 3. For a patient with a laryngeal mass, it is valuable to
scopist’s inexperience or lack of patient cooperation. Care inspect the relationship of the mass to the laryngeal
must be taken to avoid oversedation and apnea that can lead to inlet without causing undue trauma.
urgent airway management in a patient with a difficult air- 4. Compared with (older) optical fiberscopes, flexible
way. Local anesthetic toxicity rarely occurs in adult patients, videoscopes are preferred for patients with upper
but the local anesthetic dosage must be carefully controlled for airway tumors or when there is blood in the airway.
young children. Passage of the fiberscope or tracheal tube can
provoke laryngospasm and/or bronchoconstriction. Adequate
airway anesthesia usually prevents such airway responses. The
fiberscope should be gently passed, as forceful insertion may
traumatize the airway. QUESTIONS
Oxygen insufflation through the working channel of the
fiberscope has been reported to cause gastric distention. This is 1. Why does administration of an antisialagogue (e.g.
an extremely rare event, although the patient’s abdomen glycopyrrolate) improve the quality of topical airway
should be observed periodically for any evidence of distention anesthesia for awake, tracheal intubation?
(Table 29.2). Answer: Pharyngeal secretions impede the diffusion of
topical anesthetics across mucous membranes. Drying of
secretions enhances the quality of topical anesthesia.
T A B L E 2 9 . 2 Potential Complications of 2. What cranial nerves provide sensation to the upper
Awake, Tracheal Intubation airway?
Answer: Sensory input to the upper airway is supplied by
Oversedation the trigeminal, glossopharyngeal, and vagus nerves.
Local anesthetic toxicity
3. Why do videoendoscopes produce a higher resolution
Gastric distention image than optical endoscopes?
Airway obstruction Answer: Resolution and field of view of an image pro-
Laryngospasm vided by an optical endoscope are determined by the
number of fibers in the imaging bundle. A bundle with
Bronchoconstriction
more fibers produces an image of higher resolution. A
Airway trauma videoendoscope uses a CCD chip instead of an optical
imaging bundle.
15259_Ch29.qxd 3/14/09 6:59 PM Page 109
CHAPTER 29 • AWAKE TRACHEAL INTUBATION 109
References 7. Ovaassapian A. The flexible bronchoscope: a tool for the anes-

thesiologist. Clin Chest Med 2001;22:281–299.
1. American Society of Anesthesiologists Task Force on Difficult 8. Langeron O, Semjen F, Bourgain J-L, et al. Comparison of the
Airway Management. Practice guidelines for management of the intubating laryngeal mask airway with the fiberoptic intubation
difficult airway. Anesthesiology 2003;98:1269–1277. in anticipated difficult airway management. Anesthesiology
2. Simmons ST, Schleich AR. Airway regional anesthesia for awake 2001;94:968–972.
fiberoptic intubation. Reg Anesth Pain Med 2002;27:180–192. 9. Joo HS, Kapoor S, Rose DK, et al. The intubating laryngeal
3. Bergese SD, Khabiri B, Roberts WD, et al. Dexmedetomidine mask airway after induction of general anesthesia versus awake
for conscious sedation in difficult awake fiberoptic intubation fiberoptic intubation in patients with difficult airways. Anesth
cases. J Clin Anesth 2007;19:141–144. Analg 2001;92:1342–1346.
4. Gerlach AT, Dasta JF. Dexmedetomidine: an updated review. 10. Biboulet P, Aubas P, Dubourdieu J, et al. Fatal and nonfatal car-
Ann Pharmacother 2007;41:245–254. diac arrests due to anesthesia. Can J Anaesth 2001;48:326–332.
5. Reed AP. preparation of the patient for awake flexible fiberoptic 11. Langeron O, Amour J, Vivien B, et al. Clinical review:
bronchoscopy. Chest 1992;101:244–253. management of difficult airways. Critical Care 2006;10:243–247.
6. Roberts JT. Preparing to use the flexible fiber-optic laryngo-
scope. J Clin Anesth 1991;3:64–75.
15259_Ch30.qxd 3/14/09 7:16 PM Page 110
CHAPTER 30
Is There a Future for Succinylcholine?
Stephen F. Dierdorf
CASE FORMAT: REFLECTION positive pressure ventilation and 5 cm of positive end-expi-

ratory pressure, arterial oxygen saturation remained in the
A 26-year-old woman presented for an emergency laparo- low-to-mid 80s. An arterial blood gas showed a PaO2 of 62
scopic appendectomy. Her medical history is unremark- with an inspired oxygen fraction of 1.0. After the appendec-
able, and she has not had previous surgery. She began tomy was completed, the patient was transferred to the in-
having abdominal pain 48 hours before admission to the tensive care unit, and mechanical ventilation was continued.
hospital. She had eaten a breakfast of toast and scrambled She was extubated without difficulty 30 hours after surgery.
eggs 2 hours before arrival in the emergency department.
Preoperative examination revealed normal upper airway
anatomy and normal cardiorespiratory systems. Laboratory
measurements including a complete blood count and se-
rum electrolytes were normal other than an elevated white
blood count.
DISCUSSION
The patient’s overall health status was very good,
and there was nothing in her medical history to suggest What is the risk of perioperative pulmonary
any potential interactions between systemic diseases and aspiration?
anesthesia. Older studies report the incidence of aspiration in patients re-
The primary consideration is a patient with a full stom- ceiving general anesthesia as 1 per 2000 to 3000. A more recent
ach for an emergency procedure. The main goal during study reported the incidence to be 1 in 7000. Whether this de-
the induction period was to intubate the trachea and iso- crease represents a true reduction in the incidence of aspira-
late the airway from the gastrointestinal tract as quickly as tion is not clear. Aspiration is more likely to occur during
possible to minimize the risk of regurgitation and aspira- emergency surgery and in patients with significant coexisting
tion of gastric contents. The choice of a hypnotic induction diseases. Although the overall risk of death from perioperative
drug for this patient was not critical. The selection of a mus- aspiration is low (1 in 35,000–99,000), patients who do aspirate
cle relaxant to facilitate tracheal intubation was a more im- have a 50% chance of developing a respiratory complication
portant choice. Should the choice be succinylcholine or a and a 5% to 7% chance of dying. The relative infrequency of
nondepolarizing muscle relaxant? The advantages of suc- perioperative pulmonary aspiration should not allow anesthe-
cinylcholine are rapid, predictable onset and short dura- siologists to become complacent about its risks.1,2
tion of action. For this young woman, the risk of myalgia
and the possibility of serious, unpredictable side effects of
succinylcholine led to the selection of cisatracurium as the Is there a standardized rapid sequence
muscle relaxant of choice. induction?
In the operating room, standard preinduction monitors The introduction of curare into clinical practice in 1942 ush-
(electrocardiogram, automated blood pressure device, pulse ered in a new era in anesthesiology. Muscle relaxation could
oximeter) were placed. Prior to induction, midazolam 3 mg then be produced with specific muscle relaxants without
and fentanyl 100 ␮g were administered intravenously, and having to use high doses of inhaled anesthetics. At that time,
preoxygenation was performed for 3 minutes. Anesthesia curare was used as an adjunct to anesthesia and not specifi-
induction was performed with propofol 2 mg/kg and cally for tracheal intubation. The introduction of succinyl-
cisatracurium 0.1 mg/kg. As soon as the patient was uncon- choline in the 1950s provided anesthesiologists with a drug
scious, an assistant applied cricoid pressure, and positive that produced rapid, profound muscle relaxation suitable
pressure ventilation with oxygen and sevoflurane was car- for tracheal intubation. Succinylcholine became central to
ried out. Two minutes after administration of cisatracurium, the evolution of the technique for rapid sequence induction
direct laryngoscopy was done. After the laryngoscope was (RSI) to minimize the risk of aspiration pneumonitis in pa-
inserted, the patient retched, and gastric contents were seen tients with a full stomach. The term rapid sequence induction
to enter the trachea. The trachea was quickly intubated, and has been defined by the era during which the anesthesiolo-
positive pressure ventilation with 100% oxygen was per- gist trained and was never truly standardized. The classic
formed. Arterial oxygen saturation declined to 82. Despite RSI consisted of preoxygenation for 3 to 5 minutes, pretreat-
ment with a small dose of a nondepolarizing muscle relaxant
110
15259_Ch30.qxd 3/14/09 7:16 PM Page 111
CHAPTER 30 • IS THERE A FUTURE FOR SUCCINYLCHOLINE? 111
(prevention of fasciculation and increased intragastric pres-

T A B L E 3 0 . 1 Side Effects of Succinylcholine
sure), administration of an induction hypnotic, cricoid pres-
sure as soon as the patient was unconscious, administration Fasciculation
of succinylcholine, no positive pressure ventilation by mask,
and tracheal intubation. There have been many modifica- Myalgia
tions to this sequence with respect to mask ventilation and Increased intragastric pressure
type of muscle relaxant. Routine use of the pulse oximeter Increased intraocular pressure
demonstrated how quickly arterial oxygen saturation can de-
cline in a patient presenting for emergency surgery. Mask Increased intracranial pressure
ventilation is now often performed when the patient be- Hyperkalemia
comes apneic. Cricoid pressure is regarded as optional, as
Malignant hyperthermia
it can provoke retching and emesis and may obstruct the
upper airway. Pediatric anesthesiologists have significantly Bradycardia
modified the RSI technique by substituting rocuronium for Rhabdomyolysis
succinylcholine and using gentle positive pressure ventila-
tion.3 Children with normal pulmonary compliance can be Masseter spasm
easily ventilated with a peak airway pressure of 10 to 12 cm Prolonged apnea (cholinesterase deficiency)
water. Although the list of side effects from succinylcholine
is lengthy, and newer muscle relaxants have challenged
its indications, succinylcholine is still widely used inside
and outside the operating room to facilitate rapid tracheal often. Proof of sugammadex’s efficacy without significant
intubation.4 side effects will only come after widespread clinical use. Ra-
pacuronium was touted as the replacement for succinyl-
choline, and it was not until the drug was released for general
Are there suitable alternatives to clinical use that rapacuronium-induced bronchospasm was
succinylcholine? reported with increasing frequency. The frequency and seve-
There is no doubt that the use of succinylcholine has been re- rity of the bronchospasm led to its withdrawal from clinical
stricted with the availability of short-acting nondepolarizing practice.
muscle relaxants such as rocuronium and cis-atracurium. To
produce rapid profound relaxation with these drugs, however,
requires four times the ED95 resulting in a long recovery What is the role of succinylcholine in modern
period. anesthetic practice?
Side effects from succinylcholine began to be recognized Succinylcholine has been in continuous clinical use for nearly
soon after its widespread use became common practice. 60 years. It has been a life-saving drug when rapid tracheal
These side effects include prolonged apnea (pseudocho- intubation has been required. Although succinylcholine has
linesterase deficiency), myalgia, rhabdomyolysis, masseter accumulated an extensive list of minor and major side effects,
spasm, increased intraocular pressure, increased intragastric it is still a valuable muscle relaxant in the anesthesiologist’s
pressure, hyperkalemia, bradycardia, and a trigger for malig- pharmacologic armamentarium. The most important indica-
nant hyperthermia. After a cause-and-effect relationship was tions for the use of succinylcholine are RSI and when pro-
established between succinylcholine and a side effect, meth- found relaxation is required for a short period of time. The
ods to avoid the side effect were aggressively pursued. The indications for succinylcholine depend on several factors rela-
ability to prevent or attenuate these side effects has prolonged tive to the clinical situation and the concern for possible side
the use of succinylcholine for many years. Rocuronium has effects. Absolute contraindications to succinylcholine use in-
emerged as the most useful of the nondepolarizing muscle re- clude patients with postburn injury, spinal cord transaction,
laxants for rapid tracheal intubation if succinylcholine is con- susceptibility to malignant hyperthermia, and patients with
traindicated. Although rocuronium compares favorably to primary myopathies. Most other contraindications are rela-
succinylcholine regarding rapidity of onset and creating situ- tive, and the risk of complications must be weighed against
ations favorable for tracheal intubation, the dose of rocuro- the benefits of rapid tracheal intubation (Table 30.1). There
nium (1–1.5 mg/kg) required to produce the best conditions are techniques for reducing the incidence and severity of some
for intubation results in a long duration of action.5–7 Studies of the side effects of succinylcholine. Fasciculation and myal-
performed in pediatric patients show a more favorable gia may be attenuated by pretreatment with one of several
comparison between rocuronium (0.9–1.2 mg/kg) and suc- drugs, including lidocaine, nonsteroidal anti-inflammatory
cinylcholine (1.5 mg/kg) with respect to onset of action and medications, or a small dose of nondepolarizing muscle relax-
intubation conditions.8,9 Time to recovery at those doses of ant (Table 30.2).10
rocuronium is 40 to 45 minutes. If rocuronium in higher The future for succinylcholine is unclear. The highly specific
doses is comparable to succinylcholine, the greatest challenge antagonist for rocuronium, sugammadex, may make succinyl-
to succinylcholine use may not be another muscle relaxant, choline obsolete. Other drugs, however, have failed to relegate
but a reversal drug: sugammadex. Sugammadex is a biologi- succinylcholine to historical annals. The combination of rocuro-
cally inactive cyclodextrin that is a highly specific antagonist nium and sugammadex will require extensive clinical use be-
to rocuronium. If sugammadex proves to be as effective as fore it replaces succinylcholine. Until that time, succinylcholine
initial studies indicate, succinylcholine will become used less will still be in use.
15259_Ch30.qxd 3/14/09 7:16 PM Page 112
112 CHAPTER 30 • IS THERE A FUTURE FOR SUCCINYLCHOLINE?
Answer: Rocuronium has the most rapid onset of effect

T A B L E 3 0 . 2 Drugs That Reduce
of the non-depolarizing muscle relaxants currently
Post-Succinylcholine Myalgia available for clinical use and is a suitable alternative to
succinylcholine.
Defasciculating dose of a nondepolarizing muscle relaxant
Pancuronium, rocuronium, vecuronium, atracurium 2. Why are patients with primary myopathies more likely
to develop hyperkalemia after the administration of
Side effects: blurred vision, heavy eyelids, diplopia,
succinylcholine?
dyspnea
Answer: Patients with primary myopathies such as
Sodium channel blockers (lidocaine) Duchenne muscular dystrophy have abnormal muscle
Nonsteroidal anti-inflammatory drugs membranes that are fragile and susceptible to damage
Benzodiazepines (weak effect) from depolarization. Disruption of muscle membranes
results in the release of large amounts of potassium from
the muscle cytoplasm into the circulation.
3. Pretreatment with what types of drugs prevents or
SUMMARY
attenuates succinylcholine-induced myalgia?
The patient in this case was undergoing emergency surgery Answer: Pretreatment with a defasciculating does of a
and was considered to have a full stomach and to be at risk for non-depolarizing muscle relaxant, lidocaine, or non-
aspiration pneumonia based on the time of her last oral intake steroidal anti-inflammatory drugs has been shown to
and probable delayed gastric emptying from appendicitis. reduce the incidence of myalgia after succinylcholine.
Cisatracurium is slow and unpredictable in onset compared
with succinylcholine and rocuronium. Paralysis was incom- References
plete when direct laryngoscopy was attempted, and the patient
retched and vomited. Succinylcholine or rocuronium would 1. Warner MA. Is pulmonary aspiration still an important problem
in anesthesia? Curr Opin Anaesthesiol 2000;13:215–218.
have been a better choice for muscle relaxation. Stimulation
2. Sakai T, Planinsic RM, Quinlan JJ, et al. The incidence and
with a peripheral nerve stimulator before direct laryngoscopy outcome of perioperative pulmonary aspiration in a university
would have undoubtedly shown incomplete paralysis, and as- hospital: a 4-year retrospective analysis. Anesth Anlg 2006;103:
piration could have been avoided. 941–947.
3. Weiss M, Gerber AC. Rapid sequence induction in children—it’s
not a matter of time! Pediatr Anesth 2008;18:97–99.
KEY MESSAGES 4. Stedeford J, Stoddart P. RSI in pediatric anesthesia—is it used by
nonpediatric anesthetists? A survey from south-west England.
Pediatr Anesth 2007;17:235–242.
1. Patients requiring emergency surgery are at increased 5. Mencke T, Knoll H, Schreiber J-U, et al. Rocuronium is not as-
risk for aspiration pneumonitis. sociated with more vocal cord injuries than succinylcholine after
2. There are suitable alternatives for succinylcholine for rapid-sequence induction: a randomized, prospective, controlled
trial. Anesth Analg 2006;102:943–949.
elective surgery.
6. Karcioglu O, Arnold J, Topacoglu H, et al. Succinylcholine or
3. Succinylcholine may still be the most suitable muscle rocuronium? A meta-analysis of the effects on intubation condi-
relaxant for RSI. tions. Int J Clin Pract 2006;12:1638–1646.
7. Sluga M, Ummenhofer W, Studer W, et al. Rocuronium versus
4. Positive pressure ventilation should be rapidly instituted succinylcholine for rapid sequence induction of anesthesia and
after aspiration occurs. endotracheal intubation: a prospective, randomized trial in
emergent cases. Anesth Analg 2005;101:1356–1361.
8. Cheng CAY, Aun CST, Gin T. Comparison of rocuronium and
suxamethonium for rapid tracheal intubation in children.
Paediatr Anaesth 2002;12:140–145.
QUESTIONS 9. Zelicof-Paul A, Smith-Lockridge A, Schnadower D, et al. Con-
troversies in rapid sequence intubation in children. Curr Opin
1. If succinylcholine is contraindicated for a rapid Ped 2005;17:355–362.
sequence induction, what muscle relaxant produces 10. Schreiber J-U, Lysakowski C, Fuchs-Bader T, Tramer MR.
satisfactory conditions for tracheal intubation in the Prevention of succinylcholine-induced fasciculation and myalgia.
shortest period of time? Anesthesiology 2005;103:877–884.
15259_Ch31.qxd 3/14/09 7:16 PM Page 113
CHAPTER 31
Cuffed Tracheal Tubes for Children
Stephen F. Dierdorf
CASE FORMAT: REFLECTION the site of the tracheal tube cuff. The patient was extubated
36 hours after bronchoscopy. Three months after surgery,
A 7-year-old, 35-kg girl presented for repair of an aortic she presented with dyspnea. Bronchoscopy performed with
coarctation and ventricular septal defect. Although she was general anesthesia showed a stenotic area at the midtra-
asymptomatic, a systolic heart murmur was detected dur- chea (Fig. 31.1).
ing a routine physical examination. She is quite active
physically while playing competitive soccer and gymnas-
tics. Previous surgery included bilateral myringotomies at
2 years of age as well as a tonsillectomy and adenoidec-
DISCUSSION
tomy at 4 years of age. The parents reported no complica-
tions from previous anesthesia other than nausea and
What are the advantages of a cuffed tracheal
vomiting. The patient’s preoperative vital signs were as
tube?
follows: temperature, 37.0°C; right arm blood pressure,
145/85 mm Hg; right leg blood pressure, 80/50 mm Cuffed tracheal tubes permit an air seal between the tracheal
Hg; heart rate, 92 beats per minute; and respiratory rate, tube and the tracheal wall. The seal permits controlled positive
18 breaths per minute. A grade II/VI systolic heart murmur pressure ventilation without a leak and loss of inspired vol-
was present. Satisfactory preoperative sedation was ume. The leak around an uncuffed tracheal tube is hard to
achieved with oral midazolam 0.5 mg/kg administered control, and as pulmonary or chest wall compliance decreases,
30 minutes before induction. Anesthesia was induced with effective ventilation diminishes, and the risk of aspiration of
sevoflurane in oxygen. After induction, an intravenous gastric and pharyngeal contents around the tracheal tube in-
catheter was inserted into a vein in the patient’s right fore- creases. Leakage of exhaled carbon dioxide will give a falsely
arm, and a cannula was inserted into the right radial ar- low end-tidal carbon dioxide reading. Other advantages of
tery. Muscle relaxation was achieved with 0.5 mg/kg of cuffed tracheal tubes include more reliable low-flow anesthe-
rocuronium, and the trachea was intubated with a 6.0-mm sia, less need for tracheal tube replacement, and reduced oper-
uncuffed orotracheal tube. Positive pressure ventilation ating room pollution with trace anesthetic gases.
demonstrated a large leak around the tracheal tube (12 cm
water [H2O]). The tracheal tube was replaced with a 6.0-
Are children more vulnerable to postintubation
cuffed orotracheal tube; 3 mL of air injected into the pilot
complications?
balloon produced an air seal. Anesthesia maintenance was
performed with nitrous oxide (N2O) and sevoflurane in oxy- The controversy surrounding the use of cuffed tracheal tubes
gen and a continuous infusion of remifentanil 0.3 μg/kg in pediatric patients has persisted for decades.1 Many pediatric
per minute. The surgical procedure and separation from anesthesiologists recommend that cuffed tracheal tubes should
cardiopulmonary bypass were uneventful. The patient was not be used in children younger than 8 years of age. This rec-
transferred directly to the intensive care unit. She was ommendation is based on the anatomy of the child’s larynx and
weaned from mechanical ventilation and extubated 4 hours trachea. The infant larynx is vertically compact, the epiglottis is
after admission to the intensive care unit. Thirty minutes short, and the aryepiglottic folds are thick. The glottis is 7 mm
after extubation, she developed inspiratory stridor that was in the anteroposterior axis and 4 mm in the lateral axis. The
not relieved by inhaled racemic epinephrine and intra- narrowest dimension of the neonatal airway is 4 to 5 mm at the
venous dexamethasone. She was reintubated with a 5.5-mm subglottis. The cricoid ring has a thick submucosa with abun-
inner diameter uncuffed tracheal tube. There was no audible dant mucus-producing glands. From birth to 3 years of age,
leak around the 5.5-mm tracheal tube. Tracheal extubation there is rapid proportional growth of the larynx. The anatomic
was attempted 12 hours later with similar results, and the relationships of the laryngeal structures are therefore, con-
patient was reintubated. An ear, nose, and throat surgeon stant.2 Tracheal mucosal edema produces a proportionately
recommended that microlaryngoscopy and bronchoscopy larger decrease in the cross-sectional area of the child’s trachea
should be performed under general anesthesia in the oper- compared with the adult. Tracheal wall pressure exceeding
ating room. Laryngoscopy and bronchoscopy revealed 30 cm H2O in adults may compromise perfusion of the tracheal
tracheal wall edema, erythema, and mucosal ulceration at wall causing ischemia and permanent tracheal damage.
Tracheal perfusion pressure in young children is undoubtedly
113
15259_Ch31.qxd 3/14/09 7:16 PM Page 114
114 CHAPTER 31 • CUFFED TRACHEAL TUBES FOR CHILDREN
T A B L E 3 1 . 1 Impact of Airway Edema on

Cross-Sectional Area
Adult
Cricoid
diameter Area
(mm) Area (1-mm edema) Decrease
20 31.4 mm3 25.4 mm3 19%
Infant
3
5 19.6 mm 7.06 mm3 61%
effects. The relationship between tracheal tube placement and

complications is far more complex in children than adults. Most
Figure 31.1 • Endoscopic View of Tracheal Stenosis. pediatric tracheal tubes are merely smaller versions of adult tra-
cheal tubes, and the design is not based on pediatric anatomy.
There is no standardization for pediatric tracheal tubes.
less than for the adult. The air leak test is commonly used to Tracheal tube wall thickness and cuff thickness vary among
determine optimal tracheal tube fit. If a leak is present at 25 cm manufacturers and among different tubes from the same man-
H2O, fewer postoperative adverse respiratory events have been ufacturer. Cuff position relative to the tip of the tracheal tube
reported.3 The air leak test, however, may not be as predictive varies greatly. The problems presented by poor design include
of postextubation stridor in children younger than 7 years of long cuffs and a substantial increase in outer tracheal tube diam-
age.4 N2O can diffuse into the tracheal tube cuff and increase eter by thick cuffs.8 In extreme cases, the proximal cuff may rest
the intracuff pressure to high levels. The rate of diffusion and at the level of the cricoid or the glottic inlet, while the tip of the
subsequent pressure increase depends on the surface area for tube is in the midtrachea.
gas exchange, the permeability of the cuff material, and the The development of a new type of tracheal tube specifically
thickness of the cuff5 (Table 31.1). designed for children may herald a new era in pediatric
The pediatric airway is vulnerable to injury at three levels: tracheal tubes. The Microcuff Paediatric Tracheal Tube
the glottic inlet, the cricoid (subglottis), and the midtrachea. (Microcuff GmbH, Weinheim, Germany) employs a very thin
Examination of children after prolonged tracheal intubation (10 ␮) polyurethane low-pressure cuff that is placed distally
frequently reveals damage to the posterior commissure where on the tracheal tube. Intracuff pressures at “just seal” average
the tracheal tube usually rests, at the level of the cricoid, and in 11 cm H2O for the Microcuff tube compared with 21 to 36 cm
the trachea from pressure against the tracheal wall. The ideal H2O for more conventional tracheal tubes.9,10 Currently, most
tracheal tube would be as narrow as possible at the levels of the of the studies done with this tracheal tube have been published
vocal cords and cricoid, but it would be able to produce an air by the same group, and confirmation of these studies is
seal in the trachea. The uncuffed tube that produces a reason- needed. The design of this tracheal tube is theoretically sound
able seal in the trachea may be too large at the level of the glot- and provides a template for other manufacturers to follow.
tis and the cricoid. A cuffed tube may be closer to ideal if the Routine tracheal tube cuff pressure monitoring or the use
cuff is thin, properly fitted for the child’s airway, and exerts a of an automated pressure relief valve may be indicated for any
low pressure against the tracheal wall at a “just seal” volume cuffed tracheal tube. Precise pressure monitoring eliminates
or slightly lower. the assumption that pressure is satisfactory.11
The consequences of intubation injury can be minor such
as hoarseness or more serious, requiring reintubation and
long-term therapy. The administration of dexamethasone to SUMMARY
reduce mucosal edema and inflammation has been and re-
mains controversial; however, most pediatric anesthesiologists This case illustrates several important concepts about tracheal
and otolaryngologists use dexamethasone in clinical practice.6 intubation and tracheal tubes in children. Cuffed tracheal tubes
in pediatric patients can be used and have several advantages.
Great care, however, must be taken to ensure that there is no
Can tracheal tubes be designed specifically excessive pressure on the tracheal wall. Arbitrary inflation vol-
for children? umes for tracheal tube cuffs are to be discouraged, as the cuff
Detailed analyses of currently available tracheal tubes have pressure is unknown. Diffusion of N2O into the cuff can
shown considerable variation among manufacturers regarding markedly increase the intracuff pressure. It is unfortunate for
depth of insertion, outer wall thickness, cuff position on the this patient that she had an excellent surgical result but is left
tube, and cuff thickness.7 Most currently available pediatric tra- with a serious postintubation complication that will require ex-
cheal tubes lack the careful design and precision manufacturing tensive therapy. The development of pediatric-specific tracheal
that might greatly reduce the incidence of postintubation side tubes may reduce the likelihood of complications in the future.
15259_Ch31.qxd 3/14/09 7:17 PM Page 115
CHAPTER 31 • CUFFED TRACHEAL TUBES FOR CHILDREN 115
increase. The trachea is a relatively rigid tube and the

KEY MESSAGES
intracuff cuff pressure will increase as nitrous oxide
diffuses into the cuff.
1. The use of cuffed endotracheal tubes in children is
highly controversial.
2. N2O diffusion into the tracheal tube cuff can markedly References
increase intracuff pressure and increase the risk of
1. Fine GF, Borland LM. The future of the cuffed endotracheal
tracheal wall ischemia.
tube. Pediatr Anesth 2004;14:38–42.
3. The leak test may not predict adverse airway events 2. Isaacson G. The larynx, trachea, bronchi, lungs, and esophagus.
after extubation. In: Bluestone CD, Stool SE, Alper CM, et al, eds. Pediatric
Otolaryngology. 4th Ed. Philadelphia: Saunders, 2003:1361–1370.
4. Pediatric tracheal tubes need to be specifically 3. Suominen P, Taivainen T, Tuomenin N, et al. Optimally fitted
designed for children. tracheal tubes decrease the probability of postextubation adverse
events in children undergoing general anesthesia. Pediatr Anesth
2006;16:641–647.
4. Mhanna MJ, Zamel YB, Tichy CM, Duper DM. The “air leak”
QUESTIONS test around the endotracheal tube, as a predictor of postextuba-
tion stridor, is age dependent in children. Crit Care Med 2002;
30:2639–2643.
1. How does the anatomy of the infant airway at the laryn- 5. Dullenkopf A, Gerber AC, Weiss M. Nitrous oxide diffusion into
geal level differ from the anatomy of the adult airway? tracheal tube cuffs: comparison of five different tracheal tube
Answer: The adult airway is cylindrical in shape with the cuffs. Acta Anaesthesiol Scand 2004;48:1180–1184.
6. Lukkassen MA, Markhorst DG. Does dexamethasone reduce
narrowest area at the level of the vocal cords. The infant
the risk of extubation failure in ventilated children? Arch Dis
larynx is cone shaped and the narrowest area is at the Child 2006;791–793.
level of the cricoid cartilage. 7. Weiss M, Dullenkopf A. Cuffed tracheal tubes in children:
past, present, and future. Expert Rev Med Devices 2007;4:
2. What is the impact of airway edema on the cross- 73–82.
sectional area of a pediatric airway? 8. Weiss M, Dullenkopf A, Gysin C, et al. Shortcomings of cuffed
Answer: Inflammation of the airway lining produces a pediatric tracheal tubes. Br J Anaesth 2004;92:78–88.
comparable amount of edema in both adults and chil- 9. Dullenkopf A, Schmitz A, Gerber AC, Weiss M. Tracheal seal-
dren. The reduction in cross-sectional area caused by in- ing characteristics of pediatric cuffed tracheal tubes. Pediatr
flammatory edema can be three to four times greater in Anesth 2004;14:825–830.
the infant as compared to the adult. 10. Dullenkopf A, Gerber AC, Weiss M. Fit and seal characteris-
tics of a new paediatric tracheal tube with high volume-low
3. Does the inhalation of nitrous oxide increase the pres- pressure polyurethane cuff. Acta Anaesthesiol Scand 2005;49:
sure and volume in a tracheal tube cuff? 232–237.
11. Dullenkopf A, Bernet-Buettiker V, Maino P, Weiss M.
Answer: Nitrous oxide diffuses into air filled cavities Performance of a novel pressure release valve for cuff pressure
much faster than nitrogen can diffuse out of the cavity. If control in pediatric tracheal tubes. Pediatr Anesth 2006;16:
the cavity is non-expandable, the intracavity pressure will 19–24.
15259_Ch32.qxd 3/14/09 7:19 PM Page 116
CHAPTER 32
Role of Intraoperative BIS Monitoring
Stephen F. Dierdorf
analyze power and frequency. Bispectral analysis adds addi-

tional information that examines the phase relationships of
the sinusoids. The bispectral index is a dimensionless number
A 45-year-old, 97-kg male was scheduled to undergo a la-
based on processing of the EEG with bispectral analysis and
parotomy for colon cancer resection. He had a history of
clinical information. The BIS of the awake patient is 90 to100.
mild hypertension that was controlled with 100 mg of
Moderate hypnosis is indicated by a number of 60, and deep
losartan per day. He had undergone no prior surgery and
hypnosis is indicated by 40 (Fig. 32.1).1–3
had no allergies. The patient’s heart rate was 66 beats
The clinical purpose of BIS monitoring is to determine
per minute, and his blood pressure was 124/78 mm Hg.
the level of hypnosis during sedation and general anesthesia
He was concerned about the safety of anesthesia and
with the hope of more precise administration of anesthetic
asked the anesthesiologist a few questions.
drugs. Depth of anesthesia is a difficult term to define and
cannot be represented by a single monitor. Depth of anesthe-
sia incorporates hypnosis, analgesia, and reflex responses.
How safe is anesthesia, and what monitors The neural function that has gained the most attention with
will be used during my surgery? respect to monitoring is intraoperative awareness. Whether
routine BIS monitoring reduces the incidence of awareness is
The safety of anesthesia has improved dramatically in the past
controversial.4,5
30 years. Increased safety can be attributed to increased knowl-
The patient was brought to the operating room. The electro-
edge of pathophysiology, the introduction of better anesthetic
cardiogram, blood pressure cuff, pulse oximeter, and BIS sensor
drugs, and the development of more and better monitors. All
were applied before the induction of anesthesia. Anesthesia was
patients receiving anesthesia are observed with standard mon-
induced with 2.5 mg/kg of propofol, and 0.8 mg/kg of rocuro-
itors such as a continuous electrocardiograph, pulse oximeter,
nium was administered to provide muscle relaxation for tra-
blood pressure cuff, and capnograph. These monitors are con-
cheal intubation. Positive pressure ventilation with sevoflurane
sidered to be the standard of care by most regulatory and pro-
in oxygen was provided until muscle relaxation was achieved.
fessional anesthesiology organizations. The primary function
Three minutes after the administration of propofol, the patient’s
of these required monitors is the evaluation of cardiorespira-
blood pressure was 70/45 mm Hg with a heart rate of 58 beats
tory function during the perioperative period. An optional
per minute. The BIS was 9.
monitor that may be used is a device that watches neurologic
function to monitor effects of the anesthetic and detect cerebral
ischemia. Although there are several neurologic monitors
available, the BIS monitor (Aspect Medical Systems, Newton, Can routine BIS monitoring reduce the incidence
MA) is the most frequently used. Other neurologic monitors in of hypotension during induction?
clinical use include the SEDline (Hospira, Lake Forest, IL), the Administering an induction drug by an intravenous bolus tech-
Narcotrend (Schiller AG, Baar, Switzerland), Entropy (GE nique is based on an assumption of how much drug each patient
Healthcare, UK), the Cerebral State Monitor (Danmeter A/S, will require. Variability of individual patient drug response
Odense, Denmark), and the AEP/2 Monitor (Danmeter, would suggest that such assumptions are not always accurate,
Odense, Denmark). and the rate of drug administration may influence hemo-
dynamic responses.6 A carefully titrated drug administration
based on BIS response reduces the risk of a relative drug over-
How does the BIS monitor work, and what dose and subsequent hypotension.7 A BIS index of less than 40
does it measure? is frequently associated with hypotension. Slow administration
The electroencephalograph (EEG) measures a complex signal of the induction drug either by small bolus injections or contin-
of brain electrical activity. Continuous monitoring of multiple uous infusion to a BIS index of 50 produces a satisfactory level
channels of the raw EEG is not practical in the operating of anesthesia with less decrease in blood pressure and heart rate.
room for the anesthesiologist. Signal processing techniques to This is especially evident in geriatric patients.
render the EEG more informative have been developed in re- The sevoflurane concentration was decreased, and 5 mg
cent years. These processing techniques break the EEG signal of ephedrine was given intravenously. Within 2 minutes, the
into a family of sinusoids with three basic elements: ampli- patient’s blood pressure increased to 105/70 mm Hg, and the
tude, frequency, and phase angle. Most processing methods BIS increased to 50.
116
15259_Ch32.qxd 3/14/09 7:19 PM Page 117
CHAPTER 32 • ROLE OF INTRAOPERATIVE BIS MONITORING 117
BIS 100 T A B L E 3 2 . 1 Perioperative Neural Monitors

Awake, Memory Intact
BIS monitor
80 SEDLine (Hospira, Lake Forest, IL)
Sedation AEP Monitor/2 (Danmeter, Odense, Denmark)
Entropy (GE Healthcare, UK)
60 Cerebral State Monitor (Danmeter A/S, Odense,
General Anesthesia Denmark)
Narcotrend (Schiller AG, Baar, Switzerland)
“Deep” Hypnosis, Memory Function Lost
40
“Near” Suppression
Increasing
Burst Suppression
20 glycopyrrolate, 0.01 mg/kg. Sustained tetanus was demon-
strated with a peripheral nerve stimulator. The patient
opened his eyes upon command, the BIS was 94, and the tra-
chea was extubated. His immediate postoperative course was
0 Cortical Silence normal. An anesthesiology colleague asked whether routine
BIS monitoring should be required.
Figure 32.1 • The Bispectral Index Scale.
Should routine BIS monitoring be required?

Function of the central nervous system is complex, and cur-
rently available monitors are primitive in comparison. The BIS
What BIS number (value) is consistent with monitor is not the only available neural monitor, and others
adequate hypnosis during the maintenance may offer advantages that have not yet been fully researched.
phase of anesthesia? When properly used and interpreted, the BIS monitor can pro-
There is no precise BIS number that is consistent with an ad- vide information that allows the anesthesiologist to provide
equate level of hypnosis during anesthesia maintenance. In improved management of anesthesia. The BIS monitor has
general, a range of 50 to 60 seems desirable. Titration of been used to a greater extent than any previous neural monitor,
maintenance anesthesia with isoflurane to a range of 50 to but it should most likely be regarded as a first step in the devel-
60 produces faster recovery in elderly patients.8 There is con- opment and clinical application of routine neural monitoring to
cern that consistently low BIS levels (⬍45) may be associated the practice of anesthesiology.13,14 The designation of a moni-
with adverse outcomes.9 This study has been highly con- tor as a standard monitor introduces an extensive list of regula-
troversial and requires confirmation. Elderly patients tory and legal requirements that may imply a greater value to
(⬎60 years) seem to have an increased risk of long-term post- the monitor than it actually has.
operative cognitive dysfunction after major noncardiac Neural monitors of the future should give very specific in-
surgery.10 formation about the functional status of the patient’s central
Routine BIS monitoring during anesthesia has been nervous system and the integrity of cerebral perfusion and me-
shown to reduce anesthetic consumption, time to extuba- tabolism. The development of advanced neural monitors
tion, nausea and vomiting, and recovery room time.11,12 should assist anesthesiologists with actually defining and meas-
Prediction of emergence may be influential in avoiding im- uring the depth of anesthesia (Tables 32.1 and 32.2).
mediate postoperative respiratory complications. If the pa-
tient attains clinical evidence of recovery and the BIS is ⬎90,
there seems to be minimal risk of airway obstruction and
laryngospasm.
There is considerable anecdotal experience that profound T A B L E 3 2 . 2 Advantages of Routine BIS
decreases in the BIS index may indicate cerebral ischemia.
These case reports describe a variety of clinical scenarios such Monitoring
as cardiac arrest, hypotension, anaphylaxis, or cardiac dys- Reduce incidence of awareness
rhythmias that may decrease cerebral perfusion. The BIS
level usually decreases to less than 10 but increases if cerebral More predictable emergence
perfusion returns in a timely manner. Whether the rapid Decreased time to extubation
return of the BIS to normal anesthetic ranges after a period of Less nausea and vomiting
cerebral hypoperfusion has prognostic significance is as yet
undetermined. Improved nursing utilization
At the conclusion of surgery, residual neuromuscular Teaching tool
blockade was reversed with neostigmine, 0.07 mg/kg and
15259_Ch32.qxd 3/14/09 7:19 PM Page 118
118 CHAPTER 32 • ROLE OF INTRAOPERATIVE BIS MONITORING
incidence of intraoperative hypotension, postoperative

KEY MESSAGES
nausea and vomiting, immediate postoperative respira-
tory complications, and reduce recovery time.
1. The bispectral index is a dimensionless number based
on processing of the EEG with bispectral analysis and
clinical information. References
2. Depth of anesthesia incorporates hypnosis, analgesia, 1. Sigl JC, Chamoun NG. An introduction to bispectral analysis for
and reflex responses. the electroencephalogram. J Clin Monit 1994;10:392–404.
2. Rosow C, Manberg P. Bispectral index monitoring. Anes Clin N
3. Routine BIS monitoring during anesthesia has been Amer 1998;2:89–107.
shown to reduce anesthetic consumption, time to tra- 3. Johansen JW, Sebel PS. Development and clinical application of
cheal extubation, nausea and vomiting, and recovery electroencephalographic bispectrum monitoring. Anesthesiology
room time. 2000;93:1336–1344.
4. Myles PS, Leslie K, McNeil J, et al. Bispectral index monitoring to
4. The BIS monitor is not the only available “depth of prevent awareness during anaesthesia: the B-Aware randomized
anesthesia” monitor, and others may offer advantages controlled trial. Lancet 2004;363:1757–1763.
that have not yet been fully investigated. 5. Avidan MS, Zhang L, Burnside BA, et al. Anesthesia awareness
and the bispectral index. N Engl J Med 2008;358: 1097–1108.
6. Zheng D, Upton RN, Martinez AM, et al. The influence of
bolus injection rate of propofol on its cardiovascular effects and
the peak blood concentrations in sheep. Anesth Analg 1998;86:
QUESTIONS 1109–1115.
7. Heck M, Kumle B, Boldt J, et al. Electroencephalogram bispec-
tral index predicts hemodynamic and arousal reactions during
1. What variables of the electroencephalograph (EEG) induction of anesthesia in patients undergoing cardiac surgery. J
does bispectral analysis process? Cardiothor Vasc Anes 2000;14:693–697.
Answer: Bispectral evaluates and processes power, ampli- 8. Wong J, Song D, Blanshard H, et al. Titration of isoflurane
tude, and phase relationships. This analysis technique using BIS index improves early recovery of elderly patients un-
dergoing orthopedic surgeries. Can J Anaesth 2002;49:13–18.
evaluates more parameters than most processed EEG 9. Monk TG, Saini V, Weldon BC, Sigl JC. Anesthetic manage-
programs. ment and one-year mortality after noncardiac surgery. Anesth
Analg 2005;100:4–10.
2. What range of BIS values is desired during the mainte-
10. Monk TG, Weldon BC, Garvan CW, et al. Predictors of cogni-
nance phase of anesthesia? tive dysfunction after major noncardiac surgery. Anesthesiology
Answer: During the maintenance phase of anesthesia, the 2008;108:18–30.
desired BIS range is 50 to 60. It may not, however, be 11. Liu SS. Effects of bispectral index monitoring on ambulatory
possible to consistently achieve a specific range in clinical anesthesia. Anesthesiology 2004;101:311–315.
practice. 12. Punjasawadwong Y, Boonjeungmonkol N, Phongchiewboon A.
Bispectral index for improving anaesthetic delivery and postop-
3. What are the potential benefits of the routine use of the erative recovery. Cochrane Database Syst Rev 2007 Oct 17;4:
BIS monitor? CD003843.
13. Bowdle TA. Depth of anesthesia monitoring. Anesthesiology Clin
Answer: The goal of monitoring the effects of anesthesia 2006;24:793–822.
on the central nervous system is to precisely administer 14. Bruhn J, Myles PS, Sneyd R, Struys MMRF. Depth of anesthesia
the proper amount of anesthetic drug(s) to avoid over or monitoring: what’s available, what’s validated and what’s next?
under-dosing. A BIS-guided anesthetic may reduce the Br J Anaesth 2006;97:85–94.
15259_Ch33.qxd 3/14/09 7:22 PM Page 119
CHAPTER 33
Duchenne Muscular Dystrophy and

Volatile Anesthetics
Stephen F. Dierdorf
Diminished skeletal muscle strength produces an ineffective

cough that can lead to retention of pulmonary secretions and
pneumonia. Death is secondary to congestive heart failure or
A 4-year-old, 17-kg male was scheduled for bilateral in-
pneumonia.
guinal hernia repair and a muscle biopsy. His pediatrician
Despite identification of the gene defect that causes DMD
suspected that the child had Duchenne muscular dystrophy
more than 20 years ago, the pathophysiology is poorly under-
(DMD). His only prior surgery was strabismus surgery at
stood, and specific therapy has remained elusive.3 Studies of
2 years of age performed with general anesthesia without
gene therapy in a DMD (mdx) mouse model have begun.
any known complications. The suggestion that their child
Corticosteroids increase muscle strength and improve car-
may have muscular dystrophy was recent, and the boy’s
diorespiratory function.4 Afterload reduction with angiotensin-
parents asked the anesthesiologist to tell them about the
converting enzyme inhibitors can improve cardiac function and
disease.
increase ejection fraction. ␤-adrenergic blockers may also be
efficacious but may cause cardiac conduction changes.
There are other types of muscular dystrophy (Table 33.1).
Becker muscular dystrophy (BMD) most closely resembles
What is DMD? DMD. Patients with BMD usually have some dystrophin,
and the clinical course is milder with onset of symptoms later
The cytoskeleton of the muscle cell is composed of a complex
(11 years) and a longer life expectancy. BMD patients can de-
of proteins such as dystrophin, dystroglycan, sarcoglycan,
velop a severe dilated cardiomyopathy.
utrophin, syntrophin, and dystrobrevin (Fig. 33.1). Dystrophin
The parents reported nothing unusual in their son’s medical
is the largest of the proteins and the most critical component of
history, and his only previous anesthetic at age 2 was uneventful.
the dystrophin-glycoprotein complex. This complex links the
cell membrane to the contractile elements of the muscle cell
and stabilizes the membrane during contraction. Patients with
What information should be obtained from the
DMD have a mutation in the gene that regulates dystrophin
preoperative evaluation?
production, and they lack dystrophin. The absence of dys-
trophin increases the fragility of the muscle membrane render- Many children with DMD are asymptomatic, and the clinical
ing it prone to damage and release of intracellular contents into features may be subtle during the early stages of the disease.
the circulation. Skeletal muscle biopsies from patients with First-time parents may be unaware of developmental mile-
DMD demonstrate various stages of muscle cell necrosis, re- stones and are unable to report evidence of delayed motor de-
generation, and ultimately replacement of contractile muscle velopment. The anesthesiologist must be alert for any signs of
with adipose and fibrotic tissue. DMD is a sex-linked recessive skeletal muscle dysfunction such as hypotonia, delayed walk-
trait that is clinically evident in males. Progressive muscle ing and speech, gait disturbances, or pseudohypertrophy of
weakness produces symptoms between the ages of 2 and 5 years muscles (gastrocnemius). An elevated CK level may be the
with significant limitation of mobility by 12 years of age. first evidence of DMD. A preoperative cardiology consulta-
Sequential serum creatine kinase (CK) levels reflect the dis- tion and echocardiography are recommended for patients
ease’s progression. Early in the patient’s life, CK levels are ele- with suspected or known DMD.
vated. As the patient ages and significant amounts of skeletal The parents were somewhat overwhelmed about the sus-
muscle have degenerated, CK levels decrease. Although skele- pected diagnosis of DMD and were also concerned about the
tal muscle weakness produces the earliest and most obvious likelihood of an adverse event.
clinical abnormalities, cardiac and smooth muscle are affected
as well. Loss of myocardial muscle, as reflected by a progressive
decrease in R-wave amplitude on the electrocardiogram with What are the risks of anesthesia?
aging, results in dilated cardiomyopathy, dysrhythmias, and A small (⬍20 cases) but steady accumulation of case reports of
mitral regurgitation. Echocardiography with tissue Doppler adverse effects in patients with DMD has developed during the
imaging and myocardial strain measurement can reveal subtle past 2 decades.5 The cases, in varying degrees, show evidence
changes in myocardial function before the onset of symp- of severe rhabdomyolysis, hyperkalemia, metabolic acidosis,
toms.1,2 Smooth muscle involvement causes gastroparesis, de- hyperthermia, renal failure, coagulopathy, and frequently
layed gastric emptying, and an increased risk of aspiration. death (Table 33.2). The similarity of this clinical complex and
119
15259_Ch33.qxd 3/14/09 7:22 PM Page 120
120 CHAPTER 33 • DUCHENNE MUSCULAR DYSTROPHY AND VOLATILE ANESTHETICS
Figure 33.1 • Muscle Cell Cytoskeleton. (Reproduced with permission from

Duggan DJ, Gorospe JR, Fanin M, et al. Mutations in the sarcoglycan genes in patients with
myopathy. N Engl J Med 1997;336:618–624. Copyright 1997 Massachusetts Medical Society.
All rights reserved.)
malignant hyperthermia (MH) led to the suggestion that DMD operating room, routine monitors were applied. Anesthesia in-
patients are susceptible to MH. Studies in mdx mice have failed duction was performed with 8% sevoflurane in oxygen. A 22-
to establish any link between DMD and MH. The term ap- gauge IV catheter was inserted into a vein on the dorsum of the
plied to the aforementioned clinical complex in patients with child’s right hand. Rocuronium 0.3 mg/kg was administered,
DMD is anesthesia-induced rhabdomyolysis (AIR). The develop- and positive pressure ventilation with 3% sevoflurane in oxygen
ment of AIR is unpredictable, and many patients with DMD was performed without difficulty. The patient’s trachea was
have received volatile anesthetics and succinylcholine without intubated with a 5-mm inner diameter orotracheal tube and
apparent ill effects. The unpredictability of AIR may be related surgery commenced. Ten minutes after the start of surgery, the
to the timing of the anesthetic exposure relative to the ongoing T waves on the electrocardiogram began to peak. The peaked
disease process. Patients who have had a previous uneventful T waves were quickly followed by an increased duration of the
anesthetic may develop AIR during subsequent exposures. QRS complex and ventricular tachycardia. An arterial blood gas
AIR can occur during the anesthetic, during early recovery, or sample revealed FiO2, 1.0; PaO2, 412; PaCO2, 54; pH, 7.20; BE,
during late recovery from anesthesia.6 -6; and potassium, 9.0 mEq/L. The patient’s temperature was
The parents reported that their child is extremely fearful of 38.2°C. IV lidocaine (1 mg/kg) and bicarbonate (0.5 mEq/kg)
needles and becomes hysterical when receiving injections. They were administered without effect, and cardiopulmonary resus-
insisted on an inhalation induction before an intravenous line citation was initiated. Calcium gluconate, 20 mg/kg was ad-
(IV) is placed. ministered, and the ventricular tachycardia converted to a sinus
Twenty-five minutes before the planned induction, 0.5 mg/kg tachycardia of 140 beats per minute. A Foley catheter was
of midazolam in 5 mL of acetaminophen elixir was admin-
istered orally for preoperative sedation. After transfer to the
T A B L E 3 3 . 2 Clinical Features of Anesthesia-

Induced Rhabdomyolysis
T A B L E 3 3 . 1 Types of Muscular Dystrophy
Rhabdomyolysis
Duchenne Hyperkalemia
Becker Tachycardia
Emery-Dreifuss Ventricular dysrhythmias
Oculopharyngeal Metabolic acidosis
Fascioscapulohumeral Hyperthermia
Congenital Renal dysfunction
(Ulrich, Walker-Warburg) Coagulopathy
15259_Ch33.qxd 3/14/09 7:22 PM Page 121
CHAPTER 33 • DUCHENNE MUSCULAR DYSTROPHY AND VOLATILE ANESTHETICS 121
inserted, and the patient’s urine was noted to be dark red. adverse effects. The response to nondepolarizers may, however,
Another blood gas sample obtained 30 minutes after the first re- be abnormal. Studies with rocuronium indicate that the onset
vealed PaO2, 402; PaCO2, 45; pH, 7.37; BE, 0; potassium, 4.5 of peak neuromuscular blockade is delayed and that recovery
mEq/L; and CK level, 21,500. Tetanic stimulation of the ulnar is prolonged.11,12 Reversal with anticholinesterase inhibitors
nerve showed moderate fade. Neostigmine (70 ␮g/kg) and gly- (neostigmine, pyridostigmine) can generally be achieved, but
copyrrolate (10 ␮g/kg) were administered for reversal of neuro- careful monitoring of neuromuscular function is necessary.
muscular blockade. Twenty minutes after the administration of
neostigmine, tetanus was sustained, and the trachea was extu-
bated after the child was fully awake. He was transferred to the KEY MESSAGES
intensive care unit for close observation. The postoperative
course was uneventful, and the patient was discharged to home 1. DMD is an insidious disease with subclinical abnor-
after 36 hours. malities that cause changes in skeletal, cardiac, and
A muscle biopsy performed 1 month after the initial anes- smooth muscle.
thetic was diagnostic for DMD. Anesthesia for the muscle biopsy
was performed with IV ketamine, propofol, and remifentanil. 2. Volatile anesthetics can produce life-threatening rhab-
domyolysis with acute hyperkalemia, myoglobinuria,
and fever that may mimic MH.
What is the best treatment for AIR? 3. The best initial therapy of acute hyperkalemia is the
The most immediate threat to the patient with AIR is acute administration of IV calcium.
hyperkalemia, and the plasma potassium level may exceed 12
mEq/L. The characteristic electrocardiogram changes from
acute hyperkalemia progress rapidly from peaked T waves to
a prolonged QRS complex, to a severely prolonged QRS com-
plex, to ventricular tachycardia, to ventricular fibrillation. The
QUESTIONS
best initial treatment of acute hyperkalemia is IV calcium (20
mg/kg). For the patient with acute transient hyperkalemia 1. What is the best immediate therapy for succinylcholine-
seen with AIR, one dose of calcium is generally sufficient. If induced hyperkalemia with cardiac dysrhythmias?
hyperkalemia persists, another dose of calcium can be admin-
istered and an infusion of insulin and glucose begun. The risk Answer: The best immediate therapy for succinylcholine-
of renal dysfunction from deposition of myoglobin in the renal induced hyperkalemia is the intravenous administration
tubules can be reduced with hydration and the administration of calcium. At the cardiac cell level, calcium is a direct
of mannitol. Serial arterial blood gas measurements are valu- antagonist to potassium. Since the hyperkalemia is tran-
able for treatment of acidosis and electrolyte abnormalities. sient, one dose of calcium is generally sufficient.
2. What is anesthesia-induced rhabdomyolysis (AIR)?
Are volatile anesthetics contraindicated in Answer: AIR is a clinical complex that occurs in patients
patients with DMD? with primary myopathies (Duchenne muscular
dystrophy) characterized by rhabdomyolysis, acidosis,
Whether volatile, inhaled anesthetics are contraindicated in pa-
hyperkalemia, and hyperthermia. AIR can be triggered
tients with DMD is controversial. The unpredictability of AIR
by succinylcholine and inhaled, volatile anesthetics.
prevents scientifically based recommendations, but the severity
Although AIR resembles malignant hyperthermia, AIR
of AIR suggests avoidance of volatile anesthetics.7–9 It can be
is probably a different entity.
speculated that younger patients with DMD may be more likely
to develop AIR because muscle tissues are undergoing both 3. Why is the muscle membrane of patients with Duchenne
necrosis and regeneration. Later in life (adolescence) when mus- muscular dystrophy (DMD) fragile and easily damaged?
cle becomes fibrotic, there may be less likelihood of AIR. The
Answer: The cytoskeleton of the muscle membrane is a
presence of cardiomyopathy, which is more likely in adolescents
complex of large proteins that protect and maintain the
with DMD, increases the possibility of severe myocardial de-
integrity of the muscle cell. Patients with DMD lack
pression from volatile anesthetics.
dystrophin a major component of the cytoskeleton.
The predictability of AIR is unlikely until there is a better
The muscle membrane consequently lacks the strength
understanding of how the pathophysiology of DMD can pro-
of normal membranes and can be damaged by excessive
duce adverse effects from anesthetics. Volatile anesthetics are
depolarization.
best avoided but if needed, should be used judiciously, for as
short a time as possible, and with alertness for the develop-
ment of AIR. References
1. Beynon RP, Ray SG. Cardiac involvement in muscular dystro-
Are muscle relaxants contraindicated for phies. QJM 2008; 101:337–344.
2. Mori K, Hayabushi Y, Inoue M, et al. Myocardial strain imag-
patients with DMD?
ing for early detection of cardiac involvement in patients with
Succinylcholine is contraindicated for patients with DMD.10 Duchenne’s progressive muscular dystrophy. Echocardiography
Nondepolarizing muscle relaxants have been used without 2007;24:598–608.
15259_Ch33.qxd 3/14/09 7:22 PM Page 122
122 CHAPTER 33 • DUCHENNE MUSCULAR DYSTROPHY AND VOLATILE ANESTHETICS
3. Deconinck N, Dan B. Pathophysiology of Duchenne muscular 8. Hayes J, Veyckemans F, Bissonnette B. Duchenne muscular dys-
dystrophy: current hypotheses. Pediatr Neurol 2007;36:1–7. trophy: an old anesthesia problem revisited. Pediatr Anesth 2008;
4. Buschby K, Straub V. Nonmolecular treatment for muscular 18:100–106.
dystrophies. Curr Opin Neurol 2005;18:511–518. 9. Lerman J. Inhalation agents in pediatric anesthesia—an update.
5. Girshin M, Mukherjee Clowney R, Singer LP, et al. The post- Curr Opin Anesthesiol 2007;20:221–226.
operative arrest of a 5 year-old male: an initial presentation 10. Birnkrant DJ, Panitch HB, Benditt JO, et al. American College of
of Duchenne’s muscular dystrophy. Pediatr Anes 2006;16: Chest Physicians consensus statement on the respiratory and re-
170–173. lated management of patients with Duchenne muscular dystrophy
6. Phadke A, Broadman LM, Brandom, et al. Postoperative hyper- undergoing anesthesia or sedation. Chest 2007;132:1977–1986.
thermia, rhabdomyolysis, critical temperature, and death in a 11. Wick S, Muenster T, Schmidt J, et al. Onset and duration of
former premature infant after his ninth anesthetic. Anesth Analg rocuronium-induced neuromuscular blockade in patients with
2007;105:977–980. Duchenne muscular dystrophy. Anesthesiology 2005;102:915–919.
7. Yemen TA, McClain C. Muscular dystrophy, anesthesia and the 12. Muenster T, Forst J, Goerlitz P, et al. Reversal of rocuronium-
safety of inhalational agents revisited, again. Pediatr Anesth 2006; induced neuromuscular blockade in patients with Duchenne
16:105–108. muscular dystrophy. Pediatr Anesth 2008;18:252–255.
15259_Ch34.qxd 3/14/09 7:23 PM Page 123
CHAPTER 34
Anesthesia for Magnetic Resonance

Imaging
Stephen F. Dierdorf
and technical information from manufacturers should be con-

sulted to determine suitability for MRI.2
The bioeffects of MRI are caused by three different types of
A 4-month-old, 4.2-kg male was scheduled for an outpa-
electromagnetic radiation: (a) static magnetic field, (b) a gra-
tient cranial magnetic resonance imaging scan (MRI) be-
dient magnetic field, and (c) a radiofrequency (RF) electro-
cause of an irregular breathing pattern and possible focal
magnetic field. RF may generate excessive heat in metallic
seizures. He was born preterm at 34 weeks postconceptual
components such as pacemaker leads or thermodilution
age and required a stage I Norwood procedure for hy-
catheters and melt the conductive components. RF energy can
poplastic left heart syndrome. He was discharged to home
be different in magnetic fields of different strength. Implants
2 weeks after surgery and has been feeding and growing
that are safe at one field strength may not be safe at lesser or
well since discharge. The patient’s vital signs were as fol-
stronger field strengths. Strong magnetic fields can induce
lows: heart rate, 130 beats per minute; blood pressure,
small voltages changes in blood, which is electrically conduc-
85/54 mm Hg; respiratory rate, 28 breaths per minute;
tive. The voltage changes can induce ST- and T-wave changes
and room air arterial oxygen saturation, 77%. The mother
in the electrocardiogram reading. The physics of the interac-
asked the anesthesiologist a few questions as follows.
tion of strong magnetic fields, RF energy, and patients can be
complex, and expert analysis by magnetic physicists may be
required when safety questions arise.
How does anesthesia for an MRI differ from Factors that make anesthesia for patients in the MRI suite
anesthesia in the operating room? different from the operating room include lack of patient ac-
cessibility for airway management, noise level, and the lack of
The physical environment in the MRI suite is much different
immediately available resuscitation equipment.3
from the environment in the operating room.1 Magnetic fields
generated in the MRI magnet are quite strong compared with
the earth’s magnetic field. The gauss (G) and the tesla (T) are Who will be responsible for sedating my child?
units of magnetic field strength. One tesla equals 10,000 gauss.
The strength of the earth’s magnetic field is 0.6 G. Clinical MR Sedation policies and personnel responsible for sedation vary
field strengths are 0.5 to 3 T. Magnetic fields of greater than 3 T greatly among institutions. The demand for sedation outside the
are used for research, but in coming years, they may be used operating room for diagnostic and interventional procedures in
clinically. The ever-increasing magnetic strengths used for clin- children has increased dramatically in the past decade. Although
ical imaging complicate determination of suitability for equip- the risk of a serious adverse outcome from sedation is low, the
ment in the magnetic environment. incidence of timely rescue interventions is greater than 1 in 100.
The MRI area has been divided into four zones depending This requires the immediate availability of resuscitation equip-
on the proximity to the magnet and the strength of the mag- ment and personnel trained in respiratory management.4 The
netic field (Table 34.1). The intense magnetic field in the MRI goal for sedation is a cooperative and comfortable child who can
suite is not compatible with standard anesthesia machines and maintain a patent airway with satisfactory ventilation and oxy-
monitors. Any magnetic object in the field may become a pro- genation. The line, however, between moderate sedation and
jectile as the object is drawn into the magnet. Serious injuries deep sedation is not easily defined, and the likelihood of passing
have been reported in patients and personnel struck by mag- into a level of deep sedation is high.5 Physicians responsible for
netic objects. A strong handheld magnet (1000 G or greater) sedation at different institutions include radiologists, emergency
should be available for preliminary testing of equipment for po- department physicians, critical care physicians, and anesthesiol-
tential magnetic attraction. Patients with implanted ferromag- ogists. The presence of the anesthesiologist provides an individ-
netic objects may be at risk for injury or damage to the device ual with expert airway management skills and someone who can
from the strong magnetic field. The current classification places quickly convert to a general anesthetic if sedation fails.
metallic objects into one of three categories: (a) MR safe, (b) MR The patient’s mother was assured that at this institution, all
conditional, and (c) MR unsafe. The safety of MR imaging of sedation for imaging procedures is supervised by a pediatric
patients with implanted cardiovascular devices is controversial. anesthesiologist with the assistance of trained nurses. All pa-
Correct identification of the device and a risk/benefit analysis of tients undergo a thorough preoperative evaluation, and a plan
the value of the image avoid both an unsafe MRI in some pa- for sedation is developed for each child depending on his or
tients and denial of an MRI in other patients. Specific references her coexisting problems.
123
15259_Ch34.qxd 3/14/09 7:23 PM Page 124
124 CHAPTER 34 • ANESTHESIA FOR MAGNETIC RESONANCE IMAGING
T A B L E 3 4 . 1 Magnetic Resonance Imaging Zones
Zone I: Outside the magnetic field. Accessible to the general public

Zone II: Area between freely accessible area (zone I) and controlled zones III and IV
Patient and family member movement is supervised. Patient screening is usually
done in zone II.
Zone III: Area where injury can occur if unscreened personnel or patients can incur in-
juries if noncompatible ferromagnetic objects or equipment are present. Zone III
must be strictly restricted.
Zone IV: Magnetic resonance scanner room. This room must be clearly delineated, and a
large red “Magnet On” light must be clearly visible. If cardiopulmonary resusci-
tation is required in zone IV, MR-trained personnel should stabilize the patient
and evacuate to zone II as quickly as feasible.
Is my baby at risk from the contrast agent? cardiopulmonary complications. Sedation with oral hypnotics
The patient’s mother had heard about the potential risks from requires fewer invasive procedures but has a greater likeli-
MRI contrast agents and asked about her infant. Nephrogenic hood of unacceptable patient movement.8 After a discussion
systemic fibrosis (NSF), initially called nephrogenic fibrosing with the mother, the anesthesiologist decided to sedate the in-
dermopathy has been associated with gadolinium-containing fant with oral chloral hydrate.
MRI contrast agents. NSF is characterized by tissue fibrosis that Sedation and/or anesthesia for children undergoing diag-
causes skin thickening and joint contractures. Collagen dep- nostic procedures requires a system that ensures proper pre-
osition can also occur in the lung, skeletal muscle, heart, anesthesia evaluation, technique selection, airway management,
diaphragm, and esophagus. Gadolinium is similar to calcium monitoring, and the presence of a health care provider who
regarding molecular size and bonding and can displace calcium can promptly and effectively manage sedation failure and car-
in a variety of human tissues. Free gadolinium ions interfere diorespiratory complications.9,10 Because there is a greater risk
with macrophage function and cause premature cell death. of adverse outcomes from procedures performed outside the
Noncomplexed gadolinium is unsuitable for use in humans. operating room, careful regard for potential complications is
Contrast agents complex gadolinium with other molecules that important.11
are generally safe for humans with a half-life of 1.3 hours in pa-
tients with normal renal function. Patients with chronic renal
failure have a gadolinium half-life of 30 to 120 hours. Chronic
T A B L E 3 4 . 2 Techniques for Sedation for
renal failure with accompanying metabolic acidosis favors dis-
sociation of gadolinium complexes with release of free gadolin- Neuroimaging
ium and deposition of gadolinium salts in muscle, skin, liver, Sedation
and bone. Patients with chronic renal failure appear to be at
increased risk for NSF because of decreased gadolinium excre- Oral sedatives
tion. Current clinical recommendations are to use alternative Chloral hydrate
contrast agents in patients with chronic renal failure. If gadolin-
Pentobarbital
ium is absolutely necessary, dialysis can markedly enhance the
clearance of gadolinium.6,7 The risk of NSF is negligible in Midazolam
patients with normal renal function. Opioids
Intravenous sedatives
What are the options for sedation and Propofol
anesthesia?
Dexmedetomidine
It was explained to the infant’s mother that there are several
options (Table 34.2). There is no clear advantage to any hyp- General anesthesia
notic, and the selection of a particular technique depends on Inhalation anesthesia
the patient’s condition and anticipated length of the proce- Pharyngeal airway
dure. Sedation with an oral hypnotic such as chloral hydrate or
pentobarbital may provide satisfactory sedation for comple- Supraglottic airway
tion of the MRI. If an intravenous line can be inserted, propo- Tracheal intubation
fol may be used. An inhalation induction with sevoflurane can
Total intravenous anesthesia
be performed followed by intravenous cannulation and laryn-
geal mask airway insertion or tracheal intubation. The pri- Supraglottic airway
mary goals of sedation or anesthesia for children during an Tracheal intubation
MRI examination are a quiescent infant and minimal risk of
15259_Ch34.qxd 3/14/09 7:23 PM Page 125
CHAPTER 34 • ANESTHESIA FOR MAGNETIC RESONANCE IMAGING 125
Thirty minutes after the oral administration of 50 mg/kg of adenotonsillar hyperplasia have an increased risk of airway
chloral hydrate, the infant was not adequately sedated, and an obstruction during sedation. General anesthesia with a laryn-
additional 50 mg/kg was given. The patient was ready for the geal mask airway or tracheal tube would be preferred for
MRI scan 15 minutes after the second dose. The child was patients with those conditions.
sleeping comfortably but could be aroused. The scan, how- The infant has been stable with respect to cardiovascular
ever, had to be stopped after 10 minutes because of excessive function and should tolerate sedation or general anesthesia.
patient movement. Inhaled sevoflurane is well tolerated if ventricular function is
good (preanesthetic echocardiogram). During an inhalation
induction with sevoflurane, the inspired concentration should
What is the plan for failed sedation? be slowly increased and must be decreased once controlled
The options for managing the patient when sedation alone ventilation is initiated. Controlled ventilation increases the
fails to produce a satisfactory condition for the MRI scan uptake of inhaled anesthetics and may produce undesired de-
depend on what system has been developed at the particular creases in blood pressure and heart rate.
institution. At some institutions, the radiologists assume re- A recovery area in the immediate vicinity of the MRI suite
sponsibility for sedation protocols and implementation. If improves patient flow and operational efficiency. The recov-
sedation fails, the patient is rescheduled for a day when an ery area can be staffed with recovery room nurses or nurses
anesthesiologist is available. If the anesthesiology depart- trained and oriented by the recovery room staff.
ment operates the system, an anesthesiologist is usually im-
mediately available to provide general anesthesia. There has
been no attempt to standardize sedation/anesthesia protocols
for MRI examinations. There has been a trend toward in-
stitutional development of dedicated sedation teams led KEY MESSAGES
by critical care physicians, emergency room physicians, or
anesthesiologists.12 1. In the vicinity of an MRI scanner, patients with
The infant was removed from the MRI room into an induc- implanted ferromagnetic objects may be at risk for
tion room in a zone II area. Because he was still well sedated, injury or damage to the device from the strong mag-
a 24-gauge intravenous catheter was inserted into a vein in the netic field.
dorsum of his right hand. Anesthesia was induced with keta- 2. Sedation and/or anesthesia for children undergoing
mine 1 mg/kg followed by rocuronium 0.6 mg/kg and positive diagnostic procedures requires a system that ensures
pressure ventilation provided with 1% sevoflurane in an proper preanesthetic evaluation, technique selection,
oxygen-air mixture. The patient’s trachea was intubated with airway management, monitoring, and the presence of
a 3.5-mm inner diameter tracheal tube. The monitors were re- a health care provider that can promptly and effec-
moved, and the infant was transferred to the MRI room that tively manage sedation failure and cardiorespiratory
was equipped with an MRI-compatible anesthesia machine. complications.
After completion of the scan, the infant was transferred to the
induction room for emergence and extubation. Recovery from 3. There has been a trend toward institutional develop-
anesthesia was performed in a recovery area of the MRI suite ment of dedicated sedation teams led by critical
(zone II). care physicians, emergency room physicians, or
Considerations for this particular patient include the his- anesthesiologists.
tory of prematurity and the potential effect of sedatives and
anesthesia on postanesthesia ventilation and the history of
cyanotic heart disease. The effects of sedatives and inhaled
anesthetics on postanesthesia respiratory control are variable
and difficult to predict in the individual patient. A primary
QUESTIONS
concern is the effect of such drugs on airway patency and res-
piratory control. Airway patency during the normal awake 1. What is the mechanism by which nephrogenic systemic
state occurs because of a complex interaction between the cen- fibrosis (NSF) occurs after exposure to MRI contrast
tral nervous system and the muscles of the upper airway. Deep agents?
sedation interferes with that system and causes airway ob-
struction at the base of the tongue and the glottic inlet.13 Answer: Gadolinium, the primary MRI contract agent,
Standard maneuvers to alleviate airway obstruction, such as is similar to calcium with respect to molecular size and
chin lift and jaw thrust, do not always alleviate the obstruc- bonding and can displace calcium in human tissues and
tion, and positive pressure ventilation may be required.14 Lack cause fibrosis. Patients with renal failure are more
of patient accessibility in the MRI unit can delay recognition of susceptible to NSF because the elimination time for
obstruction and timely intervention. Capnography permits a gadolinium is prolonged.
rapid diagnosis of hypoventilation. After completion of the
study, close monitoring for several hours would be required 2. What mechanism causes MRI-induced interference with
and overnight observation indicated if there is any concern re- the electrocardiograph (ECG)?
garding the risk of apnea. Recovery from a general anesthetic Answer: The radiofrequency field generated by a strong
may be faster than recovery from high doses of long-acting magnetic field can produce small voltage changes in the
sedatives. Children with a history of obesity, sleep apnea, or blood that cause ST-T wave changes in the ECG.
15259_Ch34.qxd 3/14/09 7:23 PM Page 126
126 CHAPTER 34 • ANESTHESIA FOR MAGNETIC RESONANCE IMAGING
3. In what zones of the magnetic resonance imaging suite 7. Kuo PH, Kanal E, Abu-Alfa AK, Cowper SE. Gadolinium-based
is injury to patients or personnel most likely to occur? MR contrast agents and nephrogenic systemic fibrosis. Radiology
2007;242:647–649.
Answer: Injury to patients and personnel can occur in 8. Dalal PG, Murray D, Cox T, et al. Sedation and anesthesia pro-
zones III and IV if noncompatible ferromagnetic objects tocols used for magnetic resonance imaging studies in infants:
are present. Movement in these areas must be restricted provider and pharmacologic considerations. Anesth Analg 2006;
and any objects screened for magnet compatibility. 103:863–868.
9. Cote CJ, Wilson S. Guidelines for monitoring and manage-
ment of pediatric patients during and after sedation for diagnos-
tic and therapeutic procedures: an update. Pediatrics 2006;118:
References 2587–2602.
1. Kanal E, Barkovich AJ, Bell C, et al. ACR guidance document 10. Cote CJ, Notterman DA, Karl HW, et al. Adverse sedation
for safe MR practices: 2007. AJR 2007;188:1447–1474. events in pediatrics: a critical incident analysis of contributing
2. Levine GN, Gomes AS, Arai AE, et al. Safety of magnetic reso- factors. Pediatrics 2000;105:805–814.
nance imaging in patients with cardiovascular devices. Circulation 11. Robbertze R, Posner KL, Domino KB. Closed claims review of
2007;116:2878–2891. anesthesia for procedures outside the operating room. Curr Opin
3. Gooden CK, Dilos B. Anesthesia for magnetic resonance imag- Anesthesiol 2006;19:436–442.
ing. Int Anesthesiol Clin 2003;42:29–37. 12. Cutler KO, Bush AJ, Godambe SA, Gilmore B. The use of a
4. Cravero JP, Bilke GT, Beach M, et al. Incidence and nature of pediatric emergency-staffed sedation service during imaging: a
adverse events during pediatric sedation/anesthesia for proce- retrospective analysis. Am J Emerg Med 2007;25:654–661.
dures outside the operating room: report from the pediatric 13. Eastwood PR, Platt PR, Shepherd K, et al. Collapsibility of
sedation research consortium. Pediatrics 2006;118:1087–1096. the upper airway at different concentrations of propofol.
5. Reeves ST, Havidich JE, Tobin DP. Conscious sedation of chil- Anesthesiology 2005;103:470–477.
dren with propofol is anything but conscious. Pediatrics 2004; 14. Meier S, Geiduschek J, Paganoni R, et al. The effect of chin
114:e74–e76. lift, jaw thrust, and continuous positive airway pressure on the size
6. Grobner T, Prischl FC. Gadolinium and nephrogenic systemic of the glottic opening and on stridor score in anesthetized, sponta-
fibrosis. Kidney International 2007;72:260–264. neously breathing children. Anesth Analg 2002;94: 494–449.
15259_Ch35.qxd 3/14/09 7:24 PM Page 127
CHAPTER 35
Evidence-Based Prevention of Postoperative

Nausea and Vomiting
Richard J. Pollard
sual, and vestibular apparatus) as well as the oropharynx, me-

diastinum, peritoneum, and genitalia.
The central nervous system has several receptors that can
A 25-year-old, 5⬘ 9⬙, 57-kg triathlete was running on a
influence nausea and vomiting. The area postrema has large
street when she fell and injured her arm. A distal radial
concentrations of dopamine (D2), opioid, and serotonin
fracture was diagnosed in the emergency department, and
(5HT3) receptors. The nucleus tractus solitarius is rich in
an orthopaedic surgeon was consulted. The patient was
enkephalins and histaminic (H1) muscarinic and cholinergic
scheduled for repair of the fracture in the ambulatory sur-
receptors. Neurokinin-1 (NK1) receptors are found in the nu-
gery center. Intravenous (IV) morphine (6 mg) was admin-
cleus tractus solitarius and in the dorsal motor nucleus of the
istered in the emergency department for analgesia. She
vagus nerve. Before the surgery, the patient asked the anesthe-
was very anxious about the surgery and her subsequent
siologist the following question.
rehabilitation.
The patient had not undergone surgery or anesthesia
previously. She did not use tobacco, alcohol, illicit drugs, or
nonprescribed drugs. She did have a history of significant What are my specific risk factors for PONV?
motion sickness. Physical examination revealed a lean, ath- The risk factors for PONV can be categorized as: (a) patient
letic-appearing young woman. Her blood pressure was specific, (b) anesthetic, and (c) surgical (Table 35.1). The most
90/60 mm Hg with a heart rate of 55 beats per minute. important patient-specific factors for PONV are female gen-
Because the surgeon had a busy clinic and was only der, young age, nonsmoker, and a previous history of PONV
available in the late afternoon, the patient was fasting for or motion sickness. Other patient-specific risk factors include a
more than 10 hours. She was very concerned about postop- history of migraine headaches, anxiety, hypovolemia, and an
erative nausea and vomiting (PONV) because she remem- American Society of Anesthesiologists low-risk classification.1,2
bered that her mother had suffered from this complication. Anesthetic-related risk factors include the use of volatile anes-
thetics, nitrous oxide (N2O), intraoperative, or postoperative
opioids.3 The influence of the reversal of nondepolarizing mus-
cle relaxants with neostigmine on PONV is controversial.
Earlier studies indicated that reversal with greater than 2.5 mg
What is the pathophysiology of PONV? of neostigmine increased the incidence of PONV. A recent
The underlying mechanisms that cause PONV are complex analysis suggests that the association between neostigmine ad-
and involve both mechanical and neurologic processes. The ministration and PONV is limited. Duration and type of sur-
mechanical act of vomiting requires coordination of the respi- gery have been implicated as determinants of PONV. For
ratory, gastrointestinal, and abdominal muscles. Neurologic every 30 minutes of surgical time, there is a predictable 60% in-
control of the mechanical process occurs in the vomiting cen- crease in subsequent nausea. This means that a baseline risk of
ter located in the lateral reticular formation of the medulla ob- 10% is increased to 16% after 30 minutes of surgery and then
longata. This center is in close proximity to the nucleus of the further increased to ⬎25% after 1 hour of surgery. For adults,
solitary tract in the brainstem and has access to the motor there is an increased risk of PONV with intra-abdominal sur-
pathways responsible for the act of vomiting. The vomiting re- gery, especially gynecologic and laparoscopic operations.
flex involves the gastrointestinal tract and the chemoreceptor Neurosurgical, ophthalmic, and ear, nose, and throat proce-
trigger zone (CTZ) in the area postrema. Mechanoreceptors dures are also associated with an increased risk of PONV.
and chemoreceptors in the lining of the gut initiate the reflex. Apfel et al. suggested a simplified PONV predictive score
These receptors are stimulated by contraction and distention that included four factors: (a) female gender, (b) nonsmoker,
of the gut (mechanoreceptors) or by the presence of noxious (c) history of PONV or motion sickness, and (d) the need for
materials (chemoreceptors). Once these receptors are acti- postoperative IV opioids.4 When 0, 1, 2, 3, or 4 risk factors
vated, signals are sent via the vagus nerve to activate the CTZ. were present, the risk of PONV was 10%, 21%, 39%, 61%, or
The location of the CTZ in the area postrema allows the CTZ 79% respectively. This simplified risk stratification enables
to be activated by chemical stimuli from the blood and cere- clinicians to estimate the likelihood of PONV in individual
brospinal fluid. Other sites can directly affect the vomiting patients and make appropriate adjustments in technique.
center via separate neurologic connections. These sites include Based on Apfel’s scoring system, this patient has three
the central nervous system (cerebral cortex, labyrinthine, vi- risk factors: female gender, non-smoker, and history of
127
15259_Ch35.qxd 3/14/09 7:24 PM Page 128
128 CHAPTER 35 • EVIDENCE-BASED PREVENTION OF POSTOPERATIVE NAUSEA AND VOMITING
T A B L E 3 5 . 1 Risk Factors for Postoperative Nausea and Vomiting
Patient Specific Anesthesia Related Surgery Related

Female Volatile gases Time ⬎30 minutes
Young age Nitrous oxide HEENT procedures
Nonsmoker Intravenous opioids Major gynecological procedures
Previous PONV Neostigmine ⬎2.5 mg Laparoscopy
Motion sickness Gastric suctioning
Migraines
Anxiety
Hypovolemia
Low American Society
of Anesthesiologists status
Items in regular type are major risk factors. Boldface items are minor risk factors.
HEENT, head ears eyes nose throat; PONV, postoperative nausea and vomiting.
motion sickness. This placed the patient’s risk at 61%. The A transdermal scopolamine patch applied the night before
use of preoperative IV opioids, low American Society of surgery or 4 hours before the end of surgery can significantly
Anesthesiologists classification, anxiety, and relative hypov- reduce the incidence of PONV.8 The slow onset of effect and
olemia increased that risk. side effects such as dry mouth and dizziness, however, may di-
minish the utility of scopolamine.
Although droperidol is an effective antiemetic, its use has
Do the risks of PONV in children differ from been effectively reduced or discontinued in the United States
those in adults? because of the “black box” warning from the Food and Drug
Eberhart et al. applied a multivariate analysis to determine the Administration concerning the potential risks of cardiac dys-
potential for PONV in children.5 Risk factors for PONV in rhythmias.9
children included (a) duration of surgery greater than 30 min- The NK1 receptor antagonists, such as aprepitant, com-
utes, (b) age 3 years or older, (c) strabismus surgery, and (4) a prise the newest class of drugs purported to decrease PONV.
history of PONV in the patient, a sibling, or parent. When 0, NK1 receptors are found in the areas of the brain that control
1, 2, 3, or 4 risk factors are present, the risk of PONV for the the vomiting reflex, and NK1 receptor antagonists may be es-
patient was 9%, 10%, 30%, 55%, or 70%, respectively. pecially effective in patients with centrally mediated PONV.10
The patient requested some form of premedicant that Other drugs that have been reported to reduce the inci-
would decrease the likelihood of her developing PONV. dence of PONV, but have not been rigorously studied as yet
are haloperidol, dexmedetomidine, naloxone, and nalmefene.
Are there any premedicants that reduce the
risk of PONV?
There are at least four receptor systems that influence T A B L E 3 5 . 2 Antiemetic Drugs
PONV. Conventional wisdom in the management of pa-
5-HT3 Receptor Antagonists Anticholinergics
tients at risk for PONV advocates the use of a technique that
targets different receptor sites (Table 35.2). Multiple studies Ondansetron Scopolamine
have shown the efficacy of combination versus single-agent Dolasetron Antihistamines
antiemetic prophylaxis.6,7 Agents used in clinical practice in-
clude 5-hydroxytryptamine (5-HT3) receptor antagonists Tropisetron Dimenhydrinate
(ondansetron, dolasetron, granisetron, and tropisetron), dex- Granisetron NK1 Receptor
amethasone, and transdermal scopolamine. antagonists
The 5-HT3 receptor antagonists are most effective when Corticosteroids Aprepitant
administered near the conclusion of surgery. These agents are
equally effective in reducing the incidence of PONV and are Dexamethasone Phenothiazines
all safe at recommended doses. Butyrophenones Promethazine
The corticosteroid dexamethasone has been shown to be ef-
Droperidol
fective as an antiemetic when given at the induction of anes-
thesia in doses of 4 to 5 mg. The efficacy of dexamethasone is Haloperidol
similar to that of the 5-HT3 receptor antagonists.
15259_Ch35.qxd 3/14/09 7:24 PM Page 129
CHAPTER 35 • EVIDENCE-BASED PREVENTION OF POSTOPERATIVE NAUSEA AND VOMITING 129
A prophylactic regimen is recommended for patients at tion in rescue trials. Evidence suggests that in patients who have
moderate to high risk for PONV. Prophylaxis is not generally failed to respond to ondansetron prophylaxis, more ondansetron
recommended for low-risk PONV patients; however, because is no more effective than placebo. Logically, a drug that acts at a
PONV is one of the largest and most costly complications after different receptor site would be a better choice.13
anesthesia, the anesthesiologist should consider whether the Several days after an otherwise uneventful recovery, the
risks and cost of prophylaxis are justified for every patient. It patient asked her anesthesiologist about future treatment op-
has been shown that patients are willing to pay up to $100 of tions regarding PONV.
their own money for completely effective antiemetics. An
anesthesiology resident consulted with a senior colleague re-
garding the best anesthetic technique to prevent PONV in the In the future, are there nonpharmacological
patient described in this case. options that might be effective for this patient
in the treatment of PONV?
Some nonpharmacologic treatments for PONV may be effec-
What is the best anesthetic technique to tive. Techniques such as acupuncture, acupoint stimulation, and
prevent PONV in this patient? transcutaneous nerve stimulation may have antiemetic efficacy
Anesthesia-related risk factors for PONV include the use of comparable to standard treatments. There may be some resist-
volatile inhaled anesthetics, N2O, intraoperative or postopera- ance in clinical practice to utilization of nontraditional thera-
tive IV opioids, and reversal of nondepolarizing muscle relax- pies; however, some patients are familiar with the techniques
ants with neostigmine at doses greater than 2.5 mg. The use of and will insist on their use. If patients request such therapy, it
regional anesthesia provides a ninefold decrease in the inci- would be best to consult a clinician familiar with the techniques.
dence of PONV in all populations.11 If general anesthesia is re- Although the patient’s nausea resolved fully before discharge,
quired, using propofol for induction and during maintenance she was concerned that the symptoms would return later.
phases of anesthesia decreases the incidence of PONV by 19%
during the first 6 postoperative hours. Propofol used in a total
IV anesthesia technique reduces the risk of PONV by 25%. What can the patient expect on discharge from
Volatile inhaled anesthetics have been identified as the pri- the surgical unit?
mary cause of PONV within the first 2 hours after surgery. Nausea and vomiting occurs in one third of ambulatory surgi-
The incidence of PONV when both volatile anesthetics and cal patients after discharge from surgery centers. Prophylactic
N2O are used may be as high as 59%.12 Avoidance of N2O de- therapy should be administered to patients susceptible to late
creases the risk of PONV by 12%. PONV. The use of longer-acting agents in combination seems
Whether to use IV narcotics during the perioperative period to offer the best outcome.14,15
remains a quandary for anesthesiologists. On one hand, opioids
reduce postoperative pain while smoothing intraoperative he-
modynamic changes. On the other hand, narcotics increase the KEY MESSAGES
risk of PONV. Nonnarcotic analgesics such as nonsteroidal
anti-inflammatory drugs and cyclo-oxygenase-2 inhibitors may 1. Anesthesia-related risk factors for PONV include the
have a role in reducing the need for opioids and reducing the in- use of volatile inhaled anesthetics, N2O, IV opioids,
cidence of PONV. A technique using regional anesthesia or and reversal of nondepolarizing muscle relaxants with
local infiltration anesthesia in conjunction with nonnarcotic neostigmine at doses greater than 2.5 mg.
analgesics may eliminate the need for perioperative opioids.
Other preventive modalities such as supplemental oxygen 2. When 0, 1, 2, 3, or 4 risk factors were present, the
or prophylactic orogastric suctioning have not been proven to incidence of PONV in adults undergoing general anes-
reduce PONV. thesia is 10%, 21%, 39%, 61%, or 79%,
The anesthesiologists agreed that the lowest-risk technique respectively.4
for this patient would be a regional technique such as a brachial 3. A prophylactic regimen is recommended for patients
plexus block and sedation with propofol with minimal or no at moderate to high risk for PONV.
opioids. Because the patient expressed a strong preference for
general anesthesia, a scopolamine patch was applied at the con-
clusion of the preoperative interview. Dexamethasone (5 mg)
was administered intravenously with the induction of anesthe- QUESTIONS
sia and ondansetron (4 mg) administered just before emergence
from anesthesia. 1. What are major patient risk factors for postoperative
Despite this aggressive prophylactic regimen, the patient nausea and vomiting?
experienced severe nausea on waking in the postoperative Answer: Major risk factors for postoperative nausea
care unit. include female gender, young age, and a history of
motion sickness.
Is ondansetron the drug of choice in this case? 2. What receptors influence postoperative nausea and
There have been very few studies regarding the treatment of pa- vomiting?
tients who have failed antiemetic prophylaxis. The 5-HT3 re- Answer: Dopamine, opioid, serotonin, cholinergic, and
ceptor antagonists have been the most frequently tested medica- neurokinin-1 receptors influence nausea and emesis.
15259_Ch35.qxd 3/14/09 7:24 PM Page 130
130 CHAPTER 35 • EVIDENCE-BASED PREVENTION OF POSTOPERATIVE NAUSEA AND VOMITING
These receptors are concentrated in the central nervous 6. Henzi I, Walder B, Tramer MR. Dexamethasone for the preven-
system in the areas of the area postrema, the nucleus tion of postoperative nausea and vomiting. Anesth Analg 2000;
tractussolitarius, and the motor nucleus of the vagus 90:186–194.
nerve. 7. Tramer MR. A rational approach to the control of postoperative
nausea and vomiting: evidence from systematic reviews. Part II.
3. What anesthetic factors increase the likelihood of post- Recommendations for prevention and treatment, and research
operative nausea? agenda. Acta Anaesth Scand 2001;45:14–19.
8. Kranke P, Morin AM, Roewer N, et al. The efficacy and safety
Answer: Anesthetic factors that may increase the of transdermal scopolamine for the prevention of postoperative
likelihood of postoperative nausea include the use of nausea and vomiting. Anesth Analg 2002;95:133–143.
volatile, inhaled anesthetics and nitrous oxide, 9. Habib AS, Gan TJ. The use of droperidol before and after the
administration of postoperative opioids, and possibly Food and Drug Administration black box warning: a survey of
the use of neostigmine to reverse neuromuscular the members of the Society for Ambulatory Anesthesia. J Clin
blockade. Anes 2008;20:35–39.
10. Gan TJ, Apfel CC, Kovac A, et al. A randomized, double-blind
comparison of the NK1 antagonist, aprepitant, versus ondansetron
for the prevention of postoperative nausea and vomiting. Anesth
References Analg 2007;104:1082–1089.
1. Stadler M, Bardiau F, Seidel L, et al. Difference in risk factors 11. Khalil SN, Farag A, Hanna E, et al. Regional anesthesia com-
for postoperative nausea and vomiting. Anesthesiology 2003;98: bined with avoidance of narcotics may reduce the incidence of
46–52. postoperative vomiting in children. Middle East J Anesthesiol
2. Van den Bosch JE, Moons KG, Bonsel GJ, et al. Does measure- 2005;18:123–132.
ment of preoperative anxiety have added value for predicting 12. Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six in-
postoperative nausea and vomiting? Anesth Analg 2005;100: terventions for the prevention of postoperative nausea and vom-
1525–1532. iting. N Engl J Med 2004;350:2441–2451.
3. Apfel CC, Kranke P, Katz MH, et al. Volatile anesthetics may be 13. Gan TJ, Meyer T, Apfel CC, et al. Consensus guidelines for man-
the main cause of early but not delayed postoperative vomiting: a aging postoperative nausea and vomiting. Anesth Analg 2003;97:
randomized controlled trial of factorial design. Br J Anaesth 62–71.
2002;88:659–668. 14. Gupta A, Wu CL, Elkassabany N, et al. Does the routine pro-
4. Apfel CC, Laara E, Koivuranta M, et al. A simplified risk score for phylactic use of antiemetics affect the incidence of post discharge
predicting postoperative nausea and vomiting. Anesthesiology nausea and vomiting following ambulatory surgery? A system-
1999;91:693–700. atic review of randomized controlled trials. Anesthesiology 2003;
5. Eberhart LH, Geldner G, Krnake P, et al. The development and 99:488–495.
validation of a risk score to predict the probability of postopera- 15. Gan TJ, Meyer T, Apfel CC, et al. Society for Ambulatory
tive vomiting in pediatric patients. Anesth Analg 2004;99: Anesthesia guidelines for the management of postoperative nausea
1630–1637. and vomiting. Anesth Analg 2007;105:1615–1628.
15259_Ch36.qxd 3/15/09 7:11 AM Page 131
CHAPTER 36
Ultrasound Guidance for Central Venous

Cannulation
Bryan V. May
poor peripheral venous access, administration of vasoactive

drugs, acute hemodialysis, rapid infusion of large volumes of
resuscitation fluids, cardiac pacing, hyperalimentation, and
An 81-year-old male presented with a 2-hour history of
hemodynamic monitoring.1 In the perioperative period, indica-
weakness and substernal chest pain caused by moderate
tions are generally hemodynamic monitoring, infusion of va-
physical activity. His medical history was significant for hy-
soactive drugs, and fluid administration.
pertension, chronic atrial fibrillation, multiple transient is-
chemic attacks, and type 2 diabetes mellitus. A 12-lead
electrocardiogram revealed atrial fibrillation with an in- What are the complications from central
complete right bundle branch block, 2-mm ST depression venous catheterization?
in leads II, III, and AVF. Physical examination revealed an
alert and mildly uncomfortable elderly man. The patient’s
The potential complications from central venous cannulation
vital signs were as follows: blood pressure, 164/72 mm
are many and can be fatal (Table 36.1).2,3 Chronic complica-
Hg; heart rate, 92 beats per minute (irregularly irregular);
tions such as infection, thrombosis, or catheter fracture are re-
and respiratory rate, 28 breaths per minute. Chest auscul-
lated to the duration that the catheter is in place and are not
tation revealed no heart murmurs and faint bibasilar rales.
common for short-term placement (such as for perioperative
The abdominal examination was normal. Cardiac en-
use). The nidus for infection, however, can be introduced
zymes were consistent with myocardial ischemia (elevated
during the insertion procedure, and every central venous can-
troponin I and creatine kinase MB levels). A transthoracic
nulation, whether for short- or long-term placement must be
echocardiogram obtained in the emergency department re-
managed with good sterile technique.
vealed inferior wall akinesis and a reduced left ventricular
Complications that occur during the insertion procedure in-
ejection fraction (35%). Other transesophageal echocar-
clude hemorrhage (arterial or venous), hematoma formation,
diogram findings were concentric left ventricular hypertro-
inadvertent carotid artery puncture, dysrhythmias, pneu-
phy and a small patent foramen ovale with left-to-right
mothorax, catheter malposition, perforation of great vessels,
shunting. Carotid artery duplex ultrasound showed bilat-
pseudoaneurysm formation, arteriovenous fistula, brachial
eral high-grade stenosis of both carotid arteries and a par-
plexus injury, guidewire loss, catheter knotting, and cannula-
tially thrombosed left internal jugular vein. Urgent coronary
tion failure. Operator experience and technique certainly influ-
artery angiography showed significant three-vessel coro-
ence the complication rate. Physicians with greater experience
nary disease that was not amenable to angioplasty or stent
(⬎50 insertions) have a high success rate and a low incidence of
placement. The patient was scheduled for emergent coro-
complications. Most anesthesiologists have substantial experi-
nary artery bypass grafting.
ence with central venous cannulation at the conclusion of their
During the brief preoperative interview, it was ex-
training. Data from the American Society of Anesthesiologists
plained to the patient that after induction of anesthesia and
Closed Claims Project indicated that the complications gener-
tracheal intubation, a central venous catheter would be in-
ating litigation included wire/catheter embolism, cardiac tam-
serted into the right internal jugular vein (RIJV), and a
ponade, carotid artery puncture/cannulation, hemothorax, and
catheter would be inserted into the pulmonary artery via
pneumothorax.4
the heart. The patient queried the anesthesiologist as to the
Infection from a central venous catheter site is a serious and
need for such a catheter and potential complications.
potentially lethal complication. Every effort must be made to
avoid infection. Adherence to strict sterile technique during
catheter insertion is essential. The use of biopatches to cover
the insertion site and use of antibiotic-impregnated catheters
may also reduce the infection rate; however, emergence of an-
tibiotic-resistant bacteria is of concern. The application of an-
What are the indications for central venous tibiotic ointment to the catheter insertion site has not been
cannulation? shown to reduce the likelihood of infection and can promote
Every year, more than 5 million central venous catheters are fungal colonization of the catheter.5
inserted into patients in the United States, and 200,000 are in- The patient was transported to the operating room for
serted into patients in the United Kingdom. Indications include coronary artery bypass grafting. He had a peripheral intra-
131
15259_Ch36.qxd 3/15/09 7:11 AM Page 132
132 CHAPTER 36 • ULTRASOUND GUIDANCE FOR CENTRAL VENOUS CANNULATION
carotid artery is identified, and the needle is inserted at the

T A B L E 3 6 . 1 Complications of Central Venous
apex of the triangle lateral to the carotid artery and directed
Catheterization away from the carotid artery. If the vein is not entered, the
needle can be methodically redirected more medially in small
Bleeding increments until the vein is found. The color of the blood can
Infection be used to differentiate venous from arterial blood, but this
Thrombosis method is not always accurate. If it is uncertain which vessel
has been cannulated, a pressure transducer can be attached to
Carotid artery injury the needle or a small-bore catheter for vessel identification.
Stroke Anatomic landmarks are easily discernible in patients with
Hematoma formation well-defined anatomy. Obese patients, those with limited neck
mobility, and infants do not have well- defined anatomic land-
Pneumothorax marks, and techniques dependent on anatomic identification
Hemothorax will not be as reliable.
A 22-gauge finder needle was inserted via a central approach
Cardiac perforation
(apex of the two heads of the sternocleidomastoid muscle) in an
Cardiac tamponade attempt to locate the RIJV; multiple attempts with the finder
Pseudoaneurysm formation needle were required to locate this vein. An 18-gauge, 4-inch
needle attached to a 5-mL syringe was inserted in the same
Arteriovenous fistula plane as the finder needle and advanced. Bright red blood was
Vertebral artery injury aspirated. After syringe removal, bright red blood pulsated
Dysrhythmias from the needle. The needle was removed, and pressure was
applied to the puncture site. Despite the pressure, a hematoma
Catheter fracture developed on the right side of the patient’s neck. With the con-
Brachial plexus injury tinued application of pressure, the hematoma stopped expand-
Horner’s syndrome ing. An ultrasound device with a 5-MHz probe was brought
to the operating room. Ultrasound imaging of the right neck
showed that the RIJV was lying directly on top of the carotid
artery. Imaging demonstrated a hematoma surrounding and
compressing the RIJV. Although the caliber of the RIJV was
venous catheter and a right radial arterial line in place. After decreased by the hematoma, ultrasound guidance facilitated
induction of general anesthesia, a transesophageal echocardio- catheterization of the RIJV.
gram probe was inserted, and his right neck was positioned In this case, the patient’s RIJV was lying directly above the
and prepared for central venous cannulation and insertion of carotid artery. The finder needle eventually located the RIJV,
a pulmonary artery catheter. but the cannulation needle penetrated the RIJV and punc-
tured the carotid artery. Ultrasound guidance allowed prompt
identification of the RIJV leading to successful cannulation.
What are the anatomic landmarks for central Ultrasound imaging to facilitate central venous cannulation
venous cannulation? was first reported in the anesthesia literature in the 1970s, and
The three veins normally used for central venous cannulation many studies have shown the usefulness of ultrasound, espe-
are the internal jugular vein (right vein more frequently than cially for the internal jugular vein.6,7 Broad acceptance by
the left), subclavian vein, and the femoral vein. The femoral anesthesiologists has been slow to occur. In 2001, the Agency
vein is rarely chosen for hemodynamic monitoring or inser- for Healthcare Research and Quality and in 2002, the National
tion of a pulmonary artery catheter. There is some controversy Institute for Clinical Excellence recommended ultrasound
as to whether the pressure measured in the femoral vein is a guidance for elective cannulation of the internal jugular vein
true reflection of central venous pressure, and the distance in adults and children. This document has had little impact on
from the femoral vein insertion site to the pulmonary artery practicing anesthesiologists. There are several practical rea-
exceeds the length of most pulmonary artery catheters. sons that ultrasound guidance for central venous catheter in-
Femoral vein cannulation is more commonly performed in sertion has not become more prevalent. The evidence that
small children than in adults. ultrasound guidance is clearly superior to traditional anatomic
Most anesthesiologists use the RIJV as the insertion site for techniques has not been convincing.8,9 Ultrasound equipment
central venous cannulation. The RIJV has a consistent location has not been routinely available in every operating room, and
in the carotid sheath. It is a relatively short, valveless vessel delays in finding and preparing the ultrasound machine are
leading straight to the superior vena cava and the right atrium. considered unjustified if the equipment is unavailable.
Additional advantages include a decreased risk of pneumo-
thorax, as the right lung lies more caudad than the left and
avoidance of the left-sided thoracic duct. The central approach How can ultrasound guidance facilitate central
to the RIJV is very common and depends on the location of the venous catheterization of the RIJV?
apex of the triangle formed by the sternal and clavicular heads The two commonly used techniques for ultrasound guidance
of the sternocleidomastoid muscle. The internal jugular vein is are static and dynamic (real-time). The static method is rela-
usually lateral or anterolateral to the carotid artery. The tively quick and requires no sterile preparation of the ultra-
15259_Ch36.qxd 3/15/09 7:11 AM Page 133
CHAPTER 36 • ULTRASOUND GUIDANCE FOR CENTRAL VENOUS CANNULATION 133
T A B L E 3 6 . 2 Technique for Dynamic Ultrasound-Guided Central Venous Cannulation
1. Position the patient’s head with ultrasound guidance. The head should be rotated to maximize the distance from the
carotid artery to the internal jugular vein and maximize the right internal jugular vein’s diameter.
2. The cannulation site is prepped and draped in sterile fashion.
3. The ultrasound probe is inserted into a sterile sheath.
4. The internal jugular vein is identified. The jugular vein is easily compressed and should be lateral to the carotid artery,
which is round and pulsatile.
5. The internal jugular vein is centered on the ultrasound screen.
6. The puncture needle is inserted at a 45-degree angle along the intercept path with the vein.
7. The accuracy of vessel puncture is determined by ultrasound, blood color, or pressure transduction.
8. The guidewire is threaded into the vein, the vein is dilated, and a catheter is threaded into the vessel.
sound probe. The operator identifies and centers the vein on an echogenic line as it passes through tissue planes. The short
the ultrasound probe. An indelible mark is placed on the skin axis is generally used to localize the vein and avoid the carotid
to identify the needle insertion point, and a second mark is artery. It may be beneficial to rotate the transducer 90° to the
made distal to the first along the course of the vein. The line longitudinal plane to better identify the tip of the needle as it
determined by the two points guides the operator as to the approaches the vessel lumen. The dynamic technique is more
course of the vein. The probe is removed, and the patient is cumbersome than the static technique and requires practice
prepped and draped for cannulation. for a lone operator. An assistant who can hold and manipulate
The dynamic method requires placing the probe in a ster- the probe while the operator is inserting the needle can be
ile sheath after the patient has been prepped and draped quite helpful.
(Table 36.2). The operator uses the probe to locate the vein, The ultrasound probe can be useful for positioning the pa-
which is usually lateral to the carotid artery and is easily com- tient’s head. Head rotation can alter the relationship of the in-
pressed with pressure on the probe (Figs. 36.1 and 36.2). Once ternal jugular vein to the carotid artery. Ultrasound imaging
identified, the vein is centered on the ultrasound screen, and can help determine optimal rotation to maximize the distance
the needle is inserted at a 45-degree angle toward the vein between the carotid artery and jugular vein and can maximize
along the anticipated intercept path. The needle can be seen as the vein’s diameter.
Figure 36.1 • Axial Ultrasound Image of the Left Figure 36.2 • Axial Ultrasound Image of the Left
Anterior Neck. The internal jugular vein can be seen lateral to Anterior Neck. Application of pressure to the ultrasound
the carotid artery and appears patent when minimal pressure is ap- transducer compresses the internal jugular vein, making identifi-
plied to the ultrasound transducer. CA, carotid artery; IJV, internal cation and cannulation difficult. CA, carotid artery; IJV, internal
jugular vein; Thy, thyroid gland; TP C6, transverse process of sixth jugular vein; Thy, thyroid gland; TP C6, transverse process of
cervical vertebra. sixth cervical vertebra.
15259_Ch36.qxd 3/15/09 7:11 AM Page 134
134 CHAPTER 36 • ULTRASOUND GUIDANCE FOR CENTRAL VENOUS CANNULATION
Should ultrasound guidance for central venous

cannulation be a standard of care for 2. At the level of the apex of the triangle formed by the
anesthesiologists? sternal and clavicular heads of the sternocleidomastoid
Declaring a device or technique as a standard of care requires muscle, the internal jugular vein usually lays lateral or
clear evidence of efficacy and ready availability of the device. anterolateral to the carotid artery.
The evidence to date does not demonstrate clear superiority. 3. Applying gentle pressure via the ultrasound probe will
Part of the failure to prove that ultrasound guidance is better compress the internal jugular vein but not the adjacent
may be a lack of training with ultrasound guidance. The RIJV carotid artery.
is generally easy to recognize with ultrasound, but cannulation
is not always easy. The ultrasound image provides a two-
dimensional image, but anatomy is three dimensional. It is not
always easy to accurately determine the position of the cannu- QUESTIONS
lation needle with ultrasound. A standardized, formal teaching
program in ultrasound guidance for central venous catheteri- 1. What are the major complications of central venous
zation may improve performance to the point that a clear dif- cannulation via the internal jugular vein?
ference in insertion efficiency with reduced complications is Answer: Major complications include hemorrhage,
evident.10 hematoma formation, stroke, perforation of major
Experience is another factor that may make the case for vessels, and cardiac tamponade.
ultrasound guidance less clear. Anesthesiologists are gener-
ally very experienced with central venous cannulation using 2. What are the advantages of ultrasound guided cannu-
anatomic landmark techniques, and comparative studies lation of the internal jugular vein?
with anesthesiologists may be less convincing than with less- Answer: Ultrasound identification of the internal jugular
experienced practitioners. If anesthesiologists acquire ultra- vein is especially helpful when normal anatomic land-
sound guidance skills, it may ultimately prove ultrasound to marks are not easily defined. Obese patients, patients
be a superior technique even in the hands of experienced with limited cervical mobility, and infants are cases
practitioners.11 where ultrasound guidance is quite helpful.
Ultrasound machines have become more commonplace in
the operating room. Stand-alone units as well as trans- 3. What is the primary way to differentiate the carotid
esophageal echocardiogram machines equipped with external artery from the internal jugular vein with an ultrasound
probes are often readily available. The development of small probe?
high-quality ultrasound units will undoubtedly increase access Answer: The carotid artery is round, pulsatile, and
for the anesthesiologist. Probe selection depends on the patient’s relatively non-compressible. The internal jugular vein is
size and the depth of the vessel. Better resolution is achieved generally irregular in shape and easily compressed with
with a high-frequency ultrasound probe. Tissue penetration, the probe.
however, decreases with increasing frequency.
The preponderance of evidence suggests that ultrasound
guidance will eventually be the standard of care. Anes- References
thesiologists should become skilled with both anatomic land- 1. Taylor RW, Palagiri AV. Central venous catheterization. Crit
mark and ultrasound-guided central venous catheterization. If Care Med 2007;35:1390–1396.
anatomic landmark techniques fail, ultrasound may reveal why 2. Kusminsky RE. Complications of central venous catheterization.
failure occurred and may provide guidance for successful J Am Coll Surg 2007;204:681–696.
cannulation. 3. Garden AL, Laussen PC. An unending supply of “unusual”
As anesthesiologists obtain more experience with ultra- complications from central venous catheters. Pediatr Anesth
2004;905–909.
sound-guided central venous cannulation, the procedure
4. Domino KB, Bowdle TA, Posner KL, et al. Injuries and liability
should become more successful, safer, and more efficient.12 related to central vascular catheters. Anesthesiology 2004;100:
1411–1418.
5. McGee DC, Gould MK. Preventing complications of central ve-
nous catheterization. N Engl J Med 2003;348:1123–1133.
6. Randolph AG, Cook DJ, Gonzales CA, et al. Ultrasound guid-
KEY MESSAGES ance for placement of central venous catheters: a meta-analysis of
the literature. Crit Care Med 1996;24:2053–2038.
7. Hind D, Calvert N, McWilliams R, et al. Ultrasonic locating de-
1. Indications for central venous line insertion include vices for central venous cannulation: meta-analysis. BMJ 2003;
poor peripheral venous access, administration of 327:361–367.
vasoactive drugs, acute hemodialysis, rapid infusion 8. Grebnik CR, Boyce A, Sinclair ME, et al. NICE guidelines for
of large volumes of resuscitation fluids, cardiac central venous catheterization in children. Is the evidence base
pacing, hyperalimentation, and hemodynamic sufficient? Br J Anaesth 2004;92:827–830.
monitoring. 9. Hayashi H, Amano M. Does ultrasound imaging before punc-
ture facilitate internal jugular vein cannulation? Prospective
15259_Ch36.qxd 3/15/09 7:11 AM Page 135
CHAPTER 36 • ULTRASOUND GUIDANCE FOR CENTRAL VENOUS CANNULATION 135
randomized comparison with landmark-guided puncture in 11. Chapman GA, Johnson D, Bodenham AR. Visualisation of needle
ventilated patients. J Cardiothor Vasc Anesth 2002;16:572–575. position using ultrasonography. Anaesthesia 2006;61:148–158.
10. Feller-Kopman D. Ultrasound-guided internal jugular access. A 12. Calvert N, Hind D, McWilliams R, et al. Ultrasound for central
proposed standardized approach and implications for training venous cannulation: economic evaluation of cost-effectiveness.
and practice. Chest 2007;132:302–309. Anaesthesia 2004;59:1116–1120.
15259_Ch37.qxd 3/15/09 6:25 AM Page 136
CHAPTER 37
Regional Anesthesia Outcomes
Justin Lane and Brian D. O’Donnell
3. What is the patient’s ventricular function?

4. Is the patient on his or her optimal medical regimen?
A 68-year-old man was scheduled for elective repair of an To answer these questions, the patient’s clinical history
asymptomatic 6.5-cm abdominal aortic aneurysm. He had holds a number of vital pieces of information: (a) he is asymp-
a myocardial infarction 3 years previously, resulting in en- tomatic regarding intercurrent ischemic heart disease; (b) he
dovascular stenting of his left anterior descending and cir- has excellent exercise tolerance; (c) he is in sinus rhythm, and
cumflex coronary arteries. He remained asymptomatic of his ventricular function is normal; (d) he was taking an an-
recurring anginal symptoms. The patient was a smoker tiplatelet agent, a ␤-blocker, an angiotensin-converting en-
with a 50 pack-year history but quit after the myocardial zyme inhibitor, and a statin; and (e) his heart rate and blood
infarction. He returned to normal activity, lost weight, and pressure are well controlled. The patient received coronary
could climb two flights of stairs without difficulty. He had artery stents to the anterior cardiac circulation, and the my-
no known drug allergies, and his medications were as ocardium supplied by this area is at risk in the event of stent oc-
follows: aspirin, 75 mg daily; atorvastatin, 10 mg daily; clusion. However, the American Heart Association/American
atenolol, 25 mg twice daily; and enalapril, 5 mg daily. College of Cardiology states that “. . . because additional coro-
He had a previous uneventful general anesthetic for in- nary restenosis is unlikely to occur more than 8 to 12 months
guinal hernia repair 10 years ago. after PCI [percutaneous coronary intervention], it is reasonable
On examination, the patient’s vital signs were as to expect ongoing protection against untoward perioperative is-
follows: temperature, 36.5o C; blood pressure, 125/90 mm chemic complications . . .” The amount of stress that may pro-
Hg; heart rate, 50 beats per minute; and respiratory rate, duce ischemia is uncertain in this patient.
16 breaths per minute. His body mass index was 28. Therefore, whether alterations to medication and further
Examination of the cardiovascular and respiratory systems cardiovascular evaluations are necessary must be considered.
was normal. Airway examination revealed Mallampati Continuing antiplatelet therapy with aspirin may contribute
grade I with normal mouth opening and a four-finger thyro- to additional blood loss, however, the phenomenon of late
mental distance. The patient’s electrocardiograph reading stent stenosis following antiplatelet therapy discontinuation
revealed sinus rhythm with normal PR and QRS intervals but justifies continuation in this setting.2 ␤-Blockade should be
with voltage evidence of left ventricular hypertrophy (Fig. continued in the perioperative period, and the patient’s heart
37.1). Transthoracic echocardiography was performed and rate should be titrated to less than 65 beats per minute.1,3
showed mild concentric left ventricular hypertrophy, struc- Favorable outcomes have been reported with the con-
turally normal valves with trivial mitral regurgitation, and tinuation of statin therapy; discontinuation of long-term
normal function with an ejection fraction calculated at 58%. statin therapy worsens perioperative cardiac outcomes.4
Review of the patient’s blood results (Table 37.1) re- Angiotensin-converting enzyme inhibitor therapy was dis-
vealed evidence of renal impairment, prompting discontin- continued in this case because of renal impairment. Finally,
uation of angiotensin-converting enzyme inhibitor therapy. Polldermans et al3 report that the further investigation of pa-
tients with ␤-blockade and good heart rate control is unnec-
essary and delays surgery. In summary, the best available ev-
How might this patient’s preoperative idence supports the continuation of aspirin, atenolol, and
physiological status be optimized? atorvastatin in this man’s case, thereby permitting surgery
The American Heart Association/American College of without further cardiac assessment.
Cardiology 2007 revised guidelines on preoperative assess-
ment of patients undergoing noncardiac surgery1 stratify this What would be the optimal anesthetic plan for
man into a high-risk group with an expected incidence of ei- this man’s open aortic aneurysm repair?
ther cardiac death or nonfatal myocardial infarction of more
The intraoperative management of this case warrants a num-
than 5%. With regard to reducing risk in those with known
ber of considerations including appropriate monitoring,
coronary artery disease, the guidelines ask four questions:
choice of anesthesia technique, transfusion threshold, the use
1. What is the amount of myocardium in jeopardy? of coronary vasodilators, heart rate titration and analgesic
2. What is the ischemic threshold, that is, the amount of technique, to name but a few. Particular attention should be
stress required to produce ischemia? paid to intra- and postoperative pain management.
136
15259_Ch37.qxd 3/15/09 6:25 AM Page 137
CHAPTER 37 • REGIONAL ANESTHESIA OUTCOMES 137
Figure 37.1 • This electrocardio-

gram shows evidence of left ventricu-
lar hypertrophy with the combined
S wave in V3 and the R wave in aVL
measuring ⬎28mm (Cornell Criteria
[Casale PN, et al. Circulation 1987;75:
565–572]). Also note the associated left
ventricular strain pattern, manifest as
T-wave inversion, most evident from
V3 to V6.
The anesthetic plan for this man included the following: been associated with improved cardiac outcomes in this pa-
tient group.1 Nitrates may assist in afterload and blood pres-
• Invasive monitoring of cardiovascular parameters
sure control following placement of the intraoperative aortic
• Nitrous oxide-free general anesthesia with endobrachial in-
cross-clamp.
tubation and positive pressure ventilation
Invasive blood pressure monitoring is best used during
• Epidural catheter placement at the T8 level for intra- and
major vascular surgery, facilitating detection of beat-to-beat
postoperative analgesia using a combination of local anes-
variation, thus allowing rapid intervention when necessary.6
thetic agent (bupivacaine) and strong opiate (fentanyl)
The use of central venous cannulae is also recommended in this
• High-dependency unit or intensive care unit admission fol-
case to facilitate the administration of vasoactive medications
lowing surgery
and examine trends in central venous pressure. Pulmonary ar-
tery catheters are not routinely recommended and may con-
What is the rationale for this anesthetic plan? tribute to patient morbidity.7
Monitoring Noninvasive monitoring with an electrocardio-
gram, SpO2, and noninvasive blood pressure should be em- Anesthesia Technique General anesthesia is the preferred
ployed as routine. The use of online ST-segment monitoring anesthesia modality for open repair of aortic aneurysms. There
with electrocardiogram leads placed in either V5 and V4 con- are no data describing definite benefits regarding the use of
figuration may facilitate the detection of intraoperative and specific general anesthetic techniques or agents. Balanced anes-
postoperative myocardial ischemia and infarction.5 Detecting thesia with muscle relaxation and multimodal analgesia is
intraoperative coronary ischemia may facilitate the early ad- advocated. Of particular importance is the maintenance of nor-
ministration of coronary vasodilators (nitrates). However, rou- mal cardiovascular parameters, especially heart rate and blood
tine use of either ST-segment monitoring or nitrates has not pressure. Titration of the patient’s heart rate to 65 beats per
minute or less with ␤-blockers has been shown to reduce the
likelihood of developing cardiovascular complications in the
T A B L E 3 7 . 1 Preoperative Blood Results
postoperative period.3
Nitrous oxide (N2O) should be avoided in this case for a
Parameter Result number of reasons. Myles et al reported an increase in major
morbidity in patients undergoing laparotomy using N2O-based
Hemoglobin 16.2 g/dL anesthesia. Complications such as postoperative confusion and
Platelet count 425 ⫻ 103 per mm3 postoperative nausea and vomiting were also significantly in-
White cell count 8.7 ⫻ 103 per mm3 creased after exposure to N2O.19 N2O may also lead to gaseous
expansion of intestinal lumen, making access to the retroperi-
Prothrombin time 12 seconds toneum difficult for the surgeon.
Activated partial 28 seconds
thromboplastin time Analgesia Effective analgesia is an essential component to
Sodium 148 mEq/L balanced anesthesia. It has been described as a fundamental
human right.8 Pain contributes significantly to negative out-
Potassium 4.3 mEq/L comes following surgery. Poor postoperative analgesia has
Urea 8.4 mmol/L been associated with higher rates of respiratory tract infection9
and myocardial ischemia,10,11 prolonged hospital stay, un-
Creatinine 219 mmol/L
planned hospital admission, and increased usage of opiate
Glucose 5.1 mmol/L analgesia.12 Poor postoperative pain control has also been im-
plicated in increased procedural cost.13
15259_Ch37.qxd 3/15/09 6:25 AM Page 138
138 CHAPTER 37 • REGIONAL ANESTHESIA OUTCOMES
At the physiologic level, pain results in alterations to neu- of fentanyl. Adjuvants, such as paracetamol should be given
roendocrine responses referred to as the surgical stress response. around the clock (intravenously every 6 hours during the high-
The surgical stress results in increased sympathetic activity, dependency unit stay and orally afterward). Nonsteroidal anti-
which in turn increases heart rate, contractility, and peripheral inflammatory drugs should be avoided because of this patient’s
vascular resistance. This may lead to a reduction in myocardial impaired renal function.
oxygen supply, thereby precipitating ischemia. Pain was measured on a verbal rating scale (0–10) at rest
Epidural analgesia provides superior analgesia compared and on movement. Zero corresponded to no pain, and 10 cor-
to conventional opiate-based systemic regimens.9,14,15 responded to the worst imaginable pain. Measurement oc-
Epidural analgesia blunts the surgical stress response and re- curred hourly for the first 24 hours and every 4 hours. The
sultant sympathetic stimulation, which may confer a cardio- epidural infusion was titrated to keep the dynamic pain score
protective effect. It may also produce vasodilation of epicardial at 3 or less at all times. The epidural catheter was removed
blood vessels, improving myocardial blood flow and prevent- on the third postoperative day. Removal was timed to be
ing myocardial ischemia.16,17 An epidural catheter placed at a minimum of 12 hours after and 4 hours before subcu-
the level corresponding to the most proximal dermatome of taneous low-molecular-weight heparin (deep venous throm-
the surgical incision ensures reliable and predictable analgesia. bosis prophylaxis) as per American Society of Regional
Appropriate thoracic epidural catheter placement is recom- Anesthesia/European Society of Regional Anesthesia con-
mended for major abdominal surgery.18 sensus guideline.20
In summary, balanced anesthesia with effective epidural In summary, a 68-year-old man with significant comorbidi-
analgesia contributes significantly to improving patient outcome. ties underwent major aortic surgery to repair an abdominal
A 14-gauge intravenous cannula was placed in the patient’s aortic aneurysm. Continuation of long-standing medication
right forearm, and 1 L of Hartmann’s solution was adminis- pre-operatively and the use of thoracic epidural analgesia facil-
tered over 45 minutes. An epidural catheter was placed before itated the safe conduct of anesthesia, blunting the adverse ef-
induction of general anesthesia at the level of T8. After a nega- fects of major vascular surgery on the myocardium.
tive aspiration test for blood and cerebrospinal fluid, a test dose
of 2 mL 0.25% bupivacaine was administered. This dose failed
to produce signs consistent with an intrathecal block at 10 min-
utes. Invasive arterial blood pressure was next established. KEY MESSAGES
General anesthesia was induced using fentanyl (2 ␮g/kg),
propofol (1.5 mg/kg), and vecuronium (0.1 mg/kg). The pa- 1. Pain contributes to negative postoperative outcomes
tient’s airway was intubated with an 8.5-mm internal diame- following major abdominal surgery such as myocar-
ter cuffed endotracheal tube, and his lungs were ventilated dial ischemia.
with 50% oxygen in air to achieve normocarbia. Anesthesia 2. Epidural analgesia is superior to opiate-based systemic
was maintained with sevoflurane titrated to effect. analgesia and attenuates the surgical stress response.
Hemodynamic parameters (heart rate and blood pressure)
were kept within 10% of the starting values. Central venous 3. Thoracic epidural analgesia, particularly when main-
access was established after anesthesia induction. An addi- tained postoperatively, may help to prevent periopera-
tional 10 mL of 0.25% bupivacaine was administered into the tive myocardial ischemia and infarction.
epidural catheter at this stage.
The intraoperative course was uneventful with an aortic
cross-clamp time of 40 minutes. Intravenous glyceryl trini-
trate was used to control the patient’s blood pressure during QUESTIONS
the cross-clamp period. Phenylephrine 100-␮g bolus doses
were used to control blood pressure when the aortic cross- 1. What is the role of thoracic epidural analgesia in the
clamp was released. The total estimated blood loss was 750 prevention of myocardial ischemia in abdominal aortic
mL, resulting in a hemoglobin level of 11.2 g/dL at the end aneurysm repair?
of the case. No blood products were administered. Answer: Pain contributes to negative postoperative out-
Intraoperative analgesia consisted of an epidural infusion of comes following major abdominal surgery such as myocar-
0.1% bupivacaine with 2 ␮g/mL of fentanyl at a rate of 8 mL dial ischemia. Neuroendocrine responses and sympathetic
per hour. Intravenous paracetamol 2 g was also adminis- activation increase myocardial oxygen demand and reduce
tered. Immediately following surgery, the sevoflurane was supply. Extradural analgesia provides superior pain relief
discontinued, neostigmine and glycopyrrolate neuromuscu- to opiate-based analgesia and attenuates the surgical neu-
lar block reversal were given, and the trachea was extubated. roendocrine stress response. Thoracic epidural analgesia
The patient was transferred to the high-dependency unit also dilates epicardial blood vessels improving myocardial
where he made an uneventful recovery over the following blood flow. Thus, epidural analgesia may help prevent
48 hours. complications such as postoperative myocardial ischemia
and infarction.
How should this man’s pain be managed after 2. What are the considerations for removing an epidural
surgery? catheter in a patient receiving deep vein thrombosis
Epidural analgesia should be continued and titrated to effect prophylaxis using subcutaneous low-molecular-weight
with a continuous infusion of 0.1% bupivacaine with 2 ␮g/mL heparin?
15259_Ch37.qxd 3/15/09 6:25 AM Page 139
CHAPTER 37 • REGIONAL ANESTHESIA OUTCOMES 139
Answer: Neuraxial instrumentation in patients receiving electrocardiogram with online ST-segment monitoring.
low-molecular-weight heparin may increase the risk of Anesthesiology 2002;96:264–270.
extradural hematoma and resultant neurological injury. 6. The Association of Anaesthetists of Great Britain and Ireland.
Neuraxial instrumentation (catheter removal or inser- Standards of Monitoring During Anaesthesia and Recovery 4th Ed.
Available at: http://www.aagbi.org/publications/guidelines/docs/
tion) should be timed to be a minimum of 12 hours after
standardsofmonitoring07.pdf. Accessed May 19, 2008.
and 4 hours before administering subcutaneous low- 7. Practice guidelines for pulmonary artery catheterization: an up-
molecular-weight heparin. Published American Society date report by the American Society of Anesthesiologists Task
of Regional Anesthesia /European Society of Regional Force on Pulmonary Artery Catheterization. Anesthesiology
Anesthesia consensus guidelines exist. 2003;99:988–1014.
8. Brennan F, Carr DB, Cousins M. Pain management: a funda-
3. Why do traditional outcome measures show no differ- mental human right. Anesth Analg 2007;105: 205–221.
ence following regional anesthesia compared with 9. Rodgers A, Walker N, Schug S, et al. Reduction of postoperative
general anesthesia? mortality and morbidity with epidural or spinal anaesthesia:
Answer: Traditional outcome measures (mortality and results from overview of randomised trials. BMJ 2000;321:1493.
major morbidity) show no difference when studied 10. Beattie WS, Badner NH, Choi P. Epidural analgesia reduces
across large patient populations. Although pain has not postoperative myocardial infarction: a meta-analysis. Anesth
Analg 2001;93:853–858.
been considered a traditional outcome, the superiority of 11. Meissner A, Rolf N, Van Aken H. Thoracic epidural anesthesia
regional anesthesia techniques over systemic opioids has and the patient with heart disease: benefits, risks, and controver-
been consistently shown. There are proven benefits in sies. Anesth Analg 1997;85:517–528.
certain situations and certain subgroups. The use of neu- 12. Pavlin DJ, Chen C, Penaloza DA, et al. Pain as a factor compli-
raxial anesthesia in patients with coronary artery disease cating recovery and discharge after ambulatory surgery. Anesth
undergoing major cardiac or vascular surgery appears Analg 2002;95:627–634.
beneficial and is more pronounced for thoracic than 13. Williams BA, Kentor ML, Vogt MT, et al. Economics of nerve
lumber epidurals and when epidurals are used in the block pain management after anterior cruciate ligament recon-
postoperative period. struction: potential hospital cost savings via associated postanaes-
thesia care unit bypass and same-day discharge. Anesthesiology
2004;100:697–706.
14. Liu SS, Block BM, Wu CL. Effects of perioperative central neu-
References raxial analgesia on outcome after coronary artery bypass surgery:
1. Feisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 a meta-analysis. Anesthesiology 2004;101:153–161.
Guidelines on Perioperative Cardiovascular Evaluation and 15. Rigg JR, Jamrozik K, Myles PS, et al. Epidural anaesthesia and
Care for Noncardiac Surgery: a Report of the American College analgesia and outcome of major surgery: a randomised trial.
of Cardiology/American Heart Association Task Force on Lancet 2002;359:1276–1282.
Practice Guidelines (Writing Committee to Revise the 2002 16. Liu SS, Wu CL. Effect of postoperative analgesia on major post-
Guidelines on Perioperative Cardiovascular Evaluation for operative complications: a systematic update of the evidence.
Noncardiac Surgery). Anesth Analg 2008;106:685–712. Anesth Analg 2007;104:689–702.
2. McFadden EP, Stabile E, Regar E, et al. Late thrombosis in 17. Nygard E, Kofoed KF, Freiberg J, et al. Effects of high thoracic
drug-eluting coronary stents after discontinuation of antiplatelet epidural analgesia on myocardial blood flow in patients with is-
therapy. Lancet 2004;364:1519–1521. chemic heart disease. Circulation 2005;111:2165–2170.
3. Polldermans D, Bax JJ, Schouten O, et al. Should major vascular 18. Procedure Specific Postoperative Pain Management Working
surgery be delayed because of preoperative cardiac testing in in- Group. Available at: http://www.postoppain.org/frameset.htm.
termediate-risk patients receiving beta-blocker therapy with Accessed May 19, 2008.
tight heart rate control? J Am Coll Cardiol 2006;48:964–969. 19. Myles PS, Leslie K, Chan MT. Avoidance of nitrous oxide for
4. La Manach Y, Godet G, Coriat P, et al. The impact of postoper- patients undergoing major surgery: a randomized controlled
ative discontinuation or continuation of chronic statin therapy on trial. Anesthesiology 2007;107:221–231.
cardiac outcome after major vascular surgery. Anesth Analg 20. Horlocker TT, Wedel DJ, Benzon H, et al. Regional anesthesia
2007;104:1326–1333. in the anticoagulated patient: defining the risks (the second
5. Landesberg G, Mosseri M, Wolf, Y et al. Perioperative myocar- ASRA Consensus Conference in Neuraxial Anesthesia and
dial ischemia and infarction: identification by continuous 12-lead Anticoagulation). Reg Anesth Pain Med 2003;28:172–197.
15259_Ch38.qxd 3/18/09 12:11 PM Page 140
CHAPTER 38
Ultrasound Guidance for

Peripheral Nerve Blockade
Brian D. O’Donnell
CASE FORMAT: REFLECTION cilitate nerve localization. A sterile transparent cover was
placed over the transducer, and sterile ultrasound gel was
A 95-year-old, 63-kg woman fell down a flight of stairs. used as an acoustic couplant. The nerve block solution
She sustained a comminuted midhumeral fracture to her consisted of equal parts 2% (20 mg/mL) lidocaine with
right arm and a Lisfranc fracture-dislocation of her right 1:200,000 adrenaline mixed with 0.5% (5 mg/mL) bupi-
foot. Both fractures required operative management. vacaine. Clonidine was added to this solution. The final
Other than mild ecchymosis around her right eye and block solution contained 10 mg/mL lidocaine, 2.5 mg/mL
some tenderness in her right flank, she had suffered no bupivacaine, and 7.5 ␮g/mL clonidine. In total, 20 mL of
other injuries. block solution was used (200 mg lidocaine, 50 mg bupi-
The patient had a history of falls and sustained a hip vacaine, and 150 ␮g clonidine).
fracture 3 years earlier, which required a hemiarthro- Anesthesia for the open reduction internal fixation of
plasty, performed under general anesthesia. At that time, the foot fracture was performed using combined sciatic
she was discovered to have aortic stenosis with a gradient and femoral blocks. With the patient in a supine position,
of 85 mm Hg across the aortic valve. No cardiothoracic the right groin was prepared aseptically and was
surgical intervention was planned. Before her fall, she was scanned to reveal the femoral vessels and femoral nerve.
independently mobile and self-caring, living in sheltered Once the femoral nerve was identified and centered in
accommodation. Her medication consisted of aspirin the scanning field, a Stimuplex A50 needle (B. Braun
75 mg daily and metoprolol 10 mg daily. She had no Medical, Melsungen, Germany) was introduced at the lat-
known drug allergies. eral edge of the scanning probe. The needle was ad-
On examination, the patient’s vital signs were as vanced under direct vision, in long axis, toward the
follows: temperature, 36.5 oC; blood pressure, 155/75 femoral nerve. On reaching the nerve, a test dose of 0.5
mm Hg; heart rate, 52 beats per minute; and respiratory mL of block solution was injected and observed to sur-
rate, 16 breaths per minute. The patient’s breath sounds round the nerve, and an additional 4.5 mL of block solu-
were vesicular. Auscultation of her precordium revealed a tion was injected (Fig. 38.2).
loud pansystolic murmur loudest at the left sternal border, ra- Next, the patient’s sciatic nerve was blocked at a level
diating to the carotids. There was a palpable thrill on the an- just proximal to the popliteal fossa. With the patient still in
terior chest wall. Her physical examination was otherwise the supine position, the lateral thigh was prepared asepti-
unremarkable. cally. Flexing the knee slightly, the ultrasound transducer
The patient’s electrocardiograph reading revealed was placed transversely in the popliteal fossa. The
sinus rhythm with left axis deviation and left ventricular hy- popliteal vessels, tibial, and peroneal nerves were identi-
pertrophy (Fig. 38.1). A transthoracic echocardiogram fied. The tibial nerve was centered in the scanning field
was performed and showed concentric left ventricular hy- and traced proximally to visualize the site at which the sci-
pertrophy, severe aortic stenosis, and mild mitral regurgita- atic nerve bifurcated. At this level, a Stimuplex A100 nee-
tion. The gradient across the aortic valve was estimated to dle (B. Braun Medical) was inserted in the lateral thigh at
be 105 mm Hg with an estimated valve surface area of the level of the scanning probe. The needle was advanced
less than 0.5 cm2. under direct vision, in long axis toward the sciatic nerve.
Following discussion with the patient, it was decided On reaching the nerve, a test dose of 0.5 mL of block so-
to proceed with both surgeries consecutively under re- lution was injected and observed to surround the nerve. An
gional anesthesia. An 18-gauge intravenous cannula was additional 7.5 mL of block solution was injected, which fa-
placed on the dorsum of the patient’s left hand, and 1 L of cilitated complete bathing of the nerve in local anesthetic
Hartmann’s solution was slowly administered. Routine elec- solution (Fig. 38.3).
trocardiograph, pulse oximetry (SaO2), and noninvasive Finally, the brachial plexus on the patient’s right side
blood pressure were attached and used for hemodynamic was blocked using a supraclavicular approach. With the
monitoring throughout the case. A 35% oxygen mask was patient in a supine position, the right supraclavicular fossa
used to deliver supplemental oxygen. was prepared aseptically. The ultrasound probe was
A SonoSite Titan unit (SonoSite, Titan, Bothwell, WA) placed in an anteroposterior orientation, and the area was
with a 7- to 10-MHz Linear 38 mm probe was used to fa- scanned to reveal the supraclavicular artery, the first rib,
140
15259_Ch38.qxd 3/18/09 12:11 PM Page 141
CHAPTER 38 • ULTRASOUND GUIDANCE FOR PERIPHERAL NERVE BLOCKADE 141
the pleura, and the brachial plexus. Once the brachial

plexus was identified and centered in the scanning field,
a Stimuplex A50 needle was introduced at the anterior
LA
edge of the scanning probe. It was then advanced under N
direct vision, in long axis, toward the brachial plexus. On FA
reaching the plexus, a test dose of 0.5 mL of block solu-
tion was injected and observed to fill the brachial plexus
FN
sheath. An additional 6.5 mL of block solution was in-
jected (Fig. 38.4).
Motor and sensory block was tested in the distribu-
tion of the brachial plexus, femoral, and sciatic nerves.
Once satisfactory anesthesia had been achieved, seda-
tion was provided using 2 mg midazolam. Surgery pro-
ceeded uneventfully, taking 4.5 hours in total. During the
surgery, the patient received 2 L of Hartmann’s solution,
1.5 g cefuroxime, and 2 g intravenous paracetamol. At
the end of surgery, she fulfilled the recovery room bypass
criteria and was discharged pain free from the operating Figure 38.2 • Ultrasound-Guided Femoral Nerve
room to the ward. Postoperative pain was managed with Block. The image shows the performance of a femoral nerve
a combination of oral oxycodone and paracetamol. The block with needle visible in the long axis of the ultrasound beam.
patient made an uneventful recovery from anesthesia and FN, femoral nerve; FA, femoral artery; N, needle; LA, local anes-
surgery and was discharged to convalescent care on the thetic (test dose, 0.5 mL).
fifth postoperative day.
Why choose a peripheral nerve block?

Improved Outcome? Outcome studies have not shown im-
proved morbidity and mortality rates with the use of peripheral
nerve blocks. Studies to date have been underpowered to detect
such rare occurrences as perioperative death. Outcomes such as
pain, nausea and vomiting, ambulation, and time to hospital
discharge, however, have all been improved with the use of
peripheral nerve block in many clinical contexts.1–3 Brachial
plexus blocks have been associated with improved pain
outcomes following upper limb surgery.4–6 A combination of
Figure 38.1 • Twelve-lead electrocardiograph show-

ing features of left ventricular hypertrophy. Voltage
criteria for LVH include:
LA
Limb leads
• R wave in lead 1 plus S wave in lead III ⬎25 mm
• R wave in lead aVL ⬎11 mm TN PN
• R wave in lead aVF ⬎20 mm
• S wave in lead aVR ⬎14 mm
Precordial leads
• R wave in leads V4, V5, or V6 ⬎26 mm
• R wave in leads V5 or 6 plus S wave in lead V1 ⬎35 mm
• Largest R wave plus largest S wave in precordial leads
Figure 38.3 • Ultrasound-Guided Sciatic Nerve Block.
⬎45 mm
Image showing the two parts (tibial and common peroneal) of the
(Reproduced with permission from Edhouse J, Thakur RK, Khalil sciatic nerve in the proximal popliteal fossa surrounded by local
JM. ABC of clinical electrocardiography conditions affecting the left anesthetic. TN, tibial nerve; PN, common peroneal nerve; LA,
side of the heart. BMJ 2002;324:1264–1267.) local anesthetic.
15259_Ch38.qxd 3/18/09 12:11 PM Page 142
142 CHAPTER 38 • ULTRASOUND GUIDANCE FOR PERIPHERAL NERVE BLOCKADE
T A B L E 3 8 . 1 Physicochemical Properties of
Local Anesthetics
BP N
Protein Lipid
pKa Binding (%) Solubility
Lidocaine 7.8 65 366
SA
Bupivacaine 8.1 96 3460
R
ITS period. Clonidine has been shown to prolong brachial plexus
blocks when administered into the perineural space.11,12
Why ultrasound guidance?

Block Success Rates? Poor success rates have hampered the
Figure 38.4 • Ultrasound-Guided Supraclavicular use and development of peripheral nerve block techniques.
Brachial Plexus Block. Image showing the performance of a Blind techniques rely on imprecise end points such as paraesthe-
supraclavicular brachial plexus block, with needle visible in the sia or motor response to nerve stimulation. Ultrasound guidance
long axis of the ultrasound beam. SA, subclavian artery; R, first facilitates placing the block needle directly adjacent to the target
rib; BP, brachial plexus (resembles a bunch of grapes); N, needle; nerve, allowing visualization of needle, nerve, and injectate.
ITS, intra-thoracic space. Needle reposition is facilitated, ensuring circumferential spread
of injectate around the nerve. Ultrasound guidance has been
shown to increase the likelihood of a successful block (from 80%
to 95%) when compared with nerve stimulation for three-in-
peripheral nerve blocks facilitated excellent anesthesia and
one blocks.13,14 The only study evaluating brachial plexus block
postoperative analgesia in this case.
techniques suggests equivalence between ultrasound and nerve
stimulation.15 Currently, comparative studies have not been
Reduced Physiologic Insult? General anesthesia agents cause performed with sciatic nerve block.
significant cardiac depression, vasodilatation, and hemody-
namic derangement.7 Although these physiologic changes are Onset Time? Not only have poor success rates hampered
normally well tolerated in health, this patient had severe aor- peripheral nerve block development, slow block onset times
tic stenosis, which predisposes to anesthesia-related cardiovas- similarly make peripheral nerve blocks a less attractive anes-
cular morbidity and mortality. thetic option. When compared with general anesthesia, pe-
General anesthesia also alters respiratory mechanics, result- ripheral nerve blocks have been shown to take on average
ing in lung atelectasis and intrapulmonary shunt, thereby pre- 11 minutes longer to provide effective anesthesia.16
disposing the patient to postoperative complications such as Ultrasound guidance permits deposition of a local anesthetic
hypoxemia and pneumonia.8 Regional anesthesia permits tar- agent directly adjacent to the nerve structure. The physico-
geted anesthesia of surgical site and facilitates surgery in chemical properties of local anesthetic agents (pKa, lipid sol-
awake or lightly sedated, cooperative patients. The unwanted ubility) and the relative concentration of the drug (2% vs.
aforementioned physiologic derangements were avoided in 0.25%) largely determine block onset times. Also, the closer
this case. the solution is deposited to the nerve, the faster the agent will
work. Therefore, greater precision in injectate placement as
Lower Level Monitoring Required? Monitoring for this sur- seen with ultrasound guidance, has resulted in a reduction in
gery under general anesthesia would have necessitated the block onset time.15,17
placement of invasive arterial and central venous cannulae.9
Vasopressor support, to correct predictable hemodynamic de- Reduction in Dose? The dose of the local anesthetic agent
rangement accompanying general anesthesia, may have been used to perform peripheral nerve blocks has been greatly
required. Effective peripheral nerve block obviated the need reduced when compared with traditional techniques.
to use general anesthesia in this case. Marhofer et al14 demonstrated a reduction in dose when ultra-
sound was compared with nerve stimulation for three-in-one
block. Casati et al18 estimated the ED-50 of 0.5% ropivacaine
Why use a mixture of lidocaine, bupivacaine for femoral nerve block to be 15 mL under ultrasound guid-
and clonidine? ance and 26 mL for nerve stimulation. Willschke et al19 used as
The physicochemical properties of lidocaine and bupivacaine little as 0.075 mL/kg for ilioinguinal/iliohypogastric blocks in
are summarized in Table 38.1.10 Lidocaine with a pKa of 7.7 has children. Clinical experience, as illustrated in this case, suggests
a rapid onset of action. Bupivacaine, with 98% protein binding, the potential to dramatically reduce the dose of the agent re-
will provide an extended block well into the postoperative quired to produce successful peripheral nerve block. However,
15259_Ch38.qxd 3/18/09 12:11 PM Page 143
CHAPTER 38 • ULTRASOUND GUIDANCE FOR PERIPHERAL NERVE BLOCKADE 143
the optimal dose of local anesthetic agent for brachial plexus demonstrating an improvement in patient safety with the
and sciatic blocks has not yet been defined. use of ultrasound guidance for regional anesthesia. In ex-
In summary, ultrasound guidance permitted the safe and pert hands, ultrasound guidance reduces local anesthetic
effective conduct of regional anesthesia in a patient with upper dose, speeds block onset and facilitates avoidance of im-
and lower limb fractures, for whom general anesthesia carried portant related structures (arteries and veins). It may ap-
significant risks. Improved block success rates and reduced pear logical that these conditions confer a greater level of
onset times as seen with ultrasound guidance provided the safety than blind techniques. This has not been borne out
confidence to proceed using regional anesthesia alone. In this by prospective data as of yet.
case, ultrasound guidance permitted same-day treatment of
both upper and lower limb fractures, which may not have
been possible with other nerve localization techniques because References
of dose limitations. 1. Liu SS Wu C. Effect of postoperative analgesia on major postop-
erative complications: a systematic update of the evidence.
Anesth Analg 2007;104:689–702.
KEY MESSAGES 2. Richman JM, Liu SS, Courpas G, et al. Does continuous periph-
eral nerve block provide superior pain control to opioids? A
In experienced hands, ultrasound guidance meta-analysis. Anesth Analg 2006;102:248–257.
3. Liu SS, Strodtbeck WM, Richman JM, Wu CL. A comparison of
1. Permits precise nerve localization and perineural local regional versus general anesthesia for ambulatory anesthesia: a
anesthetic deposition. meta-analysis of randomized controlled trials. Anesth Analg
2005;101:1634–1642.
2. Facilitates a reduction in local anesthetic dose. 4. Hadzic A, Williams BA, Karaca PE, et al. For outpatient rotator
cuff surgery, nerve block anesthesia provides superior same-day
3. Improves the success rates of nerve block techniques. recovery over general anesthesia. Anesthesiology. 2005;102:
4. Speeds the onset time of peripheral nerve block. 1001–1007.
5. Singelyn FJ, Lhotel L, Fabre B. Pain relief after arthroscopic
shoulder surgery: a comparison of intraarticular analgesia,
suprascapular nerve block, and interscalene brachial plexus
QUESTIONS block. Anesth Analg 2004;99:589–592.
6. Hadzic A, Arliss J, Kerimoglu B, et al. A comparison
of infraclavicular nerve block versus general anesthesia for
1. Does ultrasound guidance facilitate reducing the dose hand and wrist day-case surgeries. Anesthesiology 2004;101:
of local anesthetic agent needed to perform successful 127–132.
neural blockade. 7. Akata T. General anesthetics and vascular smooth muscle: direct
Answer: Yes. Ultrasound guidance permits precise actions of general anesthetics on cellular mechanisms regulating
perineural needle and injectate placement. Visualization vascular tone. Anesthesiology 2007;106:365–391.
8. Magnusson L, Spahn DR. New concepts of atelectasis during
of circumferential perineural spread is accepted as the general anaesthesia Br J Anaesth 2003;91:61–72.
end point for ultrasound-guided peripheral nerve block. 9. The Association of Anaesthetists of Great Britain & Ireland.
This permits neural blockade with very small volumes of Recommendations for Standards of Monitoring During
local anesthetic agent (Riazi S, Carmichael N, Awad I, Anaesthesia and Recovery, 4th Ed. http://www.aagbi.org/
et al. Effect of local anaesthetic volume (20 vs 5 ml) on publications/guidelines/docs/standardsofmonitoring07.pdf.
the efficacy and respiratory consequences of ultrasound- Accessed March 6, 2009.
guided interscalene brachial plexus block. Br J Anaesth 10. Strichartz GR, Sanchez V, Arthur GR, et al. Fundamental prop-
2008;101:549–556). erties of local anesthetics. II. Measured octanol:buffer partition
coefficients and pKa values of clinically used drugs. Anesth
2. Does ultrasound guidance make the practice of Analg 1990;71:158–170.
regional anesthesia under deep sedation or general 11. Iohom G, Machmachi A, Diarra DP, et al. The effects of
anesthesia safe? clonidine added to mepivacaine for paronychia surgery
under axillary brachial plexus block. Anesth Analg 2005;100:
Answer: No, occult intraneural injection or intraneural 1179–1183.
catheter placement resulting in nerve injury is still 12. Hutschala D, Mascher H, Schmetterer L, et al. Clonidine added
possible. Conscious patients may report pain or to bupivacaine enhances and prolongs analgesia after brachial
dysesthesia should this occur. Deep sedation and general plexus block via a local mechanism in healthy volunteers. Eur J
anesthesia will abolish this feedback. Real-time ultra- Anaesthesiol 2004;21:198–204.
sound guidance may detect needle tip position, but it may 13. Marhofer P, Schrogendorfer K, Koinig H, et al. Ultrasonographic
not prevent an operator-dependent phenomenon such as guidance improves sensory block and onset time of three-in-one
intraneural injection. It is best practice to perform blocks. Anesth Analg 1997;85:854–857.
14. Marhofer P, Schrogendorfer K, Wallner T, et al. Ultrasonographic
regional anesthesia in conscious patients. guidance reduces the amount of local anesthetic for 3-in-1 blocks.
3. Does ultrasound guidance improve the safety of Reg Anesth Pain Med 1998;23:584–588.
15. Casati A, Danelli G, Baciarello M, et al. A prospective, random-
regional anesthetic techniques? ized comparison between ultrasound and nerve stimulation
Answer: The term safety implies clinical efficacy without guidance for multiple injection axillary brachial plexus block.
adverse event or harm. There is no conclusive evidence Anesthesiology. 2007;106:992–996.
15259_Ch38.qxd 3/18/09 12:11 PM Page 144
144 CHAPTER 38 • ULTRASOUND GUIDANCE FOR PERIPHERAL NERVE BLOCKADE
16. Liu SS, Strodtbeck WM, Richman JM, Wu CL. A comparison of 18. Casati A, Baciarello M, Di Cianni S, et al. Effects of ultrasound
regional versus general anesthesia for ambulatory anesthesia: a guidance on the minimum effective anaesthetic volume required
meta-analysis of randomized controlled trials. Anesth Analg. to block the femoral nerve. Br J Anaesth 2007;98:823–827.
2005;101:1634–1642. 19. Willschke H, Bösenberg A, Marhofer P, et al. Ultrasonographic-
17. Williams SR, Chouinard P, Arcand G, et al. Ultrasound guid- guided ilioinguinal/iliohypogastric nerve block in pediatric anes-
ance speeds execution and improves the quality of supraclavicu- thesia: what is the optimal volume? Anesth Analg. 2006;102:
lar block. Anesth Analg 2003;97:1518–1523. 1680–1684.
15259_Ch39.qxd 3/15/09 6:29 AM Page 145
CHAPTER 39
Continuous Ambulatory Regional

Anesthesia
Jason Van der Velde
CASE FORMAT: REFLECTION during the preoperative clinic were reiterated to both the pa-
tient and her husband. These instructions were reinforced
A 56-year-old woman was scheduled for an elective arthro- with a patient information leaflet. The leaflet explained how
scopic shoulder rotater cuff repair and subacranial decom- to use the catheter, cautioned the patient to care for the in-
pression. She was a well-controlled asthmatic, on regular sensate arm, and described the possible drainage that could
budesonide 200 ␮g through a metered dose inhaler who occur. In addition, the sheet mentioned side effects including
had never required hospital admission for her asthma. a sagging eyelid, smaller pupil, slight redness of the eye,
In the preoperative assessment clinic, a continuous and a possible decrease in deep breathing especially while
ambulatory regional anesthetic technique was recom- lying down. The day and time when the catheter should be
mended to the patient for optimal pain management. removed were written on the sheet. The patient was dis-
Specific informed consent was obtained for perineural in- charged home that evening, in care of her husband, with the
terscalene catheter placement prior to general anaesthe- contact numbers of the orthopaedic admissions ward, the
sia after discussing the risks, benefits, alternatives, and district nurse team, and a letter for her general practitioner.
management of potential complications. Motor and sen- The patient awoke at home at 3:00 AM with pain in
sory examination of her shoulder was performed at this the lateral deltoid only. Her husband telephoned the
clinic appointment. ward, and an immediate admission was initiated. On ar-
On the day of surgery, the catheter was placed in the rival, the patient’s pain scores were found to be 7/10,
anesthetic room with standard monitoring and intravenous and rescue pain relief ( intramuscular morphine) was pre-
(IV) access. Real-time ultrasound was used for guidance scribed as required. The perineural infusion was main-
throughout the procedure, which was conducted under stan- tained for an additional 48 hours, as it continued to pro-
dard aseptic conditions consisting of sterile skin preparation vide excellent pain relief to all other aspects of her
and draping of both patient and equipment. shoulder. The patient was discharged home on minor
After infiltration of skin and subcutaneous tissue with a analgesics thereafter, and her outpatient rehabilitation
local anesthetic, an 18-gauge thin-walled needle was in- and recovery continued uneventfully.
serted into the interscalene space between the anterior and
the middle scalene muscle. Preservative-free bupivacaine
(0.5% 20 mL) with 1:200,000 epinephrine was injected. A
20-gauge polyamide catheter was inserted through the nee- CASE DISCUSSION
dle to a depth of 3 cm beyond the needle tip. The catheter
was secured with a clear adhesive dressing. The patient Although greatly improving patients’ long-term quality of
was noted to have both a dense motor and sensory block life, shoulder procedures can be extremely painful. Immediate
30 minutes later. postoperative pain is costly, particularly in terms of length of
General anesthesia was then induced with fentanyl hospital stay and rehabilitation time. With the number of pro-
100 ␮g and propofol 150 mg. Anesthesia maintenance cedures predicted to increase as the population ages, novel ap-
was achieved with sevoflurane and a 50:50 oxygen:air mix proaches to pain management are constantly being sought.
through a laryngeal mask airway. An uneventful 2-hour pro-
cedure followed under general anesthesia without catheter Anesthetic and Analgesic Options
infusion. Paracetamol 1g was administered intravenously
Pain is greatly exacerbated in the rehabilitation phase of treat-
during the procedure.
ment, particularly during physiotherapy. This pain has been
The patient was pain free in the postanesthesia re-
shown to have a direct bearing on the functional outcome of
covery area. Having confirmed the correct position of the
the procedure.1 Current postoperative analgesic regimens
perineural catheter with a thoracic inlet radiograph, a
should ideally include a multimodal prescription of oral minor
disposable elastomeric infusion pump was attached and
analgesics combined with rescue opioids.
set to infuse plain preservative-free 0.25% bupivacaine at
In this particular patient, it is unclear whether this avenue
5 mL per hour.
has been fully explored prior to her initial discharge home. It
On conclusion of the day’s operating list, the anesthetist
appears that she had a single dose of IV paracetamol intraop-
visited the patient on the ward. Instructions initially given
eratively, and no nonsteroidal anti-inflammatory drugs
145
15259_Ch39.qxd 3/15/09 6:29 AM Page 146
146 CHAPTER 39 • CONTINUOUS AMBULATORY REGIONAL ANESTHESIA
T A B L E 3 9 . 1 Comparison of Local Anesthetics
Lidocaine Bupivacaine Levobupivacaine Ropivacaine

Block Plain 60–120 180–360 180–360 140–200
duration (min) With 90–180 300–480 160–220
epinephrine
Onset Rapid Slow Slow Moderate
Sensory block Dense Dense Dense Dense
Motor block Moderate Dense Dense Moderate
Safety Moderately Highly Improved safety Favorable safety
cardiotoxic cardiotoxic over bupivacaine profile compared to
bupivacaines, with
less diaphragmatic
impairment
(NSAIDs) were given, possibly because of exaggerated anxi- when using a dilute local anesthetic solution. If a long-acting
ety that this may worsen her asthma. Aspirin and NSAIDs local anesthetic agent is used to establish the block, as in the
may cause bronchoconstriction in approximately 10% of case presented (Table 39.1), at about 16 hours postinsertion,
asthmatic patients, although they also relieve it in approxi- gaps may become evident as patchy pain. These gaps may
mately 0.3% of patients.10 As the primary mechanism is be- occur in the early hours of the morning, when staffing levels
lieved to be inhibition of the cyclooxygenase 1 (COX-1) en- are low or when an ambulatory patient is at home. It is there-
zyme, patients with aspirin sensitivity often display fore preferable to establish blocks with a short-to-medium act-
cross-reactions to nonselective NSAIDs that inhibit the ing agent such as 1% prilocaine, lidocaine, or mepivacaine. If
COX-1 enzyme.11 Because acetaminophen is a weak in- there is an area not covered by the infusion, this will become
hibitor of the COX-1 enzyme, patients with aspirin-induced evident a few hours post procedure, thus facilitating an early
asthma should not take more than 1000 mg in a single dose, alternative analgesic strategy.9
but COX-2 selective NSAIDs appear to be safe in this patient
population.11 Patient Selection Weighed Against
Regional anesthesia is the cornerstone of multimodal anal-
gesic regimens. Single-shot plexus blocks were first used to Potential Complications
reduce the amount of systemic opioids administered periopera- Shoulder arthroscopy and arthroplasty are performed in
tively. The interscalene brachial plexus block provides analgesia many centers as ambulatory procedures using continuous
that is superior to morphine in shoulder arthroplasty.2 The ad- ambulatory regional anesthesia techniques to control postop-
vantages of a single-shot nerve block may be extended using erative pain.5 Patient satisfaction is high,6 the technique has
perineural local anesthetic infusions. They have the additional reduced oral opioid requirements and sleep disturbances
benefit of expediting and improving functional recovery. The while improving range of motion.
safety and efficacy of various continuous regional anesthesia Although regional anesthetic techniques provide site-specific
techniques using portable infusions or patient-controlled bo- analgesia with minor, if any, systemic side effects,7 it is impor-
luses of local anesthetic agents through indwelling perineural tant to remember that whereas the technique itself does not al-
catheters has been demonstrated.3 ways require inpatient supervision, the patients’ premorbid con-
Interscalene brachial plexus blockade may be combined dition may. Patients must be able to manage at home with the
with a general anesthetic or used as the primary anesthetic risks posed by an insensate limb. Appropriate patient selection
technique for shoulder arthroscopy. Regional anesthesia for weighed against potential complication risks, education, and
shoulder arthroscopy has been shown to require significantly follow-up are crucial when prescribing outpatient infusions.
less nonsurgical intraoperative time (53 ⫾ 12 vs. 62 ⫾ 13 min- Regional anesthesia is not associated with a greater inci-
utes, p ⫽ .0001) and also decreased post-anesthesia care unit dence of neurologic complications than general anesthesia. The
stay (72 ⫾ 24 vs. 102 ⫾ 40 minutes, p ⫽ .0001) compared with American Society of Anesthesiologists closed-claims studies
general anesthesia.4 Administration of regional anesthesia re- suggest that the majority of reported neurological complica-
sulted in significantly fewer unplanned admissions for severe tions are actually associated with general anesthesia and incor-
pain management, sedation, or nausea/vomiting than general rect patient positioning.
anesthesia and was accompanied by a failure rate of 8.7%. The Complications such as hematoma formation, hoarseness,
increasing use of ultrasound to guide perineural catheter and Horner’s syndrome have been reported. These issues are
placement may lead to improved success rates. attributed to needle misplacement or local anesthetic either
Pain management during the transition from a dense sur- spreading to upper cervical nerve roots (C3, C4) or anteriorly to
gical block to an analgesic block is a challenge. This may occur block the phrenic nerve in front of the anterior scalene muscle.
15259_Ch39.qxd 3/15/09 6:29 AM Page 147
CHAPTER 39 • CONTINUOUS AMBULATORY REGIONAL ANESTHESIA 147
All patients should be counseled regarding the high incidence QUESTIONS

of varying degrees of ipsilateral diaphragm paralysis. This occurs
subclinically in most patients and is rarely an issue unless there is
1. Is a long-acting local anesthetic agent ideal for
a significant cardiac or respiratory comorbidity. Moderate or se-
establishing the initial block before starting a
vere functional limitation or a baseline room-air oxygen satura-
continuous ambulatory infusion?
tion of less than 96% is not necessarily a contraindication for re-
gional anesthesia, but inpatient supervision should be mandated Answer: No. It is preferable to establish blocks with
to manage any potential pulmonary complications. a short-to-medium acting agent to diagnose and manage
More serious side effects of regional anesthesia include inadequate or patchy analgesia before a patient’s
vasovagal attacks, pneumothoraces, total spinal anesthesia, discharge.
high epidural block, and inadvertent intravascular injection.
The latter are very rare and will usually present periopera- 2. What steps can be taken to avoid inadvertent
tively, allowing immediate management. intravascular injection of local anesthetic?
If ambulatory catheter dislocation or pump malfunction oc-
curs, particularly early on during ambulatory regional anesthe- Answer: Inadvertent intravascular injection of local
sia, patients are at high risk of experiencing severe surgical pain anesthetic is best avoided by maintaining verbal contact
and are usually unresponsive to oral opioids and require hospi- with the patient, frequent aspirations, looking for disap-
tal re-admission. Patients should therefore not be discharged pearance of motor twitch after injection of the first mL
home if they will be alone and need to be counseled to take of local anesthetic solution (or tissue expansion with
prompt actions if block failure occurs. Patients should also be visualization of the needle tip with ultrasound guidance),
made aware of early signs of systemic local anesthetic toxicity and using an adrenalin-containing test solution to evalu-
and should be able to demonstrate clearly how to disconnect the ate and re-evaluate a perineural catheter.
infusion pump and access urgent medical help if this occurs.
Infusion Considerations 3. What is the management of inadvertent intravascular
injection of bupivacaine resulting in systemic toxicity?
Three interscalene catheter infusion strategies have been com-
Answer: The cornerstone of bupivacaine systemic toxicity
pared:8 continuous infusion alone, basal infusion with patient-
is a 1.5mL/kg bolus of intralipid 20% over 1 minute fol-
administered boluses, and patient-controlled boluses alone. A
lowed by an infusion at 0.25mL/kg/min over 20 minutes
basal infusion of 5 mL/h of bupivacaine 0.125% combined
whilst continuing all necessary cardiopulmonary resusci-
with patient-controlled analgesia boluses (2.5 mL/30 min)
tative efforts. Repeating boluses at 5 minute intervals
proved to be the most appropriate technique.
thereafter or increasing the rate of infusion to
Electronic pumps, although costly, are useful for accurate
0.5mL/kg/min until a stable circulation is restored may
quantification of the agent infused. They are an ideal delivery
be considered.
option for in-hospital use. On the other hand, elastomeric dis-
posable pumps appear to be more reliable because of simplicity.9
They are essentially high-flow resistance devices and therefore
are inherently safer in preventing inadvertent boluses of large References
amounts of local anesthetic. They are ideal for ambulatory 1. Cameron B. Factors affecting the outcome of total shoulder
home use because they are less bulky than electronic pumps. arthroplasty. Am J Orthop 2001;30:613–623.
There are logistical and financial advantages to undertak- 2. Richman JM, Liu SS, Wu C, et al. Does continuous peripheral
ing shoulder surgery in an ambulatory setting; however, the nerve block provide superior pain control to opioids? A meta-
approach is limited by postoperative pain being inadequately analysis. Anesth Analg 2006;102:248–257.
controlled by oral medication alone. Additional continuous 3. Capdevila X, Dadure C, Bringuier S, et. Al. Effect of patient-
ambulatory regional anesthesia appears to meet the challenge controlled perineural analgesia on rehabilitation and pain
of providing a reliable extension of postoperative analgesia fol- after ambulatory orthopedic surgery. Anesthesiology 2006;105:
lowing painful surgery. 566–573.
4. D’Alessio J, Rosenblum M, Shea K, et al. A retrospective com-
parison of interscalene block and general anesthesia for ambula-
tory surgery shoulder arthroscopy. Regional Anesthesia 1995;20:
KEY MESSAGES 62–68.
5. Ilfeld B, Wright T, Enneking K, et al. Shoulder arthroplasty as
1. Regional anesthesia is the cornerstone of multimodal an outpatient procedure using ambulatory perineural local anes-
analgesia following painful surgery. Its benefits could thetic infusion: a pilot feasibility study. Anesth Analg 2005;101:
be extended beyond hospital stay by continuous am- 1319–1322.
bulatory perineural infusions. 6. Fredrickson MJ, Ball CM, Dalgleish AJ. Successful continuous
interscalene analgesia for ambulatory shoulder surgery in a
2. Continuous ambulatory regional anesthesia decreases private practice setting. Reg Anesth Pain Med 2008;33:
length of hospital stay by providing analgesia that 122–128.
permits greater passive limb mobility and the avoid- 7. Bryan N, Swenson J, Greis E, et al. Indwelling interscalene
ance of IV opioids. Patient selection and counseling is catheter use in an outpatient setting for shoulder surgery:
paramount. Technique, efficacy, and complications. J Shoulder Elbow Surg
2007;16:388–395.
15259_Ch39.qxd 3/15/09 6:29 AM Page 148
148 CHAPTER 39 • CONTINUOUS AMBULATORY REGIONAL ANESTHESIA
8. Singelyn F, Seguy S, Gouverneur J. Interscalene brachial plexus 10. Babu KS, Salvi SS. Aspirin and asthma. Chest 2000; 118:
analgesia after open shoulder surgery: continuous versus patient- 1470–1476.
controlled infusion. Anesth Analg 1999;89:1216–1220. 11. Knowles SR, Drucker AM, Weber EA, Shear NH.
9. Russon K, Sardesai A, Ridgway S, et al. Postoperative shoulder Management options for patients with aspirin and nonsteroidal
surgery initiative (POSSI): an interim report of major shoulder anti-inflammatory drug sensitivity. Ann of Pharmacother 2007;
surgery as a day case procedure. BJA 2006;97:869–873. 41:1191–1200.
15259_Ch40.qxd 3/15/09 6:30 AM Page 149
CHAPTER 40
Postoperative Analgesia in a
Trauma Patient With Opioid
Addiction
Brian D. O’Donnell
brain. The femoral nerve is the peripheral nerve that supplies

sensation to the femur.2 This patient had received 25 mg IV
morphine without analgesic benefit. His recent conversion
A 19-year-old male was brought to the emergency depart-
from smoked to IV heroin use suggests tolerance to opiates.
ment by ambulance following a motor vehicle accident. He
Tolerance to opiates is defined as a right-shift in the dose re-
was a restrained rear seat passenger who suffered an
sponse curve, resulting in higher drug doses needed to produce
open fracture to his right femur after retropulsion of the dri-
the desired effect.3 In patients taking long-term opiates, ade-
ver’s seat onto his knee. He had no other injuries.
quate analgesia is difficult to achieve.4 Agitation in this setting
On examination, the patient’s vital signs were as
may be as a result of pain. Keep in mind that agitation may be
follows: heart rate, 110 beats per minute; blood pressure,
caused by injuries such as head trauma, hypoxia from pneu-
105/65 mm Hg; respiratory rate, 24 breaths per minute;
mothorax, or hypovolemic shock resulting from blood loss.
temperature, 35.5°C; and SaO2, 98% on room air. Primary
Agitation may also be caused by opiate withdrawal. Because
and secondary trauma surveys revealed an open midshaft of
this patient had a recent “fix,” and primary and secondary sur-
femur fracture with bone protruding through a wound on the
veys had outruled head, chest injury, and hemorrhagic injury,
anterior thigh. The wound was soiled with particulate matter
it was assumed that pain was the primary cause of agitation.
from the crash site. The patient’s Glasgow Coma Scale
The presence of an occult injury causing agitation was consid-
score was 15, there were no external signs of head injury,
ered at all times. Peripheral nerve block is one appropriate
and he had no memory loss. He was extremely agitated and
analgesic option in these circumstances.
complaining of severe pain. Trauma radiology included a
Following a thorough preoperative assessment, the attend-
lateral cervical spine, chest, and pelvic radiographs (all of
ing anesthesiologist decided to manage pain in the emergency
which showed normal results). His hemoglobin level was
room using a femoral nerve block.
11.4 g/dL, and coagulation as well as biochemistry param-
The procedural aspects of the femoral nerve block were ex-
eters were normal.
plained to the patient, who provided verbal consent for the
Of note, this young man was a heroin user. He had
block. He agreed to cooperate and remain still during the
smoked heroin for 3 years and had recently begun inject-
block. Electrocardiogram, noninvasive blood pressure, and
ing because of diminished drug effect. The absolute quan-
SaO2 monitors were attached. The open fracture was covered
tity of heroin use could not be determined. The patient had
with a sterile surgical drape, and the patient’s groin was pre-
never been on a treatment program, and his last “fix” was
pared aseptically. A Sonosite Titan unit (SonoSite, Titan,
4 hours before the accident.
Bothwell, WA) with a linear 38-mm 7-to 10-MHz probe was
In the emergency room, a 14-gauge intravenous (IV)
used to guide block placement. A sterile transparent cover was
cannula was placed, and the patient received 2 liters of
placed over the ultrasound probe, and sterile ultrasound jelly
Hartmann’s solution. Pain was managed with 25 mg IV mor-
was used as an acoustic couplant. The patient’s groin was
phine sulphate with little effect. The patient received 1.5 g
scanned to reveal the femoral vessels and femoral nerve.
cefuroxime, 500 mg metronidazole, and a tetanus inocula-
A Stimuplex A50 needle (B. Braun Medical, Melsungen,
tion. He was scheduled for emergency surgery, and the op-
Germany) was advanced under direct vision in long axis to-
erating room was alerted and made ready for his arrival.
ward the femoral nerve (Fig. 40.1). Once the needle reached
On initial preoperative assessment in the emergency
the desired perineural space, 0.5 mL of 2% lidocaine with
room, the patient was very agitated and complaining of se-
1:200,000 adrenaline was injected after careful aspiration. The
vere pain.
solution was observed to surround the nerve. An additional
9.5 mL of 2% lidocaine with 1:200,000 adrenaline was then
slowly injected (Fig. 40.2). Over the next 10 minutes, the pa-
tient’s pain improved, and his level of agitation lessened.
How might the patient’s pain and agitation be Approximately 90 minutes later, the patient was moved to
managed before surgery? the operating room where surgical toilet of the wound and in-
Acute pain after trauma originates from nociceptors at the site tramedullary nailing of the femur fracture was planned.
of injury.1 Nociceptor activation results in a pain signal being Although lucid and cooperative, the patient was anxious and
conveyed along sensory fibers in peripheral nerves to the spinal requested general anesthesia, as he did not want to be awake
cord and via a variety of pathways to several areas within the during surgery.
149
15259_Ch40.qxd 3/15/09 6:30 AM Page 150
150 CHAPTER 40 • POSTOPERATIVE ANALGESIA IN A TRAUMA PATIENT
preference and these factors, the anesthesiologist decided to

proceed with general anesthesia.
The patient was considered to have a full stomach, as he
had suffered a painful traumatic injury and had received
opiate analgesics, both known to predispose to impaired gas-
tric emptying.5 Routine monitoring (electrocardiogram,
FA noninvasive blood pressure, SaO2) was attached to the pa-
FV FN tient, and a second 16-gauge IV line was placed. General
anesthesia was induced using a rapid sequence technique
with propofol, suxamethonium, and the Sellick maneuver.
The patient’s airway was managed with an 8.5-mm cuffed
endotracheal tube secured at 23 cm at the incisors.
Anesthesia was maintained with 50% oxygen in air and 3%
sevoflurane. Intraoperative analgesia consisted of 2 g IV
paracetamol and 75 mg IV diclofenac sodium. The surgery
took 3 hours to complete. During this time, an additional
4 liters of Hartmann’s solution was administered. No blood
Figure 40.1 • Image Showing the Femoral Artery, products were administered, and the patient remained he-
Vein, and Nerve with the Use of Directional Color-flow modynamically stable throughout the procedure. His hemo-
Doppler. FA, femoral artery; FN, femoral nerve; FV, femoral globin level was 9.1 g/dL at the end of surgery.
vein. On emergence in the recovery room, the patient com-
plained of mild pain in his leg and could demonstrate return
of femoral nerve motor function by flexing his quadriceps
muscles. Over the next 30 minutes, his pain increased.
How should anesthesia be provided for this
man?
Both general and spinal anesthesia were considered. Spinal How might pain be managed in the
anesthesia would facilitate rapid and effective anesthesia. postoperative setting?
However, the combination of vasodilation associated with Multimodal analgesia involves the administration of two or
spinal anesthesia and relative hypovolemia from the femur more analgesic agents that have a different mechanism of
fracture may have precipitated dramatic hemodynamic insta- action.6 The American Society of Anesthesiologists Task Force
bility. Spinal anesthesia would necessitate turning the patient on Acute Pain Management advocates the use of multimodal
into the lateral position to gain access to the central neuraxis. analgesia for the management of acute pain.7 Multimodal
This maneuver would have been technically difficult because analgesic regimens have been shown to provide superior
of the patient’s open femur fracture. In view of the patient’s analgesia compared with single agents.8,9 Nonsteroidal anti-
inflammatory drugs (NSAIDs) and paracetamol are standard
components to multimodal analgesia. Opiates administered en-
terally or parenterally are used in combination with paraceta-
mol and NSAIDs for the treatment of severe pain. Because of
LA
this patient’s tolerance to opioid medications, effective analge-
sia would be difficult to achieve with an opiate-based analgesia
N regimen.
FV A continuous femoral nerve block would provide excellent
FN analgesia in this setting. Femoral catheters have been used suc-
cessfully to provide analgesia following femur fracture in
non–opioid-dependent patients.10,11 As the initial femoral
nerve block had worn off, it was safe to proceed with inserting
a femoral catheter. Placing a catheter under anesthesia
(general or regional) is a controversial matter. It might be ar-
gued that the advent of ultrasound guidance minimizes the
risk of inadvertent intraneural needle or catheter placement.
However, it is accepted that an awake patient, reporting dyses-
thesia or pain during a nerve block procedure, is an early
warning of intra-neural injection. Therefore, peripheral nerve
blocks are probably best placed in patients who can report
Figure 40.2 • Image Showing a Femoral Nerve Block symptoms of intraneural injection.12 Pain on intraneural injec-
being Performed with the Block Needle Visualized tion has been disputed as a reliable indicator of intraneural in-
along the Long Axis of the Ultrasound Beam. FA, jection.13 In this case, however, it was judged prudent to allow
femoral artery; FN, femoral nerve; LA, 0.5-mL test dose local the initial rescue block to wear off before placing the per-
anesthetic; N, needle with arrows depicting needle path. ineural catheter.
15259_Ch40.qxd 3/15/09 6:30 AM Page 151
CHAPTER 40 • POSTOPERATIVE ANALGESIA IN A TRAUMA PATIENT 151
The patient’s right groin was fully prepared aseptically KEY MESSAGES
under sterile conditions. A hernia towel covered the groin
and facilitated access to the expected puncture site. The ul- 1. Heroin use and subsequent opioid tolerance reduce
trasound probe was covered with a sterile sheath, and sterile the efficacy of opioid analgesics necessitating an alter-
ultrasound jelly was used both inside and outside the sheath nate approach to acute pain management.
as an acoustic couplant. An 18-gauge Tuohy needle and
epidural catheter set were used (Fig. 40.3). The groin was 2. A mechanistic approach to pain management identi-
scanned to reveal the femoral vessels. The Tuohy needle was fied femoral nerve block as an appropriate component
inserted in long axis toward the femoral nerve. On contact of an analgesic regimen for femur fracture.
with the nerve, 0.5 mL 2% lidocaine with 1:200,000 adrena- 3. Femoral nerve block formed a component of the multi-
line was injected and observed to be just outside the per- modal analgesic regimen used in this case, which also
ineural space. Minor adjustments were made to the needle consisted of NSAIDs and paracetamol.
tip position, and another 0.5 mL injectate confirmed satisfac-
tory needle tip placement. An additional 9 mL of 2% lido- 4. Ultrasound guidance facilitated the precise placement
caine with 1:200,000 adrenaline was injected to dilate the of needle, injectate, and catheter adjacent to the
space to accommodate the perineural catheter. The catheter femoral nerve.
was placed through the needle approximately 2 cm beyond
5. Regional anesthesia should ideally be performed only
the needle tip. Correct catheter placement was confirmed by
when patients are able to report symptoms of neural
observing the location of injectate administered through the
injury.
catheter. Next, the catheter was tunneled to a site lateral and
distal to the insertion site and secured with Steri-Strips (3M,
St. Paul, Minnesota, USA) and a transparent dressing. An in-
fusion of 0.25% bupivacaine at a rate of 5 mL per hour was
commenced and continued for 3 days post-operatively. The
QUESTIONS
catheter was removed on the third postoperative day.
1. What is meant by the terms opiate tolerance and
The patient made an uneventful recovery from anesthesia addiction?
and surgery and had excellent analgesia provided by a combi-
nation of femoral nerve catheter, diclofenac sodium 75 mg Answer:
twice daily, and 1g paracetamol four times per day. On the • Opioid tolerance is a predictable pharmacological
first postoperative day, the patient received counseling on adaptation to continued opioid exposure resulting in a
heroin cessation and agreed to be placed in a methadone treat- rightward shift in the dose-response curve. Patients
ment program. require increasing amounts of the drug to maintain the
same pharmacological effects.
• Addiction:
° Psychological dependence: Need for a specific
psychoactive substance either for its positive effects
or to avoid negative effects associated with its
withdrawal.
° Physical dependence: State of adaptation to a
substance characterized by the emergence of a
withdrawal syndrome during abstinence
2. Why was the femoral nerve catheter placed only when
the initial block had worn off?
Answer: Inadvertent intraneural injection or catheter
placement may result in serious nerve injury. Patients
will usually report pain or dysesthesia should these occur
during catheter placement (patient feedback). A nerve,
which has already been blocked with local anesthetic
solution, loses patient feedback and therefore, the poten-
tial exists to inflict serious nerve injury. It is best practice
to allow the initial block to wear off before placing the
Figure 40.3 • Image Showing the Equipment used to perineural catheter.
Place an Ultrasound-Guided Perineural Catheter.
Note the standard aseptic preparation pack with sterile fenes- 3. Does ultrasound guidance make the practice of
trated drape, an 18-gauge Tuohy needle, catheter, and attach- regional anesthesia under deep sedation or general
ments (standard epidural kit from B. Braun Medical, Melsungen, anesthesia safe?
Germany). Also note sterile ultrasound gel and a sterile sheath Answer: No, occult intraneural injection or intraneural
with which to cover the ultrasound probe, providing a sterile in- catheter placement resulting in nerve injury is still
terface between patient and ultrasound probe. possible. Conscious patients may report pain or
15259_Ch40.qxd 3/15/09 6:30 AM Page 152
152 CHAPTER 40 • POSTOPERATIVE ANALGESIA IN A TRAUMA PATIENT
dysesthesia should this occur. Deep sedation and general 7. Ashburn MA, Caplan RA, Carr DB, et al. Practice guidelines
anesthesia will abolish this feedback. Real-time ultra- for acute pain management in the perioperative setting: an up-
sound guidance may detect needle tip position, but it may dated report by the American Society of Anesthesiologists Task
not prevent an operator-dependent phenomenon such as Force on Acute Pain Management. Anesthesiology 2004;100:
1573–1581.
intraneural injection. It is best practice to perform
8. Elia N, Lysakowski C, Trame‘ r MR, et al. Does multimodal
regional anesthesia in conscious patients. analgesia with acetaminophen, nonsteroidal anti-inflammatory
drugs, or selective cyclooxygenase-2 inhibitors and patient-
controlled analgesia morphine offer advantages over morphine
References alone? Anesthesiology 2005;103:1296–1304.
1. Fink WA. The pathophysiology of acute pain. Emerg Med Clin 9. Cepeda MS, Carr DB, Miranda N, et al. Comparison of morphine,
N Am 2005;23:277–284. ketorolac, and their combination for postoperative pain: results
2. Enneking FK, Chan VW, Greger J, et al. Lower-extremity pe- from a large, randomized, double-blind trial. Anesthesiology.
ripheral nerve blockade: essentials of our current understanding. 2005;103:1225–1232.
Reg Anesth Pain Med 2005;30:4–35. 10. Mutty CE, Jensen EJ, Manka MA, et al. Femoral nerve block for
3. Mitra S, Sinatra RS. Perioperative management of acute pain in diaphyseal and distal femoral fractures in the emergency depart-
the opioid-dependent patient. Anesthesiology 2004;101: 212–227. ment. J Bone Joint Surg Am 2007;89:2599–2603.
4. Carroll IR, Angst MS, Clark JD. Management of perioperative 11. Stewart B, Tudur Smith C, Teebay L, et al. Emergency de-
pain in patients chronically consuming opioids. Reg Anesth Pain partment use of a continuous femoral nerve block for pain relief
Med 2004;29:576–591. for fractured femur in children. Emerg Med J. 2007;24:113–114.
5. Murphy DB, Sutton JA, Prescott LF, et al. Opioid-induced delay 12. Hu P, Harmon D, Frizelle H. Patient comfort during regional
in gastric emptying: a peripheral mechanism in humans. anesthesia. J Clin Anesth 2007;19:67–74.
Anesthesiology 1997;87:765–770. 13. Bigeleisen P. Nerve puncture and apparent intraneural in-
6. Kehlet H, Dahl JB. The value of “multimodal” or “balanced jection during ultrasound-guided axillary block does not
analgesia” in postoperative pain treatment. Anesth Analg invariably result in neurologic injury. Anesthesiology 2006;105:
1993;77:1048–1056. 779–783.
15259_Ch41.qxd 3/15/09 6:31 AM Page 153
CHAPTER 41
Alzheimer’s Disease
and Anesthesia
Owen O’Sullivan
CASE FORMAT: REFLECTION dia (32 beats per minute) was effectively treated with gly-
copyrrolate 200 mg, and six boluses of phenylephrine
An 81-year-old, 50-kg woman presented to the emergency 50 ␮g were required to maintain a mean arterial pressure
department following a fall at home. She was accompa- of ⱖ65 mm Hg. Oropharyngeal temperature was moni-
nied by her daughter, who witnessed her mother tripping tored, and a warming blanket as well as warmed intra-
and falling awkwardly on her right side. The patient was venous fluids were used.
in obvious distress when her right hip was moved and ap- After the patient’s blood pressure was stabilized, a
peared to have a swollen and bruised right thigh. She was right-sided femoral nerve block was performed, asepti-
agitated, and staff had difficulty obtaining a relevant his- cally, under ultrasound guidance. A total of 20 mL of
tory from her. The patient’s vital signs were as follows: 0.25% levobupivicaine with 100 mg of clonidine was
blood pressure, 170/80 mm Hg; heart rate, 104 beats per administered. The surgical procedure was well tolerated.
minute; temperature, 36.2oC; and respiratory rate, 20 Intraoperatively, proparacetamol 1g was administered
breaths per minute. intravenously.
A collateral history from the patient’s daughter reveals On completion of the procedure, residual neuromus-
a recent diagnosis of Alzheimer’s disease (AD) following a cular block was reversed with neostigmine (plus glycopy-
steady decline in cognitive function over the last 3 years. rronium). The patient was extubated at an appropriate
The patient was also being treated for hypothyroidism and point and transferred to the recovery room. The recovery
depression. She had an uneventful cholecystectomy 5 years staff felt she was grimacing and bringing her hand to her
ago. The patient was taking the following medications once right thigh. She remained drowsy and disorientated when
daily: donepezil 5 mg, thyroxine 50 ␮g, and omeprazole engaged, not responding to direct questioning about
40 mg. pain. Morphine 2 mg was given intravenously, and after
Clinical examination of respiratory and cardiovascular about 50 minutes in recovery, the patient appeared settled
systems was noncontributory, and on neurological assess- and was transferred to the surgical ward. Postoperative
ment, no sensory-motor deficits were found. Intravenous analgesia was prescribed as paracetamol 1 g orally/
access was established, and samples were taken for full rectally every 6 hours and morphine 5 mg (0.1 mg/kg)
blood count, coagulation profile, urea and electrolytes, intramuscularly as required.
thyroid function, and glucose. IV morphine sulphate 5 mg Over the next few days, the patient was more agitated
was administered before transferring the patient to the radi- than normal, and the nursing staff found it difficult to assess
ology department. Radiology revealed a fractured neck of the patient’s pain intensity. After 5 days, the agitation had
the femur on the right. A computed tomography brain scan settled, and the patient was transferred to a rehabilitation
was also performed, which showed no acute changes. The unit. She made a good recovery, however, her daughter
results of the laboratory investigations are summarized in felt she was more confused and less independent 3 weeks
Table 41.1. The patient consented for a bipolar hemi- after surgery.
arthroplasty.
At the preoperative assessment, the anesthetist felt that
the risks of performing a regional block outweighed the
benefits, particularly as it appeared that the patient would
be very uncooperative and was unlikely to reliably report CASE DISCUSSION
symptoms (e.g., paraesthesia). The anesthetist elected to
perform the procedure under general anesthetic, supple- AD is the most common form of dementia, affecting an esti-
mented with regional anesthesia. Standard monitoring was mated 5.1 million Americans. In the United States, an estimated
applied preoperatively, consisting of pulse oximetry, elec- $148 million is spent annually on AD and other dementias; 1 in
trocardiogram, and noninvasive blood pressure monitor- 8 individuals over 65 years of age has this neurodegenerative
ing. Anesthesia was induced with fentanyl 50 ␮g, propo- disease, rising to almost half aged 85 or older.1 With life ex-
fol 80 mg, and vecuronium 6 mg and was maintained with pectancy ever increasing and no cure at hand, the impact of AD
sevoflurane in a mixture of oxygen and air. An orotracheal in day-to-day medical practice increases each year. The German
tube was inserted. After induction, an episode of bradycar- physician Alois Alzheimer first described the disease in 1906.
He noted microscopic changes at autopsy in the brain of a
153
15259_Ch41.qxd 3/15/09 6:31 AM Page 154
154 CHAPTER 41 • ALZHEIMER’S DISEASE AND ANESTHESIA
The definitive diagnosis of AD can only be made on post-

T A B L E 4 1 . 1 Results of Laboratory
mortem examination of the patient’s brain. The Diagnostic and
Investigations Statistical Manual, 4th edition2 provides one example of many
criteria used to diagnose probable AD (Table 41.2).
Hb 10.3g/dL (↓) Na⫹ 144 mmol/L The exact pathogenesis of the disease remains unknown,
⫹
WCC 10.4 ⫻ 10 /L
9
K 4.5 mmol/L however, it is thought that the loss of cholinergic neurons in
the forebrain basal nuclei plays a central role in the character-
Plt 289 ⫻ 109/L Urea 8.2
istic memory and learning deficits.3 The etiology of AD is also
mmol/L (↑) unknown, however, several risk factors have been identified.
INR 1.1 Creatinine 122 The most important of these is advancing age and family his-
␮mol/L (↑) tory (particularly in early-onset AD). A number of specific
APTT 38 seconds TSH 3.3 mIU/L genes have been implicated in the development of early-onset
AD, in which the onset of AD is before 65 years of age.
Glucose 6.9 mmol/L Thyroxine 145 Genetic mutations on chromosomes 1, 14, and 21 have been
nmol/L (↑) identified in many of these cases, inherited in an autosomal
APTT, activated partial thromboplastin time; Hb, hemoglobin; INR, dominant fashion, which make up less than 5% of all AD
international normalized ratio; K⫹ potassium; Na⫹, sodium; Plt, cases. Polymorphisms of the apolipoprotein E gene on chro-
platelets; TSH, thyroid-stimulating hormone; WCC, white cell count. mosome 19 have also been identified as altering susceptibility
for AD.4
In recent years, there has been increasing interest regarding
an Alzheimer’s-anesthesia link. In vitro studies have shown
51-year-old woman who died after 4 years of progressive halothane and isoflurane to promote amyloid oligomeriza-
dementia. His findings included abnormal clumps (amyloid tion.5,6 This process has been replicated in vivo in transgenic
plaques) and tangled bundles of fibers (neurofibrillary tangles), mice, however, it did not result in additional cognitive decline
now considered the hallmarks of the disease that bears his in cognitively impaired mice.7 To date, human studies have
name. shown no conclusive link between exposure and risk of devel-
AD is a gradually progressive condition. Problems with oping AD.8,9 Such a link, if one did exist, would be very diffi-
memory are the first symptoms, with other aspects of cogni- cult to demonstrate, largely because anesthesia is administered
tion and behavior (difficulty performing everyday tasks, un- to facilitate surgery (often emergency), and isolating its effect
derstanding, and speaking) developing later in the disease’s from other elements such as the surgical stress response can be
course. Late-stage symptoms of AD such as anxiety, aggres- difficult. Although the patient described herein showed subjec-
sion, and wandering herald the inevitable requirement for tive evidence of deterioration postoperatively, keep in mind that
total care. AD is a progressive disorder, and deterioration is inevitable.
T A B L E 4 1 . 2 Diagnostic Criteria for Alzheimer’s Type Dementia
Multiple Cognitive Deficits Involving

A. Memory impairment and one or more of the following:
• Aphasia
• Apraxia
• Agnosia
• Disturbance of executive functioning
B. With impairment and a significant decline in social or occupational functioning as a result of
these deficits
C. A gradual onset and continuing cognitive decline
D. Not caused by
• Other central nervous system conditions that cause progressive deficits in memory and
cognition (e.g., cerebrovascular disease, Parkinson’s disease)
• Systemic conditions known to cause dementia (e.g., hypercalcemia, hypothyroidism)
• Substance-induced conditions
E. Not occurring exclusively during the course of a delirium
F. Not better explained by another psychiatric disorder (e.g., a major depressive disorder,
schizophrenia)
Adapted from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Arlington,
VA: American Psychiatric Association, 1994.
15259_Ch41.qxd 3/15/09 6:31 AM Page 155
CHAPTER 41 • ALZHEIMER’S DISEASE AND ANESTHESIA 155
T A B L E 4 1 . 3 General Considerations Regarding Anesthesia for the Elderly
Pharmacological Considerations Other General Considerations

Reduced minimum alveolar concentration Increased likelihood of ischemic heart disease and
Reduced intravenous anesthetic dose requirements cerebrovascular insufficiency
Increased proportion of body fat Decreased lung volumes
Reduction in skeletal muscle Decreased response to hypercapnia and hypoxemia
Reduced renal clearance Increased closing capacity
Reduced hepatic metabolism and albumin production Increased incidence of atelectasis and postoperative
Increased ␣-glycoprotein production respiratory tract infections
Of particular importance in positioning: Deep vein thrombosis is more common
Limited joint movement Increased incidence of diabetes mellitus
Weak bones Impaired hearing
Thin skin Increased intraoperative heat loss
There is no cure yet for AD. The mainstay of symptomatic however, they allow minimal disturbance of mental capacities.
treatment at present is the use of cholinesterase inhibitors Sedative premedications may worsen confusion and agitation.
(donepezil in this case), which increase the amount of acetyl- Monitoring should take into account potential of poor func-
choline available in the depleted cholinergic nerves. In terms of tional reserve. General considerations of anesthesia in the eld-
anesthetic considerations, these drugs have systemic cholinergic erly should be taken into account (Table 41.3).
features. This can translate into reduced heart rate variability Pain management may be challenging and is often under-
and increased susceptibility for bradycardia, as we saw in this treated in elderly patients with cognitive impairment. One
patient. Extreme bradycardia should be treated with an anti- study of elderly patients posthip fracture showed that cogni-
cholinergic drug, which does not cross the blood-brain barrier tively impaired patients received only one-third the amount of
(e.g., glycopyrrolate). Cholinesterase inhibitors also appear to opioid analgesia compared with cognitively intact individuals.12
antagonize the effects of neuromuscular blocking agents.11 Possible reasons for this include poor pain assessment in pa-
Preoperative assessment should involve the patient’s family tients with communication difficulties and concern for using
or caregivers, as the patient’s ability to understand, communi- analgesics, which may deteriorate cognitive function or other
cate, and cooperate may be significantly impaired. Explanations comorbidities. This is despite the fact that inadequate analgesia
and questions should be simple and stated in a clear fashion. can lead to poorer clinical outcomes, cognitive dysfunction, de-
Multiple comorbidities are common in this age group, and time pression, longer hospital stays, and compromised pulmonary
may be required to establish these as well as to ascertain the pa- function.13
tient’s regular medications. In a trauma patient with poor com- Appropriate pain assessment tools should be utilized, using
munication, efforts should be made to rule out concealed injury self-reporting (preferable) or nonverbal cues as appropriate to
(e.g., rib fractures, intracranial trauma). If agitation is a major patient’s degree of understanding and communication. Facial
feature, small amounts of judiciously administered benzodi- expression may be affected in late dementia adding further
azepine may be required. complication to assessment. Once an appropriate tool has been
Acquiring consent for patients with AD can prove difficult. selected, it should be used consistently with regular reassess-
It is up to the doctor to establish the patient’s capacity to under- ment. Assessment should include duration of pain relief, abil-
stand information and make an informed decision or seek con- ity to ambulate and adequately cough, side effects, and patient
sent from a relevant other. There is no clear standard or formal satisfaction. Analgesia using an epidural route, local anesthetic
guideline available at present. Wishes of relatives and any ad- infiltration, or peripheral nerve blockade can reduce opioid
vance directives should be taken into consideration. Legal as- requirement. If opioids are required, an appropriate route of
pects relating to consent also vary in different jurisdictions. A administration should be chosen. Patient-controlled analgesia
diagnosis of dementia does not automatically assume incompe- may be beyond the cognitive or physical ability of the patient.
tence. AD is progressive; therefore, in early stages, patients will Intramuscular injection results in slower absorption and pos-
retain enough cognitive capacity to consent themselves. The sible toxicity with repeated dosing and should therefore be
difficult task is to establish at what point a patient be protected avoided. The use of nonsteroidal anti-inflammatory drugs is
from making a “bad decision.” It is not clear whether the pa- often restricted in the elderly population because of altered
tient in this case retained sufficient cognitive function to make metabolism and excretion leading to drug accumulation.
an informed decision or whether an effort to establish compe- Although regional anesthesia techniques were welcome in
tence was made. This was certainly a deficiency in her manage- this case scenario, performing them in an uncooperative pa-
ment. It would seem unlikely that the otherwise uncooperative, tient or under general anaesthesia is questionable. Ultrasound
agitated patient was able to give a meaningful consent. guidance does not protect from intraneural (or intravascular)
In preparing for anesthesia, each patient should be evalu- injection. A better option in this patient would have been an il-
ated on an individual basis taking into consideration comorbid iacus block. Spread of local anesthetic beneath the iliacus fas-
conditions and the procedure itself. Regional techniques can cia produces a high success rate of anesthesia of both the
be challenging because of poor cooperation and agitation, femoral and lateral cutaneous nerve of the thigh (which inner-
15259_Ch41.qxd 3/15/09 6:31 AM Page 156
156 CHAPTER 41 • ALZHEIMER’S DISEASE AND ANESTHESIA
vates the anterolateral thigh, the incision area).14 As this is a Answer: Appropriate and consistent pain assessment
compartment block, it can be performed safely in anesthetized tools should be employed in managing analgesia in pa-
patients. The needle insertion point is high at the patient’s tients with AD. Self-reporting is still preferable, how-
thigh in the gutter between the sartorius and quadriceps mus- ever, nonverbal cues may need to be utilized as the dis-
cle. A blunt needle is inserted perpendicular to the skin. An ease and communicative abilities deteriorate. Keep in
initial loss of resistance is identified on penetrating the fascia mind that the commonly used nonverbal cue of facial ex-
lata. A second loss of resistance indicates penetration of the pression will also be affected later in the disease. When
fascia iliaca. Performed preoperatively in this case, it would an appropriate tool is established, it should be applied
have avoided the need for systemic opioids with associated regularly, especially during movement and coughing.
side effects. To extend the duration of the block, a continuous Side effects attributable to analgesics should also be
iliacus block could have been subsequently administered noted. Opioid- sparing measures such as the use of
under general anesthesia, leaving an epidural catheter in place epidural or peripheral nerve blocks should decrease the
and using a standard infusion of local anesthetic solution (e.g., likelihood of such side effects. If opioids are required, the
levobupivacaine 0.2% titrated to effect). most appropriate means of administering them should be
chosen. Patient-controlled analgesia devices require an
adequate level of cognitive function and physical dexter-
KEY MESSAGES ity to operate. Pharmacologic alterations that occur in the
elderly should also be considered.
1. AD is increasing in prevalence with increasing life
expectancy.
References
2. Cholinesterase inhibitors, the mainstay of treatment, 1. Alzheimer’s Association. Every 72 seconds someone in America
have anesthetic implications. develops Alzheimer’s. Alzheimer’s Disease Facts and Figures
2007. Available at www.alz.org. Accessed May 17, 2008.
3. Anesthesia should be tailored on an individual basis
2. American Psychiatric Association. Diagnostic and Statistical
taking into consideration the degree of patient Manual of Mental Disorders, 4th ed. Arlington, VA: American
cooperation as well as comorbid conditions. Patient Psychiatric Association, 1994.
consent and pain management may be particularly 3. Coyle JT, Price DL, DeLong MR. Alzheimer’s disease: a disorder
challenging. of cortical cholinergic innervation. Science 1983;219:1184–1190.
4. Farrer LA, Cupples LA, Haines JL, et al. Effects of age, sex, and
ethnicity on the association between apolipoprotein E genotype
and Alzheimer disease. A meta-analysis. APOE and Alzheimer
QUESTIONS disease meta-analysis consortium. JAMA 1997;278:1349–1356.
5. Eckenhoff RG, Johansson JS, Wei H, et al. Inhaled anesthetic en-
1. Has anesthesia been shown to cause AD? hancement of amyloid-beta oligomerization and cytotoxicity.
Answer: Despite significant interest into the possibility of 6. Xie Z, Dong Y, Maeda U, et al. The inhalation anesthetic isoflu-
anesthesia causing AD, to date, there is no evidence of rane induces a vicious cycle of apoptosis and amyloid beta-
such a link in humans. However, even if there were a protein accumulation. J Neurosci 2007;27:1247–1254.
link between the two, this would be very hard to demon- 7. Bianchi SL, Tran T, Liu C, et al. Brain and behavior changes in 12-
strate because it is difficult to isolate anesthetic factors month-old Tg2576 and nontransgenic mice exposed to anesthetics.
from other factors surrounding surgery (e.g., pain, surgi- Neurobiol Aging 2008;29:1002–1010.
cal stress responses). In vitro studies using halothane and 8. Gasparini M, Vanacore N, Schiaffini C, et al. A case-control
study on Alzheimer’s disease and exposure to anesthesia. Neurol
isoflurane have resulted in cellular processes (amyloid Sci 2002;23:11–14.
oligomerization) that are similar to those thought to 9. Bohnen NI, Warner M, Kokmen E, et al. Alzheimer’s disease
cause AD. and cumulative exposure to anesthesia: a case-control study. J
Am Geriatr Soc 1994;42:198–201.
2. Can patients with AD consent to surgical procedures? 10. Livingston G, Katona C. How useful are cholinesterase in-
Answer: Keep in mind that a diagnosis of dementia does hibitors in the treatment of Alzheimer’s disease? A number
not automatically assume incompetence. AD is progres- needed to treat analysis. Int J Geriatr Psychiatry 2000;
sive, and early in the disease, patients may retain enough 15:203–207.
cognitive capacity to consent themselves. It is the respon- 11. Sánchez Morillo J, Demartini Ferrari A, Roca de Togores López
sibility of the treating doctor to establish whether this ca- A. Interaction of donepezil and muscular blockers in
Alzheimer’s disease. Rev Esp Anestesiol Reanim 2003;50:97–100.
pacity has been retained or if consent should be sought 12. Morrison RS, Siu AL. A comparison of pain and its treatment in
from a relevant other. There are no guidelines available advanced dementia and cognitively intact patients with hip frac-
at present to aid this process, and importantly, legal as- ture. J Pain Symptom Manage 2000;19:240–248.
pects of consent vary across different jurisdictions. The 13. Karani R, Meier DE. Systemic pharmacologic postoperative pain
wishes of family members and advance directives should management in the geriatric orthopaedic patient. Clin Orthop
also be considered. Relat Res 2004;:26–34.
14. Barrett J, Harmon D, Loughnane F, et al. Peripheral nerve
3. What elements are important in the postoperative pain blocks and peri-operative pain relief. 1st ed. Philadelphia:
management of a patient with AD? Saunders; 2004.
15259_Ch42.qxd 3/15/09 6:31 AM Page 157
CHAPTER 42
Sickle Cell Disease
Siun Burke
CASE FORMAT: REFLECTION The patient’s inspired oxygen concentration was in-
creased to 70%, he was volume resuscitated with crystalloid
A 4-year-old boy was scheduled on the emergency trauma and red cell concentrate, actively rewarmed, and the sur-
list for a right hand nerve and tendon repair. The boy was gery was expedited.
of West African origin and had only recently arrived in the In the recovery room, the child complained of severe
country. He sustained a right hand laceration 6 hours pre- pain and continued to have a low oxygen saturation of
viously when he ran into a glass door. On preoperative as- 91% and PO2 was 65 mm Hg.
sessment, the child was pale and irritable; he was com- Hemoglobin analysis confirmed that the child had
plaining of thirst, as he had been kept fasting since arrival sickle cell disease (SCD). He was transferred to the high-
to the hospital in preparation for surgery. At 15 kg, he was dependency unit, managed with supplemental oxygen, fluid
in the 40th percentile for weight. His mother said he lost and blood resuscitation, and judicious opioid analgesia.
about “a cup full” of blood earlier. Two days later, the patient developed shortness of
There were multiple venipuncture marks on the child’s breath, a wheeze, and a high temperature of 39.4°C. His
left arm; the pediatrician had difficulty with venipuncture chest radiograph showed a new right upper lobe pulmonary
and decided that as the child’s operation was imminent, he infiltrate (Fig. 42.1). This finding was diagnosed as acute
should have a cannula inserted and blood taken under chest syndrome (ACS), and the child was started on ceftriax-
general anesthesia instead. one, clarithromycin, and regular paracetamol.
Finally, the anesthetist asked the child’s mother if there On postoperative day 5, the patient was discharged
was any family history of blood diseases or problems with to the general ward. His family was counseled regarding
general anesthesia. She had limited English and was anx- his sickle cell status, its implications for other family mem-
iously trying to calm her son. The child’s mother said he bers, and for any future illnesses and general anesthetics
was from a healthy family, although he seemed to get the child may have.
coughs and colds more frequently than her other children.
He never had a general anesthetic, but other family mem-
bers had undergone uneventful anesthesia.
Two hours later, after 8 hours of fasting, the ope- CASE DISCUSSION
rating room finally became available. With routine moni-
tors in place, the child had an uneventful inhalational in- Discussion points:
duction, and a 20-gauge cannula was inserted in his left
forearm. A laryngeal mask airway was placed, and the 1. Pathophysiology of SCD
child resumed spontaneous respiration of an oxygen, ni- 2. Preoperative screening for sickle cell status
trous oxide, and sevoflurane mixture. The fraction of in- 3. Optimal perioperative management SCD
spired oxygen was 0.3. Maintenance fluids were com- 4. Acute chest syndrome
menced at 50 mL per hour. A tourniquet was inflated to
100 mm Hg above the patient’s systolic blood pressure,
and the surgeon proceeded to repair the tendons and PATHOPHYSIOLOGY OF SCD
nerves. On closer inspection, the surgeon discovered
more extensive injuries than expected and informed the SCD is an autosomal recessive disease that results from the sub-
anesthetist that he would require at least 2 more hours of stitution of valine for glutamic acid at position 6 of the ␤-globin
operating time. gene, leading to production of a defective form of hemoglobin,
An hour later, the child started to become hypotensive. hemoglobin S (HbS). Patients who are homozygous for the HbS
His blood pressure was 70/34 mm Hg and he was tachy- gene have sickle cell disease. Patients who are heterozygous for
cardic with a heart rate of 139 beats per minute. His oxy- the HbS gene are carriers of the condition (sickle cell trait).
gen saturation read 92%, and his temperature was Under stressful conditions, carriers may display some clinical
33.2°C. Information for the patient’s arterial blood analy- manifestations. If both members of a couple are carriers, they
sis is shown in Table 42.1. have a 25% risk of producing a child who is homozygous for the
HbS gene.
157
15259_Ch42.qxd 3/15/09 6:31 AM Page 158
158 CHAPTER 42 • SICKLE CELL DISEASE
balance between vasoconstriction and vasodilatation and pro-

T A B L E 4 2 . 1 Arterial Blood Analysis
and anti-coagulation is disturbed, leading to ischemia, vaso-oc-
Normal Values
clusion, and pain.2
PO2 9.2 kPa 11–14 kPa Preoperative Screening for Sickle
PCO2 8.5 kPa 4–6.5 kPa Cell Status
Ph 7.19 7.35–7.45 Sickle cell disease is a genetic disorder affecting diverse popula-
tions. Those at risk include African, Hispanic Mediterranean,
Bicarbonate 19 mEq/L 22–26 mEq/L Middle Eastern, and Asian Indian. The perioperative period
Lactate 4 mmol/L ⬍2 mmol/L is a well-recognized and predictable time of disease exacerba-
Hemoglobin 6.4 g/dL 10–12 g/dL tions.3 Preoperative screening of at-risk populations is recom-
mended as a method to decrease perioperative morbidity.
A solubility test is used to screen for SCD, a deoxygenating
agent is added to the blood, and if 25% or more of the hemoglo-
The hallmark of SCD is a group of devastating symptoms bin is HbS, the cells will sickle and form a turbid suspension.
known collectively as a sickle cell crisis. Sickle cell crises are For confirmation, abnormal samples undergo further testing,
episodes of pain that occur with varying frequency and are either hemoglobin electrophoresis or high-pressure liquid
usually followed by remission.1 chromatography.4
In the case history presented herein, the fact that the pa- The National Institute for Clinical Excellence guideline
tient’s siblings were well and underwent uneventful general on preoperative testing, June 2003, states that all patients of
anesthesia in the past does not preclude this child from having ethnic origin considered to be at risk, whose sickle cell status
a sickle cell crisis, as the risk of heterozygous parents produc- is unknown, should be offered screening with genetic coun-
ing a homozygous child is 25%. seling before anesthesia and surgery.5 The advantages and
Deoxygenated HbS is 50 times less soluble in blood than disadvantages of preoperative screening for sickle cell status
deoxygenated adult hemoglobin. Deoxygenation of HbS leads are summarized in Table 42.2. A preoperative screening test
to hydrophobic interactions between HbS molecules causing for the child in the case history presented herein would have
the classic sickle shape. The sickle-shaped red blood cells have detected his sickle cell status and allowed the anesthetist to
reduced deformability, thereby obstructing the microvascu- tailor an anesthetic that would have avoided any factors that
lature. This results in vicious cycle of tissue hypoxia and aci- precipitate sickling.
dosis, which promotes further sickling.2 Also the impaired
stability of HbS leads to increased breakdown of the molecule
resulting in the release of large amounts of toxic iron and heme T A B L E 4 2 . 2 Preoperative Screening for Sickle
compounds into the cell. This produces oxidant damage to the Cell Status
cell membrane, disruption of the phospholipid bilayer, protein
distribution, and normal membrane function. This results in Advantages of Preoperative Screening
increased adhesion to the vascular endothelium inducing en- • Avoids the potential disaster of a perioperative sickle cell
dothelial damage and dysfunction. The endothelial regulatory crisis in a patient with undiagnosed sickle cell disease.
• As heterozygous parents and siblings may be asymp-
tomatic, there may not be a family history in patients
with sickle cell disease.
Disadvantages of Preoperative Screening
• Low yield of positive test results.
• Low risk of a crisis if every patient considered at risk
for sickle cell disease receives a well-conducted general
anesthetic avoiding factors that precipitate sickling.
• Risks of indiscriminate preoperative screening result-
ing in unnecessary surgical cancellations, surgical de-
lays, duplication of screening, and misdiagnosis.
• Children often consider venipuncture to be the worst
part of the hospital experience.
• Lack of appropriate medical follow-up and parental
counseling in the busy perioperative period.
• Increased diversity of mixed-race populations with low
accuracy of self-reported ethnicity.
Figure 42.1 • Chest Radiograph Showing a Right • Cost of screening.
Upper Lobe Infiltrate.
15259_Ch42.qxd 3/15/09 6:31 AM Page 159
CHAPTER 42 • SICKLE CELL DISEASE 159
The patient had been fasting for several hours preopera-

T A B L E 4 2 . 3 Perioperative Transfusion in
tively without intravenous fluids, and intraoperative mainte-
nance fluids were minimal without adjustment for fasting Sickle Cell Disease8
time or blood loss. A tourniquet was used for more than
2 hours, which contributed to hypoxia and acidosis. The oper- Group 1 Children who are currently No
ating room was cold, there was no warming apparatus, and well and undergoing minor transfusion
the child’s temperature dropped significantly. His hemoglobin surgery (myringotomy)
level was not checked preoperatively. Group 2 Children who are currently May require
Optimal Perioperative Management well and undergoing top-up
intermediate surgery transfusion
of Patients With SCD
(tonsillectomy) to Hb
AVOID HYPOXIA 8–10 g/dL,
As many patients with SCD have impaired oxygen delivery HbS level
secondary to pulmonary damage, widespread vasculopathy, will remain
increased blood viscosity, anemia, impaired vascular regula- elevated
tion, and disturbed nitrous oxide signaling. Controlled venti-
Group 3 Children with a history of Exchange
lation with a high-inspired oxygen concentration would have
improved oxygenation in this patient’s case. major SCD complications transfusion
Although in vitro evidence of increased sickling in the (stroke, ACS) or a history to achieve
presence of acidosis exists, no benefit has been detected from of hospital admissions for HbS level
alkalinization. Tourniquet use may increase hypoxia and aci- painful crises or children ⬍30%
dosis, but there are reports of uneventful use in SCD, and each undergoing major surgery Total Hb
case should be considered independently.6 Judicious use of a (intra-abdominal or thoracic should not
tourniquet at minimal inflation pressures and for the mini- procedures) exceed
mum time possible may have reduced the degree of acidosis 12 g/dL
evident in the child presented in this case.
ACS, acute chest syndrome; Hb, hemoglobin; Hbs, hemoglobin S; SCD
HEMOGLOBIN DILUTION indicates sickle cell disease.
Adapted from Sickle Cell Disease Transfusion; Clinical Guideline
Intravascular dehydration increases hemoglobin concentra- Great Ormond Street Hospital for Children, NHS Trust.8
tion and consequently the rate of sickling. All patients should
be adequately hydrated preoperatively, and careful attention
must be paid to intraoperative fluid balance. However, there is
no evidence to support aggressive fluid hydration of patients distress, or chest pain.9 It is a frequent cause of hospital
with SCD.6 In the case described herein, the child should have admission and the leading cause of mortality in young adult
been commenced on intravenous fluids preoperatively with SCD patients. Repeated episodes predispose individuals to
careful calculation of pre- and intraoperative fluid deficits. chronic pulmonary disease including pulmonary hypertension.
The incidence following invasive surgical procedures such as
DILUTION OF SICKLE CELLS intra-abdominal procedures or joint replacement is approxi-
Perioperative red cell transfusion remains a controversial topic. mately 10% to 15%.10 Risk factors include HbSS genotype, low
A large prospective randomized trial published in 1995 found fetal haemoglobin (HbF) concentrations, and high steady-state
no benefit to aggressive transfusion (HbS ⬍30) compared with leukocyte and hemoglobin concentrations. Nearly half of the
a conservative transfusion strategy, but there was a higher inci- patients are in the hospital for a diagnosis other than ACS,
dence of transfusion-related complications7 (Table 42.3). with superimposition of the disorder during hospital care.
Specific causes can be identified in approximately 38% of
AVOID HYPOTHERMIA patients, infections in 29%, and fat embolism in 9%. Infections
Hypothermia has been suggested as a perioperative trigger for are equally divided between bacterial viral mycoplasma and
SCD complications, however, there is no publication to chlamydial infections suggesting a macrolide antibiotic as an
demonstrate a link. As normothermia is a basic standard of important treatment adjunct.10
anesthetic care for the general surgical population, it should The pathophysiology of ACS is linked to hypoxic pulmonary
also be a goal for patients with SCD. vasoconstriction. The combination of regional hypoxia and
A preoperative diagnosis of SCD in the case presented vasoconstriction will not only increase HbS polymerization and
herein would have ensured a careful approach to fluid man- sickling but will also increase capillary transit time causing
agement, accounting for preoperative blood loss and dura- exacerbation of endothelial dysfunction via mediators such as
tion of fasting, minimum use of a tourniquet, and strict hypoxia, cytokines, and free radical species.
maintenance of the child’s temperature throughout the ACS is typically detected 48 hours postoperatively.
procedure. Prevention requires early mobilization, good control of sur-
gical pain, incentive spirometry, physiotherapy, and atten-
ACS tion to pulmonary function. Rates of complications and mor-
ACS is defined as a new lobar infiltration on a chest radi- tality figures are age dependent, increasing in individuals
ograph accompanied by fever greater than 38.5°C, respiratory over 20 years of age.
15259_Ch42.qxd 3/15/09 6:31 AM Page 160
160 CHAPTER 42 • SICKLE CELL DISEASE
T A B L E 4 2 . 4 Causes of Acute Chest Syndrome QUESTIONS

Infectious Causes Noninfectious Causes 1. Which organs are affected by sickle cell disease?
Bacteria Answer: Sickle cell disease is a multisystemic disease
which impacts many major organs. The kidneys may
• Pneumococcus • Pulmonary infarction
undergo hypertrophy, develop tubular acidosis, tubular
• Gram-negative bacteria • Hypoventilation deficiencies, proteinuria, nephritic syndrome, and end
• Chlamydia pneumonia secondary to rib stage renal disease. The lungs develop pulmonary hyper-
• Mycoplasma pneumonia infarction or opioid tension in 5% to 30% of patients. The spleen may
administration undergo autoinfarction and hyposplenism. Skin
manifestations include chronic leg ulcers and there may
• Fat embolism
be osteonecrosis of the femoral and humeral heads. The
• Pulmonary edema eye may develop retinitis proliferans.
Viruses 2. By what mechanism does HbS arise?
• Respiratory syncytial Answer: HbS arises when a single nucleotide substitution
virus CTG for GAG in the sixth codon of the beta globin gene
• Parainfluenza results in the substitution of phenylalanine for glutamic
acid. One in 14 people of African heritage are asympto-
• Influenza matic carriers of sickle cell anaemia. One in 700 newborns
Adapted from Credit Valley Hospital Clinical Practice Guideline. of African heritage is affected by sickle cell anaemia.
Management of Sickle Cell Disease in Children, 2004.9
3. What are the benefits of hydroxyurea treatment in sickle
cell disease?
Answer: Hydroxyurea is a cytotoxic drug that reduces
the production of red cells containing a high level of
sickle haemoglobin which tend to arise from rapidly di-
Treatment involves supplemental oxygenation and ven- viding precursors and favours the production of fetal
tilatory support as required; bronchodilators should be used haemoglobin.11 The number of white blood cells and
to treat bronchospasm and antibiotics if pneumonia super- platelets are also reduced. The metabolism of hydrox-
venes. Inhaled nitric oxide may improve alveolar-arterial yurea results in the release of nitric oxide which also
oxygen gradients and reduce pulmonary artery pressure stimulates HbF production. Increased concentration
(Table 42.4). of HbF results in decreased red cell sludging and vaso-
occlusion with subsequent decreased ischaemia and
necrosis. An increased production of nitric oxide results
in more normal vascular tone and decreased pulmonary
artery hypertension. In a study of 299 patients by
KEY MESSAGES Charache et al.,11 the incidence of painful crises reduced
from 4.5 to 2.5 per year; the rates of acute chest syndrome
1. Sickle cell disease is an autosomal recessive disease and blood transfusion also reduced considerably. After 9
that results in production of a defective form of years, there was a 40% reduction in mortality in those
hemoglobin, hemoglobin S (HbS). Deoxygenation of who received hydroxyurea. Recommendations for hy-
HbS causes the classic sickle shape with reduced droxyurea therapy include patients with frequent pain
deformability that obstructs the microvasculature. episodes, history of acute chest syndrome, other severe
vaso-occlusive events, or severe symptomatic anaemia.
2. According to the National Institute for Clinical
Excellence guidelines, all patients of ethnic origin
considered to be at risk, whose sickle cell status is References
unknown, should be offered screening with genetic 1. Koshy M, Weiner SJ, Miller ST, et al. Surgery and anesthesia in
counseling before anesthesia and surgery. sickle cell disease. Cooperative study of sickle cell diseases. Blood
1995;86:3676–3684.
3. Optimal perioperative management of patients with
2. Firth PG. Anaesthesia for peculiar cells—a century of sickle cell
SCD requires avoiding factors that may precipitate a disease. BJA advance access published on September 1, 2005.
sickle cell crisis (e.g., hypoxia, acidosis, intravascular Br J Anaesth 2005;95:287–299.
dehydration, hypothermia, and venous stasis). 3. Buck J, Davies SC. Surgery in sickle cell disease. Hematol Oncol
Clin North Am 2005;19:897802.
4. ACS is the leading cause of mortality in young adults
4. Crawford MW, Galton S, Abdelhaleem M. Preoperative screen-
with SCD. It is defined as a new lobar infiltration on ing for sickle cell disease in children: clinical implications. Can J
chest radiograph accompanied by fever greater than Anesth 2005;52:1058–1063.
38.5°C, respiratory distress, or chest pain. 5. The use of routine preoperative tests for elective surgery. NICE
Guidelines, June 2003.
15259_Ch42.qxd 3/15/09 6:31 AM Page 161
CHAPTER 42 • SICKLE CELL DISEASE 161
6. Tobin JR, Butterworth J. Sickle cell disease: dogma, science, and 9. Credit Valley Hospital, Clinical practice guideline: Management
clinical care. Anesth Analg 2004;98:283–284. of Sickle Cell Disease in Children. 2004.
7. Buck J, Casbard A, Llewelyn C, et al. Preoperative transfusion in 10. Stuart MJ, Nagel RL. Sickle cell disease. Lancet 2004;364:
sickle cell disease: a survey of practice in England. Eur J Haematol 1343–1360.
2005;75:14–21(8). 11. Charache S, Barton FB, Moore RD, et al. Hydroxyurea and
8. Transfusion guidelines for neonates and older children. Br J sickle cell anemia. Clinical utility of a myelosuppressive “switch-
Haema 2004;124(4):433–453. ing” agent. The Multicenter Study of Hydroxyurea in Sickle Cell
Anemia. Medicine (Baltimore) 1996;75:300–326.
15259_Ch43.qxd 3/15/09 6:32 AM Page 162
CHAPTER 43
Anaphylaxis
Mansoor A. Siddiqui
CASE FORMAT: STEP BY STEP What is the differential diagnosis?

Clinically, it is neither possible nor necessary to differentiate
A 27-year-old man was admitted to the accident and emer- between anaphylaxis and anaphylactic reactions at the time
gency department, feeling febrile, with a 1-day history of ab- of presentation, as both respond to the same treatment.
dominal pain, nausea, and vomiting for the last 12 hours. Symptoms of anaphylaxis have their onset within minutes
He had been fit and healthy in the past and was not taking but occasionally can occur late following exposure to the
any medication. The patient smoked 10 cigarettes per day, causative agent. Symptoms can be masked under general
and drank alcohol occasionally. He had not been eating or anesthesia (Table 43.1).
drinking for 8 hours before admission and had vomited Individuals with a history of atopy, asthma, or food aller-
twice during the preceding 3 hours. He had not undergone gies appear to be at increased risk of latex allergy but possibly
surgery in the past and had no known drug allergies. not anaphylaxis to neuromuscular-blocking drugs.5,6 There
The patient’s examination revealed the following: is evidence that patients receiving ␤-blockers (showing unop-
temperature, 37.8°C; dehydration, mild; heart rate, 110 posed ␣-adrenergic effects and therefore being more resistant
beats per minute; blood pressure, 90/50 mm Hg; respira- to adrenaline) and those with asthma suffer more severe
tory rate, 20 breaths per minute on auscultation; and nor- reactions.13,14
mal vesicular breathing. On abdominal palpation, there Additional differential diagnoses to consider include vasova-
was tenderness in the right iliac fossa. The patient’s air- gal reactions. They can mimic anaphylaxis and are characterized
way was evaluated as Mallampati grade I with normal by hypotension, bradycardia, pallor, weakness, nausea, vomit-
dentition. Investigations showed the following: hemoglo- ing, and diaphoresis. Urticaria, pruritus, angioedema, tachycar-
bin, 16.8 g/dL; hematocrit, 0.41; white blood cell count, dia, and bronchospasm, however, are not vasovagal responses.
13.5 ⫻ 109; and platelets, 198 ⫻ 10. Acute respiratory decompensation from severe asthma at-
The patient was diagnosed as having acute appendici- tacks, foreign body aspiration, and pulmonary embolism can
tis and was scheduled for emergency open appendicec- mimic respiratory symptoms suggestive of anaphylaxis, but
tomy by the surgical team. An 18-gauge intravenous (IV) other characteristics such as pruritus, urticaria, and an-
cannula was inserted and fluid resuscitation commenced. gioedema are lacking.
After receiving 500 mL of Hartmann’s solution, the patient’s Seizure disorders, myocardial infarction, and arrhythmias
heart rate decreased to 90 beats per minute, and his blood can be readily distinguished clinically. Patients with heredi-
pressure increased to 110/60 mm Hg. A dose of prophy- tary angioedema do not exhibit pruritus and urticaria; a fam-
lactic antibiotic (co-amoxiclav, 1.2 g) was administered at ily history is usually present.
the surgeon’s request and the patient was transferred to the It is likely that this patient has had an allergic reaction or
operating room. anaphylaxis to one of the substances he received in the periop-
After preoxygenation for 3 minutes, anesthesia was erative period.
achieved using fentanyl 100 ␮g, propofol 250 mg, and sux-
amethonium 100 mg as part of a rapid sequence induction.
A cuffed oroendotracheal tube (inner diameter, 8.5 mm) What is the pathophysiology of anaphylaxis?
was inserted without difficulty and fixed at 23 cm after aus- Any drug administered in the perioperative period can cause a
cultating for bilateral air entry. Atracurium 40 mg was ad- severe immune-mediated hypersensitivity reaction after expo-
ministered 5 minutes later. sure to a foreign protein (antigen) that stimulates im-
Two minutes after atracurium administration, the pa- munoglobulin E (IgE) production. Non–immune-mediated
tient’s airway pressure was noted to increase rendering his reactions account for 30% to 40% of hypersensitivity reac-
lungs progressively more difficult to ventilate. On examinations.4 They neither involve IgE nor prior exposure to this
tion, his face was flushed, and urticarial rashes were ob- antigen.
served on his skin. His heart rate was 120 beats per It is not possible to clinically differentiate between immune
minute, and his blood pressure was 80/40 mm Hg. On and non–immune-mediated reactions. Anaphylactoid reac-
auscultation, the patient’s chest was wheezy, and air entry tions are more likely to involve skin features (94% vs. 72%),5,6
decreased bilaterally. Marked facial swelling occurred in and anaphylactic reactions are more severe.5
2 to 3 minutes. The time course of anaphylaxis can be classified as unipha-
sic, protracted, or biphasic. Reactions typically follow a
162
15259_Ch43.qxd 3/15/09 6:32 AM Page 163
CHAPTER 43 • ANAPHYLAXIS 163
T A B L E 4 3 . 1 Clinical Manifestations of Suspected Anaphylactic Reactions
Specific Sign During

Organ System Symptom Sign Anesthesia
Cutaneous Itching Rash, erythema, flushing,
urticaria, angioedema
Respiratory Lump in the throat Stridor Difficult to ventilate
Hoarseness Wheezing ↑Peak airway pressure
Dysphonia Pulmonary edema SpO2
Dyspnea Cyanosis ↑EtCO2
Cardiovascular Angina Tachycardia ↓ EtCO2
Light-headedness Arrhythmias ↑Hematocrit
Faintness Hypotension ST segment, T-wave changes
Cardiac arrest
Gastrointestinal Nausea Vomiting
Abdominal pain Diarrhea
Adapted from Soetens FM, Vercauteren MP. Allergic reactions during anaesthesia: diagnosis and treatment. Jurnalul Roman de Anestezie Terapie
Intensiva 2008;15:43–50.
uniphasic course, that is, they respond rapidly to treatment 2. Corticosteroids (100 to 500 mg hydrocortisone IV slowly)
and do not recur. In some patients, symptoms may fail to im- 3. Bronchodilators may be required for persistent bron-
prove or may worsen as the effect of adrenaline wears off (pro- chospasm
tracted anaphylaxis); however, 20% will be biphasic in nature.7
The patient was immediately commenced on 100% oxygen.
The second phase usually occurs after an asymptomatic period
With help on the way, the adrenaline ([1:10,000], 50–100 ␮g
of 1 to 8 hours, but there may be a delay of up to 24 hours.
over 1 minute) was administered, followed by two additional
Prolonged observation in these cases is needed.8
increments. A rapid infusion of 0.9% sodium chloride was
started. The patient was positioned supine with the legs
How would this case be managed slightly elevated. At this point, his blood pressure increased to
intraoperatively? 100/50 mm Hg. His airway pressure normalized, and ven-
tilation of his lungs was once again easy. The surgery was
Anaphylaxis is a medical emergency that requires immediate
restarted, and the patient was stabilized, chlorpheniramine
treatment. Even a severe anaphylactic reaction is associated
10 mg was administered by slow IV infusion. Hydrocortisone
with a prompt and successful response to appropriate treat-
100 mg was administered intravenously. At this point, the pa-
ment in most patients. This patient should be managed ag-
tient was hemodynamically stable with a heart rate of 90 beats
gressively according to the existing Association of
per minute, blood pressure of 110/70 mm Hg, and clear chest
Anaesthetists of Great Britain and Ireland guidelines:3
on auscultation. His skin looked normal. Surgery proceeded to
1. Stop administration of all agents likely to have caused laparotomy because of peritonitis. The surgeon requested
anaphylaxis. muscle relaxation.
2. Call for help.
3. Maintain airway, give 100% oxygen, and lay patient flat
with legs elevated. What would be the additional management of
4. Give epinephrine (adrenaline). This may be given intra- choice?
muscularly in a dose of 0.5 mg to 1.0 mg (0.5 to 1 mL of In terms of anaphylactic risk, neuromuscular blocking agents
1:1,000) and may be repeated every 10 minutes accord- (NMBAs) could be classified into three groups: high risk
ing to the arterial pressure and pulse until improvement (succinylcholine and rocuronium), intermediate risk (vecuro-
occurs. Alternatively, 50 to 100 ␮g intravenously (0.5 to nium, pancuronium), and low risk (mivacurium, atracurium,
1 mL of 1:10,000) over 1 minute has been recommended cisatracurium).2
for hypotension with titration of further doses as As cross-reactivity between NMBAs occurs in up to 60% of
required. patients, no other agent should be used without prior testing.2
5. Start rapid IV infusion with colloids or crystalloids. Adult Thus, the best additional prophylactic strategy would be to
patients may require 2 to 4 liters of crystalloids. avoid using NMBAs, which implies an attempt to deepen
anesthesia, taking advantage of muscle relaxation produced by
Secondary therapy consists of: inhalational agents. If this step fails to provide adequate relax-
1. Antihistamines (chlorpheniramine 10 to 20 mg by slow ation, and bearing in mind that succinylcholine is the most
IV infusion) likely culprit in this scenario, a short-acting low-anaphylactic-
15259_Ch43.qxd 3/15/09 6:32 AM Page 164
164 CHAPTER 43 • ANAPHYLAXIS
risk NMBA such as mivacurium may be used. This drug may • The primary and attending team, if different, are also in-
have the extra advantage of not requiring reversal, thus mini- formed about the incident and are given a copy of case
mizing further histamine release. Pretreatment with antihist- notes.
amines and corticosteroids in this case may limit the severity of • The National Medicines Board or appropriate body should
potential reactions, although there is currently little evidence be informed regarding the incident. A national database may
to support their routine use for this sole purpose. allow physicians to determine the precise incidence of allergic
Following administration of mivacurium 8 mg, surgery reactions to various substances relative to their market share,
was finished quickly, and the patient’s trachea was extubated thus making comparisons between countries possible.
uneventfully. • The case is discussed at a departmental mortality and mor-
A blood sample (5–10 mL) was taken in three plain bottles bidity meeting. Ideally, a departmental policy regarding
for mast cell tryptase measurement. The first sample was taken follow-up and a standard checklist of actions should be de-
about 15 minutes after the event, the second after 1 hour, and signed and implemented.
the third after 6 hours. The samples were spun, separated, and
refrigerated at 4°C for testing within 48 hours (can be stored at KEY MESSAGES
⫺20°C for longer).
1. Anaphylaxis is a severe, potentially fatal systemic
How would this patient be managed allergic reaction with a variable clinical picture. There
postoperatively? is no valid predictor of anaphylaxis, and previous
Posttreatment observation of these patients is required, be- exposure is not necessary.
cause of the potential for the second phase of reactivity. The
2. Epinephrine in incremental doses is the mainstay of
anesthetist should take responsibility in investigating the pa-
early treatment.
tient for the cause of anaphylaxis.
This patient was admitted to the high-dependency unit 3. Further evaluation, diagnostics, and reporting are
overnight. The serum concentration of mast cell tryptase taken highly desirable in the interest of the patient and the
1 hour after the reaction was 27 ng/mL (normal ⬍1 ng/mL). anesthetist when faced with subsequent surgery.
This abnormal result confirms that the patient had an ana- Diagnosis is made with intraoperative tests (mast cell
phylactic reaction, but it does not identify the cause. Serum tryptase) and postoperative tests (radioallergosorbent
mast cell tryptase measurement has a positive predictive value tests for specific IgE antibodies and skin tests).
for the diagnosis of anaphylaxis of 95.3% and a negative pre-
dictive value of 49%.6 Thus, a negative test does not rule out
anaphylaxis completely. Also, tryptase levels are unlikely to be
elevated in mild systemic reactions. QUESTIONS
The patient should be advised about the importance of fur-
ther testing before discharge. For these tests, the patient is 1. What is anaphylaxis and what is its incidence during
sent to an allergologist in a regional allergy center. The radio- anesthesia?
allergosorbent test is a technique for measuring antigen-
Answer: Anaphylaxis is a severe allergic reaction to any
specific antibodies in serum. If a fast result is needed, this is the
stimulus, usually having sudden onset and usually lasting
test of choice based on the fact that the concentration of spe-
less than 24 hours, involving one or more body systems
cific IgE antibodies is the same during the reaction as after 4
and producing one or more symptoms such as hives,
to 6 weeks.16
flushing, itching, angioedema, stridor, wheezing, short-
Skin tests (which may take the form of skin prick or intra-
ness of breath, vomiting, diarrhea, and shock. The inci-
dermal tests) should be done 6 weeks after the reaction.
dence of anaphylaxis is estimated to be between 1 in
Before 4 weeks, the intracellular stocks of histamine and
10,000 and 1 in 20,000 anesthesia cases.
other mediators are still lower than normal, therefore in-
creasing the probability of a false-negative result. For the 2. Which substance is most often associated with anaphy-
same reason, drugs that could modify the skin’s response lactic reactions during anesthesia?
have to be avoided (e.g., antihistamines, angiotensin-convert-
Answer: Any substance or drug administered in the peri-
ing enzyme inhibitors, nonsteroidal anti-inflammatory
operative period can potentially produce life-threatening
drugs, vasoconstrictors, neuroleptics). Because of the risk of
immune-mediated hypersensitivity reactions.
life-threatening reactions, challenge tests are not done except
Neuromuscular blocking agents (55%), latex (22.3%), and
for local anesthetics.15
antibiotics (14.7%) are the substances most frequently
A copy of the entire patient’s records (i.e., copies of anes-
associated with anaphylactic reactions.
thetic chart, drug charts, full details of reaction, and reports of
tests done) is sent to both the allergologist and the general 3. What are the principles of intra- and postoperative
practitioner. In addition: management of anaphylaxis?
• Patients and their family members are to be informed about Answer: Anaphylactic reactions cannot be clinically
the incident. A full account of the events, a written record distinguished from non–immune-mediated reactions
of the reaction, and advice regarding future anesthetics (which account for 30%–40% of hypersensitivity
should be given. The patient is encouraged to carry an anes- reactions). Therefore, any suspected anaphylactic reac-
thetic card or medic alert bracelet. tion must be extensively investigated using combined
15259_Ch43.qxd 3/15/09 6:32 AM Page 165
CHAPTER 43 • ANAPHYLAXIS 165
peri- and postoperative testing to confirm the nature of References

the reaction, to identify the causative substance, and to
provide recommendations for future anesthetics. 1. Mertes PM, Lexenaire MC, Alla F. Anaphylactic and anaphylac-
toid reactions occurring during anaesthesia in France 1999–2000.
Guidelines have been issued by the Association of
Anaesthesiology 2003;99:536–545.
Anaesthetists of Great Britain and Ireland to standardize 2. Laxenaire MC, Mertes PM. Anaphylaxis during anaesthesia.
the emergency treatment of anaphylaxis.3 These are: Br J Anaesthesia 2001; 87:549–558.
3. Lang DM, Alpern MB, Visitainer PF, et al. Increased risk for ana-
a. Stop administration of all agents likely to have caused phylactic reactions from contrast media in patients in B-adrenergic
anaphylaxis. blockers or with asthma. Ann Inter Med 1991; 115:270–276.
b. Call for help. 4. Lang DM. Anaphylactoid and anaphylactic reactions. Hazards
c. Maintain airway, give 100% oxygen and lay patient of B blockers. Drugs Saf 1995;12:299–304.
flat with legs elevated. 5. Mertes PM, Laxenaire MC. Allergy and anaphylaxis in anaesthe-
d. Give adrenaline. This may be given intramuscularly sia. Minerva Anestesiol 2004;70:285–291.
in a dose of 0.5 mg to 1 mg (0.5 to 1 mL of 1:1000) and 6. Stark BJ, Sullivan TJ. Biphasic and protracted anaphylaxis.
may be repeated every 10 minutes according to the ar- J Allergy Clin Immunol 1986;78:76–83.
terial pressure and pulse until improvement occurs. 7. Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second
Alternatively, 50 to 100 ␮g intravenously (0.5 to symposium on the definition and management of anaphylaxis:
summary report—second National Institute of allergy and infec-
1 mL of 1:10,000) over 1 minute has been recom- tious disease/food allergy and anaphylaxis network symposium.
mended for hypotension with titration of further J Allergy Clin Immunol 2006;117:391–397.
doses as required. 8. Association of Anaesthetists of Great Britain and Ireland:
e. Start rapid IV infusion with colloids or crystalloids. Suspected anaphylactic reactions associated with anaesthesia.
London 2003. http://www.aagbi.org. Accessed May 2008.
Secondary therapy consists of: 9. Mertes PM, Laxenaire MC. Adverse reactions to neuromuscular
blocking agents. Curr Allergy Asthma Rep 2004;4:7–16.
1. Give antihistamines (chlorpheniramine 10—20 mg by 10. Laroche D, Lefrancois C, Gerard J, et al. Early diagnosis of ana-
slow IV infusion) phylactic reactions to neuromuscular blocking drugs. Br J Anaesth
2. Give corticosteroids (100—500 mg hydrocortisone IV 1992;69:611–614.
slowly) 11. Soetens FM, Vercauteren MP. Allergic reactions during anaes-
3. Bronchodilators may be required for persistent thesia: diagnosis and treatment. Jurnalul Roman de Anestezie
bronchospasm. Terapie Intensiva 2008;15:43–50.
15259_Ch44.qxd 3/15/09 6:32 AM Page 166
CHAPTER 44
Persistent Postsurgical Pain
Peter John Lee
CASE FORMAT: REFLECTION and 10 represented the worst possible pain. The patient
was prescribed paracetamol 1000 mg and diclofenac
A 64-year-old woman presented to her general practitioner sodium 75 mg as required. The paravertebral block
with a lump in the left upper quadrant of her left breast. On catheter was removed before she was transferred to the
examination, a hard nodule was detected, and she was re- ward.
ferred to a general surgeon for further investigation. On the first postoperative day, the patient com-
Mammography and breast biopsy confirmed the presence plained of mild pain while at rest and moderate-to-severe
of a 3-cm invasive adenocarcinoma. Computed axial to- pain during physiotherapy and while mobilizing. The
mography showed no evidence of metastatic disease. The paracetamol was discontinued, and the patient com-
patient was scheduled for a left mastectomy and axillary menced on co-codamol (codeine phosphate 15 mg/
node clearance. paracetamol 500 mg). The patient reported some relief
The patient had previously undergone a total abdomi- from pain at rest and was discharged on the fourth post-
nal hysterectomy under general anesthesia. She was taking operative day.
pravastatin 20 mg daily for dyslipidemia but was otherwise Three months later, after an outpatient consultation,
fit and healthy. She was anxious at the postoperative inter- the surgical team reported that the patient complained of
view and was particularly apprehensive about pain after moderate pain in the left axilla for which she took parac-
her operation, as she had experienced considerable pain etamol and ibuprofen. She was referred to a pain special-
following her hysterectomy. ist for further treatment.
Physical examination of the patient was unremarkable
apart from the lump in her left breast, and the results of
a full blood picture, urea, and electrolytes were all normal.
Her electrocardiogram and chest radiograph were
unremarkable.
CASE DISCUSSION
Before surgery, and with standard monitoring in
progress, a paravertebral block was performed on the pa-
Persistent postsurgical pain (PPSP) is defined as pain that de-
tient. The third thoracic vertebral body was identified with
veloped after a surgical procedure, is of at least 3 months’ du-
the patient in a sitting position, and, under aseptic condi-
ration in which other causes for the pain have been excluded,
tions, following local infiltration, a 22-gauge Tuohy needle
and whereby the possibility that the pain is continuing from a
was inserted 3 cm lateral to the most cephalad aspect of
preexisting problem has been explored and excluded.1
the spinous process. The needle was advanced to 3.5 cm
Women who undergo breast surgery experience chest wall,
to make contact with the transverse process. The needle
breast, or scar pain (11%–57%), phantom breast pain
was then “walked” above the transverse process until a
(13%–24%), and arm and shoulder pain (12%–51%). The
loss of resistance to air confirmed the correct location.
incidence of pain in one or more of these sites is close to 50%
A catheter was inserted into the paravertebral space,
1 year after breast surgery for cancer.2
and following a test dose, bupivacaine 0.5% 20 mL was Risk Factors for PPSP
administered.
Anesthesia was induced using propofol 180 mg, and There are several risk factors for PPSP3 (Table 44.1).
muscle relaxation was achieved with atracurium 35 mg.
Following tracheal intubation, anesthesia was maintained Demographic and Psychosocial Factors Age is a risk factor
with inhaled sevoflurane in an air/oxygen mixture. for the development of PPSP. The incidence of PPSP after
Paracetamol 1000 mg and diclofenac 75 mg were mastectomy is 26% in patients older than 70 years, 40% in
administered intravenously during surgery. Surgery was those 50 to 69 years, and 65% in those 30 to 49 years.4
completed within 1 hour, and the patient’s trachea was Preoperative anxiety, although a predictor of clinically mean-
extubated following reversal with glycopyrrolate and ingful acute pain,5 is not an independent contributor to the
neostigmine. prediction of either the presence or the intensity of PPSP after
In the postanesthesia care unit, the patient reported a breast surgery.6 Prescribing an anxiolytic in this case could
pain score of 4, in which a score of 0 represented no pain, have relieved the patient’s anxiety and decreased acute postop-
erative pain.
166
15259_Ch44.qxd 3/15/09 6:32 AM Page 167
CHAPTER 44 • PERSISTENT POSTSURGICAL PAIN 167
been theorized that PPSP results from sensitization, the block-

T A B L E 4 4 . 1 Risk Factors for Persistent
ade of sensitization by regional technique may help with pre-
Postsurgical Pain vention. Paravertebral block for breast surgery decreases the
incidence of pain symptoms, the intensity of motion-related
1. Demographic and psychosocial factors pain, and the intensity of pain at rest at 12 months.15 Multimodal
2. Preoperative pain analgesia with gabapentin and topical application of a eutectic
3. Type of surgery mixture of local anesthetic decreases the postoperative analgesic
requirements and the incidence and intensity of PPSP 3 months
4. Concomitant treatments after breast surgery.16 Multimodal analgesia using a continuous
5. Genetic factors paravertebral block and regular acetaminophen and parecoxib
decreased the incidence of PPSP at 10 weeks.12
6. Postoperative pain
Although satisfactory analgesia at rest was achieved in this
case, movement-evoked pain was described as moderate to se-
vere and was not treated adequately. The paravertebral
catheter could have been left in situ, and an infusion of local
Preoperative Pain The evidence on preoperative pain as a anesthetic could have been administered postoperatively or
risk factor for PPSP is conflicting. A retrospective study a combination of nonsteroidal anti-inflammatory drugs and
showed a significant correlation between preoperative breast paracetamol with opioids administered regularly. The use of
pain and phantom breast syndrome.7 A prospective trial found multimodal analgesia techniques, which has been shown to
no correlation between preoperative breast pain and the risk of provide optimal dynamic pain relief with minimal side effects,
developing PPSP.6 may prevent PPSP.
The perioperative use of tricyclic antidepressants and anti-
Type of Surgery PPSP is more common after breast-conserving convulsants may also benefit in the prevention of PPSP.
surgery than after radical surgery.8 The antiepileptic drugs gabapentin and pregabalin are effica-
cious in the treatment of neuropathic pain associated with di-
Concomitant Treatments There is a higher incidence of PPSP abetic peripheral neuropathy and postherpetic neuralgia.17
in patients who undergo chemotherapy9 or radiotherapy.6 The Pregabalin binds to the alpha2delta subunit of calcium chan-
patient in this scenario would certainly undergo chemotherapy nels, reducing depolarization-induced calcium influx and
or radiotherapy following surgery. thereby decreasing the release of excitatory neurotransmitters,
including glutamate, noradrenaline and substance P.17 A sin-
Genetic Factors A genetic influence on the development of gle dose of gabapentin administered to patients before mastec-
PPSP has been shown in animals.10 Three genetic variants of tomy decreases postoperative morphine consumption and pain
the gene encoding catechol-O-methyltransferase have been during movement.18 Gabapentin, as part of a multimodal
identified, and five combinations of these variants are strongly analgesic regimen, decreased the incidence of PPSP at 10
associated with variation in the sensitivity to experimental weeks after breast surgery.19 Gabapentin could certainly have
pain and with the development of a long-term pain disorder.11 been used in this case.
Excitatory neurotransmitters, acting through N-methyl-D-
Postoperative Pain Severe acute pain after breast surgery is a aspartate receptors, are implicated in the process of sensitiza-
risk factor for the development of PPSP,6 and adequacy of tion and development of PPSP. Ketamine, an N-methyl-D-
postoperative analgesia is an important determinant of aspartate receptor antagonist, is an antihyperalgesic drug that
PPSP.12. modulates excitatory neurotransmission, decreasing both me-
Decreasing the Incidence of PPSP chanical hyperalgesia around the wound and incidence of
residual pain in patients undergoing bowel surgery.20 As part
Peripheral and central sensitization of the nervous system is im- of a multimodal analgesic technique along with intraoperative
plicated in the development of PPSP. Nociception-induced epidural anesthesia, ketamine reduces the incidence of PPSP 1
hyperalgesia observable in the postoperative period is a conse- year after major digestive surgery.21
quence of surgical tissue and nerve trauma.13 Nociceptive inputs There are no specific recommendations regarding the use
alter subsequent sensory nervous system processing, both pe- of ketamine in this scenario.
ripheral and central.14 This neuroplasticity is initially excitatory Perioperative administration of the N-methyl-D-aspartate
(termed sensitization) and develops from activation (acute, tran- receptor antagonist amantadine did not prevent the develop-
sient, and activity-dependent) via modulation (subacute, slower, ment of postmastectomy pain syndrome in patients who un-
still reversible functional changes) through to modification derwent breast surgery with axillary lymph node dissection.22
(chronic structural and architectural changes).13 Nociceptive ex-
citatory neuroplasticity is expressed clinically as increased sensi-
tivity to pain. Peripheral nervous system excitation increases KEY MESSAGES
sensitivity to painful stimulus in the area of damaged tissue.
1. The incidence of PPSP following breast surgery is
Changes Underlying the 48%.
Development of PPSP
2. Severe acute postoperative pain is the most significant
Providing adequate postoperative analgesia after breast surgery risk factor for PPSP after breast surgery.
decreases the incidence and intensity of PPSP. Because it has
15259_Ch44.qxd 3/15/09 6:32 AM Page 168
168 CHAPTER 44 • PERSISTENT POSTSURGICAL PAIN
6. Poleshuck EL. Risk factors for chronic pain following breast

3. Multimodal analgesic techniques, including conduction cancer surgery: a prospective study. J Pain 2006;7:626–634.
blockade by regional technique, reduce the incidence 7. Kroner K, Krebs B, Skov J, et al. Immediate and long-term
and severity of PPSP. phantom breast syndrome after mastectomy: incidence, clinical
characteristics and relationship to pre-mastectomy breast pain.
4. The gabapentinoid antiepileptic drugs (gabapentin Pain 1989;36:327–334.
and pregabalin), and the N-methyl-D-aspartate recep- 8. Tasmuth T, Kataja M, Blomqvist C, et al. Pain and other symp-
tor antagonist ketamine show promise in perioperative toms after different treatment modalities of breast cancer. Ann
prevention of PPSP. Oncol 1995;6:453–459.
9. Tasmuth T, Kataja M, Blomqvist C, et al. Treatment-related
factors predisposing to chronic pain in patients with breast
cancer—a multivariate approach. Acta Oncol 1997;36:625–630.
QUESTIONS 10. Seltzer Z, Wu T, Max MB, et al. Mapping a gene for neuropathic
pain-related behaviour following peripheral neurectomy in the
mouse. Pain 2001;93:101—106.
1. What is the definition of PPSP? 11. Diatchenko L, Slade GD, Nackley AG, et al. Genetic basis for in-
Answer: PPSP is defined as pain that developed after a dividual variations in pain perception and the development of a
surgical procedure, is of at least 3 months’ duration in chronic pain condition. Human Mol Genet 2005;14:135–143.
which other causes for the pain have been excluded, and 12. Iohom G, Abdalla H, O’Brien J, et al. The associations between
whereby the possibility that the pain is continuing from a severity of early postoperative pain, chronic postsurgical pain and
preexisting problem has been explored and excluded. plasma concentration of stable nitric oxide products after breast
surgery. Anesth Analg 2006;103:995–1000.
2. What techniques have been successfully used to reduce 13. Wilder-Smith OH, Tassonyi E, Crul BJP, et al. Quantitative
the incidence of PPSP after breast surgery? sensory testing and human surgery: effects of analgesic manage-
ment on postoperative neuroplasticity. Anesthesiology 2003;98:
Answer: Providing adequate postoperative analgesia after 1214–1222.
breast surgery decreases the incidence and intensity of 14. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in
PPSP. Multimodal analgesia using continuous paraverte- pain. Science 2000;288:1765–1769.
bral block and regular acetaminophen and parecoxib, or 15. Kairaluoma PM, Bachmann MS, Rosenberg PH, et al.
a eutectic mixture of local anesthetic and gabapentin has Preincisional paravertebral block reduces the prevalence of
decreased the incidence of PPSP after breast surgery. chronic pan after breast surgery. Anesth Analg 2006; 103:
703–708.
3. In what way might pregabalin prevent sensitization of 16. Fassoulaki A, Triga A, Melemeni A, et al. Multimodal analgesia
the pain system? with gabapentin and local anaesthetics prevents acute and
chronic pain after breast surgery for cancer. Anesth Analg 2005;
Answer: Pregabalin binds to the alpha2delta subunit of 101:1427–1432.
calcium channels in neurons, reducing depolarization- 17. Ben-Menacern E. Pregabalin pharmacology and its relevance to
induced calcium influx and thereby decreasing the clinical practice. Epilepsia 2004;45:13–18.
release of excitatory neurotransmitters, including 18. Dirks J, Fredensborg BB, Christensen D, et al. A randomized
glutamate, noradrenaline, and substance P at the level study of the effects of single-dose gabapentin versus placebo on
of the dorsal horn. postoperative pain and morphine consumption after mastectomy.
19. Gilron I. Is gabapentin a broad-spectrum analgesic? Anesthesiology
References 2002;97:537—539.
20. De Kock M, Lavand’homme P, Waterloos H, et al. ‘Balanced
1. Macrae WA. Chronic pain after surgery. Br J Anaesth 2001;87:
analgesia’ in the perioperative period: is there a place for keta-
88–98.
mine? Pain 2001;92:373–380.
2. Perkins FM, Kehlet MD. Chronic pain as an outcome of surgery.
21. Lavand’homme P, De Kock M, Waterloos H, et al. Intraoperative
epidural analgesia combined with ketamine provides effective pre-
3. Macrae WA. Can we prevent chronic pain after surgery? In:
ventive analgesia in patients undergoing major digestive surgery.
Shorten GD, Carr D, Harmon D, et al, eds. Postoperative Pain
Management. Philadelphia: Saunders Elsevier, 2006:259–264.
22. Eisenberg E, Pud D, Koltun L, et al. Effect of early administra-
4. Smith WCS, Bourne D, Squair J, et al. A retrospective cohort
tion of the N-methyl-D-aspartate receptor antagonist amanta-
study of post-mastectomy pain syndrome. Pain 1999;83:91–95.
dine on the development of postmastectomy pain syndrome: a
5. Katz J, Poleshuck E, Andrus CH, et al. Risk factors for acute
prospective pilot study. J Pain 2007;8:223–229.
pain and its persistence following breast cancer surgery. Pain
2005;119:16–25.
15259_Ch45.qxd 3/15/09 6:33 AM Page 169
CHAPTER 45
Opioid-Induced Hyperalgesia
James O’Driscoll
CASE FORMAT: REFLECTION boluses of 5 mg morphine and noted that the pain seemed
out of proportion for the procedure given the multimodal ap-
A 29-year-old, ASA II (American Society of proach taken, particularly the local infiltration. The patient’s
Anesthesiologists), 80-kg male admitted to the plastic sur- Verbal Rating Score at this stage remained at 8, his heart
gery department sustained significant injuries to his right rate was100 beats per minute, and noninvasive blood pres-
hand while as a passenger in a car involved in a road traf- sure was 140/94 mm Hg. As soon as the patient had set-
fic accident. He had extensive lacerations to both the pal- tled, he was discharged from the PACU to the general ward
mar and dorsal aspects of his right, dominant hand and on oral paracetamol and diclofenac around the clock as
had clinical evidence of tendon and nerve damage. He well as oxycodone as required for breakthrough pain.
also had fractures of the first and second phalanges of his Two hours later, the anesthetist was called to review
third finger. It was therefore proposed to explore and re- the patient’s pain on the ward. The patient reported in-
pair the wound under anesthesia. creased pain scores (Verbal Rating Score, 7) and had not
The patient had a history of intravenous (IV) drug responded to oral analgesia in the form of oxycodone. His
abuse (heroin) but was not currently using and had been heart rate was 110 beats per minute and noninvasive
abstinent for 2 months. He also had a history of long-term, blood pressure was 150/88 mm Hg. Morphine-based pa-
well-controlled asthma and was using salbutamol and tient- controlled analgesia was prescribed in addition to
beclamethasone metered-dose inhalers. His examination regular paracetamol as well as nonsteroidal anti-inflamma-
was unremarkable. tory drugs, and the patient seemed to have improved when
The various options for anesthesia including general, reviewed 1 hour later.
regional, and combined techniques were discussed with In the morning, the acute pain team reviewed the pa-
the patient. He requested a general anesthetic and refused tient, and he reported moderate pain control. Examination
all offers of regional/nerve blockade despite explanation of the patient-controlled analgesia delivery system showed a
of these techniques and reassurance regarding efficacy total consumption of 120 mg of morphine over 16 hours
and safety. and a bolus demand/delivery ratio of 4:1. It was felt that his
On arrival in the operating room, appropriate monitor- pain control was suboptimal despite all the appropriate
ing was established, and after preoxygenation with 100% measures.
oxygen, anesthesia was induced with 2 ␮g midazolam, The patient subsequently made a full recovery and
250 mcg fentanyl, and 300 mg propofol. A size 4 laryn- never demonstrated any evidence of a return to IV drug
geal mask airway was placed, and the position was con- abuse. In the weeks following surgery, the patient reported
firmed by auscultation and capnography. Anesthesia was that pain control was excellent.
maintained uneventfully with sevoflurane in an oxygen/air
mixture and assisted ventilation in a pressure support mode
until return of spontaneous ventilation. Analgesia adminis-
tered consisted of 2 g paracetamol IV, 75 mg diclofenac
CASE DISCUSSION
IV, 15 mg morphine IV, and wound infiltration by a surgeon
at end of the procedure with 10 mL 0.25% bupivacaine. The finding of increased postoperative pain and postopera-
The total anesthesia time was 3 hours, and the patient’s tive opioid consumption in a patient receiving a high rather
vital signs were stable throughout. than a low intraoperative opioid dose indicates the possibility
After the procedure, the patient was transferred to the of opioid-induced hyperalgesia (OIH) in this patient.
postanesthesia care unit (PACU), and 10 minutes later, he Alternatively, this patient may have experienced acute toler-
began to complain of pain. His Verbal Rating Scale score ance to analgesic opioid effects. No firm conclusions can be
was 8 out of 10 (scale, 0–10), his pulse was 110 beats per drawn. Differentiation between OIH and tolerance requires
minute, and noninvasive blood pressure was 140/88 mm a method directly assessing pain sensitivity, and implement-
Hg. Further bolus doses of morphine were administered to a ing such a method into clinical practice is difficult.
total of 10 mg in accordance with PACU protocol. Twenty OIH
minutes later the patient complained again of pain and was
reviewed by the anesthetist. He gave the patient two further OIH is a phenomenon whereby opioid drugs prescribed to al-
leviate pain may paradoxically make the patient more sensitive
169
15259_Ch45.qxd 3/15/09 6:33 AM Page 170
170 CHAPTER 45 • OPIOID-INDUCED HYPERALGESIA
to painful stimuli. There is strong animal evidence for the

phenomenon particularly with long-term opioid administra- 3. The cornerstone of managing OIH is dose reduction of
tion.1 There is, however, a growing body of evidence for its oc- the culprit opioid and the use of multimodal analgesia.
currence in humans. OIH is most commonly described in the
setting of long-term use or withdrawal from long-term use as
is the case of the patient described herein.2 Increased pain sen- QUESTIONS
sation after opioids for acute pain has also been reported, par-
ticularly with remifentanil.3 1. What is OIH, and in what clinical settings is it likely to
Various potential mechanisms have been proposed, but occur?
none appears to be definitive. There may be sensitization of Answer: OIH is a clinical condition whereby opioid drugs
peripheral nociceptors, enhanced production and release, or such as morphine or any opioid drug prescribed to relieve
decreased reuptake of nociceptive neurotransmitters, or sen- pain may paradoxically increase the patient’s perception of
sitization of second-order neurons. We do know that c-fos pain. The exact mechanism by which this occurs is un-
expression is increased and that blockade of N-methyl-D- known, but there is strong evidence for the involvement of
aspartic acid or excitatory amino acid receptors prevent several nociceptive pathways and regulatory mechanisms
hyperalgesia associated with opioid use.4 such as the excitatory amino acids and N-methyl-D-
aspartic acid receptor. OIH has most often been described
Management of OIH in the setting of long-term pain, in patients with prolonged
The first step is to have a high index of suspicion and to iden- exposure to opioid medication. It has also been described
tify patients who may be at risk of developing OIH. Currently, following acute exposure to opioids such as remifentanil.
this group would mainly be those on long-term opioid therapy. 2. Can OIH be prevented?
Any opioid has the potential to cause OIH. A multimodal ap-
proach to analgesia is essential, as the use of adjuvants (regional Answer: Little is known about the exact mechanism,
anesthesia, clonidine, ketamine) attenuates/blocks the develop- thereby making strategies for prevention difficult. It is
ment of OIH.4 known that a multimodal approach to analgesia in both
There was potential for improvement in the management the acute and chronic settings is essential. This also limits
of our patient. It would be important to discover the exact exposure to opioid medications and all their undesirable
reasons for patient refusal of regional anesthesia (even just as effects.
adjuvant) and to address his concerns in an attempt to 3. What is the treatment for OIH?
change his mind. It is very likely that a brachial plexus block
would have provided optimal intra- and postoperative anal- Answer: Treatment of OIH can be difficult when it does
gesia in his case. Perhaps the addition of other drugs such as occur. Keep in mind that reducing the dose or changing
clonidine or ketamine may have helped once pain control to a different opioid can help alleviate the problem. Drug
was found to be unsatisfactory in the PACU. Gabapentin has rotation is becoming a common strategy in the long-term
been shown to prevent OIH in rats, explained by the fact that use of opioids for pain management to maintain efficacy
neuropathic pain and OIH share common pathophysiologic and reduce side effects. In addition, clonidine and keta-
mechanisms.5 Another important observation is that OIH is mine may be added to the armamentarium of pain man-
often related to a particular drug in a particular patient. agement in these cases.
Therefore, rotating drugs both in the acute and long-term
pain setting can help to reduce this phenomenon.4 As soon as References
a high-dose, opioid-induced hyperalgesic effect is suspected,
1. Zissen MH, Zhang G, McKelvy A, et al. Tolerance, opioid-
dose reduction of the causative agent and/or switching to induced allodynia and withdrawal associated allodynia in infant
another opioid agonist (in this case fentanyl or sufentanil) is and young rats. Neuroscience 2007;144:247–262.
a logical next step. 2. Meyer M, Wagner K, Benvenuto A, et al. Intrapartum and post-
partum analgesia for women maintained on methadone during
pregnancy. Obstet Gynecol 2007;110:261–266.
3. Schmidt S, Bethge G, Forster MH, et al. Enhanced postoperative
sensitivity to painful pressure stimuli after intraoperative high
KEY MESSAGES dose remifentanil in patients without significant surgical site
pain. Clin J Pain 2007;23:605–611.
1. OIH is a pronociceptive phenomenon that can occur 4. Koppert W, Schulz M. The impact of opioid-induced hyperalge-
with acute or long-term opioid administration. sia for postoperative pain. Best Pract Res Clin Anaesthesiol
2007;21:65–83.
2. Disappearance of opioid treatment effects coupled 5. Van Elstraete AC, Sitbon P, Mazoit JX, Benhamou D.
with unexplained pain expansion may indicate OIH. Gabapentin prevents delayed and long-lasting hyperalgesia in-
duced by fentanyl in rats. Anesthesiology 2008;108:484–494.
15259_Ch46.qxd 3/15/09 12:59 PM Page 171
CHAPTER 46
Transurethral Resection of
Prostate Syndrome
John Dowling
As there were no contraindications to a neuraxial anes-

thetic technique, a spinal anesthetic was planned for the pro-
cedure and discussed with the patient.
A 74-year-old, 92-kg man (American Society of
Upon arrival at the operating room, a wide-bore (16-gauge)
Anesthesiologists II with long-standing, well-controlled hy-
cannula was inserted in the patient’s left wrist, and 500 mL of
pertension) was admitted for transurethral resection of
Hartmann’s solution was administered. Standard monitoring
prostate (TURP) for benign prostatic hypertrophy. He had
was instituted (ECG, oxygen (O2) saturation, and noninvasive
an uneventful inguinal hernia repair under general anes-
blood pressure monitoring). Forty percent O2 was administered
thesia 8 years previously. His medications included a
via a Venturi fixed performance mask. A spinal anesthetic was
␤-adrenergic antagonist (bisoprolol) and an HMG Co-A
performed at the level of L3 to L4 with the patient in the sitting
reductase inhibitor (pravastatin).
position under strict aseptic conditions. Three mL of 0.5% hy-
The patient underwent a full preoperative evaluation
perbaric bupivacaine was injected into clear, free-flowing cere-
including a past medical and anesthetic history and rele-
brospinal fluid. After 10 minutes, a motor and sensory block to
vant physical examination. Table 46.1 summarizes his
the level of T10 was noted and deemed adequate for starting the
preoperative blood results. The patient’s preoperative elec-
procedure. The attending anesthetist kept in regular verbal con-
trocardiogram (ECG) reading was normal.
tact with the patient. A senior surgical trainee began the proce-
dure with his consultant surgeon supervising at chair side.
Baseline monitoring (immediately post-spinal blockade)
showed a heart rate of 66 beats per minute, blood pressure of
What are the main anesthetic considerations 114/74 mm Hg, O2 saturation of 99%, and the patient’s ECG
for this patient? trace showed normal sinus rhythm.
TURP is performed by passing a loop through a special cysto- Fifty minutes into the procedure, the patient complained of
scope (resectoscope). Using direct visualization and continu- a headache and dizziness and was noted to be somewhat con-
ous irrigation, prostatic tissue is resected by applying a cutting fused and restless. His heart rate was found to have fallen to
current to the loop. This procedure is performed on a predom- 52 beats per minute, and he was noted to be hypertensive
inantly elderly population, therefore, anesthesia carries a mor- (blood pressure, 162/106 mm Hg). The patient became pro-
tality risk of 0.2% to 6%, which correlates best with the gressively more anxious and in addition was now dyspneic. He
American Society of Anesthesiologists’ physical status scale. then complained of feeling cold, and a subsequent tempera-
Although this patient is on statins, because he is 74 years old, ture measurement showed him to be markedly hypothermic
he has a high chance of cerebrovascular and cardiovascular (33.8°C).
atherosclerotic disease. In addition, being hypertensive in-
creases his risk of perioperative myocardial events because of
possible left ventricular hypertrophy. His ECG reading, how- What differential diagnosis should be
ever, was normal. Despite the fact that ␤-blockers reduce the considered at this stage?
patient’s ability to compensate for hypotension, they should be • TURP syndrome
continued in the perioperative period, as they have proven • Hypoxia
benefit in terms of perioperative morbidity/mortality in pa- • Hemorrhage
tients with ischemic heart disease. • Myocardial infarction
A neuraxial block is considered the most suitable tech- • Cerebrovascular event
nique for TURP, although general anesthesia has a similar • Hypothermia
morbidity and mortality profile. A subarachnoid block to T10 • Bladder perforation
is desirable, as it provides excellent anesthesia without impor- • Septicemia (gram-negative)
tant hypotension for the patient and adequate perineal and
pelvic floor relaxation for the surgeon. Compared with gen-
eral anesthesia, regional anesthesia appears to reduce the inci- What is the most likely diagnosis, and how
dence of postoperative deep venous thrombosis, and it is less could this be rapidly ascertained?
likely to mask signs of bladder perforation symptoms or The most likely diagnosis is TURP syndrome and could be
TURP syndrome. confirmed via a stat sodium (showing hyponatremia).
171
15259_Ch46.qxd 3/15/09 12:59 PM Page 172
172 CHAPTER 46 • TRANSURETHRAL RESECTION OF PROSTATE SYNDROME
body water with normal total body sodium. In general, if

T A B L E 4 6 . 1 Preoperative Blood Results
the serum sodium concentration falls to 120 mEq/L, signs
Measured Preoperative and symptoms of dilutional hyponatremia may ensue.
Variable Value Normal Range
2. Fluid overload may give rise to pulmonary edema and
⫹
cardiac failure especially in individuals with preexisting
Na 136 135–146 mEq/L cardiovascular compromise, as well as cerebral edema.
K⫹ 4.1 3.5–5.0 mEq/L 3. Glycine toxicity results in impairment of consciousness
and transient blindness. This is thought to be related to
Creatinine 0.087 0.06–0.12 mmol/L
glycine acting as an inhibitory neurotransmitter at both
Urea 4.4 2.5–6.7 mmol/L central nervous system and retinal sites.1
Hemoglobin 14.7 14–17 g/dL
White blood cells 5.7 4.3–10.8 ⫻ 109/L What other signs and symptoms may indicate
the presence of or an evolving TURP syndrome?
1. Cardiovascular system: The presence of hypertension and
bradycardia may reflect a hypervolemic state; hypotension
The classic triad of features that constitute the TURP syn- may then ensue representing emerging cardiac failure.
drome are (a) dilutional hyponatremia, (b) fluid overload with In addition, glycine is known to be directly cardiotoxic to
consequent pulmonary and cerebral edema, and (c) glycine the myocardium.
toxicity.1 2. Central nervous system: Confusion and agitation pro-
In the TURP procedure, resecting prostatic tissue opens up gressing to unconsciousness reflects hyponatremia, cere-
the large and extensive network of prostatic venous plexuses. bral edema, and glycine toxicity.
Continuous irrigation is used to distend the bladder and 3. Pulmonary system: Fluid overload may result in pul-
remove blood and tissue from the operative view. A hypo- monary edema and hypoxemia.
osmotic glycine solution is most commonly utilized for this 4. Hematologic system: Dilutional anemia may ensue.
purpose because of its favorable optical and electrical proper- 5. Nausea and vomiting may result from hyperammone-
ties in transurethral surgery. A variable amount of this irrigat- mia—in severe cases progressing to encephalopathy
ing solution will be absorbed intravascularly over the course (ammonia is a major by-product of glycine metabolism).
of the procedure. Absorption of large amounts of this fluid 6. Hypothermia may occur as a result of using a cold irrig-
(⬎2 L) results in a constellation of symptoms commonly de- ant solution.3
scribed as TURP syndrome.
The critical physiologic derangement of central nervous An arterial blood gas analysis was quickly performed, and
system function is not only hyponatremia, but also acute hy- the results are shown in Table 46.2.
poosmolality because the blood-brain barrier is largely imper-
meable to sodium but freely permeable to water. The cerebral How could the most obvious abnormalities
edema caused by acute hypo-osmolality can increase intracra- be explained?
nial pressure with consequent bradycardia, hypertension, and
neurologic symptoms.1 The patient’s Na⫹ measurement of 111 mEq/L reflects a de-
crease in serum Na of 25 mEq/L. A diagnosis of TURP syn-
drome can be made on the basis of the arterial blood gas
What factors influence the volume of solution findings. Typically, if the serum Na⫹ levels drop to below
absorbed intravascularly? 120 mEq/L, signs and symptoms of water intoxication will be
1. Hydrostatic pressure, which is determined by the height seen.1 In addition, the blood gas shows that the patient was
of the irrigating fluid above the patient. The irrigating
bag must be kept as low as possible to achieve adequate
flow of irrigant (usually 60–70 cm).
2. Number and size of opened venous sinuses
3. Procedure duration and experience of the operating sur- T A B L E 4 6 . 2 Intraoperative Arterial Blood Gas
geon. The most important preventive measure during
Measured Value Result Normal Range
surgery is preserving the prostatic capsule. Violation of
the capsule aids entry of irrigation fluid into the peripro- pH 7.38 7.35–7.45
static and retroperitoneal space. pO2 9 11–14.5 kPa
4. Venous pressure: More fluid is absorbed if the patient is
hypovolemic or hypotensive.2 Of note, smoking is the pCO2 4.8 4.5–6.0 kPa
only patient factor known to be associated with large- Na⫹ 111 135–146 mEq/L
scale fluid absorption during TURP.9 K⫹ 4.7 3.5–5 mEq/L
Cl⫺ 102 100–106 mEq/L
What are the origins and manifestations of the
classic triad of symptoms? Base excess 1.2 ⫺2–⫹2
1. Dilutional hyponatremia found in TURP syndrome is a Hemoglobin 12.6 14–17 g/dL
hypervolemic hyponatremia representing excess total
15259_Ch46.qxd 3/15/09 12:59 PM Page 173
CHAPTER 46 • TRANSURETHRAL RESECTION OF PROSTATE SYNDROME 173
hypoxemic (PO2 of 9), indicating respiratory compromise and A diagnosis of pulmonary edema was made on the basis of
probable pulmonary edema. A dilutional anemia is also seen clinical and radiology findings (Fig. 46.2). The patient was in-
(hemoglobin level of 12.6), reflecting the large intravascular tubated, and transfer to the intensive care unit was arranged.
fluid load. He was ventilated using a synchronized intermittent manda-
tory ventilatory mode. He was also started on a hypertonic
saline infusion to slowly correct his hyponatremia (at a rate of
What would be the emergency management in approximately 1 mmol/L per hour). When hemodynamically
this case? stable, the patient was started on a bolus of intravenous
Treating TURP syndrome depends on early recognition, and frusemide to treat his fluid overload and consequent pul-
therefore, the anesthetist should maintain a high degree of clin- monary edema. Twenty-four hours later, the pulmonary
ical vigilance. Initial management should follow the airway edema and hyponatremia had resolved, the patient was extu-
breathing and circulation guidelines (ABC). The operating bated, and he made an uneventful recovery.
surgeon should be informed, and the procedure should be dis-
continued as soon as sites of bleeding have been controlled.5
Cardiovascular compromise including bradycardia and hy- What are the current controversies regarding
potension may require treatment with anticholinergic and/or treatment of TURP syndrome?
adrenergic agents, particularly in this case, in which the patient In the past, fluid restriction was suggested as a potential ther-
has been on ␤-blocker therapy. apy to improve hyponatremia, yet this method did not address
Subsequently, the surgery was rapidly terminated, and the the hypovolemia and low cardiac output that frequently fol-
patient was monitored in the recovery room. His SpO2 was lowed the discontinuation of irrigating solution. Several stud-
between 92% and 95% on a Venturi face mask delivering 60% ies support the use of hypertonic saline in the correction of the
O2. A 12-lead ECG was performed, which showed widening existing hyponatremia.2,3 Treatment is recommended when
of the QRS complex on the ECG trace (Fig. 46.1). measured serum sodium is below 120 mEq/L or when there
are obvious signs and symptoms of hyponatremia. In addition,
studies have shown a higher frequency of neurological dis-
What arrhythmias and other cardiac ability and death among individuals who either did not re-
manifestations may be seen in a patient ceive or when there was a delay in instituting hypertonic
with TURP syndrome? saline therapy.6 As a general rule, a correction of serum
When serum sodium levels fall to less than 120 mEq/L, signs of sodium by 1 mmol/L per hour may be considered as a safe rate
cardiovascular depression can occur; less than 115 mEq/L may but should be guided by improvements in the patient’s neuro-
cause bradycardia, widening of the QRS complex, ST-segment logical status. Hypertonic saline 3% is suggested as an initial
elevation, ventricular ectopic beats, and T-wave inversion.3 A fluid therapy, which can be adjusted in relation to serial
serum sodium level of less than 110 mEq/L may cause respira- serum sodium measurements and clinical improvement of
tory and cardiac arrest. the patient. Hypertonic saline has been shown to counteract
The patient subsequently developed severe respiratory dis-
tress and was unable to maintain adequate O2 saturations on
high-flow O2.
Figure 46.1 • QRS Widening on Electrocardiogram. Figure 46.2 • Pulmonary Edema.

15259_Ch46.qxd 3/15/09 12:59 PM Page 174
174 CHAPTER 46 • TRANSURETHRAL RESECTION OF PROSTATE SYNDROME
cerebral edema and expand plasma volume; the theoretical 2. What is the main advantage of performing the proce-
risk of causing pulmonary edema has not been seen in clinical dure under neuraxial blockade rather than general
usage.7 anesthesia?
Although the risk of pontine myelinolysis is more imme- Answer: With the patient awake, it is possible to keep
diate in the setting of chronic hyponatremia, the literature in constant verbal contact with him and thus detect any
still advocates a gradual sodium correction even in the acute early signs of confusion or restlessness, which may indi-
phase.6 cate an evolving TURP syndrome. This aspect of patient
Intravenous frusemide may be used to counteract the acute monitoring is lost with general anesthesia.
pulmonary edema and promote diuresis. No studies advocate
its routine use in the treatment of fluid absorption, and in fact, 3. What are the attributes of an ideal irrigation fluid for
it may exacerbate a preexisting hyponatremic hypovolemic TURP? How are these similar to those that are currently
picture. In situations when pulmonary edema is not estab- available?
lished, the best practice is probably to withhold frusemide Answer: The ideal irrigation fluid should be optically
until the patient is hemodynamically stable and a hypertonic clear, nonelectrolytic (and therefore nonconductive of the
saline infusion has been started.8 electrosurgical current) and isotonic. Numerous noncon-
Preventive measures, such as low-pressure irrigation, ductive fluids are available, such as glycine 1.5%, sorbitol
might reduce the extent of fluid absorption but do not elimi- 3%, mannitol 5%, and sterile water. The most commonly
nate this complication. Alternative surgical techniques, such as used irrigation fluid, glycine 1.5% solution is optically clear
the use of bipolar resectoscopes and prostate vaporization may and non-electrolytic but hypo-osmolar (200 mOsm/L);
influence fluid absorption and its consequences. therefore, large amounts may be absorbed systemically
through the vascular prostate bed. Direct toxicity and me-
tabolism of glycine can account for some of the neurologic
symptoms of TURP syndrome. The 6-carbon alcohols,
mannitol and sorbitol, both act as osmotic diuretics, in
KEY MESSAGES
slightly varying concentrations. Solutions approximating
3% of either of the 6-carbon alcohols are most often used.
1. Absorption of small amounts of fluid occurs in 5% to These solutions are purposely prepared moderately hypo-
10% of patients undergoing TURP and results in an tonic to maintain their transparency. Sterile water offers
easily overlooked mild TURP syndrome. a very clear view of the operating field (and is therefore
2. Most symptoms appear 30 to 45 minutes after surgery often used for cystoscopy), but it is highly hypotonic and
is completed, at which time hyponatremia is explained may result in hemolysis of erythrocytes and possible renal
by natriuresis and not by dilution. However, symptoms failure when absorbed in large amounts through vascular
related to fluid absorption develop in 3% to 5% of openings.
patients.
3. Furosemide should be used cautiously. In the absence
of pulmonary edema, its use should be best delayed References
until the patient is hemodynamically stable and hyper- 1. Gravenstein D. Transurethral resection of the prostate syndrome:
tonic fluid therapy has been instituted. a review of the pathophysiology and management. Anesth Analg
Judicious correction of hyponatremia with hypertonic 1997;84:438–446.
saline has been shown to improve patient outcome. 2. Hahn RG. Fluid absorption in endoscopic surgery. Br J Anaesth
2006; 96:8–20.
3. Porter M, McCormick B. Anaesthesia for transurethral resection
of the prostate. Update in Anaesthesia 2003;16.Article 8.
4. Scheingraber S, Heitmann L, Werner W, et al. Are there acid
base changes during transurethral resection of the prostate?
QUESTIONS Anesth Analg 2000;90:946–950.
5. Ghanem AN, Ward JP. Osmotic and metabolic sequelae of vol-
umetric overload in relation to the TURP syndrome. Br J Urol
1. What key precautions can surgeons and anesthetists
1990;66:71–78.
take to prevent the occurrence of TURP syndrome? 6. Ayus JC, Krothapalli RK, Arieff AI. Treatment of symptomatic
Answer: The likelihood of developing TURP syndrome hyponatremia and its relation to brain damage. N Engl J Med
can be lessened by limiting the surgical procedure’s 1987;317:1190–1195.
duration, by reducing the height and thus pressure of 7. Beal JL, Freysz M, Berthelon G, et al. Consequences of fluid
the irrigating solution, by attempting to preserve the absorption during transurethral resection of the prostate using
prostatic capsule during the resection, by ensuring the distilled water or glycine 1.5 per cent. Can J Anaesth 1989;36:
278–282.
patient is optimally hydrated preoperatively, and com- 8. Crowley K, Clarkson K, Hannon V, et al. Diuretics after
pensating for intraoperative blood loss (often difficult to transurethral prostatectomy: a double-blind controlled trial com-
appreciate). As continuous absorption of irrigating fluid paring frusemide and mannitol. Br J Anaesth 1990;65:337–341.
may be assumed, only minimal volumes of Na contain- 9. Hahn RG. Smoking increases the risk of large-scale fluid ab-
ing maintenance intravenous fluids should be infused sorption during transurethral prostatic resection. J Urol 2001;
during the procedure. 166:162–165.
15259_Ch47.qxd 3/15/09 6:34 AM Page 175
CHAPTER 47
Anesthesia and Sleep-Disordered

Breathing
Leon Serfontein
airway management and intubation should be considered in

patients with known or suspected OSA.4
OSA is a syndrome characterized by periodic, partial, or
A 47-year-old, 5⬘ 7⬙, 85-kg (body mass index, 29.4 kg/m2)
complete obstruction of the upper airway during sleep. There
male was scheduled for a semiurgent posterior cervical
are practice guidelines for the perioperative management of
discectomy following acute C7–8 disc herniation with
patients with OSA.16 A good starting point is to stratify the pa-
radicular symptoms to his right hand.
tients using the terms mild, moderate, and severe as defined by
The patient had a history of chronic “neck problems”
the laboratory where the study was done.16
requiring intermittent use of nonsteroidal anti-inflammatory
drugs for analgesia. He had no other medical problems
of note. He had smoked 10 to 15 cigarettes a day for
Which important details in the patient’s history
20 years. Ten years previously, he had undergone gen-
need to be investigated to support the
eral anesthesia for an inguinal hernia repair, after which
diagnosis of OSA?
he had awoken with a very sore, hoarse throat. He was
told subsequently that it had been “very difficult to insert Symptoms and signs of OSA are listed in Table 47.1. The
the breathing tube.” No notes or further details of the strongest of these associations are snoring, witnessed apneas,
event were available. The patient was taking an herbal and obesity. Other risk factors include male gender,12 aging,13
throat spray at night, which he believed helped reduce menopausal status,14 black race,15 alcohol, and smoking.
snoring.
On examination, the patient was of stocky build and
slightly overweight with a potentially difficult airway on as- Given the fact that no formal diagnosis of OSA
sessment (Mallampati grade III, thyromental distance 6 cm, can be made at this time, how should this
a short neck with a large circumference and limited mobil- patient be managed?
ity especially on extension). His blood pressure was This patient should be managed as if he has OSA. Up to
150/90 mm Hg, and his pulse rate was 85 beats per 20% of adults have at least mild OSA.6 In a substantial num-
minute. All other clinical observations were normal. ber of these patients, the condition remains undiagnosed and
The laboratory investigations were as follows: full untreated.5
blood count, hemoglobin, 16.8 g/dL; hematocrit, 0.51; Ideally, the severity of OSA may be determined by sleep
platelets, 218 ⫻ 109/L; electrolytes, normal. The electro- studies. If a sleep study is not available, such patients should be
cardiogram reading showed no abnormalities. treated as if they have moderate sleep apnea unless one or more
of the signs or symptoms is severely abnormal (e.g., markedly
increased body mass index or neck circumference, respiratory
pauses that are frightening to the observer), in which case
they should be treated as if they have severe sleep apnea.16
In addition, polycythemia in this patient’s case may indicate
What conclusions derived from the assessment severe OSA.
could have important implications for this If a sleep study had been done, the results should be used
patient’s perioperative management? to determine the perioperative anesthetic management of a
• The likelihood of difficulty in airway management and/or patient. Because procedures differ among laboratories, the
intubation. American Society of Anesthesiologists’ Task Force on
• High suspicion of previously undiagnosed obstructive sleep Perioperative Management of Patients with OSA recommends
apnea (OSA). The presence of polycythemia may indicate that stratification of OSA should be done using the terms none,
severe OSA (Table 47.1). mild, moderate, or severe as defined by the laboratory where
the study was done rather than the actual apnea-hypopnea
index (the number of episodes of sleep-disordered breathing
What is the relationship between difficult per hour). If this is not indicated, it may be approximated as
intubation and OSA? shown in Table 47.2.
Patients with difficult airways are at substantially increased An anesthetic plan was discussed with the patient. He was
risk of OSA.3 Conversely, the possibility of difficulty with told that an awake fiberoptics-assisted intubation would be
175
15259_Ch47.qxd 3/15/09 6:34 AM Page 176
176 CHAPTER 47 • ANESTHESIA AND SLEEP-DISORDERED BREATHING
T A B L E 4 7 . 1 Symptoms7,9 and Signs10 T A B L E 4 7 . 2 Statification of Patients with

Associated With Increased Risk Obsructive Sleep Apnea9
of Obstructive Sleep Apnea11
Severity of OSA Adult AHI Pediatric AHI
Snoring (prominent, habitual) Obesity None 0–5 0
Witnessed apneas Increased neck Mild OSA 6–20 1–5
(gasping/choking) circumference Moderate OSA 21–40 6–10
Excessive/persistent daytime Hypertension Severe OSA ⬎40 ⬎10
sleepiness
AHI, apnea-hypopnea index; OSA, obstructive sleep apnea.
Family history Presence of difficult Reproduced with permission from Gross JB, Bachenberg KL,
airway predictors Benumof JL, et al. Practice guidelines for the perioperative manage-
Right heart failure* ment of patients with obstructive sleep apnea: a report by the
American Society of Anesthesiologists Task Force on Perioperative
Polycythemia* Management of patients with obstructive sleep apnea. Anesthesiology
2006;104:1081–1093.
*Severe obstructive sleep apnea.
performed. The patient was very anxious and requested pre- the airway, an orotracheal tube 8.5 was inserted with
medication. Diazepam 10 mg was prescribed orally. fiberoptic assistance. Anesthesia was induced with propofol
and maintained with sevoflurane delivered in a mixture of
50:50 oxygen:nitrous oxide. Vecuronium 8 mg was given
Assuming that the patient is likely to suffer for muscle relaxation. Following prone positioning, the sur-
from OSA, what would be the advantages of gery proceeded uneventfully and was finished 2 hours later.
using an asleep technique for instrumenting the Throughout the course of the surgery, the patient received
airway? paracetamol 2 g, diclofenac sodium 75 mg, and morphine
Provided that spontaneous ventilation is maintained, or the 8 mg intravenously.
ability to ventilate the patient is confirmed before a long-acting
muscle relaxant is given, advantages include: (a) eliminating
the need for sedation (awake technique) and (b) the ability to What are the important safety considerations
better gauge the potential for or the degree of obstruction and when extubating this patient’s trachea?
the likelihood of requiring devices to improve airway patency • Full reversal of neuromuscular blockade should be ensured
postoperatively (e.g., nasal airway, continuous positive airway and neuromuscular recovery should be ascertained (prefer-
pressure machine). ably with a nerve stimulator) before extubation.
• Extubation should occur with an oral or nasopharyngeal
airway in place and only after spontaneous ventilation is
What are the main considerations regarding established and the patient is conscious (rousable).
the choice of drugs used for anesthesia and • The preferred recovery position for the patient is the lat-
analgesia in this patient in the perioperative eral posture.1 Placing his head in the sniffing position and
period? displacing the mandible forward will further reduce the
• Premedication with sedatives or opioids should ideally be tendency for airway collapse.2
avoided. • Continuous positive airway pressure therapy should be ap-
• Drugs used during general anesthesia should be chosen and plied if obstruction occurs despite the simple measures men-
dosed in such a way to minimize the extent and duration of tioned in this list (and in all cases of diagnosed OSA whereby
any inhibitory effect on this patient’s ability to maintain the therapy has been prescribed or used preoperatively).
normal airway patency and ventilation postoperatively.
After reversal of neuromuscular blockade, the patient was
• The provision of adequate postoperative analgesia should
extubated awake in the supine position. In the recovery area,
be accomplished in a multimodal fashion to reduce the need
he complained of pain and was given a further 4 mg of mor-
for opioids. This includes the use of paracetamol, nons-
phine in incremental doses. He desaturated a number of
teroidal anti-inflammatory drugs, and local anesthetics for
times to as low as 92%, and the anesthesiologist decided that
incision infiltration. This patient would have conceivably
supplemental oxygen should be continued on the ward.
benefited from wound infiltration with a long-acting local
After a stable period of around 45 minutes, the patient was
anesthetic.
sent back to the ward. Approximately 6 hours after admis-
In the anesthetic induction room on the morning of sur- sion to the ward, the patient was found by a nurse to be
gery, a 14-g cannula was inserted. Midazolam 4 mg and fen- unarousable, with minimal breathing efforts and a SpO2 of
tanyl 100 mg were given intravenously in incremental doses, 70%. His radial pulse was palpable, and his blood pressure
as well as glycopyrrolate 200 ␮g. Following topicalization of was 85/55 mm Hg.
15259_Ch47.qxd 3/15/09 6:34 AM Page 177
CHAPTER 47 • ANESTHESIA AND SLEEP-DISORDERED BREATHING 177
After an unsuccessful attempt at intubation by the anes-

KEY MESSAGES
thetic trainee on call, a laryngeal mask airway was inserted,
and a total of 800 mcg naloxone was given in increments in-
1. OSA is a syndrome characterized by periodic, partial,
travenously. The patient responded well to these measures
or complete obstruction of the upper airway during
over the course of the next 20 minutes. He subsequently re-
sleep.
moved the laryngeal mask airway himself. The patient was
2. Patients with difficult airways are at substantially
taken to the intensive care unit fully conscious with a SpO2 of
increased risk of OSA.3 Conversely, the possibility
96% on a 35% oxygen mask and recovered from the event
of difficulty with airway management and intubation
with no permanent sequelae.
should be considered in patients with known or
suspected OSA.4
What simple measures could have 3. Practice guidelines exist for the perioperative manage-
minimized/prevented this complication? ment of patients with OSA.16 They target the preoper-
ative assessment (risk stratification) and preparation,
• Although supplemental oxygen is mandatory in the postop-
intraoperative (choice of anesthesia technique), and
erative period, to the inexperienced observer, this may mask
postoperative management (analgesia, oxygenation,
the presence of obstructive episodes by reducing recurrent
patient positioning and monitoring).
desaturation. This may have been the case in this patient.
• Patient positioning: The literature supports an improvement
in apnea-hypopnea index scores when adult patients with
OSA sleep in the lateral, prone, or sitting positions rather gabapentin 1200 mg or less decreased pain intensity at 6 and
than the supine position in the nonperioperative setting. 24 hours postoperatively. Twenty-four-hour cumulative opi-
This would suggest that positional measures may be of use oid consumption was also significantly reduced.17
to prevent airway collapse even in the postoperative setting, It is likely that this patient would have benefited from
although the literature does not provide specific guidance in gabapentin 900 mg administered 1 to 2 hours before surgery,
this regard. It is unclear if this patient was encouraged to and the advantages include anxiolysis, decreased pressor re-
maintain a sitting or lateral posture postoperatively. sponse to intubation, and less acute postoperative pain.
• An appropriate postoperative nursing environment is crucial. Repeated doses, however, carry the risk of increased sedation
This patient should have ideally spent his recovery period in and withdrawal phenomenon.
a high-dependency area. Airway patency was likely to deteri- Another option for this patient would have been a remifen-
orate postoperatively because of residual levels of anesthetic tanil infusion used for sedation during fiberoptic intubation.
agents, opioid analgesics, or drugs used for sedation.
• Monitoring: The literature is insufficient to offer guidance
regarding the appropriate duration of postoperative respi- QUESTIONS
ratory monitoring in patients with OSA. However, hospi-
talized patients who are at increased risk of respiratory 1. How is OSA defined?
compromise from OSA should have continuous pulse Answer: OSA is defined as cessation of airflow for
oximetry monitoring after discharge from the recovery ⬎10 seconds despite continuing ventilatory effort, 5 or
room. If frequent or severe airway obstruction or hypox- more times per hour of sleep, and usually associated with
emia occurs during postoperative monitoring, initiating a decrease in SaO2 of ⬎4%.
nasal continuous positive airway pressure or nasal intermit-
tent positive pressure ventilation should be considered.16 2. What symptoms and signs are associated with an
increased risk of OSA?
Would there be an alternative to 3. Which predictors for difficult mask ventilation are
benzodiazepines in this case? commonly associated with OSA?
Gabapentin, as a potential multimodal perioperative drug, Answer: History of snoring, obesity, and advanced age
would have been a more suitable drug choice. Since its intro- are commonly associated with OSA.
duction in 1993 as an adjunctive anticonvulsant, its use has
extended into more acute situations, particularly in the peri- Snoring (prominent, habitual) Obesity
operative period. Witnessed apneas Increased neck
Gabapentin is known to decrease preoperative anxiety; sig- (gasping/choking) circumference
nificantly lower Visual Analog Scale anxiety scores have been Excessive/persistent daytime Hypertension
shown in patients given gabapentin as opposed to placebo be- sleepiness
fore knee surgery.17 Gabapentin has been proven to blunt he-
Family history Presence of difficult
modynamic response to laryngoscopy and intubation. Patients
airway predictors
receiving 800 mg of gabapentin 1 hour before surgery had sig-
Clinical features of
nificantly decreased mean arterial pressure and heart rate dur-
right heart failure*
ing the first 10 minutes after endotracheal intubation com-
Clinical features of
pared with either 400 mg gabapentin or placebo.17
polycythemia*
A meta-analysis of gabapentin administration for acute
postoperative pain showed that a single preoperative dose of *Severe OSA.
15259_Ch47.qxd 3/15/09 6:34 AM Page 178
178 CHAPTER 47 • ANESTHESIA AND SLEEP-DISORDERED BREATHING
References 10. Ballieres Clin Endocrinol Metab 1994; 8: 601–28. Flemons WW.
Clinical practice. Obstructive sleep apnea. New Engl J Med 2002;
1. Isono S, Tanaka A, Nishino T. Lateral position decreases col- 347:498–504.
lapsibility of the passive pharynx in patients with obstructive 11. Davies RJ, Ali NJ, Stradling JR. Neck circumference and other
sleep apnea. Anesthesiology 2002;97:780–785. clinical features in the diagnosis of obstructive sleep apnoea syn-
2. Connolly LA. Anesthetic management of obstructive sleep apnea drome. Thorax 1992;47;101–105.
patients. J Clin Anesth 1991;3:461–469. 12. Pillar G, Malhotra A, Fogel R, et al. Airway mechanisms and ven-
3. Hiremath AS, Hillman DR, James AL, et al. Relationship be- tilation in response to resistive loading during REM sleep: the influ-
tween difficult tracheal intubation and obstructive sleep apnoea. ence of gender. Am J Respir Crit Care Med 2000;162: 1627–1632.
Br J Anaesth 1998;80:606–611. 13. Bixler EO, Vgontzas AN, Ten Have T, et al. Effects of age on
4. Siyam MA, Benhamou D. Difficult endotracheal intubation sleep apnoea in men: prevalence and severity. Am J Crit Care
in patients with sleep apnea syndrome. Anesth Analg 2002;95: Med 1998;157:144–148.
1098–1102. 14. Young T. Menopause, hormone replacement therapy, and sleep-
5. Phillips B. Sleep apnoea: underdiagnosed and undertreated. disordered breathing: are we ready for the heat? Am J Respir
Hospital Practice 1996;31: 193–194. Crit Care Med 2001;163:597–598.
6. Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive 15. Redline S, Tisher PV, Hans MG, et al. Racial differences in
sleep apnea: a population health perspective. Am J Respir Crit sleep-disordered breathing in African-Americans. Am J Respir
Care Med 2002;165:1217–1239. Crit Care Med 1997;155:186–192.
7. Grunstein RR, Wilcox I. Sleep-disordered breathing and obesity. 16. Gross JB, Bachenberg KL, Benumof JL, et al. Practice guidelines
Ballieres Clin Endocrinol Metab 1994;8:601–628. for the perioperative management of patients with obstruc-
8. Davies RJ, Stradling JR. The relationship between neck tive sleep apnea: a report by the American Society of
circumference, radiographic pharyngeal anatomy, and the Anesthesiologists Task Force on Perioperative Management of
obstructive sleep apnoea syndrome. Eur Respir J 1990;3: patients with obstructive sleep apnea. Anesthesiology 2006;104:
509–514. 1081–1093.
9. Hillman DR, Platt PR, Eastwood PR. The upper airway during 17. Kong VKF, Irwin MG. Gabapentin: a multimodal perioperative
anaesthesia. Br J Anaesth 2003;91:31–39. drug? Br J Anaesth. 2007;99:775–786.
15259_Ch48.qxd 3/15/09 6:36 AM Page 179
CHAPTER 48
Herbal Medicine and Anesthesia
Ashit Bardhan and Craig Dunlop
CASE FORMAT: REFLECTION sac compression. In the absence of objective neurologic

signs, the patient was managed conservatively, with anal-
A 33-year-old woman presented at term in spontaneous gesia as required and mobilization as tolerated.
labor, requesting analgesia. She had previously had a nor- The patient’s history was reviewed for possible risk
mal vaginal delivery, during which she had received effec- factors for epidural hematoma. At this stage, she admitted
tive epidural analgesia. She had no significant medical to taking oral Arnica when labor began to “reduce per-
problems, had experienced an uneventful pregnancy, had ineal bruising and aid healing following delivery.” She
no allergies, and denied taking any medications. Epidural had omitted to mention this at the time, as she felt that
analgesia was offered and informed consent was obtained. herbal remedies were safe and were not classified as med-
After establishing intravenous access, an epidural icines. By the time of the epidural insertion, she had taken
catheter was inserted aseptically on the first attempt in the three doses of two tablets. Examination of the packaging
L3–4 interspace. Effective analgesia was obtained. The pa- revealed no information as to active constituents. An
tient had an uneventful labor and gave birth about 6 hours Internet search suggested that Arnica montana contained
later to a live male infant by normal vaginal delivery. “coumarin derivatives” and may potentiate anticoagulant
Before discharge from the labor ward, the epidural effects. More formal evidence was limited to a journal let-
catheter was removed. She remained an inpatient for an- ter stating that ingestion may result in an anticoagulant
other day before being discharged home. effect from coumarin constituents.1
The following day at home, the patient began to de- The patient’s symptoms improved over the course of
velop central back pain and an associated headache. Both 4 days, and she was discharged home. She was reviewed
were relieved with simple analgesia including paracetamol 3 weeks later and had complete pain resolution.
and diclofenac. She did not seek medical attention at this
point. The headache did not recur, but the back pain re-
turned and gradually increased in severity over the subse-
quent 48 hours. By this stage, she was in severe pain with DISCUSSION
restricted mobility and presented to the emergency depart-
ment for review. She was afebrile and generally well, Complementary and alternative medicine is increasing in pop-
reported no altered sensation or weakness of the lower ularity, encompassing herbal and dietary supplements as well
limbs, and no symptoms of bladder or bowel disturbance. as alternative medical theories such as homeopathy and tradi-
Examination revealed tenderness over the epidural inser- tional Chinese medicine. Estimates of usage in patients vary
tion site with no neurologic signs in the lower limbs. She re- from 4.8% to 42%.2–6 Of these percentages, approximately
quired opiate analgesia to provide effective pain relief. 70% of patients are thought to not routinely disclose their
The patient’s blood test results were as follows: hemo- usage to medical staff,4 as in the patient described in this case.
globin, 12.6 g/dL; white blood cell count, 13.5 ⫻ 109/L The danger lies with the assumption that the term natural is
elevated; neutrophils, 10.22 ⫻ 109/L (elevated); platelets, synonymous with safe. A survey of herbal medicine use in par-
220 ⫻ 109/L; erythrocyte sedimentation rate, 83 mm/hr turients showed that only 14.6% of those using herbal reme-
elevated; international normalized ratio, 1.0; activated dies considered them to be medications.2
partial thromboplastin time, 30 seconds; sodium, 133 Although the therapeutic profile of Arnica provides a pos-
mmol/L; potassium, 3.9 mmol/L; urea, 4.8 mmol/L; and sible explanation as to the occurrence of epidural hematoma in
serum creatinine, 64 mmol/L. the patient in this case, a causal relationship could not be ret-
A differential diagnosis of epidural abscess or rospectively ascertained. Also, she would have been likely to
epidural hematoma was considered, and the patient was be offered an epidural even if the information regarding
admitted for further investigation and analgesia. An urgent Arnica usage had been provided. A coagulation screen before
neurosurgical consultation was requested, and a magnetic insertion may have been prudent.
resonance imaging scan of the lumbar spine was per- Under United States law, herbal and homeopathic medica-
formed (Fig. 48.1). tions are classified as dietary supplements, thus exempting
The magnetic resonance imaging scan revealed an them from regulations applicable to the introduction of pre-
epidural hematoma located at L3–4 with significant thecal scription medicines.7 The effect of this classification is to rein-
force the belief that they are not drugs and additionally has
179
15259_Ch48.qxd 3/15/09 6:36 AM Page 180
180 CHAPTER 48 • HERBAL MEDICINE AND ANESTHESIA
and examined the incidence of adverse events in the perioper-

ative period.16 In their population, 80% of patients took self-
prescribed traditional Chinese herbal medicine, and they
found an increased risk of adverse effects in the preoperative
period including hypokalemia and prolonged activated partial
thromboplastin time. No significant association was found
between the use of any type of traditional Chinese herbal
medicine and the occurrence of either intraoperative or post-
operative events.
There is little information regarding guidelines for manag-
ing patients taking herbal medications in the perioperative
period. The American Society of Anesthesiologists has pub-
lished a leaflet for doctors containing information about more
commonly encountered substances,7 as well as an information
leaflet for patients.17 Awareness of the risks and direct ques-
tioning, along with patient education, remain the cornerstone
of management.
KEY MESSAGES
1. The use of herbal medicine is often not reported to

medical staff.
2. Although often assumed to be “natural” and thus
innocuous, herbal medicines may potentially have
significant adverse effects.
3. Manufacture of herbal medicines is not governed
by the same strict criteria as that of conventional
Figure 48.1 • Magnetic Resonance Image of the pharmaceuticals.
Spine, Lateral View. 4. Good quality evidence of therapeutic or adverse
effects of herbal medications is lacking, leading to
reliance on anecdotal incidents and case reports.
removed the incentive to generate evidence for therapeutic
or adverse effects. The presence and concentration of active
constituents is often extremely difficult to assess and may vary
among brands.8 Licensing requirements in the United
Kingdom are somewhat more rigorous but still fall short of QUESTIONS
preclinical animal and controlled clinical trials considered
standard in the pharmaceutical industry.9 1. What are the readily available herbal preparations that
Of the more well-known supplements, the effects of most may increase bleeding tendency?
concern in the perioperative period are those of cardiovascular Answer:
instability, drug interactions, altered coagulation, and altered • Garlic: Has antiplatelet effects and may potentiate
sedation. Ephedra (ma-huang) may precipitate hypertension warfarin resulting in an increase in international
and has been associated with cerebrovascular accidents, arrhyth- normalized ratio.
mias, myocardial infarction, and sudden cardiac death.10–12 • Ginger: Inhibits thromboxane synthetase, increasing
Garlic and ginkgo may alter platelet aggregation and prolong bleeding time.
bleeding times,13 while ginseng may have a procoagulant ef- • Ginkgo: May increase bleeding in patients taking anti-
fect.14 Kava, St. John’s Wort, and Valerian root may all increase coagulant or antithrombotic therapy.
sedative effects and prolong emergence.13 Diet may also pro- • Ginseng: Variable. May have antiplatelet properties,
voke serious adverse effects. Grapefruit juice is known to inhibit but may also reduce effectiveness of warfarin.
cytochrome CYP3A4, which plays a role in metabolism of • Also: Arnica, feverfew, vitamin E.7
statins and in this setting, may precipitate rhabdomyolysis.
Traditional Chinese herbal medicine may be even more 2. Which herbal products should be discontinued before
challenging in that patients may be prescribed complex com- surgery?
binations of ingredients, leading to difficulty in assessment of Answer: Garlic, ginseng, and Valerian root should be
what they are actually taking. Additionally, these herbal med- discontinued at least 1 week before surgery. St. John’s
icines commonly contain significant contaminants, such as Wort should be discontinued at least 5 days before sur-
heavy metals.15 One of the few prospective studies investigat- gery. Ephedra, ginkgo, Kava, and licorice should be
ing outcomes followed a cohort of 601 patients in Hong Kong discontinued at least 1 day beforehand.18
15259_Ch48.qxd 3/15/09 6:36 AM Page 181
CHAPTER 48 • HERBAL MEDICINE AND ANESTHESIA 181
3. Does St. John’s Wort decrease the efficacy of digoxin? 8. Harkey MR, Henderson GL, Gershwin ME, et al. Variability in
commercial ginseng products: an analysis of 25 preparations. Am
Answer: Yes. St. John’s Wort is a potent inducer of the J Clin Nutr 2001;73:1101–1106.
hepatic cytochrome P450 microsomal enzymes, thus 9. Medicines and Healthcare Products Regulatory Agency. Safety
increasing the metabolism of digoxin. This additionally of herbal medicinal products. 2002. Available at www.mhra.
affects levels of warfarin, theophylline, cyclosporine, gov.uk. Accessed: May 2008.
anticonvulsants, and antiretrovirals.10 10. Hodges PJ, Kam PC. The peri-operative implications of herbal
medicines. Anaesthesia 2002;57:889–899.
11. Drew A. Herbal medicines: ma huang. Current Therapeutics
July 2000;82–83.
References 12. Haller C, Benowitz N. Adverse cardiovascular and central nerv-
1. Shiffman MA. Warning about herbals in plastic and cosmetic ous system events associated with dietary supplements contain-
surgery (letter). Plast and Reconstr Surg 2001;108:2180–2181. ing ephedra alkaloids. N Engl J Med 2000;343:1833–1838.
2. Skinner CM, Rangasami J. Preoperative use of herbal medicines: 13. Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioper-
a patient survey. B J Anaesth 2002;89:792–795. ative care. JAMA 2001; 286:208–216.
3. Tsen LC, Segal S, Pothier M, et al. Alternative medicine use in 14. Yuan CS, Wei G, Dey L, et al. American ginseng reduces war-
presurgical patients. Anesthesiology 2000;93:148–151. farin’s effect in healthy patients: a randomized, controlled trial.
4. Kaye AD, Clarke RC, Sabar R, et al. Herbal medications: cur- Ann Intern Med 2004;141:23–27.
rent trends in anesthesiology practice—a hospital survey. J Clin 15. Kam PCA, Liew S. Traditional Chinese herbal medicine and
Anesth 2000;12:468–471. anaesthesia. Anaesthesia 2002;57:1083–1089.
5. Hepner DL, Harnett, M, Segal S, et al. Herbal medicine use in 16. Lee A, Chui PT, Aun CST, et al. Incidence and risk of adverse
parturients. Anesth Analg 2002;94:690–693. perioperative events among surgical patients taking traditional
6. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative chinese herbal medicines. Anesthesiology 2006;105:454–461.
medicine use in the United States, 1990–1997: results of a follow- 17. American Society of Anesthesiologists. What you should know
up study. JAMA 1998;280:1569–1575. about herbal and dietary supplement use and anesthesia. 2003.
7. American Society of Anesthesiologists. Considerations for anes- Available at www.asahq.com. Accessed: May 2008.
thesiologists: what you should know about your patients’ use of 18. Heyneman CA. Preoperative considerations: which herbal prod-
herbal medicines and other dietary supplements. 2003. Available ucts should be discontinued before surgery? Crit Care Nurse
at www.asahq.com. Accessed: May 2008. 2003;23:116–124.
15259_Ch49.qxd 3/15/09 6:39 AM Page 182
CHAPTER 49
Levosimendan and Acute

Heart Failure
Dorothy Breen
CASE FORMAT: REFLECTION 6 mcg/kg followed by an infusion of 0.2 ␮g/kg per minute
was administered. Six hours later, the patient developed
A 47-year-old female presented to the emergency depart- rapid atrial fibrillation at 130 beats per minute. Her blood
ment with increasing shortness of breath. In the preceding pressure remained stable, and she was treated with amio-
week, she had woken several times during the night unable darone. She also received potassium supplementation, as
to breathe or lie flat. The patient had no history of chest pain her plasma potassium concentration had decreased to
or palpitations, was well known to the cardiology service, 3.0 mmol/L. Over the next 24 hours, the patient’s dyspnea
and had a history of ischemic cardiomyopathy. Six years improved significantly, but her renal function continued to
previously, she had undergone coronary artery bypass graft deteriorate (Table 49.2).
surgery; she also had a pacemaker in situ. Her medications
were frusemide 20 mg twice per day, bisoprolol 10 mg
once per day, and enalapril 5 mg once per day. On exam-
ination, the patient was alert but cyanosed and in marked REVIEW
respiratory distress. Her respiratory rate was 35 beats per
minute; pulse,105 beats per minute, regular; and blood This patient presented with an episode of severe acute on
pressure, 130/75 mm Hg. On auscultation, crepitations chronic heart failure. Despite the frequency with which this
were audible at both lung bases. Examination of the car- clinical situation occurs, therapeutic options are limited, and as
diovascular system revealed an elevated jugular venous many as 25% of patients die within 6 months of presentation.1
pressure, displaced apex, and a third heart sound. The This patient was initially treated with oxygen, diuretics, and a
emergency physician administered 60% oxygen by face peripheral vasodilator. Current guidelines emphasize these
mask and 60 mg of frusemide intravenously. The following treatments as the cornerstones of therapy.2,3 Loop diuretics are
tests were ordered: arterial blood gases (Table 49.1), full by far the most common agents used in this setting despite the
blood count, urea, electrolytes, glucose, creatinine, liver lack of data from large clinical trials on their use.4 The absence
function tests, troponin level (Table 49.2), and an electro- of hypotension in this case facilitated the use of a vasodilator
cardiogram. The patient’s chest radiograph is shown in (glyceryl trinitrate). CPAP was well tolerated and alleviated
Figure 49.1. There was some clinical improvement, but the patient’s initial hypoxemia (Table 49.1).
oxygen saturation measured by pulse oximetry was 89%. It The onset of renal dysfunction is of concern. Inadequate
was decided to notify the intensive care team. Continuous renal blood flow caused by poor cardiac output and hypov-
positive airway pressure (CPAP) via face mask (positive olemia resulting from aggressive diuresis contributed in this
end-expiratory pressure, 10 cm water; 60% oxygen) and instance (Table 49.2). Short-term inotropic support is said to be
an intravenous infusion of glyceryl trinitrate were com- indicated when there is evidence of hypoperfusion (i.e., the
menced. In the intensive care unit, an echocardiograph was onset of renal dysfunction in this case). Dobutamine was the ini-
performed, and left ventricular ejection-fraction was tial agent chosen for this purpose. However, the evidence to
estimated at 20%. This was a notable reduction from previ- support the use of inotropes in this setting is not clear.5,6 ␤-
ous estimates. Troponin levels were not elevated, and there Agonists (e.g., dobutamine) and phosphodiesterase inhibitors
were no new changes on the electrocardiogram. Six hours (e.g., milrinone) are typically chosen for their ability to inodilate.
after admission, the patient was found to be tolerating CPAP More recently, levosimendan has received attention as a novel
well but desaturated rapidly if the mask was removed even inotrope for this purpose. Levosimendan enhances myocardial
for brief periods. In addition, her renal function had started sensitivity to calcium by binding to cardiac troponin C and does
to deteriorate. The intensivist reviewed her and commenced so in a calcium-dependent manner. Thus, the effect is greatest
dobutamine 5 ␮g/kg per minute. The following day, the pa- at times of high intracellular calcium concentration (i.e., during
tient still required face mask CPAP, glyceryl trinitrate, and systole) and least at times of low intracellular calcium concentra-
regular intravenous frusemide 60 mg three times daily. A tion (i.e., during diastole). Unlike other agents, levosimendan is
different intensivist was now on duty and found the situation capable of improving contractility without increasing myocar-
unchanged except that the patient’s renal parameters had dial oxygen demand. In addition, it activates adenosine triphos-
continued to deteriorate (Table 49.2). He decided to admin- phate-dependent potassium channels in vascular smooth muscle
ister levosimendan in place of dobutamine. A bolus dose of producing peripheral and coronary vasodilation. In theory,
these properties make levosimendan an ideal agent for use in
182
15259_Ch49.qxd 3/15/09 6:39 AM Page 183
CHAPTER 49 • LEVOSIMENDAN AND ACUTE HEART FAILURE 183
T A B L E 4 9 . 1 Arterial Blood Gases Taken in the

Emergency Room
FiO2 0.6 FiO2, 0.6;
via Venturi PEEP,10 cm
Face Mask Water via CPAP
pH (7.35–7.45) 7.64 7.62
PaCO2 (7.35–7.45) 31 mm Hg 33 mm Hg
PaO2 55 mm Hg 85 mm Hg
(85–100 mm Hg)
Bicarbonate 33 mmol/L 32 mmol/L
(22–26 mEq/L)
CPAP, continuous positive airway pressure; PEEP, positive end-expira-
tory pressure.
The most striking finding is hypoxemia, which corrects with the appli-
cation of CPAP via face mask. Note also that alkalemia is present. The
elevated bicarbonate level indicates metabolic alkalosis, but there is no
evidence of respiratory compensation; in fact, the PaCO2 is low. There
are two acid-base processes here: metabolic alkalosis and respiratory
alkalosis. The metabolic alkalosis is most likely caused by diuretic ther-
apy, and the respiratory alkalosis is caused by tachypnea resulting from
pulmonary edema.
Figure 49.1 • The Patient’s Chest Radiograph on

Admission. A pacemaker and evidence of previous sternotomy
are clearly seen. The heart is enlarged. There is a diffuse bilateral
infiltrate with Kerley B lines (predominantly at the right base).
The appearances are consistent with pulmonary edema.
T A B L E 4 9 . 2 Biochemical Results Obtained at 0, 12, and 24 Hours After Admission
Values Initial 12 Hours 24 Hours

Sodium (135–145 mmol/L) 130 131 133
Potassium (3.5–5.5 mmol/L) 3.1 3.5 3.0
Urea (3.0–8.0 mmol/L) 10 16 26
Creatinine (0.07–0.1 mmol/L) 0.10 0.14 0.16
Magnesium (0.7–1.0 mmol/L) 0.61 0.92 1.0
Bilirubin (␮mol/L) 6 11
GGT (0–50 U/L) 15 21
ALP (32–110 U/L) 44 32
LDH (110–250 U/L) 122 118
AST (0–40 U/L) 22 23
ALT (0–40 U/L) 26 34
Glucose (4.0–7.5 mmol/L) 6.3 14.6 8.2
Troponin (0.0–0.2 ng/mL) 0.03 0.05
BNP pg/mL 752 705 575
ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BNP, B-type natriuretic
peptide; GGT, ␥-glutamyl transferase; LDH, lactate dehydrogenase.
The initial presence of hyponatremia, hypokalemia, and hypomagnesemia indicate chronic loop diuretic use. At 12 hours, the
electrolyte abnormalities have been corrected, but the patient’s renal function has started to deteriorate. The result at 24 hours
shows a disproportionate elevation in the urea: creatinine ratio (normally, 50–100:1); this most likely represents dehydration
as a result of high-dose diuretic use. Hypokalemia recurs after levosimendan administration. Plasma BNP levels are elevated
to those seen in congestive cardiac failure, although there is some decline with therapy.
15259_Ch49.qxd 3/15/09 6:39 AM Page 184
184 CHAPTER 49 • LEVOSIMENDAN AND ACUTE HEART FAILURE
this patient. The deteriorating renal function prompted the sec- ventricular impairment similar to this case (ejection fraction
ond intensivist to change from dobutamine to levosimendan in ⱕ 35%). Patients in the levosimendan group had better symp-
the patient discussed in this case. tomatic improvement, greater decreases in plasma B-type
In the setting of acute heart failure, levosimendan is the natriuretic peptide (BNP) levels, and shorter duration of hos-
most widely studied inotrope to date. Encouraging results pital stay when compared with those who received placebo.12
from initial studies have fueled enthusiasm for the drug. The Patients taking levosimendan showed a trend toward a
RUSSLAN investigators explored the safety and efficacy of greater mortality at 90 days (35 deaths in the placebo group
levosimendan versus placebo in patients with left ventricular vs. 45 in the levosimendan group). Mortality was not a pri-
failure following myocardial infarction. Five hundred patients mary end point of REVIVE-11, but the outcome data seem
were randomized to receive either placebo or levosimendan in at odds with earlier smaller studies. Atrial fibrillation devel-
one of four different dosing regimens.7 Levosimendan oped in the patient described in this case following levosi-
administered at 0.1 to 0.2 ␮g/kg per minute had equivalent mendan administration. In REVIVE 11, atrial fibrillation,
incidences of hypotension and ischemia when compared with hypotension, and ventricular tachycardia occurred more fre-
placebo. Although not a primary end point, mortality was quently with levosimendan than with placebo.
lower in the levosimendan group at 14 days (11.7% vs. 19.6%) This patient had symptomatic improvement and a decrease
and 180 days (22.6% vs. 31.4%). in BNP levels when switched to levosimendan. To determine if
The LIDO trial examined 203 patients similar to the this result translates into improved survival, the evidence from
present case (low output heart failure and documented left larger outcome studies is needed.
ventricular ejection fraction ⬍0.35).8 Patients were randomly SURVIVE represents the largest outcome study to date of
assigned to receive either levosimendan (24 ␮g/kg bolus fol- levosimendan use in patients with acute decompensated heart
lowed by an infusion of 0.1 ␮g/kg per minute) or dobutamine failure.13 In this recently published randomized, double-blind,
(5–10 ␮g/kg per minute) each for 24 hours. The primary end international trial, 1327 patients were assigned to receive a
point of the trial was the proportion of patients showing he- 24-hour infusion of either dobutamine (5–40 ␮g/kg per
modynamic improvement as measured by ⱖ30% increase in minute) or levosimendan (bolus, 12 ␮g/kg followed by an in-
cardiac output and a ⱕ 25% reduction in pulmonary capillary fusion 0.1–0.2 ␮g/kg per minute). Despite a decrease in plasma
wedge pressure. A significantly greater proportion of patients BNP levels, there was no difference in mortality at 31 days
in the levosimendan group compared with the dobutamine (12% in the levosimendan group vs. 14% in the dobutamine
group (28% vs. 15%) reached this endpoint. Analysis of mor- group) or at 180 days (26% in the levosimendan group vs. 28%
tality data revealed a significantly greater mortality rate in the in the dobutamine group). It has been observed that the failure
dobutamine group at both 31 days (8% vs. 17%) and 180 days to demonstrate survival benefit in the SURVIVE study could
(26% vs. 38%). in part be attributed to the fact that some patients had low
Subgroup analysis in the LIDO trial showed that the use systolic pressure and may have been in cardiogenic shock, ren-
of ␤-blockers, as in the case described, enhanced the hemody- dering them unsuitable for treatment with levosimendan.10
namic effects of levosimendan but diminished those of dobu- The patient described in this case presented with severe acute
tamine. Furthermore, decreases in mean potassium levels on chronic heart failure. Subgroup analysis of the SURVIVE
were observed in the levosimendan group over the 24 hours data has shown that a trend toward a lower 31-day mortality
of the study. Despite initial supplementation, the patient’s rate was observed in those with a prior history of heart failure.
potassium levels fell with the administration of levosimendan Is levosimendan a better choice than dobutamine for the
in this case (Table 49.2). patient described here? Given the available evidence to date,
This study and others led to the inclusion of levosimendan no clear case can be made for a better outcome with the use of
for use in patients with symptomatic low-output cardiac fail- one agent over another. Proponents of levosimendan can be
ure without hypotension in the 2004 European heart failure reassured by the amount of data that exists when compared
guidelines.2 The durations of action of levosimendan and with other agents currently in use for acute heart failure.2,10
dobutamine differ. Levosimendan has an active metabolite Future trials should focus on subgroups that may benefit most
OR-1896 that has a long half-life. The clinical hemodynamic from levosimendan. Patients such as the woman described in
effects of levosimendan can persist for up to 7 to 9 days after this case (on ␤-blocker therapy, with acute on chronic heart
discontinuation of the drug. In this respect, the validity failure, and normotensive) represent a potential target popula-
of comparing a 24- hour infusion of levosimendan with a 24- tion for such further study.
hour infusion of dobutamine has been questioned.9
The CASINO study was designed to enroll 600 patients
with acute decompensated heart failure. Patients were ran- KEY MESSAGES
domized to receive a 24-hour infusion of levosimendan,
dobutamine, or placebo.5,10,11 The trial was terminated after 1. Levosimendan is a novel inodilator, and its mode of ac-
299 patients were enrolled because of improved outcome in tion is mediated via myocardial sensitization to calcium.
the levosimendan group. Mortality at 6 months was 18% for
the levosimendan group, 28.3% for the placebo group, and a 2. Smaller studies point to the safety and efficacy of lev-
remarkable 42% in the dobutamine group. osimendan in relieving symptoms, reducing BNP levels,
Two larger clinical trials have been designed to confirm and improving hemodynamic profile.
these initial positive findings regarding the use of levosimen- 3. The largest clinical trial to date failed to show a long-
dan. REVIVE-11 compared levosimendan with placebo in term mortality benefit when compared with dobutamine.
600 patients with acute decompensated heart failure and left
15259_Ch49.qxd 3/15/09 6:39 AM Page 185
CHAPTER 49 • LEVOSIMENDAN AND ACUTE HEART FAILURE 185
QUESTIONS 4. Allen LA, O’Connor CM. Management of acute decompensated

heart failure. Can Med Assoc J 2007;176:787–805.
5. De Luca L, Colucci WS, Nieminen MS, et al. Evidence-based
1. What is the mechanism of action of levosimendan? use of levosimendan in different clinical settings. Eur Heart J
Answer: Levosimendan is a positive isotrope which 2006;27:1908–1920.
enhances myocardial sensitivity to calcium by binding 6. Thackray S, Eastaugh J, Freemantle N, et al. The effectiveness
troporin C in a calcium sensitive manner. and relative effectiveness of intravenous inotropic drugs acting
through the adrenergic pathway in patients with heart failure: a
2. In patients with acute decompensated heart failure, meta-regression analysis. Eur J Heart Fail 2002;4:515–529.
does levosimendan confer a survival advantage 7. Moiseyev VS, Poder P, Andrejevs N, et al. Safety and efficacy of
compared to dobutamine? a novel calcium sensitizer, levosimendan, in patients with left
ventricular failure due to an acute myocardial infarction. A ran-
Answer: Probably not. The best evidence (SURVIVE domized, placebo-controlled, double-blind study (RUSSLAN).
TRIAL) indicates similar mortality for patients who re- Eur Heart J 2002;23:1422–1432.
ceived on or other of these drugs at 31 and 180 days. 8. Follath F, Cleland JG, Just H, et al. Efficacy and safety of intra-
venous levosimendan compared with dobutamine in severe low-
3. What is the duration of action of levosimendan? output heart failure (the LIDO study): a randomised double-blind
Answer: Although usually administered by continuous trial. Lancet 2002;360:196–202.
infusion, clinical hemodynamic effects can persist for 7 to 9. Delaney A, Bradford C, McCaffrey J, et al. Is there a place for
levosimendan in the intensive care unit? Crit Care Resusc 2007;9:
9 days after discontinuation of the infusion due to an ac-
290–292.
tive metabolite with a long elimination half life. 10. Cleland JG, Ghosh J, Freemantle N, et al. Clinical trials update
from and cumulative meta-analyses from the American college
of cardiology: WATCH, SCD-HeFT, DINAMIT, CASINO,
References INSPIRE, STRATUS-US, RIO-Lipids and cardiac resyn-
1. Mebazza A, Nieminen M, Packer M, et al. Levosimendan vs. chronisation therapy in heart failure. Eur J Heart Fail 2004;6:
dobutamine for patients with acute decompensated heart failure. 501–508.
The SURVIVE randomized trial. JAMA 2007;297:1883–1891. 11. Zairis MN, Apostolatos C, Anastasiadis P. The effect of a
2. Nieminen MS, Bohm M, Cowie MR, et al. ESC Committee for calcium sensitizer or an inotrope or none in chronic low output
Practice Guidelines (CPG). Executive summary of the guidelines decompensated heart failure: results from the calcium
on the diagnosis and treatment of acute heart failure: the task sensitizer or an inotrope or none in low output decompensated
force on acute heart failure of the European society of cardiology. heart failure (CASINO). J Am Coll Cardiol 2004;43:
Eur Heart J 2005;26:384–416. 206A–207A.
3. Heart failure society of America: HFSA 2006 comprehensive 12. Teerlink JR, Packer M, Colucci WS, et al. Levosimendan pro-
heart failure practice guidelines. Evaluation and management of vides rapid and sustained relief in patient global assessment of
patients with acute decompensated heart failure. J Card Fail acutely decompensated heart failure: the REVIVE 11 study. J
2006;12:86–103. Card Fail 2006;12:S86.
15259_Ch50.qxd 3/15/09 6:41 AM Page 186
CHAPTER 50
Antiplatelet Agents,
Low-Molecular-Weight Heparin,
and Neuraxial Blockade
Leon Serfontein
CASE FORMAT: REFLECTION applied. An intravenous 16-gauge cannula was inserted in

his left hand, followed by insertion of an epidural at the
A 67-year-old, 83-kg man diagnosed with a rectal carci- T9–10 interspace with the patient in the sitting position.
noma was scheduled for an abdominoperineal resection. Blood was aspirated through the epidural catheter and
On initial screening, there was no evidence of metastatic failed to clear on flushing or on incremental withdrawal of
disease. The patient had dyslipidemia, long-standing the catheter. The epidural catheter was reinserted at T8–9
well-controlled hypertension, and coronary artery dis- without complications. After administration of a negative
ease. Six months previously, he had presented to the test dose (lidocaine 2% with adrenaline 1:200,000 U/mL),
emergency department with chest pain and was diag- preoxygenation (100% oxygen tidal breathing for 3 min-
nosed with unstable angina for which he had undergone utes) was performed, and general anesthesia was induced.
coronary angioplasty with stenting of two vessels. Since The patient received fentanyl 100 ␮g, propofol 160 mg,
then, he had been angina-free and had good exercise tol- and vecuronium 8 mg intravenously. Anesthesia was main-
erance (able to walk briskly for 20 to 30 minutes and to tained with sevoflurane in air:oxygen (50:50). Another 16-
climb two flights of stairs without rest or shortness of gauge cannula was inserted in the patient’s right external
breath). He had stopped smoking after his cardiac event jugular vein. A bolus of bupivacaine 0.25% 10 mL was ad-
but admitted to smoking 10 to 15 cigarettes a day for ministered via the epidural catheter in divided doses
nearly 35 years prior to that. followed by an infusion of bupivacaine 0.125% with fen-
The patient was currently taking the following medica- tanyl 2 mcg/mL at 10 mL.hr⫺1. The surgical registrar
tions once per day: aspirin 150 mg, atorvastatin 20 mg, inserted a urinary catheter. After infusion of the first liter
diltiazem 360 mg, and esomeprozole 20 mg. He had dis- of Hartmann’s solution, paracetamol 2 g and diclofenac
continued clopidogrel 7 days previously as per the sur- 75 mg were administered intravenously.
geon’s instruction. As surgery proceeded, “generalized ooze” was noted
The patient’s cardiorespiratory examination was unre- in the operative field. The patient’s hemodynamic stability
markable. His vital signs were as follows: temperature, was maintained with intravenous fluids and intermittent bo-
36.7°C; pulse rate, 76 beats per minute; blood pressure, luses of phenylephrine (total, 400 mcg). Hartmann’s solu-
145/80 mm Hg; and respiratory rate, 18 breaths per tion (2500 mL), hydroxy-ethyl 6% (130:4) (500 mL), and
minute. two units of packed red blood cells were administered in-
The patient’s electrocardiogram reading revealed sinus traoperatively. The patient’s measured total blood loss was
rhythm with no evidence of ischemia or previous infarction, 1400 mL.
and his chest radiograph was normal. An echocardiogram At 12:00, the patient’s trachea was extubated, and he
performed after his stenting showed mild concentric left ven- was taken to the high-dependency unit. During the next
tricular hypertrophy, left ventricular ejection fraction of 60%, 24 hours, he complained of abdominal pain intermittently,
and normal valves. and bolus doses of bupivacaine 0.25% (6 mL each) were
The results of the patient’s blood work were as follows: administered per epidural with good effect. The patient
full blood count, normal (hemoglobin, 13.4 g/dl; platelets, also complained of weakness in his legs but was reassured
190 ⫻ 109/L); electrolytes, normal; coagulation screen, by the nurses that it was a normal effect of the epidural.
normal (international normalized ratio, 0.9; activated Upon instruction from the surgical team, enoxaparin 40 mg
partial thromboplastin time, 25 seconds); and cholesterol, subcutaneously was administered at 6:00 on the evening
6.5 mmol/L. of the operative day.
An anesthetic plan was discussed with the patient on At 3:00 PM on the first postoperative day, the patient
the evening before surgery. It was decided to place a tho- complained of back pain and was unable to move his lower
racic epidural catheter for perioperative pain management limbs. A magnetic resonance imaging scan was performed,
before inducing general anesthesia. As the patient was which identified a large epidural hematoma extending from
anxious, diazepam 10 mg was prescribed. It was noted T7 to T11. An emergency decompressive laminectomy was
that enoxaparin 40 mg had been administered subcuta- performed to evacuate the hematoma. The patient recov-
neously at 6:00 PM. ered with a degree of residual lower body muscle weakness
The patient arrived to the operating room at 8:30 and sensory loss, which improved partially over the course
on the following morning, and standard monitoring was of the subsequent 6 months.
186
15259_Ch50.qxd 3/15/09 6:41 AM Page 187
CHAPTER 50 • ANTIPLATELET AGENTS, LOW-MOLECULAR-WEIGHT HEPARIN 187
DISCUSSION greater risk of epidural hematoma. In the case of therapeutic

anticoagulation with LMWH, this time period should be fur-
ther extended to 24 hours.7 After the removal of an epidural
Antiplatelet Agents and Neuraxial catheter, a minimum of 2 hours should elapse before subse-
Blocks quent LMWH administration.7
Antiplatelet agents are commonly prescribed for primary and The previously mentioned guidelines apply to once-daily
secondary prevention of cardiovascular disease and to decrease dosing of LMWH, which was applied in the patient described
the incidence of acute cerebrovascular and cardiovascular herein and which approximates European practice. Although
events. Long-term dual therapy with aspirin and clopidogrel the biochemistry and pharmacology of LMWHs vary, there is
in this patient was indicated to maintain patency of his coro- a lack of comparative studies. Experience in Europe indicates
nary stents.1,2 that the incidence of epidural hematoma associated with dif-
In the case described, the anesthetist and the surgical team ferent LMWHs is similar.7
were confronted with the need to balance the risk of increased
blood loss if the antiplatelet agents were continued during the Managing High-Risk Patients
perioperative period, with that of coronary thrombosis if the The incidence of epidural hematoma is less than 1 in 150,000
drugs were stopped abruptly. In a meta-analysis of 41 studies epidurals and less than 1 in 220,000 spinal anesthetics.10 In pa-
evaluating aspirin-related bleeding risks in a wide range of tients receiving a LMWH, the incidence of epidural hematoma
surgical procedures, aspirin was found to increase the rate of is approximately 1 in 3000 patients undergoing continuous
bleeding complications (ranging from mild to severe) by a fac- epidural anesthesia and 1 in 40,000 patients undergoing spinal
tor of 1.5 without an increase in surgical mortality or morbid- anesthesia.11 Several patient characteristics have been associ-
ity (with the exception of intracranial surgery and possibly ated with an increased risk of developing spinal hematoma
transurethral prostatectomy).3 after neuraxial anesthesia (Table 50.1).12 Based on these, the
The well-established benefits of epidural anesthesia had patient in this case was at greater risk of this particular compli-
to be weighed against the rare but potentially devastating cation. He had received nonsteroidal anti-inflammatory drugs
complication of epidural hematoma.4,5 This decision should (aspirin and diclofenac) in conjunction with other anticoagu-
be made on an individual basis, but any attempt to make an lants and a vessel puncture on catheter insertion. Ideally, the
evidence-based decision is limited by the rarity of epidural subsequent dose of LMWH should be delayed for 24 hours
hematomata. The American (American Society of Regional after the traumatic puncture.6,7
Anesthesia and Pain Medicine) and European guidelines sum-
marize other evidence-based reviews and represent the collec-
tive experience of recognized experts in the field. T A B L E 5 0 . 1 Risk Factors for Developing
The elimination half-life of clopidogrel is short (4 hours),
Spinal Hematoma
but recovery from the drug is long (7 days) because of irre-
versible platelet inhibition.8 Neuraxial blockade is therefore Patient Factors
contraindicated in a patient who has taken clopidogrel within
seven days.7 In the case of the patient described herein, neu- Female gender
raxial block was appropriately performed 7 days after clopido- Increased age
grel had been discontinued. This interval should be extended Impaired hemostasis
to 14 days for ticlopidine, another thienopyridine derivative.6
Nonsteroidal anti-inflammatory drugs do not appear to Anatomic anomalies of spinal cord/vertebral column
add to the risks of neuraxial blockade, except when used in Anesthetic Factors
combination with other drugs that affect clotting mecha- Repeated, difficult needle/catheter placement
nisms.6 This patient received a low-molecular-weight heparin
(LMWH) preoperatively as well as aspirin. If a nonsteroidal Traumatic (bloody) punctures
anti-inflammatory drug were to be administered, a cyclooxy- Epidural (cf. spinal) technique
genase-2 selective inhibitor would have been a better choice in
Thromboprophylaxis Management Factors
this case because of its minimal effect on platelet function.6
LMWH with concomitant antiplatelet or
Timing of Needle Placement and anticoagulant administration
Catheter Removal LMWH administration in the presence of an
It is necessary to time epidural needle placement and catheter indwelling epidural catheter
removal relative to the timing of anticoagulant drug adminis- Immediate pre-, intra-, or early postoperative LMWH
tration. This patient was at moderate-to-high risk for develop- administration
ing venous thromboembolism, making LMWH an important
part of his management.9 Twice-daily LMWH dosing
Epidural needle insertion should be performed at least 10 LMWH, low-molecular-weight heparin.
to 12 hours after the preceding dose of LMWH. The same in- Modified from Horlocker TT, Wedel DJ, Benson H. Regional anesthe-
terval should be allowed to elapse from the last dose of sia in anticoagulated patients: defining the risks. Reg Anesth Pain Med
LMWH until the epidural catheter is removed. As will be 2003;28:172–198.
highlighted later, this step may have to be altered in patients at
15259_Ch50.qxd 3/15/09 6:41 AM Page 188
188 CHAPTER 50 • ANTIPLATELET AGENTS, LOW-MOLECULAR-WEIGHT HEPARIN
The provision of safe neuraxial anesthesia/analgesia concur- An indwelling epidural catheter should not be removed
rent with anticoagulation requires education of the entire pa- while the patient is therapeutically anticoagulated.
tient care team. Patients at increased risk should be identified by • Avoiding combinations of drugs (perioperatively) that
and to the responsible clinicians and nurses. One option in this independently alter coagulation.
case would have been to avoid greater concentrations (⬎1.25%)
2. What are the symptoms of cord compression from an
of bupivacaine for “top-ups,” thus allowing better assessment
epidural hematoma?
and earlier detection of neurologic dysfunction. Magnetic reso-
nance imaging is the diagnostic tool of choice for detecting Answer: Symptoms include severe back pain, new-onset,
epidural hematoma. Emergency decompressive laminectomy is or persisting sensory or motor deficit outlasting the
the treatment of choice.13,14 Overall, a less severe preoperative expected duration of the neuraxial block and bowel or
neurological deficit and early hematoma evacuation (within bladder dysfunction within the postoperative period.
6 hours) are associated with better neurological recovery.15,16 3. Following removal of an indwelling epidural catheter,
Newer and more effective anticoagulants are continuously how long is the wait before the next dose of prophylac-
being developed. Examples include the new synthetic pentasac- tic heparin could be safely administered?
charide fondaparinux, and razaxaban, each of which has potent
antifactor Xa activity and is intended for thromboprophylactic Answer: A minimum of 2 hours.
use. Because of their efficacy and longer elimination half-
lives, these drugs pose additional problems for the anesthetist. References
Alternative anesthetic and analgesic techniques should be con- 1. Burger W, Chemnitius JM, Kneissl GD, Rücker G. Low-dose
sidered for patients considered to be at unacceptably high risk aspirin for secondary cardiovascular prevention—cardiovascular
of epidural hematoma. Safer neuraxial alternatives such as risks after its preoperative withdrawal versus bleeding risks with
spinal (cf. epidural) anesthesia or peripheral nerve blockade are its continuation—review and meta-analysis. J Int Med 2005;257:
among these options. In general, superficial limb blocks, the 399–414.
anatomical landmarks for which are well defined or easily 2. Bergqvist D, Wu CL, Neal JM. Anticoagulation and neuraxial re-
visualized with ultrasound imaging and performed where a gional anesthesia: perspectives. Reg Anesth Pain Med 2003;28:163.
3. Rodgers A, Walker N, Schug S, et al. Reduction of postoperative
developing hematoma can be easily accessed and compressed,
mortality and morbidity with epidural or spinal anaesthesia: re-
are not contraindicated in patients receiving anticoagulation.7 sults from overview of randomised trials. Br Med J 2000;321:1.
4. ACC/AHA/SCAI Guideline update for percutaneous coronary
intervention. Executive summary. J Am Coll Cardiol 2006;47:
KEY MESSAGES 216–235.
5. AHA/ACC Guidelines for secondary prevention for patients
1. Neuraxial blockade is contraindicated in a patient with coronary and other atherosclerotic vascular disease: 2006
who has taken clopidogrel within 7 days. update. Circulation 2006;113:2363–2372.
6. Second Consensus Conference on Neuraxial Anesthesia and
2. Epidural needle insertion as well as epidural catheter Anticoagulation. April 25–28, 2002.
removal should be performed at least 10 to 12 hours 7. Horlocker TT, Wedel DJ, Benson H. Regional anesthesia in an-
after the preceding dose (prophylactic regimen) of ticoagulated patients: defining the risks. Reg Anesth Pain Med
LMWH. 2003;28:172–198.
8. Weber AA, Braun M, Hohlfeld T, et al. Recovery of platelet
3. Magnetic resonance imaging is the diagnostic tool of function after discontinuation of clopidogrel treatment in
choice for detecting epidural hematoma, and emergency healthy volunteers. Br J Clin Pharmacol 2001; 52:333–336.
decompressive laminectomy is the treatment of choice. 9. Anonymous. Practice parameters for the prevention of venous
thromboembolism. The Standards Task Force of The American
4. A less severe preoperative neurological deficit and Society of Colon and Rectal Surgeons. Dis Colon Rectum 2000;
early hematoma evacuation (within 6 hours) are associ- 43:1037–1047.
ated with better neurological recovery. 10. Horlocker TT, Wedel DJ, Schroeder DR, et al. Preoperative an-
tiplatelet therapy does not increase the risk of spinal hematoma
with regional anesthesia. Anesth Analg 1995;80:303–309.
11. Horlocker TT, Wedel DJ. Neuraxial block and low molecular-
QUESTIONS weight heparin: balancing perioperative analgesia and thrombo-
prophylaxis. Reg Anesth Pain Med 1998;23:164.
12. Horlocker TT, Wedel DJ. Anticoagulation and neuraxial block:
1. How could the risk of epidural hematoma associated historical perspective, anesthetic implications, and risk manage-
with neuraxial anesthesia be minimized? ment. Reg Anesth Pain Med 1998;23:129–134.
Answer: 13. Binder DK, Sonne DC, Lawton MT. Spinal epidural hematoma.
• Identifying patients at unacceptably high risk and Neurosurg Q 2004;14:51–59.
considering alternative anesthetic/analgesic techniques 14. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants
and spinal–epidural anesthesia Anesth Analg 1994;79:1165–1177.
such as peripheral nerve blocks when feasible.
15. Kreppel D, Antoniadis G, Seeling W. Spinal hematoma: a liter-
• Performing spinal anesthesia in preference to epidural ature survey with meta- analysis of 613 patients. Neurosurg Rev
anesthesia when possible. 2003;26:1–49.
• Timing needle insertion and epidural catheter removal 16. Lawton MT, Porter RW, Heiserman JE, et al. Surgical manage-
appropriately in the presence of perioperative anticoag- ment of spinal epidural hematoma: relationship between surgical
ulation (to occur at the nadir of anticoagulant activity). timing and neurological outcome. J Neurosurg 1995;83:1–7.
15259_Ch51.qxd 3/15/09 6:41 AM Page 189
CHAPTER 51
Neuroprotection During Cerebral

Aneurysm Surgery
Peter John Lee
CASE FORMAT: REFLECTION Shortly after administration of thiopentone 250 mg IV,

the patient’s blood pressure decreased to 80/45 mm Hg.
A 54-year-old, 65-kg woman presented to the emergency The nasopharyngeal temperature was 35.1° C. Arterial
department with sudden-onset severe headache, vomiting, blood gas, electrolyte, and glucose analysis were performed
and drowsiness. Her Glasgow Coma Scale score was 13. as shown here:
Computed axial tomography showed diffuse subarachnoid
hemorrhage (SAH) from an aneurysm. Four-vessel cerebral pH 7.37 Na⫹ 140 mmol/L⫺1
angiography was performed and revealed a ruptured pCO2 6.3 kPa K⫹ 5.1 mmol/L⫺1
aneurysm on the anterior communicating artery. Nimo-
pO2 11.3 kPa Cl⫺ 100 mmol/L⫺1
dipine 60 mg was administered to the patient orally, and
phenytoin 975 mg was administered intravenously over 20 HCO3⫺ 25 mmol/L Glucose 12 mmol/L⫺1
minutes. The patient was scheduled to undergo aneurysm BE 0 mmol/L
clipping on the following morning.
SaO2 96%
The patient had a 10-year history of hypertension for
which she took indapamide 2.5 mg and atenolol 25 mg After placement of the temporary clip, IV phenyle-
each morning. She denied symptoms of cardiac disease but phrine boluses of 50 ␮g were administered as required to
admitted to smoking 20 cigarettes each day for 20 years. maintain the patient’s blood pressure within a mean arte-
The patient denied cocaine use. rial pressure of 70 to 80 mm Hg. Ninety minutes later,
On arrival to the operating room, the patient’s GCS after placing the permanent clip on the aneurysm, the sur-
score had deteriorated to 11. Her blood pressure was geon removed the temporary clip. The total surgical blood
140/90 mm Hg, and her heart rate was 85 beats per loss was approximately 200 mL and was replaced with
minute. She had no focal neurological deficit. 250 mL colloid. Normal saline 2000 mL was administered
The results of a full blood picture, urea, electrolytes, and over the course of the operation. The surgery lasted for
blood glucose performed in the emergency department 150 minutes.
were all normal. Electrocardiograph and chest radiograph During surgical closure, the cooling blanket tempera-
readings were unremarkable. Two units of cross-matched ture setting was increased to 38°C. Fentanyl 200 ␮g was
blood were made available. administered at this time. The inspired concentration of in-
Standard monitoring was commenced in the operat- halational agent was decreased, and reversal of neuro-
ing room, and a 16-gauge intravenous (IV) cannula was muscular block was achieved using glycopyrrolate 500 ␮g
inserted (an 18-gauge IV cannula was already in situ). and neostigmine 2.5 mg. The patient’s trachea was extu-
A cannula was placed in the patient’s left radial artery bated when she demonstrated a satisfactory spontaneous
for arterial pressure monitoring. Fentanyl 150 ␮g IV was ventilatory pattern and nasopharyngeal temperature was
administered. Anesthesia was induced with propofol 37°C. Twenty minutes after discontinuing the inhalational
150 mg, and muscle relaxation was achieved with vecuro- agent, the patient had emerged sufficiently to obey com-
nium 8 mg. Following tracheal intubation, anesthesia was mands. She did not cough with extubation, and her blood
maintained with inhaled sevoflurane at one minimum alve- pressure was 135/92 mm Hg at the time.
olar concentration in an air/oxygen mixture. A nasopha- The patient was transferred to the postanesthesia care
ryngeal temperature probe was inserted, and a forced-air unit where she was noted to be drowsy but rousable with a
cooling blanket was placed on the patient, with the temper- Glasgow Coma Scale score of 14. She had no focal neuro-
ature set to 32°C. Immediately before pinning the patient’s logical deficit. Morphine was administered intravenously to
head in a Mayfield surgical frame, fentanyl 200 ␮g was a total of 8 mg, titrated to patient request, and she was trans-
administered IV, and her scalp was infiltrated with bupiva- ferred to the high-dependency unit for continued monitoring.
caine 0.5% 5 mL. Cerebral angiography 2 weeks after surgery showed
After incision of the dura and when optimal exposure obliteration of the aneurysm and no additional aneurysms.
was obtained, the surgeon announced his intention to The patient was maintained on nimodipine for 21 days
place a temporary clip on the A1 segment of the anterior after surgery and was discharged home having made a full
communicating artery. neurological recovery.
189
15259_Ch51.qxd 3/15/09 6:41 AM Page 190
190 CHAPTER 51 • NEUROPROTECTION DURING CEREBRAL ANEURYSM SURGERY
CASE DISCUSSION accumulation of lactic acid and decrease in pH. The buffering
capacity of the brain is exceeded, and reactive oxygen species
Cerebral aneurysms have a prevalence of 0.2% to 9.9% in the are generated leading to cell membrane rupture and neuronal
general population.1 The incidence of SAH resulting from necrosis. The hyperglycemia noted in this patient should have
ruptured cerebral aneurysms ranges from 6 to 16 per 100,000, been corrected.
depending on the population under study.2,3 In the United In clinical practice, it is advisable to avoid glucose-containing
States, this figure accounts for 25,000 to 30,000 cases of SAH solutions and to correct hyperglycemia aggressively (target
per year.4 concentration, 5–9 mmol/L⫺1) in patients with focal cerebral
The application of temporary clips to a cerebral artery dur- ischemia.
ing surgical exploration and repair of an intracranial Temperature
aneurysm is performed when the risk of rupture is high.
Temporary clipping causes a period of focal cerebral ischemia Hypothermia can offer some degree of neuroprotection in
and the anesthetist should institute measures for neuroprotec- focal and global ischemia. Early studies have shown that
tion in this situation. hypothermia decreases cerebral metabolic rate (CMR) in a
temperature-dependent fashion, with the greatest effect at
Neuroprotection very low temperatures (18°C–22°C) achievable only with car-
diopulmonary bypass. The effects of mild hypothermia (cool-
Neuroprotective strategies are intended to modify intra-
ing to 32°C–35°C) were found to be negligible. Reduction in
ischemic cellular and vascular biological responses to depriva-
brain temperature by 2°C to 4°C has been shown to be neuro-
tion of the cellular energy supply to increase tissue tolerance to
protective in rats. The protective effects of hypothermia are
ischemia and/or reperfusion resulting in improved outcome.5
more likely to be dependent on changes at several steps in the
Uncontrolled release of glutamate during ischemia and the
ischemic cascade than on change in CMR alone. Possible
consequent excessive stimulation of postsynaptic receptors are
mechanisms include suppression of glutamate release and de-
implicated in the initiation of neuronal injury, a process
crease in nitric oxide production leading to a reduction in free
known as excitotoxicity. Neuronal apoptosis occurs early dur-
radical-triggered lipid peroxidation. Disappointingly, a
ing ischemia and is responsible for some of the continued neu-
prospective trial has shown that short-duration intraoperative
ronal loss that is seen following the insult.
hypothermia (33°C) did not improve 3-month neurologic out-
Blood Pressure come after craniotomy for good-grade patients with aneurys-
mal subarachnoid hemorrhage.6
Maintaining a high normal cerebral perfusion pressure Hypothermia causes shivering with increased oxygen de-
(CPP) can augment collateral blood flow to the ischemic mand, is associated with arrhythmias and cardiac ischemia,
penumbra, minimize secondary injury, and result in im- decreased platelet activity, disordered coagulation, and in-
proved neurological outcome. This is particularly germane creased infection rate.
when a temporary clip has been applied, and collateral per- The conflicting nature of such study results as well as the
fusion to affected areas can occur through Willisian chan- paucity of prospective trials in the area leave many anesthetists
nels, pial-to-pial collaterals, or leptomeningeal pathways. unsure of hypothermia’s role in neuroprotection. The mild hy-
CPP should be maintained at a greater level in patients who pothermia achieved in the patient discussed in this case would
are chronically hypertensive and whose autoregulatory have provided little neuroprotection and may have contributed
curves are shifted to the right. It may be best to maintain the to the delay in emergence. A timely emergence is important so
blood pressure of such individuals close to their pre-SAH that prompt neurologic examination can be performed.
measurements. In this case, the anesthetist maintained the Without doubt, hyperthermia has adverse effects on the
mean arterial pressure between 70 to 80 mm Hg; in the postischemic brain. Spontaneous hyperthermia, common in
absence of accurate data on the patient’s baseline blood pres- the postischemic brain, is associated with poor outcome in
sure, this is acceptable management. humans and should be treated aggressively.7
Partial Pressure of Carbon Dioxide IV Anesthetic Agents
During periods of focal cerebral ischemia, ventilation should The protective effect of barbiturates in focal cerebral ischemia
be altered to ensure normocapnia. Hypercapnia can cause has been shown in one human trial and in numerous animal
intracerebral “steal” by preferentially vasodilating vessels trials.
in the noninjured area and decreasing intracellular pH. This effect is thought to be caused by suppression of the
Hypocapnia does not cause the putative inverse-steal phe- CMR, which produces a progressive decrease in electroen-
nomenon and can increase the size of the region at risk of cephalographic activity and a reduction in the rate of adeno-
ischemic damage. The hypercapnia seen in the arterial blood sine 5-triphosphate depletion. It may also result from cerebral
gas analysis in this case (pCO2, 6.3 kPa) should have been blood flow (CBF) redistribution to peri-ischemic areas, free
corrected promptly. radical scavenging, and potentiation of ␥-aminobutyric acid
activity.
Blood Glucose The potential for barbiturates to confer long-term neuro-
Hyperglycemia increases damage in focal ischemia and is an protection has not been investigated.
independent predictor of poor outcome in patients who have Propofol may have beneficial effects on cerebral physiol-
focal ischemic injury. During incomplete ischemia, glucose ogy. It decreases CMR and CBF. It can also protect the brain
is metabolized anaerobically by glycolysis, with a resultant against ischemic injury in rats. Neuroprotection by propofol
15259_Ch51.qxd 3/15/09 6:41 AM Page 191
CHAPTER 51 • NEUROPROTECTION DURING CEREBRAL ANEURYSM SURGERY 191
might result from a direct scavenging effect on reactive oxy- “Triple-H” Therapy
gen species generated during ischemia and reperfusion.8
Propofol, compared with nitrous oxide and fentanyl, decreases Vasospasm after surgery is a major cause of morbidity and
neuronal injury and favorably modulates apoptosis-regulating mortality following SAH. Constriction of the cerebral arterial
proteins for at least 28 days. This suggests that propofol could vasculature occurs as free subarachnoid blood under high
be neuroprotective over a long postischemic period, particu- pressure comes into contact with the surfaces of vessels, partic-
larly if the insult is mild.9 Because propofol has negative in- ularly in the basal cisterns. The mainstay of medical treatment
otropic and vasodilatory properties, it may decrease CPP if a of cerebral vasospasm, in addition to calcium channel block-
large dose is administered rapidly. ade with nimodipine, is “triple-H” therapy: hypervolemia
Ketamine increases intracranial pressure, CMR, and CBF. (an increase in the volume of circulating plasma), induced
However, it also inhibits glutamatergic neurotransmission at arterial hypertension, and hemodilution. Postoperative
the N-methyl-D-aspartate receptor, which is highly activated “triple-H” therapy has been used in many centers, on the basis
by the excitatory transmitter release that occurs during is- that it augments CBF, prevents delayed ischemia, and im-
chemia. There are no human data supporting the use of keta- proves clinical outcome. However, the efficacy of “triple-H”
mine in brain protection. therapy has not been proven by prospective study.13 Although
Lidocaine blocks apoptotic cell death in vitro, and, in an- induced hypertension results in a significant increase in
tiarrhythmic doses, it decreases infarct size and improves neu- regional CBF and brain tissue oxygenation, hypervolemia/
rologic outcome in a rat model of transient ischemia.10 Opioids hemodilution induce only a slight increase in regional CBF,
(such as fentanyl, used in this case) are useful adjuncts as they while brain tissue oxygenation does not improve14 (Table 51.1).
limit the need for higher-dose volatile anesthetics with atten-
dant cerebral vasodilation and increased CBF. Evidence as to
whether opioids produce neuroprotection is lacking. The KEY MESSAGES
short half-life of fentanyl in moderate doses allows timely
postsurgical neurological evaluation. 1. Maintaining a high normal CPP can augment collat-
The use of thiopentone in this patient was appropriate. eral blood flow to the ischemic penumbra, minimize
Propofol can also be used as a neuroprotective agent and can secondary injury, and result in improved neurological
circumvent the delayed emergence seen with large doses of outcome.
barbiturates. 2. Hyperglycemia increases damage in focal neurologic
Inhalational Anesthetic Agents ischemia and is an independent predictor of poor out-
come in patients who have focal ischemic injury.
Inhalational anesthetic agents can decrease ischemic cerebral 3. Hyperthermia has adverse effects on the postischemic
injury. Both halothane and sevoflurane reduce the volume of brain.
infarction after focal ischemia.11 This occurs because these 4. The efficacy of “triple-H” therapy (hypervolemia ⫺[an
agents attenuate excitotoxicity by inhibiting glutamate release increase in the volume of circulating plasma], induced
and postsynaptic glutamate receptor-mediated responses. The arterial hypertension, and hemodilution) has not been
neuroprotection offered by isoflurane, and possibly other in- proven by prospective study.
halational agents, appears to be short-lived; a reduction in
neurologic injury is seen when evaluated at 2 days but not
14 days after ischemic injury.12
Like the barbiturates, most inhalational anesthetic agents
produce progressive electroencephalographic depression in a QUESTIONS
dose-dependent manner, with a similar reduction in CMR.
Halothane is a potent cerebral vasodilator that can produce 1. What is neuroprotection?
a marked increase in intracranial pressure. Hyperventilation Answer: Neuroprotection is modification of intraischemic
can be used to prevent this increase but must be instituted be- cellular and vascular biological responses to deprivation of
fore introducing the halothane, as the vasodilatory effects the cellular energy supply to increase tissue tolerance to is-
occur faster than the onset of metabolic suppression. chemia and/or reperfusion resulting in improved outcome.
Enflurane is a less potent cerebral vasodilator and more potent
depressant of CMR. Greater doses of enflurane produce cere- 2. What is the best ventilatory strategy to use during
bral seizure activity when combined with hypocarbia. general anesthesia for cerebral aneurysm repair?
Isoflurane is the least potent cerebral vasodilator and most ef- Answer: Ventilation should be carried out to achieve
fectively decreases CMR. Greater intracranial pressure in- normocapnia. Hypercapnia can cause intracerebral “steal”
creases with its use, hyperventilation minimizes the effect and by preferentially vasodilating vessels in the noninjured
can be safely instituted after introduction of the agent. area and decrease intracellular pH. Hypocapnia can
Desflurane and sevoflurane have similar properties to isoflu- increase the size of the region at risk of ischemic damage.
rane. The lower blood-gas solubility of desflurane and
sevoflurane allow more prompt awakening. 3. What inhalational agents are suitable for use in a case
Interestingly, sevoflurane has been shown to provide in which neuroprotection is desirable?
longer-term protection in an experimental model of focal cere- Answer: Desflurane and sevoflurane are suitable for use
bral ischemia. The use of sevoflurane in the patient presented in a case in which neuroprotection is desirable. Both of
in this case was appropriate. these agents offer some neuroprotection with easy control
15259_Ch51.qxd 3/15/09 6:41 AM Page 192
192 CHAPTER 51 • NEUROPROTECTION DURING CEREBRAL ANEURYSM SURGERY
T A B L E 5 1 . 1 Evidence-Based Status of Plausible Interventions to Reduce Perioperative Ischemic Brain Injury
Pre-ischemic Post-ischemic Sustained

Efficacy in Efficacy in Pre-ischemic Post-ischemic protection in Sustained
Experimental Experimental Efficacy in Efficacy in experimental protection
Intervention Animals Animals Humans Humans animals in humans
Moderate hypothermia ⫹⫹ ⫹⫹ ⫺/⫹ ⫹⫹* ⫹⫹ ⫹⫹
Mild hyperthermia ⫺⫺⫺ ⫺⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺⫺ ⫺⫺
Hyperventilation ⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺
Normoglycemia ⫹⫹ ⫺⫺ ⫹ ⫹ ⫹⫹ ⫺⫺
Hyperbaric oxygen ⫹⫹ ⫺⫺ ⫺⫺ ⫺/⫹ ⫺⫺ ⫺⫺
Barbiturates ⫹⫹ ⫺ ⫹ ⫺ ⫺⫺ ⫺⫺
Propofol ⫹⫹ ⫹ ⫺ ⫺⫺ ⫺⫺ ⫺
Etomidate ⫺⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺
Nitrous oxide ⫺ ⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺
Isoflurane ⫹⫹ ⫺⫺ ⫺⫺ ⫺⫺ ⫹⫹ ⫺⫺
Sevoflurane ⫺⫺ ⫺⫺ ⫺⫺ ⫹⫹ ⫺⫺
Desflurane ⫹⫹ ⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺
Lidocaine ⫹⫹ ⫺⫺ ⫹ ⫺⫺ ⫺⫺ ⫺⫺
Ketamine ⫹⫹ ⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺
Glucocorticoids ⫺⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺ ⫺⫺
⫹⫹, repeated physiologically controlled studies in animals/randomized, prospective, adequately powered clinical trials; ⫹, consistent suggestion by case
series/retrospective or prospective small sample size trials, or data extrapolated from other paradigms; ⫺/⫹, inconsistent findings in clinical trials; may be
dependent on characteristics of insult; ⫺, well-defined absence of benefit; ⫺ ⫺, absence of evidence in physiologically controlled studies in animals/
randomized, prospective, adequately powered clinical trials; ⫺ ⫺ ⫺, evidence of potential harm; *, out-of-hospital ventricular fibrillation cardiac arrest.
Reproduced with permission from Fukuda S, Warner DS. Cerebral protection. Br J Anaesth 2007; 99:10–17.
of vasodilation. The low blood-gas solubility of these 8. Sitar SM, Hanifi-Moghaddam P, Gelb A, et al. Propofol prevents
agents allows prompt awakening. peroxide-induced inhibition of glutamate transport in cultured
astrocytes. Anesthesiology 1999;90:1446–1453.
9. Engelhard K, Werner C, Eberspacher E, et al. Influence of
propofol on neuronal damage and apoptotic factors after incom-
References plete cerebral ischaemia and reperfusion in rats: a long-term
1. Rinkel GJ, Djibuti M, Algra A, et al. Prevalence and risk of rup- observation. Anesthesiology 2004;101:912–917.
ture of intracranial aneurysms: a systematic review. Stroke 1998; 10. Lei B, Cottrell JE, Kass IS. Neuroprotective effect of low-dose li-
29:251–256. docaine in a rat model of transient focal cerebral ischemia.
2. Linn FH, Rinkel GJ, van Gijn J. Incidence of subarachnoid hem- Anesthesiology 2001;95:445–451.
orrhage: role of region, year, and rate of computed tomography: 11. Warner DS, McFarlane C, Todd M, et al. Sevoflurane and
a meta-analysis. Stroke 1996;27:625–629 halothane reduce focal ischaemic brain damage in the rat.
3. Broderick JP, Brott T, Tomsick T, et al. The risk of subarach- Possible influences on thermoregulation. Anesthesiology 1993;
noid hemorrhage in blacks as compared to whites. N Engl J Med 79:985–992.
1992;326:733–736. 12. Kawaguchi M, Kimbro JR, Drummond JC, et al. Effects of
4. van Gijn J, Rinkel GJE. Subarachnoid hemorrhage: diagnosis, isoflurane on neuronal apoptosis in rats subjected to focal
causes and management. Brain 2001;124:249–278. ischaemia. J Neurosurg Anesthesiol 2000;12:385.
5. Fukuda S, Warner DS. Cerebral protection. Br J Anaesth 2007; 13. Treggiari MM, Walder B, Suter PM, et al. Systematic review of
99:10–17. the prevention of delayed ischemic neurological deficits with
6. Todd MM, Hindman BJ, Clarke WR, et al. Mild intraoperative hypertension, hypervolemia, and hemodilution therapy follow-
hypothermia during surgery for intracranial aneurysm. N Engl J ing subarachnoid hemorrhage. J Neurosurg 2003;98:978.
Med 2005;352:135–145. 14. Muench E, Horn P, Bauhuf C, et al. Effects of hypervolaemia
7. Kammersgaard LP, Jorgensen HS, Rungby JA, et al. Admission and hypertension on regional cerebral blood flow, intracranial
body temperature predicts long-term mortality after acute stroke: pressure, and brain tissue oxygenation after subarachnoid haem-
the Copenhagen Stroke Study. Stroke 2002; 33:1759–1762. orrhage. Critical Care Med 2007;35:1844–1851.
15259_Ch52.qxd 3/15/09 6:42 AM Page 193
CHAPTER 52
Anesthesia for Cerebral Aneurysm

Coiling
Ashit Bardhan
CASE FORMAT: REFLECTION blood pressure) were applied. One 16-gauge cannula
was inserted on the dorsum of the patient’s left hand after
A 65-year-old, 75-kg male was admitted to the emergency 1% lignocaine infiltration at the site. A 20-gauge arterial
department with a severe headache and decreased level cannula was inserted in the left radial artery for invasive
of consciousness. His Glasgow Coma Scale score was 14. monitoring of blood pressure also after local infiltration with
A computed tomographic scan showed subarachnoid hem- 1% lignocaine. After 3 minutes of preoxygenation with
orrhage (SAH). An angiogram demonstrated (Fig. 52.1) 100% oxygen, anesthesia was induced using intravenous
that the source of the SAH was an 8-mm posterior commu- propofol 200 mg and fentanyl 150. Muscle relaxation was
nicating artery aneurysm. achieved with intravenous atracurium 40 mg. Anesthesia
The patient had smoked 3 to 5 cigarettes per day for was maintained using an infusion of propofol (target con-
the previous 30 years. He walked 2 kilometers each day on trol infusion targeted plasma concentration was 4 ng/L)
level ground and denied chest pain or dyspnea on exertion. and remifentanil (target control infusion, 6–9 ng/L).
He had undergone an appendectomy at 16 years of age Bispectral index monitoring was commenced and main-
for which the anesthetic had been uneventful. tained ⬍60 by titrating the propofol infusion. Convected
The patient’s neurologic examination revealed a warm air was circulated on the patient’s body (Bair
Glasgow Coma scale of 14 (Table 52.1); he opened his Hugger; Arizant Inc, Eden Prairie, MN), for which the tem-
eyes in response to voice (3), was oriented and convers- perature was set at 38°C. Once the right femoral artery
ing (5), and obeyed commands (6). He was judged to be was successfully cannulated, 100 IU/kg of heparin was ad-
Hunt and Hess grade II (Table 52.2) and also grade II by ministered. Three minutes later, the activated clotting time
World Federation of Neurological Surgeons Grading was 345 seconds. Using a microcatheter, the neuroradiol-
(Table 52.3). His pupils were 6 to 7 mm in diameter, were ogist catheterized the aneurysm and then successfully de-
equal, and reacted normally to light. He had no neuro- posited platinum coils within the aneurysm sac until it was
logic deficit. Electrocardiogram (ECG) and chest radi- occluded. Propofol and remifentanil infusion were discontin-
ograph readings were unremarkable. The patient’s serum ued. Reversal of neuromuscular block was achieved by ad-
urea was 6.5 mmol/L; creatinine, 85 mmol/L; sodium, ministering 2.5 mg neostigmine and 500 ␮g glycopyrro-
130 mmol/L; and glucose, 8.5 mmol/L. His hemoglobin late. During the procedure, 1 L of 0.9% sodium chloride
concentration was 14.6 g/dL, and his white blood cell had been administered. Within 12 minutes of discontinuing
count was 12 ⫻ 109/L. the anesthetic agents, the patient was able to obey com-
The patient had been fasting for 6 hours and had mands, and his trachea was extubated without coughing.
received 60 mg of oral nimodipine (additional doses had He was transferred to the postanesthesia care unit, and
been prescribed every 4 hours thereafter). A prophylactic after 30 minutes, he was oriented, alert, awake, and com-
dose of phenytoin 1.125 g (15 mg/kg) had been admin- fortable. His vital signs were normal and he was dis-
istered intravenously on admission over 30 minutes in the charged to the neurosurgical observation ward. Regular ni-
emergency department. modipine and phenytoin were prescribed for 3 weeks, and
In view of the hyponatremia, the patient’s estimated the patient was scheduled for a repeat cerebral angiogram
fluid losses were replaced with 0.9% sodium chloride. As in 6 months.
part of the multidisciplinary approach to managing a cere-
bral aneurysm, the neurosurgeon and neuroradiologist dis-
cussed definitive treatment options such as clipping and CASE DISCUSSION
coiling of the aneurysm. On the basis of findings of the
International Subarachnoid Aneurysm Trial (ISAT)1 trial,
ISAT
they decided to proceed to coiling of the aneurysm on the
following day. The ISAT is the only large-scale, multicenter, prospective,
On the next morning, the patient received the pre- randomized control trial that has compared endovascular
scribed dose of nimodipine. He received no premedicant, as coiling and neurosurgical clipping for ruptured intra-cerebral
he volunteered that it was not necessary. In the neuroradiol- aneurysm. A total of 2143 patients were randomly allocated,
ogy suite, standard monitors (ECG, SpO2, and noninvasive 1073 to the endovascular and 1070 to the neurosurgical arms.
The trial included patients with ruptured aneurysms that
193
15259_Ch52.qxd 3/15/09 6:42 AM Page 194
194 CHAPTER 52 • ANESTHESIA FOR CEREBRAL ANEURYSM COILING
Figure 52.2 • Postcoiling Angiogram.

Figure 52.1 • Precoiling Angiogram.
T A B L E 5 2 . 1 Glasgow Coma Scale
Score 6 5 4 3 2 1
Eyes N/A N/A Opens eyes Opens eyes in Opens eyes in Does not
spontaneously response to voice response to open eyes
painful stimuli
Verbal N/A Oriented, converses Confused, Utters inappropriate Incomprehensible Makes no
normally disoriented words sounds sounds
Motor Obeys Localizes painful Flexion / Abnormal flexion Extension to Makes no
commands stimuli withdrawal to to painful stimuli painful stimuli movements
painful stimuli
N/A, not applicable.
T A B L E 5 2 . 2 Hunt and Hess Grading Scale for T A B L E 5 2 . 3 World Federation of Neurological

Subarachnoid Hemorrhage Surgeons Grading Scheme for
Subarachnoid Hemorrhage
Grade Clinical Description
I Asymptomatic or minimal headache and Grade Glasgow Coma Scale Motor Deficit
slight nuchal rigidity I 15 Absent
II Moderate- to- severe headache, nuchal II 13 or 14 Absent
rigidity, no neurological deficit other than III 13 or 14 Present
cranial nerve palsy
IV 7–12 –
III Drowsiness, confusion, or mild focal deficit
V 3–6 –
IV Stupor, moderate- to- severe hemiparesis,
and possibly early decerebrate rigidity and
vegetative disturbance
V Deep coma, decerebrate rigidity, and mori-
bund appearance
15259_Ch52.qxd 3/15/09 6:42 AM Page 195
CHAPTER 52 • ANESTHESIA FOR CEREBRAL ANEURYSM COILING 195
were amenable to treatment with clipping or coiling. Patients What is the role of nimodipine?
randomly allocated to coiling experienced a 23.7% incidence Nimodipine, a calcium channel blocker, improves outcome
of neurological dependency or death compared with a 30.6% after SAH.3 Nimodipine therapy (60 mg orally or by naso-
incidence in patients randomized to clipping. These results gastric tube every 4 hours; maximal daily dose 360 mg)
showed that the absolute benefit of coiling over clipping should be started in all patients at admission and continued
was 7.4%. This figure equates to a number needed to treat of for 21 days. Nimodipine administered as a continuous infu-
14 patients, for one to avoid death or dependency at 1 year sion is no more effective than when administered orally, but
after rupture. it is associated with a greater incidence of hypotension.
Several aspects of this study need to be emphasized to place Intravenous nimodipine should be administered via a central
the findings into proper clinical perspective. Only 22.4% of the venous catheter. In addition, the infusion system must be
initially screened 9559 patients with ruptured aneurysms un- protected from light. If an adequate and stable blood pres-
derwent randomization; ⬍10% of the patients were at high sure (systolic blood pressure 130–150 mm Hg) cannot be
clinical risk, and approximately 95% of them had aneurysms maintained, hemodynamic management takes priority over
in the anterior cerebral circulation with a size of ⬍10 mm. nimodipine administration. In general, nimodipine renders
Complete occlusion of the aneurysm was achieved more often patients prone to hypotension, especially when they are in-
in the surgically treated group compared with the endovascu- travascularly depleted and during anesthesia induction. As
larly treated group (82 vs. 66%). Late aneurysm rebleeding nimodipine does not reliably relieve angiographically docu-
was more common in the coiled group (0.2% per year) than in mented vasospasm, its beneficial effect may be caused by a
the open surgical group (0.06% per year); however, rebleeding general brain protective mechanism.2
was uncommon in both treatment groups and did not reverse
the benefit of endovascular treatment at 7-year follow-up.2
How is grading and neurologic
What is coiling of a cerebral aneurysm? assessment used?
Coiling is a procedure in which a microcatheter is inserted Clinical grading scales such as that of Hunt and Hess 4 or the
through the femoral artery, navigated into the aneurysm sac World Federation of Neurological Surgeons 3 are used to stan-
allowing detachable coils to be advanced into the sac until the dardize clinical assessment and to estimate patients’ prognosis.
aneurysm is occluded. The original coils are named Guglielmi Focal neurologic deficits and change in mental status are the
Detachable Coils after Dr. Guido Guglielmi, the developer of basis of the Hunt and Hess grading scale, which has been used
the technique. as a predictor of outcome. A frequently overlooked part in this
classification is that, if patients have medical comorbidities,
such as hypertension, severe atherosclerotic disease, chronic
What are the advantages of coiling? pulmonary disease, diabetes mellitus, and severe vasospasm,
Coiling is a minimally invasive procedure. It also avoids the the grade should be the next less favorable one. The World
complications associated with craniotomy. Recovery time is Federation of Neurosurgical Societies has introduced a new
shorter than after clipping. Within the setting described of grading system that has more accurate prognostic value and
the ISAT trial, coiling was associated with a better outcome is partially based on the Glasgow Coma Scale of patients on
(in terms of neurologic dependency or death) than surgical arrival.5 Knowledge and understanding of the grading scales
clipping. are required for effective communication among physicians,
assessment of the severity of the patient’s underlying patho-
physiologic abnormalities, and rational planning of the peri-
How is the decision made to coil a cerebral operative anesthetic management.2
aneurysm?
Several factors are important in deciding if an aneurysm is
What type of electrolyte abnormalities
suitable for coiling. The following factors favor coiling: small
may occur?
aneurysm sac size (but not too small, ⬎3 mm), favorable neck
size (not wide), no branches coming out of the dome of the Common electrolyte abnormalities include hyponatremia,
aneurysm, certain locations where surgical access is difficult hypokalemia, hypomagnesemia, and hypocalcemia. Hypo-
(basilar artery, parophthalmic artery), advanced age, and se- magnesemia occurs in more than 50% of patients with SAH
vere systemic disease. Approximately 7 out of 10 ruptured and is associated with delayed cerebral ischemia and poor out-
aneurysms are suitable for coiling. In many cases, aneurysms come.6,7 If hyponatremia is caused by the syndrome of inap-
can be secured using either technique. propriate anti-diuretic hormone secretion, normovolemia
should be maintained with isotonic saline.8
What is the optimal timing for intervention?

Cerebral vasospasm usually develops 3 to 12 days after SAH, Which type of anesthetic technique
lasts on average 2 weeks, and affects 60% to 70% of patients is generally used to facilitate coiling?
with SAH. It frequently results in cerebral ischaemia, and is Conscious sedation, “neurolept” anesthesia, and general anes-
the major cause of morbidity and mortality in these patients. thesia have been described. Anesthetists in most hospitals use
After SAH has been diagnosed, it should be repaired at the general anesthesia with tracheal intubation.7 Airway manage-
earliest possible time before cerebral vasospasm develops. ment using a laryngeal mask airway has also been advocated.
15259_Ch52.qxd 3/15/09 6:42 AM Page 196
196 CHAPTER 52 • ANESTHESIA FOR CEREBRAL ANEURYSM COILING
What types of premedication are used? What type of complications are possible?
If the patient is alert and very anxious, an anxiolytic can be Non-central nervous system complications include contrast
prescribed.8 A small dose of benzodiazepine is usually suffi- allergic reactions, contrast nephropathy, and groin or
cient. On the other hand, in cases of altered consciousness, retroperitoneal hematomata. Central nervous system compli-
sedative premedication should be avoided. Opiates are best cations can be categorized based on the timing of the proce-
avoided, as they can cause respiratory depression. The patient dure: intraprocedural, early, and late postprocedural.
might already be taking a calcium channel antagonist such as Intraprocedural complications include rebleed from aneurysm
nimodipine as a neuroprotective agent or for decreasing the rupture or ischemic stroke caused by vessel occlusion (from
incidence of vasospasm. Anticonvulsants, corticosteroids, and thrombosis, embolization, branch occlusion, or dissection).
antibiotics might be used as premedicants depending on the Early postprocedural complications include rebleeding and
patient’s status and requirements. In patients with obesity or delayed thromboembolism. The main late postprocedural
gastroesophageal reflux, H2- receptor antagonists such as ran- complication is aneurysm regrowth (from coil compaction or
itidine or metoclopramide are used to decrease the risk of pul- aneurysm growth).
monary aspiration of gastric contents.9
CONCLUSION
What type of electrocardiographic changes
take place? Anesthesia for coiling of cerebral aneurysms requires a
SAH can be associated with marked systemic and pulmonary thorough understanding of the pathophysiology of SAH.
hypertension, cardiac arrhythmias, myocardial dysfunction Anesthesia is provided in a setting with which the anesthetist
and injury, and neurogenic pulmonary edema. ECG abnor- may not be familiar; often, trained assistance is not readily
malities (e.g., QTc prolongation, repolarization abnormalities) available, and there is the potential for catastrophic complica-
have been reported in 25% to 100% of cases, along with an tions such as re-bleeding or perforation.
increase in serum concentration of cardiac troponin in 17% to
28%, of creatine kinase- MB isoenzyme in 37%, and of left ven-
tricular dysfunction in 8% to 30% of cases. In most cases, my-
ocardial dysfunction seems to correlate more with the degree of KEY MESSAGES
neurologic deficit than with the severity of ECG abnormali-
ties.2 Cardiac injury and dysfunction usually resolve over time With respect to the anesthetic care of patients undergoing
and do not seem to directly affect morbidity and mortality.10 coiling of cerebral aneurysms:
1. It is necessary for the anesthetist to familiarize
What type of monitoring is used? him/herself with the neuroradiology suite before
undertaking care of such patients.
Monitoring standards in a neuroradiology interventional
suite should be equivalent to those available in the operating 2. Thorough neurologic assessment of the patient is
room. Invasive blood pressure monitoring and urine output required pre- and postoperatively.
measurement are required. A central venous catheter is not
3. Maintaining hemodynamic stability throughout the
regularly inserted, as large fluid shifts are not expected.
procedure is important to avoid the risk of secondary
Neurophysiologic monitoring is used in some hospitals but is
injury caused by hypoperfusion or aneurysm rupture.
not a common practice.
4. Communication between the anesthetist and the
interventional team is important.
What are the principles of anesthetic
management?
The goal during anesthesia induction for repair of cerebral
aneurysms is to minimize the risk of aneurysm rupture. The
incidence of aneurysm rupture during induction is approxi- QUESTIONS
mately 2%.11 As there is no skull decompression during the pro-
cedure, the risk of aneurysm rupture is present until it is coiled 1. What is the principal finding of the ISAT trial?
successfully. Anesthesia is maintained by total intravenous anes- Answer: The principal finding of the ISAT trial is that
thesia or a combination of low-dose propofol and remifentanil patients randomly allocated to coiling experienced a
in conjunction with small dose of a volatile agent. Cannulation 23.7% incidence of neurologic dependency or death com-
of the femoral artery is associated with greatest stimulation. pared with a 30.6% incidence in patients randomized to
Overall, the anesthetic requirement is not great. Systemic hy- clipping.
potension should be avoided, and “low-normocapnia” should
be maintained. During emergence, if the aneurysm is secured, 2. What nimodipine regimen is indicated in patients
a systolic blood pressure of 160 mm Hg has been reported to with SAH?
result in a favorable outcome. The safe upper limit for an Answer: Nimodipine (60 mg orally or by nasogastric tube
unsecured aneurysm is not clear.7 every 4 hours; maximal daily dose, 360 mg) should be
15259_Ch52.qxd 3/15/09 6:42 AM Page 197
CHAPTER 52 • ANESTHESIA FOR CEREBRAL ANEURYSM COILING 197
administered to all SAH patients at admission and 4. Hunt WE, Hess RM. Surgical risk as related to time of inter-
continued for 21 days. vention in the repair of intracranial aneurysms. J Neurosurg
1968;28:14–20.
3. What electrolyte abnormalities are most commonly 5. Avitsian R, Schubert A. Anaesthetic considerations for intraop-
associated with SAH? erative management of cerebrovascular disease in neurovascular
surgical procedures. Anesthesiol Clin 2007;25:Issue 3.
Answer: Common electrolyte abnormalities associated 6. Van den Bergh WM, Algra A., van der sprenkel JW, et al.
with SAH include hyponatremia, hypokalemia, hypo- Hypomagnesemia after SAH. Neurosurgery 2003;52:276–282.
magnesemia, and hypocalcemia. 7. Lakhani S, Guha A, Nahser SC. Anaesthesia for endovascular
management of cerebral aneurysm. Eur J Anaesthesiol 2006;23:
902–913.
References 8. Rosas AL. Anaesthesia for INR: part II: preoperative assessment,
1. Molyneux A, Kerr R, Yu L, et al. International Subarachnoid premedication. Internet J Anesthesiol 1997;1. Available at: www.
Aneurysm Trial (ISAT) of neurosurgical clipping and endovas- ispub.com/ostia/index.php?xmlFilepath=journals/ija/vol1n2/
cular coiling in 2413 patients with intracranial aneurysm: a ran- neuroan2.xml. Accessed February 27, 2009.
domised comparison of effects on survival, dependency, seizures, 9. Ahmed A. Anaesthesia for interventional neuroradiology. J
rebleeding, subgroups and aneurysm occlusion. Lancet 2005;366: Ayub Med Coll Abbottabad 2007;19:80–84.
809–817. 10. Diebert E, Barzilai B, Braverman A, et al. The clinical signifi-
2. Priebe HJ. Aneurysmal subarachnoid haemorrhage and the cance of elevated troponin I in patients with non traumatic
anaesthetist. Br J Anaesth 2007;99:102–118. subarachnoid haemorrhage. J Neurosurg 2003;98:741–746.
3. Drake CG, Hunt WE, Sano K, et al. Report of World Federation 11. Tsementzis SA, Hitchcock ER. Outcome from ‘rescue clipping’
of Neurological Surgeons Committee on a universal subarach- of ruptured intracranial aneurysm during induction of anaesthe-
noid haemorrhage grading scale. J Neurosurg 1988;68:985–986. sia and endotracheal intubation. J Neurol Neurosurg Psychiat
1985;48:160–163.
15259_Ch53.qxd 3/15/09 6:43 AM Page 198
CHAPTER 53
Emergency Reversal of
Rocuronium-Induced Neuromuscular
Blockade Using Sugammadex
Mohan Mugawar
CASE FORMAT: REFLECTION a breath (100% oxygen) to the patient’s lungs via face
mask and Guedel airway. Shortly afterward, the patient
A 38-year-old female (American Society of Anesthesio- resumed spontaneous ventilation and regained conscious-
logists physical status I) presented with radicular low back ness. SpO2 rapidly returned to 97% to 99%. Reassessment
pain of 3 months’ duration. After appropriate investiga- of the patient revealed a TOF ratio of 0.9, 115 seconds
tions and discussion of the treatment options with her, after sugammadex administration (Fig. 53.1).
she was scheduled for elective lumbar laminectomy. The The patient was fully conscious, alert, well oriented,
patient’s medical history was unremarkable. She had un- neurologically intact, hemodynamically stable, and there-
dergone uneventful general endotracheal anesthesia for a after maintained oxygen saturation of 100% on room air.
tonsillectomy at 5 years of age and spinal anesthesia for She was observed for 2 hours in a postanesthetic care unit
an elective caesarean section 2 years previously. and was stable without any signs of recurarization. After
The preoperative evaluation revealed a moderately complete recovery from anesthesia, a full explanation of
obese woman who was 165 cm in height and weighed the events was made to the patient, and the events were
85 kg. Cardiorespiratory assessment was normal. Pre- recorded in detail in her medical record. The patient was
operative laboratory data were within the normal ranges. provided with written information regarding her airway
The airway assessment revealed prominent upper incisors, management and was asked to relay this to any future
interincisor gap ⬎3 cm, thyromental distance 8 cm, and anesthetist and to her primary care physician. She was
Mallampati grade II. The patient’s neck appeared short; the also advised about the option of obtaining a Medic Alert
cervical spine mobility was normal. In the operating room, bracelet. Her surgery was rescheduled, and awake
an intravenous (IV) cannula was inserted, and an infusion of fiberoptic intubation was planned.
compound sodium lactate commenced. Routine standard
monitoring was applied including neuromuscular monitor-
ing using train-of-four stimulation (TOF watch).
After 3 minutes of preoxygenation, anesthesia was in- CASE DISCUSSION
duced by an experienced anesthesiologist with fentanyl
100 ␮g and propofol 200 mg. With some difficulty, posi- Sugammadex (Org 25969) is the first selective muscle relaxant
tive pressure was applied via face mask, and some chest binding agent, designed to reverse the steroidal neuromuscular
expansion was noted; rocuronium IV 1.2 mg/kg was ad- blocking agents (NMBAs), particularly rocuronium.1 It is a
ministered. Mask ventilation became progressively more modified ␥-cyclodextrin, forms inactive tight 1:1 complexes
difficult after the administration of rocuronium despite vigor- with, and functions as an irreversible chelating agent for
ous jaw thrust and placement of an appropriately sized oral aminosteroidal NMBAs. The administration of sugammadex
airway. Three attempts at rigid laryngoscopy were made— results in a rapid decrease in the concentration of free rocuro-
the first two by the initial anesthetist and the third by an- nium in the plasma and subsequently in the synaptic cleft at the
other senior colleague who was called to assist. Having neuromuscular junction, resulting in rapid normalization of
optimized head and neck position, Macintosh 3, 4 and neuromuscular function. Sugammadex has no effect on
McCoy blades were used without acquiring a view even of acetylcholinesterase or any receptor system in the body.
the arytenoids. Between laryngoscopy attempts, manual Therefore, the need for administering anticholinesterases
ventilation was attempted using a two- operator technique; and anticholinergic (-muscarinic) agents and the associated
these attempts, however, were unsuccessful. Insertion of a adverse effects are avoided. Sugammadex-rocuronium com-
laryngeal mask airway did not enable effective manual ven- plexes are highly hydrophilic and are therefore excreted rapidly
tilation. These attempts at securing a patent airway had and in a dose-dependent manner. Sugammadex is biologically
taken approximately 4 minutes. The patient became pro- inactive and appears to be safe and well tolerated by patients.2
foundly hypoxic with SpO2 ⬍80%. While urgent prepara- Sugammadex reverses profound NMB induced by aminos-
tion was made for cricothyrotomy, sugammadex 16 mg/kg teroidal nondepolarizing NMB agents rapidly and effectively in
was administered by rapid IV bolus (the drug was available a dose-dependent manner.3–5 The optimal dose required to re-
because trials of sugammadex were underway at the insti- verse profound blockade has not yet been fully elucidated.
tution). Ninety seconds later, it became possible to deliver However, sugammadex administration in doses of 4, 8, 12, and
16 mg/kg resulted in reversal of profound rocuronium-induced
198
15259_Ch53.qxd 3/15/09 6:43 AM Page 199
CHAPTER 53 • EMERGENCY REVERSAL OF NEUROMUSCULAR BLOCKADE 199
Rocuronium 1.2
mg/Kg
Sugammadex 16
mg/Kg
100%
50%
12:02:03 PM 12:06:23 PM 12:10:38 PM 12:14:53 PM 12:19:08 PM 12:23:23 PM 12:27:38 PM 12:31:53 PM 12:36:08 PM 12:40:23 PM
Figure 53.1 • TOF-Watch SX trace (Bluestar Enterprises, Inc, Chanhassen, MN) of the twitch height and T4/T1
ratio after IV administration of rocuronium and sugammadex. Recovery of twitch height (T1) of 90% and TOF ratio of
0.9 returned approximately 115 seconds after sugammadex administration.
NMB to a TOF ratio of 0.9 in (mean values) of 15.8, 2.8, 1.4 an irreversible chelating agent for aminosteroidal
and 1.9 minutes, respectively.3 (The TOF ratio taken to indi- NMBAs.
cate adequate reversal of/recovery from NMB is 0.9, as this
level is required for normal function of vital muscle groups, 2. What is the TOF ratio normally accepted to indicate
including those of the pharynx, to avoid postoperative respira- adequate reversal of /recovery from NMB?
tory complications.6,7) Answer: 0.9
Administering sugammadex in clinical practice could de-
crease the incidence of postoperative residual curarization. Use 3. What hemodynamic adverse effects are associated with
of sugammadex could also facilitate the use of rocuronium for sugammadex administration?
rapid sequence induction by providing a faster onset/offset of Answer: None of clinical importance. Sugammadex is bi-
NMB profile compared with succinylcholine. As in the patient ologically inactive and appears to be safe and well toler-
described in this case, sugammadex offers the potential to rap- ated by patients.2
idly terminate profound NMB if the anesthetist is confronted
with a “cannot intubate, cannot ventilate” situation.
References
1. Bom A, Bradley M, Cameron K, et al. A novel concept of revers-
ing neuromuscular block: chemical encapsulation of rocuronium
KEY MESSAGES bromide by a cyclodextrin-based synthetic host. Angew Chem
Int Ed Engl 2002;41:266–270.
1. Sugammadex is a selective, novel reversal agent of 2. Naguib M. Sugammadex: another milestone in clinical
neuromuscular pharmacology. Anesth Analg 2007;104: 575–581.
NMB induced by aminosteroid nondepolarizing NMB
3. de Boer HD, Driessen JJ, Marcus MAE, et al. Reversal of
agents. rocuronium-induced (1.2 mg/kg) profound neuromuscular
2. Administration of sugammadex 8 mg/kg can reverse block by sugammadex. Anesthesiology 2007;107:239–244.
profound rocuronium-induced NMB in approximately 4. Sparr HJ, Vermeyaen KM, Beaufort AM, Rietbergen H, et al.
90 seconds. Early reversal of profound rocuronium induced neuromuscular
3. A TOF ratio of 0.9 or greater is the threshold that blockade by sugammadex in a randomised multicenter study.
corresponds to adequacy of reversal of/recovery Anesthesiology 2007;106:935–943.
from NMB. 5. Suy K, Morias K, Cammu G, et al. Effective reversal of moderate
rocuronium-or vecuronium-induced neuromuscular block with
sugammadex, a selective relaxant binding agent. Anesthesiology
2007;106:283–288.
6. Eriksson LI, Sundman E, Olsson R, Nilsson L, et al. Functional
QUESTIONS assessment of the pharynx at rest and during swallowing in
partially paralysed humans: simultaneous videomanometry and
1. What is the mechanism of action of sugammadex? mechanomyography of awake human volunteers. Anesthesiology
1997;87:1035–1043.
Answer: Sugammadex is a modified ␥-cyclodextrin, 7. Kopman AF. Surrogate endpoints and neuromuscular recovery
forms inactive tight 1:1 complexes with, and functions as (editorial). Anesthesiology 1997;87:1029–1031.
15259_Ch54.qxd 3/15/09 6:45 AM Page 200
CHAPTER 54
Awareness During Anesthesia
Justin Lane
CASE FORMAT: STEP BY STEP What factors relevant to this case influence the
risk of intraoperative awareness?
A 36-year-old primigravida presented for emergency ovar- Pregnancy is associated with as great as 30% decrease in min-
ian cystectomy. At 30 weeks’ gestation, she had been in imum alveolar concentration value.2 Analysis of the
the hospital for 2 days with severe abdominal pain, nau- American Society of Anesthesiologists closed claims data-
sea, and vomiting. Intramuscular pethidine (meper-idine) base4 has identified five factors that increase the risk of recall
50 mg and prochlorperazine 12.5 mg were administered under general anesthesia: (a) female gender, (b) gynecological/
to control the symptoms. The patient, a nurse, had no his- obstetrical procedures, (c) use of opioids, (d) use of muscle re-
tory of anesthesia-related problems. laxants, (e) and lack of use of a volatile anesthetic agent. At
On assessment the patient, was found to be nor- least four of these factors apply to the patient in this case. It
motensive (blood pressure, 115/75 mm Hg), with a pulse is likely that the emergency nature of the procedure also
rate of 92 beats per minute. Her blood glucose was nor- increases the risk.
mal, and in her laboratory workup, it was noted that she Following an uneventful surgical procedure, the patient’s
had an increased white blood cell count 17 ⫻ 10 9/L trachea was extubated, and she was transferred to the postanes-
and serum urea 11 mg/dL. An ultrasound of the patient’s thesia care unit. Routine postanesthesia monitoring was carried
abdomen and pelvis confirmed the diagnosis of ovarian out in the postanesthesia care unit. A combination of regular
cyst torsion. Assessment of her upper airway revealed intravenous paracetamol every 6 hours and intramuscular
Mallampati grade II and thyromental distance of 7 cm. pethidine (meper-idine) 50 mg every 4 hours was prescribed as
Her incisor separation and mandibular mobility were were antiemetics and supplemental oxygen. The transverse ab-
normal. In view of her history and abnormal serum urea, dominis plane (TA) block performed intraoperatively appeared
she was commenced on Hartmann’s solution at 200 mL to be effective, as no analgesics were administered in the
per hour to improve her hydration status before surgery. postanesthesia care unit. Hartmann’s solution 125 mL per hour
The anesthetic plan was discussed with the patient. was administered until the patient could tolerate fluids orally.
A general anesthetic was described, using a “rapid se- On the second postoperative day, the patient informed
quence induction” technique, and a transversus abdo- the surgeon that she thought she recalled hearing alarms
minis plane block1 was to be performed intraoperatively and people discussing her case while the operation was in
for analgesia. progress.
Following application of standard monitors, a rapid se-
quence induction of anesthesia and tracheal intubation were
What is awareness under anesthesia?
performed using sodium thiopentone (5 mg/kg) and suxam-
ethonium (1.5 mg/kg) after denitrogenation2 (preoxygena- Awareness is a rare complication of general anesthesia, which
tion with 100% oxygen for 5 minutes). A wedge was placed can have serious psychological sequelae for the patient and se-
under the patient’s right buttock to decrease the likelihood of rious financial implications for the hospital in which it occurs.
supine hypotension. Sevoflurane End tidel (ET) 0.5% to It can be classified as: (a) awareness with explicit memory—
0.8% in nitrous oxide/oxygen (50:50 mixture), vecuronium, the patient has conscious recollection of intraoperative events
and fentanyl were administered according to the anes- or (b) awareness with implicit memory—the patient has no
thetist’s clinical judgment. Although BIS monitoring3 (Aspect recollection of intraoperative events.5
Medical Systems, Norwood, MA) was applied (and BIS was One to two people per thousand may describe some degree
⬍60 throughout the surgery), the anesthetist titrated sevoflu- of awareness during their anesthetic; of these, 33% describe
rane administration according to the patient’s heart rate and pain as part of their experience.6 More than 50% of “aware”
blood pressure rather than to the BIS value. The difficult air- patients describe hearing conversations and sounds within the
way cart was kept in the operating room. A fetal monitor operating room. About 25% of such patients have experiences
was applied before induction and was monitored by the relating to endotracheal tube insertion.
attending obstetrician. Any suggestion of a case of awareness under anesthesia
must be followed up (Table 54.1). A review of the anesthetic
200
15259_Ch54.qxd 3/15/09 6:45 AM Page 201
CHAPTER 54 • AWARENESS DURING ANESTHESIA 201
T A B L E 5 4 . 1 Protocol for Managing Possible T A B L E 5 4 . 2 Anesthetic Factors Contributing to

Case of Awareness Under Awareness
Anesthesia6,10,11
• Equipment problems: empty vaporizer, circuit leak
Visit the patient as soon as possible after the event. • Drug errors: mislabeled syringes, inadequate drug
Take a full history and document the patient’s exact mem- doses
ory of events, conversations, names, events, and sounds. • Technique: opioid use, light anesthesia in emergency
Check with other staff who would have been present in situations
theatre during the event. • Airway problems: laryngospasm, difficult intubation
Review the anaesthesia case notes for evidence of a possi- Reproduced with permission from Osborne G, Bacon A, Runciman K,
ble cause, e.g., tachycardia, hypertension in the case of et al. Crisis management during anaesthesia: awareness and anaesthesia.
“light anaesthesia.” Quality and Safety in Health Care 2005;14;16–25.
Give a full explanation of events to the patient.

Plan for patient follow up, including psychological
support.
Reassure the patient that further safe general anaesthesia In general, what factors contribute to the
is possible. occurrence of awareness in modern anesthetic
Try to determine the cause, review the notes, and check practice?
the machine and circuit. Patients undergoing specific types of surgical procedures are at
Notify the patient’s GP. greater risk of awareness:6
Make a detailed record of the event for future reference. • Cardiac surgery: up to 1 in 100
• Trauma and emergency surgery: up to 1 in 20
• Emergency caesarean section under general anesthesia: 4 in
1000.
record for the procedure is the first step. The drugs and The patient’s question (regarding the anesthetist’s role) is
doses administered should be verified if possible. The levels understandable and legitimate, as anesthetic factors can pre-
of volatile agents used alone or in combination with nitrous dispose a patient to awareness (Table 54.2).
oxide should be noted. It may be necessary to check the serv-
ice date on the anesthetic machine, especially the vaporizer.
The anesthetist involved in the case should visit the patient,
and a witness should be present. The purpose of the visit is to
KEY MESSAGES
elicit a full history of what the patient experienced and in
particular, what he or she heard. It is certainly not to deny
1. Intraoperative awareness occurs more commonly in
the possibility that awareness under anesthesia may have
females and in patients undergoing obstetric-
occurred. The patient should be reassured that the claims are
related surgery, cardiac surgery, or emergency
taken seriously, and that if she wishes to discuss the issue fur-
procedures.
ther, it will be facilitated. Detailed notes regarding the claim
2. BIS monitoring does not decrease the incidence of
should be made at the time of the initial interview. A full
intraoperative recall/awareness.7,8 Intraoperative
range of support services should be made available including
awareness can occur even when BIS values are within
psychologists and counselors. If an explanation is possible, it
target ranges.8
should be provided. The patient will also require reassurance
3. Anesthetic departments should have a readily avail-
that further anesthesia can be given safely. The patient’s gen-
able protocol in place to deal with possible cases of
eral practitioner (primary care doctor) needs to be informed
awareness, should they arise.
of the incident. The relevant medical indemnity organiza-
tion and the hospital management should also be informed
(Table 54.1).
The responsible anesthetist arranged to meet with the
patient in the presence of a hospital representative on the QUESTIONS
day after she described her experience to the surgeon. The
meeting took place in a quiet consulting room, and as she 1. Which patients are at greatest risk of experiencing
described her recollections, the patient became tearful. intraoperative awareness?
She described great difficulty in sleeping and feeling anxious Answer: Females and patients undergoing obstetric-
since her operation. She asked what her anesthetist had done related or cardiac surgery or emergency procedures
that allowed her to be aware of her surroundings during the are at greatest risk of experiencing intraoperative
operation. awareness.
15259_Ch54.qxd 3/15/09 6:45 AM Page 202
202 CHAPTER 54 • AWARENESS DURING ANESTHESIA
2. What is the initial appropriate step in responding to a 2. Ni Mhuireachtaigh R, O’Gorman DA. Anesthesia in pregnant
patient’s account of awareness? patients for nonobstetric surgery. J Clin Anesth 2006;18:60–66.
3. Punjasawadong Y, Boonjeungmonkol N, Phongchiewboon
Answer: The responsible anesthetist should visit the A. Bispectral index for improving anaesthetic delivery and post-
patient as soon as possible after the event. operative recovery. Cochrane Database of Systematic Reviews
2007. Issue 4. Art No. CD003843. DOI: 10.1002/14651858.
3. What proportion of patients who describe an aware- CD003843.pub2
ness experience report pain as a dominant element of 4. The ASA Closed Claims Project. Available at: www.asa
their recollection? closedclaims.org. Accessed October 31, 2007.
5. Anaesthesia UK. Available at: www.anaesthesiauk.com.
Answer: Only 33% of patients who describe an awareness Accessed October 31, 2007.
experience report pain as a dominant element of their 6. The Royal College of Anaesthetists. Information for patients.
recollection. Section 8: Awareness “ risks associated with your anaesthetic.”
Available at: http://www.rcoa.ac.uk/docs/awareness.pdf. Accessed
November 23, 2008.
References 7. Osborne GA, Bacon AK, Runciman WB, et al. Crisis manage-
1. McDonnell JG, O’Donnell B, Curley G, et al. The analgesic ment during anaesthesia: awareness and anaesthesia. Quality and
efficacy of transversus abdominis plane block after abdominal Safety in Health Care 2005;14;16–25.
surgery: a prospective randomised controlled trial. Anesth Analg 8. Avidan MS, Zhang L, Burnside BA, et al. Anesthesia awareness
2007;104:193–197. and the bispectral index. N Engl J Med 2008;358: 1097–1108.
15259_Ch55.qxd 3/15/09 6:48 AM Page 203
CHAPTER 55
Mitochondrial Disease and

Anesthesia
Dorothy Breen
chest infections. Antibiotics were prescribed 2 days previously

for a lower respiratory tract infection. The patient’s heart rate
was 60 beats per minute, blood pressure was 105/60 mm Hg,
A 16-year-old, 4⬘7⬙, 50-kg girl with mitochondrial disease
and her temperature was 37.9°C. The cardiovascular examina-
was scheduled for a cochlear implant. The anesthesiolo-
tion was normal, and her lung fields were clear. There was bi-
gist in charge decided to consult his standard textbooks
lateral ptosis and evidence of skeletal muscle wasting.
before reviewing the patient. Unfortunately, he found very
little information relevant to mitochondrial disease and
anaesthesia.
What factors are important in assessing this
patient preoperatively?
Preoperative assessment should take account of the potential
for multisystem involvement and the varying degrees of sever-
What is mitochondrial disease, and how does it ity. Surgery and anesthesia pose a considerable stress to a
manifest? patient with an already deranged bioenergy metabolism.
Mitochondrial disease comprises a heterogeneous group of Infection in this setting places even further demands. Given the
disorders in which the primary abnormalities are errors in the presence of pyrexia and the history of a recent respiratory tract
synthesis of mitochondrial proteins caused by defects in nu- infection, it is wise to postpone the surgery. Furthermore, anes-
clear DNA, mitochondrial DNA, or mitochondrial transfer thesia in this patient requires much more detailed assessment
RNA.1 The mitochondrion is traditionally viewed as the and planning. KSS, although rare, is one of the better-
“powerhouse” of the cell, as it contains all the machinery nec- described entities in the spectrum of mitochondrial cytopathies
essary for the Krebs cycle, fatty acid oxidation, and oxidative that exist (Table 55.1). Cardiac involvement is a feature of KSS,
phosphorylation. The mitochondrion is also unique in that it and conduction defects are common. Thorough nervous sys-
is the only cellular organelle with its own DNA (mitochondr- tem and neuromuscular assessment should also be performed
ial DNA). Mitochondrial DNA encodes some of the compo- to determine the extent of skeletal muscle involvement, neuro-
nents of the respiratory chain enzyme complexes. Five enzyme logic deficit, and presence of seizure disorders. Respiratory
protein complexes are involved in oxidative phosphorylation. function is often impaired in patients with mitochondrial dis-
Adenosine triphosphate synthesis takes place at complex V. ease. It is important to assess the presence of bulbar symptoms,
During division of a fertilized ovum, defective mitochondria recurrent aspiration, and respiratory muscle weakness.3,4
can become more or less concentrated in one organ or another.
Tissues that are postmitotic at birth and have high-energy
requirements tend to be most affected (muscle, brain, nerves, What tests should be ordered preoperatively?
retinas, liver, and kidneys), but theoretically, any organ can be The results of preoperative spirometry are given in Table
involved. Clinical manifestations can range from mild to se- 55.2. Full blood count, blood glucose, arterial blood gases,
vere and are progressive over time. All modes of inheritance renal, and liver function are presented in Table 55.3. An
have been observed, but acquired defects also exist. All these electrocardiogram, chest radiograph, and echocardiogram
factors contribute to the difficulty in diagnosing patients with were requested and the patient’s previous anesthetic record
mitochondrial disease. These disorders were initially termed was obtained.
the mitochondrial myopathies, given that muscle was most often Elevated lactate and blood gas disturbances tend to occur in
identified as the predominant tissue affected. More recently it times of crisis in these disorders. It is important to establish
is recognized that any organ can be affected at any age; as such, preoperative values, as some patients will have a raised lactate
the term mitochondrial cytopathies is more appropriate.2 at baseline. The presence of hepatic dysfunction in this patient
Both the girl and her mother were present at the preopera- underscores the multiorgan nature of mitochondrial disease.
tive assessment. The patient’s mitochondrial disease had been The finding of left bundle branch block on the electrocar-
confirmed as Kearns-Sayre syndrome (KSS). At 9 years of age, diogram is indicative of the cardiac conduction defects that
she had undergone a muscle biopsy under general anesthesia at frequently occur in patients with KSS. Cardiomyopathy has
a pediatric facility. Her main presenting features were progres- also been described,5 necessitating an echocardiogram, which
sive ptosis, skeletal muscle fatigability, and deafness. More re- was normal in this case. The patient’s chest radiograph
cently, she had developed difficulty swallowing and repeated showed clear lung fields and a normal heart size.
203
15259_Ch55.qxd 3/15/09 6:48 AM Page 204
204 CHAPTER 55 • MITOCHONDRIAL DISEASE AND ANESTHESIA
T A B L E 5 5 . 1 Some of the Described Clinical Syndromes in Mitochondrial Disease
Acronym/Name Features
KSS (Kearns-Sayre syndrome) Ophthalmoplegia, cardiac conduction block, deafness,
retinitis pigmentosa, and skeletal muscle weakness
MELAS Mitochondrial encephalomyopathy, lactic acidosis, and
stroke-like episodes
MERRF Myoclonic epilepsy and ragged red fibers on muscle biopsy
NARP Neuropathy, ataxia, retinitis pigmentosa, and ptosis
MNGIE Mitochondrial neurogastrointestinal encephalopathy
LHON Leber hereditary optic neuropathy. Also Wolff-Parkinson-
White syndrome and neuropathy
Leigh’s syndrome Subacute sclerosing encephalopathy
What type of premedication should be given? Was this the most suitable anesthetic technique
Any form of sedative as a premedication was omitted in in this case?
this case. Patients with mitochondrial disease are extraordi- In reality, the safest anesthetic technique for patients with mito-
narily sensitive to sedatives and hypnotics. Respiratory chondrial disease is not known. Although many patients have
failure and alterations in conscious level can occur even at undergone anesthesia safely, there have been case reports descri-
low doses. bing worsening of underlying neurologic deficit, respiratory
Fasting can precipitate hypoglycemia and a metabolic cri- failure, high- degree atrioventricular block conduction block,
sis. The fasting period should be kept as short as possible. If malignant hyperthermia, and death following anesthesia.6–8
necessary, dextrose infusions can be used to supplement this Because of the limited information available in relation to
period. Lactate-containing intravenous fluids should be mitochondrial disease and anesthesia, there are no absolute
avoided. recommendations. Each anesthetic has to be tailored to the in-
The previous anesthetic record in this instance showed that dividual patient. Malignant hyperthermia has been reported
the patient had previously safely undergone a nontriggering in the setting of mitochondrial cytopathy.6,7 There are con-
anesthetic. The patient’s mother accompanied her to the oper- flicting opinions, however, as to whether a nontriggering tech-
ating room. Intravenous access was obtained and standard nique is required in mitochondrial disease. The use of inhaled
monitoring instituted. anesthetic agents has been widely described.9 As with other
Anesthesia was induced using 10-mg increments of propo- anesthetic drugs, there appears to be enhanced sensitivity to
fol. Once it was established that the patient’s airway could be these agents.10 In patients with KSS who are at risk of serious
maintained by manual ventilation, 25 mg of atracurium was arrhythmia, isoflurane and sevoflurane are the preferred
administered to facilitate tracheal intubation. Analgesia was agents. On the basis of the patient’s previous anesthetic his-
achieved using paracetamol 1 g and fentanyl 20 ␮g. Anesthesia tory, inhaled agents were not used in this case. Obtaining pre-
was maintained thereafter via propofol infusion and an vious anesthetic records is vital, as so little is known about
air/oxygen mixture. safety of anesthesia in patients with these disorders.
Patients with myopathy as a predominant feature of their
disease are at risk of suxamethonium-induced hyperkalemia.
Notwithstanding the additional risk of malignant hyperther-
mia, it therefore seems prudent to avoid using this agent.
T A B L E 5 5 . 2 Spirometry Results Propofol has been used safely in many patients with mito-
chondrial disease despite the fact that it can directly impair
Predicted
mitochondrial function. Caution is required with dosages of
Predicted Measured (%)
all hypnotic agents because of extreme sensitivity. A case of
FVC (L) 2.16 1.60 74% induction of anesthesia after as little as 75 mg of thiopentone
FEV1 (L) 2.14 1.56 73% in an adult has been described.11
Metabolic homeostasis during anesthesia for these patients
FEV1/FVC 99% 98% 99% is an important consideration. Ensuring that the patient does
(%) not experience hypothermia and shivering is imperative. A
Both the FEV1 and FVC are reduced, but the ratio of FEV1/FVC is normal glucose and acid-base status should also be maintained.
preserved. These findings are typical of a restrictive lung disease. In this The presence of left bundle branch block is of concern be-
case, it is caused by a respiratory muscle dysfunction. A reduction of cause patients with KSS undergoing anesthesia are at risk of
FEV1 and FVC in the range 65% to 85% of predicted values signifies sudden high-grade atrioventricular block.12 An isoprenaline
that the impairment is mild. infusion and access to external/temporary pacing should be
available during anesthesia.
15259_Ch55.qxd 3/15/09 6:48 AM Page 205
CHAPTER 55 • MITOCHONDRIAL DISEASE AND ANESTHESIA 205
T A B L E 5 5 . 3 Full Blood Count, Blood Glucose, Arterial Blood Gases, and Renal
and Liver Function
Sodium (135–145 mmol/L) 143 Hemoglobin (11–15 g/dL) 12.5
Potassium (3.5–5.5 mmol/L) 3.7 White blood cells (4–11 ⫻ 109/L) 11
Urea (3.0–8.0 mmol/L) 6.2 Red blood cells (3.8–5 ⫻ 1012/L) 4.6
Creatinine (0.07–0.1 mmol/L) 0.07 Platelet count (150–440 ⫻ 109/L) 300
Magnesium (0.7–1.0 mmol/L) 0.89 Hematocrit 34%–47% 38
Bilirubin (␮mol/L) 6 Glucose (4.0–7.5 mmol/L) 6.2
GGT (0–50 U/L) 79 Lactate (0.3–2.0 mEq/L) 1.0
ALP (32–110 U/L) 109 pH (7.35–7.45) 7.38
LDH (110–250 U/L) 298 PaCO2 (7.35–7.45) 39
AST (0–40 U/L) 256 PaO2 (85–100 mm Hg) 89
ALT (0–40 U/L) 240 Bicarbonate (22–26 mEq/L) 24
ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase.
Full blood count, glucose, electrolytes, lactate and renal parameters are all within normal limits. Hepatic dysfunction indi-
cates liver involvement in this case. Reassuringly, there is no evidence of hypercapnic respiratory failure. This finding would
be consistent with the spirometry findings of only mild restrictive lung disease.
At the end of the procedure, values obtained for capillary QUESTIONS

glucose concentration and arterial blood gas estimation were
similar to those obtained preoperatively. The patient’s temper- 1. Can mitochondrial cytopathies present in adulthood?
ature was 36.5°C, but there were no twitches evident follow-
ing train-of-four nerve stimulation. An additional 50 minutes Answer: Yes.
elapsed before four twitches could be elicited. The anesthesi- 2. Can suxamethonium be safely administered to patients
ologist then discontinued the propofol and administered 100% with a mitochondrial cytopathy?
oxygen. Following tracheal extubation, the patient was ob-
served in the postanaesthesia care unit for an extended period. Answer: No. Opinion is divided on whether such pa-
Her vital signs were normal, and she appeared comfortable. tients are at risk of malignant hyperthermia. Patients
with myopathy are at additional risk of suxamethonium
induced hyperkalemia.
Was the delay in recovery of neuromuscular
function to be expected? 3. Is Ringer's Lactate a suitable choice as replacement
Administering a standard dose of atracurium (0.5 mg/kg) in this fluid in these patients?
patient most likely contributed to the prolonged action. As with Answer: No. It contains lactate.
other anesthetic agents, patients with mitochondrial disease are
extraordinarily sensitive. When possible, these agents should be
avoided, as they contribute to postoperative respiratory muscle
References
weakness.13,14 They have been used safely, however, at reduced 1. Muravchick S, Levy RJ. Clinical implications of mitochondrial
dosage and with careful monitoring of neuromuscular function. dysfunction. Anesthesiology 2006;105:819–837.
Shorter-acting agents are preferable. The likelihood of renal or 2. Cohen BH, Gold DR. Mitochondrial cytopathy in adults: what
hepatic dysfunction (present in this case) makes atracurium and we know so far. Cleve Clin J Med 2001;68:625–642.
3. Gold DR, Cohn BH. Treatment of mitochondrial cytopathies.
cisatracurium the agents of choice. Semin Neurol 2001;21:309–325.
4. Barohn RJ, Clanton T, Zarife S, et al. Recurrent respiratory in-
KEY MESSAGES sufficiency and depressed ventilatory drive complicating mito-
chondrial myopathies. Neurology 1990;40:103–106.
5. Tveskov C, Angelo-Nielsen K. Kearns-Sayre and dilated car-
1. The anesthetic management plan should be tailored to diomyopathy. Neurology 1990;40:553–554.
the individual patient. 6. Ohtani Y, Miike T, Ishitsu T, et al. A case of malignant hyper-
thermia with mitochondrial dysfunction (letter). Brain Dev
2. Surgery should be delayed if there is evidence of con-
1985;7:249.
current infection. 7. Fricker R, Raffelsberger T, Rauch-Shorny S, et al. Positive ma-
3. Maintenance of normothermia, normoglycemia, and lignant hyperthermia susceptibility in vitro test in a patient with
acid-base status is imperative. mitochondrial myopathy and myoadenylate deaminase defi-
ciency. Anesthesiology 2002;97:1635–1637.
4. Lactate-containing solutions should be avoided. 8. Casta A, Quackenbush EJ, Houck CS, et al. Perioperative
white matter degeneration and death in a patient with a defect
15259_Ch55.qxd 3/15/09 6:48 AM Page 206
206 CHAPTER 55 • MITOCHONDRIAL DISEASE AND ANESTHESIA
in mitochondrial oxidative phosphorylation. Anesthesiology 12. Kitoh T, Mizuno K, Otagi T, et al. Anesthetic management for
1997;87:420–425. a patient with Kearns-Sayre syndrome. Anesth Analg 1995;
9. Shipton EA, Prosser DO. Mitochondrial myopathies and anaes- 80:1240–1242.
thesia. Eur J Anaesthesiol 2004;21:173–178. 13. Wisely NA, Cook PR. General anaesthesia in a man with mito-
10. Morgan PG, Hoppel CL, Sedensky MM, et al. Mitochondrial chondrial myopathy undergoing eye surgery. Eur J Anaesthesiol
defects and anesthetic sensitivity. Anesthesiology 2002;96: 2001;18:333–335.
1268–1270. 14. Edmonds JL. Surgical and anesthetic management of patients
11. James RH. Thiopentone and opthalmoplegia plus. Anaesthesia with mitochondrial dysfunction. Mitochondrion 2004;4:
1985;40;88. 543–548.
15259_Ch56.qxd 3/15/09 6:48 AM Page 207
CHAPTER 56
Emergence Agitation in
Pediatric Patients
Mansoor A. Siddiqui
CASE FORMAT: REFLECTION During this period of agitation, the patient’s heart
rate was 140 beats per minute, his blood pressure was
A 5-year-old boy was scheduled for inpatient surgery for 120/70 mm Hg, and his respiratory rate was 35 breaths
elective bilateral myringotomy and ventilator tube inser- per minute. He was reassured by the nurse, administered
tion. He had been fit and healthy and was not taking any O2 40% via face mask, and his mother was invited into
medication. He had not undergone anesthesia in the past. the recovery room. His mother’s presence helped to calm
The boy’s mother told him that “he is going to the hospital the child to some extent. Fentanyl 0.5 mcg.kg⫺1 was ad-
to have his ears fixed, and he is going to be asleep for ministered intravenously. Over 5 to 10 minutes, his agi-
that.” On examination in the day ward, the boy appeared tated behavior resolved, his heart rate decreased to 95
anxious. He was offered toys but, unlike the other children beats per minute, his blood pressure to 100/50 mm Hg,
in the ward at that time, he did not play with them. Both of and his respiratory rate decreased to 25 breaths per
his parents were present, and they also looked anxious. minute. The child appeared content and comfortable sit-
The boy tended to hold onto to his mother and seemed ting in his mother’s lap.
afraid when the nurses or doctors approached. After the boy was observed and monitored for 30 min-
The patient’s heart rate was 120 beats per minute, his utes in the recovery room, he was transferred to the inpa-
blood pressure was 100/50 mm Hg, and his respiratory tient ward where he remained for another 3 hours until he
rate was 25 breaths per minute. He had not taken food or had eaten, drank, passed urine, and his vitals signs were
drink for 6 hours before his early morning admission. His at preoperative levels. He was reviewed in the inpatient
upper airway was evaluated as Mallampati grade I with ward by the anesthetist before discharge, whose note in
normal dentition (no loose teeth). Informed consent was the medical record described him as “comfortable and
obtained from his parents for rectal administration of anal- calm.” The patient was discharged home with a prescrip-
gesic suppositories. The boy was premedicated with mida- tion for oral analgesics (paracetamol and ibuprofen) “as
zolam 0.5 mg/kg orally 30 minutes before his scheduled required” for 5 days.
procedure. Two days after discharge, the boy’s parents reported
The child’s mother accompanied him into the ope- to their family doctor that he was reluctant to eat and was
rating room. With standard monitors (electrocardio- sleeping for only 1 to 2 hours at a time. They also noted
gram, noninvasive blood pressure, and SpO2) in place, that, despite receiving the maximum prescribed doses of
anesthesia was induced with oxygen (O2)/nitrous oxide paracetamol and ibuprofen, he continued to complain of
(N2O) and sevoflurane as he sat in his mother’s lap. He discomfort. They were reassured and advised to continue
was then gently positioned on the operating table. to administer oral analgesics as required. Three days later,
Intravenous (IV) access was obtained with a 22-gauge IV the parents reported that the abnormal eating and sleeping
cannula, and a size 2 laryngeal mask airway was in- pattern appeared to have resolved.
serted. Anesthesia was maintained with sevoflurane
(1%–3% inspired) in O2/N2O (1:2). Diclofenac and parac-
etamol suppositories were administered before the proce-
dure began.
The procedure was carried out uneventfully in approxi- CASE DISCUSSION
mately 10 minutes. While the patient was breathing sponta-
neously, sevoflurane and N2O were discontinued (replaced Emergence agitation can manifest as a number of behavioral
by 100% O2), and the laryngeal mask airway was removed patterns that children display during recovery from anesthe-
while he was still deeply anesthetized. The patient’s mouth sia. Two scales that have been used to categorize and grade
and oropharynx were gently suctioned. Three minutes later, postoperative behavior in children are the Post Anesthetic
he started to move his arms and legs and pushed the face Behavior Scale (Table 56.1)1) and the Pediatric Anesthesia
mask away. At this stage, he was transferred to the recov- Emergence Delirium scale (Table 56.2).2
ery room where he quickly became extremely agitated. He The Pediatric Anesthesia Emergence Delirium scale score
started crying, calling for his “mama.” He persistently demonstrates negative correlation with a child’s age and time
reached for his ears and vomited once. to awakening and is significantly greater in children who
receive sevoflurane than in those who receive halothane.2
207
15259_Ch56.qxd 3/15/09 6:48 AM Page 208
208 CHAPTER 56 • EMERGENCE AGITATION IN PEDIATRIC PATIENTS
T A B L E 5 6 . 1 Postanesthetic Behavior Scale T A B L E 5 6 . 3 Possible Etiological Factors

Related to Emergence Agitation
1. Sleeping
2. Awake, calm Patient Factors
3. Irritable, crying Age14,15

4. Inconsolable crying Child’s temperament15
5. Severe restlessness, disorientation, thrashing around Preoperative anxiety9
Reproduced with permission from Cole JW, Murray DJ, McAkiter JD, Parent’s anxiety11
et al. Emergence behaviour in children: defining the incidence of excite- Hypoxia36
ment and agitation following anesthesia. Pediatr Anesth 2002:12:442–447.
Hypercarbia36
Hypoglycemia36
Hyponatremia36
Emergence agitation is distressing for the child and his or
her parents; its incidence will also influence the numbers of Surgical Factors
nurses needed to staff the recovery room. It can be associated Otorhinolaryngologic surgery14,15
with physical injury and can prolong the patient’s stay in the Pain16,19
postanesthetic care unit/recovery room3 (Table 56.3).
Anesthetic Factors
Rapid emergence19
STRATEGIES TO DECREASE Choice of inhalational agent (60% with sevoflurane
EMERGENCE AGITATION vs. 20% with halothane)19
It is important to identify patients with risk factors for emer- Intrinsic characteristics of anesthetic agents16,37,38
gence agitation, so that appropriate measures can be taken. Residual drug effects (e.g., ketamine, droperidol,
hyoscine, atropine)36
Anxiety Midazolam1
As many as 65% of children undergoing anesthesia and sur-
gery develop intense anxiety, preoperatively.4 Preoperative
anxiety is a subjective feeling of tension, apprehension, nerv-
ousness, and worry. Some of the causes of increased anxiety important in decreasing preoperative anxiety. Preparing chil-
include separation from parents, uncertainty about anesthesia dren for surgery can prevent psychological and behavioral
or surgery and about the outcome of the operation.5 manifestations of anxiety.6 Various distraction techniques
Preoperative anxiety is an important etiological factor in the have been used to decrease preoperative anxiety in the anes-
development of emergence agitation. thetic induction room, the including presence of clown doc-
The incidence of postoperative agitation/delirium is tors7 and a handheld video game.8
greater in anxious (9.7%) compared with nonanxious (1.5%)
children.3 Increased preoperative anxiety is also associated Temperament
with greater postoperative pain, analgesic consumption,
postoperative anxiety, sleep disturbance, and altered eating A child’s baseline temperament may be associated with the
patterns in 5- to 12-year-old children.3 Preoperative prepara- likelihood of his or her developing emergence agitation.
tion of children, their parents, and their environment are Children with a history of temper tantrums are more likely to
develop emergence agitation.9 Various scales exist to assess a
child’s baseline temperament. One such scale is EASI (emo-
tionality, activity, sociability, and impulsivity), for which reli-
T A B L E 5 6 . 2 Pediatric Anesthesia Emergence ability has been demonstrated.10 Younger, more emotional,
Delirium Scale more impulsive, and less sociable children are more likely to
develop emergence agitation. Parents of children in this
1. The child makes eye contact with the caregiver. group were also significantly more anxious.11
2. The child’s action is purposeful.
3. The child is aware of his or her surrounding. Parental Presence During Anesthesia
Induction
4. The child is restless.
Parental presence during induction of anesthesia can be used
5. The child is inconsolable. to treat or reduce preanesthetic anxiety. It has been shown to
Reproduced with permission from Sikich N, Lerman J. Development enhance the effect of oral midazolam premedication on emer-
and psychometric evaluation of the pediatric anesthesia emergence gence behavior of children undergoing general anesthesia.12
delirium scale. Anesthesiology 2004;100:1138–1145. Parental presence has no additive effect on the child’s compli-
ance during the anesthetic induction.12 A combination of
15259_Ch56.qxd 3/15/09 6:48 AM Page 209
CHAPTER 56 • EMERGENCE AGITATION IN PEDIATRIC PATIENTS 209
written, pictorial, and verbal information would improve the

T A B L E 5 6 . 5 Adjunct Medications
process of informed consent.13
• Midazolam 0.2 mg/kg premedication40–42
Age
• Clonidine ␮g/kg orally premedication43
Emergence agitation is observed more frequently in pre-
school children.14,15 Possible etiologic factors include psycho- • Clonidine 1 to 3 mcg/kg intraoperatively (decreases
logical immaturity, genetic predisposition, and the type of incidence of emergence agitation from 39% to 0%)44,45
procedure.1,16–18 • Ketamine 6 mg/kg premedication46
Anesthetic Factors • Fentanyl 2 ␮g/kg intranasally intraoperatively
(decreases incidence of emergence agitation from
Emergence agitation occurs in 60% of children after sevoflu- 23% to 2%)19 or 2.5 ␮g/kg intravenously14,26,47
rane anesthesia.19 A central nervous system excitatory effect of
sevoflurane20 and epileptiform activity during induction with • Dexmedetomidine 1␮g/kg after anesthetic induc-
sevoflurane have been reported.21 Induction using sevoflurane tion25,41
alone is associated with a greater incidence of emergence agi- • Ketorolac 1 mg/kg intraoperatively24
tation compared with when N2O is coadministered (35% vs.
5%).22 Whether awakening occurs rapidly or slowly does not
appear to influence the incidence of emergence agitation
(35.7% vs. 32, 6% respectively)16 (Table 56.4).
anxiety, and temper tantrums can occur postoperatively in
Surgical Factors and Adjunct as many as 50% of children.4 The Post-Hospital Behaviour
Medications Questionnaire is designed to evaluate maladaptive behav-
ioral responses in children after surgery. It has shown
Surgical procedures involving otorhinolaryngologic surgery good test-retest reliability and is a useful standardized tool
and head and neck surgery are associated with a greater inci- for assessing postoperative behavior.27 Using the Post-
dence of emergence agitation. It has been speculated that this Hospital Behaviour Questionnaire, it has been shown that
is caused by a “sense of suffocation.”23 children’s preoperative anxiety and emergence status were
Postoperative pain has been consistently implicated as an significant predictors of presence or absence of new mal-
important cause of emergence agitation.16,19,23,24 In children, adaptive behavior.11 The odds ratio for one or more new-
emergence agitation and pain behavior may be indistinguish- onset maladaptive behaviors is 1.43 for children with marked
able.25 The presence of pain as a predisposing factor to postop- emergence agitation.11
erative agitation explains the effectiveness of analgesic drugs,
either in prophylaxis or treatment of agitation. Opioid admin-
istration considerably decreases the incidence of postoperative
agitation26 (Table 56.5).
One or more of these interventions may be selected for KEY MESSAGES
managing children at greatest risk for emergence agitation.
1. Emergence delirium in children is defined as “a dis-
Long-Term Consequences turbance in a child’s awareness of and attention to
his or her environment with disorientation and per-
Emergence agitation in the recovery room is usually self- ceptual alterations including hypersensitivity to stimuli
limiting and resolves without pharmacologic intervention.1,3 and hyperactive motor behavior in the immediate
However, long-term sequelae can result. New maladaptive postoperative period.”2
behaviors such as nightmare crying, enuresis, separation
2. It is usually a self-limiting condition, appearing in the
immediate postoperative period and resolving sponta-
neously in 5 to 15 minutes28,29 but can last longer in
T A B L E 5 6 . 4 Modification of Anesthetic 2% to 3% of patients.1,30
Technique to Minimize Likelihood 3. Emergence agitation is defined as “a state of mild
of Emergence Agitation restlessness and mental distress that, unlike delirium,
is not always accompanied by a significant change
• Using nerve blocks to minimize postoperative pain in behavior.”31
• Parental presence during induction of anesthesia12 4. Emergence agitation can result from pain, physiological
• Caudal anesthesia for lower abdominal surgery38 compromise, or anxiety.32
• Avoiding inhalational agents especially those with low 5. As many as 10% to 50% of children (compared with
solubility19 5% of adults) demonstrate alerted behavior during
• Using total IV anesthesia37 emergence.33–35 Age, history of temper tantrums, type
of surgery, and the anesthetic technique are important
• IV bolus of propofol at the end of surgery39 predisposing factors.
15259_Ch56.qxd 3/15/09 6:48 AM Page 210
210 CHAPTER 56 • EMERGENCE AGITATION IN PEDIATRIC PATIENTS
QUESTIONS 9. Paul AT, Tonya MP, Susan T, et al. Assessment of risk factors
for emergence distress and postoperative behavioural changes in
children following general anaesthesia. Pediatric Anesth 2004;14:
1. What is emergence delirium and emergence agitation? 235–240.
Answer: Emergence delirium can be defined as “a distur- 10. Buss AH, Plomin R. Theory and measurement of EAS tem-
bance in a child’s awareness of and attention to his or perament: early developing personality traits. Hillsdale, NJ: L.
her environment with disorientation and perceptual Erlbaum Associates, 1984:98–130.
alterations including hypersensitivity to stimuli and hy- 11. Kain N, Caldwell-Andrews, Mayes LC, et al. Preoperative anx-
iety and emergence delirium and postoperative maladaptive be-
peractive motor behavior in the immediate postoperative
haviours. Anesth Analg 2004;99:1648–1654.
period.” Emergence agitation can be defined as “a state of 12. Arai YC, Ito H, Kandatsu N, et al. Parental presence during in-
mild restlessness and mental distress that does not always duction enhances the effect of oral midazolam on emergence
suggest a significant change in behavior.” behaviour of children undergoing general anesthesia. Acta
Anaesth Scand 2007:51:858–861.
2. What are the possible etiological factors contributing to 13. Astuto M, Rosano G, Rizzo G, et al. Preoperative parental infor-
the development of emergence agitation in children? mation and parents’ presence at induction of anaesthesia.
Answer: In children, preoperative anxiety, age, tempera- Minerva Anestesiol 2006;72:461–465.
ment, parents’ anxiety, type of surgery, type of anesthetic, 14. Finkel JC, Cohen IT, Hannallah RS, et al. The effect of in-
and adjunct medications all influence the likelihood of tranasal fentanyl on the emergence characteristics after sevoflu-
rane anesthesia in children undergoing surgery for bilateral
emergence agitation occurring. It is more commonly seen
myringotomy tube placement. Anesth Analg 2001;92:1164–1168.
in preschool children, with a history of temper tantrums 15. Anono J, Ueda W, Mamiya K, et al. Greater incidence of delir-
and those with separation anxiety undergoing ear, nose, ium during recovery from sevoflurane anaesthesia in pre school
and throat surgery under inhalation anesthetic (sevoflu- boys. Anesthesiology 1997:87:1298–1300.
rane, in particular). Pain is an important etiological factor. 16. Muto R, Miyasaka K, Takata M, et al. Initial experience of com-
plete switch over to sevoflurane in 1550 children. Pediatr Anesth
3. How can emergence agitation be prevented? 1993;3:229–233.
Answer: In children, methods to decrease preoperative 17. Welborn LG, Hannallah RS, Norden JM, et al. Comparison of
anxiety include careful explanation (written, verbal, emergence and recovery characteristics of sevoflurane, desflu-
pictorial) to the child of what to expect, psychological rane, and halothane in pediatric ambulatory patients. Anesth
Analg 1996;83:917–920.
preparation, parental presence during anesthesia induc-
18. Wells LT, Rasch DK. Emergence delirium after sevoflurane
tion, use of distraction techniques such as clowns or anaesthesia: a paranoid delusion? Anesth Analg 1999;88:
handheld video games, premedication (e.g., clonidine), 1308–1310.
and effective perioperative analgesia. Other methods 19. Naito Y, Tamai S, Shingu K, et al. Comparison between sevoflu-
include avoidance of inhalational anesthetic agents, rane and halothane for paediatric ambulatory anaesthesia. Br J
administering an IV bolus of propofol before waking the Anaesth 1991;67:387–389.
child, the use of regional anesthetic techniques such as 20. Eger EI. New inhaled anaesthetics. Anesthesiology 1994;80:
caudal block, and perioperative administration of 906–922.
fentanyl, clonidine, dexmedetomidine, or ketorolac. 21. Adachi M, Ikemoto Y, Kubo K, et al. Seizure-like movements
during induction of anaesthesia with sevoflurane. Br J Anaesth
1992:68:214–215.
22. Sarner J, Levine M, Davis P, et al. Clinical characteristics of
References sevoflurane in children Anesthesiology 1995:82:38–46.
1. Cole JW, Murray DJ, McAlister JD, et al. Emergence behaviour 23. Eckenhoff JE, Kneale DH, Dripps RD. The incidence and eti-
in children: defining the incidence of excitement and agitation ology of post anaesthetic excitement. Anesthesiology 1961;22:
following anaesthesia. Pediatr Anesth 2002;12:442–447. 667–673.
2. Sikich N, Lerman J. Development and psychometric evaluation of 24. Davis PJ, Greenberg JA, Gendelman M, et al. Recovery charac-
the pediatric anesthesia emergence delirium scale. Anesthesiology teristics of sevoflurane and halothane in preschool aged children
2004;100:1138–1145. undergoing bilateral myringotomy and pressure equalization
3. Voepel-Lewis T, Malviya S, Tait AR. A prospective cohort study tube insertion. Anesth Analg 1999;88:34–38.
of emergence agitation in the pediatric post anesthesia care unit. 25. Berrin I, Mustafa A, Alpern DT, et al. Dexmedetomidine
Anesth Analg 2003:96:1625–1630. decreases emergence agitation in pediatric patients after
4. Kain ZN, Mayes LC, O’Connor TZ, et al. Preoperative anxiety sevoflurane anaesthesia without surgery. Pediatr Anesth 2006;
in children, predictors and outcomes. Arch Pediatr Med 1996; 748–753.
150:1238–1245. 26. Cohen IT, Finkel JC, Hannallah RS, et al. The effect of fentanyl
5. Kain ZN, Caldwell-Andrews AA, Wang SM. Psychological on the emergence characteristics after desflurane or sevoflurane
preparation of the parent and pediatric surgical patient. anaesthesia in children. Anesth Analg 2002; 94:1178–1181.
Anesthesiol Clin North Am 2002;20:69–88. 27. Vernon DT, Schulman JL, Foley JM. Changes in children’s be-
6. Kain ZN, Caldwell-Andrews AA. Preoperative psychological havior after hospitalization. Am J Dis Child 1966;111:581–593.
preparation of the child for surgery: an update. Anesthesiol Clin 28. Olympio MA. Postanesthetic delirium: historical perspectives.
North Am 2005;23:597–614. J Clin Anesth 1991;3:60–63.
7. Laura V, Simona C, Arianna R, et al. Clown doctors as a treatment 29. Moore JK, Moore EW, Ellion RA, et al. Propofol and halothane
for preoperative anxiety in children. Pediatrics 2005;116:563–567. versus sevoflurane in paediatric day case surgery: induction and
8. Patel A, Schiebe T, Davidson M, et al. Distraction with a hand- recovery characteristics. Br J Anaesth 2003;90:461–466.
held video game reduces pediatric preoperative anxiety. Pediatr 30. Holzki J, Kretz FJ. Changing aspects of sevoflurane in pediatric
Anesth, 2006;16:1019–1027. anesthesia:1975–99 (editorial). Pediatr Anesth 1999;9:283–286.
15259_Ch56.qxd 3/15/09 6:48 AM Page 211
CHAPTER 56 • EMERGENCE AGITATION IN PEDIATRIC PATIENTS 211
31. Galford RE. Problems in anesthesiology: approach to diagnosis. agitation in children undergoing strabismus surgery during
Boston, MA: Little, Brown & Company, 1992:341–343. sevoflurane anesthesia. Anesthesiology 2007;107:733–738.
32. Voepel-Lewis T, Burke C. Differentiating pain and delirium is 40. Ko YP, Huang CJ, Hung YC, et al. Premedication with low
only part of assessing the agitated child. J Perianesth Nurs 2004; dose midazolam reduces the incidence and severity of emer-
19:298–299. gence agitation in pediatric patients following sevoflurane anes-
33. Lerman J, Davis PJ, Welborn LG, et al. Induction, recovery and thesia. Acta Anesthesiol Sin 2001;39:169–177.
safety and characteristics of sevoflurane in children undergoing 41. Riva J, Lejbussiewicz G, Papa M, et al. Oral premedication with
ambulatory surgery. Anesthesiology 1996;84:1332–1340. midazolam in paediatric anaesthesia. Effects on sedation and
34. Baum VC, Yemen TA, Baum LD. Immediate 8% sevoflurane gastric contents. Pediatr Anesth 1997;191–196.
induction in children: a comparison with incremental sevoflu- 42. Kogan A, Katz J, Erfat R, et al. Premedication with midazolam
rane and incremental halothane. Anesth Analg 1997;85: in young children: a comparison of four routes of administration.
313–316. Pediatr Anesth 2002;12:685–689.
35. Lepouse C, Lautner CA, Liu L, et al. Emergence delirium in 43. Almenrader N, Pessariello M, Coccetti B, et al. Premedication in
adults in the post anaesthetic care unit. Br J Anaesth 2006;96: children: a comparison of oral midazolam and oral clonidine.
747–753. Pediatr Anesth 2007;17:1143–1149.
36. Picard V, Dumont L, Pellegrini M. Quality of recovery in 44. Bock M, Kunz P, Schreckenberger R, et al. Comparison of cau-
children: sevoflurane versus propofol. Acta Anaesthesiol Scand dal and intravenous clonidine in prevention of agitation after
2000;44:307–310. sevoflurane in children. Br J Anaesth 2002;88:790–796.
37. Cohen IT, Finkel JC, Hannallah RS, et al. Rapid emergence does 45. Malviya S, Voepal-Lewis T, Ramamurthi R, et al. Clonidine for
not explain agitation following sevoflurane anaesthesia in infants the prevention of emergence agitation in young children: efficacy
and children: a comparison with propofol. Pediatric Anesth and recovery profile. Pediatr Anesth 2006;16:554–559.
2003; 13:63–67. 46. Kararmaz A, Kaya S, Turhanoglu S, et al. Oral ketamine pre-
38. Aouad MT, Kanazi GE, Siddik-Sayyed SM, et al. Preoperative medication can prevent emergence agitation in children after
caudal block prevents emergence agitation in children follow- desflurane anaesthesia. Pediatr Anesth 2004; 14:477–482.
ing sevoflurane anesthesia. Acta Anaesthesiol Scand 2005;49: 47. Galinkin JL, Fazil LM, Cuy RM, et al. Use of intranasal fentanyl
300–304. in children undergoing myringotomy and tube placement dur-
39. Aouad MT, Yazbeck-Karam VG, Nasr VG, et al. A single dose ing halothane and sevoflurane anaesthesia. Anesthesiology 2000;
of propofol at the end of surgery for the prevention of emergence 93:1378–1383.
15259_Ch57.qxd 3/15/09 6:49 AM Page 212
CHAPTER 57
The Acute Pain Team Role in
Management of a Patient With
Traumatic Upper Limb Amputation
Owen O’Sullivan
is lacking and (for ethical reasons) difficult to acquire. The

more general issue of the association between postoperative
pain management and patient outcome has recently been
A 46-year-old fisherman was taken to the emergency room
critically reviewed.1,2
of a small regional hospital on a Saturday morning. An ac-
cident in the harbor area resulted in a traumatic (avulsion)
amputation of his forearm proximal to the wrist, and para- What are the pain management options for
medics had attended to him at the site within minutes. The this patient?
amputated limb had been packed in ice, and bleeding The American Society of Anesthesiologists guidelines for the
was controlled with direct pressure. On arrival to the emer- management of acute pain in the perioperative period are
gency department, 2 hours after the accident, he walked summarized in Table 57.1.
in with the aid of coworkers and was immediately brought At the receiving hospital, the plastic surgeon who decided
to the resuscitation room. that the amputated limb was not suitable for replantation
An emergency medicine physician promptly carried out assessed the patient. An anesthetist (who had received a med-
a primary survey. The patient’s upper airway was patent; ical summary by telephone) arrived to assess the patient. The
vesicular breath sounds were audible on auscultation bilat- patient was hemodynamically stable but remained distressed
erally. His heart rate was 120 beats per minute; blood pres- and in pain with a verbal rating scale (VRS) score for pain of
sure, 190/100 mm Hg; and Glasgow Coma Scale, 15/15. 10/10. Having considered the risks and potential benefits
No other injuries were identified. Intravenous access was (delay in surgery, potential for axillary arterial injury, mini-
established, blood was sampled for routine investigations mizing operative stress response and anesthetic drug and opi-
(full blood picture, urea and electrolytes, serum glucose, oid requirements, and lessening risk of postoperative acute
lactate and arterial blood gas analysis were all normal), and long-term pain), the anesthetist elected to perform a
an intravenous (IV) morphine bolus was administered (in- supraclavicular block and to insert a catheter for continuous
crements of 2 mg IV totalling 12 mg over 80 minutes), and titratable analgesia. After explaining the procedure to the
prophylactic antibiotics were administered as the trauma patient, full asepsis was observed and the block was per-
team evaluated the injury. It was decided that, in view of formed and catheter inserted under ultrasound guidance
the patient’s general good condition and the relatively using a 21-gauge insulated needle. An initial dose of 25 mL
short injury/decision interval, that replantation should be of 0.25% levobupivacaine was administered. The patient was
considered at the regional plastic surgical referral service reassessed 20 minutes later, just before transfer and was
based in a hospital approximately an hour away. It was found to be much more comfortable with a VRS score of 2/10.
decided to transfer the patient urgently. Before transfer, During this 20-minute interval, the anesthetist provided the
the anesthetic service was contacted, as the patient was acute pain team (APT) (through the on-call pain nurse) with
still in extreme pain despite cumulative administration of a verbal summary of the case.
morphine 18 mg IV and paracetamol 2 g IV over approx- Prior to induction of general anesthesia (using a rapid
imately 4 hours. sequence induction technique), the patient reported pain in
the limb at rest as VRS of 3/10. Six hours had elapsed since
the injury. A further 10 mL of 0.25% bupivacaine was in-
jected through the supraclavicular catheter before surgical
What is the purpose of relieving or managing incision.
pain in patients who have suffered traumatic The operation, wound exploration, debridement, and
injury? a bone-shortening revision of the stump were uneventful.
Apart from humanitarian indications for treating pain after A continuous infusion of 0.1% bupivacaine (initially 8 mL per
trauma, inadequate analgesia can exacerbate the stress re- hour) was commenced via the supraclavicular catheter at
sponse, which can result in myocardial ischemia and stroke. the end of the procedure. Regular paracetamol 1 g IV and
Untreated pain is also associated with complications such as diclofenac 75 mg IV were prescribed, as was morphine 10 mg
impaired cough and ileus. However, evidence proving that intramuscularly for breakthrough pain. Because the anes-
pain control improves morbidity and mortality in this setting thetist was concerned about the risk of the patient developing
212
15259_Ch57.qxd 3/15/09 6:49 AM Page 213
CHAPTER 57 • MANAGEMENT OF A PATIENT WITH TRAUMATIC LIMB AMPUTATION 213
T A B L E 5 7 . 1 Acute Perioperative Pain Management
Institutional policies and procedures • Education and training for health care providers
for providing perioperative pain • Monitoring of patient outcomes
management • 24-hour availability of anesthetist providing perioperative pain management
• Use of a dedicated acute pain service
• Standardized, validated instruments to facilitate the regular evaluation and
documentation of pain intensity, the effects of pain therapy, and side effects
caused by the therapy
Preoperative evaluation of the patient • Evaluate patient factors
• Type of surgery, expected severity of postoperative pain, underlying medical
conditions, the risk-benefit ratio for the available techniques, patient’s pref-
erences, or previous experience with pain
• A directed pain history, a directed physical examination, and a pain control plan
Preoperative preparation of the patient • Adjust or continue medications that when suddenly stopped may provoke a
withdrawal syndrome
• Treatment(s) to reduce preexisting pain and anxiety
• Premedication(s) before surgery as part of a multimodal analgesic pain man-
agement program
• Patient and family education
• Include misconceptions that overestimate the risk of adverse effects and ad-
diction
Perioperative techniques for pain • Use therapeutic options such as epidural, intrathecal opioids, systemic opioid
management patient-controlled analgesia, and regional techniques after thoughtfully con-
sidering the risks and benefits for the individual patient
• Used in preference to intramuscular opioids ordered “as needed”
• Special caution should be taken when continuous infusion modalities are
used, as drug accumulation may contribute to adverse events
• Therapy selected should reflect the individual anesthetist’s expertise, as well
as the capacity for safe application of the modality in each practice setting
(including the ability to recognize and treat adverse effects)
Multimodal techniques for pain • Unless contraindicated, all patients should receive an around-the-clock
management regimen of nonsteroidal anti-inflammatory drugs, COX-2 selective in-
hibitors, or acetaminophen.
• Consider regional blockade with local anesthetics.
• Dosing regimens should be administered to optimize efficacy while mini-
mizing the risk of adverse events. The choice of medication, dose, route, and
duration of therapy should be individualized.
Adapted from Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists
Task Force on Acute Pain Management. Anesthesiology. 2004;100:1573–1581.
phantom limb pain (PLP), he also prescribed gabapentin Dutch study of upper limb amputees showed that the preva-
300 mg orally starting on the first postoperative day (300 mg lence of PLP was 51% (95% confidence level, 36%–63%);
every 12 hours on day 2 and 300 mg every 8 hours on day 3). phantom sensation, 76%; and stump pain, 48.6%.4 Although
A written referral was sent to the APT to facilitate follow-up most of the patients with PLP reported having “moderate”
of the patient’s pain management. to “very much” pain, only 4 of 99 respondents received
medical treatment for phantom pain. In 77% of cases, the in-
dication for surgery was trauma. The use of N-methyl-D-
Can phantom symptoms be prevented after aspartate receptors has been implicated in the development
traumatic amputation? of PLP, and the use of memantine (an N-methyl-D-aspartate
Pain perceived at the site previously occupied by an ampu- receptor antagonist) in a brachial plexus blockade post-
tated limb is common and can be very difficult to treat. A operatively in traumatic upper limb amputations has been
15259_Ch57.qxd 3/15/09 6:49 AM Page 214
214 CHAPTER 57 • MANAGEMENT OF A PATIENT WITH TRAUMATIC LIMB AMPUTATION
shown to decrease the intensity of PLP (but not beyond

KEY MESSAGES
6 months.)5
Some evidence exists that gabapentin, commonly used in
1. The American Society of Anesthesiologists guidelines
several neuropathic pain syndromes, is useful in treating
for perioperative pain management include the preop-
postamputation PLP.6 However, a study evaluating its effec-
erative assessment and preparation of patients and
tiveness when administered for 30 days postoperatively failed to
multimodal techniques for pain management.
show a reduction in incidence or intensity of postamputation
pain.7 Therefore, its use in the case described is not “evidence 2. To function optimally, an APT must operate as part of
based.” a multidisciplinary acute rehabilitation program.
Over the following 24 hours, the patient remained rela-
tively comfortable, self-reporting pain as VRS 2 to 4/10. As his 3. To date, the cost-effectiveness of establishing an APT
first postoperative day was a Sunday, the APT did not review has not been definitively established.
him until his second postoperative day. At this point, the team
completed a full pain history (including previous experience of
pain and use of pain medications) and examination including QUESTIONS
the insertion site of the supraclavicular catheter. Gabapentin
was discontinued. The APT visited the patient each day, as-
1. What are the important elements of an acute pain
sessing his pain and modifying its management throughout
team/service?
his admission.
Answer: The important elements of an acute pain
team/service are (a) designated personnel for provision
of 24-hour APS, (b) regular assessment and docu-
What is the role of the APT in the management mentation of pain scores, (c) development of protocols
of such patients? to achieve goals for postoperative mobilization and
A variety of organizations have recommended establishing rehabilitation, (d) education of ward nurses,
structures to provide dedicated postoperative pain service.3,8 (e) patient education, and (f) regular audit (including
Rawal identified important components of an acute pain serv- cost-effectiveness).
ice (APS) in a recent review article9:
2. What proportion of upper limb amputees will
• Designated personnel for provision of 24-hour APS experience phantom limb symptoms?
• Regular assessment and documentation of pain scores at
Answer: The majority of upper limb amputees will expe-
rest and at movement
rience phantom limb symptoms (pain, 51%; phantom
• Maintaining scores below a predetermined threshold
sensation, 76%).4
• Appropriate assessment tools for children and those with
cognitive impairment 3. Is establishment of an APT cost-effective?
• Development of protocols to achieve goals for postoperative
Answer: Although this has not been demonstrated
mobilization and rehabilitation
definitively to date, a body of related evidence indicates
• Education of ward nurses
that establishment of an APT may be cost-effective.
• Patient education
• Regular audit (including cost-effectiveness)
More than 10 years after the relevant recommendations of
References
the Royal College of Anaesthetists,8 a survey showed that 1. Lui SS, Wu CL. Effect of postoperative analgesia on major post-
83% of hospitals in the United Kingdom had an established operative complications: a systematic update of the evidence.
APS. However, most were open only Monday through Anesth Analg 2007;104:689–702.
2. White PF, Kehlet H. Postoperative pain management and pa-
Friday with reduced out-of-hours coverage with only 5%
tient outcome: time to return to work. Anesth Analg 2007;104:
covering 24 hours.10 The establishment of an APS is associ- 487–489.
ated with lesser postoperative pain ratings and can decrease 3. Practice guidelines for acute pain management in the periopera-
postoperative nausea and vomiting and postoperative uri- tive setting: an updated report by the American Society of
nary retention.11 A review of 10 economic evaluations of Anesthesiologists Task Force on Acute Pain Management.
APS programs failed to demonstrate their cost-effectiveness Anesthesiology. 2004;100:1573–1581.
definitively. This review was limited by the poor quality of 4. Kooijman CM, Dijkstra PU, Geertzen JH, et al. Phantom pain
the evaluations.12 The establishment of an APS is presently a and phantom sensations in upper limb amputees: an epidemio-
prerequisite for accreditation for training by the Royal logical study. Pain. 2000;87:33–41.
College of Anaesthetists13 and the Australian and New 5. Schley M, Topfner S, Wiech K, et al. Continuous brachial plexus
blockade in combination with the NMDA receptor antagonist
Zealand College of Anaesthetists. To function optimally, memantine prevents phantom pain in acute traumatic upper
an APT must operate as part of a multidisciplinary acute re- limb amputees. Eur J Pain 2007;11:299–308.
habilitation program.14 To justify provision of sufficient 6. Bone M, Critchley P, Buggy DJ. Gabapentin in postamputa-
resources to fully implement the APT “concept,” further ev- tion phantom limb pain: a randomized, double-blind, placebo-
idence is required regarding the clinical and economic con- controlled, cross-over study. Reg Anesth Pain Med 2002;27:
sequences. 481–486.
15259_Ch57.qxd 3/15/09 6:49 AM Page 215
CHAPTER 57 • MANAGEMENT OF A PATIENT WITH TRAUMATIC LIMB AMPUTATION 215
7. Nikolajsen L, Finnerup NB, Kramp S, et al. A randomized 11. Werner MU, Søholm L, Rotbøll-Nielsen P, et al. Does an acute
study of the effects of gabapentin on postamputation pain. pain service improve postoperative outcome? Anesth Analg 2002;
Anesthesiology. 2006;105:1008–1015. 95:1361–1372.
8. Working Party of the Commission on the Provision of Surgical 12. Lee A, Chan S, Chen PP, et al. Economic evaluations of
Services. Pain after surgery. London: Royal College of Surgeons acute pain service programs: a systematic review. Clin J Pain.
of England, College of Anaesthetists, 1990. 2007;23:726–733.
9. Rawal N. Organization, function, and implementation of acute 13. Smith G, Power I, Cousins MJ. Acute pain: is there scientific ev-
pain service. Anesthesiol Clin North Am 2005;23:211–225. idence on which to base treatment [editorial]? Br J Anaesth 1999;
10. Powell AE, Davies HT, Bannister J, et al. Rhetoric and reality on 82:817–819.
acute pain services in the UK: a national postal questionnaire 14. Kehlet H. Acute pain control and accelerated postoperative
survey. Br J Anaesth 2004;92:689–693. surgical recovery. Surg Clin North Am 1999;79:431–443.
15259_Ch58.qxd 3/15/09 6:50 AM Page 216
CHAPTER 58
Occupational Exposure to
Anesthetic Agents
Jason Van der Velde
used alone compared with when sevoflurane and N2O are

administered in combination.28
In rodents, long-term exposure to low concentrations of
A trainee anesthesiologist lodged a grievance with her
halogenated anesthetic agents impairs curiosity, exploratory be-
hospital attributing the spontaneous abortion of her third
havior, learning and memory function, and increases anxiety.29
pregnancy to exposure to anesthetic gases at work as a
The behavioral changes related to long-term exposure in hu-
causative factor. The hospital’s management strenuously
mans and its associated risk to professional performance have
denied these allegations citing that its policy of regularly
yet to be thoroughly investigated.
monitoring the operating rooms’ air quality showed that
A concern raised by pediatric operating room nurses sur-
her working environment consistently conformed to interna-
rounded the interpretation of maximum safe levels of atmos-
tional occupational health standards. Opinions within the
pheric sevoflurane. A maximum limit of 2 parts per million
hospital were divided, and considerable tensions mounted
(ppm) in the atmosphere was quoted as that set by national
over this emotive issue.
health safety legislation. Yet a hospital staff member recalled
18 ppm being monitored during one of the sampling periods.
Operating room staff, becoming increasingly concerned for
Does occupational exposure to anesthetic their own safety, were not satisfied by managerial assurances
gases represent a health risk to health care that the manufacturers’ recommended safe limit is 20 ppm.
workers?
Most occupational exposure limits (OELs) in force today are
What is an OEL ?
loosely based on meta-analysis1–3 of nine major studies4–12 car-
ried out between 1971 and 1985 that examined the associations The National Institute of Occupational Safety and Health
between (a) occupational exposure to nitrous oxide (N2O) (NIOSH) in the United States America clearly states that it is
and/or some volatile anesthetic agents and (b) a range of ad- unable to identify a safe OEL for waste anesthetic gases.30
verse health effects, notably spontaneous abortion. Limitations Current recommendations from NIOSH are that potential
of these investigations include inadequate power, failure to risks should be minimized by “reducing exposures to the
measure personal exposures, and failure to take account of greatest extent possible.” Table 58.1 lists the range of advised
confounding factors such as the variety or absence of scaveng- OELs as set by various international health authorities. Unless
ing systems used and any additional environmental pollutants. indicated, they are expressed as a time-weighted average expo-
Several subsequent major studies neither ruled out these con- sure in an 8-hour working day.31
cerns, nor demonstrated significant association between expo- Manufacturers advise a maximum exposure limit to known
sure and adverse health outcomes.13–19 hazards. In a recent study, formation of micronucleated lym-
The authors of two large epidemiologic studies have con- phocytes was compared in two groups of anesthetic personnel
cluded that occupational exposure to volatile agents may be exposed to different levels of waste anesthetic agents. The re-
related to immunologic, neurologic, renal, or hepatic toxic sults indicate that the current range of international limits ap-
effects.20,21 Observational studies have shown associations be- pears to be appropriate (at least in terms of this marker).32
tween exposure to halogenated agents and a deficit in manual Some staff members believed that volatile anesthetic agents
dexterity, headache, depression, anxiety, loss of appetite, mem- were efficiently scavenged in the pediatric operating rooms,
ory loss, and change in intellectual function.22–25 Clearly, it whereas others were convinced that, if they could smell the
would require substantial collaboration to build a conclusive agents, the concentrations present could not be “safe.”
evidence base.
The adverse health effects associated with N2O exposure
alone are spontaneous abortion (relative risk ⬵ 1.3 to 1.9) What is the difference between personal expo-
and infertility.26,27 If the use of N2O is to fall out of favor, it sure risk and monitored environmental level?
is conceivable that exposure to other volatile anesthetics will Operating room anesthetic agent concentrations are usually
increase. This has been specifically investigated using both monitored from a fixed point in the room using photoa-
environmental and personal monitoring. Fortunately, the coustic infrared spectrometry, “monitored environmental
occupational exposure to sevoflurane is not greater when it is level.” Because of air movement and scavenging, anesthetic
216
15259_Ch58.qxd 3/15/09 6:50 AM Page 217
CHAPTER 58 • OCCUPATIONAL EXPOSURE TO ANESTHETIC AGENTS 217
T A B L E 5 8 . 1 Recommended Occupational Exposure Levels for Anesthetic Vapors in Various Countries
N2O Halothane Enflurane Isoflurane Sevoflurane Desflurane

Austria – 5 – – – –
Denmark 100 5 2 – – –
France – 2 – – – –
Germany 100 5 20 – – –
Great Britain 100 10 50 50 – –
Italy 100 – – – – –
Norway 100 5 2 2 – –
Sweden 100 5 10 10 – –
Switzerland 100 5 10 10 – –
US-NIOSH 25 2 2 2 2 2
US-ACGIH 50 50 75 – – –
US-NIOSH, National Institute of Occupational Safety and Health; US-ACGIH, American Conference of Governmental Industrial Hygienists.
agent levels may not be uniform throughout the room. By chromatography-mass spectrometry for determination of
placing the sampling device at the shoulder of a staff mem- N2O and sevoflurane in urine and environmental samples is
ber, that is, sampling directly from their personal breathing accurate and sufficient for this purpose.
zone, a more accurate “personal exposure level” may be The unscavenged use of on-demand N2O:O2 in poorly
measured. Inhalational induction with sevoflurane and N2O ventilated labor rooms is widespread. There is a strong posi-
in pediatric practice was found to violate NIOSH-recom- tive correlation between environmental concentrations and
mended personal exposure levels approximately 50% of the midwives’ biological uptake of N2O. N2O in biological tis-
time based on the personal samples but not in the room sam- sues is poorly soluble and therefore should be eliminated
ples.33 This personal exposure risk appears to strongly corre- rapidly between shifts. Interestingly, 50% of midwives stud-
late with anesthetic technique and training. ied had non-zero baseline values of N2O in their urine on
During maintenance of pediatric anesthesia, the use of un- arrival to the workplace and these 50% showed very high
cuffed endotracheal tubes and the Ayres T-Piece can lead to levels.36
greater monitored environmental levels of anesthetic agents.34 It is unlikely that staff working in postanesthesia care
OELs are, however, rarely violated provided efficient pres- units are exposed to important amounts of volatile agents
sure/exhaust ventilation, above 12 air exchanges per hour, and from the low concentrations expired by recovering patients.
efficient active scavenging systems are in place. When compared with their colleagues on surgical wards, bi-
Personal exposure risk monitoring reveals that during ological concentrations of N2O for recovery room personnel
maintenance of anesthesia with laryngeal mask airways in were 3.1 ppm versus 1.17 ppm.37
adults, sevoflurane concentrations frequently exceed 2 ppm Following this risk assessment, a number of simple strate-
and 50 ppm for N2O. Alarmingly, these findings occurred de- gies were investigated to reduce staff exposure.
spite the use of low-flow circle circuits, gas scavenging, and
correct laryngeal mask airway insertion technique and sizing.35
What means are available to minimize
To address increasing staff concerns, the hospital manage-
occupational exposure of health care workers
ment instituted a thorough review of the areas of the hospital
to anesthetic agents?
where anesthetic agents were administered or where patients
recovering from anesthesia were monitored. Scavenging When Mapleson D circuits were equipped with
an airway pressure-limiting valve allowing direct connection
to an anesthetic gas extractor, the ambient levels of sevoflurane
Do areas other than operating rooms pose a and N2O measured in the breathing area around the anesthe-
risk of occupational exposure to anesthetic siologist decreased from 7 (26) to 1.1 (1) ppm (p 0.001).38
agents?
The monitoring for environmental pollutants by direct reading Ventilation When surgeons and scrub nurses were asked
instrumentation such as photoacoustic infrared spectrometry is about symptoms related to occupational exposure, a greater
expensive and restricts normal staff movements, potentially incidence of noticing a “smell of gas” was registered for the
leading to spurious results. group without an extractor (87% vs. 11% in the extractor group,
Personal environmental sampling using passive diffusion p 0.003). Higher rates were also found for general discomfort
tubes or by urine collection is cost-effective and a method that (62% vs. 11%, p 0.05), nausea (62% vs. 0%, p 0.009), and
staff find both acceptable and convenient. The use of gas headache (62% vs. 0%, p 0.009) in the absence of the extractor.
15259_Ch58.qxd 3/15/09 6:50 AM Page 218
218 CHAPTER 58 • OCCUPATIONAL EXPOSURE TO ANESTHETIC AGENTS
Anesthetic Practice The practice of anesthesiology is not con- 7. Cohen EN, Brown BW, Bruce DL, et al. Occupational disease
fined to the operating room. Investigations examining the ef- among operating room personnel: a national study. Anesthesiology
fects of sevoflurane and N2O exposure on gene mutation,39 1974;41:321–340.
specifically, the incidence of sister chromatid exchanges in pe- 8. Corbett TH, Cornell RG, Endres JL, et al. Birth defects among
children of nurse-anesthetists. Anesthesiology 1974;41:341–344.
ripheral lymphocytes, concluded that a 2-month rotation out of
9. Knill-Jones RP, Newman BJ, Spence AA. Anaesthetic practice
the operating room environment returned the incidence of gene and pregnancy: controlled survey of male anesthetists in the
mutation to that of the general population. United Kingdom. Lancet 1975;2:807–809.
10. Cohen EN, Brown BW, Bruce DL, et al. A survey of anesthetic
health hazards among dentists. J Am Dent Assoc 1975;90:
1291–1296.
KEY MESSAGES 11. Cohen EN, Gift HC, Brown BW, et al. Occupational disease in
dentistry and chronic exposure to trace anesthetic gases. J Am
1. Definitive (level 1) evidence regarding the risk of Dent Assoc 1980;101:21–31.
occupational exposure to anesthetic agents is lacking. 12. Tomlin PJ. Health problems of anesthetists and their families in
the west midlands. Br Med J 1979;1:779–784.
2. Personal environmental monitoring provides the best 13. Ericson A, Kallen B. Survey of infants born in 1973 or 1975 to
measure of occupational exposure to anesthetic Swedish women working in operating rooms during their preg-
agents. nancies. Anesth Analg 1979;58:302–305.
14. Pharoah POD, Alberman E, Doyle P, et al. Outcome of preg-
3. Exposure can be decreased through training, technical nancy among women in anaesthetic practice. Lancet 1977;1:34–36.
innovation, and optimizing working practices. 15. Rosenberg PH, Vanttinen H. Occupational hazards to repro-
duction and health in anesthetists and pediatricians. Acta
Anaesthesiol Scand 1978;22:202–207.
16. Axelsson G, Rylander R. Exposure to anaesthetic gases and spon-
taneous abortion: response bias in a postal questionnaire study.
QUESTIONS Int J Epidemiol 1982;11:250–256.
17. Heidam LZ. Spontaneous abortions among dental assistants, fac-
1. Which adverse health outcomes may be associated tory workers, painters, and gardening workers: a follow-up
study. J Epidemiol Community Health 1984;38:149–155.
with occupational exposure to N2O?
18. Lauwerys R, Siddons H, Misson CB. Anaesthetic health hazards
Answer: The adverse health effects associated with among Belgian nurses and physicians. Int Arch Occup Environ
N2O exposure alone include spontaneous abortion Health 1981;48:195–203.
(relative risk ⬵ 1.3 to 1.9) and infertility. 19. Hemminki K, Kyyronen P, Lindbohm M. Spontaneous abor-
tions and malformations in the offspring of nurses exposed
2. What means are available to minimize occupational to anaesthetic gases, cytostatic drugs, and other potential haz-
exposure of health care workers to anesthetic agents? ards in hospitals, based on registered information of outcome.
J Epidemiol Community Health 1985;39:141–147.
Answer: Optimizing scavenging, environmental ventila- 20. Martínez-Frías ML, Bermejo E, Rodríguez-Pinilla E, Prieto L.
tion, anesthetic practice, and regular personal monitor- Case-control study on occupational exposure to anesthetic gases
ing can minimize occupational exposure of health care during pregnancy. Int J Risk Safety Med 1998;11:225–231.
workers to anesthetic agents. 21. Vessey MP, Nunn JF. Occupational hazards of anaesthesia. BMJ
1980;201:696–698.
3. What is NIOSH? 22. Cook TL, Smith M, Starkweather JA, et al. Behavioral effects of
Answer: NIOSH stands for the National Institute of trace and subanesthetic halothane and nitrous oxide in man.
Occupational Safety and Health (in the United States). Anesthesiology 1978;49:419–424.
23. Levin ED, Bowman RE. Behavioral effects of chronic exposure
to low concentrations of halothane during development in rats.
Anesth Analg 1986;65:653–659.
References 24. Zacny JP, Sparacino G, Hoffmann PM, et al. The subjective,
1. Buring JE, Hennekens CH, Mayrent SL, et al. Health experi- behavioral and cognitive effects of subanesthetic concentrations
ences of operating room personnel. Anesthesiology 1985;62: of isoflurane and nitrous oxide in healthy volunteers.
325–330. Psychopharmacology (Berl). 1994;114:409–416.
2. Tannenbaum TN, Goldberg RJ. Exposure to anesthetic gases 25. Zacny JP, Yajnik S, Lichtor JL, et al. The acute and residual ef-
and reproductive outcome: a review of the epidemiologic litera- fects of subanesthetic concentrations of isoflurane/nitrous oxide
ture. J Occup Med 1985;27:659–668. combinations on cognitive and psychomotor performance in
3. Boivin J. Risk of spontaneous abortion in women occupationally healthy volunteers. Anesth Analg 1996;82:153–157.
exposed to anaesthetic gases: a meta-analysis. Occup Environ 26. Tannenbaum TN, Goldberg RJ. Exposure to anesthetic gases
Med 1997;54:541–548. and reproductive outcome: a review of the epidemiologic litera-
4. Cohen EN, Bellville JW, Brown BW. Anesthesia, pregnancy, ture. J Occup Med 1985;27:659–668.
and miscarriage: a study of operating room nurses and anes- 27. Boivin J. Risk of spontaneous abortion in women occupationally
thetists. Anesthesiology 1971;35:343–347. exposed to anaesthetic gases: a meta-analysis. Occup Environ
5. Knill-Jones RP, Rodrigues LV, Moir DD, et al. Anaesthetic Med 1997;54:541–548.
practice and pregnancy: controlled survey of women in the 28. Schiewe-Langgartner F. [Exposure of hospital personnel to
United Kingdom. Lancet 1972;1:1326–1328. sevoflurane]. [Article in German]. Anaesthesist. 2005;54:667–672.
6. Rosenberg P, Kirves A. Miscarriages among operating theatre 29. Ozer M, Baris S, Karakaya D, et al. Behavioural effects of
staff. Acta Anaesthesiol Scand 1973;53(Suppl):37–42. chronic exposure to subanesthetic concentrations of halothane,
15259_Ch58.qxd 3/15/09 6:50 AM Page 219
CHAPTER 58 • OCCUPATIONAL EXPOSURE TO ANESTHETIC AGENTS 219
sevoflurane and desflurane in rats. Can J Anesth 2006;53: level in operating rooms. Int J Hyg Environ Health2007;210:
7653–658. 133–138.
30. National Institute of Occupational Safety and Health. Criteria 35. Hoerauf K, Koller C, Jakob W, et al. Isoflurane waste gas expo-
for a recommended standard: occupational exposure to anesthetic sure during general anaesthesia: the laryngeal mask compared
gases and vapors. Cincinnati: US Dept of Health, Education, and with tracheal intubation. Br J Anaesth 1996;77:189–193.
Welfare (DHEW), 1977. 36. Henderson KA, Matthews IP, Adisesh A, Hutchings, AD.
31. Hoerauf KH, Wallner T, Akca O, et al. Exposure To sevoflu- Occupational exposure of midwives to nitrous oxide on delivery
rane and N2O. Anesth Analg 1999;88:925–929. suites. Occup Environ Med 2003;60;958–961.
32. Wiesner G, Hoerauf K, Schroegendorfer K, et al. High-level, 37. Nayebzadeh A. Exposure to exhaled nitrous oxide in hospitals
but not low-level, occupational exposure to inhaled anesthetics is post-anesthesia care units. Ind Health 2007;45:334–337.
associated with genotoxicity in the micronucleus assay. Anesth 38. Sanabria Carretero P. [Occupational exposure to nitrous oxide
Analg 2001;92:118–122. and sevoflurane during pediatric anesthesia: evaluation of an
33. Hoerauf K, Wallner T, Akc O, et. al. Exposure to sevoflurane anesthetic gas extractor]. [Article in Spanish]. Rev Esp Anestesiol
and nitrous oxide during four different methods of anesthetic in- Reanim 2006;53: 618–625.
duction. Anesth Analg 1999;88:925–929. 39. Eroglu A. A comparison of sister chromatid exchanges in lym-
34. Krajewski W. Occupational exposure to nitrous oxide—the role phocytes of anesthesiologists to non anesthesiologists in the same
of scavenging and ventilation systems in reducing the exposure hospital. Anesth Analg 2006;102:1573–1577.
15259_Ch59.qxd 3/15/09 7:22 AM Page 220
CHAPTER 59
Fetal Oxygen Saturation and

Caesarean Section
Siun Burke
CASE FORMAT: STEP BY STEP tocaval compression, use of vasopressors, and fluid loading.1 A
recent Cochrane review concluded that there was no evidence
A 28-year-old, 100-kg, term primigravida presented in to show that regional anesthesia was superior to general anes-
labor requesting epidural analgesia. thesia in terms of major maternal or neonatal outcomes.2 It
must be remembered that the absolute risk of maternal mortal-
ity associated with general anesthesia for caesarean section is 32
per million, which is 17-fold greater than that with regional
What are the risks associated with epidural anesthesia.3 The incidence of failed tracheal intubation in the
analgesia in labor? obstetric population, 1 in 250,4 is as many as 10 times greater
See Table 59.1. than that in the general population. Recognizing the risks to the
mother associated with general anesthesia has led to an in-
The epidural was inserted on the second attempt, and a creased use of regional anesthesia for caesarean deliveries.
bolus dose of 10 mL 0.25% bupivacain--e with 50 ␮g of fentanyl The anesthetist reassured the patient that there was no
was administered followed by an epidural infusion of levobupi- major difference in neonatal outcome between general, spinal,
vacaine 0.125% at 12 mL per hour. The patient, however, con- or epidural anesthesia. In view of her elevated body mass
tinued to complain of discomfort with each contraction. Four index and potentially difficult airway, he felt regional anesthe-
hours later, a vaginal examination revealed minimal progress, sia was preferable to general anesthesia.
and the patient was scheduled for an emergency lower-seg- The patient was prescribed antacid prophylaxis, and a
ment caesarean section. 16-gauge intravenous cannula was inserted. In the operating
room, with routine monitors in place, the anesthetist pro-
ceeded with spinal anesthesia. Following dural puncture with
How should the anesthetist proceed?
a 25-gauge pencil-point spinal needle and aspiration of clear
A detailed preoperative assessment will enable early identifi- cerebrospinal fluid, the anesthetist administered 12.5 mg of
cation of a poorly functioning epidural and any potential prob- hyperbaric bupivacaine intrathecally.
lems if spinal or general anesthesia is deemed necessary.
On preoperative assessment, the patient’s past medical his-
tory was unremarkable. However, she had a short stature and What are the risks of administering spinal
was morbidly obese with a body mass index of 46 kg/m2. anesthesia following inadequate epidural for
Examination revealed a Mallampati grade III airway. lower-segment caesarean section?
The patient’s vital signs were normal; her blood pressure
was 120/64 mm Hg, and her heart rate was 92 beats per Spinal anesthesia after epidural analgesia may result in an
minute. The epidural block was assessed, and despite augmen- unpredictable final block height. One retrospective review es-
tation with 20 mL of bupivacaine 0.5%, only extended to T10 timated the incidence of high spinal anesthesia to be 11% in
and was patchy. The anesthetist explained to the patient that patients after prior failed epidural blockade versus fewer than
the epidural was ineffective and that the operation would pro- 1% in patients undergoing spinal anesthesia alone.5 This may
ceed under spinal anesthesia. The patient asked whether any be explained by the volume of the dural sac being restricted by
form of anesthesia was superior in terms of neonatal outcome. fluid in the epidural space. There is controversy regarding the
optimal dose of hyperbaric bupivacaine in this setting; some
investigators advocate reducing the dose by 20% to 30%,6
How should the anesthetist respond to whereas others believe this increases the risk of a second unsat-
this query? isfactory block.7
A meta-analysis comparing different methods of anesthesia Whichever approach is used, early recognition of an inade-
for caesarean section and neonatal acid base status analyzed quate epidural block is important to avoid persisting with fur-
27 studies and concluded that spinal anesthesia could not be ther doses of epidural local anesthetic. An assessment of the
considered safer than general anesthesia or epidural anesthe- urgency of the situation will help guide further anesthetic
sia for the fetus.1 management.
Adverse maternal circulatory changes associated with spinal Spinal anesthesia should be followed by careful position-
anesthesia may result from excessive sympathetic blockade, aor- ing and frequent block assessment. The parturient should be
220
15259_Ch59.qxd 3/15/09 7:22 AM Page 221
CHAPTER 59 • FETAL OXYGEN SATURATION AND CAESAREAN SECTION 221
T A B L E 5 9 . 1 Complications of Epidural T A B L E 5 9 . 2 Determinants of Fetal

Analgesia Oxygenation
Immediate Maternal oxygen delivery • Uterine artery blood flow

Hypotension (systolic blood pressure ⬍100 mm Hg or a to the placenta • Oxygen capacity of
decrease of 25% below preblock average) maternal blood
• Oxygen affinity of
Urinary retention
maternal blood
Local anesthetic-induced convulsions*
Oxygen transfer across • Oxygen-diffusing
Local anesthetic-induced cardiac arrest* the placenta capacity
Delayed Fetal oxygen-carrying • Umbilical vein blood flow
Postdural puncture headache capacity • Oxygen capacity of fetal
Transient backache blood
• Oxygen affinity of fetal
Epidural abscess or meningitis*
blood
Permanent neurologic deficit*
*Very rare.
Reproduced with permission from Vincent RD Jr, Chestnut DH.
Epidural analgesia during labor. American Family Physician 1998;58:
1785–1792. What are the determinants of fetal oxygenation?
Oxygen delivery to the fetus (mmol/min) is given by the prod-
uct of umbilical blood flow and the oxygen content of umbili-
cal venous blood (Table 59.2).
assessed regularly for difficulty in phonation, swallowing, Maternal oxygen delivery to the placenta is affected by uter-
breathing, and weakened handgrip. Extra vigilance is ine artery blood flow, oxygen content of maternal uterine ar-
required if a bolus has been administered via the epidural tery blood, hemoglobin concentration, and saturation. Uterine
in the 30 minutes prior to spinal anesthesia, if the blood flow at term is 10% of cardiac output. Hypotension, uter-
patient weighs more than 120 kg, or if the height is less ine contractions, and vasoconstriction can all decrease uterine
than 4⬘8⬙.6 The use of a combined spinal epidural tech- blood flow.
nique allows a smaller intrathecal dose to be used with the In the case described, maternal hypotension and desatura-
option of “topping up” using the epidural catheter if the tion reduced oxygen delivery to the placenta.
block is inadequate. The fetus has about 42 mL of oxygen reserves, and its oxy-
In this case, the patient was 100 kg, of short stature, and gen consumption is 20 mL/min. A fetus deprived of oxygen
had just received an epidural top-up before spinal anesthesia. can survive 10 minutes (rather than 2 minutes one might ex-
After the spinal, the patient’s blood pressure decreased to pect from these values) by shunting blood flow to vital organs
74/53 mm Hg, and her heart rate dropped to 62 beats per and decreasing oxygen consumption.
minute. She experienced nausea, removed the wedge, and The fetus has many protective mechanisms to ensure its
lay supine. For the first time, late decelerations (fetal heart oxygen extraction capacity. The hemoglobin concentration is
rate ⬍90 beats per minute) were evident on the cardiotacho- higher (15 to 16 g/dL). Fetal hemoglobin is 80% to 90% satu-
graph (Fig. 59.1). rated at a pO2 of 35mm Hg, whereas adult hemoglobin is only
Figure 59.1 • Cardiotachograph

Showing Late Decelerations.
15259_Ch59.qxd 3/15/09 7:22 AM Page 222
222 CHAPTER 59 • FETAL OXYGEN SATURATION AND CAESAREAN SECTION
O2 Sat % T A B L E 5 9 . 3 Umbilical Artery Blood Gas

100
Normal Values
Fetus Mother
80 pO2 1.8 kPa 2.38 ⫹/⫺0.9
Mother pCO2 7.2 kPa 7.49 ⫹/⫺1.13
60 pH 6.98 7.24 ⫹/⫺0.07
Fetus
Base excess ⫺14 ⫺3.6 ⫹/⫺2.7
40 Lactate 6.4 ⬍2
20
How should the anesthetist proceed?

Management of High/Total spinal anesthesia requires early
0 20 40 60 80 100
detection and supportive management of airway, breathing,
Fetus Mother and circulation.
Following preoxygenation, application of cricoid pressure,
PO2 mmHg and induction of general anesthesia, laryngoscopy revealed a
Figure 59.2 • Fetal and Adult Oxyhemoglobin
Cormack and Lehane grade 3 view.
Dissociation Curves.
It was not possible to intubate the trachea, and the oxygen
saturation decreased below 70%. The anesthetist managed to
manually ventilate the patient via a face mask, and the oxygen
saturation increased to 82%.
30% saturated at this pO2. This difference is caused by a left- After several minutes, a baby boy was born. His Apgar scores
ward shift in the fetal oxyhemoglobin dissociation curve.8 were 2 and 3 at 1 and 5 minutes, respectively (Table 59.3).
(Fig. 59.2).
Supplemental oxygen (6 L per minute via 40% Ventimask
[Flexicare Medical Limited, Mid Glamorgan, United Is umbilical cord blood gas analysis useful in
Kingdom]), Hartmann’s solution 500 mL, and repeated doses of the assessment of the newborn?
phenylephrine (100 ␮g, ⫻3) were administered rapidly, and the Umbilical cord blood gas analysis is now recommended in all
patient was repositioned with a left lateral tilt. Her blood pres- high-risk deliveries by both the British and American Colleges
sure improved to 90/53 mm Hg, and SpO2 increased to 95%. of Obstetrics and Gynecology. Umbilical artery pH has a meta-
bolic and a respiratory component, the latter largely determined
by maternal respiration. Isolated fetal respiratory acidosis is usu-
Is supplemental oxygen beneficial during a ally the result of short-lived impairment in the uteroplacental or
caesarean section? fetoplacental circulation, and ongoing impairment results in
Studies during general anesthesia for caesarean delivery have progressive metabolic acidosis caused by anaerobic glycolysis.
shown improved pO2 and Apgar scores with increased inhaled Consequently, most severe fetal acidosis is mixed. Base excess is
fractions of oxygen. A study of hyperoxia versus normoxia in independent of respiration and is thus a better index of the
epidural anesthesia showed better umbilical artery base excess metabolic component and key to evaluating the recent prenatal
in the hyperoxia group.9 Some investigators believe maternal environment.1 Base excess usually decreases by a total of 3
hyperoxia is necessary to build up a reserve of fetal pO2, as mmol/L in uncomplicated labor and by 1 mmol/L every 30 min-
fetal oxygenation ceases after uterine incision after which un- utes under conditions when there are frequent heart rate decel-
expected delays could cause damage.10 Patients who undergo erations. The most profound fetal compromise, uterine rupture,
spinal anesthesia may be under particular risk because of its changes pH by 1 mmol/L every 2 to 3 minutes.13
restrictive effect on ventilation. Portman et al. developed a validated score for predicting
It has been argued that maternal hyperoxia could cause multiorgan impairment following perinatal asphyxia. They
hypoventilation, CO2 retention, and subsequent placental found that a score combining a measure of cardiotachograph
vasoconstriction. Administration of oxygen to the mother at abnormality, umbilical artery base excess, and low 5-minute
5 liters per minute has been shown to reduce intervillous Apgar score was strongly associated with morbidity.14 Lactate
blood flow significantly.11 A maternal FiO2 of 0.6 produces a measured in umbilical cord blood is almost entirely fetal in
significant increase in free radical activity in both maternal origin. Umbilical cord lactate has been shown to correlate with
and fetal blood.12 Nevertheless, maternal hyperoxia during fetal pH and base excess.15
labor has been shown to increase pO2 in the compromised The neonate was intubated, stabilized, and transferred to
fetus.1 the neonatal intensive care unit. A senior anesthetist arrived,
Five minutes later, the patient became distressed, she and the mother was intubated with the aid of a gum elastic
started to complain of paraesthesia in her arms and difficulty bougie. The case proceeded uneventfully, and the mother was
breathing, and then her voice became weak. On examination, extubated once fully awake in the recovery room. The neona-
there was only minimal chest rise with each inspiration. The tologist informed her that the baby had two seizures in the
oxygen saturation fell to 82%. preceding hour and his prognosis was guarded.
15259_Ch59.qxd 3/15/09 7:22 AM Page 223
CHAPTER 59 • FETAL OXYGEN SATURATION AND CAESAREAN SECTION 223
KEY MESSAGES paraesthesia and weakness of the arms and hands,

difficulty breathing, altered phonation, and loss of
1. Careful preoperative assessment of the parturient will consciousness.
allow early identification of a poorly functioning
epidural and of potential problems with spinal or References
epidural anesthesia. This review will ensure that senior
experienced personnel and all necessary equipment 1. Reynolds F, Seed PT. (2005) Anaesthesia for caesarean section
are available in case of emergency. and neonatal acid-base status: a meta-analysis. Anaesthesia 2005;
60:636–653.
2. Spinal anesthesia following inadequate epidural block- 2. Afolabi BB, Lesi FEA, Merah NA. Regional versus general
ade can result in an unpredictable final block height. anaesthesia for caesarean section. Cochrane Database of
Extra vigilance is required if a bolus has been admin- Systematic Reviews: Reviews 2006, Issue 4.
istered via the epidural in the 30 minutes before spinal 3. Hawkins JL. Maternal morbidity and mortality: anesthetic
causes. Can J Anesth 2002;49:6R.
anesthesia, if the patient weighs greater than 120 kg
4. Hawthorne L, Wilson R, Lyons G, Dresner M. Failed intubation
or if the height is less than 4⬘8⬙. revisited: 17-yr experience in a teaching maternity unit. Br J
3. Early recognition is a key to management of high total Anaesth 1996;76:680–684.
spinal anesthesia. Treatment is supportive and begins 5. Furst SR, Reisner LS. Risk of high spinal anesthesia following
failed epidural block for cesarean delivery. J Clin Anaesth 1994;
by addressing airway, breathing, and circulation.
Volume 7, Issue 1.
6. Dadarkar P, Philip J, Weidner C, et al. Spinal anesthesia
for cesarean section following inadequate labor epidural
QUESTIONS analgesia: a retrospective audit. Int J Obstet Anesth 2004;13:
239–243.
7. Stocks G. When using spinal anaesthesia for caesarean section
1. What population of cardiac output does uterine blood
after the epidural has failed, the normal dose of spinal anaesthetic
flow constitute at full term? should be used. Int J Obst Anesth 14:56–57.
Answer: 10% 8. Murphy PJ. The fetal circulation. Contin Educ Anaesth Crit
Care Pain 2005;5:107–112.
2. Outline the steps that may resolve peripartum fetal aci- 9. Ramanathan S, Gandhi S, Arismendy J, et al. Oxygen transfer
dosis during caesarean delivery. from mother to fetus during cesarean section under epidural
Answer: Oxygen delivery to the fetus (mmol/min) is anesthesia. Anesth Analg 1982;61:576–581.
10. Jordan M. Women undergoing caesarean section under regional
given by the product of umbilical blood flow and the
anaesthesia should routinely receive supplementary oxygen. Int J
oxygen content of umbilical venous blood. Maternal Obstet Anesth 2002;11:282–285.
oxygen delivery to the placenta is affected by uterine 11. Jouppila P, et al. The influence of maternal oxygen inhalation on
artery blood flow, oxygen content of maternal uterine human placental and umbilical venous blood flow. Eur J Obstet
artery blood, hemoglobin concentration, and saturation. Gynaecol Reproduct Biol 16:151–156.
Treating maternal hypotension with a fluid bolus or 12. Khaw KS, Wang CC, Ngan Kee WD, et al. Effects of high-
vasoconstrictors will help to improve fetal oxygenation. inspired oxygen fraction during elective Caesarean section under
A left lateral tilt will reduce the incidence of aortocaval spinal anaesthesia on maternal and fetal oxygenation and lipid
compression, which may compromise fetal blood flow. peroxidation. Br J Anaesth. 2002;88:18–23.
The oxygen content of maternal blood can be increased 13. Ross M. Base excess during cord occlusion. Am J Obstet Gynecol
2003;189:1811–1812.
by supplying the parturient with supplemental oxygen.
14. Portman RJ, Carter BS, Gaylord MS, et al. Predicting neonatal
3. What is the clinical presentation of total spinal morbidity after perinatal asphyxia: a scoring system. Am J Obstet
Gynecol 1990;162:174–182.
anesthesia?
15. Westgren M, Divon M, Horal M, et al. Routine measurements of
Answer: Total spinal anesthesia may present with umbilical artery lactate levels in the prediction of perinatal out-
increased maternal anxiety, hypotension, bradycardia, come. Am J Obstet Gynecol 1995;173:1416–1422.
15259_Ch60.qxd 3/15/09 6:51 AM Page 224
CHAPTER 60
Vasoconstrictors for Hypotension

During Caesarean Section
James O’Driscoll
hypotension. The most promising preventive strategies are

preloading, administering intrathecal opioids (for a local
anesthetic-sparing effect), leg compression, or a combination
A fit, healthy 29-year-old primigravida presented for elec-
of these methods.3
tive lower-segment caesarean section. The indication for
After the spinal anesthetic was administered, the patient
surgery was breech presentation of the fetus at 39 weeks’
was returned to the supine position with left lateral tilt, and
gestation. Preoperative assessment revealed only a history
ephedrine 6 mg was administered intravenously.
of postoperative nausea and vomiting after a tonsillectomy
when the patient was 15 years of age. Hemoglobin con-
centration was 12.3 g/dL. The options for anesthesia were
Is prophylactic ephedrine effective in preventing
discussed with the patient, and it was agreed that regional
hypotension after spinal block?
anesthesia in the form of a spinal anesthetic was the most
appropriate. Ephedrine has been found to be ineffective in preventing hy-
On arrival in the operating room, appropriate moni- potension when used in small doses, and when used in greater
toring was established (Table 60.1). doses, it is more likely to cause hypertension.4
After 5 minutes, assessment of the patient’s perception of
cold (ice) revealed a bilateral sensory block to T6 and surgery
What does appropriate monitoring mean in proceeded. Shortly afterward, the patient complained of
this setting? nausea, and an additional dose of ephedrine was adminis-
At this stage, the appropriate monitors are electrocardiogram, tered. Her blood pressure remained low at 80/50 mm Hg and
noninvasive blood pressure, and SpO2. did not respond to two additional doses of ephedrine (each 6
A 16-gauge intravenous cannula was inserted after skin in- mg). At this point, phenylephrine 100 ␮g was administered
filtration with 1% lidocaine, and 1500 mL of compound sodium intravenously. The patient’s systolic blood pressure increased
lactate was administered intravenously over 20 minutes. to 110 mm Hg, and her nausea eased. Five minutes later, the
patient’s blood pressure decreased again (Table 60.1), and she
complained of both nausea and discomfort. Again, her blood
What is the rationale for fluid preloading pressure increased after a bolus of phenylephrine 100 mcg in-
before spinal anesthesia? travenously. Extra doses of phenylephrine were required to
Fluid preloading before spinal anesthesia is done in an attempt maintain her blood pressure at this level, and a live male in-
to prevent or decrease the degree of hypotension caused by the fant was delivered 25 minutes after the spinal block was ad-
regional sympathetic blockade. For patients undergoing ministered. His Apgar scores were 9 (at 1 minute) and 10 (at
lower-segment caesarean section, preloading is no more effec- 5 minutes). Umbilical cord pH measurements were arterial,
tive than administering fluid at the time or immediately after pH 7.2 and venous, pH 7.26. Blood loss during the surgery
performance of the block.1 Colloid fluids have been shown to was approximately 850 mL.
be more effective than crystalloids for this purpose.2
Bupivacaine (0.5% 2 mL) and fentanyl (25 ␮g) were in-
jected into the intrathecal space with the patient in the sitting Is phenylephrine more effective than ephedrine
position under aseptic conditions using a 25-gauge pencil- in treating systemic hypotension in this setting?
point (Whitacre) spinal needle (BD Medical - Medical Surgical A recent study has shown that phenylephrine is superior to
Systems, Franklin Lakes, NJ). ephedrine when administered by infusion for treatment of hy-
potension in patients undergoing lower-segment caesarean
section under spinal anesthesia. Phenylephrine had less effect
Does the dose of local anesthetic administered on fetal acid-base status, although this finding has not been
influence the likelihood and degree of linked to fetal outcomes in any significant manner.1,5,6
hypotension? Although ephedrine and phenylephrine have been the most
Lesser doses of local anesthetic, particularly with the addition commonly used and studied agents, other vasoconstrictors
of opioids, appear to decrease the frequency and degree of such as metaraminol also may be effective.
224
15259_Ch60.qxd 3/15/09 6:51 AM Page 225
CHAPTER 60 • VASOCONSTRICTORS FOR HYPOTENSION DURING CAESAREAN SECTION 225
T A B L E 6 0 . 1 Vital Signs
Initial Block 5 min 10 min 15 min 20 min 25 min 30 min 35 min

Heart Rate 98 110 92 88 76 120 100 98 102
Non-invasive blood 130/80 138/72 70/42 80/60 110/80 100/72 98/62 116/68 110/62
pressure (mm Hg)
SpO2 (%) 98 95 96 96 97 94 95 96 96
for fluid loading but do have the potential to cause

KEY MESSAGES
adverse effects such as pruritus, allergy, and renal
dysfunction.
1. Early recognition and treatment of hypotension
following spinal block for caesarean section is vital 3. What is the treatment of choice for systemic hypoten-
for maintaining maternal comfort. Evidence for sion following spinal anesthesia for caesarean section?
adverse fetal outcome is lacking.
Answer: For treatment of hypotension, phenylephrine is
2. Several strategies for preventing hypotension have more effective than ephedrine, particularly when used by
been found to be ineffective when used alone but infusion. Phenylephrine also seems to be beneficial in
have shown promise in combination.3 terms of fetal acid base balance with less effect on cord
pH measured at delivery, although this does not seem to
3. Ephedrine and phenylephrine are the most commonly be related to fetal outcome unless it is abnormal for an-
used vasoconstrictors in this setting; the latter is more other reason. Phenylephrine administered by infusion
effective for treating systemic hypotension and has also seems to be superior to phenylephrine administered
potentially fewer effects on the fetus. by bolus dose alone. The optimal strategy seems to be a
combination of techniques with anticipation of hypoten-
sion, and rapid treatment is a priority.
QUESTIONS
References
1. Is prophylactic administration of a vasoconstrictor(s) 1. Mercier FJ, Bonnet MP, De la Dorie A, et al. Spinal anaesthesia
effective in preventing hypotension during a caesarean for caesarean section: fluid loading, vasoconstrictors and hypoten-
section? sion. Ann Fr Anesth Reanim 2007;26:688–693.
2. Cyna AM, Andrew M, Emmett RS, et al. Techniques for pre-
Answer: Administering a vasoconstrictor(s) prophylac- venting hypotension during spinal anaesthesia for Caesarean
tically can decrease the frequency and magnitude of section. Cochrane Database Syst Rev 2006;(4):CD002251.
hypotension after spinal anesthesia for caesarean section 3. Kaya S, Karaman H, Erdogan H, et al. Combined use of low-dose
but does not reliably do so. No one agent has been shown bupivacaine, colloid preload and wrapping of the legs for prevent-
to be superior to another in terms of prophylaxis. ing hypotension in spinal anaesthesia for caesarean section. J Int
Med Res 2007;35:615–625.
2. Does fluid preloading decrease the incidence or 4. Lee A, Ngan Kee WD, Gin T. A dose-response meta-analysis
severity of hypotension during caesarean section under of prophylactic intravenous ephedrine for the prevention of
spinal anesthesia? hypotension during spinal anaesthesia for elective caesarean
delivery. Anesth Analg 2004;98:483–490.
Answer: Fluid loading is inconsistent in preventing 5. Cooper DW, Gibb SC, Meek T, et al. Effect of intravenous
hypotension in this setting. Preloading seems to be no vasopressor on spread of spinal anaesthesia and fetal acid-base
more effective than what is often called: co- (at the time equilibrium. Br J Anaesth 2007;98:649–656.
of block) or post- (immediately after block) loading. 6. Ngan Kee WD, Khaw KS. Vasopressors in obstetrics: what
Colloids have been shown to be superior to crystalloids should we be using? Curr Opin Anaesthesiol 2006;19:238–243.
15259_Ch60.qxd 3/15/09 6:51 AM Page 226
15259_Index.qxd 3/15/09 6:52 AM Page 227
INDEX
Page numbers followed by f or t indicate material in figures or tables, respectively.
A Agitation diagnostic criteria for, 154, 154t

ABD. See Autologous blood donation emergence key messages on, 156
Abdominal aortic aneurysm, regional anes- in children, 207–211 laboratory findings in, 153, 154t
thesia in repair of, 136–139 adjunct medications and, 209, 209t pain assessment in, 155
Abdominal compartment syndrome age and, 209 pathogenesis of, 154
definition of, 49 anesthetic factors in, 209, 209t patient consent in, 155
secondary, hypertonic saline for anxiety and, 208 preoperative assessment in, 155
prevention of, 49 etiological factors in, 208t risk factors for, 154
Abortion, spontaneous, occupational grading scales for, 207, 208t symptoms of, 154
exposure and, 216 long-term consequences of, 209 treatment of, 155
ACC. See American College of Cardiology parental presence during induction AMA. See American Medical Association
ACE inhibitors. See Angiotensin-converting and, 208–209 American College of Cardiology (ACC)
enzyme inhibitors strategies to decrease, 208–209 on ␤-adrenergic antagonist perioperative
Acetaminophen, for total knee arthroplasty, temperament and, 208 use, 39t
63t, 64 definition of, 209 on cardiac risks in surgery, 40, 40t, 136
Acid-base balance, fetal, 222–223, 222t in opioid-addicted trauma patient, definition of myocardial infarction, 38–39
Acute chest syndrome (ACS), 157, 159 management of, 149 on statin perioperative use, 2–3
causes of, 159, 160t AHA. See American Heart Association American College of Endocrinology, on
definition of, 159 AION. See Anterior ischemic optic glycemic control, 11
radiographic findings in, 157, 158f neuropathy American Diabetes Association, 11
risk factors for, 159 AIR. See Anesthesia-induced rhabdomyolysis American Heart Association (AHA)
treatment of, 159 Air leak test, in tracheal intubation, 114 on ␤-adrenergic antagonist perioperative
Acute normovolemic hemodilution (ANH), Airway management. See also Tracheal use, 39t
80–81 intubation on cardiac risks in surgery, 40, 40t, 136
Acute pain team (APT) as anesthesiologist’s most important task, American Medical Association (AMA), on
components of, 214 103, 104 statin perioperative use, 2–3
cost-effectiveness of, 214 in bariatric surgery, 87–88 American Society of Anesthesiologists (ASA)
in traumatic amputation, 212–215 difficulties in on acute perioperative pain management,
Adrenaline. See Epinephrine ASA practice guidelines on, 104, 106 212, 213t
␤-Adrenergic agonists, for heart failure, 182 awake, tracheal intubation for, 106–109 on blood loss and transfusion, 85
␤-Adrenergic antagonists in bariatric surgery, 87–88 on difficult airway, 104, 106
for Duchenne muscular dystrophy, 119 definition of, 104 on herbal medicine, 180
first-, second-, and third-generation, 5, 6t in mask ventilation, 103–105 on obstructive sleep apnea, 175
for hypertension, 95, 96t, 97 obstructive sleep apnea and, 175–178 on postoperative visual loss, 31, 32–33
and myocardial oxygen supply/demand, 99 preoperative evaluation for, 103–105, 104t American Society of Regional Anesthesia,
perioperative use of, 5–8 as source of adverse outcomes, 103 guidelines for anticoagulated
cardiac risk factors and, 7, 7t, 137 Alanine aminotransferase (ALT), patients, 14–15
current regimens of, 6 abnormal preoperative levels ␧-Aminocaproic acid. See Epsilon-
hemodynamic control in, 6 of, 51–54, 52f aminocaproic acid
highest benefit potential from, Albumin, for perioperative fluid Amputation, traumatic, pain management in
plan for, 6 resuscitation, 55–57 acute pain team in, 212–215
individual patient differences and, 6–7 composition of preparations, 55, 56t options for, 212–213, 213t
key messages on, 7 disadvantages of, 55, 56t purpose of, 212
for myocardial infarction, 38, 39–40, 39t key messages on, 56 Analgesia. See specific types and procedures
noncardiac surgery risks and, 7, 7t outcomes with, 56, 56f Anaphylaxis, 162–165
recommendations for, 6–7, 39, 39t vs. saline, 55–56 biphasic, 162–163
risks of, 6 Alkaline phosphatase, abnormal preopera- differential diagnosis of, 162
pharmacologic effects of different types of, tive levels of, 51–54, 52f intraoperative management of, 163
5–6 ALT. See Alanine aminotransferase key messages on, 164
preoperative use of, 136 Alzheimer, Alois, 153–154 neuromuscular blocking agents and,
Adult respiratory syndrome, hypertonic Alzheimer’s disease 163–164
saline resuscitation in, 48–49 anesthesia in, 153–156 pathophysiology of, 162–163
AEP/2 Monitor, 116 anesthesia link to, 154 postoperative management of, 164
227
15259_Index.qxd 3/15/09 6:52 AM Page 228
228 INDEX
Anaphylaxis (continued) Anxiety patient outcome in, 89, 89t

protracted, 162–163 and emergence agitation in children, 208 types of, 87, 88f
signs and symptoms of, 162, 163t and hypertension, 96 Becker muscular dystrophy, 119
uniphasic, 162–163 Aortic aneurysm, abdominal, regional Benzodiazepines
vasopressin for, 92 anesthesia in repair of, in cerebral aneurysm coiling, 196
Anemia 136–139 in obese patients, 88
definition of, 84 APC. See Anesthetic myocardial Beta blockers. See ␤-Adrenergic antagonists
preoperative, risks with, 84 preconditioning Biliopancreatic diversion, 87, 88f
Anesthesia. See specific types and procedures Apnea. See Sleep apnea Bilirubin, abnormal preoperative levels of,
Anesthesia-induced rhabdomyolysis (AIR) Aprepitant, for nausea/vomiting prevention, 51–54, 52f
clinical features of, 120t 128 Birth. See Caesarean section
in Duchenne muscular dystrophy, 119–121 Aprotinin Bispectral index (BIS) monitoring, 116–118
treatment of, 121 in cardiac surgery, 22–24 clinical purpose of, 116
Anesthetic myocardial preconditioning for minimizing need for blood transfu- process of, 116
(APC), 100–101 sion, 81, 84 routine
clinical relevance of, 101 APT. See Acute pain team and hypotension reduction, 116
drugs affecting, 100–101, 101t ARBs. See Angiotensin receptor blockers requirement for, 117
mechanisms of, 100, 100t Argatroban, in heparin-induced thrombocy- scale of, 116, 117f
Aneurysm. See Abdominal aortic aneurysm; topenia, 46, 46t value in maintenance phase, 117
Cerebral aneurysm Arnica, and anesthesia, 179 Bivalirudin, in heparin-induced thrombocy-
Angiography, of cerebral aneurysm, 193, 194f Arrhythmia, in transurethral resection of topenia, 46, 46t
Angiotensin-converting enzyme (ACE) prostate syndrome, 173, 173f Bleeding, in cardiac surgery
inhibitors Aspartate aminotransferase (AST), causes of, 22
for Duchenne muscular dystrophy, 119 abnormal preoperative levels postoperative management of, 25
for hypertension, 95, 96t of, 51–54, 52f prevention of
and intraoperative hypotension, 97 Aspiration, perioperative, risk of, 110 antifibrinolytics and aprotinin for,
in PCI, surgical considerations with, 136 Aspirin 22–24
Angiotensin receptor blockers (ARBs) in heparin-induced thrombocytopenia, 46 importance of, 22
for hypertension, 95, 96t and neuraxial blockade, 187 pharmacological approaches for, 23
and intraoperative hypotension, 97 for percutaneous coronary intervention, 77 recombinant factor VIIa for, 25–26
ANH. See Acute normovolemic hemodilution for perioperative myocardial infarction, 40 reoperation for, incidence and risks of,
Anterior ischemic optic neuropathy surgical risks with, 136 22–23
(AION), 31 Association of Anaesthetists of Great Britain risk factors for, 22
Anticoagulation and Ireland, 163 Blood conservation
alternatives, in heparin-induced thrombo- AST. See Aspartate aminotransferase intraoperative strategies for, 80–82, 84–85
cytopenia, 46 Atracurium pharmacologic methods of, 81, 81t
and bleeding in cardiac surgery, 22 and anaphylaxis, 163 Blood pressure. See Hypertension;
and epidural anesthesia/analgesia, 14–15, in mitochondrial disease, 204, 205 Hypotension
186–188 Autologous blood donation (ABD), 80, 84 Blood transfusion
and neuraxial blockade, 186–188 contraindications to, 81t ASA guidelines on, 85
in off-pump coronary artery bypass, 19–20 costs of, 80 indications for, 81, 81t, 85
for perioperative myocardial infarction, 40 procedure for, 80 minimizing need for, 80–82, 84–85
Anticonvulsants Awake, tracheal intubation, 106–109 risks of, 80
for neuroprotection, 196 complications of, 108 in sickle cell disease, 159, 159t
for obstructive sleep apnea patients, 177 device or technique for, 107–108 thresholds for, 83–86
for phantom limb pain, 212–213, 214 patient preparation for, 106–107, 107t BNP. See B-type natriuretic peptide
for preventing opioid-induced hyperalge- supraglottic airways vs., 108 Brachial plexus block
sia, 170 Awareness, 200–202 for preventing opioid-induced hyperalge-
for preventing persistent postsurgical pain, anesthetic factors in, 201, 201t sia, 170
167 clinical signs of, 202 for shoulder arthroplasty, 146
Antidepressants, for preventing persistent definition and classification of, 200–201 supraclavicular
postsurgical pain, 167 with explicit memory, 200 for traumatic upper limb amputation,
Antidiuretic hormone. See Vasopressin with implicit memory, 200 212–214
Antiemetics, 128–129, 128t key messages on, 201 ultrasound guidance for, 140–143, 142f
Antifibrinolytics protocol for managing possible cases of, Brachial plexus injury, in cardiac surgery, 27,
in cardiac surgery, 22–24 200–201, 201t 28, 28f
efficacy of, evidence for, 23 risk factors for, 200 Brain injury
risks associated with, 23–24 surgical factors in, 201 cardiac surgery and, 35–37
for minimizing need for blood transfu- prevention of
sion, 81, 84 in cerebral aneurysm surgery, 189–192
Antihistamines, for anaphylaxis, 163 B evidence-based status of interventions
Antihypertensive drugs, 95, 96t Barbiturates, for neuroprotection, 190–191 for, 192t
Antiplatelet drugs Bariatric surgery traumatic, hypertonic saline resuscitation
and neuraxial blockade, 186–188 airway management in, 87–88 in, 48–50
in PCI, surgical considerations with, anesthesia for, 87–90 Breast surgery, persistent pain after, 66–168
77–79, 136 drug pharmacokinetics in, 88 Breathing, sleep-disordered. See Sleep
for perioperative myocardial infarction, 40 intraoperative monitoring in, 88 apnea
15259_Index.qxd 3/15/09 6:52 AM Page 229
INDEX 229
Bronchodilators, for anaphylaxis, 163 postoperative visual loss in, 31 Chemoreceptor trigger zone (CTZ), in
B-type natriuretic peptide (BNP), in heart statins and, 1–4 nausea and vomiting, 127
failure, 183t, 184 Cardiopulmonary bypass (CPB) Chest syndrome, acute. See Acute chest
Bupivacaine bleeding in, prevention of, 22–24 syndrome
for peripheral nerve block, 140, 142 conversion to, in off-pump bypass, 20 Childbirth. See Caesarean section
physiochemical properties of, 142, 142t vs. off-pump coronary artery bypass, 17 Children
for shoulder arthroplasty, 146t Carotid artery stenosis, 70–73 emergence agitation in, 207–211
for total knee arthroplasty, 62 Carotid artery stenting (CAS), 70–73 adjunct medications and, 209, 209t
Burn injury, hypertonic saline resuscitation anesthesia for, 72 age and, 209
in, 48–50 vs. carotid endarterectomy, 70, 72, 72f anesthetic factors in, 209, 209t
technique of, 71–72, 71f anxiety and, 208
Carotid endarterectomy (CEA), 70–71, 73 etiological factors in, 208t
C anesthetic goals in, 70 grading scales for, 207, 208t
CABG. See Coronary artery bypass surgery vs. carotid artery stenting, 70, 72, 72f long-term consequences of, 209
Caesarean section cerebral perfusion in, 71 parental presence during induction and,
appropriate monitoring in, 224, 225t regional vs. general anesthesia in, 70–71, 71f 208–209
fetal oxygen saturation in, 220–223 CAS. See Carotid artery stenting strategies to decrease, 208–209
hypotension in, vasoconstrictors for, CBF. See Cerebral blood flow temperament and, 208
224–225 CEA. See Carotid endarterectomy magnetic resonance imaging in, anesthesia
spinal anesthesia in, 220–225 Cell salvage/reinfusion, 81, 84–85 for, 123–126, 124t
supplemental oxygen during, 222 Central pontine myelinolysis, hypertonic postoperative nausea and vomiting in,
total spinal anesthesia in, 222, 223 saline and, 50 128
Calcium Central retinal artery occlusion (CRAO), rapid sequence induction in, 111
for anesthesia-induced rhabdomyolysis, 121 31–33 tracheal intubation in
in subarachnoid hemorrhage, 195 Central venous cannulation anatomic considerations in, 113
Calcium channel blockers anatomic landmarks for, 132 complications of, vulnerability to,
for cerebral aneurysm/hemorrhage, 191, complications of, 131–132, 132t 113–114
193, 195, 196 indications for, 131 cuffed tracheal tubes for, 112–115
for hypertension, 95, 96t and nerve injury, 28–29 edema and cross-sectional area in,
and myocardial oxygen supply/demand, 99 ultrasound guidance for, 131–135 113–114, 114t
for neuroprotection, 191, 196 anesthesiologist experience with, 134 injury in, levels vulnerable to, 114
Carbon dioxide, partial pressure of, in cere- dynamic, 132–133, 133f, 133t N2O diffusion in, 114
bral aneurysm surgery, 190 key messages on, 134 specifically designed tubes for, 114
Cardiac resuscitation as standard of care, 133–134 Child-Turcotte-Pugh scoring system,
vasopressin for, 91–94 static, 132–133 52, 53t
vasopressors vs. volume expansion for, Cerebral aneurysm Chinese medicine, and anesthesia, 179–181
91–94 angiography of, 193, 194f Chloral hydrate, for MRI sedation/anesthe-
Cardiac risks coiling of sia, 124–125
evaluating surgical patients with, 40, 40t advantages of, 195 Cholinesterase inhibitors, anesthetic consid-
and perioperative use of ␤-adrenergic anesthesia for, 193–197 erations with, 155
antagonists, 7, 7t management of, 196 Cirrhosis
and preoperative PCI, 40–41 technique for, 195 Child-Turcotte-Pugh scoring system in,
stratification of, 40, 41t vs. clipping, 193–195 52, 53t
Cardiac surgery complications of, 196 MELD score in, 52, 53t
␤-adrenergic antagonists and, 5–8 decision-making on, 195 preoperative abnormal liver function tests
bleeding in definition of, 195 in, 51–54
causes of, 22 key messages on, 196 Cisatracurium
postoperative management of, 25 monitoring in, 196 as alternative to succinylcholine, 111, 112
prevention of optimal timing of, 195 and anaphylaxis, 163
antifibrinolytics and aprotinin for, premedication for, 196 in mitochondrial disease, 205
22–24 electrocardiographic changes in, 196 CK-MB. See Creatine kinase
importance of, 22 electrolyte abnormalities with, 196 Clonidine
pharmacological approaches for, 23 excitotoxicity with, 190 for preventing opioid-induced hyperalge-
recombinant factor VIIa for, 25–26 prevalence of, 190 sia, 170
reoperation for, incidence and risks of, surgery for for total knee arthroplasty, 63t
22–23 blood glucose in, 190 Clopidogrel
risk factors for, 22 blood pressure in, 190 and neuraxial blockade, 187
cerebral complications of, 35 neuroprotection during, 189–192 for percutaneous coronary intervention,
heparin-induced thrombocytopenia and, partial pressure of carbon dioxide in, 190 77–78
46–47 Cerebral blood flow (CBF), neuroprotection for perioperative myocardial infarction, 40
intrathecal opioids for, 15 and, 190–191 CMR. See Cerebral metabolic rate
neuraxial analgesic techniques for, 14–16 Cerebral metabolic rate (CMR), neuroprotec- Coagulopathy, intraoperative, 83–86
off-pump bypass, 17–21 tion and, 190–191 Cognitive dysfunction, postoperative
parasternal block for, 15 Cerebral perfusion pressure (CPP), in in cardiac surgery, 35–37
postoperative cognitive dysfunction in, aneurysm surgery, 190 mechanisms of, 35–36
35–37 Cerebral State Monitor, 116 outcomes associated with, 36
postoperative neuropathy in, 27–30 Cerebral vasospasm, triple-H therapy for, 191 risk factors for, 36
15259_Index.qxd 3/15/09 6:52 AM Page 230
230 INDEX
Cognitive dysfunction (continued) D in subarachnoid hemorrhage, 196

in noncardiac surgery, 37 Danaparoid, in heparin-induced thrombocy- in transurethral resection of prostate
psychometric testing in, 36, 37 topenia, 46, 46t syndrome, 173, 173f
Coiling, of cerebral aneurysm, 193–197 DAT. See Dual-antiplatelet therapy Electroencephalography (EEG), bispectral
advantages of, 195 Delirium analysis of, 116
anesthesia for, 193–197 emergence Electromyography (EMG)
management of, 196 in children, 207–211 in peripheral nerve block injury, 59
technique for, 195 definition of, 209 in postoperative neuropathy, 27, 28, 29
vs. clipping, 193–195 hyperactive, 36 Emergence agitation
complications of, 196 hypoactive, 36 in children, 207–211
decision-making on, 195 mixed, 36 adjunct medications and, 209, 209t
definition of, 195 postoperative, 36–37 age and, 209
key messages on, 196 Depth of anesthesia anesthetic factors in, 209, 209t
monitoring in, 196 BIS monitoring of, 116–118 anxiety and, 208
optimal timing of, 195 definition of, 116 etiological factors in, 208t
premedication for, 196 DES. See Drug-eluting stents grading scales for, 207, 208t
Colloids, for perioperative fluid resuscitation, Desflurane long-term consequences of, 209
55–56 and myocardial preconditioning, 100 parental presence during induction and,
Complementary and alternative medicine, in neuroprotection, 191 208–209
and anesthesia, 179–181 in obese patients, 88 strategies to decrease, 208–209
Continuous ambulatory regional anesthesia, Dexamethasone, for nausea/vomiting temperament and, 208
145–148 prevention, 128, 129 definition of, 209
infusion considerations in, 147 Dexmedetomidine Emergence delirium
key messages on, 147 in awake, tracheal intubation, 107 in children, 207–211
patient selection vs. complications in, for nausea/vomiting prevention, 128 definition of, 209
146–147 in obese patients, 88 EMG. See Electromyography
Continuous catheters, and neurologic injury, Diabetes mellitus Endarterectomy, carotid. See Carotid
60, 60t epidemiology of, 9 endarterectomy
Continuous positive airway pressure perioperative care in Enflurane
for heart failure, 182 ␤-adrenergic antagonists in, 7 and myocardial preconditioning, 100
for obstructive sleep apnea, 176 glycemic control in, 9–13 and neuroprotection, 191
Contrast agents, risks of, 124 Difficult airway Entropy monitor, 116
Coronary artery bypass (CABG) surgery ASA practice guidelines on, 104, 106 Ephedra, and anesthesia, 180
vs. off-pump bypass, 17, 18t, 20 awake, tracheal intubation for, 106–109 Ephedrine, for hypotension, in caesarean
statins and, 1–4 in bariatric surgery, 87–88 section, 224–225
Coronary artery disease definition of, 104 Epidural anesthesia/analgesia
analgesia in, 137–138 in mask ventilation, 103–105 adverse effects of, 62
anesthesia techniques in, 136 obstructive sleep apnea and, 175–178 antiplatelet agents/anticoagulants and,
intraoperative monitoring in, 137 Difficult Airway Society Guidelines, 104 14–15, 186–188
myocardial preconditioning in, 99–102 Digoxin, St. John’s wort and, 181 for cardiac surgery, 14–16
perioperative monitoring in, 99–100 DMD. See Duchenne muscular dystrophy dosing regimen for, 15
preoperative blood results in, 136, 137t Dobutamine, for heart failure, 182–184 goals of, 15
regional anesthesia outcomes in, 136–139 Droperidol, black box warning on, 128 with heparin anticoagulation, guidelines
Coronary Artery Revascularization Drug-eluting stents (DES), 77–78 for, 14–15
Prophylaxis trial, 41 Dual-antiplatelet therapy (DAT), in percuta- risks and complications of, 14
Coronary revascularization neous coronary intervention, total spinal technique for, 15
preoperative, prevention role of, 40–41, 77 77–78 in coronary artery disease, 138
recent, management of surgical patients Duchenne muscular dystrophy (DMD) herbal medicine and, 179
with, 41, 42f, 77–79, 78t, 136 muscle relaxants and, 120, 121 in labor
Corticosteroids pathogenesis of, 119, 120f complications of, 221t
for anaphylaxis, 163 preoperative evaluation in, 119 inadequate, spinal anesthesia after,
for nausea/vomiting prevention, 128 volatile anesthetics and, 119–122 220–221
Coumarin derivatives, and anesthesia, 179 risks of, 220
COX-2 inhibitors, for total knee arthro- in obese patients, 88
plasty, 63t, 64 E thoracic, for postthoracotomy pain, 66–67,
CPB. See Cardiopulmonary bypass EACA. See Epsilon-aminocaproic acid 67f, 68f
CPP. See Cerebral perfusion pressure EASI scale, 208 for total knee arthroplasty, 62–65
CRAO. See Central retinal artery occlusion ECG. See Electrocardiography Epidural hematoma
Creatine kinase (CK-MB) Echocardiography, transesophageal in anticoagulated patients, 14–15
in myocardial preconditioning, 101 in coronary disease patients, 100, 101 antiplatelet agents/anticoagulants and,
in perioperative myocardial infarction, in off-pump coronary artery bypass, 19–20 186–188
39–40 EEG. See Electroencephalography herbal medicine and, 179, 180f
Crystalloids, for perioperative fluid resuscita- Electrocardiography (ECG) incidence of, 187
tion, 55–56 in anesthesia-induced rhabdomyolysis, 121 magnetic resonance imaging of, 179,
CTZ. See Chemoreceptor trigger zone in left ventricular hypertrophy, 140, 141f 180f, 188
Cuffed tracheal tubes, for children, 112–115 in myocardial infarction, 77, 78f managing patients at high risk for, 187–188
Curare, 110 in off-pump coronary artery surgery, 17–20 risk factors for, 187, 187t
15259_Index.qxd 3/15/09 6:52 AM Page 231
INDEX 231
in total knee arthroplasty, 62, 63 Gag reflex, in awake, tracheal intubation, 106 classification of, 44
treatment of, 188 Garlic, and anesthesia, 180 delayed-onset, 45
Epinephrine Gastric banding, 87, 88f diagnosis of, 45
for anaphylaxis, 163 Gastric bypass, 87, 88f Iceberg Model of, 44
for cardiac resuscitation, 91–93 Ginger, and anesthesia, 180 rapid-onset, 45
for peripheral nerve block, 140, 142 Ginkgo, and anesthesia, 180 scoring systems for, 45
Epsilon-aminocaproic acid (EACA) Ginseng, and anesthesia, 180 thrombosis with, 45
in cardiac surgery, 23–24 Glasgow Coma Scale, in subarachnoid hem- treatment of, 45–46
for minimizing need for blood orrhage, 193, 194t, 195 type I, 44
transfusion, 81 Glossopharyngeal nerve, in awake, tracheal type II, 44–45
Erythropoietin, for minimizing need for intubation, 106 clinical presentations of, 45
blood transfusion, 81, 84 Glucose level. See also Hyperglycemia complications of, 45
European Society of Cardiology, definition of in cerebral aneurysm surgery, 190 pathophysiology of, 44–45
myocardial infarction, 38–39 perioperative targets for, 11, 11t risk factors for, 45
Excitotoxicity, with cerebral aneurysm, 190 Glycemic control, perioperative, 9–13 Heparin-induced thrombocytopenia-
Glycine toxicity, in transurethral resection of thrombosis (HITT), 45
prostate syndrome, 172 Hepatitis, preoperative abnormal liver
F Glycoprotein IIb/IIIa inhibitors, for perioper- function tests in, 51–54
Femoral nerve block ative myocardial infarction, 40 Herbal medicine
for opioid-addicted trauma patient, Glycopyrrolate, in awake, tracheal intuba- and anesthesia, 179–181
149–151, 150f, 151f tion, 106–107 ASA information on, 180
for total knee arthroplasty, 63 Grapefruit juice, and anesthesia, 180 natural vs. safe, 179
ultrasound guidance for, 140–143, 141f, Guglielmi, Guido, 195 Hip arthroplasty, revision, blood loss and
149–151, 150f, 151f Guglielmi Detachable Coils, 195 conservation in, 83–86
Femoral vein, central venous cannulation HIT. See Heparin-induced
via, 132 thrombocytopenia
Fentanyl H HITT. See Heparin-induced
in awake, tracheal intubation, 107 Haloperidol, for nausea/vomiting preven- thrombocytopenia-thrombosis
in obese patients, 88 tion, 128 Horner’s syndrome
in total knee arthroplasty, 62 Halothane cardiac surgery and, 28
Fetal oxygenation and Alzheimer’s disease, 154 continuous ambulatory regional anesthesia
in caesarean section, 220–223 and emergence agitation in children, 207 and, 146
determinants of, 221–222, 221t and myocardial preconditioning, 100 HTS. See Hypertonic saline
Fetal oxyhemoglobin dissociation curve, and neuroprotection, 191 Hunt and Hess grading scale, 193, 194t, 195
221–222, 222f Heart failure, acute 5-Hydroxytrytamine receptor antagonists,
Fiberscopes, for awake, tracheal intubation, arterial blood gases in, 183, 183t for nausea/vomiting preven-
107–108 biochemistry results in, 183, 183t tion, 128, 129
Flexible fiberscopes, for awake, tracheal levosimendan for, 182–185 Hydroxyurea, for sickle cell disease, 160
intubation, 107–108 radiographic findings in, 183, 183f Hyperalgesia, opioid-induced, 169–170
Fluid overload Hematoma, epidural Hyperglycemia
in pneumonectomy, 74–75 in anticoagulated patients, 14–15 in cerebral aneurysm surgery, 190
in transurethral resection of prostate antiplatelet agents/anticoagulants and, perioperative prevention of, 9–13
syndrome, 172–174 186–188 poor patient outcome with
Fluid preloading, for spinal anesthesia, 224 herbal medicine and, 179, 180f mechanisms of, 9
Fluid resuscitation incidence of, 187 studies of, 10–11
albumin for, 55–57 magnetic resonance imaging of, 179, 180f, Hyperkalemia
hypertonic saline for, 48–50 188 in anesthesia-induced rhabdomyolysis, 121
vasopressin for, 91–94 managing patients at high risk for, 187–188 in mitochondrial disease, 204
Fondaparinux risk factors for, 187, 187t Hypertension
in heparin-induced thrombocytopenia, in total knee arthroplasty, 62, 63 anesthesia and, 95–98
46, 46t treatment of, 188 classification of, 96t
and neuraxial blockade, 188 Hemodilution, for cerebral vasospasm, 191 definition of, 95
Four Ts scoring system, 45 Hemoglobin dilution, in sickle cell disease, induced arterial, for cerebral vasospasm,
Furosemide, for transurethral resection of 159 191
prostate syndrome, 174 Hemoglobin S, in sickle cell disease, 157–158 intraoperative cardiovascular lability in,
Hemorrhagic shock, vasopressin for, 92 96–97
Heparin pathogenesis of, 95
G and bleeding in cardiac surgery, 22 perioperative management in, 96
Gabapentin epidural anesthesia/analgesia with, 14–15 postponing surgery in, 95–96
for obstructive sleep apnea patients, 177 low-molecular-weight, and neuraxial treatment of, 95, 96t
for phantom limb pain, 212–213, 214 blockade, 186–188 white coat, 96
for preventing opioid-induced in off-pump coronary artery bypass, 19–20 Hyperthermia
hyperalgesia, 170 for perioperative myocardial infarction, 40 and cerebral injury, 190
for preventing persistent postsurgical Heparin-induced thrombocytopenia (HIT), malignant
pain, 167 44–47 in Duchenne muscular dystrophy,
for total knee arthroplasty, 63t anticoagulation alternatives in, 46, 46t 119–120
Gadolinium, risks of, 124 cardiac surgery in patient with, 46–47 in mitochondrial disease, 204
15259_Index.qxd 3/15/09 6:52 AM Page 232
232 INDEX
Hypertonic saline (HTS) International Subarachnoid Aneurysm Trial LHON. See Leber hereditary optic
for acute lung injury, 48–49 (ISAT), 193–195 neuropathy
administration of, 49 Intraneural injection (INI), 58, 60, 150, 155 Lidocaine
characteristics of, 49t Intrathecal opioids in neuroprotection, 191
complications of, 49–50 for cardiac surgery, 15 for peripheral nerve block, 140, 142
for prevention of abdominal compartment for total knee arthroplasty, 62 physiochemical properties of, 142, 142t
syndrome, 49 Intubation, tracheal. See Tracheal intubation for shoulder arthroplasty, 146, 146t
for resuscitation, 48–50 ION. See Ischemic optic neuropathy Liver function test, preoperative abnormali-
for transurethral resection of prostate IPC. See Ischemic preconditioning ties in, 51–54, 52f
syndrome, 173–174 ISAT. See International Subarachnoid Liver transplantation, vasopressin use in,
types of, 49 Aneurysm Trial 92–93
Hypervolemia, for cerebral vasospasm, 191 Ischemic optic neuropathy (ION), 31–33 LMA. See Laryngeal mask airway
Hypocalcemia, in subarachnoid hemorrhage, anterior, 31 LMWH. See Low-molecular-weight heparin
195 posterior, 31 Local anesthesia. See Regional anesthesia;
Hypoglycemia, prevention and management Ischemic preconditioning (IPC), 100–101 specific types
of, 12 ISH. See Isolated systolic hypertension Low-molecular-weight heparin (LMWH),
Hypoglycemic agents, oral, in hospitalized Isoflurane and neuraxial blockade,
patients, 11 and Alzheimer’s disease, 154 186–188
Hypokalemia, in subarachnoid hemorrhage, in mitochondrial disease, 204 Lumbosacral nerve injury, in cardiac
195 and myocardial preconditioning, 100 surgery, 27
Hypomagnesemia, in subarachnoid hemor- Isolated systolic hypertension (ISH), 96t, 97 Lung injury, acute, hypertonic saline resusci-
rhage, 195 Isoprenaline, in mitochondrial disease, 204 tation in, 48–49
Hyponatremia Lysine analogs, in cardiac surgery, 23–24
hypertonic saline and, 50
in subarachnoid hemorrhage, 195 J
in transurethral resection of prostate Joint replacement M
syndrome, 172–174 knee, peripheral nerve blockade vs. MABL. See Maximal allowable blood loss
Hypotension epidural analgesia for, 62–65 Magnesium levels, in subarachnoid hemor-
in caesarean section, vasoconstrictors for, revision hip, blood loss and conservation rhage, 195
224–225 in, 83–86 Magnetic resonance imaging (MRI)
induced, for blood conservation, 81 shoulder, continuous ambulatory regional bioeffects of, 123
during induction, BIS monitoring and, 116 anesthesia for, 145–148 contrast agent risks in, 124
intraoperative dedicated sedation teams for, 125
antihypertensive agents and, 97 of epidural hematoma, 179, 180f, 188
vasopressin for, 93 K in infants and children, anesthesia for,
Hypothermia Kava, and anesthesia, 180 123–126, 124t
intraoperative, and blood loss, 85 Kearns-Sayre syndrome (KSS) physical setup for, 123, 124f
for neuroprotection, 190 anesthesia in, 203–206 Ma-huang, and anesthesia, 180
in sickle cell disease, 159 clinical features of, 204t Malabsorptive procedures, for obesity, 87
Hypovolemia. See Fluid resuscitation Ketamine Malignant hyperthermia (MH)
in neuroprotection, 191 in Duchenne muscular dystrophy,
for preventing opioid-induced 119–120
I hyperalgesia, 170 in mitochondrial disease, 204
Iceberg Model, of heparin-induced thrombo- for preventing persistent postsurgical pain, Mask ventilation, difficult
cytopenia, 44 167 vs. difficult tracheal intubation, 103
Iliacus block, in Alzheimer patients, 155 for total knee arthroplasty, 63t grading scale for, 104, 104t
Iloprost, in heparin-induced thrombocytope- Knee arthroplasty, total. See Total knee prediction of, 103–105
nia, 46 arthroplasty Mastectomy, persistent pain after, 166–168
Imaging, in infants and children, anesthesia KSS. See Kearns-Sayre syndrome Maximal allowable blood loss (MABL), 84–85
for, 123–126 MELAS. See Mitochondrial encephalomy-
Immunomodulation, hypertonic saline opathy, lactic acidosis, and
resuscitation in, 48–49 L stroke-like episodes
INI. See Intraneural injection Labor. See Caesarean section Memantine, for preventing phantom limb
Inotropes, for heart failure, 182–185 Laryngeal mask airway (LMA), 103, 104 pain, 213–214
Insulin Laryngeal nerve injury, in cardiac surgery, Mepivacaine, for shoulder arthroplasty, 146
basal, 12 28 MERFF. See Myoclonic epilepsy and ragged
correction-dose or supplemental, 12 Laryngoscopy, hypertension and, 96–97 red fibers on muscle biopsy
dose for infusion titration, based on hourly Leber hereditary optic neuropathy (LHON), Metformin, for hospitalized patients, 11
glucose checks, 10t 204t MH. See Malignant hyperthermia
loading dose and initial infusion rate, 10t Left ventricular hypertrophy, 140, 141f Microcuff Paediatric Tracheal Tube, 114
metabolic effects of, 9–10 Leigh’s syndrome, 204t Midazolam, in awake, tracheal intubation,
perioperative use of, 9–13 Lepirudin, in heparin-induced thrombocy- 107
prandial, 12 topenia, 46, 46t MIDCAB. See Minimally invasive direct
sliding scale therapy, 11–12 Levobupivacaine, for shoulder arthroplasty, access coronary bypass
subcutaneous regimen, 12 146t Minimally invasive direct access coronary
Internal jugular vein, central venous cannu- Levosimendan, for acute heart failure, bypass (MIDCAB), 17
lation via, 132–134, 133f 182–185 Mitochondrial cytopathies, 203
15259_Index.qxd 3/15/09 6:52 AM Page 233
INDEX 233
Mitochondrial disease ischemic, 100–101 Neuroprotection

anesthesia in, 203–206 pharmacologic, 99–102 in cerebral aneurysm surgery, 189–192,
clinical manifestations of, 203 Myoclonic epilepsy and ragged red fibers on 196
definition of, 203 muscle biopsy (MERRF), 204t evidence-based status of interventions for,
key messages on, 205 192t
premedication in, 204 Nimodipine
preoperative assessment in, 203–204, 204t, N for cerebral aneurysm/hemorrhage, 191,
205t Nalmefene, for nausea/vomiting prevention, 193, 195, 196
recovery of neuromuscular function in, 205 128 for neuroprotection, 191, 196
spirometry in, 203, 204t Naloxone, for nausea/vomiting prevention, NIOSH. See National Institute of
syndromes of, 203, 204t 128 Occupational Safety and
Mitochondrial encephalomyopathy, lactic Narcotrend monitor, 116 Health
acidosis, and stroke-like NARP. See Neuropathy, ataxia, retinitis Nitrous oxide
episodes (MELAS), 204t pigmentosa, and ptosis avoidance, in patients with coronary artery
Mitochondrial myopathies, 203 National Institute of Occupational Safety and disease, 137
Mitochondrial neurogastrointestinal en- Health (NIOSH), 216–217, 217t diffusion, in pediatric intubation, 114
cephalopathy (MNGIE), 204t Nausea and vomiting, postoperative occupational exposure to, 216–218
Mivacurium, and anaphylaxis, 163 in children, 128 and postoperative nausea/vomiting, 127
MNGIE. See Mitochondrial neurogastroin- discharge expectations for, 129 NMBAs. See Neuromuscular blocking
testinal encephalopathy key messages on, 129 agents
Model for end-stage liver disease (MELD) nonpharmacologic treatment of, 129 N-methyl-D-aspartate receptor antagonists
score, 52, 53t pathophysiology of, 127 for preventing persistent postsurgical
Monitored environmental level, 216–217 prevention of pain, 167
Morphine, and myocardial preconditioning, anesthetic technique for, 129 for preventing phantom limb pain, 213–214
100 evidence-based, 127–130 Nonimmune heparin-associated thrombocy-
MRI. See Magnetic resonance imaging premedicants for, 128–129, 128t topenia, 44
Multimodal analgesia risk factors for, 127–128 Nonsteroidal anti-inflammatory drugs, and
in obstructive sleep apnea, 177 anesthetic-related, 127, 128t, 129 neuraxial blockade, 187
for preventing opioid-induced Apfel score of, 127–128 Norepinephrine, for cardiac resuscitation,
hyperalgesia, 170 patient-specific, 127, 128t 91–93
for preventing persistent postsurgical pain, surgery-related, 127, 128t NSF. See Nephrogenic systemic fibrosis
167 NCS. See Nerve conduction studies
for total knee arthroplasty, 15, 63t, 64 Neostigmine, and postoperative nausea/
Muscle relaxants vomiting, 127, 129 O
in Duchenne muscular dystrophy, 120, 121 Nephrogenic systemic fibrosis (NSF), 124 Obesity
in tracheal intubation, succinylcholine use Nerve block. See also Peripheral nerve classification of, 88t
as, 110–112 blockade; specific types surgery for
Muscular dystrophy for awake, tracheal intubation, 106 airway management in, 87–88
Duchenne Nerve conduction studies (NCS) anesthesia in, 87–90
pathogenesis of, 119, 120f in peripheral nerve block injury, 59 drug pharmacokinetics in, 88
volatile anesthetics and, 119–122 in postoperative neuropathy, 28 intraoperative monitoring in, 88
types of, 119, 120t Neural monitors, 116–118, 117t patient outcome in, 89, 89t
Myalgia, succinylcholine and, 111, 112t Neuraxial analgesia. See also Epidural types of, 87, 88f
Myocardial infarction anesthesia/analgesia Obstetrics. See also Caesarean section
definitions of, 38–39 antiplatelet agents/anticoagulants and, intraoperative awareness in, 200
ECG findings in, 77, 78f 186–188 Obstructive sleep apnea
PCI for, surgical considerations after, for cardiac surgery, 14–16 anesthesia and, 175–178
77–79 for total knee arthroplasty, 62–65 ASA recommendations on, 175
perioperative, 38–43 for transurethral resection of prostate, 171 and bariatric surgery, 87–88
biochemical markers of, 39, 39t Neurokinin receptor antagonists, for nau- benzodiazepine alternatives in, 177
evaluating risk for, 40, 40t sea/vomiting prevention, 128 definition of, 177
interventions for, 40 Neuromuscular blocking agents (NMBAs) difficult intubation in, 175
limiting ischemia in, 38 and anaphylaxis, 163–164 extubation safety in, 176–177
mechanisms of, 38 reversal of intubation in, 175–176
PCI for prevention of, 40–41 emergency, sugammadex for, 198–199 key messages on, 177
pharmacologic treatment of, 39–40, 39t TOF ratio for, 198–199, 199f management without formal diagnosis,
preconditioning and, 99–102 Neuropathy, ataxia, retinitis pigmentosa, and 175–176
presentation of, 39 ptosis (NARP), 204t opioids and, 63–64
Myocardial oxygen supply/demand Neuropathy, postoperative, in cardiac patient positioning in, 176–177
balance between, medications to improve, surgery, 27–30 perioperative analgesia and anesthesia in,
99 key messages on, 29 176
primary determinants of, 99 management of, 29 postoperative monitoring in, 177
Myocardial preconditioning mechanism of, 27–28 risk factors for, 175
anesthetic-induced, 100–101 presentation of, 28 severity of, 175, 176t
clinical relevance of, 101 prevention of, 29 signs and symptoms of, 175, 176t
drugs affecting, 100–101, 101t prognosis of, 29 Obturator nerve block, in total knee
mechanisms of, 100, 100t studies of, 28 arthroplasty, 63
15259_Index.qxd 3/15/09 6:52 AM Page 234
234 INDEX
Occupational exposure, to anesthetic agents, P genetic factors in, 167

216–219 Pain management. See specific procedures and incidence of, decreasing, 167
anesthetic practice and, 218 types key messages on, 167–168
key messages on, 218 Pancuronium, and anaphylaxis, 163 postoperative pain and, 167
minimizing, 217–218 Parasternal block, for cardiac surgery, 15 preoperative pain and, 167
outside operating room, 217 Paravertebral nerve blockade, for thoracic risk factors for, 166–167, 167t
personal exposure vs. monitored surgery, 66–69 sensitization in, 167
environmental level, technique of, 67, 69f surgery type and, 167
216–217 vs. thoracic epidural analgesia, 66–67, Personal exposure level, 216–217
scavenging and, 217 67f, 68f Phantom limb pain (PLP), prevention of,
ventilation and, 217 Patient positioning 212–214
Occupational exposure limits (OELs), in bariatric surgery, 87–88 Phenylephrine, for hypotension, in caesarean
216–217, 217t in central venous cannulation, 133 section, 224–225
Off-pump coronary artery bypass (OPCAB), in obstructive sleep apnea, 176–177 Phosphodiesterase inhibitors, for heart
17–21 and postoperative neuropathy, 27–28, 29 failure, 182
anesthesia plan in PCI. See Percutaneous coronary Phrenic nerve injury, in cardiac surgery, 28
best, development of, 19 intervention PION. See Posterior ischemic optic
patient history and, 17, 18f Pediatric Anesthesia Emergence Delirium neuropathy
anesthetic management in, and patient Scale, 207, 208t PLP. See Phantom limb pain
outcome, 19 Percutaneous coronary intervention (PCI) PNB. See Peripheral nerve blockade
conversion to CPB in, indications for, 20 preoperative, preventive role of, 40–41, 77 Pneumonectomy
hemodynamic changes in, 19–20, 19f recent, management of surgical patients fluid overload in, 74–75
heparin reversal in, 20 with, 41, 42f, 77–79, 78t, 136 pulmonary edema after, 74–76
intraoperative monitoring in, 17–19 Perineural catheter, for opioid-addicted chest x-ray of, 74–75, 75f
key messages on, 20 trauma patient, 150–151, 151f key messages on, 75
minimally invasive direct access, 17 Perioperative care risk factors for, 75, 75t
reperfusion abnormalities in, 20 ␤-adrenergic antagonists in, 5–8 ventilatory management of, 75
stabilizer device in, 17, 18f albumin in, 55–57 SpO2 decrease in, initial response to, 74
surgical approaches to, 17 aprotinin and antifibrinolytics in, 22–24 PNI. See Peripheral nerve injury
vs. traditional CABG, 17, 18t, 20 glycemic control in, 9–13 Polytrauma, hypertonic saline resuscitation
typical, 17 pain management in, ASA guidelines on, in, 48–50
OIH. See Opioid-induced hyperalgesia 212, 213t PONV. See Postoperative nausea and
Ondansetron, for nausea/vomiting prevention, statins in, 1–4 vomiting
128, 129 Perioperative complications Positioning, patient. See Patient positioning
OPCAB. See Off-pump coronary artery cognitive dysfunction, 35–37 Post Anesthetic Behavior Scale, 207, 208t
bypass myocardial infarction, 38–43 Posterior ischemic optic neuropathy (PION),
Opioid(s) nausea and vomiting, 127–130 31
addiction to, analgesia/anesthesia in, neuropathy, 27–30 Postoperative nausea and vomiting (PONV)
149–152 visual loss in, 31–34 in children, 128
intraoperative, 150 PeriOperative ISchemic Evaluation trial, 99 discharge expectations for, 129
postoperative, 150–151 Peripheral nerve blockade (PNB) key messages on, 129
preoperative, 149 central nervous system toxicity of, 58 nonpharmacologic treatment of, 129
intrathecal lidocaine, adrenaline, and bupivacaine mix pathophysiology of, 127
for cardiac surgery, 15 for, 140, 142 prevention of
for total knee arthroplasty, 62 lower level monitoring required with, 142 anesthetic technique for, 129
and myocardial preconditioning, 100 neurologic complications of, 58–61 evidence-based, 127–130
in neuroprotection, 191 with continuous catheter, 60, 60t premedicants for, 128–129, 128t
in obese patients, 88 incidence of, 59–60, 59t, 60t risk factors for, 127–128
and obstructive sleep apnea, 63–64 with single injection, 59t, 60t anesthetic-related, 127, 128t, 129
and postoperative nausea/vomiting, for opioid-addicted trauma patient, Apfel score of, 127–128
127–128, 129 149–151, 150f, 151f patient-specific, 127, 128t
tolerance to, 149, 169 outcome studies of, 141–142 surgery-related, 127, 128t
Opioid-induced hyperalgesia (OIH), reduced physiological insult with, 142 Postoperative visual loss (POVL), 31–34
169–170 for total knee arthroplasty, 62–65 anatomical considerations in, 31
key messages on, 170 ultrasound guidance for, 140–144, 141f, ASA practice advisory on, 31, 32–33
management of, 170 142f, 149–151, 150f, 151f key messages on, 33
mechanisms of, 170 and block success rate, 142 management of, 33
Optical fiberscopes, for awake, tracheal intu- and dose reduction, 142–143 mechanism of injury, 31
bation, 107 key messages on, 143 prevention of, 32–33
Optic nerve and onset time, 142 risk factors for, 32
anatomy of, 31 Peripheral nerve injury (PNI), postoperative, Potassium levels, in subarachnoid
injury to in cardiac surgery, 27–30 hemorrhage, 195
in cardiac surgery, 28 Persistent postsurgical pain (PPSP), 166–168 PPH. See Pulse pressure hypertension
and postoperative visual loss, 31–33 concomitant treatments and, 167 PPSP. See Persistent postsurgical pain
Oral hypoglycemic agents, in hospitalized definition of, 166 Pregabalin
patients, 11 demographic and psychosocial factors in, for preventing persistent postsurgical
Oxyhemoglobin dissociation curve, fetal vs. 166 pain, 167
adult, 221–222, 222f development of, changes underlying, 167 for total knee arthroplasty, 63t, 64
15259_Index.qxd 3/15/09 6:52 AM Page 235
INDEX 235
Pregnancy. See also Caesarean section in Duchenne muscular dystrophy, optimal perioperative management in, 159
intraoperative awareness in, 200 119–121 pathophysiology of, 157–158
occupational exposure to anesthetic agents treatment of, 121 preoperative screening for status, 158–159,
in, 216 grapefruit juice and, 180 158t
Prilocaine, for shoulder arthroplasty, 146 statins and, 3 Sleep apnea
Propofol Right internal jugular vein (RIJV), central obstructive
in mitochondrial disease, 204 venous cannulation via, anesthesia and, 175–178
for MRI sedation/anesthesia, 124 132–134, 133f ASA recommendations on, 175
and myocardial preconditioning, 100–101 Rocuronium and bariatric surgery, 87–88
in neuroprotection, 190–191 as alternative to succinylcholine, 111 benzodiazepine alternatives in, 177
in obese patients, 88 and anaphylaxis, 163 definition of, 177
and postoperative nausea/vomiting, 129 in obese patients, 88 difficult intubation in, 175
Prostate, transurethral resection of. See sugammadex for emergency reversal of, extubation safety in, 176–177
Transurethral resection of 198–199 intubation in, 175–176
prostate Ropivacaine, for shoulder arthroplasty, 146t key messages on, 177
Protamine, for heparin reversal, in off- Royal College of Anaesthetists, 214 management without formal diagnosis,
pump coronary artery RSI. See Rapid sequence induction 175–176
bypass, 20 opioids and, 63–64
Pulmonary edema patient positioning in, 176–177
postpneumonectomy, 74–76 S perioperative analgesia and anesthesia
chest x-ray of, 74–75, 75f SAH. See Subarachnoid hemorrhage in, 176
key messages on, 75 St. John’s wort, and anesthesia, 180–181 postoperative monitoring in, 177
risk factors for, 75, 75t Saline risk factors for, 175
ventilatory management of, 75 for fluid resuscitation, 48–50, 55–56 severity of, 175, 176t
in transurethral resection of prostate for transurethral resection of prostate signs and symptoms of, 175, 176t
syndrome, 172–174, 173f syndrome, 173–174 screening questions for, 64, 64t
Pulse pressure hypertension (PPH), 96t, 97 Saphenous nerve injury, in cardiac surgery, 28 Sliding scale insulin therapy, 11–12
Scavenging, and occupation exposure, 217 Sodium channel blockers, and myocardial
Sciatic nerve block oxygen supply/demand, 99
R in total knee arthroplasty, 63 Sodium levels
Ranolazine, and myocardial oxygen ultrasound guidance for, 140–143, 141f hypertonic saline and, 50
supply/demand, 99 Scopolamine, transdermal, for nausea/vomit- in subarachnoid hemorrhage, 196
Rapid sequence induction (RSI) ing prevention, 128, 129 in transurethral resection of prostate
classic, 110–111 SEDline monitor, 116 syndrome, 172–173
pediatric modification of, 111 Seizures, peripheral nerve blockade and, 58–61 Spinal anesthesia
succinylcholine for, 110–111 Sensitization for caesarean section, 220–225
Razaxaban, and neuraxial blockade, 188 in opioid-induced hyperalgesia, 170 after inadequate epidural, 220–221
Recombinant factor VIIa in persistent postsurgical pain, 167 appropriate monitoring in, 224, 225t
in cardiac surgery, 25–26 Septic shock, vasopressin for, 92 and fetal heart rate, 221, 221f
indications for, 25 Serotonin receptor antagonists, for fluid preloading for, 224
off-label administration of, 25–26 nausea/vomiting prevention, hypotension with, 224–225
risk of thromboembolic events with, 26 128, 129 risks of, 220–221
Recurrent laryngeal nerve injury, in cardiac Sevoflurane total
surgery, 28 and emergence agitation in children, 207, clinical presentation of, 223
Regional anesthesia. See also specific types 209 management of, 222
for Alzheimer patients, 155–156 in mitochondrial disease, 204 for cardiac surgery, total, 15
for awake, tracheal intubation, 106 for MRI sedation/anesthesia, 124–125 Spine surgery, postoperative visual loss in,
continuous ambulatory, 145–148 and myocardial preconditioning, 100–101 31–33
for patients with coronary artery disease, and neuroprotection, 191 Spirometry, in mitochondrial disease, 203,
136–139 in obese patients, 88 204t
for transurethral resection of prostate, occupational exposure to, 216–218 Spontaneous abortion, occupational exposure
171 Shock, vasopressin for, 92–93 and, 216
Remifentanil Shoulder arthroplasty Stabilizer device, in OPCAB, 17, 18f
and myocardial preconditioning, 100–101 anesthetic and analgesic options in, Statins
in obese patients, 88 145–146, 146t and myocardial oxygen supply/demand, 99
in obstructive sleep apnea patients, 177 continuous ambulatory regional anesthesia for perioperative myocardial infarction, 40
Renal dysfunction, in heart failure, 182–184 for, 145–148 and perioperative risk, 1–4
Resuscitation. See Fluid resuscitation Sickle cell crisis, 157–158 ACC/AMA guidelines on, 2–3
Retina Sickle cell disease, 157–161 in cardiac and vascular surgery, 1–2
anatomy of, 31 acute chest syndrome in, 157, 158f, 159, key messages on, 3
injury to, and postoperative visual loss, 160t need for future studies, 3
31–33 arterial blood analysis in, 157, 158t in noncardiovascular surgery, 2
Revision hip arthroplasty, blood loss and blood transfusion (sickle cell dilution) in, pharmacologic mechanisms of, 1
conservation in, 83–86 159, 159t safety of, 3
rFVIIa. See Recombinant factor VIIa hemoglobin dilution in, 159 withdrawal of, effect of, 2
Rhabdomyolysis hydroxyurea treatment in, 160 Stroke, cardiac surgery and, 35–37
anesthesia-induced hypothermia in, 159 Subarachnoid block, for transurethral resec-
clinical features of, 120t key messages on, 160 tion of prostate, 171
15259_Index.qxd 3/15/09 6:52 AM Page 236
236 INDEX
Subarachnoid hemorrhage (SAH) paravertebral nerve blockade for, 66–69, cardiac manifestations of, 173, 173f
coiling for, 193–197 67f, 68f classic triad of symptoms in, 172
advantages of, 195 thoracic epidural analgesia for, 66–67, differential diagnosis of, 171
anesthesia for, 193–197 67f, 68f, 69f emergency management of, 173
management of, 196 respiratory changes in, 66 intravascular absorption of solution in,
technique for, 195 Three-in-one block, in total knee 172
vs. clipping, 193–195 arthroplasty, 63 pulmonary edema in, 172–174, 173f
complications of, 196 Thrombocytopenia rapid diagnosis of, 171–172
decision-making on, 195 etiology of, 44 signs and symptoms of, 172
definition of, 195 heparin-induced. See Heparin-induced treatment of, current controversies over,
key messages on, 196 thrombocytopenia 173–174
monitoring in, 196 TKA. See Total knee arthroplasty Trauma. See also specific types
optimal timing of, 195 TOF ratio. See Train-of-four ratio pain management in
premedication for, 196 Total knee arthroplasty (TKA) in opioid-addicted patient, 149–152
electrocardiographic changes in, 196 multimodal analgesia for, 15, 63t, 64 options for, 212–213, 213t
electrolyte abnormalities with, 196 opioids and sleep apnea in, 63–64 purpose of, 212
grading and assessment of, 193, 194t, 195 peripheral nerve blockade vs. epidural Traumatic brain injury, hypertonic saline
incidence of, 190 analgesia for, 62–65 resuscitation in, 48–50
neuroprotection in surgery for, 189–192, 196 utilization rate for, 62 Tricyclic antidepressants, for preventing
triple-H therapy for, 191 Total spinal anesthesia persistent postsurgical
Subclavian vein, central venous cannulation in caesarean section pain, 167
via, 132 clinical presentation of, 223 Trigeminal nerve, in awake, tracheal
Succinylcholine management of, 222 intubation, 106
alternatives to, 111 in cardiac surgery, 15 Triple-H therapy, for cerebral vasospasm,
and anaphylaxis, 163–164 Tracheal intubation 191
contraindications to, 111, 121 air leak test in, 114 Troponins
drugs attenuating effects of, 111, 112t awake, 106–109 in heart failure, 183, 183t
in Duchenne muscular dystrophy, 120, 121 complications of, 108 in myocardial preconditioning, 101
indications for, 111 device or technique for, 107–108 in perioperative myocardial infarction,
introduction of, 110 patient preparation for, 106–107, 107t 39–40
side effects of, 111, 111t, 112t supraglottic airways vs., 108 TURP. See Transurethral resection of
for tracheal intubation, future for use of, difficult, vs. difficult mask ventilation, prostate
110–112 103 TXA. See Tranexamic acid
Sufentanil, in obese patients, 88 obstructive sleep apnea and, 175–176
Sugammadex pediatric
as alternative to succinylcholine, 111 anatomic considerations in, 113 U
for emergency reversal of neuromuscular complications of, vulnerability to, Ulnar neuropathy, postoperative, 27, 29
blockade, 198–199 113–114 Ultrasound guidance
Sulfonylureas, for hospitalized patients, 11 cuffed tracheal tubes for, 112–115 for central venous cannulation, 131–135
Superior laryngeal block, in awake, tracheal edema and cross-sectional area in, anesthesiologist experience with, 134
intubation, 106 113–114, 114t dynamic, 132–133, 133f, 133t
Supraglottic airways, vs. awake, tracheal injury in, levels vulnerable to, 114 key messages on, 134
intubation, 108 N2O diffusion in, 114 as standard of care, 133–134
Supralaryngeal airways, 104 specifically designed tubes for, 114 static, 132–133
Surgical stress response, 138 succinylcholine use in, future of, 110–112 for peripheral nerve blockade, 140–144,
Suxamethonium, in mitochondrial disease, 204 Train-of-four (TOF) ratio, in reversal of 141f, 142f
neuromuscular blockade, and block success rate, 142
198–199, 199f and dose reduction, 142–143
T Tranexamic acid (TXA) key messages on, 143
TEA. See Thoracic epidural analgesia in cardiac surgery, 23–24 and onset time, 142
TEE. See Transesophageal echocardiography for minimizing need for blood transfu- in opioid-addicted patient, 149–151,
Temperature. See Hyperthermia; sion, 81, 84 150f, 151f
Hypothermia Transesophageal echocardiography (TEE) Umbilical cord blood gas analysis, 222–223,
Terlipressin, 92, 97 in coronary disease patients, 100, 101 222t
Thiazide diuretics, for hypertension, 95, 96t in off-pump coronary artery bypass,
Thiazolidinediones, for hospitalized 19–20
patients, 11 Transfusion. See Blood transfusion V
Thiopental, in obese patients, 88 Transfusion Requirement in Critical Care Vagus nerve, in awake, tracheal intubation,
Thiopentone trial, 84 106
in mitochondrial disease, 204 Transtracheal block, in awake, tracheal intu- Valerian root, and anesthesia, 180
in neuroprotection, 191 bation, 106 Vasoconstrictors, for hypotension, in
Thoracic epidural analgesia (TEA), for Transurethral resection of prostate (TURP) caesarean section, 224–225
postthoracotomy pain, 66–67, anesthetic considerations in, 171 Vasopressin
67f, 68f preoperative blood results in, 171, 172t for anaphylactic shock, 92
Thoracotomy Transurethral resection of prostate (TURP) for cardiac arrest, 92
postoperative pain in syndrome, 171–174 for cardiac resuscitation, 91–94
mechanisms of, 66 arterial blood gas analysis in, 172–173, 172t doses of, 92, 92t
15259_Index.qxd 3/15/09 6:52 AM Page 237
INDEX 237
for hemorrhagic shock, 92 Visual loss, postoperative (POVL), 31–34 Vomiting. See Nausea and vomiting,
for intraoperative hypotension, 93 anatomical considerations in, 31 postoperative
for liver transplant patients, 92–93 ASA practice advisory on, 31, 32–33
metabolic effects of, 91–92, 92t key messages on, 33
receptors for, 91, 92t management of, 33 W
for septic shock, 92 mechanism of injury, 31 Warfarin, in heparin-induced thrombocy-
Vasospasm, cerebral, triple-H therapy for, 191 prevention of, 32–33 topenia, 46
Vecuronium risk factors for, 32 White coat hypertension, 96
and anaphylaxis, 163 Volatile anesthetics World Federation of Neurological Surgeons
in obese patients, 88 in Duchenne muscular dystrophy, grading scale, 193, 194t, 195
Ventilation, and occupational exposure, 217 119–122 World Health Organization
Videoscope, for awake, tracheal intubation, and myocardial preconditioning, 100–101 anemia definition of, 84
107–108 and postoperative nausea/vomiting, 127 myocardial infarction definition of, 38–39

Case Based Anes

Uploaded by

Copyright:

Available Formats

Case Based Anes

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Case Based Anes

Uploaded by

Copyright:

Available Formats

15259_FM.

qxd 3/19/09 12:35 AM Page i

CLINICAL LEARNING GUIDES

CLINICAL LEARNING GUIDES

GABRIELLA IOHOM, MD, PhD

CHARLES W. HOGUE, JR., MD

Acquisitions Editor: Frances DeStefano

Copyright © 2009 Lippincott Williams & Wilkins, a Wolters Kluwer business.

351 West Camden Street

530 Walnut Street

Library of Congress Cataloging-in-Publication Data

Case-based anesthesia : clinical learning guides / [edited by] George Shorten.

Dedicated to the memory of Gerard McDonnell.

Hassan M. Ahmad, MD John Dowling, BDS, MB, BCh, BAO(Hons),

Ashit Bardhan, MBBS, FCARCSI Amanda A. Fox

Roy Kan, MBBS(Singapore), MMed (Anesth) James O’Driscoll, FCARCSI

1. Statins and Perioperative Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

3. Perioperative Glycemic Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

4. Neuraxial Analgesic Techniques for Cardiac Anesthesia . . . . . . . . . . . . . . . . . . 14

5. Off-Pump Coronary Artery Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

6. Aprotinin and Antifibrinolytics in Cardiac Surgery . . . . . . . . . . . . . . . . . . . . . . 22

7. The Use of Recombinant Factor VIIa in Cardiac Surgery . . . . . . . . . . . . . . . . . 25

8. Postoperative Neuropathy After Cardiac Surgery . . . . . . . . . . . . . . . . . . . . . . . . 27

9. Postoperative Visual Loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

10. Postoperative Cognitive Dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

11. Perioperative Myocardial Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

12. Heparin-Induced Thrombocytopenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

13. Hypertonic Saline Resuscitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

14. Preoperative Liver Function Test Abnormalities . . . . . . . . . . . . . . . . . . . . . . . . 51

15. Perioperative Use of Albumin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

16. Neurologic Complications of Peripheral Nerve Blockade . . . . . . . . . . . . . . . . . 58

17. Peripheral Nerve Block Versus Epidural Analgesia for

18. Paravertebral Nerve Blockade for Thoracic Surgery . . . . . . . . . . . . . . . . . . . . . 66

19. Carotid Artery Stenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

20. Postpneumonectomy Pulmonary Edema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74

21. Perioperative Antiplatelet Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77

22. Intraoperative Blood Conservation Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . 80

23. Transfusion Thresholds and Intraoperative Coagulopathy . . . . . . . . . . . . . . . . 83

24. Anesthesia for Bariatric Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

25. Vasopressin and Resuscitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91

26. Anesthesia and Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

27. Pharmacologic Myocardial Preconditioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99

28. Predicting Difficult Mask Ventilation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

29. Awake Tracheal Intubation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106

30. Is There a Future for Succinylcholine? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110

31. Cuffed Tracheal Tubes for Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113

32. Role of Intraoperative BIS Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116

33. Duchenne Muscular Dystrophy and Volatile Anesthetics . . . . . . . . . . . . . . . . 119

34. Anesthesia for Magnetic Resonance Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . 123

35. Evidence-Based Prevention of Postoperative Nausea and Vomiting . . . . . . . 127

36. Ultrasound Guidance for Central Venous Cannulation . . . . . . . . . . . . . . . . . . 131

37. Regional Anesthesia Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136

38. Ultrasound Guidance for Peripheral Nerve Blockade . . . . . . . . . . . . . . . . . . . 140

39. Continuous Ambulatory Regional Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . 145

40. Postoperative Analgesia in a Trauma Patient With

41. Alzheimer’s Disease and Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153

42. Sickle Cell Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157

43. Anaphylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162

44. Persistent Postsurgical Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166

45. Opioid-Induced Hyperalgesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169