Clinical Blood Gases Assessment Intervention

Clinical
Blood
Gases
Assessment and
Intervention
This page intentionally left blank
Clinical
Blood
Gases
Assessment and
Intervention
Second Edition
William J. Malley, MS, RRT, CPFT

Administrative Director, Respiratory Services
The Western Pennsylvania Hospital
Program Director, School of Respiratory Care
Indiana University of Pennsylvania/The Western Pennsylvania Hospital
Pittsburgh, Pennsylvania
11830 Westline Industrial Drive
St. Louis, Missouri 63146
CLINICAL BLOOD GASES: ASSESSMENT ISBN 0-7216-8422-X

AND INTERVENTION, SECOND EDITION
Copyright 2005, Elsevier (USA). All rights reserved.
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NOTICE
Pharmacology is an ever-changing field. Standard safety precautions must be followed, but as

new research and clinical experience broaden our knowledge, changes in treatment and drug
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this publication.
Previous edition copyrighted 1990.
International Standard Book Number 0-7216-8422-X
Managing Editor: Mindy Hutchinson

Senior Developmental Editor: Melissa K. Boyle
Publishing Services Manager: Melissa Lastarria
Project Manager: Joy Moore
Designer: Amy Buxton
Printed in the United States of America
Last digit is the print number: 9 8 7 6 5 4 3 2 1

To my dad (rest in peace),
For his inspiration, spirit, and wit.
To my mom,
For her understanding and love.
To my wife, Margie,
For her infinite endurance and love.
v
Reviewers
ALLEN W. BARBARO, MS, RRT CATHERINE M. FOSS, BS, RRT, RPFT
Program Director, Respiratory Care Clinical Research Coordinator, Pulmonary
St. Lukes College and Critical Care
Sioux City, Iowa Duke University Medical Center
Durham, North Carolina
SUSAN BLONSHINE, BS, RRT, RPFT, AARC Diagnostic Specialty Section Chair
FAARC, AE-C
Director, TechEd Consultants LAVERNE YOUSEY, RRT, MSTE
Mason, Michigan Chair, Allied Health Department
Technical Director, Pediatric Pulmonary Program Director, R.C. Program
Function Laboratory Professor of Respiratory Care
Michigan State University University of Akron
East Lansing, Michigan Akron, Ohio
LINDA K. EVANS, RN, MSN

Instructor of Clinical Nursing
Sinclair School of Nursing
University of Missouri
Columbia, Missouri
vii
Preface
More than a decade has passed since the first relocated to Chapter 2 (Chapter 7 in the first
edition of Clinical Blood Gases, yet the need edition) because the skill needed to be able to
for clinicians with a comprehensive under- categorize blood gases must be mastered in the
standing of blood gas analysis and interpreta- early phase of clinical practice. In an effort to
tion persists. Overall, I suspect we do fewer be more consistent with common clinical prac-
blood gases today than we did then primarily tice and exams, I have also abandoned the use
as a result of cost-containment initiatives and of the terms acidemia and alkalemia in classi-
the ubiquitous availability of pulse oximetry. fications. Since one must have an acidosis to
Nevertheless, even today, arterial blood gases cause an acidemia, I have simply used the term
remain the undisputable gold standard in the acidosis in blood gas classification. Also, the
critical assessment of oxygenation, acid-base chapter on technical accuracy (Chapter 8 in the
balance, and ventilation. first edition) has been relocated to Chapter 5
It could be argued that because of the so that all technical issues are covered in Unit 2.
decreased incidence of blood gas sampling, In addition to overall updates regarding
blood gas analysis has become of lesser technology and clinical application, probably
importance. Indeed, the opposite is the case. the most significant enhancement to the text as
Acquisition of arterial blood gases seems to be a teaching tool is the addition of two On-Call
reserved for more critical situations, specifi- Cases within each chapter. These cases
cally in those patients where vital life functions involve critical thinking and application and
are in question. In many cases, electrolytes or deal specifically with important content con-
other analytes are measured concurrently with tained within each chapter. On-Call Cases are
blood gases to provide a more comprehensive germane to the particular content of a specific
glimpse into disease or emergent needs. chapter which differentiates them from the more
It has been my observation that with fewer comprehensive cases in Chapter 16. Detailed
blood gases being drawn, many clinicians fail discussion regarding the On-Call Cases is pro-
to maintain interpretative competence or, vided in the Answers section near the end of
worse yet, never achieve it. Thus, when a the book. Case questions are designed in a
patient crisis exists and a definitive analysis of consistent manner to encourage analytical
oxygenation, acid-base, and/or ventilation is problem-solving skills and specific action.
essential, no one may be available or suffi- Another new feature, NBRC Challenge,
ciently experienced to respond. Therefore now, offers five multiple-choice questions at the end
as perhaps never before, clinicians who are of each chapter. These questions were cross-
expert in the nuances of this assessment are referenced to the National Board for
vital. This text is written to ensure that blood Respiratory Care (NBRC) examination matrices
gas experts are never extinct. This second edition in effect at the time of development of the book.
is also designed for the critical thinker and life- Various questions may be based on any of the
long student of oxygenation, acid-base bal- various exams used for Certified or Registered
ance, ventilation, and related pathophysiology. Respiratory Therapist credentialing. Although
Because of the widespread acceptance of the NBRC matrix is continuously evolving
the first edition, the book is organized in much and specific references to the matrices may
the same manner with a few key exceptions. change, the goal of these multiple-choice ques-
Classification, or naming, of blood gases tions is critical thinking with particular reference
(referred to as interpretation by some) has been to actual job functions, experiences, and
ix
x Preface
responsibilities. The slight change in the subti- Clinical Blood Gases remains unique in its
tle to Clinical Blood Gases: Assessment and role as a medical textbook. It is not only a ref-
Intervention highlights the clinical decision- erence book but also a clearly organized, com-
making focus of the text. prehensive, interactive educational vehicle. It is
Like the first edition, the second edition of my hope that, like the first edition, it will be
Clinical Blood Gases remains the most com- enthusiastically received by respiratory thera-
prehensive, current, and easy-to-read reference pists, physicians, nurses, and other health-
for clinical issues pertaining to acid-base balance, related professionals. Most importantly, I hope
oxygenation, blood gases, and noninvasive it will be a rich source of information and
blood gas measurements. Furthermore, it again understanding that will, in turn, ultimately
provides a lavish supply of clear illustrations enhance patient care.
and tables to organize thinking and visualize
concepts. William J. Malley, MS, RRT, CPFT
Please feel free to forward any unusual cases, questions, or correspondence to William Malley at
bmalley@icubed.com.
Acknowledgments
Very few textbooks of this magnitude are writ- I am also a recipient of the tremendous
ten by a single author. I believe the value and resources and commitment to excellence from
advantage of a single author is a continuity of Elsevier. Elsevier is relentless in their pursuit of
writing style, organization, focus, and approach. accuracy and quality. Melissa Boyle, Senior
The potential disadvantage of the single- Developmental Editor, and Mindy Hutchinson,
author approach is the critical need for peer Managing Editor, have provided me with a
review and multiple viewpoints. I have been rich source of expert reviewers and feedback in
fortunate to be surrounded by outstanding col- times of uncertainty. They have also gently
leagues and a rich source of reviewers through provided me with the needed encouragement
Elsevier. and support to complete this project in the
My first source of review includes the out- midst of our harried careers, families, and
standing faculty at the Indiana University of lives. They were patient but helped me stay the
Pennsylvania/The Western Pennsylvania Hospital course. Joy Moore, Production Project
baccalaureate respiratory therapy program. Manager, and Janine White, Production Editor,
The extensive clinical and professional knowl- were also a pleasure to work with.
edge of Kathy Kinderman, Jeff Heck, Jack Albert, The advantage and resources of a first-class
Catherine Myers, and Jackie Heisler is always publisher is clearly evident to me. Without the
readily accessible. Whenever I feel uncertainty, resourceful and cordial negotiations of
I look to their remarkable clinical expertise Andrew Allen, Publishing Director, I suspect
and guidance. this second edition would never have reached
Another valuable reference for me is fruition. He provided creativity, open commu-
Bud Jozwiak, director of the excellent labora- nication, patience, and support throughout.
tories at The Western Pennsylvania Hospital. Bud Most importantly, friends, family, and co-
is an invaluable resource for accurate labora- workers who I see every day need a special
tory and technical information. Hes always thanks. My secretary, Georgeann Meyers,
readily available to provide direction, informa- Clinical Director Kathy Kinderman, and faculty
tion, and counsel. Robin Nitkulinec, Manager are always there to provide help, support, and
of Respiratory Services, Charlie Morgan, understanding in my daily work environment.
Supervisor of Pulmonary Diagnostics, and Paul Finally, my wife, Margie, who has endured the
Fiehler, MD, Medical Director, are likewise most, has provided the ultimate positive sup-
always available to provide valuable expertise. port to complete a project of this magnitude.
xi
Contents
Unit I Introduction to 4 Blood Gas Electrodes and Quality
Blood Gases, 1 Assurance, 82
1 Arterial Blood Gases, 3 Blood Gas Electrodes, 82
Introduction, 3 Total Quality Management, 90
Normal Blood Gas Values, 4 Quality Assurance, 91
Arterial versus Venous Blood, 7 Quality Control, 92
Technique, 8 Continuous Monitoring of Blood
Arterial Cannulation, 25 Gases, 103
Arterial Line/Blood Gas Point-of-Care Testing, 106
Controversy, 28 Regulations and Laboratory
Capillary Sampling, 29 Accreditation, 107
AARC Clinical Practice Guidelines, 30 Exercises, 107
Exercises, 31 5 Accuracy Check and Metabolic
2 Blood Gas Classification, 35 Acid-Base Indices, 114
Introduction, 35 Accuracy Check, 114
Systematic Approach, 36 Metabolic Acid-Base Indices, 120
Acid-Base Status, 36 Exercises, 126
Basic (Primary) Acid-Base
Disturbance(s), 38 Unit III Basic Physiology, 133
Compensation Assessment, 42 6 Oxygenation and External
Acid-Base Classification versus Respiration, 135
Interpretation, 46 Introduction, 135
Oxygenation Status, 46 External Respiration, 138
Complete Blood Gas Classification, 48 Exercises, 159
Alternative Terminology, 48
Exercises, 50
7 Oxygen Transport and Internal
Respiration, 165
Unit II Technical Issues in Blood Introduction, 165
Gas Analysis, 59 Blood Oxygen Compartments, 165
Quantitative Oxygen Transport, 179
3 Blood Gas Sampling Errors, 61
Hemoglobin Abnormalities, 181
Introduction, 61
Internal Respiration, 186
Basic Physics of Gases, 61
Exercises, 190
Potential Sampling Errors, 66
Measurement of Blood Gases 8 Acid-Base Homeostasis, 196
and Electrolytes from a Single Hydrogen Ions and pH, 196
Sample, 75 The Lungs and Regulation of Volatile
Exercises, 76 Acid, 198
xiii
xiv Contents
The Kidneys and Acid-Base Renal Function, 313

Balance, 205 Body Fluids and Electrolytes, 314
Buffer Systems, 206 Sodium Regulation in the
Henderson-Hasselbalch Equation, 210 Kidney, 317
Exercises, 218 Urinary Buffers and H+
Excretion, 322
Unit IV Clinical Oxygenation, 225 Plasma pH and [K+], 323
9 Assessment of Hypoxemia and Law of Electroneutrality, 324
Shunting, 227 Stewarts Strong Ion
Difference, 326
Overview, 227
Exercises, 327
Assessment of Hypoxemia, 228
Effects of Cardiac Output on 13 Differential Diagnosis of Acid-Base
PaO2, 228 Disturbances, 332
Assessment of Physiologic Introduction, 333
Shunting, 232 Respiratory Acidosis, 334
Differential Diagnosis of Respiratory Alkalosis, 340
Hypoxemia, 236 Metabolic Acidosis, 343
Clinical Appearance of the Patient Metabolic Alkalosis, 350
with Hypoxemia/Hypercapnia, 239
Exercises, 356
Hyperoxemia, 239
Exercises, 240 14 Mixed Acid-Base Disturbances and
Treatment, 361
10 Treatment of Hypoxemia and Overview, 361
Shunting, 246
Factors That May Complicate
Treatment, 246 Clinical Acid-Base Data, 362
Oxygen Therapy, 247 Mixed Acid-Base
Mechanical Ventilation, 256 Disturbances, 364
Positive End-Expiratory Acid-Base Treatment, 369
Pressure, 258 Exercises, 379
Body Positioning, 264
Nitric Oxide, 266 Unit VI Noninvasive Techniques
Long-term Oxygen Therapy, 267 and Case Studies, 385
Exercises, 267 15 Noninvasive Blood Gas
11 Hypoxia: Assessment and Monitoring, 387
Intervention, 272 Introduction, 388
Overview, 272 Oximetry, 388
Oxygen Supply Variables, 273 Pulse Oximetry, 393
Key Indicators of Hypoxia, 290 Transcutaneous PO2/PCO2
Exercises, 298 Monitoring, 403
Capnometry, 406
Unit V Clinical Acid Base, 305 Exercises, 415
12 Regulation of Acids, Bases, and 16 Arterial Blood Gas Case Studies, 419
Electrolytes, 307 Narcotic Overdose, 419
Overview, 307 Unexplained Acidemia, 420
Regulation of Ventilation, 308 Gastrointestinal Disturbance, 420
Contents xv
Status Asthmaticus, 421 Pulmonary Edema, 430

Acute Respiratory Acidemia, 422 Answers to Arterial Blood Gas
Nasogastric Suction, 422 Case Studies, 432
Unexplained Alkalemia, 423
Oxygenation Disturbance, 423 References, 441
Diabetic Patient, 424
Answers, 460
Acute Exacerbation of Chronic
Obstructive Pulmonary
Disease, 425 Illustration Credits, 497
Mitral Valve Replacement, 426
Index, 501
Patient with Burns, 427
Chronic Obstructive Pulmonary
Disease and Congestive
Heart Failure, 429
I
UNIT
Introduction to Blood Gases
1
Chapter
1
Arterial Blood Gases
Blood gas and pH analysis has more immediacy and potential impact on patient care than any other
laboratory determination.
National Committee for Clinical Laboratory Standards690
There is no substitute for PO2, PCO2, and pH when you are really in the dark about oxygenation status,
acid-base, or ventilatory status.
Woody Kagler, M.D.105
Outline
Introduction, 3 Puncture Technique, 16
Normal Blood Gas Values, 4 Explanation, 16
Indices, 4 Selection of Site, 16
Oxygenation, 4 Radial Puncture, 22
Ventilation, 4 Sample Handling, 24
Acid-Base Balance, 4 Arterial Cannulation, 25
Normal Ranges, 5 Complications, 25
Units of Measurement, 6 Catheter Insertion, 27
Arterial Versus Venous Blood, 7 Arterial Line Sampling, 27
Technique, 8 Blood-Conserving Arterial Line Systems, 28
Preparation and Pre-analytical Considerations, 9 Arterial Line/Blood Gas Controversy, 28
Status of Patients and Control of Infection, 9 Capillary Sampling, 29
Steady State, 10 Theory, 29
Spontaneous Variability of PaO2, 11 Technique, 29
Documenting Current Status, 11 AARC Clinical Practice Guidelines, 30
Materials, 12 Exercises, 31
INTRODUCTION
and increasingly, rely on pulse oximetry as a
The arterial blood gas report is the cornerstone complete substitute for arterial blood gas data.
in the diagnosis and management of clinical Although pulse oximetry is extremely valuable
oxygenation and acid-base disturbances. An and provides us with real-time information, it
abnormal blood gas report may be the first clue provides only one small piece in oxygenation
to an acid-base or oxygenation problem: It may assessment. Furthermore, it has been shown
indicate the onset or culmination of cardiopul- that many junior physicians and nurses do not
monary crisis and may serve as a gauge with fully understand this technology and make
regard to the appropriateness or effectiveness of serious errors in its interpretation.167
therapy. Thus, the arterial blood gas report More importantly, pulse oximetry provides
plays a pivotal role in the overall care of car- absolutely no information regarding ventilation
diopulmonary disease. Using the arterial blood and acid-base balance. In one study, more than
gas report as a reference point, this text explores 50% of surgical patients who had arterial blood
the diagnosis, assessment, and intervention of gases drawn manifested alkalemia at some point
clinical acid-base and oxygenation problems. during their hospital stay.106 With only pulse
Over the past decade, the incidence of arterial oximetry, these acid-base abnormalities may
blood gas sampling has decreased primarily for easily go unnoticed and untreated. In contrast
cost-containment reasons. Clinicians, casually to pulse oximetry, there are myriad reasons for
3
4 Unit I Introduction to Blood Gases
arterial blood gas analysis. According to Clinical in the blood in two forms, dissolved O2 and
Guidelines published by the American Associa- combined O2. The PaO2 is the partial pressure
tion for Respiratory Care (AARC), indications of O2 dissolved in arterial blood, whereas the
also include assessment of the adequacy of SaO2 is the oxygen saturation of arterial hemo-
ventilation, acid-base evaluation, diagnostic globin (an indicator of combined O2).
evaluation, quantification of response to ther- Technically, the partial pressure of oxygen
apy, and monitoring of severity and progression (denoted PO2) is defined as the pressure of O2
of disease.15 in both a gas phase and a solution in equilib-
Several studies have shown that by avoiding rium.6 In contrast, oxygen saturation is the
the use of blood gases, we may be delaying or amount of oxyhemoglobin in a solution
preventing detection of serious oxygenation and expressed as a fraction (%) of the total amount
acid-base disturbances.108111 The real incre- of hemoglobin able to bind oxygen.6 It is note-
mental cost of an arterial blood gas report is worthy that abnormal (inactive) forms of
minuscule. The neglected and unquantifiable hemoglobin (dyshemoglobins) are not consid-
cost of overlooked clues in the diagnosis of life- ered in this calculation.241
threatening disturbances (i.e., acid-base, ventila- The PaO2 is directly measured and is the
tion, and oxygenation) is immeasurable. Arterial most sensitive indicator of oxygenation directly
blood gases remain the gold standard in com- measured. The PaO2 should be a focal point of
prehensive emergency and critical care assess- every blood gas interpretation. The SaO2 is a
ment. Their value must be weighed against the calculated value and a less sensitive indicator.
potential for real, substantial cost savings and There are times when a calculated SaO2 may
patient harm. be misleading (e.g., burn patients) so it is
sometimes not included with the routine blood
NORMAL BLOOD GAS VALUES gas report. Calculated SaO2 should not be used
for further clinical calculations such as shunt
Indices fraction because it may introduce significant
Table 1-1 shows the various indices that are error.241 SaO2 can actually be measured directly
typically reported when an arterial blood gas is with co-oximetry (as opposed to calculated) in
acquired. Collectively, these indices give us cases when this value is essential. Clinical and
valuable information about the important technical issues related to co-oximetry are dis-
triad of patient oxygenation, ventilation, and cussed in Chapters 11 and 15.
acid-base balance.
Ventilation
Oxygenation The single best way to evaluate the adequacy
Arterial blood gases remain the indisputable gold of ventilation is via the PaCO2 of an arterial
standard for evaluation of arterial oxygenation. blood gas. One cannot make a definitive eval-
Dean Hess, Ph.D., RRT., FAARC168 uation of whether an individual is hypoventi-
lating or hyperventilating by observation alone.
There are two indices shown in Table 1-1 (i.e., Ventilatory status is best assessed via arterial
PaO2 and SaO2) that basically reflect the amount blood gases.
of O2 present in the blood. Oxygen is carried
Acid-Base Balance
The arterial pH is the single best indicator of
Table 1-1. NORMAL ARTERIAL BLOOD GAS global and blood acid-base status. In addition
VALUES to providing definitive information about ven-
pH 7.357.45 tilation, the PaCO2 also allows us to evaluate
PaCO2 3545 mm Hg the respiratory component of acid-base balance.
[BE] 0 2 mEq/L Thus, we can determine if a given acid-base
PaO2 80100 mm Hg problem is of respiratory system origin.
[HCO3] 24 2 mEq/L
The remaining indices shown in Table 1-1
SaO2 97%98%
([HCO3] and [BE]) are non-respiratory
Chapter 1 Arterial Blood Gases 5
acid-base indices. Non-respiratory indices are Normal Ranges

commonly referred to as metabolic indices. The various quantities shown in Table 1-1 are
Metabolic indices will be abnormal when referred to collectively as arterial blood gases
the patient has a so-called metabolic (non- (ABGs). The values indicated in Table 1-1 are
respiratory) acid-base disturbance. Actually, normal ranges for adults. Normal ranges are
the term metabolic is sometimes misleading defined by the criterion that 95% of the nor-
because the patient often does not have a prob- mal population have values that fall within this
lem with metabolism per se, nevertheless, it is range. Normal values for any laboratory meas-
well ingrained in the acid-base lexicon and will urement are established through measure-
be used in this text. ments made on individuals assumed to have
Although it is common practice, it is really normal health. The average value is calculated
unnecessary to include both [BE] and plasma as well as the dispersion of values around the
[HCO3] on a report. This practice originates average, which is described by a statistical
from the Great Transatlantic Debate4,5 term called the standard deviation.
between the Boston and Copenhagen schools A large number of measurements made on
of thought regarding acid-base diagnosis and any normal population generally yields a dis-
treatment. tribution pattern similar to the one shown in
The Boston school has always advocated Figure 1-1. The most frequent value observed
the use and application of plasma [HCO3] as would be identical to the arithmetic mean. As
the most appropriate metabolic index. This index values deviate more and more from the mean,
is calculated by most blood gas machines via they occur less and less frequently. The curve
the application of the well-known Henderson- represented in Figure 1-1 is referred to as the
Hasselbalch equation. The plasma [HCO3] is normal (or gaussian) distribution. In the nor-
also historically involved in the development mal distribution, 68% of the population has
of blood gas analysis because it was the first values that fall within 1 standard deviation
metabolic index to be routinely reported. and 95% of the values measured in the popu-
Understanding of plasma [HCO3] is also lation fall within 2 standard deviations.
essential because it is the metabolic index most Finally, 99.73% of measurements fall within
often used in respiratory care credentialling 3 standard deviations.
examinations. Normal laboratory values are generally
The Copenhagen school, on the other hand, considered to be within 2 standard deviations
advocates the use of the [BE] as the primary
metabolic indicator, purporting its superiority
both diagnostically and therapeutically. The
index of choice is really a matter of personal
preference because the patient can be treated
appropriately with use of either index. The
level of understanding of the particular index
being used has greater importance, because
68%
both indices may be misleading if their partic-
ular nuances are not well understood.
Historically, a variety of other metabolic 95%
99.73%
indices have been reported (e.g., standard bicar- 3s 2s 1s X +1s +2s +3s
bonate, total body buffer base, and CO2 com-
Figure 1-1. Normal distribution of laboratory
bining power2,3), but none of these indices
values. Of the normal population, 68% have
is currently well accepted. Furthermore, they
measurements that fall within 1 standard deviation
provide us with no additional information nec- from the mean (x). Ninety-five percent of the
essary for optimum care of patients. They may, population values fall within 2 standard devia-
however, serve as a source of confusion and tions, and 99.73% fall within 3 standard devia-
are probably best omitted from the blood gas tions. Normal laboratory values are considered to
report. be 2 standard deviations from the mean.
from the mean because these values represent and sea level (760 mm Hg) are presumed
the vast majority of the population. The distri- unless otherwise noted.
bution pattern underlying the establishment The normal PaO2 in the supine position for
of normal values is important to understand an adult 40 to 75 years old can be calculated
because 5% of the normal population has val- specifically by the formula PaO2 = 109 (0.43
ues that fall outside the normal range. age).242 A PaO2 within 8 mm Hg of the
Nevertheless, it is highly unlikely that an predicted value is considered to be normal.
abnormal value reported in this population Because the minimum normal PaO2 at 40 years
will deviate greatly from the normal range. of age in the supine position is 80 mm Hg, most
Interestingly, there are data that suggest that tables show the normal PaO2 range as being
the mean normal pH is closer to 7.38 than approximately 80 to 100 mm Hg. Technically,
7.40.3 Nevertheless, there is little support or however, a PaO2 of 80 mm Hg in a 20-year-old
reason to change the accepted normal range individual is not normal.
because the difference is minimal and the range Arterial PO2 is approximately 5 mm Hg
of 7.35 to 7.45 is well ingrained. higher in the sitting position than in the supine
Regarding the normal blood gas values position and the mean normal value at a given
shown in Table 1-1, one study showed signifi- age can be calculated more precisely by the
cantly lower values for arterial carbon dioxide formula PaO2 = 109 (0.27 age).11 In gen-
tension (PaCO2) in young women compared to eral, the difference in PaO2 associated with
values in young men.7 Mean arterial PCO2 in positional change is minimal in young adults
the female group was 33 mm Hg. Lower arte- but magnified in the elderly.
rial PCO2 in women compared with men is also In clinical practice, it is not usually practical
consistent with some earlier findings.8 Indeed, or expedient to calculate PaO2 based on these
values of 30 to 46 mm Hg may more accu- formulas. An approximate rule of thumb is
rately characterize the normal range for the sometimes useful to estimate the minimum nor-
entire population, which is calculated from mal PaO2 in adults of different ages. Minimum
seven published studies.9 While keeping these normal PaO2 should exceed 90 mm Hg if the
issues in mind, the accepted normal range of patient is younger than 45 years old. Above
35 to 45 mm Hg is used in this text for stan- the age of 45, PaO2 generally decreases with
dardization and to avoid confusion. age; however, low minimum normal PaO2
Normal values for [BE] and [HCO3] may should exceed 75 mm Hg regardless of age.242
likewise be slightly (i.e., 1 to 2 mEq/L) lower in Interestingly, PaO2 seems to progressively
women than in men.7 Nevertheless, here again, decrease between the ages of 45 to 75, then
a single accepted normal range of 24 2 mEq/L actually increases slightly and levels off beyond
for [HCO3] and 0 2 mEq/L for [BE] is used age 75.242 This is contrary to earlier beliefs.
because the difference is slight and has little
clinical significance. Units of Measurement
The mean partial pressure of oxygen dis- It is essential to have a clear understanding of
solved in arterial blood (PaO2) in a normal the particular units in which any laboratory
young male is 97 mm Hg at sea level.10 Normal value is being measured. The pH value is
oxygen saturation of arterial hemoglobin dimension-less, and SaO2 is measured as a per-
(SaO2) is 97.5%. Both PaO2 and SaO2 values centage. The [HCO3] and [BE] are usually
tend to decrease with aging. reported in milliequivalents per liter (mEq/L).
Oxygenation values may also differ slightly Nevertheless, because mEq/L is equal to mil-
with body position; they are typically higher in limoles per liter (mM/L) in ions with a univalent

the sitting position than in the supine (lying on charge (e.g., HCO3 , Na+), mM/L may also be
the back) position particularly in the obese used as the units for these values.
or elderly. Finally, altitude and the percentage The PaO2 and PaCO2 are measured in mil-
of O2 inspired also affect PaO2. The effects of limeters of mercury (mm Hg), a unit of pressure.
these variables on PaO2 are discussed in The unit torr is synonymous with (mm Hg)
Chapter 3. In this text, room air (21% oxygen) and either may be substituted interchangeably.
The International System of Units (SI) has human cells. To assess delivery, one must ana-
attempted to standardize the reporting of all sci- lyze arterial blood en route to the cells. The
entific data and has made recommendations PO2 of peripheral venous blood, on its journey
with regard to the most appropriate units that back to the heart from the cells, provides little
should be used. information concerning O2 delivery.
The recommended SI unit for pressure is the Arterial blood also provides direct informa-
pascal (Pa). Because this unit is too small for clin- tion with regard to lung function and the ade-
ical use, the kilopascal (kPa) has been recom- quacy of CO2 excretion. When PaCO2 levels
mended for use in blood gases (1 kPa = 1000 Pa). are excessive, the ventilatory system has failed
The conversion factor from mm Hg to kPa is to perform one of its primary functions
0.133. Thus, the normal range of PaO2 (i.e., 80 namely, CO2 regulation in the blood. The
to 100 mm Hg) becomes 10.6 to 13.3 kPa, and venous PCO2 level, on the other hand, is pri-
the normal PaCO2 (i.e., 35 to 45 mm Hg) marily a result of local metabolic rate and per-
becomes 4.6 to 6.0 kPa. The clinician may see fusion. Either an increase in local metabolism
PaO2 and PaCO2 reported in SI units in some or a decrease in local perfusion elevates venous
foreign literature, but the awkwardness of the PCO2. Thus, venous PCO2 varies in different
decimal units has hampered general acceptance areas of the body and provides little useful
and there has been a general retreat from SI information regarding the adequacy of pul-
units in American journals and laboratories.13 monary ventilation.
Likewise, clinicians continue to use mm Hg or Finally, arterial blood is superior to periph-
torr when they report pressure measurements eral venous blood in both acid-base and oxy-
in blood gas analysis. A chart of pressure con- genation assessment because it reflects overall
version factors between mm Hg, kPa, and cm blood or body conditions. Arterial blood gases
H2O is shown in Table 1-2. are uniform regardless of the specific artery
from which the sample was drawn. This is true
because arterial blood, after being well mixed
ARTERIAL VERSUS VENOUS
in the heart, does not change appreciably in O2
BLOOD
or CO2 composition until it reaches the sys-
Blood vessels that carry blood away from the temic capillaries. The systemic capillaries are
heart are classified anatomically as arteries, the small vessels between arteries and veins
whereas vessels that return blood to the heart within which gas exchange takes place
are called veins. Arterial blood in the systemic between blood and body tissues. In general,
circulation (Fig. 1-2) provides more information samples of blood gases taken from any artery
than systemic venous blood with regard to ven- should have identical blood gas values.
tilation and oxygenation assessment. Arterial Peripheral venous blood, on the other hand,
blood is a uniform substance presented to all reflects only localized conditions. The O2 and
organs for their metabolic needs. CO2 levels in a given peripheral vein depend on
An important concern in oxygenation the metabolic rate and perfusion of the tissue
assessment is the adequacy of O2 delivery to all traversed earlier. Because local metabolism
may vary widely, venous blood gas samples
acquired simultaneously from different periph-
eral veins likewise vary substantially. The dif-
Table 1-2. PRESSURE UNIT CONVERSION ferent PvO2 levels in various peripheral veins
FACTORS are discussed later in Chapter 7 and are shown
cm H2O mm Hg kPa in Table 7-1.
Although less accurate than arterial samples,
1.0 0.736 0.098 venous samples from a well-perfused patient
1.359 1.0 0.133 may provide a gross indication of acid-base
10.197 7.501 1.0 balance,5 electrolyte levels, or abnormal hemo-
From Burke, J.F.: Surgical Physiology. Philadelphia, globins.241 Likewise venous blood pH appears
W.B. Saunders, 1984. to correlate well with arterial blood in patients
Systemic CO2 O2
capillaries
Circulation to
tissues of head
and upper body
Lung Lung
CO2
CO2
O2
O2
Pulmonary
capillaries
Pulmonary circulation
CO2 O2
Circulation to
tissues of
lower body
Systemic circulation
Figure 1-2. Pulmonary and systemic circulation. Blood from the pulmonary circulation flows back to the left
heart after gas exchange in the lungs. Oxygenated blood flows from the left heart to the systemic circulation.
with uremic acidosis and diabetic ketoaci- Compared with the acquisition of venous
dosis.112 One should also realize that any dif- blood, arterial sampling is technically more
ference between arterial and venous blood will difficult and has greater potential for serious
be exaggerated when the general or local cir- complication. The higher arterial pressure can
culation is impaired.107 Thus, measurement of make bleeding complications more profuse.
arterial blood gases is the gold standard in the Furthermore, large clot formation or prolonged
diagnosis and clinical management of oxygena- spasm in an artery could cut off vital supply of
tion and acid-base disturbances. O2 to the tissue. Arterial blood gas samples are
also very vulnerable to improper handling
technique because of their high gas content.
TECHNIQUE
Arterial blood is one of the most sensitive spec-
The collection of arterial blood is not only techni- imens sent for clinical laboratory analysis.107
cally difficult but can be painful and hazardous to Despite these drawbacks, after appropriate
the patient. Therefore, it is essential that individuals training, arterial blood sampling may be
performing arterial puncture be familiar with the accomplished simply, safely, accurately, and
proper techniques, with the dangers of the proce- expediently by respiratory therapists, labora-
dure, and with necessary precautions. tory technologists, nurses, or physicians. The
National Committee for Clinical Laboratory following section involves pre-analytical con-
Standards107 siderations when preparing to draw an arterial
blood sample; this is followed by a description therefore, a predisposition to bleeding compli-

of a technique of arterial puncture and speci- cations. Similarly, a low platelet count or a
men collection. prolonged bleeding time on laboratory reports
should also be noted. Identification of any
Preparation and Pre-analytical coagulation disorder should activate imple-
Considerations mentation of special bleeding precautions.
Status of Patients and Control of Infection
Before attempting to perform an arterial punc- Infection Control
ture, the clinician should always be aware of The clinician should always be cognizant that
the patients primary diagnoses and current infectious diseases may be transmitted by con-
status. A brief review of the chart, inspection tact with blood. The disease foremost on our
of the patient, and observation for respiratory minds in this regard is the acquired immuno-
care modalities (e.g., O2 therapy, mechanical deficiency syndrome (AIDS). AIDS is caused
ventilation) are essential. This initial evalua- by the human immunodeficiency virus (HIV),
tion may alert the clinician to a potential com- formerly known as the human T-lymphotropic
plication or suggest that the sample should be virus type IIIlymphadenopathy-associated
drawn at a later time. When the sample is to virus. This viral disease has essentially no cure
be drawn by a non-physician, the first step is as yet and may be contracted through intimate
to verify that a written order is documented in contact with the body secretions of an infected
the patients chart. The chart should then be individual.
evaluated for factors (e.g., medications) that The body secretions that contain the great-
might suggest the need for special precaution- est amount of the virus are blood, semen, and
ary measures. vaginal secretions.17 The virus may be transmit-
ted by sexual contact, percutaneous (through
Anticoagulants/Bleeding Disorders the skin) exposure, absorption through mucous
Pharmacologic therapy should be reviewed to membranes (e.g., mouth, eyes), and through
ascertain whether the patient is undergoing anti- non-intact mucous membranes or skin (e.g.,
coagulant or thrombolytic therapy. Commonly cuts, open wounds).17 The risk that healthcare
prescribed anticoagulants include heparin, war- workers may acquire the disease is related to
farin (Coumadin), and dipyridamole. The mild the potential for percutaneous exposure or
anticoagulant effect of aspirin may be of lesser mucous membrane contact with contaminated
importance.15 Anticoagulant therapy is associ- body secretions.
ated with an increased likelihood of bleeding A major problem in controlling the spread
complication after puncture, and additional pre- of this disease is the fact that individuals
ventive measures should be taken. Consideration infected with the virus are asymptomatic early
may be given to scheduling the arterial puncture in the disease while at the same time they
approximately 30 minutes before the next are contagious. Thus, all blood samples must
scheduled dose of anticoagulant, if feasible.16 be treated as though infectious and handled
Thrombolytics (e.g., streptokinase, tissue with standard precautions.107 Standard pre-
plasminogen activator) differ from anticoagu- cautions are new guidelines that include the
lants in that they are administered to break major features of universal fluid precautions
down (lyse) blood clots rather than simply to and body substance isolation procedures.107
prevent clotting. Nevertheless, excessive bleed- Standard precautions are more comprehensive
ing after arterial puncture may also occur when than universal precautions, which only
these drugs are being administered.15 account for bloodborne pathogens. Standard
When evaluating the patients history and precautions address the transmission of all
progress notes, the clinician should be espe- bloodborne pathogens.107 Both standard pre-
cially alert for documentation of blood coagu- cautions and universal precautions are avail-
lation disorders (coagulopathy). Hemophilia, able through the Centers for Disease Control.
a genetic disorder found in men, is character- Other infectious disorders that may be
ized by a prolonged blood clotting time and, acquired through blood contact include viral
hepatitis, syphilis, Jakob-Creutzfeldt disease, after use or use of some other device to assure
and septicemia. Viral hepatitis is a generalized that inadvertent puncture cannot occur is
inflammation of the liver caused by hepatitis essential. After use, needles should be placed in
virus A, B, or C. Hepatitis vaccination, which puncture-resistant containers that are located
prevents hepatitis B on a long-term basis, is as close as is practical to the area where they are
available and healthcare workers who rou- being used.
tinely perform arterial puncture should receive
it. There is also an injection available to pre- Patient Identification and Assessment
vent hepatitis A in the short term; however, no Identification of the correct patient is extremely
protection is available for hepatitis C. Syphilis important. NCCLS document H3Procedure
is a chronic infectious venereal disease that for the Collection of Diagnostic Blood
may also be transmitted through the blood. Specimens by Venipuncturedescribes this in
Jakob-Creutzfeldt disease is a rare, fatal neu- more detail.691
rologic disorder that is transmitted by a virus. Likewise, the patient and the clinical indica-
Septicemia is a systemic infection in which tion for the sample should be assessed before
pathogens are present in the blood. acquisition. Knowledge of current vital signs
In the past, samples obtained from individ- and a general awareness of the patients back-
uals with any of the above disorders were ground and psychological status may also con-
marked as precaution samples, and special pro- tribute to acquisition of the sample smoothly
cedures were implemented to minimize the risk and efficiently. The more information the clini-
of infection to the healthcare worker. Today, cian has with regard to a particular patient, the
however, all blood samples should be handled more prepared he or she is to care for that
as if they are infected, because most individuals patient most effectively. Notwithstanding, the
who have HIV are not diagnosed and are review of the chart is most often brief in clini-
asymptomatic. cal practice due to time constraints and the
Standard precautions require diligent hand- need for efficiency.
washing and use of gloves when the hands are
likely to come into contact with body secretions Steady State
(e.g., during arterial blood gas sampling14). The When oxygen therapy or mechanical ventila-
Centers for Disease Control also recommends tion is used, a period of time is required before
the use of masks and protective eyewear (to the complete effect of the therapy is reflected in
avoid contact with mucous membranes) if a the arterial blood specimen. Similarly, the same
procedure is likely to generate droplets of blood principle is true when therapy is changed or
and aprons or gowns if blood is likely to be discontinued and following exercise. Because
splashed during a procedure.19 blood gases are often the major criteria on which
Handwashing is critical between examina- major therapeutic decisions are made regarding
tions of patients and immediately after any oxygenation and acid-base disturbances, it is
direct contact with blood. Gloves should always crucial that the blood gas results provide us
be worn when acquiring an arterial blood sam- with an accurate and current reflection of the
ple, and the gloves should be changed before patients status.
contact with each new patient. Remember, During this period of adjustment to a change
however, that gloves are an adjunct to, but not in therapy, blood gas values are in a dynamic,
a substitute for, handwashing. changing state. In time, the entire cardiopul-
Furthermore, needles must be handled care- monary system reaches a new equilibrium or
fully to prevent accidental puncture. Needle steady state. Blood gas values remain relatively
sticks are the most frequent source of transmis- constant from this point on, and the complete
sion of bloodborne diseases in healthcare work- impact of the therapy is reflected in the arterial
ers.19,20 Needles should not be purposely bent blood.
or broken by hand, removed from syringes, or Arterial blood samples must always be
manipulated by hand in any way. Specimen drawn only when the patient is in a steady state.
sampling devices in which the needle retracts The actual time required for the attainment of
a steady state differs slightly with the patients Spontaneous Variability of PaO2
pulmonary status. In patients free of overt pul- The clinician should also appreciate that some
monary disease, a steady state is likely achieved studies have shown considerable spontaneous
in as few as 1 to 3 minutes1,21 and almost cer- variability in PaO2 in apparently stable
tainly within 10 minutes.22,23 patients.169 This variability may be as much as
In patients with chronic airway obstruction, 10% and may be due to patient or machine
up to 24 minutes after a change in therapy may issues.168 The important point here is that
be necessary.24 In clinical practice, a 20- to changes in PaO2 of as much as 8 mm Hg should
30-minute waiting period is usually recom- be viewed with skepticism because they are
mended before sampling arterial blood after a commonly a result of spontaneous variability.
change in oxygen therapy or ventilation.1,15,25
As described previously, however, only 3 to Documenting Current Status
10 minutes is necessary to achieve steady-state Many times, the individual who interprets and
conditions in the absence of pulmonary disease. acts upon the blood gas report is not the same
Ideally, a patient who is breathing spon- individual who drew the sample. Therefore, it
taneously should also be at rest for at least is important that sufficient information
5 minutes before sample acquisition.14 Like- regarding the patients status at the time of the
wise, temporary fluctuations in therapy also sample be documented. Sound decisions can be
compromise steady-state conditions, which may made only in the proper context of circum-
occur if the patient removes his or her oxygen stances at the time of sampling.
mask or must be suctioned for excessive pul- Specific information regarding identifica-
monary secretions. The clinician drawing tion of the sample and the date and time of
the sample is responsible for ensuring that the acquisition is essential on the requisition slip.
patient is in a steady state before arterial This information must include the patients full
puncture. When a sample is thought to represent name and hospital or emergency room num-
nonsteady-state conditions, a repeat puncture ber. The blood vessel source should also be
with related pain, risks, and cost is probably noted (i.e., arterial, venous, or mixed venous).
necessary. Worse yet, if the nonsteady state Potential technical issues that may impact the
goes unnoticed, incorrect or inappropriate ther- quality of the sample should be noted as well.
apy may be prescribed. Thus, before arterial These might include issues such as improper
puncture, the patient must be carefully assessed storage of the sample or transportation delays.
to ensure steady-state conditions. Other desirable information includes the loca-
Samples drawn to assess response to exertion of the patient, working diagnosis, clini-
cise require special considerations. They are cal indication, name of the physician request-
best drawn at peak exercise, however, samples ing the sample, the initials of the individual
drawn within 15 seconds of termination of who obtained the sample, and the sample
exercise are acceptable.15 Outside this time site.14
range, samples may yield false-negative results The patients temperature and respiratory
for hypoxemia.15 rate should likewise be recorded. The position
Mild to moderate pain may accompany of the patient (e.g., supine, sitting) at the time
arterial puncture.26 The clinician should be of sampling and the activity of the patient
aware that pain and anxiety associated with (e.g., comatose, convulsing) may also provide
arterial sampling may in itself cause changes in valuable information when the data are inter-
ventilation that, in turn, alter blood gas results. preted. Hemoglobin concentration may be
Thus, the patient should be approached calmly useful in assessing oxygenation status or calcu-
with a quiet voice and reassurance to promote lating [BE]. Notations of fluid infusions and
physical and mental comfort14; and the sample location may likewise be useful in some cases.
should be obtained as quickly as possible. The type and flow rate of O2 therapy should
Some suggest the use of numbing agents before be checked and recorded. When positive air-
the actual puncture26 and this issue is discussed way pressure (e.g., Continuous Positive
later in this chapter. Airway Pressure [CPAP] or Biphasic Positive
Airway Pressure [BIPAP]) is being applied, the being used to evaluate the P(A-a)O2 gradient,
inspiratory and expiratory pressures being a glass syringe and an iced transport container
delivered should be observed and recorded. are also necessary. Many institutions now use
In the case of the patient receiving mechan- commercially available arterial blood gas kits
ical ventilation, a host of other variables that eliminate the need to gather all of these
should be documented. The type of ventilator materials.
and mode of ventilation should be recorded.
The respiratory rate setting on the machine as Syringe
well as the actual respiratory rate of the The basic components of a hypodermic needle
patient should be determined and included and syringe are shown in Figure 1-3. The typical
on the report. When applicable, the positive syringe is a 1-, 3-, or 5-mL self-filling, dispos-
end-expiratory pressure (PEEP) level or BIPAP able, plastic syringe that comes pre-filled with
levels should be observed on the pressure dry heparin anticoagulant. A 20- to 25-gauge,
manometer of the machine and recorded. short-beveled needle with a clear hub is usually
Finally, the fraction of inspired oxygen (FIO2) recommended for arterial sampling in the
and exhaled tidal volume (VT) should be meas- adult.14,16 Smaller (i.e., higher gauge) needles
ured and recorded. All of this information may may not be desirable in adults because they
be important for interpreting blood gas results. may obscure the visual pulsation of blood
In plotting the future course of treatment, it is characteristic of entering an artery. The vol-
essential to know clearly what has transpired. ume of the syringe should be equal to the
volume of blood to be sampled. The length
Materials of the needles range from 5/8 to 11/2 in.; the
Equipment needed for an arterial puncture longest needles are used for brachial or
includes a plastic syringe, anticoagulant, alco- femoral artery sampling.14
hol swabs, tape, and sterile gauze pads. A local In children or neonates, a 25-gauge syringe
anesthetic and sterile towel are optional. If the is preferable to minimize vessel trauma and
sample will not be run within 30 minutes or is bleeding.16 Similarly, a small (high-gauge) syringe
ON CALL CASE 1-1 ABGs and Critical Thinking

You are the only person available to care for this patient. You must assess the patient/situation and act accordingly.
A 70-year-old female in Denver arrives in the emergency ARTERIAL BLOOD GASES

room complaining of shortness of breath. She is placed pH 7.45
on 2 Lpm of oxygen via nasal cannula. A few minutes PaCO2 32 mm Hg
later, a therapist arrives and draws an arterial blood gas. PaO2 60 mm Hg
[HCO3] 20 mEq/L
ARTERIAL BLOOD GASES
pH 7.42 ASSESSMENT
PaCO2 34 mm Hg Abnormalities: List abnormal data and other noteworthy
PaO2 62 mm Hg information.
[HCO3] 21 mEq/L Explanation: List possible diseases, pathology, or other
circumstances that may have lead to this patients
ASSESSMENT
condition.
Abnormalities: List abnormal data and other noteworthy Evaluation: Suggest additional data which would be
information. useful in helping understand the situation or in making
The physician requests an additional sample 45 minutes a diagnosis.
later on room air. The patient is immediately placed on room
air and the following results are obtained in 45 minutes.
Hypodermic Syringe Hypodermic Needle

Luer tip
Needle
Needle bevel
sheath
Plunger
tip Needle
cannula
Graduations
Needle
hub
Barrel Plunger
Figure 1-3. Basic components of hypodermic needle and syringe.
may be best for arterial puncture in the patient In addition, newer syringes are often designed
receiving anticoagulant therapy to minimize more safely to prevent accidental needle punc-
actual vessel damage and bleeding, despite the tures in healthcare professionals (e.g., needle
disadvantage of masked pulsation.16 guides and retractable needles; Fig. 1-4). Some
Either glass or plastic syringes are accept- interesting points are noted in the Box 1-1.
able for specimen collection, however, there
may be substantial diffusion of room air Anticoagulant
through plastic syringes particularly when they Blood is activated to form clots after leaving the
are iced.34 PaO2 is most affected by diffusion body. If allowed to proceed, this clot formation
in plastic syringes when the PaO2 is high or (coagulation) within the specimen would inter-
when hemoglobin in the sample is low.1 When fere with the acquisition or analysis of blood
it is important to get a precise PaO2 from a samples. Even microscopic clotting can adversely
specimen (e.g., P(A-a)O2, very high leukocyte affect a blood gas analyzer. Most new blood gas
or platelet count), a glass syringe should be syringes are pre-filled with a dry anticoagulant.
used34,65,116 and the sample analyzed quickly Occasionally, however, in emergency situations,
(i.e., within 5 to 10 minutes).1,65,107 a liquid anticoagulant must be added to a
Currently, quality plastic syringes with or standard syringe before drawing a blood gas
without pre-filled heparin are available that fill sample. When adding liquid anticoagulant, it is
spontaneously upon entry into the artery and in important that the volume or type of anticoag-
most cases provide acceptable results.14 Other ulant does not alter the acid-base and oxygena-
syringe designs allow blood to fill the syringe tion values being measured.
under its own pressure and allow filling to
a predetermined volume. For example, some Type of Anticoagulant
new syringe designs allow for filling to a pre- Lithium heparin is the anticoagulant of choice
determined volume while the blood pushes air in arterial blood gas sampling.1 Lyophilized (dry)
out a vent that closes when the syringe is filled.1 heparin is usually included in prepackaged
PeachCapp
Syringe barrel
Thumb guide
Needle guide
Rubber seal insert
Directions: 2. With the syringe at 90, 3. The needle and PeachCapp

1. After sampling, slide the PeachCapp forward slide the PeachCapp back may be removed simultaneously
until the Needle Guide clears the needle. to embed the needle. by twisting the needle at its hub
and sliding it forward.
A
Before
Figure 1-4. Safe syringe designs. The
Peachtree syringe design by Marquest
Medical products (A) and the syringe
designed by Retractable Technologies
(B) are examples of syringes designed to
prevent accidental needle punctures in
After
healthcare workers. (Note: The Peachtree
Syringe by Marquest Medical is no longer
VanishPoint Retractable Needle Syringe: being produced or manufactured.)
When the plunger handle is fully depressed, a spring
mechanism automatically retracts the needle directly from
the patient into the barrel of the syringe. This virtually
eliminates any risk of accidental contaminated
needle stick injury to the healthcare worker.
B
Box 1-1 Needle Safety

In the United States in the year 2000:
The nation used more than 500 million needles.
There were 600,000 inadvertent needle punctures.
There were 30 needle stick injuries per year for each 100 hospital beds.
Only 15% of hospitals used safer needle designs because their cost was up to four times greater.
Reference: Neergard, L. (The Associated Press): Hospitals urged to use safer needles to reduce injuries, Pittsburgh Post
Gazette, November 23, 1999, p A-14.
blood gas syringes. When liquid heparin must be come prepackaged with dry lyophilized heparin
added, it should be sodium heparin (1000 IU/ and thus obviate syringe preparation with liquid
mL). Also, when samples will be drawn to meas- heparin.
ure electrolytes as well as blood gases, balanced
heparin should be used. Balanced heparin is Transport
physiologically balanced for the electrolytes Because blood is living tissue, O2 is consumed
being measured (e.g., Ca2+, K+, Cl, Na+) and and CO2 is produced as the blood sample sets
therefore should minimize any distortion of elec- in the syringe. The speed and significance of
trolyte concentrations in the sample. these changes depend on the metabolic rate.
All heparin salts have some potential Plastic syringes containing blood for blood
to cause the formation of small fibrils in the gas and/or electrolyte analysis should be main-
sample which, in turn, may interfere with tained at room temperature and analyzed
some equipment. Lithium heparin, because within 30 minutes.34,107,116 The reader should
of the quantity of lithium used, is least likely note that this is in contrast to previous practice
to cause these problems.27 As a rule, heparin when all samples were iced (see discussion
salts (lithium, sodium) in 1000 IU/mL are below). When an elevated leukocyte or platelet
the only acceptable anticoagulants for blood count is present, however, blood samples
gas analysis. Higher concentrations of heparin should be placed in ice and analyzed immedi-
(e.g., 10,000 U/mL) may alter pH and ionized ately or within 5 minutes.107,116
calcium of the sample. It was earlier practice to place all samples
immediately in an ice water bath to minimize
Volume of Anticoagulant metabolism. More recently, however, it has been
Only 0.05 mL of 1000 U/mL liquid heparin is shown that icing samples in plastic syringes is
required to anticoagulate 1 mL of blood. unnecessary unless blood is being used for spe-
Because the deadspace volume of a standard cial studies (e.g., P(A-a)O2 analysis) or more
5-mL syringe with a 1-inch, 22-gauge needle than a 30-minute delay is anticipated before
is 0.2 mL, filling the syringe deadspace with analysis.34,107
heparin provides sufficient volume to anti- When icing is necessary, the ice container
coagulate a 4-mL blood sample.1 should be large enough to allow for immersion
When liquid heparin is used, the syringe is of the syringe barrel. A mixture of ice and
heparinized by drawing a small amount into the water in the container may facilitate more uni-
syringe then distributing it throughout by work- form cooling and an immediate decrease in
ing the plunger in and out several times. Because metabolic function. The ice or ice/water should
the objective is only to coat the inner walls of be capable of maintaining the blood sample at
the syringe, the plunger is completely, albeit a temperature of 1 to 5 C.14
gently, pushed in, and any excess of heparin is
expelled.28 This procedure leaves heparin only Alcohol, Gauze and Tape
in the syringe deadspace (needle and hub). The Asepsis is the absence of disease-producing
use of minimal liquid heparin is important microorganisms. The aseptic technique is the use
because an excess of heparin is known to alter of methods that minimize the risk of infection
blood gas values.1 Most new blood gas syringes to the patient. Most importantly, the clinician
should always wear aseptic gloves for the pro- Puncture Technique
tection of both practitioner and patient. An A general procedure for performing an arterial
alcohol swab or a similar antiseptic agent is puncture is described later in this chapter. Local
used to clean and disinfect the skin before preferences and conditions determine the
puncture. A 2 2 in. sterile gauze pad should actual technique used by a specific individual
be available so that manual pressure can be or laboratory.
applied aseptically to the puncture site after
the needle is withdrawn. Pressure dressings are Explanation
not an acceptable substitute.14 Nosocomial The patient should always fully understand the
(i.e., hospital-acquired) infection is a poten- reason for a particular diagnostic test as well as
tially serious complication of arterial puncture the procedure that will be followed. The indi-
that can be avoided mainly through the use of vidual should realize that arterial blood is useful
proper handwashing and aseptic technique. for evaluating his or her breathing, blood oxy-
genation, and acid-base status. The individual
Local Anesthetic should be seated or lying in bed comfortably for
Administration of a local anesthetic to the at least 5 minutes before the procedure.107 Also
sample site to alleviate anxiety and pain is keep in mind that longer than 5 minutes may be
sometimes recommended.26 Administration of necessary for outpatients to achieve a steady
a local anesthetic may relieve discomfort and state.107 The patient should be encouraged to
minimize the risk of vasoconstriction.1 It is relax and should understand that some discom-
theoretically plausible that the pain or anxiety fort may be felt. All individuals drawing blood
associated with arterial puncture may cause gases should work hard to develop communi-
hyperventilation and alteration of blood gas val- cation skills that promote a calm, reassuring
ues, although this has not been clearly demon- environment.
strated.29 Many clinicians do not advocate the
use of local anesthesia and think that the addi- Selection of Site
tional cost, time, discomfort, and potential for Because blood gas values are identical in all
complications are not justified.1,30,31 arteries, the specific artery chosen for the acqui-
This controversy persists, however, and one sition of the sample is based on accessibility,
recent study reported that the injection of safety, departmental policy, and the patients
local anesthetic before puncture significantly comfort. Box 1-2 lists the primary physiologic
decreased the amount of pain felt and did not criteria that determine site selection. The three
make the procedure either more difficult or more vessels most commonly punctured for blood
time-consuming.26 This study concluded that gases in the adult are the radial, brachial, and
local anesthesia is indeed indicated with routine femoral arteries (Fig. 1-5). Other arteries that
arterial puncture.26 Notwithstanding, the may be used include the axillary, ulnar, dor-
National Committee for Clinical Laboratory salis pedis, and superficial temporal arteries.32
Standards (NCCLS) states that local anesthetic The carotid artery should be avoided because
with arterial puncture is optional.1 of the potential for cerebral air embolism or
If a local anesthetic is to be used, a 25-gauge damage to neighboring vital structures. Arterial
or 26-gauge hypodermic needle and a local puncture should also be avoided through skin
anesthetic (e.g., 1.0% lidocaine without epi-
nephrine) is also needed. A few drops of anes-
thetic is injected just under the skin and in the
Box 1-2 Physiologic Criteria for
tissues surrounding the vessel. The patient can
ABG Site Selection
then be calmed by showing him or her that a
needle prick cannot be felt in this area. It 1. Collateral blood flow
should be noted, however, that lidocaine with- 2. Accessibility and size of artery
3. Proximity of nerves, veins, supporting
out epinephrine may cause prolonged bleeding
structures
in patients receiving anticoagulant therapy.1
Superficial temporal
artery
Axillary
artery
Brachial
artery
Ulnar
artery
Radial
artery
Common carotid
artery
Femoral Figure 1-6. Puncture of superficial temporal
artery
artery. The superficial temporal artery may be
punctured in the newborn by using a 25-gauge
butterfly scalp vein needle.
temporal artery is usually used.14 Alternatively,

in the newborn, the umbilical arteries are eas-
ily accessible for sampling without puncture.
The umbilical arteries are patent during the
first 24 to 48 hours after birth but these arter-
ies constrict rapidly if they are not kept open
by catheterization (insertion of a catheter into
the arteries for sampling).
The ideal vessel for arterial puncture would
be large and superficial and would thus be
Dorsalis pedis
an easy target for puncture. Also, the vessel
artery would not lie extremely close to large veins
or nerves that might predispose to inadver-
tent venous puncture or significant pain or
complication in association with the proce-
Figure 1-5. Arterial puncture sites. The three dure. Most important, other arteries that could
preferred arteries for arterial puncture are the maintain perfusion to distal tissue if an
radial artery, the brachial artery, and the femoral
obstruction occurred in the punctured artery
artery.
(i.e., collateral circulation) should be available
in the general area.
lesions and through (or distal to) a surgical
shunt (e.g., dialysis).15 Complications of Arterial Puncture
In the infant, the radial and scalp (temporal) A potentially serious, albeit uncommon, com-
vessels are often recommended. The location of plication of arterial puncture is thrombosis.
the superficial temporal artery (which may be Thrombosis involves the formation of an
even wider than the radial artery) is shown in abnormal adherent clot (thrombus) on the
Figure 1-6. One of the two main branches of the inner wall of the vessel. The thrombus grows
gradually with subsequent diminution or ces-

Brachial
sation of blood flow. Thrombi are generally Humerus artery
more serious in arteries than veins due to lesser
collateral circulation. Thrombus is most likely
when a needle or cannula is left in a small
artery for an extended time.
The possibility of hemorrhage secondary to
the high arterial pressure is also of consider-
able concern, particularly in the case of
patients who receive anticoagulant therapy or
who have known blood coagulation disorders.
Hematoma, the leakage of blood into the tis- Radius Ulna
sues, is not uncommon, especially in the elderly,
who may lack sufficient elastic tissue to seal the
puncture site. The probability of hematoma or
external bleeding will vary directly with the
diameter of the needle. Hematoma is also more
likely in patients receiving anticoagulant ther-
apy or individuals with serious coagulopathies
such as patients with end-stage hepatic disease Ulnar
or cancer.107 artery
Radial
Arteriospasm (transient constriction of the artery
artery) may occur as a reflex secondary to pain
or anxiety and make it difficult or impossible to
obtain a sample. Other complications include
pain, air emboli, infection, and peripheral nerve
damage. Occasionally, vasovagal (vascular and
vagal) responses occur; these responses consist
of precordial (region over the heart and stom-
ach) distress, anxiety, feeling of impending
death, nausea, and respiratory difficulty.33 A
vasovagal reaction may also result in loss of
consciousness. The practitioner should be alert
to signs and symptoms that suggest a vasovagal
reaction (e.g., sweating, hypotension, bradycar-
dia). In the event of a vasovagal reaction, the
patient should lie down or if sitting, lower their
head and arms and loosen light clothing.107
Although it has yet to be reported, anaphy-
laxis, a severe allergic reaction, may accom-
pany the administration of a local anesthetic. In
general, the overall incidence of complication
with arterial puncture is low.32 Arterial puncture
is a safe, simple procedure35,36 that can be done
by qualified respiratory care practitioners and
other healthcare personnel.
Figure 1-7. Major arteries of the right lower arm.
Common Sample Sites
Radial Artery. The vessel of choice for punc-
ture in the adult is the radial artery (Figs. 1-7
to 1-9), which lies on the thumb side of the
forearm.10,32,35 The radial artery, although
relatively small, is very accessible. The arm is

convenient and the vessel is superficial and
easy to stabilize and palpate. The vessel is also
easily compressed over the wrist ligaments and
the incidence of hematoma is low.107 The
radial nerve and vein are not particularly close
to the artery and, most importantly, collateral
circulation is usually excellent. Conversely, the
ulnar artery is smaller, deeper, and lies close to
the ulnar nerve.
Although complications from arterial punc-
ture are rare, the non-dominant hand should
be considered whenever possible.41,697 This is
particularly true when brachial puncture is
necessary.41 Punctures should also be avoided
near the site of a surgical scar because this
may predispose to a risk for injury, especially
nerve injury.107 Selection of the non-dominant
hand is still controversial, however, and not
Ulnar considered standard of practice by some
Median
artery
nerve authorities. Some clinicians think that the site
Ulnar
nerve Radial most comfortable for the clinician and with
artery the best pulse is optimal. This approach may
increase the likelihood of optimal technique
and successful sampling and decrease the
Figure 1-8. Anatomy of the right hand and wrist. potential for complication.
Pulsations from the radial artery are palpable Pulsations from the radial artery are readily
approximately 1 inch from the crease of the wrist. palpable approximately 1 inch from the wrist
The radial nerve runs underneath the radius.
Figure 1-9. Superficial dissec-

tion of radial area. Actual
proximity of radial artery (A)
to median nerve (B) in cadaver
is shown.
A B
where the artery passes above the radius

bone (see Figs. 1-7 to 1-9). The radial nerve is
avoided at this location because its course runs
below the radius (Fig. 1-10). Notwithstanding,
radial artery puncture may still be painful if
the puncture is deep and/or the bone covering
(periosteum) is pierced.
Before performing an arterial puncture in
the radial artery, however, the presence of ade-
quate collateral circulation must be ensured.
The vessel of collateral circulation to the hand,
in the event of damage or obstruction to the
radial artery, is the ulnar artery. The ulnar
artery is capable of providing adequate perfu-
sion to the hand; however, in 3% to 5% of the
population, ulnar perfusion may be either
absent or minimal. The incidence of abnor-
malities appears to increase with age from 2%
in the first decade of life to nearly 7% after the
ninth decade.115 In the absence of adequate
collateral circulation (ulnar circulation), radial
artery puncture is not recommended. Median
A technique used to determine the adequacy nerve
of ulnar circulation is the Allen test, or more cor-
rectly, the modified Allen test. Technically, the Radial
Ulnar nerve
Allen test was first described as a method of con- nerve
firming radial artery occlusion38; nevertheless,
the basic principles involved can be used to eval-
uate the adequacy of ulnar collateral circulation. Ulna Radius
Alternatively, ulnar circulation can be assessed
with a Doppler ultrasonic flow indicator.14
The procedure for performing the modified
Allen test is shown in Figure 1-11. First, the
patient is instructed to clench the fist, thus forc-
ing blood from the hand. If the patient is unable
to actively clench the fist, it can be closed tightly
by the clinician; however, if this is necessary,
the results may be less conclusive.10 By using
his or her fingers, the clinician then applies
external pressure to both the radial and ulnar
arteries to obstruct blood flow to the hand (see
Fig. 1-11,A). Relaxation (not full extension) of
the hand at this point will result in blanching of
the palm and fingers (see Fig. 1-11,B). Care Figure 1-10. Major nerves of the right forearm.
should be taken to ensure that the patient does The radial nerve passes underneath the radius
not hyperextend his or her wrist because this bone and should not be punctured inadvertently.
may substantially affect the test results.113,118 The course of the median nerve closely parallels
Subsequent release of obstructive pressure the course of the brachial artery.
on the ulnar artery should result in flushing of
the hand (see Fig. 1-11,C) within 5 to 15 sec-
onds provided that ulnar artery blood flow
circulation may be compromised and that radial

artery puncture should be avoided. Because it is
sometimes confusing to state whether the results
are positive or negative, it is probably best to
Radial artery record test results as normal or abnormal.
The value and need for use of the Allen
test has been challenged,113,114 and in some
institutions it is no longer routinely used.114
Opponents state that the prevalence of palmar
arch arterial insufficiency is low, the patient
must be cooperative to clench the fist, results
Ulnar artery
are subjective, and it may not be a valid pre-
A dictor of negative outcome. Interestingly, many
patients may spontaneously hyperextend their
wrists, which may delay reperfusion time two-
to threefold.113
Despite these objections, the modified Allen
test is still recommended in this text as a gross
screening test. The test is simple, brief, and non-
invasive. It may alert the clinician to a potential
problem or suggest using the opposite arm for
arterial puncture.
Brachial Artery. When the radial arteries are
unsuitable for puncture, the brachial arteries
B should be considered. The brachial artery is the
major artery of the upper arm that bifurcates
(divides) into the radial and ulnar arteries just
below the elbow (see Fig. 1-7). It is a large ves-
sel that can be palpated a short distance above
the bend of the elbow on the internal surface
of the arm where it passes over the humerus.
The patients arm should be extended com-
pletely, and the wrist should be rotated until
the strongest pulse is obtained just above the
skin crease. Due to minimal vessel support by
C firm fascia or bone, the vessel may be some-
what difficult to palpate and more suscepti-
Figure 1-11. Modified Allen test. A, Blood supply
ble to hematoma. The artery should then be
to the hand is depleted. B, The hand is relaxed and
blanches. C, Pressure is released from the ulnar
traced 2 to 3 cm up the arm with another
artery. Return of color to the hand within 5 to finger.
15 seconds indicates adequate collateral circulation In Figure 1-12, it can readily be seen that
via the ulnar artery (positive response to the the course of the median nerve is parallel to the
Allen test). course of the brachial artery. Puncture of the
median nerve with associated pain may occur
while brachial puncture is being attempted.
More importantly, trauma to the median nerve
is adequate.10,14,39,40,107 This normal response with subsequent permanent nerve damage has
is considered to be a positive response to the been reported in several cases.4143 As stated
Allen test. Failure of the hand to flush in the previously, when pulses are equal, the artery
specified time, which represents a negative on the non-dominant side should be selected
response to the Allen test, indicates that ulnar for puncture because, if an injury occurs, the
Femoral Artery. The femoral artery can be

palpated just below the inguinal ligament in
Brachial the patient lying flat with the legs extended.
artery The femoral artery is, however, the least desir-
able of the three described puncture sites.31
Although its large diameter makes it an easy
Median target, the vessel lies deep below the skin adja-
nerve
cent to the femoral nerve and vein (Fig. 1-13).
Most important, puncture of the femoral
artery has been associated with serious com-
plications. Large quantities of blood may seep
from this vessel and may go unnoticed because
of its deep, inconspicuous location. Moreover,
Ulnar atherosclerotic plaques are common in this
artery area; they may dislodge and lead to distal
Radial artery occlusion. Patency of the femoral artery
artery is vital because collateral circulation is almost
nonexistent. In addition, this site may be asso-
ciated with an increased risk of infection due
to pubic hair in this region and difficulty with
aseptic technique. Thus, puncture of the
femoral artery is generally reserved for emer-
gencies; nevertheless, it may be the only option
for the hypotensive patient who has poor
Figure 1-12. Major arteries of the forearm and peripheral pulses.
the median nerve. The large median nerve runs
close and parallel to the brachial artery. Radial Puncture
The general technique used in radial artery
puncture is now described. The patient should
be seated or lying down to minimize the risk of
patient will be less incapacitated.41,44,697 a vasovagal faint.31 The patients wrist should
Interesting legal issues are shown in Box 1-3. be extended approximately to 30 degrees
Venous puncture may also occur inadver- by placing a rolled towel below the wrist
tently due to the presence of significant large (Fig. 1-14).14,31 Severe extension should be
veins in this area. The brachial artery is usually avoided because it may obliterate a palpable
considered the site of second choice in adults pulse.
because of the proximity of parallel nerves and The clinician should begin by washing the
veins. The brachial artery is not often punc- hands and then by donning gloves. A definite
tured in children and especially infants due to pulse should be palpated by gently pressing
difficulty in palpation and the absence of col- the index and middle fingers over the artery. A
lateral circulation.107 puncture should not be performed if a palpable
Box 1-3 Legal Issues

A California police officer lost use of his right hand following a blood gas procedure:
The technique of re-directing the syringe was alleged to have caused the damage.
An expert plaintiff witness testified that redirecting the syringe constituted a Singer Sewing Machine
technique.
The jury awarded the plaintiff $200,000.
Reference: DeWitt, A. L.: Routine ABGs can carry big risk too. Advance for Respiratory Care Practitioners, August 12,
1996, p 4.
Femoral nerve
Femoral vein
Figure 1-14. Radial puncture. The wrist is

Femoral
artery
extended to approximately 30 degrees with the
palm upward. The puncture is made at a 45-degree
angle opposite the blood flow with the bevel facing
upward.
opposite hand. While maintaining a palpable

pulse, the needle is then inserted 5 to 10 mm
distal to the index finger palpating the artery
and opposite the blood flow at a 45-degree
angle or less with the bevel turned upward (see
Fig. 1-14).10,14,16,46 The near-parallel insertion
minimizes vessel wall trauma and provides a
longer intraluminal pathway.31 A 45-degree
angle of insertion should be used when per-
forming a brachial puncture and femoral punc-
ture should be done with an angle nearly
perpendicular to the skin surface.14,107
The needle should be advanced slowly
because rapid insertion may force it completely
through the vessel. If the needle is advanced
too far, an acceptable technique is to with-
Figure 1-13. The femoral artery. The femoral draw it slowly until blood flow into the syringe
artery lies close to the femoral nerve and vein. commences. Similarly, redirection of the
syringe should be done gently if the initial
attempt fails to result in entry to the artery.
Redirection should not be done while the
pulse cannot be distinguished. After identifica- needle lies deep within the tissue, because the
tion of the pulse, the puncture site should be result may be excessive tearing of underlying
prepared with 70% isopropyl alcohol swabs. tissue. The needle should instead be with-
If the syringe has not been heparinized pre- drawn almost to the skin surface before
viously, this procedure should be done by redirecting it.
using the method described previously. The One must be very cautious, however, to
radial artery should again be palpated with avoid contamination of the arterial sample
one hand while holding the heparinized with even a small amount of venous blood. The
syringe much like a pencil or dart with the result could be significantly lower arterial PO2
values than those actually present in the arterial Sample Handling

blood. If an arteriovenous mixture is suspected, Needle sticks are the most frequent source of
the procedure should be repeated to ensure that transmission of blood-borne diseases in health care
a pure arterial sample is taken. workers.19,20
Occasionally, there is some question with
regard to whether the sample is arterial or It is important to prevent interface of the
venous. The characteristics of an arterial sample blood with air because this may alter blood
include the flashing pulsation as blood enters gas values. After the needle is withdrawn from
the hub of the needle, and the auto-filling of the the skin, it is quickly sealed by removing the
syringe by arterial pressure without withdrawal needle and capping the syringe in an airtight
effort. In the hypotensive patient, or if a needle fashion or following the manufacturers rec-
smaller than 23-gauge is used,107 some with- ommendations. The syringe may be gently
drawal effort (gentle slow pull) may be neces- tapped while in the upright position to force
sary, but failure to see the flash pulsation should visible air bubbles to the surface where they
arouse suspicion of venous puncture. Excessive can be expelled.
suction should not be applied because it may One must be especially careful to avoid
alter the blood gas results. When using a glass inadvertent needle self-puncture. Needle sticks
syringe, gentle pressure should also be main- are the most frequent source of transmission of
tained on the end of the plunger to prevent it bloodborne diseases in healthcare workers.19,20
from falling out. Needles used for blood sampling should be
After a sufficient sample of blood has been resheathed only with a technique that uses a
obtained, the needle is quickly withdrawn and one-hand device or by careful insertion into a
a dry, sterile gauze is placed immediately over cork or similar device that prevents the sharp
the puncture site. Digital pressure should nor- point from being accessible.15,107 Syringes
mally be applied to the site for a minimum of with attached needles should be disposed in
3 to 5 minutes.14,107 This time should be puncture-resistant disposal containers. These
increased slightly after femoral puncture. containers must have a lid and should be made
Immediately after the pressure is released, the of rigid material. The container must also be
site should be inspected for bleeding14,107; if marked clearly as a biohazard.104,107
any bleeding, oozing, or seepage of blood is The sample should be mixed with the anti-
present, pressure should be continued until coagulant by rolling the syringe between the
bleeding ceases. A longer compression time hands and by inverting the sample several
(e.g., 15 to 20 minutes) is necessary for patients times. Each of these mixing techniques should
who are taking anticoagulant therapy or who be done for approximately 5 seconds.
have bleeding disorders.16 As a general rule, samples should be main-
When bleeding is of particular concern, one tained at room temperature and analyzed
may also leave a pressure bandage on the site within 30 minutes.107,116 Recent evidence
for a short period after departure from the has shown that all blood gas samples are
bedside. However, pressure dressings are not a relatively stable for 30 minutes and that there
substitute for compression and they may pro- is no need to keep arterial blood in ice if
vide a false sense of security or lead to careless the sample is run within this time.34,107,116
technique regarding manual compression. This is an important finding because icing
Also, pressure dressings should be avoided in samples may also artificially alter electrolyte
patients with atherosclerosis because they may concentrations.
depress local circulation and promote throm- In general, procedures for puncture of other
bus formation. Other safeguards sometimes arteries are very similar to those used for radial
suggested include checking for a pulse down- puncture with minor exceptions. When per-
stream from the puncture site46 and recheck- forming brachial artery puncture, a longer nee-
ing the puncture site 5 minutes after releasing dle is used because the artery lies deep within
pressure to ensure that a hematoma has not the tissues especially in obese individuals. It is
formed.31 also more difficult to compress the brachial

A 33-year-old male police officer presents to the PaCO2 33 mm Hg

emergency department with shortness of breath. The PaO2 97 mm Hg
clinician performs a right brachial puncture for an arterial [HCO3] 24 mEq/L
blood gas. During the puncture, the officer experiences
involuntary finger movement and pain. The officer ASSESSMENT
returns to the emergency department the next day Abnormalities: List abnormal data and other noteworthy
complaining of numbness, weakness, and difficulty information or inappropriate actions.
moving his right hand. Explanation: List possible diseases, pathology, or other
circumstances that may have lead to this patients
ARTERIAL BLOOD GASES condition.
SaO2 97%
pH 7.42
artery and this must be done for at least 5 min- The radial artery is usually the vessel of
utes. Finally, when puncture of the femoral choice for arterial cannulation.14,47 Neverthe-
artery is necessary, the angle of puncture less, larger arteries may be preferred when the
should be more perpendicular to the skin risk of thrombosis is high or when the
surface.107 expected duration of cannulation is greater
than 7 days.48,49 Big arteries offer the addi-
tional advantages of easier palpation and more
ARTERIAL CANNULATION
accurate blood pressure readings.49 The large
During an acute hypotensive (fall in blood arteries of choice are the femoral and axillary
pressure) crisis, two important avenues of vessels, which have been associated with a low
patient monitoring may be inaccessible or incidence of minor complication and almost
inaccurate: arterial blood samples may be no tissue ischemia.49 Most intensive care units
almost impossible to obtain, and indirect currently attempt to remove arterial cannulas
measurement of arterial blood pressure may be within 72 hours.
misleading.
The insertion of an indwelling arterial Complications
catheter will ensure the availability of accurate Any invasive procedure such as arterial cannu-
monitoring information. In addition, an lation may be associated with complications.
indwelling catheter allows for continuous The potential benefits of invasive monitoring
monitoring, which is preferable to periodic, must always be weighed carefully against con-
intermittent measurements. The insertion of a comitant risks.
catheter into an artery for blood gas and pres- Major complications include hemorrhage and
sure monitoring is called arterial cannulation. severe vascular occlusion secondary to intra-
Although the insertion of an arterial line has luminal clot formation. On rare occasions, gan-
traditionally been done only by physicians, grene has necessitated the amputation of a finger
recent literature suggests that it can be done or a hand.50 When coolness of the extremity
safely and effectively by respiratory thera- is observed immediately after insertion of the
pists.45,70 It is important to provide special catheter, the catheter should be removed
training and protocols for insertion. With quickly because tissue damage requiring ampu-
these caveats, it appears that arterial lines can tation may occur in less than 2 hours.48 Careful
be inserted around the clock in a cost-effective attention to technique should avoid serious
manner by non-physician healthcare profes- problems. Major complications occur in less
sionals without increased complications.45,70 than 1% of cases.47 In fact, severe damage due
to vascular occlusion is estimated to occur in

less than 1% of patients.47 Heparinized
saline IV
Minor complications include pain, arte- solution
riospasm, and localized internal bleeding (i.e.,
hematoma). Temporary loss of sensation via Pressure
infusion bag
the median nerve may also occur.51 Transient
occlusion of the radial artery after cannulation
is fairly common. Twenty percent to 30% of IV pole
patients manifest partial or complete radial
artery occlusion after cannulation5254; however, Microdrip
infusion set
there appears to be no clinical tissue damage Stopcock A
resulting from the occlusion.52,53
The incidence of occlusion appears to be
related to the size of the catheter, and a small Intraflow flush
catheter may decrease the incidence of this line extension
complication.39,53 Radial artery occlusion Stopcock C
occurs more commonly in women than in
Pressure
men,52,53 perhaps because of the smaller vessel transducer
To patient
size. Furthermore, the occurrence of occlusion Stopcock B
appears to be related to the period of cannula-

To pressure
tion.54 Radial artery cannulation time should module
not exceed 6 hours in the absence of clear clin-
ical indication.
Use of a low-flow continuous irrigation sys- Figure 1-15. Pressurized arterial line system.
tem that incorporates a pressurized bag with Components of a pressurized arterial monitoring
heparin solution also helps to minimize the risk system.
of thrombus formation and dislodgment. The
system shown in Figure 1-15 is an example of a Before the development of these systems,
pressurized arterial monitoring system. Flush arterial lines were kept patent through inter-
systems should deliver 1 to 3 mL/hr to ensure mittent high-volume irrigation with heparin
patency.107 The pressurized bag is typically filled solution. Thus, a heparin solution was injected
with 1000 U of heparin. Administration of periodically into the system to purge the lines
heparin may, however, result in thrombocytope- and to avoid clots. This technique is less effec-
nia (decreased platelets) with subsequent hemor- tive and should be avoided.
rhage or thromboembolism. Heparin should be Infection is also a potential complication of
discontinued if these events occur or the platelet cannulation. In one prospective study of criti-
level falls below 100,000/mm3.107 cally ill patients, 18% developed local infection
The arterial line is set up to continuously and 5% developed septicemia.55 In a study of
monitor arterial blood pressure. A pressure healthy individuals, only a 4% infection rate was
transducer converts mechanical pressure to elec- observed.56 Some physicians contend that the
trical energy and displays it digitally or graphi- incidence of infection with arterial lines is no
cally on an oscilloscope. The intraflow flush greater than that seen with venous cannula-
assembly allows for a continuous, slow flow tion.10 Generally, the severity of infections seems
of heparin through the system to prevent clot to be related to the period of cannulation with
formation. Stopcocks A and B are used prima- the most severe infections arising when catheters
rily for assembly and calibration of the system. remain in place for longer than 4 days.55
Stopcock C is where arterial blood samples Also, a wise practice is to remove and culture
are acquired. The procedure for acquiring indwelling catheters in the presence of unex-
blood via this stopcock is described in the plained sepsis. Infections can be minimized by
section on arterial line sampling later in this aseptic preparation and application of an anti-
chapter. biotic ointment to the site after cannulation.14
Although arterial cannulation is not with-

out risk, it is a valuable method of monitoring Flush solution Patient
critically ill patients. The valuable nature of
the data obtained may justify the risk involved
especially if the need for serial blood gases is
anticipated.
Off
Catheter Insertion Sample port
The extremity to be cannulated should be Figure 1-17. Normal resting position of three-way
placed securely on a board. The use of local stopcock. In the normal resting position, the sample
anesthesia is optional but recommended for port is closed. The passage between the heparin
arterial line insertion.107 Several techniques can solution and the patient remains patent.
be used for catheter insertion depending on the
equipment available and local preferences. The
catheter may be inserted (1) over the needle, that leads to a pressurized bag of heparin
(2) through the needle, or (3) through a plastic solution. The lever on the top of the stopcock
catheter.14 can be rotated 360 degrees around in a circle.
When inserting the catheter over a needle, When the lever is not aligned directly with any
the catheter should be advanced slowly. The of the respective ports (see Fig. 1-16), flow
catheter should never be pulled back over the through all of the ports will be obstructed.
needle after it has been advanced, nor should When the lever is aligned directly with one
the needle be advanced again after it has been of the ports, only flow through that port will
withdrawn.14 If resistance is encountered, the be obstructed. Fluid can flow readily through
needle and catheter should be removed. the remaining two lines. Figure 1-17 shows the
If problems are encountered while inserting normal resting stopcock position of an arterial
the catheter through a needle, the needle and line. The pressurized heparin solution is being
catheter should always be removed simultane- forced slowly and continuously through the
ously to avoid damage to the catheter. While system. This small amount of heparin will keep
adhering to aseptic technique throughout, the the lines free and open while not impairing the
catheter should be secured after it has been bodys ability to form clots.
inserted the desired distance. When a sample is to be drawn, an empty
syringe is attached to the sample port. The stop-
Arterial Line Sampling cock is positioned such that flow to the bag is
Integral to traditional arterial line systems is obstructed while the patient and sample ports
a three-way stopcock, which is shown in remain open (Fig. 1-18). Fluid from within the
Figure 1-16. Three ports stem from the stop- arterial line is then aspirated into a syringe
cock: the patient port, a sample port, and a port (i.e., clearance syringe). The volume of fluid
Flush solution Patient

Flush solution Patient
Off
f
Of
Sample port Sample port
Figure 1-18. Sampling position of three-way

Figure 1-16. Three-way stopcock. Flow is stopcock. A syringe is attached to the sample port
obstructed through all ports in the stopcock because of the three-way stopcock. The stopcock is turned
the lever is not directly aligned with any of the ports. off to the heparin solution, and fluid is withdrawn.
withdrawn will vary with the system used but removal) as various diagnostic tests are per-
must be sufficient to ensure blood has reached formed. Critical care patients are also more
the syringe. Then, an additional small amount vulnerable than other patient populations to
should be withdrawn to prevent any blood the adverse affects of blood loss because of fre-
dilution.14 Typically, a volume of flush-blood quent coexisting anemia. The mean volume of
six times the volume of the catheter and con- blood loss per day is often 40 to 50 mL of
nections is withdrawn.107 This will ensure that blood57,58 in critical care patients; and may
unheparinized arterial blood is present imme- be as high as 377 mL/day in patients in some
diately on the patient side of the stopcock. cardiothoracic surgical intensive care units.59
The stopcock is then repositioned so that all This problem is especially important in
ports are obstructed (see Fig. 1-16). The preterm infants who have small total blood
syringe used to clear the sampling line is dis- volume.117
carded, and a new heparinized sample syringe In addition, patients with arterial lines have
is attached to the sample port. The stopcock is been shown to commonly have twofold to
again turned off to the bag, and the patients threefold increased blood loss related to phle-
blood sample is withdrawn into the syringe. botomy than other critical care patients.57,60 It
The stopcock is then returned to the is certainly plausible that the ease of blood-
obstructed position and the syringe is removed drawing from an arterial line makes blood
and prepared for transportation. sampling more casual and frequent.
To cleanse the lines, the stopcock is again Furthermore, as much as 24% to 30% of
turned off to the sample port and heparin is daily total blood drawn from traditional arte-
flushed manually through the system. This rial lines is for the purpose of clearing the
action forces the blood in the line back to the line and is then discarded.57,59 Newer blood-
patient. The stopcock is also turned off briefly conserving arterial line systems have been
to the patient, and heparin is allowed to flow developed that provide a simple and effective
out of the sample port, thus removing any method for reducing blood loss secondary to
blood residue (Fig. 1-19). A good arterial wave- line clearing.61
form should be present when the flushing pro-
cedure has been completed. Finally, the patient
ARTERIAL LINE/BLOOD GAS
is left with the stopcock in the resting position.
CONTROVERSY
Either a cap or a syringe should be placed over
the sample port to avoid contamination. In the current era of cost containment in
healthcare and particularly critical care units,
Blood-Conserving Arterial the value and number of laboratory tests being
Line Systems performed have come under great scrutiny.
Patients in critical care settings often lose large Much of this attention is appropriate because
quantities of blood via phlebotomy (blood laboratory costs comprise approximately 25%
of total hospital costs62,63 and critical care
units alone account for as much as 28% of
total hospital costs.64
Flush solution Patient Notwithstanding, although it is relatively
Off
easy to quantitate costs of these tests, it is
much more difficult to measure the value of
laboratory tests performed on critically ill indi-
viduals. A routine test in a critically ill individ-
ual may help us confirm that they are not in a
Sample port
crisis or provide a small first clue to a poten-
Figure 1-19. Flush position of three-way stop- tially fatal event or condition (e.g., arrhythmia,
cock. If the heparinized bag to the sample port is electrolyte disturbance). Appropriate use of
opened briefly, solution can flow out of the sample these tests will remain a matter of controversy,
port and rinse away all blood. science, and art. We must do all we can to save
money but we must not forget that healthcare Box 1-4 Contraindications to
is the business of saving lives. Capillary Blood Sampling
1. Posterior curvature of heel because device
CAPILLARY SAMPLING may puncture the bone
2. Callus heel of patient who has begun
Sampling of arterialized capillary blood may walking
be used as an alternative to arterial blood gas 3. Finger samples in neonates to avoid nerve
sampling in infants. Arterialized capillary sam- damage
ples may provide useful information regarding 4. Inflamed, swollen, or edematous tissue
PaCO2 and pH; however, they are of little 5. Cyanotic or poorly perfused tissue
value in estimating arterial oxygenation.66 A 6. Localized infection
brief review of the theory and principles of this 7. Previous puncture sites
technique is warranted. Reference: Capillary blood gas sampling for neonatal and
pediatric patients. AARC Clinical Practice Guideline,
Theory Respir. Care, 39:11801183, 1994.
Capillary blood can be arterialized by warm-
ing the skin and thereby increasing and accel- more than 2.0 mm deep should then be made
erating the flow of blood through the capillary. on the lateral aspects of the plantar surface
Thus, theoretically, blood gas values in the (Fig. 1-20).107 The first drop of blood should be
capillary approach arterial values. When wiped away, and the sample should freely flow
peripheral perfusion in the patient is normal, into a 75- to 100-L, heparinized capillary
arterialized capillary pH and PCO2 will corre- tube. Squeezing the blood into the capillary
late well with PaCO2 and arterial pH.6769 tube is unacceptable and may alter the values
Indeed, even arterialized capillary PO2 will obtained.66 An alcohol sponge or suitable sub-
correlate well with PaO2 provided PaO2 is less stitute should be pressed gently against the
than 60 mm Hg and peripheral perfusion is sample site to stop the flow of blood.
good. Higher PaO2 values do not correlate
well with arterialized capillary PO2 values
even with good perfusion.68,69 Typically, PO2
values of capillary samples will be consider-
ably lower.
Technique
In infants, the capillary bed most often used for
sampling is the heel. Nevertheless, the earlobe or
the tip of a finger (or toe) may also be used.
Punctures should not be performed over the
central area of the foot, the posterior curvature
of the heel, or through a previous puncture
site.107 Box 1-4 lists potential contraindications
to performance of this procedure.
The site should be heated carefully to a tem-
perature no higher than 42 C.65,107 This tem-
perature can increase blood flow sevenfold.107
Warming can be accomplished with warm com-
presses, a waterbath, a heat lamp, or commer-
cially available hot-packs. Inadequate warming
of the site will result in a poor correlation Figure 1-20. Site for arterialized capillary heel
between arterial and capillary values.66,107 sample. Heel puncture for arterialized capillary
The skin should be cleaned with an antisep- sample should be done on the lateral aspects of
tic solution such as alcohol. A puncture no the plantar surface.
AARC CLINICAL PRACTICE

The end of the capillary tube where the sam-
GUIDELINES
ple was obtained should be sealed immediately.
A metal flea (small piece of metal) is usually The AARC has established Clinical Practice
then carefully placed in the other end of the Guidelines for a variety of respiratory therapy
capillary tube before it is sealed. A magnet is modalities and diagnostic tests. Table 1-3 high-
then applied to the metal flea from the outside lights some of the key points of those Clinical
of the capillary tube. The magnet is moved Practice Guidelines related to arterial blood gas
backward and forward along the capillary tube and capillary sampling. Please refer to the actual
for approximately 10 seconds to thoroughly guidelines for more comprehensive information
mix the blood and heparin. The sample is then on each of these procedures.15,65,66
analyzed as soon as possible.
Table 1-3. AMERICAN ASSOCIATION FOR RESPIRATORY CARE CLINICAL PRACTICE GUIDELINES:
NUTS AND BOLTS
Sampling for Arterial Blood In-vitro pH and Blood Gas Capillary Blood Gas Sampling for
Gas Analysis Analysis and Hemoximetry Neonatal and Pediatric Patients
Anaerobic arterial blood Anaerobic arterial or Free flowing capillary blood

acquired from percutaneous mixed venous blood from sample from incision with
puncture or indwelling percutaneous puncture or lancet or similar device
catheter indwelling catheter
To assess: To assess: To assess:
1) Acid-base status 1) Acid-base status 1) Acid-base status
2) Ventilation 2) Ventilation 2) Ventilation
3) Oxygenation 3) Oxygenation
4) Dyshemoglobin saturations
Hazards: Hazards: Hazards:
1) Hematoma 1) Infection of specimen 1) Infection
2) Arteriospasm handler 2) Burns
3) Emboli 3) Hematoma
4) Anaesthetic reaction 4) Bone calcification
5) Hemorrhage 5) Nerve damage
6) Vascular trauma 6) Bruising
7) Vascular occlusion 7) Pain
8) Vasovagal reaction 8) Bleeding
9) Pain
10) Infection
11) Nerve damage
Key points: Key points: Key points:
1) Ensure steady state 1) 8-hr QC 1) Not good indicator PaO2
(2030 min) 2) Proficiency testing 2) Dont squeeze sample out
2) Analyze promptly program 3) Ensure proper site warming
<15 min not iced 4) Incision <2.5 mm deep
<1 hr if iced 5) Avoid procedure on infants
3) Perform Allen test <24 hr old
4) Heparinize (1000 U/mL)
5) Universal precautions
References: Sampling for arterial blood gas analysis. AARC Clinical Practice Guideline, Respir. Care, 37:913917, 1992;
Blood gas analysis and hemoximetry: 2001 Revision and Update. AARC Clinical Practice Guideline, Respir. Care,
45:498501, 2001; Capillary blood gas sampling for neonatal and pediatric patients. AARC Clinical Practice Guideline,
Respir. Care, 39:11801183, 1994.
EXERCISES
Exercise 1-1 Blood Gas Values

Fill in the blanks or select the best answer.
1. State the normal adult ranges and appropriate units for the following blood gas
measurements:
pH
PaCO2
[BE]
PaO2
[HCO3]
SaO2
2. State the two blood gas indices that quantitate the oxygen available in the arterial blood.
3. State the two metabolic indices commonly reported with arterial blood gases.
4. Both [HCO3] and [BE] are necessary to interpret arterial blood gas results (True/False).
5. What percentage of the total population will have blood gas values that fall within the
normal range?
6. Women tend to have (lower/identical/higher) PaCO2 than men.
7. Calculate the specific normal PaO2 in the supine position in patients of the following ages:
58 years
72 years
8. Normal SaO2 in a young patient in his or her twenties is approximately ______ %.
9. Normal PaO2 in the sitting position is approximately ______ mm Hg higher than in the
supine position in middle-age adults.
10. If the patient is younger than 45 years of age, minimum normal PaO2 should exceed _____
mm Hg. If older than 45 years of age, PaO2 decreases with age; however, it should never
be less than _____ mm Hg.
11. The International System of Units recommends (mm Hg/kPa) units for blood gas
measurements.
12. One hundred mm Hg = ______ kPa.
13. The normal range is usually considered to be within (1/2/3) standard deviations from the
mean of the population.
14. One kPa = ______ mm Hg.
15. A PaO2 of 60 mm Hg = ______ kPa.
16. PaO2 tends to (decrease/level off) after age 75.
Exercise 1-2 Arterial versus Venous Blood

1. Define the following terms: arteries and veins.

2. The best type of blood to use in assessing tissue oxygen delivery is (arterial/peripheral
venous).
3. The adequacy of CO2 excretion via the lungs is best assessed by (arterial/venous) blood.
4. Peripheral venous blood provides information primarily about (localized tissue/overall body)
conditions.
5. Venous blood samples in the well-perfused patient may fairly accurately reflect (arterial
pH/PaCO2/PaO2).
Exercise 1-3 Preparation for Arterial Sampling

1. List at least three examples of specific drugs that may interfere with normal coagulation.
2. A genetic disease seen in men that is characterized by an increased clotting time is ______.
3. Establishment of equilibrium throughout the cardiopulmonary system following application
of oxygen therapy may be called establishment of a ______.
4. In clinical practice, blood samples are not usually drawn for approximately ______ minutes
after a change in ventilator setting or oxygen therapy.
5. When blood samples are drawn during mechanical ventilation, the tidal volume and FIO2
(should/should not) be measured at the time of sampling.
6. A ______-gauge needle is usually used for arterial puncture in the normal adult.
7. A ______-gauge needle may be most appropriate in children or neonates to minimize ves-
sel trauma during arterial puncture.
8. When a sample is iced, the PaO2 will be altered due to diffusion in (glass/plastic) syringes.
9. State the recommended anticoagulant to be used for arterial puncture.
10. Sodium or lithium heparin in a concentration of (1000/10,000) U/mL is the anticoagulant of
choice.
11. The amount of sodium heparin (1000 U/mL) needed to anticoagulate 1 mL of blood is
______ mL.
12. Metabolism within a blood sample withdrawn from the body will (cease/continue).
13. The use of methods to minimize the risk of infection to the patient is called ______
technique.
14. A hospital-acquired infection is called a ______ infection.
15. Use of a local anesthetic for arterial puncture is (required/optional).
Exercise 1-4 Arterial Blood Sampling

1. List the three recommended vessels for arterial puncture in order of preference.
2. State two alternative arteries that may be punctured in unusual situations.
3. List four potential complications of arterial puncture.
4. Precordial distress, anxiety, nausea, and a feeling of impending doom are part of a clinical
picture known as a ______ response.
5. Testing for the adequacy of collateral circulation via the ulnar artery is performed via the
______ test.
6. In performing the modified Allen test, the patients hand should flush within ______ seconds
after release of digital pressure on the ulnar artery.
7. The course of the ______ nerve closely parallels the course of the brachial artery.
8. The most serious complications of arterial puncture have been associated with the
______ artery.
9. The wrist should be extended about ______ degrees for radial puncture.
10. During puncture of the radial artery, the angle of insertion should be ______ degrees or less.
11. State the two signs that indicate acquisition of an arterial sample.
12. Normally, digital pressure should be applied to the puncture site for a minimum of ______
minutes after the syringe has been withdrawn.
13. List the two primary indications for arterial cannulation.
14. When the lever of a three-way stopcock is aligned with one of the ports, that port will be
(open/closed).
15. Some advocate selection of the ____________ hand or arm for arterial blood sampling.
16. When doing a heel stick, blood (should/should not) be squeezed into the capillary tube.
Exercise 1-5 Internet Work

1. State the number of clinical practice guidelines that have been established through the
American Association for Respiratory Care (AARC) and list those related to blood gas sam-
pling (www.AARC.org).
2. List at least two contraindications cited in the AARC Clinical Practice Guidelines related to
Sampling for Arterial Blood Gas Analysis (www.AARC.org).
NBRC Challenge 1
Please select the best answer for the following multiple choice questions.
1. The modified Allen test: A) P(A-a)O2 evaluation

I. is used to evaluate the presence B) C(a-v)O 2 evaluation
of collateral circulation. C) pulmonary function study
II. is useful in evaluating the radial D) arterial blood gas
artery site for arterial puncture. E) flow-volume loop measurement
III. should be done preceding all (CRT EXAM NBRC MATRIX I,A,1,d)
venipunctures.
4. What clinical recommendation would be
A) I only
made for a 70-year-old man breathing
B) II only
room air with a PaO2 of 70 mm Hg?
C) I, II only
A) Pulmonary function studies
D) I, III only
B) Chest radiography
E) I, II, and III
C) Sleep studies
(CRT EXAM NBRC MATRIX I,C,1,c)
D) Cardiac enzyme studies
2. A bluish-colored sample with low PaO2 E) No action necessary
and high PaCO2 and of venous origin (CRT EXAM NBRC MATRIX I,B,9,c)
would be most likely when doing an
5. What is the most likely explanation of the
arterial puncture at the _________ site.
following ABG in a young female?
A) radial
PaO2 95 mm Hg
B) brachial
PaCO2 33 mm Hg
C) femoral
pH 7.43
D) dorsalis pedis
[HCO3] 25 mEq/L
E) temporal
(CRT EXAM NBRC MATRIX I,B,9,c) A) COPD
B) Acute pneumonia
3. When there are concerns regarding the
C) Neuromuscular disorder
adequacy of ventilation, acid-base
D) Severe anxiety response
balance, and oxygenation, a(n)
E) Normal
______________ would provide the most
(CRT EXAM NBRC MATRIX I,B,10,c)
comprehensive information.
Chapter
2
Blood Gas Classification
Of all the concepts employed in the diagnosis and treatment of respiratory disorders, few are more important
or less well understood than those of blood gas interpretation.
Robert R. Demers170
In interpreting blood gas data, the creative therapist considers not only the present values but attempts to
understand what came before and predict what might come afterwards.
Stephen M. Ayres171
Outline
Introduction, 35 Acid-Base Classification versus
Systematic Approach, 36 Interpretation, 46
Acid-Base Status, 36 Oxygenation Status, 46
pH Assessment, 37 PaO2 Classification, 46
Clinical Significance, 37 Normoxemia, 46
Clinical Manifestations of Abnormal pH, 37 Hyperoxemia, 46
Classification of pH, 37 Hypoxemia, 46
Basic (Primary) Acid-Base Disturbance(s), 38 Hypoxic Potential, 47
Respiratory Acid-Base Status, 38 Mild Hypoxemia, 47
PaCO2 Classification, 38 Moderate Hypoxemia, 47
Inverse Relationship (PaCO2pH), 39 Severe Hypoxemia, 47
Metabolic Acid-Base Status, 39 Efficiency of Oxygen Uptake, 48
[HCO3] Classification, 39 Normal FIO2PaO2 Relationship, 48
Direct Relationship ([HCO3]pH), 40 PaO2/%FIO2 (Oxygenation Ratio), 48
Identification of Primary Acid-Base Complete Blood Gas Classification, 48
Disturbances, 40 Alternative Terminology, 48
Base Excess [BE] Assessment, 42 Ventilatory Failure, 48
Compensation Assessment, 42 Temporal Adjectives, 49
Uncompensated Acid-Base Problems, 42 Usefulness, 49
Partially Compensated Acid-Base Problems, 43 Caveats, 50
Completely Compensated Acid-Base Exercises, 50
Problems, 44
INTRODUCTION
for example, Partially Compensated Metabolic
The techniques used in the acquisition of arterial Acidosis with Mild Hypoxemia.
blood have been discussed. In this chapter, the Sometimes this naming of the blood gas is
first step in the clinical application of arterial referred to as blood gas interpretation. Notwith-
blood gases, arterial blood gas classification, is standing, simply stating that a patient has a
explored. metabolic acidosis without understanding the
As described previously, the arterial blood nature of the acid-base disturbance is taking
gas report is the basis and cornerstone in the a very narrow view of interpretation and
assessment and management of clinical oxygena- does not facilitate optimal patient treatment.
tion, ventilation, and acid-base disturbances. The Therefore, in this text, interpretation is con-
initial objective in clinical management of these sidered in a much broader context to include
areas is to classify the blood gas information detailed analysis and evaluation of the blood
into one of several possible general categories, gas in conjunction with other patient clinical
35
and laboratory information. This requires Box 2-1 ABCs of Blood Gas
critical (diagnostic and therapeutic) thinking Classification
and is, indeed, our goal in the clinical man-
Acid-base status
agement of acid-base balance, ventilation, and
Basic primary problem(s)
oxygenation. Compensation assessment
To accomplish these important tasks, the first
important step in interpretation is blood gas
classification. Even the novice clinician dealing
with critical care patients must learn immedi- characterized as either respiratory, metabolic,
ately how to classify an ABG correctly and or both. In this step, we attempt to identify the
expeditiously. Likewise, even the novice must be primary general abnormality that is (are) tend-
able to quickly identify critical values and life- ing to pull the pH away from normal.
threatening situations. These objectives are the Next, Compensation is assessed. The bodys
aim of this chapter. normal response to a single, primary, acid-
base disturbance is to alter the acid-base com-
ponent not primarily affected (respiratory
SYSTEMATIC APPROACH
[PaCO2] or metabolic ([HCO3]) in the oppo-
The vital nature of blood gas information site direction of the primary problem. This
requires a careful, thoughtful approach. The secondary acid-base change is referred to as
variety of data that may be reported (e.g., compensation. Because this is an expected
[HCO3], SaO2, PaO2, [BE]) is a potential source occurrence in normal individuals, each blood
of confusion for the novice. Therefore, it is gas should be evaluated and classified accord-
important to process the data on a blood gas ing to the presence and extent of acid-base
report in an orderly, systematic, and thorough compensation.
manner. A step-by-step approach ensures repro- Regarding the sequence of specific indices
ducible results and helps to avoid confusion and to be analyzed on a blood gas report, it is rec-
omissions. ommended that the pH be evaluated first as an
Although acid-base balance, ventilation, index of overall Acid-base balance (Box 2-2).
and oxygenation status can often present The PaCO2 (respiratory status) is evaluated next
interrelated problems and issues, individual followed by [HCO3] (metabolic) evaluation.
and separate evaluations of these areas some- Assessment of both of these indices is necessary
times help to focus and clarify thinking. to complete both step 2 (Basic primary prob-
Although the sequence is somewhat arbitrary, lem determination) and step 3 (Compensation
in the classification system presented here, assessment).
acid-base classification (which also includes As we will see later in this chapter, the clini-
ventilation evaluation) is presented first and cian should then analyze the PaO2 (oxygenation
is followed by classification of blood oxygen classification) and consider it in respect to the
levels. FIO2 (i.e., the concentration of oxygen being
inspired) and lung oxygen exchange efficiency.
Again, Box 2-2 summarizes the sequence of
ACID-BASE STATUS
indices to be evaluated.
There are three steps in this simple ABC
approach to acid-base classification; these steps
are shown in Box 2-1. First, Acid-base status
Box 2-2 Sequence of ABG
(overall body conditions) is assessed by classi-
Evaluation
fying the arterial pH. The arterial pH is the
single best index of composite acid-base status pH
in the body. PaCO2
[HCO3]
Second, the Basic primary problem(s) (gen-
PaO2
eral type of acid-base disturbance) present is
Chapter 2 Blood Gas Classification 37
pH Assessment low pH (i.e., pH <7.10) is often associated

Clinical Significance with coma. A pH of less than 6.80 for any
The pH reported on an arterial blood gas sam- extended period is generally considered to be
ple is the single best index of overall acid-base incompatible with life.
status in the body. It is a composite reflection A high blood pH, on the other hand, has a
of the net interaction of all acids, bases, general tendency to excite the central nervous
buffers, and compensatory mechanisms. It is system. Irritability or tetany may be manifest.
the logical starting point in comprehensive When the heart muscle becomes more irrita-
acid-base assessment. Furthermore, if the pH ble, serious arrhythmias (abnormal beats)
is severely disturbed and the patient is in a life- may result. When pH remains very high, con-
threatening situation, this can be identified vulsions may occur. A pH greater than 7.80
immediately. is generally considered to be incompatible
The arterial pH is measured in the blood with life. The clinician should always take
plasma and reflects quantitatively the hydro- note of the patients symptoms to substanti-
gen ion activity in this extracellular fluid com- ate, refute, or clarify laboratory findings and
partment. Although the extracellular pH is disease.
not identical to the important intracellular pH,
alterations in the two values tend to move in Classification of pH
similar directions and correlate closely. Thus, Normal pH
the pH on a blood gas report is a good indica- Normal arterial pH is 7.35 to 7.45. The find-
tor of overall acid-base conditions. ing of a normal pH, however, does not pre-
clude further evaluation of acid-base status.
Clinical Manifestations of Abnormal pH Compensation may normalize pH and mask
Seemingly slight alterations in blood pH may primary acid-base problems that should be
have profound, life-threatening effects on body identified.
chemistry. This is likely due to the small size
of the hydrogen ion and the vast number of Abnormal pH
chemical reactions it may impact. Clinically, A pH of less than 7.35 in the arterial blood is
it is useful to be aware of the typical mani- abnormal and is called acidemia (-emia is the
festations associated with a particular pH suffix for a condition in the blood). Likewise,
disturbance. a pH in the arterial blood greater than 7.45 is
Low arterial pH has a generalized depressive also abnormal and is called alkalemia.
effect on the human nervous system (Fig. 2-1).173 A condition that tends to cause acidemia is
Symptoms may include drowsiness and lethargy. called an acidosis; therefore, all patients with
Regardless of the precipitating cause, a very acidemia must also have a primary acidosis.
Similarly, a condition that tends to cause alka-
lemia is called an alkalosis; therefore, all patients
with alkalemia must also have a primary alka-
pH Symptoms
losis. For this reason, it is customary to simply
7.80 Death call a low arterial blood pH acidosis and a high
Convulsions blood pH alkalosis (Table 2-1).
Arrhythmias
Irritability
7.40 Normal
Drowsiness Table 2-1. pH CLASSIFICATION
Lethargy Classification pH
Coma
6.80 Death Normal 7.357.45
Acidosis <7.35
Figure 2-1. Clinical symptoms associated with
Alkalosis >7.45
abnormal pH.
BASIC (PRIMARY) ACID-BASE

The technical problem with this approach
DISTURBANCE(S)
to respiratory acid-base assessment is that
It has become standard diagnostic practice to carbonic acid levels in the blood are very low,
characterize acid-base pathologic conditions and measurement of carbonic acid levels is
into one of two general categories: respiratory not technically feasible. Fortunately, however,
and/or metabolic problems. This basic patho- there is a direct linear relationship between
logic condition, sometimes referred to as a pri- arterial carbonic acid levels and PaCO2. Thus,
mary acid-base disturbance, is the root cause when PaCO2 is increased, it is indicative of
or problem that has led to (or has an inclina- increased carbonic acid in the blood, which
tion or tendency to lead to) overall acid-base tends to decrease pH (acidosis).
disruption. Logically, the converse is also true. A
To determine the primary problem, the cli- decreased PaCO2 indicates below-normal lev-
nician should first evaluate (or classify) the els of carbonic acid in the arterial blood, which
respiratory status using the PaCO2. This is fol- tends to elevate pH (i.e., alkalosis). In sum-
lowed by evaluation of the metabolic (i.e., mary, the adequacy of carbonic acid excretion
non-respiratory) acid-base status using either (respiratory acid-base function) can be assessed
the plasma bicarbonate concentration [HCO3] simply by evaluating PaCO2.
or the base excess concentration [BE]. By
understanding how these two indices may alter PaCO2 Classification
pH, the primary problem or problems can be A normal level of carbonic acid in the arterial
easily identified as described subsequently. blood corresponds to a PaCO2 level of 35 to
45 mm Hg, which is shown in Table 2-2.
Respiratory Acid-Base Status Indeed, PaCO2 can be used simply to evaluate
Evaluation or classification of the respiratory and classify the respiratory acid-base status.
component of acid-base balance is a logical
starting point in basic primary problem Respiratory Acidosis
determination because the respiratory system An increased PaCO2 level in the blood may
is the major organ system responsible for acid also be termed hypercarbia or hypercapnia.
excretion and the moment-to-moment regula- These are simply terms that indicate that the
tion of pH. amount of carbon dioxide present in the blood
Regarding acid-base balance, the specific exceeds normal. From an acid-base stand-
role of the lungs is to excrete carbonic acid point, hypercapnia means that there is an accu-
at exactly the same rate at which it is being mulation of carbonic acid in the blood. The
produced by the tissues as a result of carbon accumulation of acid in the blood is a measur-
dioxide production via metabolism. Therefore, able condition that tends to cause acidemia
if the lungs are properly excreting carbonic and therefore fits the criteria to be called a
acid, blood leaving the lungs (i.e., arterial respiratory acidosis.
blood) should have a constant, normal level of
carbonic acid. Respiratory Alkalosis
Measurement of the carbonic acid levels in Conversely, a below-normal level of CO2 in
the blood leaving the lungs would thus provide the blood is called hypocarbia or hypocapnia.
us with an index of lung effectiveness in acid-
base balance (i.e., carbonic acid excretion).
High carbonic acid levels in the arterial blood
would indicate that the lungs are failing to Table 2-2. CLASSIFICATION OF RESPIRATORY
ACID-BASE COMPONENT
adequately excrete this acid. Conversely, low
carbonic acid levels in the blood would indi- Classification PaCO2 (mm Hg)
cate excessive excretion and depletion of the
body stores. Because arterial blood is a mix- Normal respiratory component 3545
Respiratory acidosis >45
ture of all the blood that has just left the lungs,
Respiratory alkalosis <35
it is ideal for this assessment.
Regarding acid-base status, a low PaCO2 level In some cases, the adjective metabolic
indicates a depletion in blood carbonic acid may actually be misleading because many
levels. Therefore, a PaCO2 level less than 35 mm non-respiratory acid-base disturbances (e.g.,
Hg may be termed a respiratory alkalosis. vomiting) do not involve changes in meta-
bolism. In fact, some authors have suggested
Inverse Relationship (PaCO2pH) that the adjective metabolic should be replaced
To classify arterial blood gases correctly, it is with the adjective non-respiratory.174 Never-
crucial to understand that the relationship theless, the term metabolic is well ingrained
between PaCO2 and pH is inverse. In other in clinical medicine and is used throughout
words, when PaCO2 is high (i.e., respiratory this text.
acidosis), pH will tend to decrease due to the The PaCO2 is a specific, reliable, accurate,
accumulation of carbonic acid. Conversely, and simple indicator of respiratory acid-base
when PaCO2 is low (i.e., respiratory alkalosis), disturbance. No single metabolic acid-base
pH will tend to increase due to the depletion of index perfectly fits this description. In some
carbonic acid stores in the blood. cases, metabolic indices will deviate artifac-
A very common classification error for the tually from their normal ranges owing to rea-
novice is to see an abnormal pH and PaCO2 sons unrelated to primary acid-base disorders.
and assume the pH has changed because of the Nevertheless, a change in the numerical value of
PaCO2, despite the fact that the change in pH a metabolic index is most commonly due to a
and PaCO2 is not inverse. metabolic acid-base disturbance and the novice
For example, if pH is 7.20 (acidosis) and should assume this to be the case. In later chap-
PaCO2 is 20 mm Hg (respiratory alkalosis), ters, exceptions to this rule will be discussed.
both of these values are abnormal; however,
the change in pH cannot be due to the respira- [HCO 3 ] Classification
tory condition (i.e., this is not a primary respi- Although various different metabolic indices
ratory acid-base problem) but must be due to have been advocated through the years, the
some non-respiratory condition (i.e., metabolic plasma bicarbonate concentration [HCO3]
acidosis). (sometimes referred to as the actual bicarbon-
If indeed the abnormal PaCO2 had caused ate) is probably the most widely used index
an abnormal pH, the pH would be high (alka- and is seen on many clinical, professional, cre-
losis) because the relationship must be inverse dentialling examinations. Initial blood gas
to assume cause and effect. Therefore, in this classification examples in this text will include
example, it is clear that the change in pH only the [HCO3] as a metabolic index to avoid
must be due to some other (non-respiratory) confusion. Also, as mentioned previously, there
cause. To reiterate this important principle; if are some uncommon situations when bicar-
the change in pH is due to a respiratory condi- bonate values may be misleading (discussed in
tion, the relationship between pH and PaCO2 Chapter 5). It is best for the novice to assume
must be inverse. the bicarbonate is always a clear and concise
indicator of metabolic status. Logically, one
Metabolic Acid-Base Status should first learn the general rules of classifica-
All the numerous conditions that may poten- tion and later address unusual exceptions.
tially alter pH have been grouped into two major
categories to facilitate differential diagnosis. Normal Metabolic Status
Blood gas acid-base evaluation involves classi- Bicarbonate represents the most important
fication of the data based on these two com- base in the blood plasma. The normal value
ponents. Respiratory disturbances include all for plasma bicarbonate in the arterial blood is
those conditions that alter PaCO2 levels in the 24 2 mEq/L, which is shown in Table 2-3.
blood. Metabolic disturbances, on the other
hand, are defined by exclusion. Any acid-base Metabolic Acidosis
disturbance that is not respiratory in origin is The numeric value of bicarbonate decreases in
called a metabolic disturbance. response to either an accumulation of blood
Table 2-3. CLASSIFICATION OF METABOLIC Identification of Primary Acid-Base

ACID-BASE COMPONENT Disturbances
Classification [HCO3]* [BE]* As previously described, the pH should be
evaluated first to get an overall view of acid-
Normal metabolic 24 2 02 base status. Then, the PaCO2 and [HCO3]
component should be evaluated. If all three parameters
Metabolic acidosis <22 <2 (pH, PaCO2, [HCO3]) are in their normal
Metabolic alkalosis >26 >+2 ranges (Example 2-1), the classification is sim-
*Base excess and bicarbonate in mEq/L. ply Normal Acid-Base Status and therefore no
primary acid-base problem is present.
Example 2-1
fixed acids or to a loss of blood base. This Classification of Primary Blood Gas Problems
occurs due to blood acid-base buffering, which pH 7.38 (normal):
is discussed in a later chapter. Therefore, a PaCO2 Effect on pH [HCO3] Effect on pH
decreased bicarbonate concentration indicates 38 mm Hg 23 mEq/L
a non-respiratory condition that tends to cause
acidemia (i.e., metabolic acidosis). Quantita- When pH is outside the normal range, one
tively, as shown in Table 2-3, a metabolic must determine the basic (primary) acid-base
acidosis can be defined as a [HCO3] less than disturbance. The key to successful classifica-
22 mEq/L. tion is to identify whether the primary problem
is respiratory (PaCO2 is abnormal and inverse
Metabolic Alkalosis direction to pH change) or metabolic ([HCO3]
Conversely, the numeric value of bicarbonate is abnormal and change is in the same direc-
increases in response to increased blood base tion as pH).
or to a fall in fixed acid levels. Thus, bicar- Table 2-4 highlights these key relationships,
bonate values higher than normal indicate which must be memorized to identify the pri-
metabolic alkalosis. Numerically, as shown in mary acid-base problem. Figure 2-2 illustrates
Table 2-3, metabolic alkalosis can be defined the paths by which one can identify primary
as a [HCO3] greater than 26 mEq/L. acid-base disturbances in patients with acido-
sis or alkalosis. In some less common cases,
Direct Relationship ([HCO3]pH) both respiratory and metabolic components
Unlike the inverse relationship between PaCO2 may be pulling pH in the same direction. When
and pH, the relationship between [HCO3] and there are two primary acid-base problems both
pH is direct. In other words, a low [HCO3] pulling pH in the same direction, the problem
(e.g., 18 mEq/L termed a metabolic acidosis) is said to be Mixed or Combined.
tends to cause a low pH. Likewise, an increased In Example 2-2, the primary problem is
[HCO3] (e.g., 30 mEq/L termed a metabolic clearly metabolic because [HCO3] is decreased
alkalosis) tends to increase pH. (normal 24 2 mEq/L) along with a decreased
Here again, if one is to assume cause and
effect (i.e., a primary acid-base problem), the
relationship between the metabolic index and
pH must make sense. For example, if pH is Table 2-4. EFFECT OF PaCO2 AND [HCO3]
7.60 and the [HCO3] is 18 mEq/L, this cannot CHANGE ON pH
be a metabolic acid-base problem because there Index Effect on pH
is not a direct relationship (i.e., pH is above
normal whereas [HCO3] is below normal). PaCO2 pH
Understanding the effect of PaCO2 and [HCO3] PaCO2 pH
[HCO3] pH
change on pH are critical to correct blood gas
[HCO3] pH
classification.
Alkalosis demonstrates two primary problems both

pulling the pH in the same direction (lower).
Again, PaCO2 is increased (which tends to
Respiratory Metabolic
lower pH because the relationship is inverse)
(PaCO2 <35) (bicarb >26) and [HCO3] is decreased (which tends to lower
pH because the relationship is direct). Thus,
PaCO2 indicates a respiratory acidosis and
[HCO3] indicates a metabolic acidosis. This
pH
may also be classified as a mixed or combined
acidosis.
A blood gas such as that in Example 2-4
Respiratory Metabolic may accompany cardiac arrest. The respiratory
(PaCO2 >45) (bicarb <22) acidosis results from decreased ventilation,
whereas the metabolic acidosis is a result of
anaerobic (without oxygen) metabolism and
Acidosis lactic acid accumulation. Although somewhat
inter-related, two primary and separate basic
Figure 2-2. The two potential categories/origins
acid-base problems coexist.
of acidosis or alkalosis. The related blood gas
values associated with each possible cause are also
noted. Example 2-4
Classification of Primary Blood Gas Problems
pH 7.10:
PaCO2 Effect on pH [HCO3] Effect on pH
pH (direct relationship). PaCO2 is within the 64 mm Hg 19 mEq/L
normal range so this cannot be a primary res-
piratory acid-base problem. This would be Example 2-5 is one of the most common
termed a metabolic acidosis. types of blood gases seen and also one of the
most commonly misclassified, particularly by
Example 2-2 the novice. As previously stated, many inexpe-
Classification of Primary Blood Gas Problems rienced clinicians, after looking at pH and
pH 7.28: PaCO2, incorrectly classify this as simply respi-
PaCO2 Effect on pH [HCO3] Effect on pH ratory alkalosis. The logic is that pH and
37 mm Hg 17 mEq/L PaCO2 are both abnormal; so the abnormal
respiratory condition must be the cause of the
In contrast, Example 2-3 shows a respira- overall pH acid-base disturbance. The error in
tory alkalosis because the PaCO2 is decreased this logic is failing to remember the relationship
and the pH is increased. The inverse relation- between PaCO2 and pH as shown in Table 2-4.
ship shows cause and effect indicative of a Whenever the individual has a primary respira-
primary acid-base problem. The [HCO3] is tory acid-base disturbance, the relationship
within the normal range so a primary meta- between PaCO2 and pH must be inverse.
bolic problem cannot be present. This basic primary acid-base disturbance in
this blood gas is a metabolic acidosis because a
Example 2-3 low [HCO3] tends to lower pH and indeed
Classification of Primary Blood Gas Problems that explains the abnormally low pH. The low
pH 7.55: PaCO2 (respiratory alkalosis that tends to
PaCO2 Effect on pH [HCO3] Effect on pH increase pH) is actually due to the normal
25 mm Hg 23 mEq/L compensatory response of the body, which is
described later in this chapter. In summary,
Example 2-4 shows a respiratory and a when determining primary problems, the key
metabolic acidosis. This blood gas actually is to understand the relationships in Table 2-4.
Example 2-5 not primarily affected. For example, when an

Classification of Primary Blood Gas Problems abnormal respiratory acidosis (i.e., primary
pH 7.20: pathologic respiratory acidosis) occurs, the
PaCO2 Effect on pH [HCO3] Effect on pH body (specifically the kidneys) responds by
20 mm Hg 17 mEq/L developing a compensatory increase in blood
base (i.e., secondary metabolic alkalosis). The
compensatory response helps protect pH and
Base Excess [BE] Assessment prevents large, abrupt, dangerous swings in
An alternative metabolic index with fairly pH. Conversely, in the presence of an abnor-
widespread popularity is the base excess [BE]. mal (primary) metabolic acidosis, the respira-
It is noteworthy for the novice in arterial blood tory system reduces blood PaCO2 levels (i.e.,
gas classification that the base excess and secondary respiratory alkalosis) in an attempt
plasma bicarbonate both provide the clinician to bring the pH toward normal.
with the same general clinical information
regarding acid-base balance. There is, in fact, Uncompensated Acid-Base Problems
no need to evaluate both of these indices. When one of the acid-base components (i.e.,
For the novice, it is recommended that, given respiratory or metabolic) is abnormal and the
a particular blood gas, only one of the meta- other is within the normal range, the abnormal
bolic indices should be classified to avoid con- condition is said to be uncompensated (e.g.,
fusion. Some unusual situations are discussed uncompensated respiratory acidosis). The
later in Chapter 5, when the two indices may absence of compensation may be seen in respi-
not completely agree with each other. ratory acid-base problems that have developed
If both indices are reported at your institu- rapidly or when the body is unable to com-
tion, the index most commonly used in your pensate due to disease or some other reason.
particular institution or region should be used Uncompensated respiratory acid-base prob-
for classification. Beginning exercises in this lems generally indicate that the problem is of
text will use bicarbonate as the metabolic acid- recent origin (i.e., acute) and that the kidneys
base index. In later examples, the base excess have not had a sufficient time to manifest
or both metabolic indices (i.e., [HCO3] and measurable compensation. Renal compen-
[BE]) values may be given. sation is a relatively slow process in that it
From a numerical standpoint, the [BE] is takes the kidneys considerable time (i.e., 48 to
easier to understand than bicarbonate since the 72 hours) to achieve maximal compensation.
normal value for base excess is 0 2 mEq/L. A As a general rule, it is unusual and, indeed,
base excess in the negative range (metabolic signals another patient problem when an
acidosis) is sometimes called a base deficit. acid-base disturbance remains uncompensated
Nevertheless, even in the presence of a base for a long time.
deficit, this index is still usually referred to as Total classification of acid-base status in
the base excess. Example 2-6 would be uncompensated respi-
Obviously, if you are using [BE] as the ratory acidosis. The patient has respiratory
metabolic index, the same rules apply. An ele- acidosis as described in the previous section
vated [BE] (e.g., +5 mEq/L) would increase pH because PaCO2 and pH are inverse. Regarding
and would be termed a metabolic alkalosis (see compensation, the respiratory acidosis is
Table 2-3). A lower [BE] (e.g., 5 mEq/L) tends uncompensated because no increase in [HCO3]
to lower pH and would be termed a metabolic (no secondary metabolic alkalosis) above the
acidosis. normal range is seen.
Example 2-6
COMPENSATION ASSESSMENT Classification of Primary Blood Gas Problems
Compensation is defined as return of an pH 7.20:
abnormal pH toward normal by the compo- PaCO2 Effect on pH [HCO3] Effect on pH
nent (i.e., respiratory or metabolic) that was 68 mm Hg 25 mEq/L
Example 2-7 would similarly represent an The clinician should understand that what
uncompensated metabolic alkalosis. After appears to be simple compensation actually
Compensation assessment for Example 2-2 could reflect a more complex, dual (i.e., mixed)
shown previously, acid-base classification would acid-base problem. Patients may have two pri-
be uncompensated metabolic acidosis rather mary, abnormal acid-base conditions that each
than simply metabolic acidosis. Example 2-3 pull the pH in a different direction and the
would likewise be termed uncompensated respi- blood gas would appear, at first glance, to be
ratory alkalosis. In all of these examples, the consistent with compensation. This is actually
acid-base component not primarily affected has not a particularly rare phenomenon and a
remained within the normal range and therefore more detailed discussion of how to recognize
no compensation is evident. mixed disturbances is described in Chapter 14.
Notwithstanding, on initial inspection and
Example 2-7 classification, whenever the respiratory and
Classification of Primary Blood Gas Problems metabolic conditions are in opposite directions
pH 7.51: (e.g., respiratory alkalosis and metabolic aci-
PaCO2 Effect on pH [HCO3] Effect on pH dosis), compensation should be assumed. A
42 mm Hg 32 mEq/L typical blood gas picture in compensation is
shown in Example 2-9. Compensation is pre-
Example 2-8 shows the presence of multiple sumed because the patient has both a respira-
(combined) acid-base disturbances, specifically tory acidosis (i.e., PaCO2 = 68 mm Hg) and
a mixed respiratory and metabolic alkalosis. a metabolic alkalosis [HCO3] = 32 mEq/L).
Example 2-8 should not be classified as Because the pH is still clearly below the nor-
uncompensated mixed respiratory and meta- mal range (acidosis), it would make sense to
bolic alkalosis. In the presence of a mixed assume that the primary problem is a respi-
(combined) acid-base disturbance, it is not nec- ratory acidosis and that the metabolic alka-
essary to classify this blood gas as being losis is a secondary disturbance as a result of
uncompensated because this would be compensation.
redundant. By definition, it is impossible to When compensation is evident but the pH
have compensation for a mixed or combined remains outside the normal range, the primary
acid-base disturbance; therefore, no mention of acid-base disturbance is said to be partially
compensation should be in the classification. compensated. Hence, Example 2-9 is clas-
sified as a partially compensated respiratory
Example 2-8 acidosis. Example 2-10 would be partially com-
Classification of Primary Blood Gas Problems pensated respiratory alkalosis. Example 2-11
pH 7.62: would be a partially compensated metabolic
PaCO2 Effect on pH [HCO3] Effect on pH alkalosis. Again, one of the most commonly
30 mm Hg 30 mEq/L seen (and misclassified) acid-base conditions is
the partially compensated metabolic acidosis
Partially Compensated Acid-Base shown earlier in Example 2-5.
Problems
It is typical to see some compensation in Example 2-9
individuals with primary acid-base distur- Classification of Primary Blood Gas Problems
bances. In fact, whenever the respiratory and pH 7.30:
metabolic components are in opposite direc- PaCO2 Effect on pH [HCO3] Effect on pH
tions (e.g., acidosis and alkalosis), we routinely 68 mm Hg 32 mEq/L
assume that compensation is present.
Examples 2-9 through 2-11 and, previously, Example 2-10
Example 2-5, all show respiratory and meta- Classification of Primary Blood Gas Problems
bolic components pulling pH in opposite direc- pH 7.58:
tions (note arrows indicating opposite effects PaCO2 Effect on pH [HCO3] Effect on pH
on pH) and suggesting compensation. 17 mm Hg 16 mEq/L
Example 2-11 7.45

Classification of Primary Blood Gas Problems
pH 7.49: A
pH 7.40
PaCO2 Effect on pH [HCO3] Effect on pH
Aci
C

dos
50 mm Hg 37 mEq/L
is
7.35
on
sati
Completely Compensated Acid-Base en
mp
Problems Co
B
Determination of the primary problem is obvi-
ous when the pH is outside the normal range Figure 2-3. Compensation for a primary acidosis.
because compensation has not yet achieved A, A normal pH of 7.4 is shown. B, The individual
complete pH correction of the primary prob- develops an acidosis that could be either respira-
lem. Notwithstanding, when the respiratory tory or metabolic. C, After complete compensa-
and metabolic components are in opposite tion, the pH rests on the lower portion of the
normal range.
directions and the pH is in the normal range, the
answer to this question is less clear. This point is
shown in Example 2-12. Is the metabolic alka- normal pH range strongly suggests that the ini-
losis compensating for a primary respiratory tial disturbance had pulled the pH down (i.e.,
acidosis or is the respiratory acidosis compen- it was an acidosis).
sating for a primary metabolic alkalosis?
Example 2-13
Example 2-12 Classification of Primary Blood Gas Problems
Classification of Primary Blood Gas Problems pH 7.42:
pH 7.37: PaCO2 Effect on pH [HCO3] Effect on pH
PaCO2 Effect on pH [HCO3] Effect on pH 50 mm Hg 30 mEq/L
50 mm Hg 28 mEq/L
Conversely, the blood gas shown in Example
The answer is that this blood gas most likely 2-13 suggests that the primary acid-base
represents an individual with a compensated problem is a metabolic alkalosis and that the
respiratory acidosis. Sometimes these blood hypercarbia observed is compensatory. In
gases are also called completely compen- other words, it would be classified as a com-
sated because the pH is in the normal range pensated metabolic alkalosis. Figure 2-4 shows
but this is somewhat redundant and therefore the likely sequence of events in this case.
not used in this text.
Primary respiratory acidosis is the most B
likely acid-base situation in Example 2-12
Co
m
because it is generally accepted that the body

pe
n sa
does not overcompensate for a primary

tio
7.45
acid-base disturbance. In other words, when
sis
n
alo
the pH reaches the normal range, compensa- C

Alk
tory mechanisms abate. pH 7.40

The most likely sequence of events is shown A
in Figure 2-3. An individual with a normal pH
(Fig. 2-3,A) develops an acute respiratory aci- 7.35
dosis (Fig. 2-3,B). After maximal renal compen- Figure 2-4. Compensation for a primary alkalosis.
sation, however, the pH is brought back to the A, A normal pH of 7.40 is shown. B, The individual
lower portion of the normal range (Fig. 2-3,C). develops an alkalosis that could be either respira-
When the pH reaches the normal range, com- tory or metabolic. C, After complete compensation,
pensatory mechanisms tend to abate. The fact the pH rests on the upper portion of the normal
that the final pH is on the lower portion of the range.
Table 2-5. DETERMINATION OF THE PRIMARY Table 2-6. CLASSIFICATION OF DEGREE OF

PROBLEM COMPENSATION
pH pH Degree of Compensation
>7.40 Alkalosis is primary; acidosis is <7.35 Partial

compensatory >7.45 Partial
<7.40 Acidosis is primary; alkalosis is 7.357.45 Complete
compensatory
when a blood gas appears to be completely

An individual with a normal pH (Fig. 2-4, A) compensated. Partial versus complete compen-
develops an alkalemia (Fig. 2-4, B). After com- sation can likewise be differentiated by the pH
pensation, the pH is returned to the upper por- as shown in Table 2-6.
tion of the normal range (Fig. 2-4, C). It should be understood that this method
Thus, when the primary problem is not for classification of the primary problem when
readily apparent, the clinician should assess pH is in the normal range is not foolproof. For
what side of 7.40 that the pH is on. Table 2-5 example, a patient with a compensated meta-
shows how the most likely primary problem bolic acidosis may hyperventilate in response
can be determined when the pH is in the nor- to an arterial puncture. This, in turn, may push
mal range. Similarly, Figure 2-5 illustrates how the pH to the alkaline side of 7.40. The num-
one can determine the likely primary problem bers in this situation would incorrectly suggest
a primary alkalosis.
When compensation is suspected and pH is
pH >7.40 in the normal range, the clinical history and
serial blood gases are more important in mak-
ing the primary acid-base diagnosis than is
PaCO2 <35 [HCO3] >26 the specific pH. More sophisticated tools (e.g.,
acid-base maps; see Chapter 14) are also very
helpful in this regard. Nevertheless, for the stu-
dent learning basic blood gas classification, it
Primary respiratory Primary metabolic is useful to use the pH method for determining
alkalosis alkalosis the probable primary problem and arriving at
an initial classification. This allows the novice
pH <7.40 to organize concepts into a meaningful, consis-
tent framework.
It is also noteworthy that, physiologically, it
is actually unusual to see complete compen-
PaCO2 >45 [HCO3] <22 sation. The maximal compensatory response
in most cases is associated only with a 50% to
75% return of pH to normal.172 Thus, most
clinical acid-base blood gases will be classified
Primary respiratory Primary metabolic
acidosis acidosis as being partially compensated despite maxi-
mal acid-base response by the body.
Figure 2-5. Primary problem determination in For the sake of completeness regarding clas-
complete compensation. When the pH exceeds
sification, it is also possible for a patient to
7.40, the patient has a primary alkalosis. If the
PaCO2 is less than 35 mm Hg, there is a primary
have two opposing acid-base conditions (e.g.,
respiratory alkalosis. Similarly, if the [HCO3] respiratory acidosis and metabolic alkalosis)
exceeds 26 mEq/L, the patient has a primary while having a pH of exactly 7.40. In this case,
metabolic alkalosis. The same approach can be it is impossible to identify a single primary prob-
used when complete compensation is present and lem based on the data alone. Thus, this blood
pH is less than 7.40. gas should be classified as simply a respiratory
acidosis and metabolic alkalosis, which implies Table 2-7. CLASSIFICATION OF PaO2 IN THE
that either condition may be primary or sec- ADULT
ondary disturbances. Again, the accuracy of Classification PaO2 (mm Hg)
this assumption requires further investigation
as discussed in subsequent chapters. Hyperoxemia >100
Normoxemia 80100
Mild Hypoxemia 6079
ACID-BASE CLASSIFICATION Moderate Hypoxemia 4559
VERSUS INTERPRETATION Severe Hypoxemia <45
By integrating the information acquired in the
preceding steps, a complete acid-base classifica-
tion can now be formulated for any blood gas.
The term classification is used here to mean shown in Table 2-7. A PaO2 value within the
stating the overall acid-base status along with normal range is called normoxemia. In clinical
carefully selected general descriptive adjectives. practice, many clinicians do not use the term
The clinician should also realize that an acid- normoxemia but state simply that (blood gas)
base classification based on only an arterial oxygenation is normal or PaO2 is normal.
blood gas is not a definitive acid-base diagnosis.
Similarly, a term such as metabolic acidosis Hyperoxemia
is not definitive. Rather, it serves as a general A PaO2 level exceeding normal limits (i.e.,
categorical classification that may help to direct >100 mm Hg) may be called hyperoxemia.
the clinician to a more definitive acid-base diag- Hyperoxemia can occur as a result of hyper-
nosis (e.g., hypoxia and lactic acidosis). ventilation or administration of oxygen ther-
Notwithstanding, acid-base classification based apy (Fig. 2-6). PaO2s are generally less than
on the arterial blood gas is a good diagnostic 130 mm Hg when the cause is hyperventilation
starting point. but may be much higher (e.g., 400 mm Hg)
with the administration of high oxygen con-
centrations. In most clinical situations, signifi-
OXYGENATION STATUS
cant hyperoxemia is undesirable and may lead
After acid-base classification, the patients oxy- to untoward consequences. Although there are
genation status should be evaluated. The rou- exceptions, as a general rule, one should try to
tine classification of oxygenation via the arterial avoid hyperoxemia.
blood gas report is essentially an evaluation
of the PaO2 and its relationship to FIO2. The Hypoxemia
SaO2 may provide valuable information about A PaO2 level less than 80 mm Hg is called
oxygenation in many clinical circumstances; hypoxemia.10,175 Hypoxemia is very common in
however, it is not directly measured with blood hospitalized patients and may be a cause for
gases or routinely classified. The clinical role
of SaO2 and other factors in oxygenation are
discussed in subsequent chapters.
Hyperoxemia
PaO2 Classification
As shown in Table 2-7, there are three possible
general outcomes in adult PaO2 classification: Hyperventilation Excessive O2 therapy
normoxemia, hyperoxemia, or hypoxemia. PaCO2 <35 FIO2 > 0.21
Newborns generally have a lower PaO2 as Figure 2-6. Causes of hyperoxemia. There are
described in Chapter 1. only two potential causes of hyperoxemia.
Hyperventilation while breathing room air may
Normoxemia cause mild hyperoxemia up to about 130 mm Hg.
The normal range for adult PaO2 on room air Most often, hyperoxemia is due to oxygen therapy
at sea level is 80 to 100 mm Hg, which is and increased inspired oxygen concentration.
serious concern. One should remember however, Hypoxic potential

that PaO2 decreases as a normal consequence of with hypoxemia
aging and mild hypoxemia is expected in the
elderly. One can approximate the impact of
aging on PaO2 with the following formula. Mild 60-80 Moderate 45-59 Severe <45
Assuming a normal PaO2 of 100 mm Hg at
10 years old, PaO2 decreases approximately
5 mm Hg for every 10 years thereafter.
Hypoxia Possible hypoxia Hypoxia
Notwithstanding, PaO2 should not be less than unlikely depending on probable
75 mm Hg at any age.242 cardiovascular
condition
Hypoxic Potential Figure 2-7. Hypoxic potential with hypoxemia.
One must keep in mind that evaluation of The potential for hypoxia is directly related to the
blood gas PaO2 is only an evaluation of how degree of hypoxemia. With mild hypoxemia,
much oxygen is dissolved in arterial blood. A hypoxia is unlikely because SaO2 remains above
more important clinical question regarding 90%. With moderate hypoxemia, hypoxia may be
oxygenation is evaluation for the presence of present if the bodys compensatory mechanisms
hypoxia. Hypoxia is a generalized state of (especially cardiac output) are unable to maintain
inadequate oxygen to the tissues or cells of the tissue oxygenation. With severe hypoxemia, it is
highly likely that the patient will have concurrent
body. Hypoxia is a very serious condition
hypoxia. Severe hypoxemia and hypoxia represent
which, if uncorrected, can lead to death of the a critical situation that must be addressed.
organism.
Complete hypoxic evaluation is a very
important and much more complex process
that is described later in this text. Nevertheless, Moderate Hypoxemia
simple classification of the PaO2 is a good first Moderate hypoxemia leads to a more substan-
step in oxygenation assessment, which can be tive decrease in blood oxygenation and typi-
done with only the use of the blood gas infor- cally requires an increased cardiac output to
mation. Simply stated, hypoxemia may lead maintain tissue oxygen delivery. In the individ-
to hypoxia. Furthermore, the likelihood of ual with a normal cardiovascular system, tis-
hypoxia (i.e., cellular oxygen deprivation) sue oxygenation is usually maintained despite
depends on the severity of the hypoxemia. For moderate hypoxemia. In the presence of car-
this reason, it is customary to specify the diovascular disease, however, the individual
degree of hypoxemia when classifying an arte- may not be capable of delivering sufficient
rial blood gas. The degree of hypoxemia can oxygen to the tissues and hypoxia may ensue.
be classified as being mild, moderate, or severe Thus, moderate hypoxemia may or may not
depending on the propensity of the PaO2 to result in hypoxia depending on the integrity of
result in hypoxia (Fig. 2-7). the patients cardiovascular system. Moderate
hypoxemia is usually corrected to decrease car-
Mild Hypoxemia diovascular work and preclude the develop-
The presence of hypoxemia does not necessar- ment of hypoxia.
ily mean that oxygen levels in the blood are
insufficient to meet cellular needs. Mild Severe Hypoxemia
hypoxemia (i.e., PaO2 value of 60 to 80 mm When hypoxemia is severe, it is unlikely that tis-
Hg), which is shown in Table 2-7, is generally sue oxygenation can be maintained even with a
well tolerated, and tissue hypoxia is rare. The normal cardiovascular system. Therefore, the
SaO2 value remains at 90% even when the patient with severe hypoxemia should be pre-
PaO2 value falls to 60 mm Hg. The presence of sumed to be in a state of hypoxia. Severe hypo-
mild hypoxemia, although not normal, is xemia requires immediate attention and action
unlikely to result in hypoxia in the absence of (e.g., oxygen administration)! Patients should
other oxygenation disturbances. never be left in a state of severe hypoxemia.
Efficiency of Oxygen Uptake Ratios less than 2 suggest substantial pulmonary

Normal FIO2PaO2 Relationship dysfunction. Generally, the lower the ratio, the
The adult PaO2 classification system is based higher the shunt component in the lungs.
on the assumption that patients are breathing It is not customary to state the FIO2 as part
room air (FIO2 of 0.21). When a patient is of the blood gas classification. Nevertheless, at
receiving oxygen therapy, the PaO2 value may the very least, the clinician should always take
be in the normal range or higher despite the note of the FIO2 when classifying a blood gas
presence of substantial pulmonary dysfunc- to get some idea as to the normalcy of pul-
tion. A PaO2 value of 80 mm Hg may be called monary gas exchange.
normoxemia and it does indicate a sufficient
amount of dissolved oxygen in the blood, nev-
COMPLETE BLOOD GAS
ertheless, it is indicative of pulmonary dys-
CLASSIFICATION
function if the patient is breathing a high
concentration of oxygen (e.g., an FIO2 of 0.8, Acid-base and oxygenation status have been
80% oxygen). Oxygen uptake in the lungs is described separately as an introduction to
very inefficient. the classification of blood gases. In clinical
In normal individuals, the PaO2 value is practice, blood gas classification refers to the
approximately four to five times higher than the combined assessment of both acid-base and
percentage of oxygen being inspired. Thus, nor- oxygenation status. Conventionally, acid-base
mal PaO2 on room air (20% O2) is approxi- status is stated first followed by classification
mately 80 to 100 mm Hg (e.g., 5 20 = 100). of the oxygenation status. Complete blood
Normal PaO2 on 40% O2 is approximately 160 gas classification of Example 2-14 below
to 200 mm Hg (e.g., 40 5 = 200). Normal would thus be partially compensated metabolic
PaO2 on 70% O2 is approximately 280 to acidosis with moderate hypoxemia. The clini-
350 mm Hg (e.g., 70 5 = 350) and so forth. cian should note that the patient is breathing
room air.
PaO2/%FIO2 (Oxygenation Ratio)
If one takes the PaO2 and divides it by the per- Example 2-14
centage of inspired oxygen (i.e., PaO2/%FIO2), (Room Air Blood Gases)
an efficiency rating of pulmonary oxygen pH 7.22
exchange can be calculated. The normal oxy- PaCO2 22 mm Hg
genation ratio is approximately 5 (100/20 = 5). [HCO3] 9 mEq/L
The lower the oxygenation ratio, the less effi- PaO2 51 mm Hg
cient oxygen uptake in the lungs is and the more
severe is the pulmonary impairment. Values in It is especially important for the novice in
the range of 4 to 5 are clinically normal. blood gas classification to complete the exer-
Ratios in the range of 2 to 3.9 indicate cises at the end of this chapter to ensure mas-
moderate pulmonary dysfunction (Table 2-8). tery of the important clinical skill of basic
blood gas classification. More sophisticated
approaches to acid-base and oxygenation
assessment are provided in later chapters.
Table 2-8. OXYGENATION RATIO
(PaO2/%FIO2) ALTERNATIVE TERMINOLOGY
Pulmonary Status Oxygenation Ratio
(PaO2/%FIO2) Ventilatory Failure
The clinician should be aware that alterna-
Normal 4.05.0 tive terminology is used sometimes to classify
Moderate pulmonary 2.03.9 these same data from an arterial blood gas
dysfunction report. Shapiro introduced the term ventila-
Substantial pulmonary <2.0
tory failure to characterize a PaCO2 greater
dysfunction
than 50 mm Hg.10

A 27-year-old woman arrives in the emergency depart- Explanation: List possible diseases, pathology, or other
ment comatose, with a very slow respiratory rate. situations which may have lead to this patients
condition.
ARTERIAL BLOOD GASES Evaluation: Suggest additional data which would be
SaO2 89% useful in helping understand the situation or in making a
pH 7.24 diagnosis.
PaCO2 69 mm Hg
PaO2 69 mm Hg INTERVENTION
[HCO3] 26 mEq/L Importance: Prioritize concern(s) of treatment in order
of urgency and/or seriousness as you see the overall
ASSESSMENT situation.
Abnormalities: List abnormal data and other noteworthy
information. Classify ABG.
The term ventilatory failure is based on the use of temporal related adjectives to classify
concept that ventilation has failed to excrete blood gases. It is well known that maximal
CO2 at the same rate that it is being produced; renal compensation for primary respiratory dis-
thus, the process of alveolar ventilation has turbances may take up to or beyond 72 hours.
failed. The advantage of this terminology is Knowledge of this fact often allows us to deter-
that it draws attention to the fact that PaCO2 mine whether a particular respiratory acid-base
is essentially a product of CO2 production problem is of recent origin.
and alveolar ventilation. Thus, the presence of
ventilatory failure suggests the potential need Usefulness
for ventilation (compared with oxygenation) In particular, an acute respiratory problem can
therapy. often be recognized by the conspicuous
The process of ventilation, however, is not absence of renal compensation. Similarly, a
an end in itself. Rather, its importance is based chronic respiratory problem is likely to mani-
on the impact that ventilation has on the fest substantial or complete compensation.
broader concerns of acid-base balance and This information may be very important in
oxygenation. For this reason and because of trying to evaluate if an individual in the emer-
the continued widespread use of acid-base gency room has chronic pulmonary disease and
focused terminology, this alternative terminol- may hypoventilate or become apneic following
ogy is not routinely used for basic blood gas oxygen therapy.
classification in this text. Table 2-9 shows the temporal adjectives
Nevertheless, the overall concept of ventila- that correlate with absent or complete com-
tory failure is useful, and the reader should be pensation. Again, remember that complete
aware of it. The clinician should understand
that ventilatory failure is synonymous with
respiratory acidosis. Table 2-9. TEMPORAL ADJECTIVES FOR
PRIMARY RESPIRATORY ACID-BASE
Temporal Adjectives PROBLEMS
The term temporal means of or pertaining to Temporal Adjective Degree of Compensation
time. The fact that the renal compensatory
Acute Uncompensated
response to respiratory acid-base disturbances
Chronic Completely compensated
is a time-dependent process has prompted the

A 68-year-old man is admitted with a history of heavy Explanation: List possible diseases, pathology, or other
smoking, a barrel chest, shortness of breath, and exces- situations which may have led to this patients
sive sputum production. condition.
Evaluation: Suggest additional data which would be use-
ARTERIAL BLOOD GASES ful in helping understand the situation or in making a
SaO2 78% diagnosis.
pH 7.32
PaCO2 68 mm Hg INTERVENTION
PaO2 48 mm Hg Importance: Prioritize concern(s) of treatment in order
[HCO3] 32 mEq/L of urgency and/or seriousness as you see the overall
situation.
ASSESSMENT
compensation for any respiratory acid-base Second, this terminology is appropriate

disturbance is uncommon. Thus, chronic prob- only for primary respiratory acid-base prob-
lems may present as partially compensated lems. The temporal nature of primary meta-
disturbances. bolic problems cannot be assessed by the
degree of compensation present. Substantial
Caveats respiratory compensation for metabolic
Several caveats or cautions should be realized acid-base problems occurs immediately (i.e.,
regarding the use of temporal adjectives. First, certainly within an hour). Therefore, the
what appears to be compensation may in fact degree of compensation in primary metabolic
be a primary acid-base problem in the opposing disorders does not provide any useful informa-
direction. The duration of a particular acid-base tion regarding the duration of the primary
disturbance is best assessed by carefully review- acid-base disorder.
ing the history and physical examination.
EXERCISES
Exercise 2-1 pH Assessment

1. The single best indicator of acid-base status in the body is the (PaCO2, [HCO3], [BE], pH).
2. The pH of arterial blood is measured in (intracellular/extracellular) fluid.
3. The pH in the arterial blood reflects (overall/local) acid-base conditions in the body.
4. The pH range generally considered compatible with life is ______ to ______.
5. A low arterial pH tends to have an overall (depressive/stimulatory) effect on the nervous
system.
6. Convulsions may be seen with severe (acidemia/alkalemia).
7. A normal pH (does/does not) ensure that all acid-base components are completely normal.
8. Technically, (acidosis/acidemia) is a below-normal pH in the blood.
9. Because all patients with acidemia must have a causative acidosis, it is common clinical
practice to refer to a low blood pH as simply ____________.
10. State the three steps (ABCs) in classification of acid-base status from a blood gas report.
11. List the four blood gas values to be assessed and the appropriate sequence of assessment.
12. Classify the following arterial blood pH measurements:
a. 7.34 d. 7.45 g. 7.62
b. 7.20 e. 7.32 h. 7.45
c. 7.60 f. 7.48 i. 7.46
Exercise 2-2 Respiratory Acid-Base Status

1. Regarding acid homeostasis, the specific role of the lungs is to excrete ______ acid at
exactly the same rate at which it is being produced by the tissues.
2. There is a direct, linear relationship between arterial carbonic acid levels and ______.
3. An increased PaCO2 level in the blood is called (hypercarbia /hypocarbia).
4. Classify the following PaCO2 values as either a respiratory acidosis, normal PaCO2, or
respiratory alkalosis.
a. 30 b. 42 c. 35 d. 20 e. 55
5. State whether the presence of the following PaCO2 values will tend to increase or
decrease pH.
a. 80 b. 58 c. 32 d. 75 e. 15
Exercise 2-3 Metabolic Acid-Base Status

1. Any acid-base disturbance that is not respiratory in origin is called a ______ disturbance.
2. Some authors have suggested that the term metabolic should be replaced with ______.
3. The plasma bicarbonate is also sometimes referred to as the ______ bicarbonate.
4. The normal value for plasma bicarbonate in the arterial blood is ______ mEq/L.
5. Classify the metabolic acid-base status as metabolic acidosis, metabolic alkalosis, or
normal [HCO3] given the following values for plasma bicarbonate.
a. 25 mEq/L b. 30 mEq/L c. 18 mEq/L
6. Determine which way the following [HCO3] values tend to move pH (increase or decrease).
a. 20 mEq/L b. 28 mEq/L c. 15 mEq/L
7. The two most commonly used metabolic indices in the basic classification of blood gases
are the ______ and the ______.
8. The normal value for base excess is ______ mEq/L.
9. A base excess in the negative range is sometimes called a _______ _______.
10. Given the following values for base excess, classify metabolic status.
a. 5 mEq/L d. 20 mEq/L
b. +5 mEq/L e. 1 mEq/L
c. +12 mEq/L f. +20 mEq/L
Exercise 2-4 Compensation Assessment

1. Return of an abnormal pH toward normal by the component that is not primarily affected is
called ______________.
2. The organ system responsible for compensation for metabolic acid-base problems is the
________ system.
3. The organ system responsible for compensation for respiratory acid-base problems is the
______ system.
4. The body responds to metabolic acidosis with (hypercarbia/hypocarbia).
5. Uncompensated respiratory acid-base problems usually indicate that the problem is
(acute/chronic).
6. Most clinical blood gases with severe primary problems manifest (partial/complete)
compensation.
7. To determine whether or not a blood gas is completely compensated, one must evaluate
the (pH/PaCO2).
8. A pH of 7.30, with a PaCO2 value of 30 mm Hg and a [HCO3] of 14 mEq/L, is classified as
a (completely/partially) compensated metabolic acidosis.
9. In the patient with a long-standing hypercapnia, one would expect to see a(n)
(increased/decreased) bicarbonate.
10. Determine the probable primary problem given the following (completely compensated)
acid-base data:
pH PaCO2 [HCO3]
a. 7.36 50 28
b. 7.38 48 28
c. 7.44 30 20
d. 7.42 51 30
e. 7.36 30 18
Exercise 2-5 Acid-Base Classification

Write the complete acid-base classification for the following:
Set A Set B
pH PaCO2 [HCO3] pH PaCO2 [HCO3]
1. 7.28 60 26 1. 7.38 54 31
2. 7.50 40 30 2. 7.25 80 33
3. 7.62 28 28 3. 7.52 23 18
4. 7.22 50 20 4. 7.44 37 24
5. 7.52 28 23 5. 7.32 32 16
6. 7.52 42 33 6. 7.32 36 17
7. 7.60 30 29 7. 7.51 15 12
8. 7.10 40 12 8. 7.49 44 34
9. 7.20 36 13 9. 7.48 64 49
10. 7.34 50 25 10. 7.25 48 20
Exercise 2-6 Alternative Terminology

1. A PaCO2 in excess of 50 mm Hg is sometimes referred to as ventilatory (insufficiency/

failure).
2. The term ______ means of or pertaining to time.
3. A/an (acute/chronic) respiratory problem can often be recognized by the conspicuous
absence of renal compensation.
4. Temporal adjectives can be used for primary (respiratory/metabolic/respiratory and meta-
bolic) acid-base problems.
5. Classify the following blood gases using temporal adjectives where possible.
pH PaCO2 [HCO3]
a. 7.35 58 30
b. 7.28 58 25
c. 7.60 26 25
d. 7.28 40 18
e. 7.55 28 25
f. 7.57 36 35
Exercise 2-7 Oxygenation Assessment

1. The routine classification of the pulmonary component of oxygenation using an arterial

blood gas is essentially an evaluation of the (SaO2/PaO2).
2. The normal range of adult PaO2 in the clinic is ______ to ______ mm Hg.
3. A PaO2 value within the normal range is called ______.
4. A PaO2 value less than 80 mm Hg is called ______.
5. In this text, the term hypoxemia refers to a low oxygen (content/partial pressure).
6. A PaO2 value exceeding normal limits (i.e., >100 mm Hg) is termed ______.
7. In general, (lower/higher) PaO2 values are seen in the newborn.
8. Mild hypoxemia (is/is not) usually associated with hypoxia.
9. SaO2 is approximately ______% at a PaO2 of 60 mm Hg.
10. The presence of hypoxia in moderate hypoxemia depends on the integrity of the
(pulmonary/cardiovascular) system.
11. The patient with severe hypoxemia (should/should not) be presumed to be in a state of
hypoxia.
12. In normal individuals, PaO2 values are approximately ______ times higher than the
percentage of oxygen being inspired.
Exercise 2-8 PaO2 Classification

Classify the following adult PaO2 values as mild, moderate, or severe hypoxemia.
Adult PaO2 (mm Hg)
1. 160
2. 31
3. 56
4. 43
5. 59
6. 415
7. 75
8. 260
9. 92
10. 80
Exercise 2-9 Complete Blood Gas Classification

Classify both the complete acid-base status and the oxygen status of the following adult
blood gases:
pH PaCO2 [HCO3] PaO2
1. 7.58 20 19 63
2. 7.44 52 33 28
3. 7.21 66 25 47
4. 7.44 31 20 111
5. 7.60 28 27 59
6. 7.50 50 37 75
7. 7.41 42 24 229
8. 7.52 41 33 45
9. 7.46 44 30 87
10. 7.44 35 23 97
Exercise 2-10 Complete Blood Gas Classification using [BE]

as Metabolic Index
Classify both the complete acid-base status and the oxygen status of the following adult blood
gases:
pH PaCO2 [BE] PaO2
1. 7.32 30 10 58
2. 7.52 34 +4 32
3. 7.32 38 6 145
4. 7.40 30 5 90
5. 7.20 50 9 60
6. 7.20 80 +2 90
7. 7.55 25 +1 72
8. 7.34 30 9 41
9. 7.37 56 +5 57
10. 7.40 38 2 350
Exercise 2-11 Complete Blood Gas Classification

Additional Examples
Classify both the complete acid-base status and the oxygen status of the following adult
blood gases:
Set A Set B
pH PaCO2 [HCO3] PaO2 pH PaCO2 [HCO3] PaO2
1. 7.10 60 18 53 1. 7.53 27 22 83
2. 7.60 26 25 42 2. 7.32 69 34 28
3. 7.40 36 22 183 3. 7.18 56 20 53
4. 7.30 30 14 90 4. 7.46 33 23 151
5. 7.20 72 26 63 5. 7.20 28 11 59
6. 7.32 70 35 82 6. 7.14 60 20 75
7. 7.59 30 28 32 7. 7.41 42 25 229
8. 7.37 30 18 41 8. 7.52 41 34 45
9. 7.41 56 34 87 9. 7.64 32 34 87
10. 7.39 58 33 350 10. 7.33 54 28 97

1. Search the Internet for arterial blood gas interpretation and list at least two sites that you
found useful.
2. State the major problems associated with using the Internet to research and learn about
various medical topics. How might you minimize these problems?
NBRC Challenge 2
1. Given: pH 7.16 B) primary metabolic acidosis.
PaCO2 68 mm Hg C) primary metabolic alkalosis.
[HCO3] 23 mEq/L D) pulmonary embolus.
PaO2 62 mm Hg E) COPD.
Which of the following would be the most
likely treatment for a patient presenting 4. A patient presents to the emergency room
with this blood gas? with the following blood gas:
A) Mechanical ventilation pH 7.50
B) Continuous Positive Airway PaCO2 29 mm Hg
Pressure (CPAP) [HCO3] 22 mEq/L
C) Oxygen via nasal cannula PaO2 42 mm Hg
D) Oxygen via mask
The patient should be treated
E) Leave patient as is
immediately with:
(CRT EXAM NBRC MATRIX III,C,1)
A) mechanical ventilation.
2. A patient in the emergency room appears B) low flow oxygen.
short of breath. The following blood gas C) oxygen via mask.
is obtained: D) sedatives.
pH 7.15 E) respiratory stimulants.
PaCO2 17 mm Hg (CRT EXAM NBRC MATRIX III,C,1)
[HCO3] 5 mEq/L
5. A blood gas is drawn from a patient on
PaO2 110 mm Hg
a general floor.
pH 7.16
What is the likely explanation for the PaCO2 55 mm Hg
shortness of breath? [HCO3] 18 mEq/L
A) Hypoxemia PaO2 42 mm Hg
B) COPD
C) Compensation for severe meta- Based on the results, the patient appears
bolic acidosis to have:
D) Primary hyperventilation I. primary respiratory acidosis.
E) Paradoxical oxygen response II. primary metabolic acidosis.
(CRT EXAM NBRC MATRIX I,B,10,c) III. primary metabolic alkalosis.
IV. tissue hypoxia.
3. An elderly patient presents to the emer-
gency room with the following blood gas. A) I and II only
pH 7.36 B) I and III only
PaCO2 58 mm Hg C) I, II, and IV
[HCO3] 31 mEq/L D) II, III, and IV
PaO2 62 mm Hg E) I, II, III, and IV
A likely diagnosis for this patient is:
A) drug overdose.
II
UNIT
Technical Issues in Blood Gas Analysis
59
Chapter
3
Blood Gas Sampling Errors
In blood gas and pH analysis, an incorrect result can often be worse for the patient than no result at all.
National Committee for Clinical Laboratory Standards1
Outline
Introduction, 61 Precautions, 68
Basic Physics of Gases, 61 Recognition of Venous Error, 68
Molecular Behavior, 61 Anticoagulant Effects, 69
Fractional Concentration, 62 Nature of Anticoagulant, 69
Partial Pressure, 62 Dilution Error, 70
Symbols, 63 Metabolism, 71
Composition of Atmospheric and Qualitative Effects of Metabolism, 71
Alveolar Air, 63 Quantitative Effects of Metabolism, 71
Humidification, 64 Plastic versus Glass Syringes and Icing, 71
External Respiration, 64 Clinical Guidelines. 72
Body Temperature and Pressure Leukocyte Larceny, 72
Saturated, 65 Alterations in Temperature, 73
Temperature, Pressure, and Volume, 65 Quantitative Effects of Alterations in
Gases in Liquids, 65 Temperature, 73
Change in Altitude, 66 Correction of Temperature of
Potential Sampling Errors, 66 Blood Gases, 74
Air in the Blood Sample, 66 Machine Temperature Error, 74
Effects of Air Contamination, 66 Summary of Sampling Errors, 75
Clinical Guidelines, 67 Measurement of Blood Gases and Electrolytes
Summary, 67 from a Single Sample, 75
Venous Sampling or Admixture, 67 Anticoagulant Errors, 75
Venous Samples, 67 Transporting/Icing Samples, 76
Venous Admixture, 68 Exercises, 76
INTRODUCTION BASIC PHYSICS OF GASES
Improper sampling technique or blood speci- Molecular Behavior

men handling may introduce marked error The basic principles of gas behavior are reviewed
into the blood gas measurements.10,72 Blood as a prerequisite to understanding potential
gas values are not particularly stable, and they blood sampling errors. Gases consist of minute
may undergo significant alteration by appar- molecules in rapid, continuous, random motion,
ently minor sampling flaws. The incidence of which is sometimes referred to as Brownian
sampling error increases when inexperienced movement. The kinetic energy (energy of motion)
clinicians are responsible for obtaining the of these molecules will generate a force as the
blood.72,73 Given the vital nature of decisions molecules collide with each other and bounce
depending on blood gas values, proper educa- from one surface to another. The force per unit
tion with regard to potential sampling errors is area generated by a gas is called pressure.
essential. Blood gas sampling technique must Pressure, in turn, can be measured by a
be given careful attention. device called a manometer. Water molecules
61
62 Unit II Technical Issues in Blood Gas Analysis
may also be present in a gas phase and likewise 200

generate pressure. The force per unit area gen- 150 250
erated by the water molecules in a gas is called
water vapor pressure. 100 300
Air is a mixture of gases that usually mm Hg
includes water vapor. The air surrounding the 50 350
0
earth is called the atmosphere. The total pres-
sure exerted by all gases in the atmosphere is
called atmospheric pressure. Atmospheric pres-
sure at sea level is approximately 760 mm Hg; O2 O2 O2 H2O
therefore, this pressure is often referred to as 1
atmosphere. The unit torr is synonymous with
O2 O2 O2
millimeters of mercury; therefore, these units
may be used interchangeably.
Gravity tends to attract molecules to the O2 O2 O2 O2
center of the earth. Therefore, atmospheric H2O
pressure is higher than 760 mm Hg below sea
level, whereas above sea level it is lower than H2O vapor pressure 40 mm Hg
Temperature 20 C
760 mm Hg. Atmospheric pressure can be
measured by a specific type of manometer Figure 3-1. Fractional concentration and partial
called a barometer. pressure of a gas in a closed container. The fractional
Because air is a mixture of gases, many dif- concentration of O2 in the dry gas phase is 100%
ferent types of gas molecules are present within (FO2 = 1.0). The total pressure on the manometer
it. Each individual gas in the mixture is like- is 240 mm Hg. The partial pressure of O2 can be
wise responsible for a portion of the total (i.e., calculated:
atmospheric) pressure. The specific pressure (total pressure water vapor pressure) F = P
exerted by a single gas is called its partial pres- (240 40 mm Hg) 1.0 = 200 mm Hg.
sure (P) or tension. The specific gas that is
being referred to is denoted by including
its chemical formula. For example, the symbol
for the partial pressure of carbon dioxide is which is shown in Figure 3-1. The true con-
PCO2. The symbol for water vapor pressure centration of O2 would be less than 100%
is PH2O. because some molecules in the container are
Daltons law states that the sum of the par- H2O rather than O2; nevertheless, the percent-
tial pressures in a mixture of gases is equal to age of O2 in the dry gas phase (i.e., excluding
the total pressure. Thus, atmospheric pressure PH2O) is 100%.
is equal to the sum of all the partial pressures
of gases that are present in the air. Partial Pressure
The partial pressure of oxygen (PO2) in Figure
Fractional Concentration 3-1 could be determined by the application of
It is important to understand the distinction Daltons law; the sum of the partial pressures
between partial pressure of a gas and frac- equals the total pressure. Because there are
tional concentration of a gas. Fractional con- only two gases in the container, the sum of
centration of a gas in a dry gas phase (F) is the their partial pressures must be equal to 240
percentage of total gas molecules occupied mm Hg. Because PH2O is given as 40 mm Hg,
by a particular gas excluding water vapor mol- the balance of pressure must be due to O2.
ecules. Fractional concentration is expressed Thus, in this example, the PO2 is 200 mm Hg.
as a decimal; for example, 21% O2 is equiva- The formula used to calculate the partial pres-
lent to an FO2 of 0.21. In a container filled sure of a gas is (see Fig. 3-1):
with only O2 and water vapor, the fractional (total pressure water vapor pressure)
concentration of O2 is 100% (FO2 = 1.0), the fractional concentration of that gas.
Chapter 3 Blood Gas Sampling Errors 63
200 gases can be calculated by:

150 250
(total pressure water vapor pressure) 0.2.
100 300
Symbols
mm Hg
50 350 The symbol FIO2 is used to refer to the per-
0
centage of inspired oxygen. It is customary to
use capital letters as symbols to indicate gas
measurements related to the lung or its func-
H2O tion (e.g., I, inspired; E, expired; A, alveolar;
O2 T, tidal). Alveoli are the tiny air sacs within the
N2 N2 N2 N2
lungs in which gas exchange with the blood
N2
takes place. Tidal refers to the movement of
N2 N2
gas into and out of the lungs during normal
(tidal) ventilation.
H2O CO2 O2
Lowercase symbols, on the other hand, are
usually reserved for measurements made in
H2O vapor pressure 40 mm Hg the blood (e.g., a, arterial; v, venous; c, capil-
Temperature 20 C
lary). A bar () over the symbol is used to
Figure 3-2. Fractional concentration and partial represent the mean or average. For example,

pressure of a gas in a mixture of gases. The total P vO 2 designates the average PO 2 in the

number of molecules in the container excluding veins. PvO 2 can be measured in the pul-
water vapor is 10. Because two of the 10 non monary artery. In this blood vessel, all venous
water molecules are O2, the FO2 is 0.2. The blood that has returned to the heart from
PO2 can be calculated: throughout the body has been thoroughly
(total pressure water vapor pressure) F = P mixed.
(240 40 mm Hg) 0.2 = 40 mm Hg.
Composition of Atmospheric
and Alveolar Air
A similar container with an identical PH2O The major gases present in dry atmospheric air
and the same total pressure is shown in Figure with their respective partial pressures and per-
3-2. However, only two of the ten nonwater centages are shown in Table 3-1. It can be seen
molecules in this mixture of gases are O2 that the normal FIO2 while breathing room air
molecules. Thus, the fractional concentration of is 0.21 and that the normal PIO2 is approxi-
oxygen (FO2) in this mixture is 0.2 (20% O2). mately 158 mm Hg. Partial pressures shown
The partial pressure of O2 in this mixture of are based on a total atmospheric pressure of
Table 3-1. COMPOSITION OF AIR AT SEA LEVEL

Dry Air Alveolar Air
Compound Partial Pressure (mm Hg) Percent Partial Pressure (mm Hg) Percent
Nitrogen 590.0 78.09 569 74.8

Oxygen 158.0 20.95 104 13.7
Carbon dioxide 0.2 0.03 40 5.3
Argon, neon, etc. 7.8 0.93 (<1) (<0.1)
Water vapor 47 6.2
760 100 760 100
From Ziment, I.: Respiratory Pharmacology and Therapeutics. Philadelphia, W. B. Saunders, 1978.
760 mm Hg present at sea level. For simplicity, Table 3-2. EFFECT OF TEMPERATURE ON
Table 3-1 shows no water vapor pressure in WATER VAPOR PRESSURE
the atmospheric air. In reality, the air that we (100% RELATIVE HUMIDITY)
breathe contains some water vapor pressure, Vapor Vapor
and the normal partial pressure of inspired Temperature Pressure Temperature Pressure
oxygen in humidified air is only approximately (C) (mm Hg) (C) (mm Hg)
148 mm Hg.
0 4.6 39 52.0
The partial pressures and percentages of
5 6.5 40 54.9
these gases in alveolar air are also shown in 10 9.1 41 57.9
Table 3-1. Two major processes are responsi- 14 11.9 42 61.0
ble for changing the quality of the air in the 16 13.5 43 64.3
alveoli compared with inspired air: humidifica- 18 15.3 44 67.8
tion and external respiration. 20 17.4 46 75.1
22 19.6 48 83.2
Humidification 24 22.2 50 92.0
The water vapor pressure actually present in 26 25.0 55 117.5
air at any particular time is a function of the 28 28.1 60 148.9
30 31.5 65 187.1
temperature and relative humidity. The
31 33.4 70 233.3
warmer the air, the more humidity it is capable
32 35.3 75 288.8
of holding. The relative humidity (RH) is a 33 37.4 80 354.9
ratio of humidity actually present in the air 34 39.5 85 433.2
(absolute humidity) compared with the 35 41.8 90 525.5
maximum amount of humidity that air at 36 44.2 95 633.7
that temperature could hold (i.e., potential 37 46.6 100 760.0
humidity). Relative humidity is expressed as 38 49.3
a percentage.
From Guyton, A. C.: Textbook of Medical Physiology,
A relative humidity of 100% means that 9th ed. Philadelphia, W. B. Saunders, 1996.
the air is holding the maximum amount of
molecular water possible at that temperature
(i.e., actual humidity = potential humidity).
Air with a relative humidity of 100% is satu- Thus, the partial pressures of other gases must
rated. Table 3-2 shows the water vapor pres- decrease as a result of the increased PH2O.
sures that would be present in air that is
saturated at various temperatures. The fact External Respiration
that warm air can hold more moisture than External respiration is the exchange of O2 and
cold air is readily apparent. CO2 between the alveoli and the blood.
Air that is completely saturated at body tem- Oxygen, of course, diffuses from the alveoli
perature (i.e., 37 C) has a PH2O of 47 mm Hg. into the blood, whereas CO2 is diffusing from
Fully saturated room air (i.e., 20 C), on the the blood into the alveoli. Therefore, it is not
other hand, has a PH2O of only 17 mm Hg. surprising that alveolar PO2 is lower than
Obviously, if gas is not fully saturated at a par- atmospheric PO2 because of the loss of O2
ticular temperature, water vapor pressure is from the alveolus to the blood. Likewise, one
less than that shown in Table 3-2. Air is heated would expect that alveolar PCO2 would be
to body temperature (37 C) and is completely higher than atmospheric PCO2 owing to the
humidified (100% RH) as it travels through influx of CO2 into the alveolus. Table 3-1 simply
the upper airway on its way to the lungs. confirms this exchange.
Therefore, it is safe to assume that PH2O in the Finally, it should be noted that alveolar PN2
alveoli is approximately 47 mm Hg. Thus, and the partial pressure of trace gases are
alveolar air has a higher water vapor pressure lower in the alveoli. These changes, however,
than atmospheric air. The total pressure in the are passive results owing to external respira-
alveolus is the same as atmospheric pressure. tion and humidification.
Body Temperature and Kelvin degrees and 0 Celsius is equivalent to

Pressure Saturated 273 Kelvin (K). The total pressure in Figure
Clinical measurements of gases are made 3-2 is 240 mm Hg, and the gas is at a tempera-
under standardized conditions for compar- ture of 20 C (293 K). If the temperature of
ison of values and reproducibility of results. the gas increased to 38 C (311 K), which is
Blood gases are measured at body temperature shown in Figure 3-3, Brownian movement and
and pressure saturated (BTPS). The BTPS kinetic energy of the gas would increase and the
notation refers to normal standardized condi- total pressure within the container would
tions within the body (i.e., temperature 37 C, increase. As show in Figure 3-3, the new pres-
ambient pressure, and PH2O of 47 mm Hg). sure is 255 mm Hg.
Similarly, the partial pressures of other
Temperature, Pressure, gases within the container also increase. Partial
and Volume pressure must be distinguished from fractional
An introduction or review of gas behavior concentration, which would not change. The
would be incomplete without some mention of partial pressure of O2 in Figure 3-3 can be
the basic gas laws; in particular, the laws that calculated as described earlier:
describe the interdependent relationships
PO2 = (total pressure PH2O)
between volume, pressure, and temperature
fractional concentration
are briefly described.
Gay-Lussacs law states that if volume and PO2 = (255 mm Hg 40 mm Hg) 0.2
mass remain fixed, the pressure exerted by a gas PO2 = 43 mm Hg
varies directly with the absolute temperature of
the gas.74 Absolute temperature is measured in The gas laws pertaining to changes in
volume are less important with regard to blood
gases but are included here for completeness.
Boyles law states that if absolute temperature
200
and mass remain unchanged, volume varies
150 250
inversely with pressure. Similarly, Charles law
100 300 states that if pressure and mass are unchanged,
volume varies directly with changes in absolute
mm Hg temperature.
50 350
0
Gases in Liquids
Gases dissolve freely in liquids. The particular
gas may or may not react chemically with the
H2O
liquid, depending on the chemical nature of
N2 O2 N2 N2
each substance. Nevertheless, all gases remain in
a free gaseous phase to some extent within the
CO2 O2
liquid. The dissolution of gases in liquids is a
N2 H2O N2 physical, not a chemical, process. Gases within
N2 N2 liquids exert pressure in much the same manner
as described in pure gaseous environments.
H2O vapor pressure 40 mm Hg Henrys law states that when a gas is exposed
Temperature 38 C to a liquid, the partial pressure of the gas in the
liquid phase equilibrates with the partial pres-
Figure 3-3. Effects of increasing temperature of
gas in a closed container. If the temperature of a
sure of the gas in the gaseous phase. Thus, if O2
closed container is increased, the speed and energy in the air is exposed to blood or water, there
of the enclosed molecules will also increase and is an exchange of O2 molecules between the
will thus raise the pressure. The concentration liquid and gaseous phases until the respective
of the molecules remains constant while partial partial pressures are equal. The progressive
pressure increases. equilibration of the partial pressure of O2
O2 O2 O2 Box 3-1 Potential Sampling Errors

(P = 100 mm Hg) (P = 100 mm Hg) (P = 100 mm Hg) Air in the blood sample
Venous sampling or admixture
Excessive or improper anticoagulant
Rate of metabolism
Temperature disparities between patient
O2 O2 O2
and machine
(P = 0 mm Hg) (P = 50 mm Hg) (P = 100 mm Hg)
A B C
Figure 3-4. Equilibration of partial pressures POTENTIAL SAMPLING ERRORS
between liquid and gas phases. Solution of oxygen
in water. A, When the oxygen first comes into con- Five common types of arterial blood sampling
tact with pure water. B, After the dissolved oxygen error are discussed: air in the blood sample,
is half way to equilibrium with the gaseous oxygen. inadvertent venous sampling or admixture,
C, After equilibrium has been established. anticoagulant effects, changes due to metabo-
lism, and alterations in temperature (Box 3-1).
The significance of each type of error and also
between the gaseous and the liquid phases is the mechanism of these changes are explored.
shown in Figure 3-4. Proper labeling of the sample is also para-
mount. If the specimen is to be submerged in
Change in Altitude water or ice, the label must remain legible.
The barometric pressure is lower as altitude Incorrect matching of laboratory results with
increases. Air at a high altitude still has a 21% the patient is unacceptable.
O2 concentration; however, the partial pres-
sure of O2 is much lower. The effect of high Air in the Blood Sample
altitude on barometric pressure and PO2 is Effects of Air Contamination
shown in Table 3-3. Clinical studies have shown that the major effect
At the summit of Mount Everest, which of an air bubble in a blood gas sample is a
has the highest altitude on earth, the PO2 is change in PaO2.7679 According to Henrys law,
approximately 42 mm Hg.75 Again, the FIO2 when a blood specimen with a PaO2 of less than
remains at 0.21 but the PO2 decreases tremen- 158 mm Hg is interfaced with an air bubble, the
dously. Thus, the normal PaO2 at a high altitude PaO2 of the blood sample spuriously increases.
(e.g., Denver) is obviously much lower than This action occurs because the partial pressure
the normal PaO2 at sea level. of O2 in the air at sea level is approximately 158
mm Hg. The magnitude of the increase depends
partly on the duration of exposure, whereas the
volume of the air bubble, although important,
Table 3-3. EFFECTS OF HIGH ALTITUDE ON
BAROMETRIC PRESSURE PO2 seems to make less difference.77 Other factors
that may determine the ultimate effect of air
Barometric Pressure PO2 in Air
Altitude (ft) (mm Hg) (mm Hg)
contamination include the temperature of the
sample and the degree of agitation (Fig. 3-5).
0 760 159 Furthermore, the change is greatest when
10,000 523 110 the patients actual PaO2 exceeds 100 mm Hg.79
20,000 349 73 This change can be explained by the chemical
30,000 226 47 relationship between O2 and hemoglobin that
40,000 141 29 is discussed in Chapter 7 under the oxyhemo-
50,000 87 18 globin dissociation curve.
From Guyton, A. C.: Basic Human Physiology, In certain clinical situations (e.g., in the
Normal Function and Mechanisms of Disease, 2nd ed. operating room where high concentrations of
Philadelphia, W. B. Saunders, 1977. inspired O2 are often used), the initial PaO2 of
PO2 with great surface area exposed to blood.

Furthermore, froth is essentially impossible to
Longer time expel. All samples with visually apparent froth
Lower temperature should be discarded.
Increased agitation
Finally, serious error is likely if air is allowed
to remain in the sample or is introduced into
the blood gas machine when the actual meas-
urements are being made. Electrodes used in
blood gas machines register incorrect results
when they are in contact with an air bubble.
True value Relative volume of air bubble Summary

The presence of air in an arterial blood gas sam-
Figure 3-5. Effect of air contamination on PaO2.
Air bubbles may seriously influence PO2, even
ple is unacceptable and may introduce notable
when very small (1% of sample volume). The effect error. The PaO2 tends to migrate toward
depends on many factors, e.g., size of air bubble 158 mm Hg; PaCO2 tends to fall, and pH may
relative to sample volume, initial oxygen status of increase if the decrease in PCO2 is substantial.
sample, and storage conditions (time, temperature, The most important change is the alteration in
agitation). PaO2, which is particularly marked when initial
PaO2 is greater than 100 mm Hg. This can be
explained by the oxyhemoglobin dissociation
the blood sample may exceed 158 mm Hg. In curve, which is explained in Chapter 7.
this event, O2 tends to migrate from the blood The expulsion of air bubbles within 2 min-
phase to the bubble and results in measure- utes and the delay in mixing the sample until
ment of an erroneously low PaO2 in the blood air bubbles have been expelled helps to prevent
sample being analyzed.76 contamination of the sample from the air. The
As shown in Table 3-1, the PCO2 in clinician must also take care not to introduce
room air is essentially zero. Thus, one would air into the blood gas machine. Thus, every
expect blood PCO2 levels to decrease if blood effort must be made to ensure the acquisition
were exposed to an air bubble. This effect of the sample under anaerobic (i.e., in the
does occur, but is less marked than the change absence of free O2) conditions.
in PO2. The different blood solubility coeffi- New blood gas syringes have been designed
cients of O2 and CO2 probably explain the which have special vent mechanisms. These
disparity in response. Finally, the pH increases vents allow the syringe to be filled to a pre-
when arterial blood is exposed to an air selected volume while air is pushed out and the
bubble as a direct consequence of the decrease vent is closed.1 Use of these syringes precludes
in PaCO2. air contamination of the sample.
When laboratory samples are unacceptable,
Clinical Guidelines this should always be documented in the labo-
Mixing or agitating a sample contaminated ratory along with the reason. In addition, cor-
with an air bubble tends to escalate the error rective measures to ensure this error will not be
(see Fig. 3-5). Also, because the duration of repeated should also be noted. This is true for
exposure to an air bubble is a factor in the all sample errors or inaccurate readings.
degree of error, all air bubbles should be
expelled immediately. Results are reasonably Venous Sampling or Admixture
stable when blood samples are not prema- Venous Samples
turely mixed and when foreign air bubbles are Inadvertent venous puncture is a potential source
expelled within 2 minutes.77 of error in blood gas sampling, particularly in
When froth is observed in a blood gas the hypotensive (low blood pressure) patient
sample, the likelihood of significant error is and when femoral artery puncture is
great. Froth represents many minute air bubbles attempted. As discussed previously, failure to
observe the characteristics of an arterial sam- The use of short-beveled needles minimizes the
ple (i.e., a flash of blood on entry into the ves- surface area available for aspiration and thus
sel, pulsations during syringe filling, and decreases the potential for venous admixture.
auto-filling of the syringe) should arouse sus- The puncture technique of overshooting the
picion of this type of error. Peripheral venous blood vessel and then withdrawing the syringe
blood has little value in oxygenation assess- should be avoided whenever possible. Most
ment. Furthermore, therapeutic decisions important, the femoral artery, where venous
based on venous blood that is assumed to be contamination or sampling is particularly
arterial may be grossly inappropriate. likely to occur, should be punctured only when
absolutely necessary.
Venous Admixture
A less recognized, albeit important, technical Recognition of Venous Error
error is contamination of the arterial sample Venous contamination error should be sus-
with a small amount of venous or capillary pected whenever the patients clinical status and
blood during an attempt at arterial puncture. picture is remarkably better than the blood gas
Entry into a vein may occur easily during an data suggest. The patient with serious acid-base
attempt to puncture the femoral artery because or oxygenation impairment is rarely asympto-
the large femoral vein lies close and posterior matic. When the laboratory data are not con-
to the artery. Overshooting any artery with gruent with the patients appearance, it is most
subsequent withdrawal may result in the likely that the laboratory data are incorrect.
entry of some venous blood into the syringe. Occasionally, there is some question with
Moreover, femoral venous anomalies, in which regard to whether a particular blood sample is
the vein may lie anterior to the artery, are fairly arterial or venous in origin. Although hypox-
common and predispose to this type of error. emia (low PO2) and hypercarbia (high blood
The addition of one-tenth part of venous PCO2) suggest that the sample is venous, one
blood to an arterial sample could produce as cannot be certain of this on the basis of blood
much as a 25% decrease in measured PaO2.80 gas numbers alone. It is not uncommon to find
For example, mixture of 0.5 mL of venous arterial hypoxemia and hypercarbia in critically
blood having a PO2 of 31 mm Hg (not unusual ill patients.
for a skeletal muscle vein81) with 4.5 mL of The technology of pulse oximetry is dis-
arterial blood having a PO2 of 86 mm Hg cussed in Chapter 15. Pulse oximetry is a
would lead to a mixture having a PO2 of noninvasive technology used to monitor O2
56 mm Hg (Table 3-4).80 Certainly, the clinical saturation of arterial blood. When pulse
treatment of a patient with a PaO2 of 56 mm Hg oximetry is being used, it may serve as a cross-
is considerably different from that of a patient check of saturation measured via arterial
with a PaO2 of 86 mm Hg. blood gases. For example, a saturation of 90%
via pulse oximetry and a blood gas saturation
Precautions of 78% strongly suggest that the blood gas
Some precautions could decrease the likeli- sample may not be arterial. This crosscheck
hood of venous sampling or contamination. may be useful when the origin of blood gases
(i.e., arterial versus venous) is in doubt.
Table 3-4. VENOUS CONTAMINATION OF AN Mixed versus Peripheral Venous Blood

ARTERIAL SAMPLE Mixed venous blood from the pulmonary
Blood Volume (mL) PO2 (mm Hg) artery typically approximates the blood gas
values shown in Table 3-5. A sample of mixed
Arterial 4.5 86 venous blood may be taken only from a catheter
Venous 0.5 31 in the patients pulmonary artery. The values
Mixed 5.0 56 shown in Table 3-5 are normal for mixed
From Doty, D. B., and Moseley, R. V.: Reliable sampling venous blood, which is an average of all venous
of arterial blood. Surg. Gynecol. Obstet., 130:701, 1970. blood returning to the heart. Occasionally, some
Table 3-5. NORMAL MIXED VENOUS GASES ON CALL CASE 3-1 ABGs and Critical
Parameters Values Thinking
pH 7.38 You are the only person available to care for this
PvCO2 48 mm Hg patient. You must assess the patient/situation
PvO2 40 mm Hg and act accordingly.
SvO2 75% A 52-year-old man is treated in the emergency
department for suspected pneumonia. An arterial
blood gas sample is drawn on room air. The sample
appears a little frothy and is bright red.
healthcare personnel presume that all venous
blood has these same valuesthis assumption
is incorrect. pH 7.50
Peripheral venous blood from different PaCO2 29 mm Hg
organs and tissues has different PvO2 values PaO2 153 mm Hg
depending on various factors, including local [HCO3] 22 mEq/L
metabolism, perfusion, and tissue function.
ASSESSMENT
For example, the PO2 of venous blood exiting
skeletal muscles may be near 34 mm Hg, Abnormalities: List abnormal data and other
whereas the PO2 of blood leaving the skin is noteworthy information.
approximately 60 mm Hg.81 Because venous
blood inadvertently sampled while attempting
an arterial puncture is peripheral venous
blood, it is impossible to predict exactly how anticoagulant must be carefully controlled.
the blood gas values will change. Lower PO2 Most new blood gas kits come with syringes
values and higher PCO2 values should be that have been pre-filled with the appropriate
expected. However, a sample cannot be judged type and amount of anticoagulant.
to be venous solely because the values nearly
approximate normal mixed venous values. Nature of Anticoagulant
Lithium heparin is the current recommended
Verification anticoagulant for blood gas and/or electrolyte
One method that has been suggested to deter- sampling.1 Sodium heparin (1000 U/mL) is still
mine whether a sample is arterial or venous is sometimes used, although it has a slightly higher
to repeat the sample while simultaneously potential to cause the formation of very small
drawing a known venous sample from the same fibrils in the sample and will likely increase [Na]
anatomic area for comparison. The discomfort, by approximately 3 mEq/L if Na is also being
expense, and potential for complication appear measured.82,241 Heparin, however, is expensive,
to make this a poor option. Alternatively, and the supply fluctuates in some parts of
a carefully acquired new sample taken by an the world. Therefore, the use of alternative anti-
experienced therapist or clinician usually pro- coagulants has been explored.72 Most other
vides a satisfactory answer to the question of anticoagulants are unsuitable for blood gas
sample accuracy. If repeated samples become samples; however, Heller-Paul oxalate and cit-
necessary, perhaps an arterial line is indicated rate have been identified as being potential sub-
to ensure that all samples are arterial. stitutes that may be cheaper and acceptable.72
Further studies are necessary before these agents
Anticoagulant Effects can be recommended for routine use.
Anticoagulation of the blood gas sample is The concentration of sodium heparin recom-
essential to prevent clotting of the specimen. mended is 1000 U/mL. The pH of this solution
Nevertheless, introduction of an anticoagulant closely approximates the normal pH of arterial
to the sample may in itself cause a technical blood. Stronger concentrations of heparin and
error. The type, concentration, and volume of other anticoagulants have pH values that differ
Table 3-6. PH OF ANTICOAGULANT Parameter value

SOLUTIONS Dilution
A
Anticoagulant pH True value
3
pH
Citrate 7.65
Heparin (1000 U/mL) 7.33
Heparin (5000 U/mL) 7.10
Oxalate 6.94
Heparin (25,000 U/mL) 6.53
EDTA 4.73 2
Adapted from Goodwin, N. M., and Schreiber, M. T.:

Effects of anticoagulants on acid-base and blood gas
PCO2
estimations. Crit. Care Med., 7:473, 1979.
Electrolytes
significantly from arterial blood and are more
likely to contaminate blood pH (Table 3-6) Figure 3-6. Effect of liquid heparin dilution on
and electrolyte readings. blood gases and electrolytes. Diluting the blood
sample (to point A) may significantly decrease
Dilution Error electrolyte values (1) and pCO2 values (2). There is
The normal technique for manually hepariniz- almost no change in pH values (3).
ing a syringe has been described previously.
The clinician must be careful not to add unnec-
essary heparin volume because it may substan- extreme, the pH, bicarbonate, and base excess
tially alter blood gas results. Inexperienced concentrations may fall more appreciably.84
clinicians sometimes add extra heparin in The PaO2 is usually relatively unchanged in
stress situations to ensure anticoagulation.72 response to heparin dilution. If the initial PaO2
This error can be avoided through proper is very high, however, heparin dilution may
education and training. result in a notable decrease.85
Blood Gas Change with Excessive Dilution Clinical Significance

Liquid heparin is essentially a weak acid equil- In some cases, even normal syringe hepariniza-
ibrated with room air. Therefore, the effects of tion technique has been purported to signifi-
heparin on an arterial blood sample are very cantly lower PaCO2 and bicarbonate values.28,86
similar to those that would occur if the sample Similarly, hematocrit and hemoglobin values
were exposed to an air bubble. Unlike air measured from heparinized arterial samples
contamination, however, the major blood gas have been falsely low owing to the dilution
error associated with excessive heparin in effect.72 Dilution correction factors are avail-
the sample is a drop in the PaCO2 (Fig. 3-6). able to correct for these errors.
Apparently, PaCO2 is affected more than PaO2 New syringe designs with minimal deadspace
because of the different solubility coefficients and the use of dry (lyophilized) crystalline
of the two gases in the liquid phase. As shown heparin have increased accuracy and virtually
in Figure 3-6, electrolyte measurements are eliminated the need for concern regarding sample
also significantly altered when simple sodium dilution.85,86,241 The concern that dried heparin
heparin is used. may increase technical error through an air bub-
A decrease in PaCO2, in turn, tends to ble effect does not appear to be justified.85 The
increase pH. Surprisingly, however, the actual only blood gas concern with dry heparin is that
pH may slightly fall (see Fig. 3-6), presumably it may not dissolve adequately or quickly which
because the low CO2 effect is offset by the low may, in turn, lead to clot formation.241
pH and bicarbonate concentration of the In laboratories still using standard 5-mL or
heparin solution.28,72,73,83 When dilution is 10-mL syringes, the sample volumes for adults
should always exceed 2 mL.16 For additional Table 3-7. EFFECTS OF METABOLISM ON
accuracy, correction factors are available for BLOOD GASES AT 37 C
PCO2 and bicarbonate level.5 As a general Measurement Direction Magnitude/Hr
rule, each 1% dilution results in a 1% decline
in PCO2. The primary concern in the clinical pH Decrease 0.05
setting is the use of a standard technique that PaCO2 Increase 5 mm Hg
allows for an accurate comparison of serial PaO2 Decrease 150 mm Hg
measurements.83 20 mm Hg

Initial PaO2 >250 mm Hg.
Neonatal Considerations
Initial PaO2 <150 mm Hg.
Neonatal blood gas samples are often drawn
into 1-mL tuberculin syringes. Thus, they are
particularly vulnerable to the dilution effects
of heparin because of the small sample volume. approximately 0.05 units.10,88 The magnitude
Whereas an adults sample may be diluted only of the drop in arterial PO2 would depend
6%, a neonatal sample may be diluted up to mainly on the initial PO2 level.
40%.72 Although the blood gas machine may Very high initial PO2 values (e.g., PaO2 >
be capable of providing results with a mere 300 mm Hg) tend to decrease precipitously,
0.2-mL neonatal sample,83 this volume may perhaps by as much as 150 mm Hg per hour.
not be sufficiently large to preclude significant Conversely, lower initial PaO2 values (e.g., 100
heparin dilution. mm Hg) tend to decrease only approximately
Error in arterial PCO2 may be 14% to 15% 20 mm Hg per hour. Furthermore, PaO2 values
if a 0.2-mL blood sample is introduced into a less than 60 mm Hg fall much less than this.
1-mL tuberculin syringe with deadspace The large discrepancy between initial high
heparin.83 Therefore, neonatal sample volumes and low PaO2 groups can be explained by
should exceed 0.6 mL to minimize dilution the oxyhemoglobin dissociation curve and O2
effects. Notwithstanding, larger samples should transport (see Chapter 7).
be avoided in neonates because blood volume At room temperature (20 to 24 C), metab-
depletion and anemia may occur with repeated olism is slowed to approximately 50% of levels
sampling.87 at 37 C.88 Thus, the changes quantified in
Table 3-7 may take 2 hours instead of 1 hour to
Metabolism occur. Placing the sample in iced water (almost
Qualitative Effects of Metabolism at 4 C) slows metabolism to approximately
Metabolism continues within blood cells in 10% of levels at 37 C.88 Thus, in iced samples,
the syringe after the blood has been drawn the quantitative changes indicated in Table 3-7
from the patient. These metabolic processes may take up to 10 hours. Placing blood gas
consume O2, produce CO2, and thus tend to samples in refrigerators is not an adequate
alter blood gas values. Likewise, the accumu- substitute for placing samples in ice, and this
lation of CO2 in the sample lowers pH. The practice should be avoided.77
speed and magnitude of these changes depend,
in large part, on the temperature of the sample. Plastic versus Glass Syringes and Icing
Generally, the extent of blood gas alterations It has long been known that blood gases (i.e.,
due to metabolism is proportional directly to oxygen, carbon dioxide) could diffuse more
the temperature of the sample. readily (thereby tending to equilibrate with
ambient gases) through plastic syringes than
Quantitative Effects of Metabolism glass syringes. Notwithstanding, however, this
Table 3-7 shows the magnitude of blood gas increased permeability through plastic syringes
changes that would occur if a sample were main- has been thought to be clinically insignificant.
tained at 37 C (body temperature). In 1 hour, Therefore, with the advent of plastic syringes
arterial PCO2 would increase by approxi- that filled freely without friction, and with
mately 5 mm Hg and pH would decrease increased attention to cost containment, it is
common to use plastic syringes for blood gas Clinical Guidelines

acquisition. In clinical practice, all room temperature
Surprisingly, it has been found that PaO2 blood gas samples should be analyzed within
and PaCO2 in iced samples within plastic 30 minutes to avoid the introduction of signif-
syringes may actually change over time in icant error.1,34,77,79 Iced samples remain gener-
opposite directions to what would be expected ally stable for 2 hours or more if the initial
by metabolism.34 In other words, PaO2 PaO2 is less than 150 mm Hg.14,34,65 Arterial
increased and PaCO2 decreased in iced sam- PCO2 and pH are especially stable in iced
ples within plastic syringes. This can only be samples. Error in these measurements is mini-
explained by the increase in solubility coeffi- mal even 2 to 4 hours after the time when the
cients caused by cooling within the sample. sample is placed in ice.7779,88 The decrease in
The change in solubility tends to lower partial PaO2 in the iced sample, however, may be sub-
pressures within the blood and enhances stantial after only 30 minutes when the initial
diffusion of ambient gases through the plastic PaO2 is high.79 The change factors shown in
syringe with the sample. Table 3-7 may also be used to approximate
When blood is cooled to 4 C, the solubility blood gas values if the sample cannot be iced
of oxygen in blood nearly doubles.34 In addi- or analyzed within 30 minutes.88
tion, the oxyhemoglobin curve is shifted to
the left and increased dissolved oxygen is Leukocyte Larceny
combined with hemoglobin. These two factors The metabolic activity responsible for blood gas
result in a decreased PaO2 within the iced changes occurs predominantly in leukocytes
blood sample. The increased diffusion gradient (white blood cells), platelets, and reticulocytes
between ambient air (PO2 155 mm Hg) and (immature red blood cells).34,75 Normal,
the sample allows additional oxygen to diffuse mature erythrocytes (red blood cells) are not
from the ambient gas to within the plastic responsible for significant metabolism and
syringe. blood gas change because 90% of their metab-
Subsequently, when the blood is re-warmed olism is anaerobic. Immature leukocytes, when
within the blood gas machine, oxygen is present, consume even more O2 than that
released from within the blood to the gaseous noted for normal leukocytes.89 The effect of
phase. The oxygen is released from hemoglobin reticulocytes on oxygen depletion is usually
due to the right shift of the oxyhemoglobin slight due to their small concentration.
curve and is also released into physical solution The term leukocyte larceny was coined by
due to the decreased solubility coefficient at the Fox to describe the rapid decrease in PaO2
higher temperature. In summary, the ambient that was observed in blood samples with high
oxygen that had diffused into the sample due to leukocyte counts (leukocytosis).89 In one case, a
cooling now results in a falsely elevated PaO2. patient with leukemia and a leukocyte count of
Surprisingly, blood gases drawn in plastic 276,000 cells/mm3 blood (normal leukocyte
syringes remain more stable within the first count is 6000 to 10,000 cells/mm3) showed a
30 minutes at room temperature as compared decline in PaO2 from 130 to 58 mm Hg in 2 min-
to iced samples.34 Therefore, if plastic syringes utes.89 The phenomenon of leukocyte larceny
are used and samples will be run within was unveiled after several patients with leukemia
30 minutes, they need not be iced. presented with unexplained hypoxemia. The
On the contrary, samples that are not likely term pseudohypoxemia has also been used to
to be run within 30 minutes or known to have describe the spuriously decreased PaO2.100
increased oxygen consumption (e.g., leukocy- In an extraordinary case, a 57-year-old man
tosis or thrombocytosis), should be iced imme- with leukemia and a leukocyte count of
diately and a glass syringe should be used for 450,000 cells/mm3 had a PaO2 of 0 in four
sampling. This same procedure should be used repeated blood samples from an arterial line.90
when high PaO2s are expected (as in the oper- Apparently, all the O2 in the blood sample was
ating room) or when determining the P(A-a)O2 consumed by the rapid metabolism of the
gradient. numerous immature leukocytes. Much of this

An arterial puncture is drawn on a 44-year-old ARTERIAL BLOOD GASES

woman who is notably cyanotic and diaphoretic. SaO2 75%
She is on a nasal cannula at 2 L/min. An experienced pH 7.53
technician noted that he observed a flash of blood PaCO2 28 mm Hg
upon entry into the artery and the syringe auto-filled. PaO2 40 mm Hg
The results of the blood gas and vital signs are [HCO3] 26 mEq/L
shown. A physician is notified of the blood gas results by
telephone. After reviewing the results, the physician
VITAL SIGNS
responds These must be venous gasesnormal venous
B/P 145/96 mm Hg PO2 is 40 mm Hg. What is your response?
RR 30/min
HR 116/min ASSESSMENT
Temp 39 C Abnormalities: List abnormal data and other noteworthy
SpO2 77% information.
consumption of O2 undoubtedly occurred at 37 C, this reading would almost double at

after the blood sample left the patients body; 47 C.92 A more modest increase in tempera-
however, the actual PaO2 in the patients blood ture from 37 to 39 C would increase arterial
may also have been very low. PO2 less markedly, from 100 to 110 mm Hg.93
The quantitative blood gas changes second- An increase in temperature would similarly
ary to metabolism shown in Table 3-7 are based increase arterial PCO2 values. Arterial blood
on normal blood conditions and cell counts. In
severe leukocytosis (e.g., leukemia) or thrombo-
cytosis, blood gas values change much more Body temperature (F)
quickly.89,91 Therefore, samples from patients 87.8 91.4 95 98.6 102.2 105.8 109.4
with these disorders should be drawn in glass 1.4
on
syringes, then iced and analyzed immediately. 1.3 cti
re
1.2 cor
tion
Correction factor
rec
2
Alterations in Temperature 1.1 PO cor
O 2
As stated previously, blood gas values should 1.0 PC
be measured under standardized BTPS condi- 0.9
tions because they are affected by temperature 0.8
changes. To ensure that blood gas values are
actually measured at 37 C, blood samples 0.7
are warmed through a water bath or similar
mechanism that is integral to the analyzer. 31 33 35 37 39 41 43
Obviously, failure to heat the sample to precisely Body temperature (C)
37 C leads to incorrect results.
Figure 3-7. Blood gas temperature correction
Quantitative Effects of Alterations in Temperature nomogram. Nomogram for correction of PO2 and
PCO2 from temperature of blood gas analyzer
The direct physical relationship between (37 C) to patients body temperature. Read PO2
temperature and pressure results in higher or PCO2 correction factor at patients body tempera-
arterial PO2 and PCO2 readings at higher ture and multiply by measured PO2 or PCO2.
temperatures (Fig. 3-7). Although normal adult (Correction for PO2 from Severinghaus; for PCO2
arterial PO2 is approximately 100 mm Hg from Kelam and Nunn.)
Table 3-8. EFFECTS OF TEMPERATURE ON physical relationship between temperature and

NORMAL BLOOD GASES pressure. They fail to account for the metabolic
Temperature (C) PO2 PCO2 pH and cardiovascular changes that accompany a
change in a patients temperature.93 For exam-
37 80 40 7.40 ple, an increase in body temperature of 1 C
39 90 44 7.37 increases the O2 requirements by 10%.2 What
30 54 30 7.50 PaO2 value is required to meet this demand?
From Walton, J. R., and Shapiro, B. A.: Value and Thus, although one can correct blood gas
application of temperature compensated blood gas data values for the direct physical effects of temper-
(Response to question). Respir. Care, 25:260, 1980. ature on partial pressure very easily, the target
blood gas values for therapy are unclear.
Notwithstanding the aforementioned, many
with normal PCO2 (40 mm Hg) at 37 C would laboratories continue to report temperature-
show a PCO2 level of 62 mm Hg at 47 C.92 corrected values,95 most likely because many
A slight rise in temperature from 37 to 39 C automated blood gas machines can readily
would increase PCO2 from 40 to 44 mm Hg.93 make these corrections. In my opinion, this
Arterial PCO2 increases approximately 5% per exercise does not provide us with more mean-
degree Celsius rise.88 An increase in arterial ingful information on which to base treatment
PCO2 also leads to a decrease in pH. The decisions. For example, the corrected data may
pH generally decreases 0.03 unit for every 2 C lead to a false sense of security in the febrile
increase in temperature.88 patient if the PaO2 is in the acceptable range
Just as an increase in temperature leads of 80 to 100 mm Hg because of the higher
to higher gas partial pressures, a decrease in temperature.96
temperature lowers gas pressure readings. In conclusion, temperature correction of
An arterial PO2 of 100 mm Hg at 37 C would blood gas data for clinical application is not
be 50 mm Hg at 27 C.94 A clinically accept- currently recommended.93,95,9799 The correc-
able arterial PO2 of 60 mm Hg at 37 C would tion of temperature may be important in
read 37 mm Hg at 30 C.94 Similarly, the par- research or academic exercises, but it is proba-
tial pressure of CO2 decreases from 40 mm Hg bly not useful in clinical application of blood
at 37 C to 30 mm Hg at 30 C, and the pH gases. Blood gases should be interpreted at
simultaneously increases from 7.40 to 7.50.93,95 37 Ca temperature at which there is a sense
The effects of both cooling and warming on of normalcy and appropriateness.9397,99 It is
normal blood gas values are compared in especially important that if temperature-
Table 3-8. adjusted results are reported, the report should
be clearly labeled as such, and results at BTPS
Correction of Temperature of Blood Gases should also be reported.65,241
Figure 3-7 can be used to approximate meas-
ured PO2 and PCO2 for the patients tempera- Machine Temperature Error
ture, and another nomogram is available to The blood gas machine must also be moni-
correct for pH90; however, their use is contro- tored carefully to ensure that blood is actually
versial.88,9396 NCCLS advocates the use of being warmed to 37 C. The absence of tem-
specific formulas (see reference 241) if blood perature control can lead to grossly inaccurate
gases are to be temperature corrected. In addi- reports (see Fig. 3-7). Older machines used
tion, if temperature-adjusted values are water baths to heat samples to BTPS. In these
reported, BTPS values must be simultaneously cases, the water bath temperature needed to be
reported to allow the clinician to make knowl- frequently monitored. Newer machines use dif-
edgeable clinical decisions.241 ferent techniques. Regardless of the technique,
The problem with temperature corrected the temperature should be maintained within
values is that normal blood gases at these 0.1 of 37 C.241 The manufacturers litera-
various temperatures are unknown. The ture should be reviewed to understand limita-
nomogram in Figure 3-4 corrects for only the tions with each machine.
Table 3-9. SUMMARY PREANALYTICAL ERRORS NUTS AND BOLTS

Sampling Error Effect Clinical Implications
Air in syringe or icing plastic syringes PaO2 * expel air bubbles immediately
PaCO2 * do not agitate syringe
pH * discard samples with froth
Venous sample or contamination PaO2 * avoid femoral artery
PaCO2 * use short-beveled needle
pH * watch for flash and auto-filling
Anticoagulant type or concentration PaO2 * use 1/1000 U/mL
PaCO2 * lithium heparin best
pH * minimize amount liquid heparin
Metabolic effects PaO2 * ice samples not run in 30 min
PaCO2 * use glass syringe if concerned
pH * run samples as soon as possible
References: 14, 15, and 65. (See list at end of text.)
Summary of Sampling Errors electrolyte values (see Fig. 3-6) especially

Table 3-9 provides a summary of the effects of ionized calcium.1 Liquid anticoagulants reduce
blood gas preanalytical error on sample ionized calcium in three ways: solution dilu-
results. Key clinical considerations are likewise tion, calcium binding, and calcium distor-
noted for each of the types of sampling errors. tion.102 The higher the concentration of the
heparin, the more calcium binding will
occur.241 Dry (lyophilized) heparin does not
MEASUREMENT OF BLOOD GASES
dilute the blood significantly but requires
AND ELECTROLYTES FROM A
sufficient time and mixing for dissolution and
SINGLE SAMPLE
proper anticoagulation.103,241
It is becoming increasingly popular to measure The electrolyte measurement problems asso-
both blood gases and electrolytes from a single ciated with liquid anticoagulants have been
sample of arterial blood. This makes good minimized by the use of dry balanced heparin.1
sense from the standpoint of blood conserva- Balanced heparin is a preparation that includes
tion, timeliness, and diagnostic value. Many physiologic amounts of calcium and other elec-
blood gas machines now provide the ability to trolytes to mitigate electrolyte error; however, it
measure routine blood gas parameters, elec- does not completely eliminate calcium distor-
trolytes (i.e., sodium, potassium, chloride, and tion.102 Even when using dry balanced heparin
ionized calcium), and other blood values (i.e., with 50 IU heparin pledgets, sample volume
glucose, hematocrit, hemoglobin, lactate) from should still exceed 0.6 mL and the syringe
a single sample. Thus, when blood gas samples should be at least half-filled to avoid potential
are obtained, potential technical errors associ- dilution errors.153154 Other forms of commer-
ated with the measurement of these other ana- cially available heparin include calcium-titrated
lytes must also be understood. or low sodium-titrated heparin.
There are several potential errors that may Other non-heparin anticoagulants have also
occur if routinely handled blood gas samples been evaluated for use in this regard such as the
are also used to measure electrolytes. In general, selective thrombin inhibitor, D-phenylalanyl-
these errors are most often due to anticoagu- L-prolyl-L-arginine chloromethyl ketone, also
lants or transporting/icing the sample. known as PPACK.101 PPACK has been shown
to be an ideal bias-free anticoagulant.101 A
Anticoagulant Errors drawback of PPACK is its expense but this
The use of simple liquid sodium or liquid would likely change if it was manufactured in
lithium heparin as an anticoagulant will lower larger quantities.
Transporting/Icing Samples potassium14 concentration and decreased ion-

Intracellular potassium is approximately 23 ized calcium. These changes may also occur if
times higher in concentration as compared to blood is vigorously mixed or if the heel is
the extracellular space. Therefore, anything squeezed while acquiring a capillary sample.104
that disturbs the stability of blood samples Potassium measurements may also increase
(e.g., pneumatic tube systems, centrifuging, or slightly following exercise or when measured
icing) has a tendency to cause hemolysis and at noon or evening.241 Ionized calcium will
spuriously increased potassium measurements. decrease in the presence of alkalosis.
Falsely increased potassium measurements In summary, samples to be used for both
may be seen in fasting individuals or after pro- blood gas and electrolyte analysis should be
longed setting of a sample. In contrast, ionized handled carefully and not iced. Un-iced
calcium tends to decrease with hemolysis samples will remain relatively stable if ana-
because intracellular Ca is about one-thousandth lyzed within 30 minutes.34 Failure to measure
of blood ionized calcium. within this time will also lead to falsely
Placing blood samples in ice water may also increased lactate measurements. As always,
lead to blood trauma, hemolysis, and changes manufacturer recommendations should be
in electrolyte measurements. As described pre- carefully reviewed and adhered to because
viously, hemolysis will result in an increased each machine may have unique considerations.
EXERCISES
Exercise 3-1 Basic Physics of Gases

1. The constant random motion of gas molecules is called ______.

2. Define pressure.
3. The force exerted by molecules of water in the air is called ______.
4. Atmospheric pressure may be measured with an instrument called a ______.
5. Atmospheric pressure at sea level is ______.
6. Atmospheric pressure is (increased/decreased) above sea level.
7. State Daltons law.
8. The energy of motion of gas molecules is called ______ energy.
9. The fractional concentration of a gas in a mixture of gases (will/will not) change with
changes in humidity and water vapor pressure.
10. The fractional concentration of a gas (will/will not) change at different altitudes.
11. State what the symbol FIO2 stands for.
12. Calculate the partial pressure of gases given the following:
Total Pressure Fractional Concentration Water Vapor Pressure
a. 760 mm Hg 0.21 47 mm Hg
b. 700 mm Hg 0.21 47 mm Hg
c. 700 mm Hg 0.50 20 mm Hg
d. 800 mm Hg 0.30 27 mm Hg
e. 500 mm Hg 1.00 17 mm Hg
13. State Gay-Lussacs law.

14. Define BTPS conditions at sea level.
15. At sea level, atmospheric air saturated with humidity at body temperature exerts a partial
pressure of oxygen of ______ mm Hg.
16. State Henrys law regarding the partial pressure of gases in liquids.
17. State whether pressure, temperature, or volume is constant in the following gas laws:
Charles law, Boyles law, Gay-Lussacs law.
18. The blood gas symbol for arterial is (a/A); symbols related to measurements made on the
blood are usually (lowercase/capital) letters.
19. The two major processes responsible for the difference between atmospheric and alveolar
air are ______ and ______.
20. Relative humidity is a measure of ______ humidity divided by ______ humidity.
Exercise 3-2 Air in Blood Gas Samples

1. Blood gas values in arterial samples (are/are not) very stable.

2. Generally, the most pronounced blood gas change associated with exposure of the
sample to a large air bubble is:
a. decreased PaCO2
b. change in pH
c. change in PaO2
3. Drawing a blood gas sample under anaerobic conditions means that the sample (is/is not)
exposed to air.
4. Which of the following two factors seems to have the greatest impact on the effects of air
bubbles on blood gas samples?
a. Duration of exposure
b. Size of air bubble
5. An air bubble affects PaO2 most if the initial PaO2 of the sample is (greater than/less than)
100 mm Hg.
6. Given the initial PaO2 values that follow, determine whether the measured PaO2 increases
or decreases when a large air bubble is introduced into the sample.
a. 40 mm Hg
b. 100 mm Hg
c. 250 mm Hg
d. 80 mm Hg
e. 180 mm Hg
7. A blood gas sample containing froth (is/is not) acceptable.
8. Blood gas samples remain relatively stable if air bubbles are discarded
within ______ minutes.
9. An air bubble always tends to (increase/decrease) blood PCO2.
10. An air bubble always tends to (increase/decrease) blood pH.
Exercise 3-3 Venous Sampling or Admixture

1. Mixture of a small amount of venous blood with an arterial sample (will/will not) significantly
alter the blood gas values obtained.
2. Blood gas samples thought to contain some venous blood should be (discarded/run quickly).
3. (Short/Long) beveled needles minimize the risk of venous contamination of an arterial blood
sample.
4. A blood sample showing a PaO2 of 40 mm Hg and PaCO2 of 48 mm Hg (means/does not
necessarily mean) that the sample is venous.
5. The PO2 in all veins (is/is not) identical.
6. Mixed venous blood can be obtained only from a (peripheral vein/pulmonary artery).
7. List the normal blood gas values for mixed venous blood.
PvO2 PvCO2 SvO2
8. Inadvertent venous sampling is particularly likely when attempting to puncture the
(brachial/femoral) artery.
Exercise 3-4 Blood Gas Anticoagulation

1. The recommended anticoagulant for blood gas sampling is ______, although ______ heparin
is sometimes still used.
2. The concentration of sodium heparin used for blood gas anticoagulation is ______ U/mL.
3. The major blood gas change associated with excessive volume of heparin is ______.
4. The pH of arterial blood (is/is not) usually significantly altered by the use of excessive
heparin.
5. The major effect of heparin on blood gas values is usually via a (chemical/dilution) effect.
6. Hematocrit and hemoglobin measured from a heparinized arterial sample may be falsely
(low/high).
7. Blood gas sample volumes in adults should usually exceed ______ mL.
8. As a general rule, a 1% heparin dilution lowers PaCO2 by ______%.
9. What two innovations in blood gas sampling have almost eliminated errors owing to
heparin dilution?
Exercise 3-5 Blood Gas Error Due to Metabolism

1. Metabolism (does/does not) continue in blood after it has left the body.
2. Indicate the effects of metabolism on the following parameters:
PaO2
PaCO2
pH
3. Normally, in 1 hour at body temperature, PCO2 increases approximately ______ mm Hg
and pH decreases ______.
4. (High/low) initial PaO2 values tend to drop rapidly owing to metabolism.
5. At room temperature, blood gas changes owing to metabolism occur approximately
______ as fast as they occur at body temperature.
6. Placing a blood gas sample in ice will slow metabolism to approximately ______% of the
metabolic rate at body temperature.
7. Non-iced blood gas samples should be run within ______ minutes to avoid significant error.
8. The PO2 change in an iced blood gas sample may be significant in ______ minutes when
the initial PaO2 exceeds 150 mm Hg.
9. Refrigerating blood gas samples (is/is not) an adequate substitute for placing the
sample in ice.
10. The three types of cells primarily responsible for aerobic metabolic activity in blood gas
samples are ______, ______ and ______.
11. The rapid fall in PaO2 that may occur because of leukocytosis is called ______.
12. Iced samples remain stable for ______ hours or more if the initial PaO2 is less than
150 mm Hg.
13. An elevated leukocyte count is called ______.
14. Immature leukocytes consume (more/less) O2 than mature leukocytes.
Exercise 3-6 Temperature Effects on Blood Gases

1. Measurement of blood gases at 39 C would lead to falsely (high/low) PaO2 and PaCO2
values in blood sampled from an afebrile patient.
2. Arterial PCO2 increases approximately ______% per degree Celsius temperature increase.
3. The pH generally decreases approximately ______ units/2 C increase in temperature.
4. An increase in body temperature of 1 C increases O2 requirements by ______%.
5. Although controversial, most clinicians believe blood gas data should (be/not be) corrected
to the actual patients temperature conditions.
Exercise 3-7 Summary of Potential Sampling Errors

Complete the phrases denoted by the acronym AVERT, which is a mnemonic for five common
blood gas sampling errors.
Exercise 3-8 Blood Gas/Electrolyte Specimens

1. Liquid anticoagulants used for blood gas sampling (will/will not) affect electrolyte results.
2. Heparin with electrolytes added to normal physiologic levels is called _________heparin.
3. The key consideration when using lyophilized heparin is appropriate (mixing/icing) of the
sample.
4. The selective prothrombin inhibitor __________ has been advocated as an ideal anticoagu-
lant for blood gas/electrolyte specimens.
5. Placing blood specimens in ice may (lower, elevate) potassium measurements.

1. Using any search engine, search for the following on the Internet:
medscape
PubMed
Medline
2. Perform a search at one of these sites on the subject of blood gases. How many items
were found in your query? What years did you search? Can you view the abstracts of these
articles at the site used? If possible, pick two abstracts and describe their conclusions.
NBRC Challenge 3
Please select the best answer for the following multiple-choice questions.
1. One must be especially cautious in inter- IV. Brownish coloration of blood
preting ________ in a patient with A) I, II only
leukemia. B) II, III only
A) PaO2 C) II, IV only
B) pH D) I, II, and III only
C) PaCO2 E) I, III, and IV only
D) [HCO3] (RRT EXAM NBRC MATRIX I,C,1,e)
E) [BE]
4. Temperature correction of blood
gases:
2. The effects of excessive liquid sodium I. clearly provides the optimal way
heparin on a blood gas sample are: to guide clinical decision-making.
I. related to the partial pressures of II. is only indicated when patient
the gases in the liquid. temperature exceeds 40 C.
II. related to the pH of the liquid III. is easily accomplished with most
heparin. blood gas machines.
III. related to the buffer systems in A) I only
the heparin. B) II only
A) I only C) III only
B) II only D) I, III, only
C) III only E) I, II, and III only
D) I, II, only (CRT EXAM NBRC MATRIX I,C,1,c)
E) I, II, and III only
5. Placing a blood sample in an ice-water
solution will interfere with analysis of
3. Which of the following suggest a blood blood:
gas sample may be venous? A) pH.
I. Observation of a flash of blood as B) hematocrit.
the syringe begins filling C) hemoglobin.
II. Bluish coloration of the blood D) electrolytes.
sample E) [HCO3].
III. Failure of syringe to auto-fill (RRT EXAM NBRC MATRIX 1,C,2,e)
Chapter
4
Blood Gas Electrodes and
Quality Assurance
Regarding bench blood gas analysis . . .
. . . we have identified a need to restate principles and knowledge which used to be better known to the
clinician before the elements of the apparatus disappeared from view in the interests of sophistication,
automation, and design.
Alistair A. Spence119
Outline
Blood Gas Electrodes, 82 Statistics, 93
Basic Electrical Principles, 82 Mean, 93
Voltage, 83 Standard Deviation, 93
Current, 83 Coefficient of Variation, 93
Ohms Law, 83 Principles and Materials, 94
Terminology, 83 Controls, 94
Electrochemical Cell Systems, 83 Control Limits, 94
Half-Cells, 83 Levey-Jennings Control Charts, 94
Structure and Function, 84 Westgard Rules, 96
PO2 Electrode, 84 Electrode Drift, 96
pH Electrode, 86 Types of Controls, 96
PCO2 Electrode, 88 Continuous Monitoring of Blood Gases, 103
Accuracy of Electrodes, 89 Introduction, 103
Total Quality Management, 90 Transcutaneous Techniques, 104
Quality Assurance, 91 Continuous Intra-Arterial Blood Gases, 104
Nonanalytical Error, 91 Miniature Electrode Systems, 104
Preanalytical Error, 91 Optode Technology, 104
Postanalytical Error, 91 Technical Issues in Continuous Intra-Arterial
Analytical Error, 91 Blood Gases, 105
Preventive Maintenance, 92 Ex vivo (On-Demand) Systems, 106
Calibration, 92 Summary, 106
Quality Control, 92 Point-of-Care Testing, 106
Internal Quality Control, 92 Regulations and Laboratory Accreditation, 107
External Quality Control, 92 Exercises, 107
BLOOD GAS ELECTRODES chemical measurements. Thus, a brief discus-

sion of basic terms and principles in dynamic
Basic Electrical Principles electricity is a logical starting point. More
Traditionally, the analysis of blood gas values recently, new techniques such as optodes, have
has been accomplished via electrochemical been used to determine blood gas values. These
devices commonly referred to as electrodes. devices and techniques will be explored near
The description and function of these specific the end of the chapter.
electrodes is presented later in this chapter. All Electricity is a form of energy resulting from
traditional electrodes used in blood gas analy- the flow of electrons through a substance that
sis measure changes in either electrical current is called a conductor. An energy source such as
or voltage and equate these changes with a battery or generator is necessary to provide
82
Chapter 4 Blood Gas Electrodes and Quality Assurance 83
the power for this electrical flow. The energy It follows that a 220-volt force will deliver
source may be thought of as an electron a higher current through a particular wire than
pump that has two connections or poles. One a 110-volt force. A fuse or circuit breaker is
pole has an excess of stored electrons and is designed to prevent the danger of fire and to
therefore negatively charged. This negative protect electronic circuitry from excessive elec-
pole is called the cathode. Conversely, the tron flow that may destroy it.
remaining pole has a relative shortage of elec- Consumption of electric power is measured
trons and has a net positive charge. The pole usually in watts. One thousand watts is equal
that is positively charged is called the anode. to 1 kilowatt (kW). Actual consumption of
To accomplish work, the electrons flow power is calculated by the formula
away from the negative pole, through a con- Watts = volt amp
ductor, and toward the positive pole. As the
electrons flow through the conductor, they can Terminology
accomplish work such as creating light or pro- As mentioned in the introduction, most blood
ducing heat. Electrons always flow from the gas values that are measured directly are ana-
negative pole to the positive pole. lyzed through electrodes. Thus, specific indi-
vidual electrodes measure PO2, pH, and PCO2.
Voltage
The force responsible for pumping these Electrochemical Cell Systems
electrons is called the electromotive force or In chemistry, an electrode is defined technically
potential.120 The greater the difference in elec- as an electric conductor or terminal through
tron concentration between the two poles, the which electricity enters or leaves a medium
greater is the electromotive force. The unit of such as an electrolyte solution.122 By using
measurement for electromotive force is the this terminology, an electrochemical cell is
volt. Voltage refers to electromotive potential, an apparatus that consists of two electrodes
and actual electron flow does not occur unless placed in an electrolyte solution.121,122 Similarly,
a conductor bridges the positive and negative an electrochemical cell system is an apparatus
poles. A potentiometer is an instrument that that incorporates one or more electrochemical
measures an unknown voltage by comparing it cells to measure a specific chemical species.
with a known reference voltage.122 Thus, from a chemical standpoint, all the tra-
ditional analytical devices used in blood gas
Current analysis should be referred to as electrochemical
The actual flow of electrons through a conduc- cell systems. Similarly, within each measuring
tor is called electrical current, and the term for device there would be at least two electrodes.
the unit of measurement is the ampere or amp. Nevertheless, clinically, these entire electro-
Different types of conductors conduct current chemical cell systems are referred to almost
to various degrees. Good conductors have low invariably as simply blood gas electrodes.123
electrical resistance, whereas poor conductors Therefore, this clinical terminology is used in
have high resistance. Long, thin wires are the text in an effort to promote consistency and
examples of conductors with relatively high avoid confusion in a commonly misunderstood
resistance. The unit of electrical resistance is subject. The entire measurement device is
the ohm. referred to as an electrode (e.g., PO2 electrode,
pH electrode, PCO2 electrode), and the term
Ohms Law electrode is reserved solely for this use.
Ohms law states that the electromotive force
is equal to the current times the resistance. Half-Cells
Within all blood gas electrodes are electrode
Electromotive force = current resistance
terminals (sites that chemists would refer to
In measurable terms as electrodes). An electrode terminal is a solid
site where electrons enter or leave a liquid
Voltage = amp ohm medium. Electrode terminals may consist of
Electrical
measurement
+ device
Figure 4-1. Generic electrode.

The basic components of an
electrode (electrochemical cell
system) include a battery, an
electrical measuring device, a
working half-cell, and a refer-
ence half-cell. Reference Working
half-cell half-cell
Electrolyte
solution
metal or glass. A single electrode terminal in cathode in the electrical system, whereas the sil-
contact with an electrolyte solution may also ver is positively charged and serves as the anode.
be called a half-cell. All electrodes require at If blood is then placed directly in contact
least two half-cells to function. with the two electrode terminals, the PO2 of
There are two types of half-cells: working the blood sample can be measured as described
half-cells and reference half-cells. The working in the following section.
or measuring half-cell is placed at the site
where the actual chemical analysis, work, or Electrochemical Reaction
electrochemical change takes place.121,123 The To initiate the flow of electrical current and the
reference half-cell is the standard against measurement of oxygen, the battery supplies
which the electrochemical change is compared the platinum cathode with a voltage of approx-
and measured (Fig. 4-1). imately 700 millivolts (mV).124 This voltage
A reference half-cell typically consists of a attracts oxygen molecules to the cathode where
solid metal and a solution of its salt (e.g., silver they react with water. The ensuing chemical
and silver chloride, mercury and mercurous reaction consumes four electrons and produces
chloride) attached to an electronic circuit. some hydroxyl ions (see Fig. 4-2). The con-
When the metal is in contact with its salt solu- sumed electrons, in turn, are replaced rapidly in
tion, a constant electrical potential or voltage the electrolyte solution as silver and chloride
is produced.121 react at the anode.
The net result of these reactions is a flow
Structure and Function of electrical current throughout the entire cir-
The structure and function of the three primary cuit, which is shown in Figure 4-2. The current
blood gas electrodes (PO2, pH, and PCO2) will generated will be in direct proportion to the
be explained. amount of dissolved oxygen (PO2) present
at the cathode (Fig. 4-3). An ammeter is a
PO2 Electrode device used to measure the flow of electrical
Basic Components current.
The PO2 electrode incorporates a battery and an
ammeter as the electrical components of the Polarography
electrode (Fig. 4-2).123 Wall electricity may be The direct relationship between PO2 and elec-
used in place of a battery. The electrode terminal trical current is true only when a specific voltage
in the working half-cell is usually made of plat- is applied initially to the cathode.123 The proper
inum. The electrode terminal in the reference voltage to use is determined by analyzing a
half-cell is made of silver/silver chloride. The polarogram, which is a graph that shows the
platinum is negatively charged and serves as a relationship between voltage and current at
Battery

Ammeter
Silver Platinum
anode cathode
OH

e
CI e + O2 + H2O

e
O2
O2 + 2 H2O + 4 e 4 OH
Figure 4-2. Basic electrochemistry of PO2 electrode. Oxygen is attracted to the platinum working
half-cell and reacts chemically with water. This reaction consumes electrons that are replaced in solution
by the reaction at the silver anode. The entire process results in the generation of electrical current in
proportion to the amount of oxygen present in the fluid.
a constant PO2 (Fig. 4-4). The electrode must Clark Electrode

operate on the plateau of the polarogram to The electrode shown in Figure 4-2 is not prac-
preserve the relationship between the PO2 and tical for the clinical measurement of blood PO2
the current. Thus, PO2 analysis via the oxygen because protein from the blood deposits on the
electrode is often referred to as a polaro- cathode and alters its electrical characteristics.
graphic technique of gas analysis.123 Clark introduced a clinical version of this elec-
trode in 1953. An illustration of a modern
Clark electrode is shown in Figure 4-5.
Current (amps)
Current (amps)
PO2 (mm Hg)

Voltage (volts)
Figure 4-3. Direct relationship between PO2 and
current. Figure 4-4. Polarogram.
Cathode
(platinum wire)
Glass rod
Plastic holster
Electrode housing
Anode (Ag/AgCI)
Phosphate buffer
O-ring
Sample inlet Sample outlet
Pt cathode (exposed end of wire)

O2-permeable membrane (polypropylene)
Cuvette
Glass window
Figure 4-5. Schematic illustration of a Clark electrode. A polypropylene membrane separates the platinum
cathode from the blood.
In the Clark electrode, blood is separated pH Electrode

from the electrode terminals by use of a special Electrode Function
membrane, which is permeable to oxygen and The pH electrode differs greatly from the PO2
is a good electrical insulator. Oxygen from the electrode in both structure and function.
blood can diffuse easily through the membrane Functionally, the pH electrode measures
into the electrolyte solution in which the reac- changes in voltage rather than actual electrical
tion with water can take place. The terminals current. Specifically, pH is measured by the
in the electrode are not bathed directly in potentiometric method by which an unknown
blood; they are bathed instead in a phosphate voltage is measured by comparison with a
buffer solution, and potassium chloride is known voltage and is then converted to pH.123
added.121 To accomplish this, the pH electrode
Most PO2 electrodes use polypropylene requires four electrode terminals instead of just
membranes; however, Mylar, Teflon, and poly- two, such as in the case of the PO2 electrode.
ethylene all have similar properties and may be A reference solution of known pH is placed
used.123 The membrane is usually secured on between two of the terminals to have reference
the electrode with a rubber O-ring (see Fig. 4-5). voltage to compare the unknown voltage
In addition, the actual blood sample remains in against. A single unique pH-sensitive glass
a chamber known as a cuvette where it is electrode terminal serves as a common elec-
warmed quickly to 37 C and is protected from trode terminal for both the reference solution
contamination by the air. and the solution of unknown pH (Fig. 4-6).
VOLTMETER
Common
pH-sensitive
AMPLIFIER glass
electrode
terminal
Ag/AgCI Hg/HgCI
half-cell half-cell
Reference solution Fluid with

with known pH H+ unknown pH
H+ H
+
H+ H+
Figure 4-6. A pH electrode.
This specially manufactured pH-sensitive it may be referred to as the working half-cell.

glass allows hydrogen ions to diffuse into it in Thus, the mercury/mercurous chloride (Hg/
proportion to the hydrogen ion concentration Hg2Cl2) component can be called the reference
of the fluid to which it is exposed. Because of half-cell.
the different solutions on either side of the Although not recommended here, the
glass, a net electrical potential (voltage) devel- pH-sensitive glass component is often referred
ops between the two fluids and is quantitated to as the working or measuring electrode,
at the voltmeter. and the other component is called the reference
The relationship between voltage and pH at electrode. In addition to the confusion sur-
a particular temperature is described by the rounding the term electrode, these terms are
modified Nernst equation.10 In general, for
each pH unit difference between the known
and unknown solutions, a difference of 61.5
mV develops. A special voltmeter converts
voltage to pH units based on the Nernst equa-
tion and visually displays the pH.
Actual electron flow (current) secondary to
the voltage differences between the two sides is
prevented by use of an amplifier between the Working
Reference half-cell
voltmeter and the reference solution. This ampli- half-cell
fier has high electrical resistance that prohibits Mercury
significant electrical current and this allows for Hg2Cl2
Ag/AgCl
measurement of small voltage differences.125 KCl inner electrode
Liquid
junction Reference solution (2)
Physical Components pH-sensitive glass
The physical components of a model pH elec- Test solution (1)
trode are shown in Figure 4-7. This system
Figure 4-7. Basic components of the pH electrode.
can be divided physically into two major com-
The reference calomel half-cell is on the left. The
ponents. One component has the pH-sensitive KCl diffuses slowly out to form a liquid junction
glass at the tip and a silver/silver chloride with the test solution. The potential difference
half-cell inside it. Because this component is the between the test solution (1) and the reference
site at which the actual blood comes in contact solution (2) is read on a voltmeter calibrated in
with the outer surface of the pH-sensitive glass, pH units.
even more misleading because the measuring would not be at body temperature and would
electrode contains the reference solution. be exposed to air.
Furthermore, the silver or silver chloride per se The modern, compact, pH electrode (Sanz
is not a working half-cell. electrode) facilitates pH measurement at 37 C
The reference half-cell shown in Figure 4-7 with a small blood sample and is accomplished
includes an electrode terminal made of mer- by drawing the blood sample into a pH-sensitive
cury coated with mercurous chloride. The term glass capillary tube. A membrane at the end of
calomel is often used for this type of electrode the capillary tube then connects the blood sam-
terminal. The calomel electrode terminal inter- ple to a large reservoir liquid junction and the
faces with a platinum wire that transmits the calomel half-cell.
change in voltage to the voltmeter.
The calomel electrode terminal is slightly PCO2 Electrode
sensitive and would be damaged if it were in Electrode Function
direct contact with blood. Therefore, it is sep- The PCO2 electrode (shown in Figure 4-8) is a
arated from blood samples by creating a salt or modified version of the pH. In the PCO2 elec-
contact bridge. The salt bridge is typically a trode, however, blood does not come in direct
potassium chloride (KCl) solution that is sepa- contact with the pH-sensitive glass. Rather,
rated from the blood by a thin membrane. The blood comes in contact with a CO2 permeable
calomel electrode terminal is used because it membrane. The membrane may be made of sil-
functions best with KCl. The salt bridge may icone rubber, Teflon, or a similar substance
also be called the liquid junction. that is readily permeable to CO2.
On the other side of the membrane is a
Sanz Electrode bicarbonate solution that is in direct contact
Although blood could be sampled in a pH elec- with the pH-sensitive glass. The bicarbonate
trode similar to the one shown in Figure 4-7, solution is also in contact with a silver/silver
this particular configuration presents several chloride (Ag/AgCl) electrode terminal. Thus,
problems. This system would require a large the PCO2 electrode actually has two Ag/AgCl
blood sample volume. Furthermore, the blood electrode terminals within it. No salt bridge is
VOLTMETER
Common
pH-sensitive
AMPLIFIER glass
electrode
terminal
Ag/AgCI Ag/AgCI
half-cell half-cell
Reference solution Bicarbonate

with known pH H+ solution
H+ H+
H+ H+ + HCO3 H2CO3 H2O + CO2
Silicone
membrane
Blood CO2
Figure 4-8. PCO2 electrode. The CO2 from the blood diffuses through the silicone membrane into the
bicarbonate solution. The hydrolysis reaction occurs in the bicarbonate solution and results in the produc-
tion of hydrogen ions in proportion to the amount of dissolved CO2 present. The difference in voltage is
then converted to PCO2 units and is indicated on the voltmeter. Note also that both metallic half-cells in
the PCO2 electrode are Ag/AgCl.
Glass electrode
terminal shaft
Plastic holster
Electrode housing
Ag/AgCI Ag/AgCI
Sodium bicarbonate Phosphate buffer
O-ring
Sample inlet Sample outlet
pH-sensitive glass membrane

Porous spacer
CO2-permeable membrane (silicone rubber)
Cuvette
Glass window
Figure 4-9. Severinghaus PCO2 electrode.
necessary because blood is not in direct contact Accuracy of Electrodes

with the electrode terminals. A relatively high degree of precision can be
As shown in Figure 4-8, a chemical reaction expected in the analysis of arterial blood gases
occurs within the bicarbonate solution as CO2 today.10 The approximate accuracy of blood gas
diffuses in. This reaction, which is known as electrodes is shown in Table 4-1.10,123,126129
the hydrolysis reaction, results in the pro- The pH is repeatedly the most reliable and
duction of hydrogen ions and a pH change of accurate measurement. The PCO2 variation in
the bicarbonate solution. The pH change is in historical studies and reports was in the range
direct proportion to the PCO2. Thus, the cor- of 1 to 5 mm Hg.123,126130 Today, the varia-
responding voltage change can be converted tion in PCO2 should be less than 1 mm Hg.
into PCO2 units and reflected on the voltmeter.
Severinghaus Electrode Table 4-1. ACCURACY OF BLOOD GAS

The clinical PCO2 electrode is also known ELECTRODES
as the Severinghaus electrode. An illustration Parameters Values
of the structure of a Severinghaus electrode is
shown in Figure 4-9. Only a very thin layer of PO2 3 mm Hg
PCO2 1 mm Hg
bicarbonate solution is exposed to the blood
pH 0.01 units
sample.

A 51-year-old man with severe thrombocytosis has a ASSESSMENT

blood gas drawn. He is also on a pulse oximeter, which Abnormalities: List abnormal data and other noteworthy
is reading 95%. information.
Explanation: List possible diseases, pathology, or other
situations which may have lead to this patients condition
SaO2 85% or these laboratory values.
pH 7.36 Evaluation: Suggest additional data that would be useful
PaCO2 37 mm Hg in helping understand the situation or in making a
PaO2 51 mm Hg diagnosis.
[HCO3] 25 mEq/L
Older PO2 electrodes were the least accu- Depending on the particular test, we may be
rate with reports of as high as 20% inaccuracy, very concerned with accuracy, turn-around
especially at high PO2 values.10,131 Variation time, cost, simplicity, sample size, etc. All these
in PO2 had been reported to be in the range of various attributes of a particular test are
3 to 20 mm Hg at normal PO2.126129 These referred to as performance characteristics.362
inaccuracies in the PO2 electrode were due at Performance characteristics, in turn, can be
least in part to the production of hydrogen subdivided into practicability characteristics
peroxide at the cathode site. Furthermore, (e.g., sample size, speed of analysis) and relia-
gases such as carbon dioxide, halothane, and bility characteristics (e.g., precision, bias).
nitrous oxide may cause small changes in cur- Ideally, quality specifications would be avail-
rent in the system.123 able for every performance characteristic.362
Newer designs in PO2 electrodes, however, Quality specifications are the heart of a quality
continue to make this electrode more accurate. management system as shown in Figure 4-10.
Currently, PaO2 results should be expected to Note that in Figure 4-10, quality manage-
be accurate to nearly 3 mm Hg at 80 mm Hg.10 ment encompasses quality assurance, quality
improvement, and quality control. A detailed
discussion of laboratory quality management
TOTAL QUALITY MANAGEMENT
is beyond the scope of this text. Excellent
Current quality management in the laboratory resources are available from the National
is much more sophisticated and clinically ori-
ented than in the past. Quality methods and
techniques are focused on insuring that the qual- Quality Management
ity of tests performed in the laboratory allow
our clinicians to practice good medicine.362 We Quality Quality
are becoming increasingly concerned with improvement control
exactly how the laboratory results impact clini-
cal decision-making. Are they being used for Quality
diagnosis, monitoring, or identifying critical specifications
levels? This is a much broader concept and
goal than simply ensuring that test numbers
fall within specific predefined limits. Quality Quality laboratory
assurance practice
Thus, many issues and concerns that were
previously ignored in laboratory quality manage- Figure 4-10. The central role of quality specifica-
ment are now becoming increasingly important. tions in quality management.
Committee of Clinical Laboratory Standards ill individuals. These individuals cannot afford
[NCCLS], the American Association for the potential consequences of incorrect infor-
Respiratory Care, and books362 related to this mation. The incidence of this type of error may
topic. Nevertheless, some of the routine com- be reduced if the individuals who receive these
ponents in quality management within the data are knowledgeable of normal clinical
blood gas laboratory will be briefly discussed. ranges for blood gases.132 It is also very impor-
tant that the individuals receiving the data read
it back to confirm accuracy. Finally, knowl-
QUALITY ASSURANCE
edge of potentially life-threatening values for
Quality assurance is a systematic process used these parameters also helps to prevent a seri-
to monitor, document, and regulate the accu- ous error being made. Ideally, results are
racy and reliability of a procedure or labora- directly printed out from the machine at a
tory measurement. Errors in blood gases may remote location, and the potential for human
occur before, during, or after actual analysis of error is eliminated.
the sample. An error that occurs before or after In summary, blood gas results must be inter-
actual analysis (e.g., an error due to improper preted in light of the potential for both preana-
sample or data handling) is called a non- lytical or postanalytical error. Unexpected blood
analytical error. On the other hand, an error that gas results should arouse suspicion. Blood gases
occurs during the actual analysis of the sample should be repeated immediately, preferably on
(e.g., error due to performance of electrode or another instrument if: (1) they are inconsistent
technician) is called an analytical error.10,123 with the patient picture, (2) they are internally
inconsistent (see Chapter 5), (3) they are at the
Nonanalytical Error extremes of the expected range.241
Preanalytical Error A comprehensive quality assurance pro-
As described in Chapter 3, an error may be gram must address the total spectrum of blood
easily introduced into blood gas data during gas analysis to include preanalytical and post-
arterial puncture or sample handling. The sam- analytical error.
ple may be inappropriately drawn or trans-
ported. Blood gas results could be attributed Analytical Error
inadvertently to the wrong patient. A patients Analytical error includes any error that occurs
status or therapy may be incorrectly assessed during the actual analysis of the blood gases.
or recorded. Preanalytical error is likely to be Most often, analytical error is related to the
the greatest source of incorrect blood gas data. apparatus rather than to the individual and to
If left unnoticed, this error may have serious the equipment rather than to the technique.
consequences on the treatment of the patient. An example of human analytical error,
A comprehensive quality assurance program however, is failure on the part of the technician
must include clearly defined departmental pro- to properly mix the sample before it is intro-
cedures and protocols for sample acquisition duced into the electrode. Failure to mix an iced
and handling. In addition, monitoring of the sample may increase the pH of the sample by
program must ensure and document that as much as 0.11 units.123
department protocol and procedures are being Also, the technician should not record
followed. blood gas values immediately after injecting
the sample into the electrode. An adequate
Postanalytical Error exposure time is necessary to achieve sample
Recording of results after analysis may be stabilization at body temperature, ambient
associated with an error in transcription. In pressure, saturated, and to ensure complete
particular, the use of telephone reports may electrode response. Most samples achieve equi-
easily lead to serious reporting error due to a librium within 1 to 3 minutes. Two or three
breakdown in verbal communication.132 times longer may be necessary, however, if
Telephone reporting is done typically in the PCO2 is extremely low or if PO2 is extremely
critical care setting and in regard to critically high in the sample.125,133
Another source of error is inherent biologic An additional problem with the PO2 elec-
variation.362 The difference between individu- trode is that the PO2 reading is lower if a gas
als is called between-subject or inter-individual is introduced into the electrode than if a liquid
biologic variation. There are two general types is introduced into the electrode. This discrep-
of biologic variation. The difference in a given ancy has been referred to as the fluid-gas
individual is called within-subject or intra- difference,123 the blood-gas factor,10,123 or the
individual variation. Intra-individual variation stirring effect.125 A rough correction factor for
may occur during daily, monthly, or yearly the fluid-gas difference is 1.04 PO2 of the gas
cycles or during the aging process. sample.123
Nevertheless, as stated earlier, most analyti-
cal error is due to the equipment itself. Various
QUALITY CONTROL
methods must be used by the laboratory tech-
nicians to ensure that the electrodes function Quality control, concerning blood gas elec-
appropriately. These methods include preven- trodes, refers to the periodic checking of an
tive maintenance and frequent calibration. instruments performance to ensure calibration,
Quality control will be discussed in the follow- stability, and reliability. Statistical methods are
ing section. used to evaluate the accuracy and precision of
blood gas measurements. Quality control is
Preventive Maintenance probably the most controllable aspect of qual-
Proper maintenance and cleaning of blood gas ity assurance. The two major types of quality
electrodes is essential. The systems must be control systems are internal quality control and
kept free of contaminants, and the membranes external quality control.
must be carefully maintained. Most impor-
tantly, the technician must be aware of and Internal Quality Control
comply with individual manufacturer specifi- Internal quality control programs are designed
cations and recommendations for each specific to ensure that the instruments (i.e., electrodes)
instrument. within a laboratory perform with precision.
They involve routine procedures and protocols
Calibration designed to detect inconsistencies in perform-
Calibration is a procedure done on blood gas ance. Internal quality control is required by
electrodes before analyzing blood samples to most external regulatory or accreditation
establish the accuracy of readings in the antici- agencies (e.g., Joint Commission for the
pated range. Standards are gases or buffer solu- Accreditation of Healthcare Organizations
tions with precise, specific blood gas values [JCAHO], College of American Pathologists
that are used to set the machine to read linearly [CAP], Clinical Laboratories Improvement
over the physiologic range. Gases used for Amendments [CLIA]).
calibration should be extremely accurate and
should be traceable to National Institute of External Quality Control
Standards and Technology (NIST) certification. External quality control, also known as pro-
Due to the many different protocols, designs, ficiency testing, is a system by which laborato-
and recommendations of various manufactur- ries can compare the accuracy of their results
ers, no specific guidelines can be provided for with the results obtained from other labo-
routine calibration. Operators must adhere to ratories. External quality control involves the
specific manufacturers recommendations.241 distribution of identical samples from a central
The PO2 electrode is the least accurate of distribution site to participating laboratories.
the three blood gas electrodes. The wide clini- The central distribution site is a noncom-
cal range of PO2 (0 to 600 mm Hg) makes it mercial, independent agency or professional
difficult for the electrode to have a linear association.
response throughout. When high PO2 is antici- Each laboratory then runs the sample and
pated (i.e., >200 mm Hg), the system should be reports the results to the distribution center.
calibrated to 100% O2. Results reported from one laboratory are then
compared with results obtained from other The normal range is shown well by the
laboratories. Based on these data, individual bell-shaped curve described in Chapter 1 (see
discrepancies can be identified and evaluated. Fig. 1-1). The degree of dispersion (i.e., scat-
A few countries, such as the United States, tering of values from the average) in a group of
have identified performance standards that numbers can be quantitated by calculating the
laboratories must meet to maintain accredita- SD. The SD is therefore a measure of variance
tion. The US CLIA 88 report documents total around the mean. The formula for calculation
error allowable for analysis of certain analytes. of the SD is shown in Equation 4-2.
This form of regulation is known as an exter-
Equation 4-2
nal quality assessment scheme.
Finally, laboratories may perform bias stud- (x x)2
ies within their laboratory if they utilize mul-
SD = n 1
tiple machines. With this technique, the same x = mean
sample is run on different machines as an addi- x = each measurement
tional indicator of control and variability. It is = sum of
recommended that these types of studies be rou- n = number of measurements
tinely performed and recorded to detect poten-
tial quality concerns within the department. For each measurement in a series of meas-
urements, the deviation from the mean is cal-
Statistics culated (x x). Each numeric deviation is then
Some fundamental statistics must be under- squared (x x)2. Next, the mean of the squared
stood to evaluate the accuracy and precision of deviations is calculated. Finally, the square root
electrodes and thus monitor quality control. of this value is taken (see Equation 4-2). Note
There are three pertinent statistical indices: the that n 1 in Equation 4-2 is used in the
mean (x), standard deviation (SD), and coeffi- denominator in place of n and is related to
cient of variation (CV). the role that these measures play in statistical
inference.134
Mean It can be seen how the SD is a measure of
The mean is a fundamental statistic that is cal- the homogeneity or dispersion of the values. A
culated by dividing the sum of all the numbers low SD (i.e., minimal dispersion) indicates that
in a group by the number of numeric entries. the values are generally homogeneous. The SD
In lay terms, the mean is known as the average. of PaCO2 in the normal population is approx-
Mathematical calculation of the mean is shown imately 2.5 mm Hg, whereas the SD of PaO2
in Equation 4-1. is close to 5 mm Hg. Thus, the normal range
(2 SD) of PaCO2 (35 to 45 mm Hg) is more
Equation 4-1
narrow (homogeneous) than the normal range
(X 1 + X 2 + X3 + L + X n )
x= n
for PaO2 (80 to 100 mm Hg).
x = mean Coefficient of Variation

= sum of When comparing the degree of variation (i.e.,
n = number of measurements dispersion) in two groups of measurements
with sharply different means, the CV is a more
Standard Deviation appropriate statistic than the SD. Calculation
When considering results of laboratory tests, it of the CV is shown in Equation 4-3.
is important to understand the difference
between the average or mean and the normal Equation 4-3
range. The mean is a single number that best SD
CV = 100
characterizes the group. The normal range x
gives a high and low value within which 95% CV = coefficient of variation
of the normal population fall when subjected SD = standard deviation
to a particular test. x = mean
X
Principles and Materials
Controls Control limit
To perform internal quality control, samples
with known blood gas values must be run peri-
odically to ensure that the machine is operat-
ing correctly. These samples in which the true
blood gas values are known are referred to as
control samples or controls. Like any group or Control limit
population, controls have their own range of
normal limits based on 2 SDs from the mean.
Thus, control limits (control normals) can be Time
established based on this information.
Figure 4-11. Quality control limits. Quality con-
The mean and SD are typically given by
trol limits are based on the normal distribution
the manufacturer for commercial controls. curve. They are set at 2 or 3 SDs from the mean.
Nevertheless, a local mean and SD may also be Values falling outside the upper and lower limits
determined by running more than 20 control indicate that the machine is not in control.
samples through a machine over time. This
procedure provides a better local standard but
may introduce error if the machines are not This type of quality control chart was intro-
well calibrated initially. duced into clinical chemistry in the 1950s by
Controls are available with high, low, and Levey and Jennings and is still referred to as a
normal values. It has been recommended that Levey-Jennings chart.
at least two levels of controls be run within A performance record is a less sophisticated
every 8-hour shift.10 Furthermore, all three lev- form of documentation that shows the date
els of controls should be run in every 24-hour and time when controls were run and desig-
day. Because very high PaO2s may be seen in nates whether results were in acceptable limits.
some blood gases (e.g., operating room, recov-
ery room), it is often recommended that a
fourth high level PaO2 be run periodically. 115
Mean + 3s
Control Limits 110

Figure 4-11 illustrates how a quality control
Observed control concentration
chart is based on sample control limits. Actual 105

control limits may be set at 2 or 3 SDs depend-
ing on the type of test and on the significance Mean
of an abnormal finding. A chart is then devel- 100
oped with horizontal lines drawn in at the
mean and the upper and lower selected control 95
limits. Results that fall between the two con-
trol lines are in control. A measurement that 90
is right on the line is also considered to be in
control. Mean 3s
85
Levey-Jennings Control Charts
Description 5 10 15 20 25 30
The results obtained from control sample meas- Run number
urements are run and progressively plotted on Figure 4-12. Levey-Jennings chart. Levey-Jennings
a control chart (Fig. 4-12). The control chart 3 SD.
control chart with control limits set as the x
shows measured results on the y-axis versus time Concentration is plotted on the y-axis versus time
of measurement (run number) on the x-axis. (run number) on the x-axis.
Dispersion increases in frequency, however, the machine

and techniques should be evaluated carefully.
A pattern of frequent random error is shown
in Figure 4-13,A and is sometimes referred to
A as dispersion.
Systematic Error. Systematic error or bias,
Trend
on the other hand, is recurrent measurable
Reported deviation away from the mean. Trending is an
values
example of systematic error in which progres-
sive controls either increase or decrease. An
B example of a trend is shown in Figure 4-13,B.
Shift Trending may be caused by an aging electrode,
an aging mercury battery, or protein contami-
nation of the electrode.
Shifting is another form of systematic error
1234 Successive values that is characterized by a relatively abrupt
C change in measurement outcome followed by
Figure 4-13. Error patterns in quality control. clustering or plateauing in a particular area.
Examples of three common changes in quality Shifting is shown in Figure 4-13,C. A shift may
control data. A, Dispersion is seen when there is result from bubbles beneath the membrane,
an increased frequency of both high and low out- change in temperature, or contamination of
liers. B, A progressive drift of the reported values calibration standards.135
from the previous mean value is called a trend.
C, A shift occurs when there is an abrupt change Accuracy versus Precision
from the established mean value.
The various types of errors that have been
described are either problems with accuracy of
Levey-Jennings charts, on the other hand, pro- the measuring device or precision of the measur-
duce graphic outcomes that may indicate a ing device. Accuracy is a measure of how closely
particular problem or concern. the measured results reflect the true or actual
value (Fig. 4-14). If a PO2 electrode consistently
Error Patterns measures PO2 10 mm Hg lower than PO2 actu-
Random Error. Random error is character- ally is, it is inaccurate. Problems related to accu-
ized by an isolated result outside of control racy are usually characterized by systematic error.
limits, which is shown in Figure 4-12 (run no. 5). Precision, on the other hand, is an index of
A single random error has minor significance dispersion of repeated measurements. If, after
and should be disregarded. When random error repeated measurements, one electrode measured
A B C
Figure 4-14. Accuracy versus precision. Analytical accuracy and precision are illustrated by the ability
to hit a known target. A, Very good accuracy and precision. B, Poor accuracy but good precision.
C, Occasional accuracy but poor precision.
PO2 to within 5 mm Hg, whereas another Troubleshooting

electrode measured PO2 to within 10 mm Hg, Troubleshooting guides are often available from
the one with the lesser dispersion would be equipment manufacturers to help the technician
more precise. detect the problem when the electrodes are not
The analogy of shooting at a target has been in control. Electrodes are generally considered to
made to compare the difference between accu- be in control when they are accurate to within
racy and precision.130 The closeness of a par- 2 SDs of known sample values. Most of the new
ticular hit to the bulls-eye represents accuracy, automated machines have sophisticated elec-
whereas the pattern of hits indicates precision tronic and computer circuitry that provides peri-
(see Fig. 4-14). Levey-Jennings charts can like- odic self-calibration and troubleshooting.
wise reflect problems with accuracy or preci- An example of an old electrode trouble-
sion (Fig. 4-15) based on the patterns of results shooting guide is shown in Table 4-2.
obtained.
Westgard Rules
Westgard and co-workers have defined specific
criteria and related actions that should follow
Stable Accuracy Precision
performance problem, problem,
when values are found to be out-of-control
shift in mean increase in (Table 4-3).628 A single measurement outside
standard two standard deviations would warrant careful
deviation
Control limit observation (Fig. 4-16,A); however, repeated
measurements outside the norms or in the same
direction requires corrective action regarding the
sensor.
A random error of greater than 3 standard
deviations requires action (see Fig. 4-16,B).
Similarly, two consecutive measurements
Control limit
more than 4 standard deviations apart (see
Observed control concentration
Fig. 4-16,D) would likewise signal the initia-

tion of corrective measures. Finally, systematic
errors as shown in Figure 4-16, C, E, and F,
also indicate the need for immediate action.
Frequency of observations
Electrode Drift
Another indication of electrode integrity is the
degree of electrode drift. Electrode drift is the
change in the measured values as the sample
Control limit rests in the electrode. Normally, electrode drift
should not exceed 1% to 2% within 5 minutes.
The pH electrode drifts slightly to the basic
side if buffer solutions are allowed to remain in
it. Nevertheless, this drift should not exceed
0.02 units/hour.123 Electrode drift is minimized
Control limit in current blood gas systems because single
point calibrations are typically performed auto-
matically at least every 30 minutes.10
Time
Types of Controls
Figure 4-15. Problems with accuracy versus
precision. Conceptual basis of control charts. The ideal quality control material would be
Frequency distributions of control observations almost identical to blood in composition and
for different error conditions (top). Display of physicochemical behavior. A variety of control
control values versus time on a control chart materials have been used to test instrument
(bottom). performance.130,136
Table 4-2. ELECTRODE TROUBLESHOOTING GUIDES

Possible Cause Corrective Action
pH ELECTRODE
Calibration
1. Drift or incorrect calibration. Recalibrate.
2. Calibration buffers are contaminated. Use fresh solution and recalibrate instrument.
Sample Handling
1. Improper handling of controls. Introduce a new control sample.
a. Ensure that sample has been at room
temperature for 24 hours before use.
b. Shake 10 seconds to equilibrate the gas/liquid
phase.
c. Break open control sample and use within 1 minute.
2. Insufficient aspiration of sample. Introduce a new sample.
a. Check for proper suction if automatic aspiration
is used.
b. Replace pump tubing, if necessary.
c. Check seals around sample chamber.
3. Air bubble entrapment in pH measuring Introduce new sample, avoiding bubble.
electrode capillary.
4. Contamination or carry-over from a Flush system thoroughly, as manufacturer directs,
previous sample. followed by a rinse.
Electrodes
1. Protein buildup on pH glass electrode. a. Clean electrode as recommended by
manufacturer.
b. If necessary, soak electrode overnight as
manufacturer directs.
2. Concentration of KCl in salt bridge is a. Add some crystals of KCl to reference electrode
incorrect (reference electrode). if saturation is required by manufacturer.
b. If 4 molar concentration is required, replace
4 molar solution on a daily basis.
c. If KCl tablet is used, replace once a month as
d. If 20% KCl is used, replace as manufacturer directs.
3. Dehydrated glass membrane. See manufacturers instructions for rehydration of
electrode.
4. Air bubble entrapped in salt bridge of Tilt repeatedly to dislodge and remove air bubble.
reference electrode.
5. KClinsufficient amount, old or caking. Replace with fresh KCl solution according to
manufacturers directions.
6. Electrode temperature not at 37 C. a. Check level of water bath.
b. Check thermometer for break in mercury
column; replace if necessary.
c. Set instrument temperature to 37 C.
d. Allow sufficient time for instrument to fully
equilibrate to 37 C before use.
e. Check water lines leading to pH bath for
crimping or air blockage.
f. Check circulation of water by pump.
7. Defective glass electrode due to aging or Replace glass electrode.
defect (hairline crack or scratches).
8. Defective pH membrane. Replace pH membrane.
From bioMrieux, Inc., Durham, NC

Continued
Table 4-2. ELECTRODE TROUBLESHOOTING GUIDEScontd.

Electrical
1. Electrical leaks, loose connectors in pH meter. Contact manufacturer for service.
2. Open circuit. Check all lines to ensure proper connection.
Test with jumper strap as manufacturer
directs.
3. Poor grounding. Check to ensure that the instrument is properly
grounded.
4. Faulty cables, loose connectors or fittings. Check for a good fit. If any cables, connectors, or
fittings are loose or broken, contact manufacturer
for service.
5. Faulty pH meter causing a shift in calibration or Contact manufacturer for service.
nonlinear curve.
PCO2 ELECTRODE
Calibration
2. Improperly certified gas tank. Use new gas tank with maximum tolerance
of 0.05%.
3. Cooling of electrode due to rapid gas flow rate Reduce gas flow rate as manufacturer directs.
(excessive bubble/sec).
4. Idle gas lines not adequately flushed or diffusion Allow sufficient time for adequate flushing,
of room air into gas tubing lines. 5 minutes at a fast flow rate, before reducing to
proper flow rate.
5. Large adjustments in current required Clean cathode and change membrane.
during calibration.
Sample Handling
a. Be sure sample has been at room temperature
for 24 hours before use.
phase.
c. Break open control sample and use within
1 minute.
2. Insufficient aspiration of sample. Introduce a new sample.
a. If automatic aspiration is used, check for proper
suction.
3. Entrapped air bubble in measuring chamber. Remove bubble by suction, flush, and introduce
a new sample.
4. Improper or insufficient cleaning of PCO2 Clean as manufacturer directs.
system.
5. Contamination or carry-over from a previous Flush system thoroughly as manufacturer directs,
sample. followed by a rinse.
6. Room air contamination. a. Check proper syringe techniques or use
adaptor.
b. Clean aspiration tip; check for pinholes in
tubing.
c. Check for poor connections or pinholes in
internal tubing.

Electrodes
1. Protein buildup on membrane. Clean as manufacturer directs, or replace
membrane.
2. Stretched or folded membrane, or improperly Replace membrane.
installed membrane.
3. Ripped, torn, or hole in PCO2 membrane. Clean electrode tip as recommended by
manufacturer and replace membrane.
4. Protein contamination of tip of PCO2 Clean electrode tip as recommended by
electrode. manufacturer and replace membrane.
5. Improperly positioned spacer or spacer not Remove electrode, remove membrane, reposition
completely wetted. and wet spacer, and replace membrane.
6. Improper electrolyte, insufficient amount, or Remove electrode assembly, replace with fresh
old electrolyte solution. electrolyte solution to the proper level.
7. Electrode temperature not at 37 C. a. Check water level in water bath.
b. Check thermometer for break in mercury column;
replace if necessary.
e. Check circulation of water by pump.
f. Reduce gas flow rate as manufacturer directs.
8. Improperly seated electrode causing flush a. Remove and reposition electrodes.
solution or sample to remain in chamber. b. Dry with cotton swab and introduce new sample.
c. If leakage continues, call manufacturer.
9. Air bubbles entrapped beneath membrane. Remove bubbles or replace membrane.
10. Bubbles in newly refilled PCO2 electrolyte Remove electrode and gently tilt to dislodge bubbles
solution. adhering to membrane or electrode walls.
11. Dehydrated electrode due to aging or See manufacturers instruction for rehydration of
improperly hydrated electrode. electrode.
12. Defective electrode due to aging or hairline Replace electrode.
crack or scratches on electrode.
13. Room air contamination from leakage around Replace O rings and seals. If leakage persists, call
electrode. manufacturer.
Electrical
1. Poor grounding on instrument. Check to ensure that the instrument is properly
grounded.
Test with jumper strap as manufacturer directs.
3. Faulty cables, loose connectors. Check for a good fit. If any cables, connectors, or
for service.
4. Faulty meter causing a shift in calibration or Contact manufacturer for service.
a nonlinear response.
PO2 ELECTRODE
Calibration
2. Improperly certified gas tank. Use new gas tank with maximum tolerance
of 0.05%.
3. Cooling of electrode due to rapid gas flow Reduce gas flow rate as manufacturer directs.
rate (excessive bubble/sec).
Continued

4. Idle gas lines not adequately flushed or diffusion a. Allow sufficient for adequate flushing,
of room air into gas tubing lines. 5 minutes at a fast flow rate, before reducing to
proper flow rate.
b. Keep gas tanks as close to the analyzer as
possible, thus reducing the length of tubing
needed.
c. Tubing specified by manufacturer must
be used.
5. Insufficient time allowed for zero setting. Allow sufficient time for zero setting as
Sample Handling
a. Be sure sample has been at room temperature
24 hours before use.
phase.
c. Break open control sample and use within
1 minute.
2. Insufficient aspiration of sample. Introduce new sample.
a. If automatic aspiration is used, check for proper
suction.
3. Entrapped air bubble in measuring chamber. Remove bubble by suction, thoroughly flush and
introduce a new sample.
4. Contamination or carry-over from a previous Flush system thoroughly as manufacturer directs,
sample. followed by a rinse.
5. Microbial contamination; insufficient cleaning of Flush with cleaner as manufacturer directs,
PO2 system. followed by a rinse.
6. Room air contamination. a. Check proper syringe technique or use
adapter.
b. Clean aspiration tip; check for pinholes in this
tubing.
c. Check for poor connections or pinholes in
internal tubing.
Electrode
1. Protein buildup on membrane. Clean as manufacturer directs or replace
membrane.
2. Stretched, folded, or improperly positioned Replace membrane.
membrane on PO2 electrode.
3. Bubbles entrapped under PO2 membrane. Remove membrane. Clean or buff top of electrode
as manufacturer directs; rinse well, and replace
membrane.
4. Improper electrolyte, insufficient amount of old Remove electrode assembly; replace with fresh
electrolyte solution. electrolyte solution to the proper level.
5. Bubbles in newly refilled PO2 electrolyte Remove electrode and gently tilt to dislodge
solution. bubbles adhering to walls of electrode.
6. Contamination of the platinum tip of the PO2 Clean electrode tip as recommended by
electrode. manufacturer and replace membrane.

7. Electrode temperature not at 37 C. a. Check water level in water bath.

b. Check thermometer for break in mercury column;
replace if necessary.
e. Check circulation of water by pump.
f. Reduce gas flow rate as manufacturer directs.
8. Improperly seated electrode causing flush Remove and reposition electrode.
solution or sample to remain in chamber. a. Dry with cotton swab and introduce new samples.
b. If leakage continues, contact manufacturer.
9. Defective electrode due to aging or hairline Replace electrode.
crack or scratches on electrode.
10. Room air contamination from leakage around Replace O rings and seals. If leakage persists, call
electrode. manufacturer.
Electrical
Test with jumper strap as manufacturer directs.
2. Poor grounding on instrument. Check to ensure that the instrument is properly
grounded.
3. Faulty cables, loose connectors. Check for a good fit. If any cables, connectors, or
for service.
4. Faulty meter causing a shift in calibration or Contact manufacturer for service.
a nonlinear response.
Gases used for this purpose. Electrodes, however, do

Gases have been used as quality control materi- not always react to the partial pressure of a gas
als for O2 and CO2 electrodes in the past in in a gas mixture and the partial pressure of a gas
much the same way that they are used as cali- in a liquid exactly the same way. This phenome-
bration standards. Gases must always be certi- non was alluded to in the discussion of calibra-
fied regarding their contents if they are to be tion of the PO2 electrode as the blood-gas factor.
Table 4-3. FIVE WESTGARD RULES

No. of Measurements Variation Action
1 () 2 SD Closely monitor
1 () 3 SD Correct sensor
2 consecutive () 2 SD Correct sensor
4 consecutive () 1 SD Correct sensor
10 consecutive (all same side mean) Correct sensor
SD, Standard deviations.

Modified from Hicks, G. H.: Blood gas and acid-base measurement. In Dantzker, D. R., MacIntyre, N. R., Bakow, E. D.
(eds): Comprehensive Respiratory Care. Philadelphia, W. B. Saunders, 1995.
+2 SD +2 SD
_ _
X X
2 SD 2 SD
A. Random error D. Dispersion error
+3 SD
+2 SD
_ _
X X
2 SD
3 SD
E. Systematic error
B. Substantial random error
+2 SD +2 SD
_ _
X X
2 SD 2 SD
C. Systematic error F. Systematic error
Figure 4-16. Westgard Rules.
Tonometered Liquids a different manner than blood to temperature

A tonometer is a device that allows for the variations.
bubbling of a gas with a known pressure Aqueous buffers can be placed in a tonome-
through a liquid until equilibrium is reached. ter and equilibrated with gases to a particular
Tonometry is the time-tested method for partial pressure. Here again, however, the prob-
preparing controls and in some institutions lems of the aqueous buffers behaving differ-
may even be the most cost-effective method.130 ently compared with blood cannot be avoided.
The major disadvantage of tonometry is that
equilibration with the fluid takes 20 minutes Whole Blood
or longer.130 Alternatively, whole blood can be placed in the
tonometer to eliminate this problem. Never-
Aqueous Buffers theless, the problems associated with handling
Again, as described under calibration, aqueous blood products (e.g., acquired immunodefi-
(i.e., waterlike) buffers of known pH may be ciency syndrome, other infections) make this
used as controls for evaluation of the pH elec- alternative less than optimal.
trode. However, electrodes have been shown to
respond differently to buffers than to blood. Emulsions
Aqueous buffers do not contain protein. They Emulsions are substances in which two immis-
also have different actual buffering capabili- cible (non-mixable) liquids are together in
ties than blood. Finally, they may respond in solution. One of the liquids is dispersed in the

A 38-year-old woman is admitted to the emergency Explanation: List possible diseases, pathology, or other
department with severe pneumonia and a temperature situations that may have lead to this patients condition
of 41 C. or these laboratory values.
Evaluation: Suggest additional data that would be
ARTERIAL BLOOD GASES useful in helping understand the situation or in making
SaO2 85% a diagnosis.
pH 7.30
(data have been temperature-corrected to 41 C) situation.
Objective: Specifically state the measurable or
ASSESSMENT observable outcomes you would like treatment to
Abnormalities: List abnormal data and other noteworthy accomplish.
information. Action: Describe your specific plan of action.
other in the form of small droplets. Certain CONTINUOUS MONITORING OF

types of emulsions have been shown to behave BLOOD GASES
similarly to blood regarding temperature
characteristics and electrode performance. Introduction
Emulsions could be tonometered and used as Although the development of blood gas elec-
controls; however, there is little evidence that trodes has greatly enhanced the care of
this is being done. patients, traditional blood gas measurements
have distinct limitations. Specifically, they are
Comercially Prepared Controls limited by the fact that they do not provide
The final type of controls and probably the us with continuous, real-time information.
most widely used are commercially prepared Electrode technology has been restricted histori-
controls that are sometimes referred to as cally to a measurement technique. Measurement
assayed liquids. Commercial controls are pre- techniques provide the clinician with infor-
pared carefully by the manufacturer to ensure mation about an isolated point in time.
concise reproducible results. They are easy to Measurement techniques may be compared
use and eliminate the time-consuming prepara- with monitoring techniques such as an electro-
tion required by tonometry.137 cardiogram tracing. Monitoring techniques,
Aqueous commercial controls have been on the other hand, provide the clinician with
widely used in the past. Their precision for pH continuous information.
and PCO2 is good but this is not generally true Likewise, blood gases are also limited
for PO2.130 Aqueous controls are temperature- because they do not provide us with real-time
dependent and can be affected simply from the information. Typically, blood is sampled at one
heat of the technicians hand.138 point in time; then, at a later time the blood
Commercially prepared fluorocarbon-based is analyzed via the blood gas electrodes. Thus,
emulsions function more like blood than sim- blood gas information is after the fact rather
ply aqueous buffers. Fluorocarbon-based emul- than here and now. Obviously, real-time
sions are probably the best commercially information is more useful in the evaluation
prepared controls.130 and management of patients. Newer techniques
are being explored, however, that allow for One concern regarding the electrochemical
continuous, real-time monitoring of blood oxygen probe is that the membrane is suscep-
gases. tible to protein deposits or platelet adhesions.
In general, these miniature electrodes are sus-
Transcutaneous Techniques ceptible to a variety of technical problems
The skin PO2 can be monitored continuously (e.g., electrode drift, current leakage, corro-
and on a real-time basis via a transcutaneous sion); greater success has been achieved with
PO2 monitor. Skin PO2, however, is often very the use of optode technology.
different than blood PO2. Furthermore, these
monitors may be associated with complica- Optode Technology
tions (e.g., skin burns). Measurement Principles
In contrast to an electrode, an optode is a sen-
Continuous Intra-Arterial Blood Gases sor that operates via optical detection of altered
Research has continued, however, in search of light.
monitoring instruments that can continuously The primary blood gas parameters (PO2,
measure blood gases in vivo (i.e., within the pH, PCO2) alter photochemical reactions that,
body). Several types of in vivo blood gas moni- in turn, affect light transmission through fiber-
tors have been described for this application.139 optic optical fibers. Fundamentally, the change
In general, these instruments use miniature elec- in light detection is proportional to the blood
trode systems or, more commonly, optodes. gas value being measured. Most optodes oper-
ate either on the basis of light absorption or
Miniature Electrode Systems fluorescence.152
The electrochemical oxygen probe consists of a Absorbance optodes, sometimes called trans-
device that could be used to continuously mon- mission optodes, transmit light through an indi-
itor in vivo PO2.140 This probe contains a cator solution and measure the light exiting the
miniature version of the Clark electrode, and solution. The exiting light will be decreased due
the entire probe is small enough that it can be to the absorption of some of the light by the
placed within a radial artery catheter. analyte being measured. The pH or PCO2 may
These miniature electrodes, however, must be measured with this technique. A schematic
be temperature-compensated because both representation of a CO2 absorbance or trans-
PO2 and electrode current are temperature- mission based optode is shown in Figure 4-17.
sensitive variables. Corrections in temperature Fluorescence optodes, on the other hand,
may be made manually by entering the measure changes in fluorescence secondary to
patients temperature into the instrument. the analyte being measured. Fluorescence is
Alternatively, corrections in temperature may light emitted from a dye at a lower frequency
be accomplished automatically via a special (i.e., longer wavelength) immediately follow-
temperature probe attachment. ing cessation of previous light exposure.
CO2
CO2
Known CO2 Light
light measurement
CO2
CO2
Figure 4-17. CO2 Absorption/Transmission Optode.

Fluorescence
Light on
Light source
Fluorescent
and measurement
Light off dye
optode
Diminished fluorescence in
presence of oxygen
O2 O2
Light on
O2
O
O2 2
Light source O2 Fluorescent
and measurement dye with
optode O2
Light off O2 oxygen
O2
O2
O2 O2
B
Figure 4-18. O2 Fluorescence Optode.
PO2 Measurement fluid being measured by fluorescence. Like the

Certain fluorescent dyes decrease their fluores- Severinghaus electrode system, CO2 diffuses
cence in the presence of oxygen.139 Furthermore, across the membrane and changes the pH of
this decrease is in proportion to the amount of the fluid being measured. Thus, PCO2 is deter-
oxygen present. Therefore, PO2 can be determined indirectly based on the measured
mined accurately via fluorescence. A schematic change in pH.
representation of fluorescence (A) and dimin-
ished fluorescence (B) in the presence of Monitoring Systems
increased oxygen is shown in the oxygen optode The Gas Stat instrument141 was the first to use
depicted in Figure 4-18. Fluorescence systems fluorescent methods to monitor arterial and
can be made very small and require no direct venous blood gases during surgery. Values
electrical contact with the patient. obtained with the Gas Stat system correlate
well with traditional blood gases although the
pH Measurement Gas Stat PO2 is consistently higher.139 The Gas
Measurement of pH may also be accomplished Stat system may possibly be more accurate
by analyzing the fluorescent properties of cer- than standard electrodes. Standard electrodes
tain weak acids at specific light wavelengths. tend to underestimate PO2 at high PaO2 val-
The degree of dissociation of the acid can be ues, which are often seen during surgery. The
determined based on these measurements. Gas Stat system, however, is a large unit that
Ultimately, the actual pH of the solution can resides away from the patient.
similarly be determined based on the degree of
dissociation of the weak acid. Technical Issues in Continuous
Intra-Arterial Blood Gases
PCO2 Measurement The technology of continuous intra-arterial
A fluorescent CO2 detector functions much blood gas (CIABG) monitoring devices has
like the fluorescent pH sensor; however, the now reached a sophisticated level. Devices
PCO2 sensor incorporates a CO2 permeable which are currently available are quite accu-
membrane between the blood and the actual rate in arterial or venous blood even during
periods of severe blood pressure or gas monitoring techniques, such as the risk of
changes.143,144 In addition, mixed venous thrombosis or infection and also the cost.
gases can be readily monitored with these Nevertheless, these new techniques may be
devices. Continuous monitoring of mixed lifesaving in certain situations and particularly
venous PCO2 may provide useful information in neonates. The future remains uncertain for
about changes in cardiac output.144 Because a continuous in vivo blood gas analysis systems.
poor cardiac output would lead to stagnant
systemic blood and an increase in PCO2, an
POINT-OF-CARE TESTING
abrupt increase in mixed venous PCO2 may be
the first clue to cardiovascular dysfunction. A great deal has been written in the last decade
Unfortunately, however, CIABG continues regarding point-of-care (POC) laboratory test-
to be plagued with a variety of technical prob- ing. Clearly, there is clinical value in being able
lems and a relatively high technical failure to ascertain laboratory values immediately and
rate.143,145 The accuracy of PaO2 has been accurately at the bedside (i.e., the point of
especially in question after large multicenter care). In most cases, the availability of this
trials.142 The accuracy of intravascular PO2 instant information will expedite clinical deci-
optodes may be compromised by thrombosis, sion-making.148 At times it can bring about
the wall effect (reading tissue wall PO2), or more rapid changes in treatment where timing
reduced blood flow in the area of the sensor.146 is of the essence.148
Ex vivo, on-demand monitors (described sub- Furthermore, with more and more health-
sequently) that locate optodes outside the body care being delivered in alternative sites and
in an arterial line may avoid these problems. homes, portable, POC blood gas systems that
There is also a decline in sensor performance provide accurate, immediate results would be
over time and they should probably not be very beneficial. POC systems are also designed
used for more than 6 days.147 to be very customer-friendly and relatively
At present, CIABG appears to be of value in error-proof for the end user because this per-
carefully selected patient populations. son may have a limited understanding of the
Nevertheless, its invasive nature and high inci- procedure and potential mistakes. The demand
dence of technical failure are worrisome. In for POC blood gas systems has spawned the
addition, it will ultimately have to withstand a development of a variety of accurate and reli-
rigorous cost-benefit analysis. able systems.149 Many of these systems also
offer the availability of concurrent electrolyte
Ex vivo (On-Demand) Systems measurements as well.149,150 The central blood
Ex vivo (on-demand) blood gas systems are also gas laboratory should carefully monitor the
available that provide reliable, accurate, samples implementation and continued use of POC sys-
within 90 seconds and avoid some of the pitfalls tems to ensure continued quality control and
of CIABG monitors. These systems differ from performance.
CIABG in that the measurement devices (e.g., The ultimate test for POC systems will be
optodes) are located outside of the patient and their ability to provide this information accu-
samples are drawn into the measurement rately and expediently at a reasonable cost.
devices on demand typically from the radial Many clinicians continue to be skeptical of the
artery. Obviously, these are not true continuous cost-benefit ratio of these devices because they
monitoring devices but they do facilitate safe, are often somewhat more expensive to run
accurate, and expedient sample acquisition on a than traditional blood gas systems. The ques-
frequent basis (i.e., as often as every 3 minutes). tion will need to be answered: Is the difference
in turnaround time clinically significant in
Summary measurable outcomes and does it justify the
The technology now exists to measure blood incremental cost?
gases quickly (e.g., ex vivo) or monitor blood Many hybrid versions of POC blood gases
gases continuously (e.g., CIABG) in clinical have also been developed for these very reasons.
practice. Care must be taken, however, because Certainly, satellite laboratories or the use of
important issues remain regarding invasive pneumatic tubes have also become increasingly
popular. In one study, a satellite laboratory in blood gas laboratories is included in site visits
the emergency department was displaced with and inspections performed by the JCAHO.
a computerized pneumatic tube delivery system In addition, there are federal guidelines for
that proved to be cost-effective.151 Not surpris- blood gas laboratories and personnel that fall
ingly, it appears that no single solution fits under the Clinical Laboratory Improvement
every organization, department, or laboratory. Amendments (CLIA) of 1967 and 1988.
A careful detailed analysis of the procedures Many laboratories are also accredited under
and systems that work best in your institution the very detailed regulations provided by the
must be carried out. The NCCLS document CAP. Administration of a blood gas lab
on POC should be reviewed if POC testing is requires careful adherence to governmental
performed at your institution. regulations and the various accreditation bod-
ies and issues. A detailed discussion of these
regulations is beyond the scope of this book.
REGULATIONS AND LABORATORY
The reader is referred to the Internet sites in
ACCREDITATION
the Exercises at the end of this chapter.
Blood gas laboratories are subject to consider-
able oversight and regulation. Evaluation of
EXERCISES
Exercise 4-1 Basic Electrical Principles

1. A type of energy resulting from a flow of electrons is called ______.

2. A negatively charged pole in a battery or generator is called the ______, whereas the
positively charged pole is called the ______.
3. The force responsible for pumping electrons is called the ______ force.
4. The unit of measurement of electromotive potential is the (joule/ampere/volt).
5. An instrument that measures an unknown voltage by comparing it with a known reference
voltage is a ______.
6. The unit of measurement of electrical current is the (watt/volt/ampere).
7. The unit of electrical resistance is the (watt/ohm/volt).
8. Write the equation for Ohms law.
9. Electric power consumption is usually measured in (amps/watts/ohms/voltage).
10. A substance through which electrons can flow is called a ______.
Exercise 4-2 Electrodes and Terminology

1. By using proper chemistry terminology, blood gases are measured by (electrodes/electro-

chemical cell systems).
2. In this text, the term electrode refers to (an entire measuring system for one of the blood
gases/an electric conductor or terminal).
3. In this text, a solid site where electrons enter or leave a liquid medium is called an (electrode/
electrode terminal).
4. Blood gas electrode terminals may be composed of ______ or ______.
5. A single electrode terminal in contact with an electrolyte solution may also be called a
______.
6. State the two types of half-cells.
7. The half-cell where the actual electrochemical change takes place is called the ______
half-cell.
Exercise 4-3 The PO2 Electrode

1. The PO2 electrode incorporates a/an (ammeter/voltmeter).

2. The electrode terminal in the working half-cell of the PO2 electrode is usually made of
(platinum/silver).
3. The reference electrode terminal in the PO2 electrode is made of (silver chloride/calomel).
4. When voltage is applied to the cathode of a PO2 electrode, oxygen reacts with water and
(consumes/produces) electrons.
5. PO2 analysis via the oxygen electrode is often referred to as a ______ technique of gas
analysis.
6. The PO2 electrode that incorporates a semipermeable membrane to prevent contact of the
blood with the electrode terminal is called the ______ electrode.
7. Most membranes on modern PO2 electrodes are made of ______.
8. The chamber that holds the blood sample in the electrode is called the ______.
9. In the electrical system of the Clark electrode, the silver is positively charged and serves
as the (cathode/anode).
10. The PO2 is directly proportional to the electrical current only in a specific (amperage/
voltage) range.
Exercise 4-4 The pH Electrode

1. In the pH electrode, a single unique pH-sensitive, ______ electrode terminal serves as a

common electrode terminal for both the reference solution and the solution of unknown pH.
2. The pH-sensitive glass in the pH electrode is the (working/reference) half-cell.
3. There (is/is not) actual flow of electrical current in the pH electrode.
4. The pH electrode works on the (potentiometric/polarographic) principle.
5. The relationship between voltage and pH at a given temperature is described by the
modified ______.
6. One of the two major components of the traditional pH electrode has the pH-sensitive
glass at the tip and a (silver chloride/calomel) half-cell inside it.
7. The reference half-cell in the pH electrode uses a (silver chloride/calomel) electrode
terminal.
8. A calomel electrode terminal is made of ______/______.
9. A salt or contact bridge may also be referred to as a ______.
10. The (silver chloride/calomel) electrode terminal functions best in KCl solution.
Exercise 4-5 The PCO2 Electrode

1. In the PCO2 electrode, blood (does/does not) come in direct contact with the pH-sensitive
glass.
2. The CO2 permeable membrane of a CO2 electrode is often made of ______.
3. (Bicarbonate/phosphate) solution is in direct contact with the glass electrode and the silver
chloride electrode terminal in the PCO2 electrode.
4. The PCO2 electrode has (one/two) AgCl electrode terminals within it.
5. A salt bridge (is/is not) necessary in the PCO2 electrode.
6. The chemical reaction that takes place in the PCO2 electrode is known as the
(carbolysis/hydrolysis) reaction.
7. The clinical PCO2 electrode is also known as the ______ electrode.
8. The PCO2 electrode actually measures (voltage/current) change.
9. PCO2 electrodes are accurate to within ______ mm Hg.
10. The least accurate of the blood gas electrodes is the (pH/PO2/PCO2) electrode.
Exercise 4-6 Quality Assurance/Preventive Maintenance

1. Total quality management in the laboratory is currently more focused on (clinical/statistical)

decision-making with laboratory results.
2. A systematic procedure used to monitor, document, and regulate the accuracy and
reliability of a given procedure or laboratory measurement is called ______.
3. Error that occurs during the actual analysis of the blood gas sample is called ______ error.
4. Failure to mix an iced sample may raise the pH by as much as (0.3/0.1/0.05) units.
5. Most blood gas samples achieve equilibration to 37 C within ______ minutes after
introduction into the machine.
Exercise 4-7 Quality Control and Statistics

1. The periodic checking of an instruments performance to ensure calibration, stability, and

reliability is called ______.
2. External quality control is also known as ______ testing.
3. The ______ is the arithmetic average.
4. A statistical measure of the dispersion of a group of numbers is the ______.
5. In the normal population, ______% of measured values will fall within 1 SD.
6. In the normal population, ______% of measured values will fall within 2 SDs.
7. (PaO2/PaCO2) has the largest SD.
8. The higher the SD, the (more/less) homogeneous is the group.
9. The most appropriate statistic for comparison of the degree of variation between two
measurements with sharply different means is the ______.
10. Coefficient of variation is expressed in units of (%/mm Hg).
Exercise 4-8 Quality Control Charts-1

1. Samples with known blood gas values that are periodically run to ensure that the machine
is operating correctly are called ______.
2. It has been recommended that at least ______ levels of controls be run every ______
hour shift.
3. State the two general types of quality control records.
4. Quality control charts are usually referred to as ______ charts or plots.
5. Recurrent measurable deviation away from the mean is called ______ error.
6. Systematic error in which progressive controls steadily increase or decrease is called
______.
7. Systematic error characterized by an abrupt change in the measured value followed by
clustering or plateauing in the new area is called ______.
8. A single control measurement outside the normal range is called ______.
9. A pattern of frequent random error is referred to as ______.
10. A result falling right on the control line of a Levey-Jennings chart is said to be ______.
Exercise 4-9 Quality Control Charts-2

1. ______ is a measure of how closely measured results reflect the true or actual value.
2. ______ is an index of dispersion of repeated measurements.
3. Dispersion on a Levey-Jennings chart indicates a problem with (accuracy/precision).
4. Shifting on a Levey-Jennings chart indicates a problem with (accuracy/precision).
5. List two potential causes of trending.
6. Drift of the pH electrode, when buffer is left in it, should not exceed ______ units per hour.
7. Buffers remaining in the pH electrode cause (alkaline/acid) drift.
8. Electrode drift should not exceed ______% within 5 minutes.
9. (Results/time) is on the y-axis of a Levey-Jennings chart.
10. (Three/two) levels of controls should be run at least once per shift.
Exercise 4-10 Types of Controls

1. Gases (do/do not) affect electrodes in the same way that liquids affect them.
2. Aqueous buffers (do/do not) contain protein.
3. A ______ is a device that typically allows for the bubbling of a gas with a known pressure
through a liquid until equilibrium is reached.
4. The major disadvantage of tonometry is (time/expense).
5. Whole blood is less than optimal as a control because it is (inaccurate/an infectious risk).
6. ______ are substances in which two immiscible liquids are together in solution, one of the
liquids being dispersed in the other in the form of small droplets.
7. (Aqueous fluids/Emulsions) behave similarly to blood.
8. The most widely used types of controls are prepared (commercially/by tonometry).
9. The precision of aqueous commercial controls is not generally good regarding
(pH/PCO2/PO2).
10. Probably the best commercially prepared controls are ______-based emulsions.
Exercise 4-11 Continuous Blood Gas Monitoring

1. Traditionally, blood gases have been a (monitoring/measurement) technique.

2. Standard blood gases (do/do not) provide us with real-time information about patients.
3. Monitoring that is done within the body is referred to as (in vivo/in vitro).
4. The electrochemical oxygen probe uses the (Clark/fluorescence) principle.
5. In vivo electrodes (must/need not) be temperature corrected.
6. Certain fluorescent dyes decrease their fluorescence in the presence of ______.
7. Continuous monitoring of mixed venous PCO2 may provide useful information about
______.
8. The first fluorescent blood gas system used in the operating room was the (Gas Stat/CDI
1000) system.
9. Inadvertent reading of tissue wall PO2 is known as the ______ effect.
10. A blood gas system where the measurement devices are outside the patient but
constantly available at the bedside is called a/an (CIABG/ex vivo) system.

1. Please go to the site cms.hhs.gov/clia. Using the FAQ section, write a short description of:
A) CMS
B) CLIA
2. Visit the College of American Pathologists site (cap.org). Explore the laboratory accreditation
site and explain what CAP accreditation means.
3. Visit Westgard.com and describe two current issues of concern regarding quality management
systems.
NBRC Challenge 4
1. When large adjustments in current are 3. An aging electrode or protein contamina-
required during calibration of the Clark tion of the electrode will lead to a Levey-
electrode or when the system behaves Jennings pattern of:
erratically: A) shifting.
A) the cathode should be cleaned and B) trending.
the membrane should be changed. C) dispersion.
B) the anode should be de-proteinized. D) random error.
C) the water bath temperature should be E) stagnatation.
re-adjusted. (RRT EXAM-NBRC MATRIX II,B,1,h,4)
D) the current should be increased
4. When there is an increase in dispersion
gradually until readings become
of values and the standard deviation
stable.
from the mean increases, there is a
E) the potentiometer should be zeroed
problem with measurement __________.
and the measurement repeated.
A) trending
(RRT EXAM-NBRC Matrix II,B,2,h,4)
B) shifting
2. Running standardized samples from a C) accuracy
laboratory outside your institution to see D) precision
how your lab compares with others is an E) proficiency
example of: (RRT EXAM-NBRC MATRIX II,B,3,a)
I) internal quality control.
5. A blood gas PaO2 error due to the wall
II) external quality control.
effect could occur with measurements
III) monitoring equipment for precision.
made via:
IV) proficiency testing.
A) transcutaneous techniques.
A) I and III only
B) ex vivo methods.
B) II and IV only
C) CIABG.
C) I, III, and IV
D) on-demand methods.
D) II,III, and IV
E) POC systems.
E) I, II, III, and IV
(RRT EXAM-NBRC MATRIX II,B,1,h,4)
(RRT EXAM-NBRC Matrix II,B,3)
Chapter
5
Accuracy Check and Metabolic
Acid-Base Indices
Of the three variables in the H-H (Henderson-Hasselbalch) equation, any one obviously can be calculated if
the other two are known.
Charles B. Spearman591
The problem in acid-base balance has been quantitation of the metabolic, or nonrespiratory, component, as
HCO3 ion concentration is strongly dependent on the PCO2.
John W. Severinghaus588
Outline
Accuracy Check, 114 Metabolic Acid-Base Indices, 120
Internal Consistency, 115 Introduction, 120
Techniques for Evaluating Internal Shortcomings, 121
Consistency, 115 Various Indices, 121
External Congruity, 118 Pre-Blood Gas Indices, 121
Laboratory to Laboratory Congruity, 119 Blood Gas Indices, 122
Patient-Laboratory Congruity, 120 Summary, 126
FIO2PaO2 Incongruity, 120 Exercises, 126
SaO2SpO2 Incongruity, 120
ACCURACY CHECK
In most state-of-the-art blood gas laboratories,
The novice in blood gas application must mas- blood gas results are directly printed to a
ter Chapter 2 before addressing the content in report from the blood gas measurement device.
this chapter. Indeed, Chapter 5 deals with the These direct printouts preclude the possibility
less frequent and more subtle technical of human errors in transcription or oral
nuances of blood gas classification and analy- reporting. The data on direct printouts can
sis and may lead to confusion if routine blood generally be assumed to be accurate assuming
gas classification is not fully understood. This controls and safeguards discussed in previous
chapter is intended for use when the clinician chapters are adhered to. Notwithstanding,
is faced with some real or perceived inconsis- occasional errors still may occur and result in
tency in the reported information. inappropriate diagnosis or treatment if they
From an educational perspective, some are not recognized.
instructors or clinicians may prefer to skip this The present chapter is included in this text
chapter until a solid foundation of clinical for completeness, comprehensiveness, and criti-
blood gas interpretation is assured. Again, this cal analysis. Literal life-and-death decisions are
chapter addresses primarily the recognition of made based on blood gas data. Errors in the
exceptions to normal blood gas classification diagnosis or management of acid-base or oxy-
and interpretation and may be more suitable as genation status may have dire consequences.
supplementary reading, reference, or advanced Therefore, individuals who are responsible for
study. these decisions must have a thorough under-
Fortunately, the types of technical errors dis- standing of each index and the normal inter-
cussed herein are less common than in the past. relationships between them. One must be able
114
Chapter 5 Accuracy Check and Metabolic Acid-Base Indices 115

A 55-year-old man in the burn unit suffers a cardiac ASSESSMENT

arrest. Blood gases drawn during the arrest are called to Abnormalities: List abnormal data and other noteworthy
the floor and reported as shown. Due to the negative information. Classify ABG.
base excess reported, the patient is given two ampules Explanation: List possible diseases, pathology, or other
of sodium bicarbonate. situations which may have led to this patients condition.
Evaluation: Suggest additional data which would be useful
in helping understand the situation or in making diagnosis.
SaO2 91%
pH 7.52 INTERVENTION
PaCO2 47 mm Hg Importance: Prioritize concern(s) of treatment in order of
PaO2 63 mm Hg urgency and/or seriousness as you see the overall situation.
[BE] 11 mEq/L
to detect inaccurate data, or explain and inter- make sense but something doesnt seem exactly
pret seemingly inconsistent information. right. Example 5-1 may serve as an example.
Thus, at some point during the assessment
of blood gas data, the clinician should briefly Example 5-1
pause and consider the plausibility, consistency, pH 7.60
and harmony of the various recorded data. PaCO2 30 mm Hg
Assessment of the consistency of the reported [HCO3] 23 mEq/L
measurements is recommended in comprehen-
sive and systematic acid-base assessment by Example 5-1 is not internally consistent.
most experts.176 To ensure accuracy, blood gas The pH is too high given a PaCO2 of 30 mm Hg
values should be evaluated for internal consis- and essentially normal metabolic status.
tency and external congruity. Actually, the pH must be approximately 7.50.
Failure to detect this inconsistency could
Internal Consistency have undesirable diagnostic or therapeutic
Techniques for Evaluating Internal Consistency consequences. A pH of 7.60 indicates severe
Most often, gross inspection of blood gases alkalemia and should be cause for serious
facilitates the detection of internal inconsisten- concern. A pH of 7.50 is common in the inten-
cies. Conceptually, acidemia (i.e., pH < 7.35) sive care unit and most often requires no
cannot be present in the absence of a causative intervention.
acidosis (i.e., PaCO2 > 45 mm Hg and/or The following discussion explores four
[HCO3] < 22 mEq/L). Likewise, alkalemia can- methods that can be used to assess internal
not occur without alkalosis. Another type of consistency when errors may be more subtle.
gross inconsistency might be the presence of a These methods are indirect metabolic assess-
normal pH with concurrent respiratory and ment, the rule of eights, the modified
metabolic acidosis. Here again, this combina- Henderson equation, and an acid-base map.
tion of circumstances is impossible. Once the All of these methods make use of the principle
basic relationship between acidosis and acidemia that the three acid-base components (i.e.,
is understood, most gross errors in blood gas pH, PaCO2, and [HCO3] or alternatively [BE])
data are easily and readily recognized. are interrelated such that if two components
Occasionally, technical error is less obvious. are known, the third component can be
In these cases, the blood gas values generally deduced.
Indirect Metabolic Assessment Table 5-2. IMPORTANT LANDMARKS OF ACUTE

The metabolic tendency (e.g., presence of PaCO2pH RELATIONSHIP
metabolic acidosis or metabolic alkalosis) can PaCO2 pH
actually be determined without ever looking at
a metabolic index. Indirect metabolic assess- 20 7.60
ment is based on the principle that any change 25 7.55
in pH must be a result of either the metabolic 30 7.50
or the respiratory component because these 35 7.45
40 7.40
components are the two sole factors that deter-
50 7.34
mine pH. If pH has changed and it is not of res-
60 7.28
piratory origin, it must be due to a metabolic 70 7.22
acid-base change. 80 7.16
90 7.10
Acute PaCO2pH Relationship
To simplify these relationships for a moment,
assume that all metabolic factors are normal
and constant. Under these circumstances, any PaCO2 decreases 10 mm Hg (i.e., from 40 to
deviation of pH from normal must be a result 30 mm Hg), pH increases 0.10 or from 7.40 to
of a change in respiratory status. If it was 7.50. Conversely, if PaCO2 increased acutely
known exactly how much a given acute change to 50 mm Hg, the expected pH (assuming nor-
in PaCO2 would alter pH, then the precise pH mal metabolic tendency) would be 7.34.
that would be present with a given PaCO2 Important landmarks in the relationship
could be predicted. between PaCO2 and pH are shown in Table 5-2.
Assuming normal, constant metabolic status, It may be useful for the clinician to memorize
the amount that pH will change in response to these relationships. When a more precise cal-
a given PaCO2 change is constant and is culation is desired, specific calculation of the
termed the acute PaCO2pH relationship. The expected pH for any PaCO2 can also be
acute PaCO2pH relationship for both increases accomplished by application of the formulas
or decreases in PaCO2 is shown in Table 5-1. shown in Box 5-1.
A different pH change factor is necessary for
a decrease in PaCO2 than for an increase in Indirect Metabolic Status
PaCO2 because of the logarithmic nature of After the expected pH has been calculated for
these relationships. a given PaCO2, it can be compared with the
actual pH on the blood gas report as a means
Expected pH of indirect metabolic assessment. Because the
Using a pH of 7.40 and a PaCO2 of 40 mm Hg acute PaCO2pH relationship holds true only
as our baseline, the expected pH that would when metabolic status is normal, if actual pH
result from a specified change in PaCO2 is equal to the expected pH it can be concluded
could thus be calculated. For example, if that metabolic status is, indeed, unchanged
and normal.
Table 5-1. ACUTE PaCO2pH RELATIONSHIP Box 5-1 Calculation of Expected pH

PaCO2 Change pH Change
IN HYPOCARBIA
DECREASE INCREASE Expected pH = 7.40 + (40 mm Hg PaCO2)
1 mm Hg 0.01 0.01
10 mm Hg 0.10
IN HYPERCARBIA
INCREASE DECREASE
1 mm Hg 0.006 Expected pH = 7.40 (PaCO2 40 mm Hg)
10 mm Hg 0.06 0.006
On the other hand, it is likewise true that if 30 mm Hg is 7.50. Therefore, in a patient with
the actual pH is not equal to the expected pH, this PaCO2 level and normal metabolic status,
the metabolic status cannot be normal. This is one would expect to find an actual pH within
intuitively correct because any alteration in pH 0.03 of 7.50.
that is not of respiratory origin must be meta- The patients actual pH in Example 5-1 is
bolic. The clinician should understand that 7.60, which is much higher than expected.
indirect metabolic assessment is only an Therefore, the patient must also have a con-
approximation (albeit a very good one) and comitant metabolic alkalosis based on the
that very small differences between actual and acute PaCO2pH relationship. The finding of
expected pH (e.g., 0.02) can be attributed to a normal metabolic index (i.e., [HCO3] 23
slight measurement error. Blood gas electrode mEq/L) is not consistent with the indirect find-
error alone may result in discrepancies of at ing. The problem in this case could have been
least 0.01. a transcription error. The patients actual pH
For this reason, a 0.03 comparison factor should have been 7.50. A pH of 7.50 would
is recommended. Indirect metabolic assess- make these data internally consistent.
ment using this factor correlates very well with In summary, metabolic status may be accu-
metabolic assessment using the base excess of rately assessed indirectly without ever seeing
extracellular fluid [BE]ecf that is described a metabolic index. In fact, using indirect
later in this chapter. metabolic assessment, a complete blood gas
The possible outcomes of indirect metabolic acid-base classification can also be made based
assessment based on comparison of actual and on the PaCO2 and pH alone in the event that a
expected pH are defined in Table 5-3. When the metabolic index is, for some reason, unavail-
actual pH is equal to the expected pH 0.03, able. This technique is likewise a useful tool in
the metabolic status must be normal. When the attempting to validate or invalidate the inter-
actual pH is significantly more acidic than nal consistency of a questionable blood gas
expected (i.e., more than 0.03 pH units lower), a report.
metabolic acidosis must be present. Conversely, A lack of internal consistency does not indicate
when actual pH is significantly more alkaline where an error has occurred. Nevertheless, it is
(more than 0.03 pH units) than expected, a clear evidence that an error is present, and the
metabolic alkalosis (nonrespiratory condition clinician or laboratory diagnostician should be
tending to cause alkalemia) must be present. alerted with regard to the need for further
These conclusions closely parallel metabolic investigation and clarification.
diagnosis that is made directly with the [BE]ecf
to be discussed later in this chapter. Rule of Eights
The values in Example 5-1 presented earlier A similar tool for detecting technical error may
are used to show the application of indirect be referred to as the rule of eights, which provides
metabolic assessment to evaluate internal a mechanism for predicting the plasma bicar-
consistency. Based on the acute PaCO2pH bonate when the pH and PaCO2 are known. If
relationship, the expected pH for a PaCO2 of the reported bicarbonate differs significantly
from the bicarbonate calculated via the rule of
eights (e.g., >4 mEq/L difference), a technical
Table 5-3. INDIRECT METABOLIC ASSESSMENT error is likely present. To calculate the predicted
Actual pHExpected pH Indirect Metabolic plasma bicarbonate, the PaCO2 is multiplied
Relationship Status by a factor that varies with the pH. The factor
to be used with a given pH can be found in
Actual pH = expected Normal metabolic Table 5-4.
pH 0.03 status
Actual pH > expected Metabolic alkalosis Modified Henderson Equation
pH + 0.03 The Henderson equation to be described later
Actual pH < expected Metabolic acidosis
in Chapter 8 can be modified to relate [H+] in
pH 0.03
nanequivalents per liter (instead of pH) to
Table 5-4. RULE OF EIGHTS Table 5-5. RELATIONSHIP BETWEEN pH

(Factor PaCO2) = Predicted bicarbonate AND [H+]
pH Factor pH [H+] nEq/L
7.60 8/8 7.80 16

7.50 6/8 7.70 20
7.40 5/8 7.60 25
7.30 4/8 7.55 28
7.20 2.5/8
7.50 32
7.10 2/8
7.45 35
7.40 40
7.35 45
7.30 50
PaCO2 and [HCO3] as shown in Equation 5-1. 7.25 56
7.20 63
Thus, if any two of these three variables are
known the third variable can be calculated. 7.15 71
7.10 79
Equation 5-1 7.00 100
PaCO 2 6.90 126
[H + ] = 24
[HCO 3 ] 6.80 159
To apply this formula, however, one must be

able to convert pH units to hydrogen ion con-
centration in nanequivalents per liter (nEq/L). For example, if the pH is measured incorrectly,
To get an idea of how minute this unit is, the [HCO3] is also wrong (although it is inter-
a nanequivalent is one millionth of an equiva- nally consistent) because it is calculated in
lent. A milliequivalent is equal to 103 equiva- the blood gas machine based on the pH and
lents. A microequivalent is equal to 106 the PCO2.
equivalents, and a nanequivalent is equal to
109 equivalents. Acid-Base Map
There is a near-linear relationship between The acid-base map is discussed in detail in
[H+] in nEq/L and pH over the pH range (7.20 Chapter 14 (see Fig. 14-1), which addresses the
to 7.50) shown in Table 5-5. It can also be seen identification of mixed acid-base disturbances.
that this linear relationship begins to deterio- Using an acid-base map, one can easily plot
rate quickly beyond this range, especially with two acid-base variables on the map and deter-
acidemia. mine the third. When readily available, the
A pH of 7.40 is equivalent to a [H+] of 40 acid-base map is probably the easiest and most
nEq/L. As a general rule, for each 0.01 change expedient way to assess internal consistency.
in pH within the range of 7.20 to 7.50, there is
a 1 nEq/L inverse change in [H+]. Thus, a pH External Congruity
of 7.50 is equal to a [H+] of 30 nEq/L, and a In addition to assessing internal consistency,
pH of 7.30 is equal to a [H+] of 50 nEq/L. the clinician should also evaluate reported data
By converting [H+] to pH, Equation 5-1 can from other laboratories and the patients gen-
be used to check internal consistency of ques- eral appearance to ensure external congruity.
tionable blood gases. This equation is especially External congruity in this context means
useful because it can be used to determine any ensuring that all laboratory tests and observa-
of the three variables (i.e., pH, PaCO2, or tions are in concert and are harmonious with
[HCO3]) if the other two variables are known. the blood gas results. A sign of incongruity is
With regard to internal consistency, it should when blood gas numbers are not in harmony
also be pointed out that acid-base values can be with the patients appearance or other labora-
internally consistent, yet they can still be wrong. tory values. Incongruity is often the first clue
regarding incorrect and/or misleading labora- presumed to be equal to the sum of CO2 dis-
tory measurements. solved in the plasma and plasma bicarbonate,
which is shown in Equation 5-2. PaCO2 may be
Laboratory to Laboratory Congruity multiplied by the conversion factor (0.03
Calculated Bicarbonate mEq/L/mm Hg) to determine the dissolved CO2
The plasma bicarbonate can be used to evalu- concentration in mEq/L.
ate external congruency because it is most often
Equation 5-2
reported by two different, unrelated laborato- [Total CO2] = [dissolved CO2] + [bicarbonate]
ries. Plasma bicarbonate is reported routinely [Total CO2] = (PaCO2 0.03) + 24
on the arterial blood gas report. However, the 25.2 = 1.2 + 24 (mEq/L)
bicarbonate reported on the blood gas report is
not directly measured. Rather, it is a calculated
value based on the Henderson-Hasselbalch Bicarbonate Calculation from Total CO2
equation. To calculate the specific [HCO3], dissolved
CO2 in mEq/L is subtracted from the reported
Total CO2 total CO2 (see Equation 5-3). The difference
The plasma bicarbonate is also usually reported represents plasma bicarbonate in mEq/L.
from the chemistry laboratory with standard Because the concentration of dissolved CO2 in
electrolytes as total CO2 ([total CO2]). Because mEq/L is so small (typically 1 to 2 mEq/L) and
plasma [HCO3] comprises approximately 95% bicarbonate represents 95% of the total CO2
of total CO2, these two measurement may essen- value, gross inspection of the total CO2 pro-
tially be viewed as being interchangeable.176,177 vides a reliable estimation of plasma bicarbonate
One caveat is that total CO2 is measured in the even without this calculation.
chemistry laboratory using venous blood, which
Equation 5-3
is typically 2 to 3 mEq/L higher in bicarbonate. [Total CO2] [dissolved CO2] = [bicarbonate]
Nevertheless, total CO2 is, for all practical 25.2 (PaCO2 0.03) = [bicarbonate]
purposes, an index of plasma bicarbonate. 25.2 1.2 = 24 (mEq/L)
Therefore, the electrolyte report may be used
as a crosscheck regarding the accuracy of the Keeping in mind the difference between
[HCO3] reported on the blood gas report. arterial and venous blood bicarbonate, gross
Historically, total CO2 was introduced as a differences (e.g., >5 mEq/L) should arouse sus-
clinical metabolic acid-base index before the picion of erroneous measurements from one of
routine availability of blood gases. Today, total the laboratories. One should also be aware
CO2 is considered to have only minimal value as that the measurement of total CO2 is fraught
an isolated index because it must be interpreted with difficulty and the potential for the intro-
in the context of pH and PaCO2. Nevertheless, duction of error. Blood for total CO2 meas-
the [HCO3] can easily be approximated from the urement should be collected anaerobically
total CO2, and this value can be compared with and serum promptly separated from whole
the blood gas bicarbonate as a gross index of blood (to avoid effects of metabolism) and
external congruity. As previously stated, total stored at 4 C until analyzed. Just as in arterial
CO2 should be expected to be slightly higher samples, excessive heparin can dilute the sam-
than bicarbonate from the blood gas report ple and contaminate results. Air contami-
because it is measured from venous blood. nation is probably one of the most common
errors.176
Total CO2 Components Despite the fact that total CO2 is directly
As discussed in Chapter 8, CO2 is transported measured and bicarbonate from a blood gas
in the blood as bicarbonate, dissolved CO2, and report is a derived calculation, the blood gas
carbamino-compounds. Bicarbonate and dis- is less prone to methodologic errors and is
solved CO2 are responsible for almost all of the probably more reliable.176 Notwithstanding,
CO2 present in the blood plasma. Therefore, there should normally be a good correlation
total CO2, usually reported in mEq/L, is between these two measurements.
The clinician must also remember that For example, if a PaO2 of 300 mm Hg is
blood gases and electrolytes are very dynamic reported in a patient who is being mechanically
measurements that may change hourly and ventilated with an FIO2 of 0.4, something
even from one minute to another. Therefore, if is wrong. Either the PaO2 is incorrect or the
this crosscheck mechanism is to be used, the FIO2 is really higher than 0.4. In any event, the
blood gases and electrolytes to be compared finding of a PaO2 more than five times higher
must have been drawn in relative temporal than the percentage of inspired oxygen is
proximity. incongruent, and the source of the error must
be sought.
Patient-Laboratory Congruity
The experienced clinician is well aware of the SaO2SpO2 Incongruity
hazards of relying too heavily on laboratory The SpO2 represents the oxygen saturation read-
measurements. Any technical measurement is ing displayed by a pulse oximeter. When oxygen
subject to error. The general appearance of the saturation of arterial blood (SaO2) is also meas-
patient is a very important aspect of evaluating ured with an oximeter or a co-oximeter, these
external congruence. For example, a pH of 7.10 two values can be compared for congruency.
in an otherwise normal, active, patient should More commonly, calculated oxygen saturation
arouse suspicion. from a standard blood gas report may be com-
This concept is especially important with pared with the SpO2.
regard to oxygenation assessment and hypox- A basic understanding of the oxyhemoglo-
emia. A PaO2 of 40 mm Hg typically elicits bin dissociation curve (discussed in Chapter 7)
tachycardia, cyanosis, and respiratory distress. is also a key to evaluating external congruity.
When the patient looks remarkably different As a rule, saturation (SpO2 or SaO2) should be
than the data would suggest, the data must be approximately 90% when PaO2 is 60 mm Hg.
questioned. When one of these values is higher or lower, the
other should follow suit in the same direction.
FIO2PaO2 Incongruity For example, a PaO2 of 50 mm Hg concurrent
Most of the information in this chapter deals with an SpO2 of 95% should arouse suspicion.
with acid-base errors rather than oxygenation There are situations (described in Chapter 7)
errors for several reasons. First, more acid-base when these relationships will be slightly
data are reported with blood gases (e.g., pH, altered (i.e., shifts of the oxyhemoglobin curve),
[BE], [HCO3]) than oxygenation data (e.g., but as a rule they should remain generally
PaO2, SaO2). In addition, clinical acid-base intact.
relationships are generally more complex and less Sometimes, a discrepancy between two dif-
well understood by many clinicians. Finally, ferent techniques of saturation measurement is
the constant mathematical relationship between expected (e.g., increased COHb or metHb may
pH, [HCO3], and PCO2 facilitates the evalua- lead to falsely elevated SpO2 as compared to
tion of internal consistency. No such precise saturation measured via co-oximetry). These
mathematical relationship exists for oxygena- situations are described in more detail in other
tion indices. chapters. Notwithstanding, a discrepancy
All this does not mean that the assurance of between two measures of oxygen saturation
accurate oxygenation data is any less important. may be the first clue to erroneous values from
Indeed, a strong argument can be made that one of the sources.
these data are in fact more important. Thus,
the clinician must also be alert to the potential METABOLIC ACID-BASE INDICES
for errors in oxygenation indices. In particular,
the PaO2 on room air should not exceed Introduction
130 mm Hg even with hyperventilation. Also, In Chapter 2, a simple, straightforward method
a PaO2 that is more than five times higher than of blood gas classification was presented.
the percentage of oxygen being inspired should Although the step-by-step sequence described
also arouse suspicion. in Chapter 2 most often leads to a correct
classification, incorrect or misleading results unravel some of the mystique and confusion
may occur if PaCO2 is significantly abnormal. associated with these indices.
Example 5-2 may serve as an example.
Various Indices
Example 5-2 All metabolic indices have been introduced
pH 7.16 into clinical medicine as tools to provide infor-
PaCO2 80 mm Hg mation about the nonrespiratory component of
[BE] 4 mEq/L acid-base balance. The PaCO2 is a clear, concise
[HCO3] 28 mEq/L marker of the respiratory acid-base component.
Standard [HCO3] 20 mEq/L An increase in PaCO2 always indicates increased
[BE]ecf 0 mEq/L carbonic acid and, conversely, a decrease in
T40 standard [HCO3] 24 mEq/L PaCO2 always reflects a decrease in carbonic
acid levels in the arterial blood. The search for
It should be noted that three new metabolic a comparable metabolic index has been fraught
indices have been introduced in this example: with confusion and controversy that persists
standard [HCO3], T40 standard [HCO3], and even presently.
[BE]ecf. The value and significance of these
indices as well as those presented earlier are PreBlood Gas Indices
explored in the following sections. Even before the routine availability of arterial
Based on the previous discussion of internal blood gases, clinicians were well aware of the
consistency, it would appear that the blood gas usefulness of plasma bicarbonate concentration
in Example 5-2 is not internally consistent. The in assessing the metabolic acid-base component.
base excess and standard bicarbonate both indi- They understood that the [HCO3] would tend
cate a laboratory metabolic acidosis, whereas to increase in metabolic alkalosis and decrease
the plasma bicarbonate indicates a laboratory in metabolic acidosis through the buffering
metabolic alkalosis. To further confuse the mechanism. Furthermore, the more severe the
issue, the [BE]ecf and the T40 standard [HCO3] metabolic acidemia, the lower the [HCO3]
suggest normal metabolic acid-base status. It would be.
turns out, however, that all the values reported
on this blood gas are correct. CO2 Combining Power
The CO2 capacity, often referred to as the CO2
Shortcomings combining power, was described in 1917 by
The reason that some metabolic indices point Van Slyke.178 Venous blood was equilibrated
in opposite directions is related to flaws or with 5.5% CO2 after removing the red blood
artifacts in the indices themselves. Many meta- cells. Then, the total CO2 content of the sepa-
bolic indices manifest distortions in the presence rated plasma was measured. Because most of the
of notable hypercapnia or hypocapnia. CO2 in plasma was in the form of bicarbonate,
In Example 5-2, the [HCO3] is falsely high this index was really an indirect measure of
as a metabolic acid-base indicator, whereas plasma bicarbonate. This outmoded index is
the standard [HCO3] and [BE]blood are falsely no longer used today.
low. The only metabolic indices that reflect
the true normal metabolic status in this Total CO2
example are the [BE]ecf and the standard Four years later in 1921, Van Slyke also
[HCO3] T40. described the total CO2.179 With this technique,
The remainder of this chapter describes the the CO2 content of true plasma or serum was
various metabolic indices that may be reported determined while taking precautions to prevent
with arterial blood gases and their individual the loss of CO2. As described earlier in this
peculiarities. Metabolic acid-base indices are chapter, this index is also a reflection of plasma
probably the most poorly understood area of bicarbonate. Total CO2 generally replaced the
clinical acid-base and blood gas application. CO2 combining power as a clinical index because
It is hoped that this discussion may help to it was much simpler to measure. Total CO2
remains a standard value reported with most Box 5-2 Effects of PCO2 Change on
routine serum electrolytes. [HCO3]
Blood Gas Indices HYPERCARBIA

Plasma Bicarbonate [HCO3] increases 1 mEq/L for 10 mm Hg PCO2
With the development of the PCO2 and pH elec- increase
trodes, the plasma bicarbonate could be calcu- HYPOCARBIA
lated easily from these measurements by using
[HCO3] decreases 1 mEq/L for 5 mm Hg PCO2
the Henderson-Hasselbalch equation. Thus, the
decrease
plasma bicarbonate concentration, [HCO3],
became a routine value reported with arterial
blood gas results. The plasma bicarbonate is
sometimes also called the actual bicarbonate. 80 mm Hg, [HCO3] will increase 4 mEq/L
Underlying Principle. As described in the (1 mEq/L for every 10-mm Hg PaCO2 increase)
discussion of buffers in Chapter 8, NaHCO3 is to 28 mEq/L. Thus, the increase in [HCO3] to
consumed in the buffering of strong fixed acids 28 mEq/L seen in Example 5-2 at the beginning
by the bicarbonate buffer system. Because of this section on metabolic indices is simply a
NaHCO3 is completely ionized, the [HCO3] result of the hydrolysis reaction. This is, in fact,
decreases in direct proportion to the amount of the [HCO3] that one would expect to find in
fixed acid buffered. Conversely, the [HCO3] any patient with an acute increase in PaCO2 to
increases in the presence of metabolic alkalosis. 80 mm Hg and no compensation. Therefore, the
Because the weak acid component of the patient in this example has no metabolic (non-
bicarbonate buffer system is carbonic acid, how- respiratory) acid-base alteration. This is a pure,
ever, this buffer system cannot buffer the excess acute, respiratory acid-base problem.
carbonic acid that would build up in a respira-
tory acidosis. Therefore, from the standpoint Standard Bicarbonate
of buffering, the [HCO3] only changes with Measurement. The effect of PCO2 on
nonrespiratory acid-base problems. Thus, it [HCO3] has prompted clinicians to seek an
would seem to be an ideal indicator of meta- alternative to this metabolic index. A logical
bolic (nonrespiratory) acid-base changes. alternative would be to place the blood sample
Hydrolysis Effect. It is indeed true that the in a tonometer and to equilibrate the sample to
plasma [HCO3] does not change as a result of a PCO2 of 40 mm Hg. This would have the
buffering in respiratory acid-base problems. effect of normalizing PCO2 within the sample
Unfortunately, however, [HCO3] changes in and thus eliminating the hydrolysis effect. This
respiratory acid-base disturbances by another procedure has in fact been used, and the result-
mechanism, the hydrolysis reaction. Because ant measurement is known as the standard
[HCO3] is one of the constituents of the hydrol- bicarbonate.
ysis reaction (see Chapter 8, Equation 4), it tends The standard bicarbonate is defined techni-
to increase in respiratory acidosis and decrease cally as the plasma bicarbonate concentration
in respiratory alkalosis via the law of mass obtained from blood that has been equilibrated
action. Thus, the plasma bicarbonate concen- at 37 C with a PCO2 of 40 mm Hg and a PO2
tration [HCO3] is not a pure metabolic index. sufficient to produce full oxygen saturation.6
As a rough guide, [HCO3] increases 1 mEq/L In VivoIn Vitro Discrepancy. This proce-
for every 10-mm Hg increase in PaCO2 above dure of standardizing the bicarbonate is done
40 mm Hg via the hydrolysis reaction180 to the sample in the laboratory under in vitro
(Box 5-2). The relationship is not linear, how- (laboratory) conditions. Unfortunately, when
ever, and when PCO2 falls 5 mm Hg below PCO2 is returned to 40 mm Hg in the patient,
normal, [HCO3] falls approximately 1 mEq/L.180 so-called in vivo conditions, a different bicar-
For example, let us assume a normal baseline bonate level results. To understand the reason
[HCO3] of 24 mEq/L and PaCO2 of 40 mm Hg for this discrepancy, the exchange of bicarbon-
in a given individual. If PaCO2 increases to ate that takes place between the plasma and
the extravascular (outside the blood vessels) fluid fluid is slightly higher (approximately 3 mEq/L)
with changes in PCO2 must be understood. than in the plasma (intravascular fluid).
Figure 5-1,A shows approximate normal Nevertheless, to show the in vivoin vitro
values for PaCO2, plasma [HCO3], and discrepancy, both intravascular and extravas-
[HCO3] of the extravascular fluid. Actually, cular [HCO3] are shown as being equal in
the [HCO3] in the interstitial (extravascular) Figure 5-1.
Extravascular
fluid
Intravascular PCO2 - 40 mm Hg
fluid [HCO3] - 24 mEq/L
[HCO3] - 24 mEq/L
A
Hypercarbia
Extravascular
fluid
Standard bicarbonate
Laboratory
sample of PCO2 - 40 Intravascular PCO2 - 85
intravascular [HCO3] - 21 fluid [HCO3] - 28
fluid
In vitro analysis
B [HCO3] - 28
Extravascular
fluid
Intravascular PCO2 - 40
fluid [HCO3] - 24
[HCO3] - 24
D In vivo effects
Figure 5-1. In vivoin vitro discrepancy in the measurement of standard bicarbonate. A, Approximate
normal values for PaCO2, intravascular plasma [HCO3], and extravascular-interstitial fluid [HCO3].
B, The effects of acute hypercarbia on [HCO3] in vivo in both intravascular and extravascular fluid spaces.
C, The results of measuring standard bicarbonate on a blood sample taken at point B. The sample is equil-
ibrated to a PCO2 of 40 mm Hg in vitro by using a tonometer, and standard bicarbonate reads below nor-
mal. The bicarbonate that was lost to the extravascular fluid is unavailable to return to the
sample. D, When PCO2 returns to normal in vivo, bicarbonate returns from the interstitial fluid and results
in a normal [HCO3].
As PaCO2 increases acutely, plasma [HCO3] purported advantage of showing the effects of
increases via the hydrolysis reaction. A portion all buffering, not just buffering done by the
of this increased bicarbonate diffuses from bicarbonate buffer system.
within the vascular fluid (i.e., within the blood Hemoglobin Dependency. Because hemo-
vessel) to the interstitial fluid. Thus, an increase globin is one of the blood buffer bases, its con-
in both plasma [HCO3] and interstitial fluid centration affects the [BB]. At normal [Hb],
[HCO3] accompanies hypercarbia and is shown [BB] is approximately 48 mEq/L.183 At a [Hb]
in Figure 5-1,B. of 8 g%, the [BB] is approximately 45 mEq/L.
When PaCO2 then quickly returns back to In contrast, at a [Hb] of 20 g%, [BB] is
normal in this individual (i.e., 40 mm Hg 50 mEq/L.183 Thus, [BB] depends on [Hb], and
in vivo), the excess bicarbonate in the extravas- normal values for [BB] are [Hb]-dependent.
cular fluid returns to the plasma and the patient Because different individuals have different
manifests a normal [HCO3] (see Fig. 5-1,D). baselines for [BB], it is not a particularly useful
If blood is drawn from the patient at the metabolic index.
point shown in Figure 5-1,B, plasma [HCO3]
is 28 mEq/L. If standard bicarbonate is to be Base Excess of Blood
measured on this same sample, it is then placed Description. A more useful way to look at
in a tonometer and is equilibrated to a PCO2 [BB] is to compare the normal [BB] for a given
of 40 mm Hg as shown in Figure 5-1,C. [Hb] with the observed [BB]. The difference
However, under these laboratory (in vitro) con- between these two values is called the base
ditions, the bicarbonate that was lost to the inter- excess of blood [BE] (Equation 5-4). Actually,
stitial fluid cannot be recaptured in the plasma. if the observed [BB] is less than the normal
Therefore, when PCO2 is returned to 40 mm Hg [BB], the [BE] is a negative value and is techni-
in vitro, a false low [HCO3] is observed. cally a base deficit. Nevertheless, it is custom-
Thus, in the presence of hypercarbia, and in ary to refer to this index as the base excess,
direct contrast to the actual bicarbonate, the regardless of the actual numeric value.
standard bicarbonate indicates a false low result.
Equation 5-4
Observed [BB] normal [BB] = [BE]
T40 Standard Bicarbonate
The T40 standard bicarbonate is an index that In VivoIn Vitro Discrepancy. Technically,
uses a nomogram to correct the standard base excess of the blood was determined orig-
bicarbonate for the in vivoin vitro discrep- inally by chemical titration. In other words,
ancy.181,182 The T40 standard bicarbonate is the milliequivalents of base or acid that had to
probably the most accurate of the bicarbonate be added or extracted from 1 L of whole blood
metabolic indices; however, it has not gained to restore a normal [BB] was measured. In clin-
widespread popularity, which is probably due ical blood gas analysis, however, the base
at least in part to the technical difficulty in meas- excess of the blood is a value acquired from a
uring or calculating standard bicarbonate T40. Siggard Anderson nomogram based on in vitro
chemical titration studies. The nomograms can
Buffer Base also correct for different [Hb].
Description. The bicarbonate buffer system These nomograms, however, were con-
is only one of the buffer systems in the blood. structed based on in vitro blood conditions.
The whole blood buffer base [BB], on the other Therefore, the [BE] is subject to the same
hand, is the sum of all the buffer bases in 1 L shortcoming as the standard bicarbonate.
of blood. Buffer base has the potential to be Some of the buffer base that diffused into the
used as a metabolic index in exactly the same extravascular fluid compartment is not recap-
way that [HCO3] is used. In other words, in tured in these in vitro titration curves.
response to buffering, [BB] decreases in the Consequently, [BE] of blood manifests false
presence of increased fixed acids (metabolic low results in the presence of hypercarbia similar
acidosis) and increases with nonrespiratory to the standard bicarbonate value. The base
(metabolic) alkalosis. Buffer base also has the excess of blood [BE] is also sometimes called
the in vitro base excess ([BE] in vitro); however excess of blood and base excess of extracellular
the term [BE] of blood or [BE]blood is recom- fluid) may be reported with the same symbol.
mended by the National Committee for The National Committee for Clinical
Clinical Laboratory Standards.6 In the presence Laboratory Standards, in their Standards for
of hypercarbia, the base excess of the blood Definitions of Quantities and Conventions
decreases roughly 1 mEq/L for every 10 mm Related to Blood pH and Gas Analysis,6 has
Hg increase in PCO2.177 suggested that this index should be called the
Unless otherwise specified, [BE] should be base excess of extracellular fluid, symbolized
assumed to be [BE]blood. The base excess of the by [BE]ecf. This practice is followed through-
blood was the metabolic index used in the clas- out the remainder of this text.
sification examples and exercises in Chapter 2. It has been found that the base excess that
would occur under in vivo conditions (e.g.,
Base Excess of Extracellular Fluid [BE]ecf) is approximately equal to the [BE] value
A better index of the change in buffer base in determined by using the base excess of the
the body would correct for shifts of bases that blood nomogram assuming an [Hb] of 5 g%.
occur under in vivo conditions between the Because the buffer line associated with an [Hb]
plasma and the interstitial fluid. In other words, of 5 g% is always used to determine [BE]ecf,
this index would reflect all of the extracellular there is really no need to know the actual [Hb]
fluid and not just the blood plasma. There is, of the patient to determine [BE]ecf.
in fact, such an index, and it is called the base pH[BE]ecf Relationship. Methods for
excess of the extracellular fluid, [BE]ecf, com- checking the internal consistency of blood gas
pared with the base excess of the blood. data were presented earlier. Hendersons equa-
Other symbols and terms that have been tion and the rule of eights were described as
used for this index include in vivo base excess techniques for ensuring accuracy when the
([BE]in vivo), standard base excess ([SBE]), plasma bicarbonate was used as the metabolic
[BE]3, and [BE]e.177 The trend in some places index. Indirect metabolic assessment was also
is to report the [BE]ecf as simply [BE].177 described and may be useful regardless of the
Unfortunately, many laboratories do not fol- metabolic index being used.
low this practice, which leads to additional One final relationship that may be useful,
confusion in that two different values (i.e., base especially for those clinicians who prefer the

A 25-year-old woman arrives in the emergency department Explanation: List possible disease, pathology, or other
in a coma. situations which may have led to this patients condition.
Evaluation: Suggest additional data which would be
ARTERIAL BLOOD GASES useful in helping understand the situation or in making
pH 7.16
[BE] blood 4 mEq/L of urgency and/or seriousness as you see the overall
[HCO3] 28 mEq/L situation.
ASSESSMENT
Table 5-6. pH[BE]ECF RELATIONSHIP acid-base status when PaCO2 is normal. When
(ASSUMING A CONSTANT PaCO2 PaCO2 is altered significantly, however, many
OF 40 mm Hg)
of these indices demonstrate artifacts. In
pH [BE]ecf (mEq/L) hypercarbia, plasma bicarbonate rises in
response to the hydrolysis reaction and the law
7.00 20 of mass action. The standard bicarbonate cor-
7.11 15 rects for PaCO2 changes in vitro but suffers
7.22 10
from in vivoin vitro discrepancies. The base
7.33 5
excess of the blood has similar drawbacks.
7.40 0
7.48 +5 Both of these indices are artificially low in the
7.55 +10 presence of hypercarbia.
7.60 +15 Standard bicarbonate T40 and base excess
7.66 +20 of the extracellular fluid correct for both
changes in PaCO2 and in vivoin vitro dis-
crepancies. Therefore, they are the most pure
[BE]ecf to the [HCO3] as a metabolic index, is metabolic indices. Overall, these indices are
the [BE]ecfpH relationship when PaCO2 is preferred when they are available.
held constant at 40 mm Hg. Table 5-6 shows Nevertheless, despite the formidable work
that for every change in [BE]ecf of 5 mEq/L, the done to find the ideal metabolic index, plasma
pH changes approximately 0.1 units. Knowledge bicarbonate and base excess of the blood are
of this relationship may also prove to be useful still probably the most common indices
in an evaluation of internal consistency. reported with arterial blood gases. The clini-
cian should understand the disadvantages of
Summary these indices in blood gas classification and
All of the metabolic acid-base indices that have interpretation. In the end, however, any of the
been used through the years share the character- indices will suffice if the clinician understands
istic that they are good indicators of metabolic their particular nuances and shortcomings.
EXERCISES
Exercise 5-1 Gross Inconsistency

Designate whether the following blood gases are mathematically consistent (C) or inconsistent (I).
pH PaCO2 [BE]
1. 7.42 28 +4
2. 7.30 40 7
3. 7.40 50 5
4. 7.25 40 0
5. 7.35 25 0
6. 7.28 60 +1
7. 7.40 50 +5
8. 7.50 30 +1
9. 7.38 30 +5
10. 7.20 25 18
Exercise 5-2 Principles of Indirect Metabolic Assessment

1. The metabolic tendency (can/cannot) actually be determined without looking at a metabolic

index.
2. The pH increases ______ units for every 10 mm Hg decrease in PCO2 acutely.
3. The pH decreases ______ units for every 10 mm Hg increase in PCO2 acutely.
4. Acute hyperventilation to a PaCO2 of 20 mm Hg results in a pH of approximately ______.
5. Acute hypoventilation to a PaCO2 of 70 mm Hg results in a pH of approximately ______.
6. If the actual pH is equal to the expected pH, it can be concluded that metabolic status is
(normal/alkalosis/acidosis).
7. When actual pH is more than 0.03 pH units lower than the expected pH, a metabolic
(alkalosis/acidosis) must be present.
8. When actual pH is more than 0.03 pH units higher than the expected pH, a metabolic
(alkalosis/acidosis) must be present.
9. If actual pH was 7.31 and the expected pH for the given PaCO2 was 7.29, metabolic status
would be considered (normal/acidosis).
10. Blood gases (can/cannot) be classified with only the PaCO2 and pH.
Exercise 5-3 Calculation of Expected pH

Calculate the expected pH for the following PaCO2 values based on the acute pHPaCO2
relationship.
PaCO2 pH
1. 50
2. 60
3. 25
4. 65
5. 20
6. 30
7. 70
8. 55
9. 22
10. 45
Exercise 5-4 Indirect Metabolic Assessment

Given the pH and PaCO2 shown below, assess the metabolic status indirectly (i.e., the expected
pH values that were calculated in the previous exercise should be compared with the actual
reported pH values).
pH PaCO2
1. 7.34 50
2. 7.30 60
3. 7.52 25
4. 7.15 65
5. 7.62 20
6. 7.56 30
7. 7.38 70
8. 7.20 55
9. 7.48 22
10. 7.34 45
Exercise 5-5 Accuracy Check by Comparing Direct and

Indirect Metabolic Status
Determine if the reported data are consistent or inconsistent by comparing the results of
indirect metabolic assessment with the value reported directly in the [HCO3] (i.e., direct meta-
bolic assessment). Note that the values for PaCO2 and pH are the same as in the previous two
exercises.
pH PaCO2 [HCO3]
1. 7.34 50 24
2. 7.30 60 31
3. 7.52 25 18
4. 7.15 65 26
5. 7.62 20 25
6. 7.56 30 30
7. 7.38 70 22
8. 7.20 55 16
9. 7.48 22 24
10. 7.34 45 29
Exercise 5-6 The Rule of Eights in Accuracy Check

Apply the Rule of Eights and label the following blood gases as consistent (C) or inconsistent (I).
pH PCO2 [HCO3]
1. 7.28 60 28
2. 7.48 56 40
3. 7.50 30 29
4. 7.20 30 20
5. 7.12 60 25
6. 7.60 40 39
7. 7.30 20 9
8. 7.58 50 30
9. 7.42 30 19
10. 7.08 70 10
Exercise 5-7 pH[H+] Conversion

Calculate the pH given the [H+] in nEq/L.
[H+] (nEq/L) pH
1. 45
2. 56
3. 32
4. 30
5. 48
6. 80
7. 60
8. 39
9. 28
10. 51
Exercise 5-8 Application of Modified Hendersons Equation

Calculate the missing variables given the following:
pH [H+] (nEq/L) PaCO2 (mm Hg) [HCO3] (mEq/L)
1. 60 30
2. 55 36
3. 45 33
4. 7.20 50
5. 40 24
6. 7.30 24
7. 20 16
8. 60 18
9. 40 30
10. 7.28 40
Exercise 5-9 Calculation of [HCO3] from Total CO2

Given the total CO2 (i.e., TCO2), calculate the plasma bicarbonate concentration (i.e., [HCO3]).
TCO2 PCO2
1. 38 60
2. 26 40
3. 18 50
4. 20 25
5. 21 35
Exercise 5-10 Metabolic Indices

1. List the two metabolic indices most often used before the routine availability of blood
gases.
2. The [HCO3] (does/does not) change in respiratory acid-base disturbances due to buffering.
3. The [HCO3] (does/does not) change in respiratory acid-base disturbances due to the
hydrolysis reaction.
4. As a rough guide, [HCO3] increases 1 mEq/L for every ______ mm Hg increase in PaCO2.
5. When PCO2 decreases ______ mm Hg, [HCO3] decreases approximately 1 mEq/L.
6. The ______ is defined technically as the plasma bicarbonate concentration obtained from
blood that has been equilibrated at 37 C with PCO2 of 40 mm Hg and a PO2 sufficient to
produce full oxygen saturation.
7. In the presence of hypercarbia, the standard bicarbonate indicates a false (high/low) value.
8. The ______ is an index that uses a nomogram to correct the standard bicarbonate for the
in vivoin vitro discrepancy.
9. The ______ is the sum of all the buffer bases in 1 L of blood.
10. The formula: (observed [BB] normal [BB] = ) is used to calculate ______.
11. [BE] of blood manifests false (low/high) values in the presence of hypercarbia.
12. The base excess of the blood is also known as (in vivo/in vitro) base excess.
13. The most accurate form of base excess is ([BE]blood/[BE]ecf).
14. The buffer line associated with an [Hb] of ______ g% is used to determine [BE]ecf.
15. For every change in [BE]ecf of 5 mEq/L, the pH changes approximately ______ units.

1. Go to NBRC.org and explain how the multiple-choice questions in this textbook relate to
their examinations.
NBRC Challenge 5
1. The following arterial blood gas is run on The PaO2 reported is 86 mm Hg. The
an emergency department patient. clinician should conclude:
pH 7.52 A) the blood gas and pulse oximeter
PaCO2 60 mm Hg readings are perfectly consistent.
[HCO3] 20 mEq/L B) the patient is normal.
PaO2 88 mm Hg C) the patient is hypoventilating.
D) the blood gas and pulse oximeter
You should conclude:
readings are incongruent.
A) the patient needs mechanical
E) the pulse oximeter can be
ventilation.
discontinued.
B) the patient needs low flow oxygen
(CRT EXAM-NBRC MATRIX I,B,10,a)
therapy.
C) the blood gas should be checked 4. A patient with otherwise normal lungs
and/or run again. is inadvertently given a respiratory
D) the primary alkalosis is respiratory stimulant. A blood gas is drawn and
and a sedative is indicated. the PaCO2 is 25 mm Hg. Before looking
E) the primary alkalosis is metabolic at the pH, one would expect it to be
and probably due to diuretic approximately:
therapy. A) 7.25
(CRT EXAM-NBRC MATRIX I,B,10,c) B) 7.35
C) 7.45
2. A patient who appears to have acute
D) 7.55
hypoventilation and is on an oxygen
E) 7.65
mask has a blood gas drawn in the emer-
(CRT EXAM-NBRC MATRIX I,C,1,e)
gency department.
pH 7.16 5. Which of the following can be concluded
PaCO2 80 mm Hg from the following arterial blood gas?
[HCO3] 28 mEq/L pH 7.16
PaO2 88 mm Hg PaCO2 80 mm Hg
[HCO3] 28 mEq/L
The blood gas indicates:
[BE] 4 mEq/L
A) complete acid-base compensation.
PaO2 72 mm Hg
B) significant acid-base compensa-
A) The [HCO3] cannot be correct.
tion by the kidney.
B) The [BE] cannot be correct.
C) a mixed acid-base disturbance.
C) The change in [BE] and [HCO3] is
D) technical error.
due to renal compensation.
E) increased plasma bicarbonate due
D) The change in [BE] and [HCO3] is
to hydrolysis.
due to hypercapnia.
(CRT EXAM-NBRC MATRIX I,B,10,c)
E) The change in [BE] and [HCO3] is
3. A patient has a pulse oximeter saturation due to chronic hyperventilation.
reading of 86 and a blood gas is ordered. (RRT EXAM-NBRC MATRIX I,B,10,c)
III
UNIT
Basic Physiology
133
Chapter
6
Oxygenation and External Respiration
Oxygenation
These two systems cooperate (respiratory and cardiovascular) to supply the needs of the tissues. One system
supplies air; the other supplies blood. Their ultimate purpose is the transfer of gases between air and all tissue
cells.
Julius H. Comroe, Jr.81
and external respiration

The prime function of the lung is to exchange gas If its (the lung) thickness were increased to 1 cm and
its relative dimensions remained the same, the interface would cover the whole of Connecticut so that its
shape is well suited to its gas exchanging function.
John B. West155
Outline
Introduction, 135 Abnormal Distribution of Pulmonary
Cardiopulmonary System, 135 Perfusion, 143
Steps in Tissue Oxygenation, 136 Abnormal Distribution of Ventilation, 145
Cardiopulmonary Interaction, 136 Ventilation-Perfusion Match, 147
Hypoxemia versus Hypoxia, 138 Deadspace and Shunting, 149
External Respiration, 138 Deadspace, 149
Ventilation, 139 Shunting, 152
Ventilation-Perfusion Matching, 139 Diffusion, 156
Normal Distribution of Pulmonary Equilibration, 156
Perfusion, 139 Surface Area, 159
Normal Distribution of Ventilation, 141 Exercises, 159
INTRODUCTION
depth and speed to meet all cellular demands;
The moment-to-moment sustenance of human consequently, the human body has evolved
life depends on a single external substance. a remarkably effective O2 delivery system that
This substance is so important that its absence facilitates the transport of atmospheric oxygen
in the environment causes irreversible damage to all cells in the body. In addition, this system
to the human condition in approximately can vary O2 delivery to match changing cellular
6 minutes. That substance is, of course, oxygen requirements.
(O2), which is essential to each of the billions It would be only partially correct to state that
of cells comprising the human body. O2 is a the respiratory system is the human physiologic
colorless, odorless gas that plays a critical role system responsible for cellular oxygenation.
in the efficient production of cellular energy. Likewise, it would be false to state that the
In its absence, production of cellular energy is cardiovascular system assumes full responsibil-
grossly inadequate, and the death of the organ- ity for cellular oxygenation in the body. Neither
ism ultimately ensues. of these systems alone can accomplish this
life-sustaining function. Rather, it is the com-
Cardiopulmonary System bined, cooperative effort of these two systems
O2 cannot directly enter all cells in the body that is required. Thus, it is valid, both concep-
from its atmospheric origin. Simply stated, O2 tually and clinically, to view these two systems
cannot penetrate into the body with sufficient as a single, integrated cardiopulmonary system
135
136 Unit III Basic Physiology
Figure 6-1. Cardiopulmonary system.
that works to accomplish the ultimate goal of volume of O2 being delivered to the tissues?).
tissue oxygenation and carbon dioxide (CO2) This step is depicted in Figure 6-2,B.
excretion (Fig. 6-1). The final link in the O2 delivery chain is the
diffusion of O2 from small systemic capillaries
Steps in Tissue Oxygenation in response to cellular metabolic needs. This
Traditionally, the complete physiologic process step, called internal respiration, involves both
of cellular oxygenation and the work of the the diffusion of O2 to the cells and its meta-
cardiopulmonary system have been divided bolic utilization by the cells (see Fig. 6-2,C).
into three steps or phases (Fig. 6-2). In step Internal respiration is defined technically as
one, ambient O2 molecules are moved from the exchange of O2 and CO2 between the sys-
their atmospheric origin to the blood supply temic capillaries and the cells or tissues. In this
within the lungs. O2 actually enters the circu- text, however, the actual metabolism that
latory system via the small blood vessels in the occurs in the cells is also considered to be part
lungs (pulmonary capillaries). O2 molecules of the process of internal respiration.
diffuse into the blood from the tiny air sacs in The common link throughout this O2 delivery
the lung known as alveoli. The exchange of O2 system is the blood and specifically the hemo-
and CO2 between the alveoli and pulmonary globin within the blood. The blood plays a pivo-
capillaries is called external respiration and is tal role in all three phases. By using the blood or
the essence of step one (see Fig. 6-2,A). hemoglobin as a focal point, the three steps in
Step two involves the quantitative transport the delivery of O2 can be thought of as simply:
of a sufficient volume of O2 from the pul- O2 loading (see Fig. 6-2,A), O2 transport (see
monary capillaries to its cellular destination. Fig. 6-2,B), and O2 unloading (see Fig. 6-2,C).
This process, which is commonly referred to as
O2 transport, requires a normal hemoglobin Cardiopulmonary Interaction
concentration as well as an adequate cardiac It is interesting and informative to observe the
output. Cardiac output may be defined as the cooperative effort exerted by the various com-
volume of blood ejected each minute from the ponents in the cardiopulmonary system. In
heart. The assessment of the adequacy of step particular, the heart and lungs often comple-
two is generally quantitative (i.e., Is a sufficient ment each other in trying to attain the goal of
Chapter 6 Oxygenation and External Respiration 137
A. External respiration B. Oxygen delivery C. Internal respiration

(O2 loading) (O2 transport) (O2 unloading)
Figure 6-2. Steps in oxygen delivery. The three steps or phases in oxygen delivery to the tissues include:
oxygen loading into the blood or external respiration (A), oxygen transport or delivery to the tissues (B),
and oxygen unloading from the blood and utilization by the tissues or internal respiration (C).
tissue oxygenation. For example, when breath- Although not really compensatory in nat-
ing is hampered and PaO2 is decreased due to ure, rapid or deep ventilation is also common
lung disease, hormones are released through in primary circulatory disturbances. Generally,
the adrenergic system that increase heart rate the heart is effective in compensating for respi-
(tachycardia) and increase blood pressure ratory oxygenation problems. Conversely, the
(hypertension). This response attempts to lungs can accomplish little when the initial
ensure that sufficient O2 reaches the cells. insult is cardiac in origin. Nevertheless, the cir-
Thus, the heart may be thought of as com- culatory and ventilatory pumps are in intimate
pensating for a respiratory deficiency. The collaboration with the common objective of
novice clinician should be aware that tachy- cellular O2 delivery.
cardia and mild hypertension may be second- Similarly, each of the three steps in cellular
ary to poor oxygenation of the blood via the oxygenation work in a cooperative manner to
lungs. ensure tissue oxygenation. For example, when
A clinical example of this concept is seen in external respiration is impaired due to chronic
the monitoring of the discontinuation of a pulmonary disease or some other condition,
mechanical ventilator from a patient. Here, mechanisms are triggered in the other two
cardiovascular parameters (e.g., pulse, electro- steps to bolster O2 delivery. O2 transport may be
cardiogram, blood pressure) are monitored to improved through the production of more red
assess if spontaneous breathing is adequate. blood cells and hemoglobin, and the cardiac
The clinician is alerted to inadequate breathing output may be increased as described above.
by cardiovascular compensatory changes that Increased red blood cells and hemoglobin due
accompany it. to a decreased arterial PO2 is a common clinical
finding in chronic pulmonary disease and is potential for irreversible organ damage. The
called secondary polycythemia. simple term hypoxia that is used in this text
In addition, the body may respond to this refers to diffuse tissue hypoxia, unless other-
problem by increasing chemical 2,3-diphos- wise stated. The foremost goal in the manage-
phoglycerate (DPG) levels. The increased DPG ment of oxygenation status is the prevention of
tends to facilitate the release of O2 from the tissue hypoxia.
blood to the cells and thus enhances cellular Severe hypoxemia (i.e., PaO2 < 45 mm Hg)
O2 delivery. Thus, here again, the concept of is highly suggestive of concurrent hypoxia. In
cooperative function is evident. lesser degrees of hypoxemia, however, hypoxia
may not be present. For example, in moderate
Hypoxemia versus Hypoxia hypoxemia (i.e., PaO2 45 to 59 mm Hg),
Hypoxemia has been defined earlier as a hypoxia often does not occur because the car-
below-normal arterial PO2. Hypoxemia is a diac output is increased and tissue O2 needs
blood condition. The term hypoxemia as used are being met. Thus, the presence of hypox-
in this text does not consider hemoglobin con- emia does not necessarily indicate the presence
centration or saturation; nor does it take into of hypoxia.
account the red blood cell count. The critical In other cases, hypoxia may be present in
question in oxygenation delivery and assess- the absence of hypoxemia. In conditions such
ment pertains not to the blood but rather to the as severe anemia or shock, the PaO2 may be
cellular O2 status. Inadequate O2 supply to the quite high; however, the tissue demands for
body tissues is called tissue hypoxia or simply O2 are not being met. Thus, hypoxia may be
hypoxia. present in the absence of hypoxemia. Although
Tissue hypoxia may be localized or general- hypoxemia and hypoxia are closely interre-
ized. Local tissue hypoxia may be seen in mus- lated, one must be careful to avoid equating
cle cells during exercise or in a specific body these distinct entities.
region that accompanies a local vascular dis-
order. Examples of local vascular hypoxia and
EXTERNAL RESPIRATION
tissue hypoxia include myocardial infarction
(i.e., heart attack) and a cerebrovascular accident The remainder of this chapter will address the
(i.e., stroke). first step in oxygenation, external respiration
Diffuse or generalized tissue hypoxia is an or oxygen loading (see Fig. 6-2,A). The normal
overall deficit of O2 throughout the body tis- function and possible pathologic changes that
sue (e.g., severe hypoxemia, low cardiac out- can occur to disrupt external respiration will
put such as in the patient with congestive heart be explored.
failure). It is of primary concern in critical care Three criteria must be met to ensure adequate
medicine to prevent diffuse hypoxia with its O2 loading via external respiration (Fig. 6-3).
Ventilation
Figure 6-3. External respiration. External

respiration requires adequate ventilation,
ventilation-perfusion matching, and diffusion.
Ventilation-
Diffusion
perfusion
match
First, an ample supply of O2 must reach the the ventilation-perfusion match. O2 loading
alveoli, which depends mainly on the ade- and CO2 excretion (i.e., external respiration)
quacy of ventilation. Ventilation is the gross can occur only in the pulmonary areas where
movement of air into and out of the lungs. a blood-air interface exists.
Second, the fresh O2 in the alveoli must be To understand the normal ventilation-
exposed to pulmonary capillary blood. This perfusion match and all the changes that can
process is often referred to as the ventilation- occur, one must understand the mechanisms
perfusion match. Finally, the ventilation- that regulate the distribution of ventilation and
perfusion interface must exist for a sufficient perfusion in the lungs. The normal distribution
time to allow for complete diffusion and of ventilation and perfusion is reviewed first
equilibration of O2. and is followed by a study of the factors
that can disrupt the normal pattern of ventila-
Ventilation tion or perfusion. Finally, the specifics of the
The total volume of oxygen that enters the ventilation-perfusion match throughout the
alveoli each minute while breathing room air lungs in health and disease are explored.
depends on the volume of alveolar ventilation.
The minute-to-minute regulation of alveolar Normal Distribution of Pulmonary Perfusion
ventilation, in turn, is controlled by the PaCO2. Gravity Dependence
Under normal circumstances, the body will The volume of blood flow is not uniform
assume sufficient ventilation to keep the PaCO2 throughout all lung segments. Rather, perfusion
in the normal range of 35 to 45 mm Hg. A is preferentially distributed to gravity-dependent
problem with ventilation is immediately recog- lung regions. Thus, in a man or woman placed
nizable because the PaCO2 will be elevated. in an upright position, the lung bases receive
the largest proportion of the cardiac output,
Ventilation-Perfusion Matching whereas the lung apices receive the least propor-
Consider for a moment a situation where the tion. When lying supine (on the back), most
volume of lung ventilation is normal, but the blood goes to the posterior lung surface while
entire volume enters the left lung. Combine this the anterior (front) surface is minimally perfused
finding with a normal volume of pulmonary (Fig. 6-4).
perfusion, but it all goes to the right lung.
Obviously, despite a normal volume of venti- Wests Zone Model
lation and perfusion, there would be no O2 West has described a three-zone conceptual
loading. model of pulmonary perfusion in which the
Although this situation is unrealistic clini- general regulation and characteristics of per-
cally, it serves to emphasize the importance of fusion are different in each zone155 (Fig. 6-5).
Figure 6-4. Gravity dependence of perfusion.

Blood flow is greatest to the most gravity-
dependent portions of the lungs. Thus, the
distribution of pulmonary perfusion depends
on the position of the body.
force available to pump blood to the upper-

most areas of the lungs.
Zone Perfusion is absent
1
In normal humans, however, even the apical
areas receive some perfusion, and technically
no zone 1 is present. Nevertheless, a decrease
Zone in blood volume, cardiac output, or right-sided
2 Perfusion is sporadic heart function could lead to the development
of pulmonary hypotension and a zone 1 phe-
nomenon in the uppermost lung regions.
Zone Zone 2. Zone 2 is a functional area where
3 Perfusion is constant
the flow of perfusion is moderate. In zone 2,
pulmonary arterial pressure is greater than
Figure 6-5. Pulmonary perfusion zones. alveolar pressure and, therefore, flow through
the capillary is initiated. Zone 2 is also charac-
terized by an alveolar pressure that exceeds
Zone 1, when it is present, is always in the pulmonary venous pressure (Pa > PA > Pv). Thus,
least gravity-dependent (uppermost) portion of flow occurs in this area because pulmonary
the lung. Conversely, zone 3 is always in the arterial pressure exceeds alveolar pressure.
most gravity-dependent (lowest) area of the Furthermore, the amount of flow depends on
lung. Of course, zone 2 is between the other the difference between the pulmonary arterial
two zones. Perfusion is absent in zone 1, spo- pressure and the alveolar pressure. Because the
radic in zone 2, and constant in zone 3. pulmonary arterial pressure is progressively
Zone 1. Zone 1 is a theoretical area of the higher as one moves toward the lower regions
lung where perfusion is nonexistent because of the lung, there is likewise a progressive
pulmonary arterial pressure is less than alveo- increase in perfusion as one moves down this
lar pressure (PA > Pa); consequently, the pul- zone (see Fig. 6-6).
monary capillary is collapsed (Fig. 6-6). The In certain areas of the lung, perfusion may
pulmonary circulation is a low-pressure system be limited by the very low pressure at the
(normal pulmonary artery pressure 25/10 mm venous end of the capillary. In these areas,
Hg) and, therefore, there is not a great deal of alveolar pressure causes the vessel to constrict
Zone 1
PA > Pa > Pv
Figure 6-6. Three-zone

pulmonary perfusion model.
In zone 1, pulmonary
Zone 2
Alveolar perfusion is absent. In zone 2,
Pa > PA > Pv
PA pulmonary perfusion is
Pa Pv intermittent, depends on the
cardiac and respiratory cycles,
Arterial and increases progressively
Venous Distance down through the zone.
In zone 3, perfusion is heavy
and constant.
Zone 3
Pa > Pv > PA
Blood flow
is not uniform. The actual distribution of ven-

tilation throughout the lungs can be explained
on the basis of regional differences in alveolar
20
compliance and airway resistance throughout
Blood flow / unit volume
the lungs. In other words, air traveling into the

lungs always follows the pathway of least
resistance and tends to flow to the alveoli with
the greatest compliance and lowest airway
10 resistance.
Gas Distribution at Functional Residual Capacity

The volume of gas remaining in the lungs
Lung following a normal exhalation is called the
bottom (Anterior rib number) Top functional residual capacity (FRC) and is
0
6 5 4 3 2 1
shown in Figure 6-8. At normal FRC, more gas
Distance resides in the upper lung zones (apices) and
less in the lung bases. As shown in Figure 6-9,
Figure 6-7. Linear perfusion pattern in the lung.
alveoli are larger in the apices and smaller in
Distribution of blood flow in the normal upright
lung.
the bases.
This regional variation in FRC volume can be
explained by regional differences in trans-
pulmonary pressure. Transpulmonary pressure
and thus to impede the flow of blood. This (PL) is the difference in pressure across the lung.
action is often called the Starling resistor or It is defined as the pressure inside the lung minus
waterfall effect. One could surmise that perfu- the pressure immediately outside the lung in
sion in zone 2 is vulnerable particularly to the the pleural space. At the alveolar level, transpul-
pressure changes that occur during the cardiac monary pressure is equal to the pressure within
and respiratory cycles. The upper lung in a the alveolus (PAlv) minus the intrapleural pres-
healthy person behaves functionally as a zone 2. sure (Ppl). Intrapleural pressure is the pressure
Zone 3. Zone 3 is the most gravity-dependent within the pleural cavity that surrounds the
lung region in which blood flow is heavy and lungs. Thus, the formula for calculating transpul-
relatively constant. Zone 3 is characterized by monary pressure is shown in Equation 6-1.
a pulmonary venous pressure that exceeds
Equation 6-1
alveolar pressure (Pa > Pv > PA).155 In zone 3, PL = PAlv Ppl
perfusion is based simply on the difference
between arterial and venous pressure, and It is common in the literature to refer to the
alveolar pressure is not important. The major- normal intrapleural pressure at rest as a single
ity of pulmonary perfusion occurs in zone 3. negative number such as (4 cm H2O).81 This is
Although the zone model may help one to slightly misleading, however, because this single
understand the functional characteristics of number is the average intrapleural pressure
pulmonary perfusion, it may sometimes be throughout the intrapleural space. Actually, the
misleading. In the actual lung, there is no clear intrapleural pressure at the base of the lung is
demarcation of lung perfusion zones. Rather, almost 8 cm H2O higher than that in the apex
there is a general, linear increase in perfusion (Fig. 6-10).155 This increase is probably related
as one moves from the apex to the base of the to the increased blood present in the bases.
lung (Fig. 6-7). Intrapleural pressure increases linearly at a rate
of approximately 0.25 cm H2O for every cen-
Normal Distribution of Ventilation timeter of distance down the lung.155
Basic Principle Alveolar size is directly related to transpul-
The distribution of ventilation throughout the monary pressure. This is because the higher the
normal lungs, like the distribution of perfusion, numeric transpulmonary pressure, the greater
Total capacity level
Inspiratory
reserve
volume Inspiratory
(IRV) capacity
Vital (IC)
capacity
(VC)
Tidal Increasing
Total volume tidal
lung (TV) volume
capacity Resting expiratory level
(TLC) Expiratory
reserve
volume Functional
(ERV) residual
capacity (FRC)
Residual Residual volume level
volume
(RV)
Figure 6-8. Lung volumes and capacities. The maximum volume of gas the lung can hold is called the
total lung capacity (TLC). The gas normally resident in the lungs between breaths is called the functional
residual capacity (FRC). The FRC consists of the residual volume (RV) and the expiratory reserve volume
(ERV). The RV cannot be exhaled even with maximal exhalation. The inspiratory capacity (IC) consists of
the inspiratory reserve volume (IRV) and the tidal volume (TV). The vital capacity (VC) is the maximum
volume that can be exhaled after a maximal inhalation.
the distending force. Conversely, a negative Figure 6-10 shows the transpulmonary
transpulmonary pressure is a net compressive pressure across the alveoli in the lung apex
force and may lead to alveolar or small airway compared with the transpulmonary pressure
collapse. The net effect of any transpulmonary across the alveoli in the lung base at normal
force depends on the actual numeric value and resting lung volume.
the forces opposing it (e.g., elastic recoil, airway
structural support). Normal Distribution of Tidal Volume
As additional air is added to the lung beyond
FRC (i.e., tidal volume [VT]), it will preferen-
tially ventilate the lung bases. At normal FRC,
compliance of basilar alveoli is greater than
compliance of apical alveoli, which are more
distended. Thus, most of the gas inhaled dur-
ing normal breathing actually ventilates the
bases (see Fig. 6-9,B). In addition, the lower
intercostal muscles and the diaphragm are dis-
placed more than the upper part of the chest
during normal inspiration, which may further
facilitate basilar expansion.156
The actual distribution of tidal ventilation
in the upright lung is shown in Figure 6-11.
A. At FRC B. Normal distribution Clearly, ventilation is greatest in the lung
of tidal volume bases. On the other hand, if one inhales more
Figure 6-9. Normal distribution of ventilation. deeply than usual (large VT), and particu-
A, The volume of gas resident in the lungs at FRC larly when inspiratory hold is used, VT is dis-
is greatest in the apices. B, Most of the tidal volume tributed more evenly throughout the entire
at FRC is distributed to the bases in healthy people. lungs.156
Transpulmonary Intrapleural
pressure pressure Alveolar pressure PL = PAlv Ppl
+10 10 PL = 0 (10)
PL = +10
+5 5 PL = 0 (5)
PL = +5
PL = 0 (2)
+2 2
PL = +2
Figure 6-10. Variable transpulmonary pressure in the lung. Transpulmonary pressure is higher in the least
gravity-dependent portions of the lung because intrapleural pressure is lower. Thus, at resting lung volume,
alveoli are progressively larger as one moves up the lung.
Summary
Most normal VT ventilation is distributed to
100 the gravity-dependent areas of the lungs, and
the distribution decreases linearly as one
80 moves up the lung. When VT is very large or
Ventilation / unit volume
when breath hold is applied, the distribution of

ventilation throughout the lung is more uni-
60
form. Also, when FRC is below normal, the
distribution of ventilation may be preferen-
40 tially to the upper lung zones or the reverse of
normal tidal distribution.
20
Abnormal Distribution of Pulmonary Perfusion
Lower zone Middle zone Upper zone
0
The normal distribution of perfusion is shown in
1 2 3 Figure 6-12,A. A number of factors are known to
Distance alter this normal pattern of pulmonary perfusion.
Figure 6-11. Normal distribution of tidal For convenience, these mechanisms are classified
ventilation. Distribution of ventilation in the as primary or compensatory mechanisms.
upright human lung. Primary disturbances are simply pathologic
Zone
Zone 2
2
Normal distribution Increased

Zone Zone
of perfusion cardiac output
3 3
Figure 6-12. Generalized

disturbances of pulmonary A B
perfusion.
Zone 1 Zone 1
Zone Zone
2 2
Decreased Increased pulmonary

cardiac output vascular resistance
Zone Zone without an increased
3 3 cardiac output
C D
changes in pulmonary perfusion. Compensatory the entire lung (see Fig. 6-12,B). The volume of
disturbances are changes in the pattern of pul- blood present in the lungs may be increased
monary perfusion in response to a change in because a greater amount is pumped to the
pulmonary ventilation. Compensatory changes lungs from the right side of the heart (e.g.,
attempt to improve or to restore ventilation- increased cardiac output). Alternatively, pul-
perfusion matching. monary blood volume may be increased due
to backpressure from poor left-sided heart
Primary Disturbances function (e.g., mitral stenosis, left-sided heart
Primary disturbances of perfusion may be local- failure) and pooling of blood in the lungs.
ized or generalized. Serious local primary dis-
turbances may be caused by pulmonary emboli Generalized Decrease in Pulmonary Perfusion
or vascular tumors that affect the pattern of per- Conversely, a generalized decrease in pul-
fusion. Drugs such as isoproterenol, nitroglyc- monary perfusion results if the cardiac output
erin, or propranolol may also alter the pattern decreases due to inadequate blood volume or
of perfusion and may affect the PaO2.157,158 heart (pump) failure. A decrease in the quan-
Most commonly, however, primary distur- tity of pulmonary perfusion causes the upper
bances are the result of a generalized increase or margins of the lung zones to move downward
decrease in pulmonary perfusion. (see Fig. 6-12,C), which, in turn, may precipi-
tate the development of a zone 1 area where
Generalized Increase in Pulmonary Perfusion ventilation is present without perfusion. It is
A generalized increase in pulmonary perfusion noteworthy that the application of positive
tends to move the borders of the perfusion pressure ventilation may be associated with a
zones upward and has an overall tendency to similar shifting of the pulmonary perfusion
distribute perfusion more equally throughout zones downward.
Overall, pulmonary perfusion could like-

wise decrease if the pulmonary blood vessels
constrict (increased pulmonary vascular resist-
Constriction of pulmonary blood
ance) and the heart is unable to pump blood vessel to compensate for
throughout the entire lung (see Fig. 6-12,D). decreased local ventilation
Normally, increased pulmonary vascular resist-
ance (PVR) is countered with an increased
right-sided heart pumping force. Thus, the nor- PAO2
mal distribution of pulmonary perfusion is
usually maintained despite an increase in PVR. A
However, when the heart is unable to increase
its pumping force because it is weak or dam-
aged, increased PVR may result in a generalized
decrease in perfusion. Constriction of airway muscle
to compensate for decreased
PVR may increase acutely due to hypox- local perfusion
emia or acidemia. Remarkably, the pulmonary
vessels are the only blood vessels in the body
that react to low O2 levels by constriction rather PACO2
than dilation, although the reason for this is
still unclear.159,160
B
PVR may similarly increase in certain
chronic conditions, such as pulmonary fibrosis. Figure 6-13. Compensatory changes in the distri-
Nevertheless, regardless of the cause or the bution of ventilation and perfusion.
duration of onset, a generalized decrease in
pulmonary perfusion may lead to a pulmonary Local Changes
perfusion zone 1. On a local level, the partial pressure of O2 in
the alveoli (PAO2) serves as the primary regu-
Compensatory Disturbances latory mechanism.158 Decreases in PAO2 that
To a certain extent, perfusion seems to distrib- result from poor ventilation to a specific lung
ute to areas of maximal ventilation in the lung. area result in profound arteriolar and venule
It has been described earlier how both ventila- constriction and thus minimize perfusion to
tion and perfusion are preferentially distribu- a poorly ventilated space (Fig. 6-13,A). The
ted to the lung bases in a normal upright human release of histamine from hypoxic mast cells has
at normal FRC. been suggested as a potential mediator of this
response,156 but regardless of the mechanism,
Macroscopic Changes the net effect is to improve the ventilation-
It can also be shown on a macroscopic level perfusion match.
that as lung volume decreases, relatively more
perfusion is distributed to nondependent lung Abnormal Distribution of Ventilation
regions. If FRC is allowed to fall completely to As described previously, ventilation is distrib-
residual volume (RV), blood flow is actually uted throughout the lung based on regional
greater at the second rib level than at the differences in compliance and resistance. Any
lung bases in an upright person.155 Again, this pulmonary disorder that leads to a change
appears to maximize the ventilation-perfusion in compliance or resistance likewise leads to
interface because at low lung volume the a change in the distribution of ventilation.
distribution of ventilation is similar. Further- Alterations in the distribution of ventilation
more, because dependent lung zones are par- may be primary or compensatory.
ticularly prone to pathologic alveolar collapse
or consolidation, an upward shift of perfu- Primary Disturbances
sion in these situations seems to be especially Increased Airway Resistance. The single most
beneficial. common cause of abnormal distribution of
Bronchospasm/ Atelectasis in
secretions in bases and
the lower airway decreased FRC
A B
Mechanical Airway
ventilation closure
C D
Figure 6-14. Abnormal distribution of ventilation.
ventilation is increased pulmonary secretions. the distribution of ventilation is shown in

The accumulation of secretions leads to Figure 6-14,B.
decreased airway diameter and turbulent gas Positive-Pressure Ventilation. The application
flow, both of which increase airway resistance. of positive-pressure ventilation disturbs the nor-
Other causes of increased airway resistance mal distribution of ventilation (see Fig. 6-14,C).
include bronchospasm, mucosal edema, arti- Positive-pressure ventilation increases the dis-
ficial airways, and external compression of tribution of ventilation to upper lung zones
the airways by an abnormal tumor or fluid while simultaneously decreasing perfusion to
space. The effects of increased secretions or these areas. Thus, the application of mechanical
bronchospasm in the lower airway on the ventilation interferes with ventilation-perfusion
distribution of ventilation are shown in matching and normal external respiration.
Figure 6-14,A. Airway Closure. Finally, a less recognized
Abnormal Functional Residual Capacity. clinical problem in ventilation distribution is
An abnormal FRC also leads to the abnormal the phenomenon of airway closure. When the
distribution of ventilation, which is true lung is compressed, such as during forced
regardless of whether the FRC is increased or expiration, a point in the expiratory phase can
decreased. Both situations lead to changes in be shown at which gravity-dependent lung
alveolar compliances throughout the lung and zones cease to ventilate (see Figure 6-14,D).
changes in the distribution of inspired gas. The Dependent lung regions are the lung zones
effect of atelectasis and a decreased FRC on that are most affected by gravity. The actual
anatomic location of these regions varies with under anesthesia,164 pain, obesity, smoking,
body position. and prolonged bedrest.165 Simple assumption
As exhalation continues beyond the point of of the supine position may in itself decrease
airway closure, gas is expired only from non- FRC (300 to 800 mL).165 Thus, in individuals
dependent lung regions. Presumably, this is prone to airway closure or in those with
because small airways in dependent lung diminished FRC, the clinician should strongly
regions are collapsed. Furthermore, the distri- suspect this gas exchange problem. In healthy
bution of ventilation of the following breath is individuals older than 65 years of age, airway
abnormal because gas is unable to enter col- closure during tidal ventilation is likely to
lapsed regions or regions that are unable to occur.165 Furthermore, the decrease in FRC
empty normally. associated with the supine position would
The mechanism for this airway closure is allow this to happen at 44 years of age in
related to the positive intrapleural pressure healthy people.165
generated during forced expiration. Positive Compensatory Disturbances. Compensatory
intrapleural pressure tends to decrease trans- disturbances in the distribution of ventilation
pulmonary pressure and creates a compressive are in response to some primary change in the
effect on the airway. Airways that are not well distribution of perfusion. In general, the body
supported with cartilage, and diseased small attempts to match ventilation to perfusion in
airways in particular, eventually collapse. given lung segments.
Collapse occurs first in dependent lung zones The compensatory change in the distribution
because this region is subjected to the lowest of ventilation is mediated primarily through
transpulmonary pressure. local changes in airway resistance. In the
Regional airway collapse during forced absence of perfusion to a particular lung seg-
expiration was the basis for the closing volume ment, local airway resistance increases and ven-
study, a pulmonary diagnostic test that gained tilation to that region is reduced. The decrease
popularity in the 1970s for its purported in the alveolar CO2 partial pressure (PACO2)
ability to detect lung disease at a very early that accompanies a decrease in perfusion
stage.161 It was speculated that individual appears to be the chemical mechanism responsi-
knowledge of the presence of early lung disease ble for constriction of muscle in the airways
(i.e., premature airway closure) would serve as (see Fig. 6-13,B).155 In addition, decreased sur-
a deterrent to smoking. However, no data are factant production secondary to poor pulmonary
available to substantiate this claim. perfusion may also contribute to decreased
In healthy young individuals, airway clo- regional ventilation.
sure does not occur until very near residual
volume (RV) and in some is not seen at all. RV Ventilation-Perfusion Match
is, of course, the volume of gas remaining in The volume of blood ejected by the heart each
the lungs after maximal expiration. In certain minute is called the cardiac minute output (Q ).
individuals (e.g., the elderly, children, obese, With very minor exceptions, all of this blood
and smokers) and particularly in the presence passes through the pulmonary capillaries
of certain predisposing factors (e.g., reduced and has the opportunity to participate in gas
bronchial muscle tone, small airway disease, exchange via external respiration. On the ven-
pulmonary edema, decreased elastic recoil in tilation side, the volume of fresh gas reaching
lungs, forced expiration), airway closure occurs the alveoli each minute is called the alveolar
at much higher lung volume.161163 In fact, minute ventilation (V A).
basal airway closure above FRC is common in The volume of blood perfusing the lungs
patients with pulmonary emphysema.155 each minute (4 to 5 L) is approximately equiva-
Of clinical concern, airway closure may lent to the amount of fresh gas reaching the
occur in susceptible individuals during normal alveoli each minute (4 to 5 L). In a gas exchange
tidal ventilation, particularly when the FRC is system that perfectly matched ventilation with
reduced. The FRC, in turn, has been reported perfusion, one would expect the volume of
as decreased in the following: supine position, blood perfusing a given alveolar-capillary (AC)
180 0.6 ideal unit, because the matching of blood and

Blood flow gas is perfect.
160 Ventilation
Although the general patterns of ventilation
(% relative to mid-lung region)
140 and perfusion are similar in the normal lung,

Blood flow or ventilation
VA /Q = the ventilation-perfusion ratios in specific AC

120
1.0 units are rarely equal to 1. The reason is that
100 perfusion is almost 20 times greater in the lung
80 3.0 bases than the apices of an upright man or
woman, whereas ventilation is only four times
60
greater in the bases than the apices.156 Thus,
40 although the general distribution of both per-
fusion and ventilation is greatest in the lung
20
bases, there is relatively more perfusion than
0 ventilation in the lung bases and relatively
Top Middle Bottom
more ventilation than perfusion in the lung
Lung region
apices.
Figure 6-15. Regional ventilation-perfusion As shown in Figures 6-15 and 6-16, ventila-
relationships. Relative ventilation, blood flow, tion volumes may be three times higher than
and V/Q relationships in three areas of the vertical perfusion volumes near the top of the nor-
lung. Alveoli at the bottom of the lung receive mal lung (i.e., ventilation-perfusion ratio = 3).
more blood flow than ventilation and therefore Conversely, perfusion volumes normally
have a V/Q less than 1.0. Alveoli near the top
exceed ventilation volumes in the lung bases,
of the lung receive somewhat less ventilation and ventilation-perfusion ratios may be as low
than the bases, however they receive much less
as 0.6. Thus, the range of ventilation-perfusion
blood flow.
values seen throughout the lungs of a normal
upright human is approximately 0.6 to 3.3,
and the average ventilation-perfusion is
unit to be exactly equal to the volume of ven- approximately 0.85.155 This range represents
tilation to that unit. For example, if an AC the normal ventilation-perfusion mismatch in
unit received 1 mL of ventilation, it should humans.166 In chronic obstructive lung disease,
likewise receive 1 mL of perfusion. If this were which is characterized by an abnor-
indeed the case, the ventilation-perfusion mal distribution of ventilation, the range of
ratio (V/Q
) of that AC unit would be equal to ventilation-perfusion ratios throughout the
one. An AC unit with a V/Q of 1 is called an lung is greater (e.g., 0.1 to 10).
Blood flow Ventilation per VA/Q

per unit lung vol. unit lung vol. 3
Figure 6-16. Ventilation and VA/Q

perfusion in the normal lung.
Regional blood flow and
ventilation. Both ventilation and Blo 2
od
blood flow decrease from bottom flo
w
to top but the ratio between
Ventilati
them changes so that the upper o n
regions are overventilated in 1
relation to their perfusion and the
lower regions are relatively
underventilated.
Bottom Top
Upright lung
. .
V/Q PO2 PCO2 ventilation-perfusion relationship is likewise
given.
3.3 132 28 An ideal ventilation-perfusion unit and the
two utmost extremes are shown in Figure 6-18.
Alveolar ventilation in the absence of perfusion
(ventilation-perfusion ratio = infinity) is true
1.0 108 39
alveolar deadspace. Conversely, perfusion in the
absence of ventilation (ventilation-perfusion
ratio = 0) is called true capillary shunting. The
0.63 89 42 concepts of pulmonary deadspace and shunting
are explored in the following section. All the var-
Figure 6-17. Regional gas exchange in the ious components that comprise total deadspace
normal lung. and total shunting are shown in Figure 6-19.
Deadspace and Shunting

Deadspace
The exchange of gases in different regions In external respiration, the term deadspace is
of the lung likewise varies according to the used to refer to ventilation that does not par-
local ventilation-perfusion ratio (Fig. 6-17). ticipate in gas exchange. Energy is consumed
The PO2 of blood leaving the lung apices may in moving this gas in and out of the lungs;
be greater than 130 mm Hg, whereas the PO2 however, there is virtually no benefit in terms
of blood leaving the lung bases may be less of gas exchange. It is useful to think of dead-
than 90 mm Hg.156 space as simply wasted ventilation. Basically,
As stated previously, the ideal AC unit ventilation may be wasted if it fails to reach an
would have a ventilation-perfusion ratio of 1. alveolus (anatomic deadspace) or if it reaches
Indeed, the ideal lung would have ventilation- an alveolus that is not adequately perfused
perfusion ratios of 1 throughout. The further (alveolar deadspace). Alveolar deadspace may
ventilation-perfusion ratios deviate from 1, the be further subdivided into true alveolar dead-
more inefficient gas exchange becomes. Even space and relative alveolar deadspace.
in the normal lung, there is a certain degree of
inefficiency or ventilation-perfusion mismatch. True Alveolar Deadspace
The range of ventilation-perfusion ratios that An alveolus that is ventilated but not perfused
may be present in cardiopulmonary disease, is called a true alveolar deadspace unit (see
however, is virtually infinite. Table 6-1 shows Fig. 6-19,F). The V/Q of a true alveolar dead-
some examples of these ratios that could space unit is infinity, which is true regardless of
exist in various AC units. Also, terminology the actual quantity of ventilation because any
that is used frequently to describe a particular number divided by zero is equal to infinity.
Table 6-1. SPECTRUM OF VENTILATION-PERFUSION UNITS (V/Q

)
Ventilation (mL) Perfusion (mL) V/Q
Unit
10 0 Absolute deadspace
10 1 10 Relative deadspace
3 1 3 Relative deadspace
1 1 1 Ideal unit
0.5 1 0.5 Relative shunt
0.1 1 0.1 Relative shunt
0 10 0 Absolute shunt
0 0 0 Silent unit
Ideal match
V
V/Q = 1
Q
V V
Q Q
V/Q = O V/Q =
True capillary shunting True alveolar deadspace
O2 does not enter blood Wasted ventilation
Figure 6-18. The extremes of V/Q mismatch. In true capillary shunting (V/Q
= 0), blood does not pick
up O2 as it passes through the lungs and therefore remains at the mixed venous PO2 level. In true alveolar
deadspace (V/Q = infinity), ventilation is wasted.
This type of deadspace may be described as Relative Alveolar Deadspace

true or absolute because not a single molecule It should likewise be apparent that any (V/Q
> 1)
entering the alveolus partakes in gas exchange. represents some surplus of ventilation even in AC
In healthy people, there is no significant true units where gas exchange is taking place. This
alveolar deadspace because even the apical pseudo-deadspace may be referred to as relative
lung receives some perfusion.155 alveolar deadspace and is shown in Figure 6-19,E.
A B C D E F G
Anatomic Capillary Relative Ideal Relative Alveolar Anatomic
shunt shunt shunt deadspace deadspace deadspace
Physiologic shunting Physiologic deadspace
Figure 6-19. Components of physiologic shunting and deadspace.

Anatomic Deadspace Mechanical Deadspace

Our discussion of deadspace has been confined Additionally, when an individual is connected
to only ventilation that reaches the alveoli but to some type of breathing appliance (e.g., mech-
does not partake in gas exchange. Another anical ventilator, oxygen mask), another form of
form of wasted ventilation is the portion of the deadspace may also be present. The volume of
inspired gas that never reaches the alveoli. The any breathing apparatus in which exhaled gas
gas remaining in the airway at the end of each remains and is inspired on the next breath
breath (see Fig. 6-19,G) is sometimes referred is called mechanical deadspace. Functionally,
to as the anatomic deadspace. The quantity mechanical deadspace represents an extension
of anatomic deadspace in an individual can of the anatomic deadspace.
be approximated as 1 mL/lb of ideal body
weight, or approximately one third of the tidal Physiologic Deadspace
volume. Thus, anatomic deadspace in an aver- The sum of all alveolar and anatomic dead-
age 150-lb individual would be approximately space is called physiologic deadspace (VD).
150 mL. In Figure 6-19, this would represent the sum of
In a given individual, the volume of anatomic E + F + G. Physiologic deadspace is expressed
deadspace is a constant that is present with normally as a percentage of tidal volume
each breath, regardless of VT. If the VT were to (VD/VT).
fall below the volume of anatomic deadspace, Measurement. At the bedside, the VD/VT
all ventilation would appear to be wasted. In may be calculated by using the Enghoff
reality, jet ventilation has shown that some modification of the Bohr equation shown in
portion of this ventilation may still reach the Equation 6-2. Data necessary to use Equation
alveoli. 6-2 can be obtained via arterial blood gases
Normally, however, for external respiration (PaCO2) and collection of mean expired gas

to take place, VT must exceed anatomic dead- samples (PECO2). Mean expired gas samples
space volume. The volume of ventilation in may be collected by using a large reservoir bag
excess of deadspace is called effective alveolar (e.g., a Douglas bag) connected to the exhala-
ventilation. Gas exchange is proportional to tion port of a breathing circuit.
the volume of alveolar ventilation.
Equation 6-2
Breathing Pattern VD PECO2

= PaCO2
Low tidal volumes are inefficient regarding VT PaCO2
alveolar ventilation because a large percentage
of each breath is wasted as anatomic dead- Normal Values. The normal VD/VT in the
space. On the other hand, large tidal volumes spontaneously breathing individual is less than
are more efficient because all ventilation in 0.4. During mechanical ventilation, however,
excess of anatomic deadspace represents alve- an increase in VD/VT is expected owing to
olar ventilation. Obviously then, a rapid, shal- changes in the distribution of ventilation and
low breathing pattern does not facilitate gas perfusion. The normal VD/VT in the patient
exchange in external respiration. With this on a mechanical ventilator is less than 0.6.10
pattern, a greater percentage of the total venti- Clinical Significance. The major clinical sig-
lation must be wasted as anatomic deadspace nificance of increased physiologic deadspace is
ventilation. A more detailed discussion of the that ventilation of that deadspace is wasted. If
effects of deadspace on alveolar ventilation and gas exchange in external respiration is to remain
PaCO2 is included in Chapter 8. adequate in the face of increased deadspace, the
When a patient is breathing through an arti- total volume of ventilation must increase beyond
ficial airway (e.g., via tracheostomy tube or normal. An increase in total ventilation can be
endotube), the volume of anatomic deadspace accomplished only with a concomitant increase
depends on the dimensions of the artificial air- in the work of breathing and consumption of
way. Generally, the use of artificial airways O2 which, in turn, places further demands on
reduces the total anatomic deadspace volume. the supply of O2 via external respiration.
Clinical Assessment. In many clinical situa- Table 6-2. COMMON CAUSES OF INCREASED
tions, measurement of the VD/VT is not practi- DEADSPACE
cal. The fact that an increase in total ventilation Anatomic: Rapid, shallow breathing
is required to maintain adequate alveolar venti- Alveolar
lation in the presence of increased physiologic True: Pulmonary emboli
deadspace, however, may provide useful diag- Decreased cardiac output
nostic information. When ventilation is exces- Relative: Chronic obstructive pulmonary disease
sive while the PaCO2 remains remarkably high Positive-pressure ventilation
or normal, increased physiologic deadspace
should be suspected.
In normal humans, a total expired venti-
lation (VE) of approximately 5 L/min results Table 6-2 lists the common causes of increased
in a PaCO2 of approximately 40 mm Hg. deadspace.
Doubling the minute ventilation to approxi-
mately 10 L/minute lowers PaCO2 to approxi- Shunting
mately 30 mm Hg. Quadrupling ventilation In the cardiopulmonary system, pulmonary
(i.e., 20 L/minute) lowers PaCO2 to almost shunting is the phrase used to describe blood
20 mm Hg. that passes through the lungs without parti-
If a patients measured VE was 10 L/minute cipating in external respiration. Shunted blood
and measured PaCO2 was 45 mm Hg, increased enters and leaves the lungs with identical blood
deadspace may be present. With this volume of gases because it does not have the opportu-
ventilation, PaCO2 should be approximately nity for gas exchange. This blood behaves as
30 mm Hg. The high PaCO2 may be evidence though it was diverted (shunted) around the
of greater than normal wasted ventilation (i.e., lungs rather than passed through the lungs.
increased deadspace component). Alternatively, There are two general mechanisms by
this situation could reflect an increased CO2 which shunting may occur. First, it occurs if
production. blood on its way to the lungs bypasses the
When available, another good index of pulmonary capillaries and returns to the
physiologic deadspace is the difference heart through some other vessel (anatomic
between the PaCO2 and the end-tidal partial shunting). Alternatively, shunting occurs when
pressure of CO2. The end-tidal partial pressure blood passes through an AC lung unit that
of CO2 (PetCO2) may be measured via cap- does not contain fresh alveolar ventilation
nometry, which is described later. The arterial (capillary shunting). Perhaps the alveolus in
end-tidal PCO2 difference [P(a et)CO2] is nor- this unit is collapsed or filled with fluid and
mally only 2 to 3 mm Hg. A high P(a et)CO2 is, therefore, not functional. Capillary shunt-
is evidence of increased physiologic deadspace. ing may be further subdivided into true and
relative capillary shunting.
Deadspace Disorders
An increase in deadspace (wasted ventilation) True Capillary Shunting
results in an increased work of breathing and As described previously, a true or absolute
the clinical cause should be identified. As capillary shunt is an AC unit in which there is
described previously, anatomic deadspace no alveolar ventilation (see Fig. 6-19,B). The
becomes a significant factor in rapid, shallow V/Q
of a true capillary shunt unit is 0. True
breathing. capillary shunting is virtually absent in the
True alveolar deadspace is typically the normal human.
result of a pulmonary embolus or decreased Pulmonary edema (e.g., left heart failure
pulmonary perfusion (e.g., decreased cardiac [Fig. 6-20] or acute respiratory distress syn-
output). Finally, relative alveolar deadspace is drome) may result in true capillary shunting by
increased when the distribution of ventilation is causing alveoli to fill with fluid. Pneumonia
abnormal such as in chronic obstructive pul- may cause a similar phenomenon with infec-
monary disease or positive-pressure ventilation. tious liquid filling alveoli. The collapse of alveoli
Alveolus Air
CO2 O2 Normal
Alveolus
Fluid Capillary
Air
Pulmonary capillary
Deadspace
hydrostatic pressure
Figure 6-20. Pulmonary edema and capillary

shunting in left heart failure. Blockage
(atelectasis) may likewise result in a true Blockage Shunt

capillary shunt. The primary pathologic mech- unit
anism in true capillary shunting is the loss of
functional alveoli.
An AC unit with no ventilation or perfusion
is called a silent unit. Silent units normally Capillary
have no direct effects on external respiration;
however, they do represent a loss of functional
surface area available for gas exchange. The
Blockage Silent
ventilation-perfusion effects of blockage of unit
ventilation or perfusion in a given AC unit are
shown in Figure 6-21.
Relative Capillary Shunting

An AC unit in which the volume of perfusion Blockage
exceeds the volume of ventilation may be
Figure 6-21. Blockage of ventilation or
referred to as a relative capillary shunt. A rela-
perfusion.
tive shunt differs from a true shunt in that
some, albeit not enough, ventilation is present
in this type of unit. A relative capillary shunt
unit has a V/Q of less than 1, but it is greater initial blood perfusing the capillary is normally
than 0 (see Fig. 6-19,C). oxygenated, whereas the final blood to perfuse
Blood traversing a relative capillary shunt the capillary would receive no O2. Thus, this
unit cannot be oxygenated completely because final blood behaves as though it had never
the supply of fresh alveolar gas is insufficient passed an AC unit or as if it were shunted past
in proportion to the supply of perfusion. The the lungs. This theoretical explanation is of
lung bases in a normal human may be charac- course an oversimplification, because gas
terized as relative shunt units. exchange does not actually stop. Nonetheless,
Conceptually, one could surmise that the it may help to show the major clinical conse-
alveolus would be depleted of O2 before all quence of relative shunting (i.e., low ventila-
the blood perfusing that unit were fully oxy- tion-perfusion units); that is, an insufficient
genated. This can be visualized as though the alveolar O2 supply.
Anatomic Shunting Equation 6-3

Some blood that leaves the heart on its way to
Qsp [C c O2 CaO2 ]
the lungs never even passes through a pulmo- =

QT [C c O2 CvO2 ]
nary capillary. It is not that this blood passes a
nonfunctional alveolus, this blood never passes 2 = oxygen content of ideal capillary
C cO
an alveolus at all (see Fig. 6-19,A). This form blood
of true/absolute shunting is called anatomic CaO2 = oxygen content of arterial blood
shunting. CvO2 = oxygen content of mixed venous
In normal humans, approximately 2% of the blood
cardiac output follows this anatomic course. Normal Values. In normal humans, there is
Vessels involved in the normal anatomic shunt no true capillary shunting, and relative capil-
include the pleural, thebesian, and bronchial lary shunting is equivalent to approximately
veins. Congenital anomalies and other disor- 1% of the cardiac output.155 The normal
ders of the cardiovascular system may cause anatomic shunt accounts for another (1% to
substantial increases in the anatomic shunt. 2%) of the cardiac output. Thus, the normal
physiologic shunt is approximately 3% of the
Physiologic Shunting cardiac output.
The physiologic shunt is the combined shunt Clinical Significance. In the clinical arena,
that results from the additive effects of the even a Q sp/QT as high as 15% is not usually of
anatomic and capillary shunts in a given individ- major clinical consequence. Notwithstanding,
ual. The physiologic shunt includes both the true the most important clinical result of increased
and relative shunt components. In Figure 6-19, physiologic shunting is failure of the shunted
the physiologic shunt is the sum of A, B, and C. blood to pick up O2 as it passes through the
The volume of blood shunted via the physi- lungs. Thus, shunting tends to cause primarily
ologic shunt each minute is symbolized Q sp. hypoxemia (Fig. 6-22).
The physiologic shunt is usually expressed as a
percentage of the total cardiac output (Q T).
Thus, the symbol for the physiologic shunt is
Q sp/Q
T. When relative shunting is ignored
and only the percentage of true shunt is meas- 100
ured, the symbol is Q s/Q
T.
), (mm Hg)
Measurement. The Q sp/Q T can be calcu-

lated at the patients bedside by using the clas- 80
sic shunt formula shown in Equation 6-3.
Formulas for determining O2 content in vari-
ous blood vessels are described in Chapter 7. It 60
) and PCO2 (
is noteworthy, however, that several variables

must be measured to calculate O2 contents
accurately. These variables include: PaO2, SaO2, 40
Pv O2, mixed venous O2 saturation (Sv O2), and
hemoglobin concentration [Hb].
PO2 (
Also, capillary O2 content cannot be meas- 20

ured directly; therefore, it is estimated based on
certain theoretical assumptions. The ideal end
capillary PO2 (PcO 2) is assumed to be equal 0
to the PAO2, and capillary blood is assumed 0 10 20 30 40 50
to be completely saturated (i.e., SO2 100%). Shunt (%)
Furthermore, calculation of mixed venous O2 Figure 6-22. Effect of increasing shunt on
content requires the acquisition of a mixed PaO2 and PaCO2. The PaO2 (closed circles) falls
venous blood sample through a special catheter precipitously, whereas PaCO2 (open circles) is
placed in the heart (i.e., Swan-Ganz catheter). hardly affected.
Mild-to-moderate increases in physiologic Table 6-3. COMMON CAUSES OF INCREASED

shunting do not affect the ability of the lungs SHUNTING
to excrete CO2 (see Fig. 6-22). Only when the Anatomic: Congenital heart defects
increase in physiologic shunting is huge are Capillary
abnormal amounts of CO2 retained in the arte- True: Congestive heart failure
rial blood. The reason why moderate physio- Acute respiratory distress syndrome
logic shunting affects arterial O2 levels but not Pneumonia
CO2 levels is related to the different mechanisms Atelectasis
by which these two gases are transported in the Relative: Pulmonary secretions
Positive-pressure ventilation
blood (see Chapter 7).
It is also noteworthy that the body responds
to hypoxemia caused by increased physiologic sometimes used as gross estimates of pulmonary
shunting by augmenting the cardiac output, shunting.
which has the effect of minimizing the fall in
arterial PaO2. Shunting Disorders
Clinical Assessment. As shown earlier, calcu- An increase in pulmonary shunting leads to
lation of the physiologic shunt requires measure- hypoxemia breathing room air. As described pre-
ment of several blood gas variables. Furthermore, viously, an increased abnormal anatomic shunt is
acquisition of mixed venous blood is necessary most often the result of a congenital heart defect.
for its determination. For these reasons, various True capillary shunting is typically the result
other indices that are easier to measure or of fluid filling alveoli (e.g., acute respiratory
calculate have been used by clinicians to estimate distress syndrome, congestive heart failure,
physiologic shunting. These indices include pneumonia) or alveolar collapse (atelectasis).
P(A a)O2, PaO2/PAO2, and PaO2/FIO2. Finally, relative capillary shunting is seen with
The application of these various indices is abnormal distribution of ventilation such as
explored in Chapter 9 in the assessment and may accompany accumulation of pulmonary
management of hypoxemia. Presently, it is suf- secretions or bronchospasm. Table 6-3 lists
ficient to say that various other indices are some of the common causes of shunt disorders.

A 72-year-old woman undergoes surgery for a leg Temp 37 C

fracture following a fall. Three days later, she has an Minute ventilation 18 L/min
acute onset of severe shortness of breath, hemoptysis,
and chest pain. ASSESSMENT
ARTERIAL BLOOD GASES information. Classify ABG.
SaO2 88% Explanation: List possible diseases, pathology, or other
pH 7.41 situations that may have led to this patients condition.
PaCO2 38 mm Hg Evaluation: Suggest additional data that would be useful in
PaO2 50 mm Hg helping understand the situation or in making a diagnosis.
[HCO3] 24 mEq/L
INTERVENTION
VITAL SIGNS Importance: Prioritize concern(s) of treatment in order
B/P 135/90 mm Hg of urgency and/or seriousness as you see the overall
RR 30/min situation.
HR 112/min

A previously healthy 47-year-old man returns from the ASSESSMENT

operating room following abdominal surgery and pres- Abnormalities: List abnormal data and other noteworthy
ents with the following ABGs and vital signs 48 hours information. Classify ABG.
after returning to the unit. He also has diminished breath Explanation: List possible diseases, pathology, or
sounds in the lung bases. other situations which may have led to this patients
condition.
SaO2 86% useful in helping understand the situation or in making
pH 7.51 a diagnosis.
PaCO2 29 mm Hg
PaO2 52 mm Hg INTERVENTION
[HCO3] 22 mEq/L Importance: Prioritize concern(s) of treatment in order
VITAL SIGNS
situation.
B/P 140/90 mm Hg Objective: Specifically state the measurable or observable
RR 24/min outcomes you would like treatment to accomplish.
HR 106/min Action: Describe your specific plan of action.
Temp 39 C
Diffusion Speed of Diffusion

Appropriate external respiration requires both The speed of gas diffusion through the AC mem-
an adequate volume of ventilation and the brane depends on a variety of factors including:
matching of this ventilation with perfusion. The molecular size, solubility coefficients, Grahams
final prerequisite for effective external respira- Law, and driving pressures.
tion is normal diffusion. There are two major Molecular Size. One factor that determines
requirements for successful pulmonary diffu- the speed of diffusion of a particular gas is
sion. First, there must be sufficient time available its molecular weight. Lighter molecules move
to allow for the complete equilibration of gases and therefore diffuse more quickly. Because O2
between the alveolus and the pulmonary capil- molecules are lighter than CO2 molecules, O2
lary blood. Second, there must be a sufficient molecules diffuse more quickly in a gaseous
number of functional AC units (surface area) to phase.
allow for an adequate volume of gas exchange. Solubility Coefficient. In a liquid medium,
however, an additional property comes into
Equilibration play; that is, the solubility of the gas in the
Available Time liquid. Gases that are more soluble in a given
The time available for gas equilibration in liquid diffuse faster throughout that liquid.
the AC unit is sometimes referred to as the This is precisely why CO2 (a larger molecule)
pulmonary capillary transit time; this is the diffuses about 20 times faster than O2 across
time that it takes for blood in the pulmonary the AC membrane, which is essentially a liquid
capillaries to pass the alveolus or the time membrane.
during which the AC interface is maintained. Grahams Law. This law summarizes these
Pulmonary capillary transit time in normal relationships by stating that diffusion of a gas
resting humans is approximately 0.75 sec- through a liquid is directly proportional to its
onds.155,166 Thus, diffusion must be completed solubility coefficient and inversely propor-
(complete equilibration) during this period. tional to the square root of its density.
Driving Pressure. The speed of diffusion of equilibration because the speed of equi-
also varies directly with the driving pressure of libration varies directly with this value.
a gas across the AC membrane. The driving Administration of supplemental O2 increases
pressure across the AC membrane for a given the driving pressure and the speed of diffusion.
gas is equal to the difference between its par-
tial pressure in the alveolus and its partial pres- Complete Equilibration
sure in the mixed venous blood entering the From a clinical standpoint, the complete equi-
capillary. As shown in Figure 6-23, the driving libration of CO2 between the alveoli and blood
pressure for O2 is approximately 63 mm Hg is never a problem because of the high solubil-
(PAO2 Pv O2) whereas the driving pressure ity coefficient of CO2. Similarly, complete
for CO2 is only 6 mm Hg (Pv CO2 PACO2). equilibration of O2 should not be a problem
The calculation of driving pressure in this under ordinary circumstances. In healthy peo-
example represents the ideal driving pressure ple, O2 equilibration across the AC unit takes
as blood enters the AC unit. Actually, the driv- approximately 0.25 seconds.155,166 Thus, O2
ing pressure must decrease progressively as equilibration occurs during the first one third of
blood travels through the capillary until theo- pulmonary capillary transit time (0.75 seconds),
retically it is equal to zero. Nevertheless, as shown in Figure 6-23. This provides for
calculation of the initial driving pressure is a large amount of reserve time for equilibra-
a reasonable method to evaluate the speed tion in normal resting humans.
PULMONARY
Artery Capillary Vein
103
100
80 Blood
mm Hg
PO2
60
40
20
.00 .25 .50 .75
Transit time in capillary Figure 6-23. O2 diffusion
(Seconds)
across the AC membrane. The
PO2 in the capillary normally
equilibrates with the alveolar
PO2 within one third of
pulmonary capillary transit time
at rest.
Capillary
PO2 = 40 Alveolar
PO2 = 103 PO2 = 100
PCO2 = 46 mm Hg PCO2 = 40 PCO2 = 40
Artery Vein
O2 CO2
Diffusion Barriers Doubling the thickness of the AC membrane

As is discussed in Chapter 7, most of the O2 in would double equilibration time (e.g., 0.25 to
the blood is carried within the red blood cells. 0.5 seconds). Nevertheless, the long time avail-
Thus, the functional barriers to diffusion of O2 able for O2 equilibration (0.75 seconds), as
include all the microscopic anatomic layers shown in Figure 6-23, ensures that complete
between the alveolus and the red blood cells, equilibration would still take place with normal
as shown in Figure 6-24. These layers include pulmonary capillary transit time.
the alveolar membrane, the interstitial fluid,
the capillary membrane, plasma, and the red Decreased Driving Pressure
blood cell. Ascent to high altitude with the resultant
decrease in PAO2 and drop in the driving pres-
Thickening of the AC Membrane sure for O2 across the AC membrane may like-
Excluding the red blood cell and plasma, wise prolong equilibration. Nevertheless, here
the normal thickness of the AC membrane again, the large reserve of extra time available
is approximately 1 m (1/1000 mm).81,155 for diffusion allows for complete equilibration.
Significant thickening of this membrane may
occur in pulmonary fibrosis or pulmonary Incomplete Equilibration
edema, which is associated with an increased Incomplete equilibration may occur, however,
volume of interstitial fluid. Thickening of the if a reduced driving pressure or thickening of
membrane, of course, would increase the dif- the alveolar capillary membrane is combined
fusion distance and prolong equilibration time. with a reduced pulmonary capillary transit
time. A reduced pulmonary capillary transit
time accompanies an increased cardiac output
because the speed of perfusion is increased.
cell Specifically, pulmonary capillary transit time
blood
Red ma may be as low as 0.34 seconds during exer-
Plas rane
emb cise.81 Thus, the net effects of exercise at high
la r m
y
Ca p il l fluid
stitia bran
e altitude may lead to severe hypoxemia even in
Inter mem
olar
Alve healthy subjects because of the low driving pres-
sure combined with the decreased pulmonary
capillary transit time.155
Similarly, incomplete O2 equilibration may
be observed during exercise in the patient with
O2 thickening of the AC membrane. Specifically, if
complete equilibration requires 0.5 seconds due
1
to AC thickening, and pulmonary capillary
Capillary transit time falls to 0.4 seconds, equilibration
will not occur.
Clinical Considerations
Diminished pulmonary capillary transit time
Alveolus
leading to incomplete equilibration is largely
responsible for the hypoxemia and shortness
of breath seen on exertion in patients with
Capillary pulmonary fibrosis. When hypoxemia is present
in these patients at rest, the mechanism is most
likely increased physiologic shunting rather than
incomplete equilibration.155
Figure 6-24. O2 diffusion barriers in external The presence of a thickened AC mem-
respiration. The barriers to AC diffusion as seen brane is sometimes referred to as an AC block
via electron microscopy in the rat lung. or a diffusion defect; however, use of these
terms is discouraged because a thickened AC number of functional AC units. The normal

membrane alone does not lead to incomplete alveolar surface area that is exposed to pul-
equilibration of O2.155 One should remember monary capillary blood is approximately 70 m2
that alveolar capillary thickening may lead to or approximately the size of a tennis court.
incomplete equilibration and hypoxemia only Because the volume of blood undergoing gas
when combined with a decreased pulmonary exchange in the lungs is only approximately
capillary transit time. This may occur during 70 mL,155 there is about 1 m2 of surface area
exercise or in the critically ill patient with an for every milliliter of blood. If one could imag-
increased cardiac output. ine 1 mL of blood spread out over a square
Less obvious factors may also present barri- meter, the vast gas exchanging capability of the
ers to diffusion. These factors include situations lungs could be appreciated.
where O2 would not normally diffuse through Pulmonary diseases that affect the archi-
red blood cell membranes or combine with tecture of the lung (e.g., emphysema, pneu-
hemoglobin. The clinical significance of these monectomy, tumors) may result in the loss of
considerations, however, appears to be minimal. functional AC units. Thus, the quantitative abil-
ity of the cardiopulmonary system to load O2
Surface Area into the pulmonary capillary blood is reduced.
Also important in the quantitative exchange of This phenomenon can be detected through
gases in external respiration is an adequate pulmonary function diffusion studies.
EXERCISES
Exercise 6-1 Introduction to Oxygenation

1. The system responsible for cellular oxygenation in the human is the (respiratory/
cardiovascular/cardiopulmonary) system.
2. Define external respiration.
3. Define O2 transport.
4. Define internal respiration.
5. The assessment of O2 transport is (qualitative/quantitative) in nature.
6. List the three phases in oxygenation using blood as the reference point.
7. The heart is (less/more) effective in compensating for respiratory oxygenation problems
than the lungs in compensating for cardiovascular oxygenation problems.
8. The body increases the amount of red blood cells and hemoglobin in the blood in
response to diminished O2 loading. The result of this response is called ______.
9. Hypoxemia is a (blood/tissue) condition.
10. The utmost goal in the management of oxygenation status is the prevention of
(hypoxemia/hypoxia).
11. Hypoxemia (may be/is never) present in the absence of hypoxia.
12. Hypoxia (may be/is never) present in the absence of hypoxemia.
Exercise 6-2 External Respiration and Normal

Pulmonary Perfusion
1. State the three criteria that must be met to ensure adequate O2 loading.
2. The minute-to-minute control of ventilation in normal humans is mediated via the
(PaO2/PaCO2).
3. Normal ventilation ensures an adequate supply of O2 to the alveoli unless the FIO2 or the
______ of the inspired gas is low.
4. A significant direct stimulation of ventilation in response to hypoxemia occurs only when
PaO2 is less than approximately ______ mm Hg.
5. Most pulmonary perfusion is normally distributed to the (most/least) gravity-dependent
lung regions.
6. Pulmonary perfusion in zone 1 of Wests model is (vast/minimal/absent).
7. A pulmonary perfusion zone 1 (is/is not) present in normal healthy humans.
8. The upper lung zones in healthy upright people function as a pulmonary perfusion zone
(1/2/3).
9. Most pulmonary perfusion occurs in zone ______.
10. Hypotension may lead to the development of a pulmonary perfusion zone ______.
Exercise 6-3 Normal Distribution of Ventilation

1. The distribution of ventilation in the lung depends on regional differences in ______ and
______.
2. At residual volume, most gas entering the lung would go to the (apices/bases).
3. The intrapleural pressure in the apices is (more/less) negative than it is in the bases of an
upright individual.
4. Calculate the transpulmonary pressure given an intrapulmonary pressure of 2 cm H2O and
an intrapleural pressure of 8 cm H2O.
5. At resting FRC, the apical alveoli are (larger/smaller) than the basal alveoli.
6. A negative PL is a net (compressive/distending) force on the lungs.
7. Transpulmonary pressure is (higher/lower) in the lung apices of an upright individual than in
the bases.
8. Most gas inhaled during normal breathing from normal FRC enters the (apices/bases).
9. The amount of air moved in and out of the lungs during normal breathing is called the
______.
10. Large tidal volumes tend to make the distribution of ventilation (more/less) even
throughout the lungs.
Exercise 6-4 Abnormal Pulmonary Perfusion

1. Changes in the pattern of pulmonary perfusion in response to a change in pulmonary

ventilation are called (primary/compensatory) disturbances.
2. Most primary disturbances of pulmonary perfusion are (localized/generalized) in nature.
3. The upper borders of the pulmonary perfusion zones tend to move (higher/lower) due to an
increased cardiac output.
4. List two situations that may shift the upper borders of the pulmonary perfusion zones
downward.
5. Cite a situation when an increased pulmonary vascular resistance could result in a
generalized decrease in pulmonary perfusion.
6. List two blood gas conditions that can increase pulmonary vascular resistance acutely.
7. Suggest a clinical disease entity that could increase generalized pulmonary vascular
resistance chronically.
8. The most potent regulator of the distribution of pulmonary perfusion on the local level is the
______.
Exercise 6-5 Abnormal Distribution of Ventilation

1. A change in FRC (will/will not) affect the distribution of ventilation.

2. State the single most common cause of abnormal distribution of ventilation.
3. Accumulated pulmonary secretions affect the distribution of ventilation primarily through
their effects on pulmonary (compliance/airway resistance).
4. Bronchospasm and mucosal edema primarily affect pulmonary (compliance/airway resist-
ance).
5. Airway closure occurs first in (gravity/nongravity) dependent lung regions.
6. Forced expiration tends to (increase/decrease) PL.
7. Airway closure occurs prematurely in (obese/thin) patients.
8. Airway closure occurs prematurely in (smokers/nonsmokers).
9. The FRC may be reduced in the (supine/sitting) position.
10. Airway closure has been reported to occur in normal individuals in the supine position
at age ______.
11. Compensatory changes in the distribution of ventilation are mediated by changes in
(PAO2/PACO2).
Exercise 6-6 Ventilation-Perfusion Matching

1. The volume of blood ejected by the heart each minute is called the ______.
2. The volume of fresh gas reaching the alveoli each minute is called the ______.
3. The ventilation-perfusion ratio of an ideal AC unit is approximately ______.
4. Although perfusion and ventilation are both greatest in the lung bases, perfusion is
relatively (less/more) than ventilation in this region.
5. The average ventilation-perfusion ratio in the lung is approximately (0.8/0.4).
6. The ventilation-perfusion ratios in the apex of the normal erect lung are about (10/3).

7. The V/Q in the base of the normal erect lung are approximately (0.6/0.2).
8. The PaO2 of blood leaving the lung apices is approximately (100/130) mm Hg.

9. A V/Q of zero is associated with a unit called a ______.

10. A V/Q of infinity is associated with a unit called a ______ unit.
Exercise 6-7 Physiologic Deadspace

1. In healthy people, there is (some/no) absolute alveolar deadspace.

2. The (higher/lower) the numeric value of a V/Q, the more wasted ventilation is present.
3. Normal anatomic deadspace ventilation per breath in a 200-lb adult is approximately
______ mL.
4. Anatomic deadspace ventilation increases in significance when VT is (high/low).
5. The sum of all types of deadspace expressed as a percentage of VT is called ______
deadspace.
6. Calculate VD/VT given:
PaCO2 = 60 mm Hg
PE CO2 = 30 mm Hg
7. The physiologic deadspace equation uses (mean/end tidal) expired PCO2.
8. The normal VD/VT in the spontaneously breathing individual is ______.
9. The normal VD/VT in the patient receiving mechanical ventilation is ______.
10. The volume of any breathing apparatus in which exhaled gas remains and is inspired on
the next breath is called ______.
11. The major clinical consequence of increased physiologic deadspace is that ventilation of
that deadspace is ______.
12. Increased deadspace ventilation will (increase/decrease) the work of breathing.
13. Increased deadspace ventilation (will/will not) directly cause hypoxemia.
14. A minute ventilation of 10 L/min in healthy people should result in a PaCO2 of approximately
(20/30) mm Hg.
15. A minute ventilation of 15 L/min and a PaCO2 of 40 mm Hg suggests (normal
deadspace/increased physiologic deadspace).
16. A PaCO2 of 25 mm Hg and a minute ventilation of 15 L/minute suggests (normal
deadspace/increased physiologic deadspace).
17. The difference in partial pressures between end-tidal and arterial (O2/CO2) is a good index
of physiologic deadspace.
Exercise 6-8 Physiologic Shunting


1. The (lower/higher) the V/Q, the lower is the PO2 that leaves the unit.
2. A ventilation-perfusion unit with no perfusion or ventilation is called a ______ unit.
3. The two forms of absolute shunting are ______ shunts and ______ shunts.
4. The normal anatomic shunt is approximately ______% of the cardiac output.
5. List three veins that contribute to the normal anatomic shunt.
6. Capillary shunting may be subdivided further into ______ and ______ capillary shunting.
7. Another term for true capillary shunting is ______ capillary shunting.
8. State two clinical causes of increased true capillary shunting.
9. The normal percentage of the physiologic shunt that passes relative capillary shunt units
is ______%.
10. The major clinical consequence of increased physiologic shunting is ______.
Exercise 6-9 Diffusion

1. State the two major concerns regarding the adequacy of diffusion in the lung.
2. The time that it takes blood to pass the alveolus during which the AC interface is maintained
is called the ______ time.
3. Pulmonary capillary transit time in a normal resting human is ______ seconds.
4. Normal O2 equilibration time with a normal AC membrane is ______ seconds.
5. In a gaseous phase, (larger/smaller) molecules diffuse faster.
6. CO2 diffuses 20 times (faster/slower) than O2 across the liquid AC membrane.
7. What law states that diffusion of a gas through a liquid is directly proportional to its
solubility coefficient and inversely proportional to the square root of its density?
8. Normal AC membrane thickness is approximately ______ m.
9. A decreased O2 driving pressure or a thickened AC membrane may result in hypoxemia if
pulmonary capillary transit time were (increased/decreased) as occurs during exercise.
10. The normal alveolar surface area is approximately ______ m2.

1. Go to google.com and do an image search on the following: (a) V/Q, (b) lungs, and (c) alveolar-
capillary gas exchange. Print out the one picture on each topic that best illustrates each
topic.
NBRC Challenge 6
1. A VD/VT study is performed on a patient A) I only

in the critical care unit. The VD/VT is B) II only
determined to be 0.6. Which of the fol- C) I and II only
lowing may explain the patients status? D) II and III only
I. Decreased cardiac output E) I, II, and III
II. Atelectasis (RRT EXAMINATION NBRC
III. Mechanical ventilation MATRIX I,C,1,c)
A) I only
4. A suspected tuberculosis patient has
B) II only
increased crackles in both lung apices.
C) I, II only
Tuberculosis is more likely to be seen in
D) I, III only
the ______ lung zones because of the
E) I, II, and III
________________.
(RRT EXAMINATION NBRC
A) upper, higher PaO2
MATRIX I,C,2,c)
B) upper, lower PaCO2
2. To calculate VD/VT, one would need to C) upper, higher PaCO2
simultaneously measure PaCO2 and: D) lower, lower PaO2
A) cardiac output. E) lower, lower PaCO2
B) end-tidal CO2. (RRT EXAMINATION NBRC
C) PAO2. MATRIX I,B,4,a)
D) alveolar ventilation.
5. A normal PaO2 at rest that decreases
E) mean exhaled CO2.
during exercise may suggest the
presence of:
MATRIX I,B,9,c)
A) pulmonary embolus.
3. Which of the following disorders would B) pneumonia.
typically lead to a Qs/Q T calculation of C) pulmonary fibrosis.
24%? D) adult respiratory distress syndrome.
I. Pulmonary embolus E) atelectasis.
II. Acute respiratory distress syndrome (RRT EXAMINATION NBRC
III. Congenital heart defect MATRIX I,C,1,a)
Chapter
7
Oxygen Transport and Internal Respiration
Oxygen transport
a proper type and quality of hemoglobin are also necessary for optimal loading and unloading of O2, and
the heart and vessels are necessary to deliver the proper amount of oxygenated blood to all tissues in
proportion to their need.
Julius H. Comroe81
and internal respiration

The pulmonary gas exchange system is not an end in itself. It exists to meet the needs of organs, tissues, and
cells.
Julius H. Comroe81
Outline
Introduction, 165 Quantitative Oxygen Transport, 179
Blood Oxygen Compartments, 165 Dissolved Oxygen Transport, 179
Dissolved Oxygen, 165 Combined Oxygen Transport, 180
Solubility Coefficients, 165 Total Oxygen Transport, 180
Linear PO2Dissolved Oxygen Hemoglobin Abnormalities, 181
Relationship, 167 Carboxyhemoglobin, 181
Significance of the PaO2, 167 Hemoglobin Variants, 182
Combined Oxygen, 167 Fetal Hemoglobin, 183
Hemoglobin, 167 Methemoglobin, 183
Saturation, 170 Hemoglobin S, 184
Oxyhemoglobin Dissociation Internal Respiration, 186
Curve, 170 Cellular Oxygen Supply, 186
Oxygen Content, 176 Distance from Capillary, 187
Arterial Oxygen Content, 176 Arteriolar Constriction/Dilation, 187
Mixed Venous Oxygen Content, 176 Cellular Oxygen Utilization, 188
Arteriovenous Oxygen Content Variable Oxygen Extraction, 188
Difference, 178 Biochemical Respiration, 188
Cyanosis, 178 Exercises, 190
INTRODUCTION BLOOD OXYGEN COMPARTMENTS

The first step in delivering oxygen to the tis- Life-sustaining oxygen molecules may be present
sues, external respiration and oxygen loading in the blood in one of two forms or compart-
into the blood, has been discussed in detail in ments. Oxygen may be carried in the dissolved
Chapter 6. The second step in tissue oxygenation state or it may be carried in the combined state.
is oxygen transport as shown in Figure 7-1,B.
In this chapter, we will explore basic physiology Dissolved Oxygen
and pathology as it relates to oxygen trans- Solubility Coefficients
port. Finally, in the last section of this chapter, As described in Chapter 3, gases may diffuse
we will explore internal respiration, the final freely between liquid and gaseous phases
link in the oxygenation system. Internal respi- depending on the difference in partial pressure
ration and oxygen unloading to the tissues will between the two phases. This principle is impor-
include the release and use of oxygen by the tant in external respiration because the alveolar-
cells (see Fig. 7-1,C). capillary unit is essentially a liquid-gas interface.
165

Figure 7-1. Steps in oxygen delivery. The three steps or phases in oxygen delivery to the tissues include:
oxygen loading into the blood or external respiration (A), oxygen transport or delivery to the tissues (B),
and oxygen unloading from the blood and utilization by the tissues or internal respiration (C).
The partial pressure of oxygen in a freshly ven-

tilated alveolus is greater than the partial pres-
sure of oxygen in the blood. Thus, when blood
is exposed to alveolar gas, the partial pressure
of oxygen increases in the blood until it equili-
brates with the alveolus. Oxygen present in the
blood in this uncombined or free state is
referred to as dissolved oxygen or oxygen in
physical solution.
The volume of gas that dissolves in a given
liquid, however, depends on the solubility PO2 = 1 mm Hg
coefficient of the gas in that particular liquid.
.003 mL O2
A gas with a high solubility coefficient has a
greater volume of gas dissolved in a particular
fluid than a gas with a low solubility coefficient,
despite the fact that both gases may have the
same partial pressure.
The solubility coefficient of oxygen in blood
at 37 C is
100 mL of blood at 37 C
0.003 mL of O2/100 mL of blood/mm Hg
Figure 7-2. Solubility coefficient of oxygen in
As shown in Figure 7-2, this means that in a blood at 37 C. The solubility coefficient of oxygen
100-mL blood sample, 0.003 mL of oxygen in blood at 37 C is 0.003 mL O2/100 mL of
are dissolved for every 1 mm Hg of oxygen blood/mm Hg or 0.003 vol%/mm Hg.
Chapter 7 Oxygen Transport and Internal Respiration 167
partial pressure. The unit vol% is usually used a liquid and the partial pressure of a gas dis-
instead of the more cumbersome milliliters solved in a liquid. The volume is the critical
of gas per 100 mL of blood. Thus, 2 vol% of component regarding quantitative oxygen
oxygen in the blood is equivalent to 2 mL delivery to the cells. Nevertheless, partial pres-
of oxygen in 100 mL of blood. sure is not without important physiologic sig-
The solubility coefficient of a gas in a par- nificance in its own right. The partial pressure
ticular fluid also depends on temperature. As a of oxygen controls the driving pressure for dif-
rule, gases become less soluble as temperature fusion of oxygen throughout the body and to
increases, which is the reason why small bub- the cells and for the combination of oxygen
bles can be observed escaping water as it is with hemoglobin.
being heated but before it comes to a boil.
Solubility coefficients expressed for clinical Combined Oxygen
practice are generally expressed at body tem- Hemoglobin
perature, ambient pressure, saturated (BTPS). The volume of dissolved oxygen is clearly inad-
equate to meet the bodys metabolic needs. We
Linear PO2Dissolved Oxygen Relationship are fortunate, however, because we have a sub-
There is a linear relationship between arterial stance present in our blood that loosely binds
PO2 and the volume of oxygen dissolved in with oxygen in sufficient quantities to meet the
arterial blood. If 0.003 vol% is present when the bodys needs while at the same time it easily
PO2 is 1 mm Hg, 0.006 vol% is present when releases this oxygen to the tissues. This unique
the PO2 is 2 mm Hg (0.003 vol% 2). It follows substance is called hemoglobin (Hb). Even more
then that 0.3 vol% of oxygen is present when remarkable, this same miracle molecule can
PO2 is 100 mm Hg. The direct, linear relation- also carry carbon dioxide and protect the pH
ship between PO2 and the volume of oxygen dis- through buffering. Oxygen present in the blood
solved in the blood persists as PO2 increases still in combination with hemoglobin is called
further to very high levels (Fig. 7-3). combined oxygen or oxyhemoglobin.
Chemically, normal adult hemoglobin
Significance of the PaO2 (HbA) is made up of a heme group and a pro-
The previous discussion described the relation- tein group (globin). The Hb molecule is very
ship between the volume of gas dissolved in large and has a molecular weight of 64,500.
6
Dissolved O2 content in mL/100 mL bood
0
0 100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 1400 1500
PO2 (mm Hg)
Figure 7-3. PO2dissolved oxygen content. There is a direct, linear relationship between PO2 and the vol-
ume of oxygen dissolved in the blood.
Globin alone consists of four chains of amino the site of this iron. Oxygen and iron form a
acids: two alpha chains, each made up of 141 loose bond in this reversible reaction because
amino acids; and two beta chains, each com- iron remains in the ferrous (Fe2+) state. Because
prised of 146 amino acids. These long rows of there are four iron sites, each Hb
amino acids are called polypeptide chains. The molecule can carry four oxygen molecules (see
four independent polypeptide chains are Fig. 7-4,C and D). A further simplified schematic
shown schematically in Figure 7-4,B, and also of normal HbA is shown in Figure 7-5.
their integration into globin (see Fig. 7-4,A). Hb resides in red blood cells (erythrocytes)
A heme group is combined with each one of where it accounts for approximately one third
these amino acid chains. Each heme group, in of the intracellular space. This pigment (i.e., Hb)
turn, is made up of a porphyrin and iron (Fe). is also responsible for giving blood its charac-
Oxygen actually combines with hemoglobin at teristic red color. It is in tremendous supply in
2 2 2 2
1 1 1 1
A B
Globin Hemoglobin
2 2 2 2
1 1 1 1
C D
Figure 7-4. Schematic drawings of globin and hemoglobin. A and B, Globin is made up of four
polypeptide chains (two alpha chains and two beta chains). C and D, Each of the four polypeptide chains
is combined with a heme group. Oxygen combines with hemoglobin at the Fe site of each heme group.
Pulmonary artery-
arteriole-capillary
from heart
Inspired
air
Expired
air

Polypeptide
CO2
chain
Heme CO2
group Alveolus
O2
O2 O2
Figure 7-5. Schematic of normal human
hemoglobin A.
To heart
pulmonary
capillary-venule-
the body, and one erythrocyte contains as many vein
as 280 million molecules.10 The normal con- Venous capillary
centration of hemoglobin [Hb] is 15 g/100 mL Figure 7-6. Erythrocytes passing through
blood in men and 13 to 14 g/100 mL blood in capillaries single-file.
women.
The erythrocytes are biconcave discs
approximately 7 m in diameter. Technically,
they are corpuscles rather than cells because In the adult, erythrocytes are produced pri-
they extrude their nuclei just before they marily in the bone marrow under the control
mature. Remarkably, the size and flexibility of of the hormone erythropoietin. Erythropoietin
erythrocytes allow them to pass through the is secreted primarily in the kidney; however,
pulmonary capillaries in single file. Figure 7-6 small quantities are also produced in the
shows erythrocytes passing through a capillary liver.222 The secretion of erythropoietin may
single file. Due to their flexibility, as they pass increase 100-fold or more in the presence of
through, they actually assume a parachute-like anemia.223
shape (Fig. 7-7). Molecular biologists have been able to syn-
Approximately 2 to 10 million erythrocytes thesize erythropoietin; recombinant human
are produced each second, and the life span of erythropoietin (Epoetin) became available in
an erythrocyte is nearly 120 days. The normal 1985.223 Recombinant human erythropoietin
count is approximately 5.4 million cells/mm3 has been shown to be effective in the treatment
in men and 4.7 million cells/mm3 of blood in of anemia secondary to renal (kidney) failure.222
women. A decrease in either the erythrocyte Moreover, synthetic erythropoietin has also
count or the [Hb] is called anemia. shown promise in the treatment of sickle cell
Figure 7-7. Single-file movement of

erythrocytes through pulmonary capillaries.
disease, anemia of prematurity, and even as a oxygen (PO2) in the blood. There is a direct, but
substitute for transfusion.224226 Its effectiveness not linear, relationship between PaO2 and SaO2.
has even caused concern related to its potential If one were to expose 100 molecules of hemo-
abuse to enhance athletic performance.227 globin in blood to progressive increases in PO2
and to plot the SO2 at each PO2, a curve similar
Saturation to that shown in Figure 7-9 would result. This
As stated earlier, each hemoglobin molecule is S-shaped curve has tremendous physiologic
capable of combining with four oxygen mole- significance and is known as the oxyhemoglobin
cules. The affinity of hemoglobin for additional dissociation curve.
oxygen molecules is increased after combina- At low PO2 values (i.e., <60 mm Hg), small
tion with each single oxygen molecule.81 Thus, increases in PO2 would result in relatively large
hemoglobin tends to combine with either four increases in SO2. For example, 50% of the
oxygen molecules or none (i.e., it is either hemoglobin molecules would be oxygenated at
carrying oxygen or it is not). Thus, we can a PO2 of only 26 mm Hg (Fig. 7-10). As PO2 is
think of hemoglobin as being either saturated elevated to 40 mm Hg, saturation increases sub-
(oxygenated) or desaturated (unoxygenated). stantially to approximately 75%. Furthermore,
Oxygenated hemoglobin is called oxyhemoglo- this general trend continues as PO2 increases to
bin. Unoxygenated hemoglobin is called deoxy- 60 mm Hg where the corresponding saturation
hemoglobin or reduced hemoglobin, although is 90%. Beyond a PO2 of 60 mm Hg, however,
the latter term is chemically incorrect.10,81 saturation increases very slowly
The percentage of hemoglobin that is carry- and does not reach 100% until approximately
ing oxygen in arterial blood is called oxygen 250 mm Hg.81
saturation of arterial blood (SaO2) or simply sat- The oxyhemoglobin dissociation curve closely
uration (Fig. 7-8). Saturation is a measure of approximates two straight lines (Fig. 7-11); a
oxygen in the combined state. One must remem- rather steep line from PO2, 0 to 60 mm Hg,
ber, however, that this is only a percentage of and a straight flat line above 60 mm Hg. The
available hemoglobin and is in no way a meas- critical difference between the two portions is
ure of the actual quantity of hemoglobin present. that on the steep lower portion of the curve, a
small change in PO2 is associated with a large
Oxyhemoglobin Dissociation Curve change in oxygen saturation. Conversely, on
The percentage of hemoglobin that actually the flat upper portion, a large change in PO2 is
carries oxygen depends on several factors, but associated with only a small change in SO2.
most importantly on the partial pressure of The effect of PO2 on saturation may be more
Comparative saturations
100% Oxygen saturation
Sites filled
Saturation =
Total sites available
Figure 7-8. Comparative saturations. Saturation is equal to the percentage of hemoglobin that is carrying
oxygen. Hemoglobin can be carrying either four molecules of oxygen (oxygenated) or none (deoxygenated).
100
90
80
70
60
SO2 (%)
50
40
30
20
10
0
0 10 20 30 40 50 60 70 80 90 100 110 120
PO2 (mm Hg)
Figure 7-9. Oxyhemoglobin dissociation curve.
100
C
90
80 B
70
60
SO2 (%)
A
50
40
30
20
10
0
0 10 20 30 40 50 60 70 80 90 100 110 120
PO2 (mm Hg)
Figure 7-10. Key landmarks on the oxyhemoglobin dissociation curve. A, In the normal oxyhemoglobin
curve, the hemoglobin is 50% saturated at a PO2 of approximately 26 mm Hg. The PO2 necessary to obtain
50% saturation is called the P50. B, The normal PO2 of mixed venous blood is 40 mm Hg. Therefore, the
normal saturation of mixed venous blood is 75%. C, A critical point to remember in clinical practice is that
at a PO2 of 60 mm Hg, saturation is still 90%. Saturation falls quickly when PO2 falls below 60 mm Hg.
100
90 Figure 7-11. The oxyhemoglobin
80 curve as two straight lines. The oxy-
70 hemoglobin curve has two distinct
60 portions: a steep lower portion and a
SO2 (%)
50 flat upper portion. Because the end of

40 oxygen loading into the blood occurs
30 on the upper portion, it may be called
20
the association portion. The end of
oxygen unloading to the tissues occurs
10
on the steep portion, thus it may be
0
called the dissociation portion.
0 10 20 30 40 50 60 70 80 90 100 110 120
PO2 (mm Hg)
100
90
80
70
60
SO2 (%)
50
40
30
20
10
0
0 10 20 30 40 50 60 70 80 90 100 110 120
PO2 (mm Hg)
Figure 7-12. Oxyhemoglobin curve as a bar graph. The bar graph shows the large changes in saturation
that accompany PO2 changes on the steep lower portion of the curve. On the upper flat portion of the curve,
large changes in PO2 only slightly change saturation because it is almost 100%.
readily visualized when saturation is plotted as approximately 35% to 90% (total of 55%).
a bar graph, as shown in Figure 7-12. Thus, on the steep lower portion of the curve
This concept can be further illustrated if we there is a large change (55%) in saturation for
compare the effect on saturation of an identical a relatively small change (40 mm Hg) in PO2.
PO2 change on the two portions of the curve Conversely, when PO2 increases 40 mm Hg
(Fig. 7-13). When PO2 increases 40 mm Hg from 60 to 100 mm Hg, saturation increases
from 20 to 60 mm Hg, saturation increases from from 90% to 97% (total 7%). Thus, on the flat
100
90
80
70
60
SO2 (%)
50
40
30
20
10
0
0 10 20 30 40 50 60 70 80 90 100 110 120
PO2 (mm Hg)
Figure 7-13. Significance of PO2 changes on different portions of the curve. Saturation increases 55%
as PO2 increases by 40 mm Hg on the steep portion of the curve, whereas saturation increases by only
7% when PO2 increases by 40 mm Hg on the flat portion of the curve.
upper portion of the curve there is a small portion of the curve. The amount of oxygen in
change (7%) in saturation for a relatively large the combined state remains relatively constant.
change (40 mm Hg) in PO2. Obviously, this A diagnostic advantage of the association por-
same principle holds true when PO2 decreases tion of the curve is that early pulmonary disease
on the respective portions of the curve. can be detected by a decrease in PaO2, and
Comprehending this critical difference is the this can be accomplished before SaO2 decreases
essence of understanding the physiologic appreciably.
implications of this curve. Dissociation Portion. The end of oxygen
unloading from the blood to the tissues occurs
Association/Dissociation Portions on the dissociation (steep) portion of the curve.
The association (i.e., combination) of oxygen Because, on this portion, a small change in PO2
with hemoglobin occurs in the lungs as the PO2 greatly affects saturation, a large amount of
increases from 40 mm Hg in mixed venous additional oxygen can be supplied to the tissues
blood to approximately 100 mm Hg. Because by allowing venous PO2 to fall to levels just
the end of oxygen loading into the blood occurs slightly below normal. For example, a large
on the flat, upper portion of the curve, it is amount of oxygen would move from the blood
sometimes referred to as the association por- to the tissues as venous PO2 decreased from 40
tion of the curve. Conversely, the steep lower to 30 mm Hg. Thus, a mechanism exists to eas-
portion of the curve is sometimes referred to as ily deliver additional oxygen to the cells if
the dissociation portion of the curve because the metabolism increases or if supply of oxygen
end of oxygen unloading occurs on this portion is compromised, such as during a decline in
as PaO2 decreases from 100 to 40 mm Hg in the cardiac output.
systemic capillaries (see Fig. 7-11). The associa- Comprehension of this portion of the oxy-
tion part of the curve is important in the lungs, hemoglobin dissociation curve is also essential
whereas the dissociation part of the curve is for understanding the value and goal of low per-
important in the tissues. centages of oxygen therapy in chronic obstruc-
Association Portion. Normal adult PaO2 is tive pulmonary disease (COPD). Because most
approximately 100 mm Hg. Normal SaO2 is patients with COPD and acute pulmonary prob-
approximately 97% to 98%. At normal PaO2 lems have PaO2 values on the steep portion of
while breathing room air, hemoglobin is almost the curve, any small increase in PaO2 greatly
100% saturated. This is generally considered to increases SaO2 values. Thus, the volume of oxy-
be a physiologic advantage because the ability gen combined with hemoglobin can be increased
of the hemoglobin to carry oxygen is maximized substantially with only a small increase in PaO2.
under ordinary conditions. Conversely, however, This is important in COPD patients to avoid the
the association portion of the curve could be adverse effects of PaO2 greater than 60 mm Hg
viewed as a physiologic disadvantage if the body on ventilation that may occur.
was trying to add additional amounts of oxygen
to the blood. Increasing the PO2 above normal Oxyhemoglobin Affinity/P50
does relatively little to add more oxygen to the P50. The oxyhemoglobin dissociation curve
blood because the hemoglobin is already maxi- is a graphic representation of how PO2 normally
mally saturated. affects the combination of oxygen with hemo-
It is likewise interesting that PO2 can decrease globin. The specific affinity of oxygen for
by 40 mm Hg below normal down to a PaO2 of hemoglobin can be quantitated by evaluating
60 mm Hg while SaO2 remains at 90%. This what partial pressure of oxygen is necessary
serves as an excellent defense mechanism in to achieve 50% saturation. This standardized
that the PaO2 may decrease substantially while index of Hb-O2 affinity that is measured at
the combination of oxygen with hemoglobin 37 C, PCO2 of 40 mm Hg, and a pH of 7.40
will be only slightly decreased. Thus, the is called the P50.184 Normal P50 is about
decrease in PaO2 observed at high altitude, or 26 mm Hg, approximately 27 mm Hg in women
during the aging process, does not significantly and 25 mm Hg in men.185 In other words,
decrease the SaO2 when one remains on the flat 26 mm Hg of oxygen pressure is normally
Decreased P50 (increased affinity) Box 7-2 Decreased Hb-O2 Affinity/

100 Temperature
Hemoglobin saturation (%)
PCO2 Right Shift of Hb-O2 Curve

80 2,3-DPG A increase in any of the following will decrease
pH
Hb-O2 affinity and will shift the oxyhemoglobin
60 dissociation curve to the right.
1. Temperature
40 Increased P50 (decreased affinity) 2. Hydrogen ion concentration ( pH)
Temperature
PCO2
3. PCO2
20 4. DPG
2,3-DPG
pH
0
0 20 40 60 80 100
Oxygen partial pressure (torr) The fact that high PCO2 and low pH
decreases Hb-O2 affinity is known as the Bohr
Figure 7-14. Oxyhemoglobin affinity. The affinity effect. An increase in oxygen similarly decreases
of hemoglobin for oxygen is expressed as the hemoglobin affinity for CO2, and this is known
P50. Increases in PCO2, temperature, or DPG; and as the Haldane effect.
decreases in pH shift the curve to the right (increased
P50 = decreased affinity). Opposite changes shift the
Clinical Effects of Hb-O2 Curve Shifts
curve to the left (decreased P50 = increased affinity).
A shift of the curve to the left and increased
Hb-O2 affinity would appear to benefit the
required to oxygenate 50% of the hemoglobin patient because hemoglobin could more easily
(see Fig. 7-10). pick up oxygen. However, hemoglobin is 97%
saturated with normal Hb-O2 affinity; therefore,
Shifts of the Curve oxygen loading is not enhanced appreciably with
At least four factors are known to alter Hb-O2 a shift of the curve to the left. Furthermore, this
affinity. As shown in Figure 7-14, temperature, increased Hb-O2 affinity impedes the release of
pH, or PCO2 may shift the oxyhemoglobin oxygen to the tissues and generally has a net
curve. In addition, the concentration of the detrimental effect.
substance 2,3-diphosphoglycerate (DPG) Decreased Hb-O2 affinity and a shift of the
within the erythrocyte is similarly known to curve to the right, on the other hand, generally
affect Hb-O2 affinity. enhances oxygen delivery to the tissues and
Affinity of oxygen for hemoglobin increases is often a valuable compensatory mechanism.
when there is a decrease in temperature, hydro- Figure 7-15 shows the amount of oxygen that
gen ion concentration, PCO2, or DPG (Box 7-1). is released to the tissues with various positions
A decrease in hydrogen ion concentration is of the curve and assuming a normal PaO2
associated with an increased pH. Conversely and mixed venous PO2 (PvO2). The amount of
(see Fig. 7-14), Hb-O2 affinity is decreased when oxygen released to the tissues is least when the
there is an increase in temperature, hydrogen ion curve is shifted to the left (see Fig. 7-15,B).
(decreased pH), PCO2, or DPG (Box 7-2). Conversely, the amount of oxygen released to
the tissues is greatest when the curve is shifted
to the right (see Fig. 7-15,C). A shift of the
curve to the right in an individual with a PaO2
Box 7-1 Increased Hb-O2 Affinity/ of 90 mm Hg and a normal PvO2 of 40 mm Hg
Left Shift of Hb-O2 Curve could enhance oxygen release to the tissues by
A decrease in any of the following will increase as much as 60%.186
Hb-O2 affinity and will shift the oxyhemoglobin In conclusion, although a shift of the curve
dissociation curve to the left. to the left tends to enhance the combination of
1. Temperature hemoglobin with oxygen, it may be detrimental
2. Hydrogen ion concentration ( pH) to the patient because the release of oxygen to
3. PCO2
the tissues will be impeded. On the other hand,
4. DPG
a shift to the right is usually beneficial because
20 100
B
A
C
16 80

O2 content (mL/100 mL)
B
12 A 60
P50 C
8 40
4 20
Tissue Arterial
0 0
0 20 40 60 80 100
PO2 (mm Hg)
Figure 7-15. Effects of shifts of curve on tissue oxygen delivery. A, The normal Hb-O2 curve and the
amount of oxygen released to the tissues from hemoglobin. B, A left shift tends to decrease tissue oxygen
release. C, A shift to the right tends to increase oxygen release to the tissues.
the release of oxygen to the tissues is enhanced. would increase P50 by 10 mm Hg (e.g., P50 = 36
This benefit may be negated, however, when mm Hg). DPG increases in various situations
PaO2 is less than 60 mm Hg. When hypoxemia and appears generally to be an adaptive mech-
is present, shifts of the curve to the right may anism in hypoxic insults. Several conditions
substantially decrease oxygen loading into that have been associated with high DPG lev-
the blood, and this factor may outweigh any els are shown in Box 7-3.
benefits in terms of oxygen unloading.186 DPG increases relatively quickly as a com-
pensatory mechanism. Measurable increases in
2,3-Diphosphoglycerate DPG may be seen within 60 minutes after stren-
Organic phosphates represent a chemical group uous exercise.189 The increase in DPG enhances
normally present in erythrocytes. These organic oxygen unloading and helps to offset deficien-
phosphates tend to bind with hemoglobin cies in the transport or loading of oxygen.
and thus reduce affinity of hemoglobin for oxy- Decreased 2,3-Diphosphoglycerate. Con-
gen.187,188 A decrease in Hb-O2 affinity will, versely, DPG concentrations may be less than
of course, shift the oxyhemoglobin dissociation normal in several conditions such as those
curve to the right. Therefore, the large amounts shown in Box 7-4. Septic shock is a cardiovas-
of organic phosphates present within the ery- cular problem associated with bacterial infection
throcytes are generally considered to be bene- of the blood. Acidemia is a below-normal pH
ficial. The most important inorganic phosphate
is DPG, primarily because it is the most
abundant.185,189
Furthermore, changes in DPG tend to have Box 7-3 Conditions Associated
a sustained effect on Hb-O2 affinity whereas the with Increased DPG
shift of the curve to the right that accompanies Anemia
an increased hydrogen ion concentration, for Hyperthyroidism
example, lasts for only a few hours.185 Hypoxemia associated with COPD
Increased 2,3-Diphosphoglycerate. A twofold Congenital heart disease
increase in DPG, which could occur clini- Ascent to high altitude
Low output heart failure
cally, would greatly enhance oxygen unloading
Healthy subjects after strenuous exercise
to the tissues. A twofold increase in DPG
Box 7-4 Conditions Associated Box 7-5 Arterial Oxygen Content

with Decreased DPG Volume of dissolved oxygen
Septic shock +
Volume of combined oxygen
Certain enzyme deficiencies
TOTAL OXYGEN CONTENT
Acidemia
Blood stored in ACD
To calculate the volume of combined oxygen

in arterial blood, one must know the hemoglo-
of the blood. The fact that acidemia decreases bin concentration [Hb], arterial oxygen satura-
DPG levels probably explains why high DPG tion (SaO2), and the oxygen-carrying capacity of
levels are not seen consistently in acute crisis of hemoglobin. The oxygen-carrying capacity of
patients with COPD.190 The increased DPG hemoglobin is a constant value of 1.34 mL O2/g
associated with hypoxemia in these patients HbO2.81 Theoretical calculations suggest that
may be offset by the decreased DPG associated this value should be 1.39 mL O2/g HbO2; how-
with acidemia. ever, this amount is never achieved in humans
Probably the most common clinical cause of because of the presence of hemoglobin vari-
DPG deficiency, however, is the intravenous ants.185 Thus, in calculations here, it is assumed
infusion of stored blood into a patient. DPG that for every gram of oxygenated hemoglobin,
decreases rapidly in blood stored in acid-citrate 1.34 mL O2 is present.
dextrose preservative and falls to approxi- The formula for calculating the volume of
mately one-third of normal after approximately combined oxygen is shown in Box 7-7. SaO2 is
1 week of storage.191 Within 2 weeks of storage multiplied by the [Hb] to determine the amount
at 4 C, DPG is almost completely absent.192 of oxygenated hemoglobin present. Then, the
Nevertheless, low DPG levels would not pre- HbO2 in grams is multiplied by the oxygen-
clude a transfusion in a patient who is anemic. carrying capacity of hemoglobin to determine
It is possible to restore DPG in stored blood the volume of oxygen in the combined state.
to normal levels within 30 minutes, which can Assuming a normal [Hb] of 15 g% and an SaO2
be accomplished by incubating the blood with of 98%, the volume of combined oxygen in
inosine, pyruvate, and phosphate.192 This pro- arterial blood is approximately 19.7 vol%.
cedure is not clinically useful, however, because Finally, the CaO2 is equal to the sum of dis-
inosine has been associated with adverse solved and combined oxygen (Box 7-8). Normal
effects when administered intravenously.189 CaO2 is approximately 20 vol%. Approximately
Furthermore, DPG levels increase to approxi- 98% of the oxygen in the blood is in the
mately 50% of normal in approximately 24 combined state (Fig. 7-16). For this reason,
hours after the administration of the blood.193 CaO2 correlates very closely with SaO2 and the
oxyhemoglobin dissociation curve as shown in
Oxygen Content Figure 7-17. PaO2, on the other hand, only
Arterial Oxygen Content reflects blood oxygen volume indirectly.
The total volume of oxygen present in arterial
blood is called arterial oxygen content (CaO2). Mixed Venous Oxygen Content
The oxygen content can be calculated by adding Obviously, venous blood returning to the heart
the volume of oxygen present in the two blood will contain less oxygen than arterial blood.
compartments, as shown in Box 7-5. The vol-
ume of dissolved oxygen in arterial blood is cal-
culated by multiplying the PaO2 by the solubility Box 7-6 Normal Volume of Oxygen
coefficient of oxygen in blood (CsO2 = 0.003 mL Dissolved in Arterial Blood
O2/100 mL blood/mm Hg). The normal volume
of oxygen dissolved in arterial blood is approxi- PaO2 CsO2 = volume of dissolved O2
(100 mm Hg) (0.003 vol%/mm Hg)
mately 0.3 vol% (0.3 mL O2/100 mL of blood),
= 0.3 vol% O2
which is calculated in Box 7-6.
Box 7-7 Normal Volume of Oxygen Combined in Arterial Blood

[Hb] SaO2 1.34 mL O2/g HbO2 = volume of combined O2
(15 g/100 mL blood) (0.98) 1.34 mL O2/g HbO2 = 19.7 vol%
Box 7-8 Normal CaO2

Dissolved O2 + Combined O2 = CaO2
0.3 vol% + 19.7 vol% = 20 vol%
19.7 vol%
O2 O2 O2 O2
Hb O2 Hb
O2 O2
O2 O2 O2 O2 O2 O2
Hb
Hb
O2 O2 O2
O2 O2 O2
O2 O2
Hb O2 O2 O2 Hb
O2
O2 O2 Hb Hb
O2 O2 O2 O2
O2
.3 vol%
Volume of Volume of
dissolved combined
O2 (2%) O2 (98%)
Figure 7-16. Distribution of oxygen in the blood.
24
Dissolved oxygen
22
Volume (mL) oxygen/100 mL blood
Combined oxygen
20
18
16
14
12
10
8
6
4
2
0
0 10 20 30 40 50 60 70 80 90 100 110 120
PO2 (mm Hg)
Figure 7-17. Oxygen content by compartment. The total oxygen content of the blood is primarily a result
of the degree of saturation of hemoglobin. Thus, this bar graph of oxygen content closely resembles the
oxyhemoglobin curve. There is, however, a small linear increase in dissolved oxygen content with increased
PO2. At normal PO2 of 100 mm Hg, 98% of oxygen is in the combined form.
Box 7-9 Mixed Venous Oxygen Content

Dissolved O2 = Pv- O2 CsO2
Dissolved O2 = (40 mm Hg) (0.003 vol%/mm Hg) = 0.12 vol%
Combined O2 = [Hb] Sv- O2 O2 carrying capacity
Combined O2 = (15 g%) (0.75) (1.34 mL O2/g) = 15.08 vol%
Oxygen content = dissolved O2 + combined O2
Oxygen content = (0.12 vol%) + (15.08 vol%) = 15.2 vol%
As discussed in Chapter 3, peripheral venous reflected an increased cardiac output. For exam-
blood varies in its oxygen volume depending ple, a C(a v)O2 of 10 vol% suggests a low car-
on the specific tissue it is returning from. diac output, whereas a C(a v)O2 of 2.5 vol%
Mixed venous blood, however (available only suggests an increased cardiac output.
from a pulmonary artery catheter), is an aver- More recently, however, it has been shown
age of all venous blood and normally has a that oxygen consumption is not constant in
PvO2 of approximately 40 mm Hg and an SvO2 critically ill patients, even over short periods.
of 75% (see Fig. 7-10). The oxygen content of Therefore, the C(a v)O2 should not be consid-
mixed venous blood can thus be calculated by ered to be a reliable indicator of cardiac output.
adding dissolved oxygen and combined oxy- The C(a v )O2 divided by CaO2 is called the
gen, which is shown in Box 7-9. oxygen extraction ratio or the oxygen utiliza-
tion coefficient. The normal oxygen extraction
Arteriovenous Oxygen Content Difference ratio is 25% (5 vol% divided by 20 vol%). This
The difference in oxygen content between arterial index may be useful for monitoring and pre-
and mixed venous blood C(a v)O2 is approx- dicting outcome in critically ill patients.228
imately 5 vol% and is shown in Box 7-10.
Thus, for every 100 mL of blood that perfuses Cyanosis
the tissues, approximately 5 mL of oxygen is Cyanosis is a clinical condition in which a
normally released to the cells. The Fick equation patients skin, mucous membranes, or nailbeds
(Box 7-11) shows the . relationship between appear blue or gray. Blue discoloration of the
cardiac minute output (Q), arteriovenous oxy- skin is sometimes referred to as peripheral
gen content difference
. C(a v)O2, and oxygen cyanosis, whereas discoloration of the mucous
consumption (VO2). Given a normal cardiac membranes may be called central cyanosis.
output of approximately 5 L/min and an arte- Peripheral cyanosis is difficult to detect in
riovenous oxygen content difference of 5 vol%, dark-skinned individuals. Cyanosis has long
the total amount of oxygen delivered and been a clinical sign known to be frequently
consumed by the tissues is approximately associated with inadequate oxygenation status
250 mL/min. and hypoxia.
In some clinical situations, oxygen consump- The color observed is a result of the increased
tion is constant over short periods; thus mak- quantity of desaturated hemoglobin present in
ing cardiac output and the C(a v)O2 inversely many types of oxygenation disturbances. The
proportional. Indeed, C(a v )O2 was often percentage of desaturated hemoglobin is the dif-
used in the past as an indicator of cardiac out- ference between total hemoglobin (100%) and
put; high gradients indicated a decrease in car- oxygenated hemoglobin (SO2). For example,
diac output, whereas low gradients supposedly if SO2 is 90%, then the percentage of desatu-
rated hemoglobin (Hb %desat) is the remainder
or 10%.
Box 7-10 Normal C(a v- )O2 Cyanosis can usually be observed when the
average quantity of desaturated hemoglobin
CaO2 Cv-O2 = C(a v-)O2
in the capillaries is approximately 5 g/100 mL
20 vol% 15.2 vol% = 4.8 vol%
of blood. The unit usually used in place of
Box 7-11 Fick Equation

Cardiac output arteriovenous oxygen content
. difference = O
. 2 consumption
Q C(a v) O2 = VO2
(5000 mL blood/min) (5 mL O2/100 mL blood) = 250 mL O2/min
g/100 mL of blood is g%. Thus, cyanosis QUANTITATIVE OXYGEN

is observed in the presence of an average TRANSPORT
of 5 g% of desaturated hemoglobin in the
capillaries. Dissolved Oxygen Transport
The average quantity of desaturated hemo- Oxygen transport, sometimes referred to as oxy-
globin in the capillary can be calculated by gen delivery, is defined as the volume of oxygen
averaging the amount of desaturated hemoglo- leaving the left ventricle of the heart each minute.
bin entering the capillary (i.e., arterial blood) Assuming that a patient had no hemoglobin
with the amount of desaturated hemoglobin and could carry oxygen only in the dissolved
leaving the capillary (i.e., venous blood), state, oxygen transport would be calculated
which is shown in Box 7-12. Normally, [Hb] is (Box 7-14). Under basal metabolic conditions,
15 g%, SaO2 is approximately 98%, and SvO2 the average young man consumes approximately
is 75%. Thus, (Hb %desat) of arterial blood is 250 mL O2/minute, whereas women consume
about 2% (i.e., 100% 98% = 2%), and (Hb slightly less. Basal metabolic conditions exist
%desat) of venous blood is approximately when an individual is resting and fasting but
25% (i.e., 100% 75% = 25%). Thus, the is not asleep.185 Dissolved oxygen transport
normal average amount of desaturated Hb (15 mL O2/minute) is clearly inadequate to
(Hb desat) is approximately 2 g% (Box 7-13). meet the tissue oxygen requirements of humans
Obviously, if arterial or venous blood is even at rest.
poorly oxygenated (highly desaturated), at some The quantity of oxygen transported in the
point, there will be an average of 5 g% of desat- dissolved state could be increased only by
urated hemoglobin and cyanosis will be evident. increasing one of the factors in the formula
It has also been observed that cyanosis is shown in Box 7-14. To meet tissue requirements,
typically seen when SaO2 decreases to approx- cardiac output would have to increase to
imately 85%.194 83 L/minute at rest and 166 L/minute during
It is important to realize, however, that exercise, assuming the volume of dissolved
cyanosis is only present when a certain quantity oxygen remained constant.81 This, of course, is
of desaturated hemoglobin is present. Thus, in impossible because the maximum cardiac output
the presence of anemia, an individual may be even during exercise in a well-conditioned
very poorly oxygenated yet cyanosis will not athlete may be only 30 to 40 L/minute.229
be seen. Conversely, in the presence of poly- Alternatively, dissolved oxygen transport
cythemia, cyanosis may be present even though could be increased by increasing dissolved
the individual is adequately oxygenated.
In summary, although cyanosis may suggest
hypoxia, its presence or absence must always be Box 7-13 Calculation of the Normal
interpreted in light of the patients actual [Hb]. Average Desaturated
Hemoglobin in Capillaries
[Hb] arterial (Hb %desat) + [Hb] venous (Hb %desat)
Box 7-12 Calculation of Average 2
Desaturated Hemoglobin (15 g%) (0.02) + (15 g%) (0.25)
in Capillaries =
2
[Hb] arterial(Hb %desat) + [Hb] venous(Hb %desat) (0.3 g%) + (3.7 g%)
= = 2 g%(Hb desat)
2 2
Box 7-14 Dissolved Oxygen Transport

(Cardiac output) (volume of dissolved O2) = dissolved O2 transport
(5000 mL blood/min) (0.3 mL O2/100 mL blood) = 15 mL O2/min
Box 7-15 Combined Oxygen Transport

(Cardiac output) (volume of combined O2) = combined O2 transport
(5000 mL of blood/min) (19.7 mL O2/100 mL blood) = 985 mL O2/min
Box 7-16 Total Oxygen Transport

(Cardiac output) (CaO2) = O2 transport
(5000 mL of blood/min) (20 mL O2/100 mL blood) = 1000 mL O2/min
oxygen content, which depends on the PaO2 and tissues each minute regardless of the method
the solubility coefficient for oxygen in blood. in which it is carried. The formula for oxygen
An increase in either of these factors would transport is shown in Box 7-16. The phrase
directly enhance oxygen transport. Because PO2 oxygen delivery is synonymous with oxygen
and oxygen content are directly related, tissue transport.
oxygen demands could be met if PO2 was suf-
ficiently high. Unfortunately, PO2 would need
120
to be approximately 2000 mm Hg to meet
basal metabolic needs. Although a PaO2 in this
range could be achieved through the adminis-
tration of FIO2 1.0 at 3 atm in a hyperbaric 100
chamber, these devices are often not available
and high FIO2 values may lead to oxygen
toxicity.
Oxygen transport % normal
80
Finally, certain blood substitutes with very
high solubility coefficients may be adminis-
tered, although their use has been limited.
60
Combined Oxygen Transport
The volume of combined oxygen transport can
be calculated as shown in Box 7-15. Using the
40
normal volume of combined oxygen in the
arterial blood, which was calculated in Box 7-7,
combined oxygen transport is approximately
985 mL O2/minute. This amount is almost four 20
times that of oxygen required under basal con-
ditions (i.e., 250 mL O2/minute). Furthermore,
during heavy exercise, oxygen consumption 0
may increase 10-fold.239 Thus, the tremendous 10 20 30 40 50 60 70
value of hemoglobin in oxygen transport can be Hematocrit
appreciated. Figure 7-18. Oxygen transport vs. hematocrit
level. Slight elevations in hematocrit increase oxygen
Total Oxygen Transport transport above normal due to increased oxygen
Total oxygen transport, or simply oxygen carrying capacity. Large increases in hematocrit
transport, is a quantitative measure of all diminish oxygen transport secondary to increased
the oxygen that is transported out to the blood viscosity and decreased cardiac output.
One can see through these calculations that as HbCO levels are expressed usually as a per-
[Hb] increases there will be a corresponding centage of total hemoglobin. Levels as high as
increase in oxygen transport as long as cardiac 10% may be observed in heavy cigarette
output remains constant. Notwithstanding, how- smokers. Crack smoking has also been associ-
ever, as [Hb] increases, there will be a correspon- ated with increased HbCO levels, which could
ding increase in blood viscosity, which, in turn, further aggravate cocaine-induced cardiac
may decrease cardiac output. Figure 7-18 illus- problems.195
trates how oxygen transport tends to increase up Carbon monoxide is produced by the incom-
to a hematocrit of approximately 33% but plete combustion of carbonaceous substances.
beyond this level, oxygen transport actually tends Thus, critically high HbCO levels generally only
to decline because of a decreased cardiac output occur after inhalation of gasoline engine
secondary to increased blood viscosity. exhaust, or in conjunction with injuries caused
by smoke inhalation (e.g., fires, etc.). Indeed,
HEMOGLOBIN ABNORMALITIES 60% to 80% of early smoke inhalation deaths
are due to HbCO rather than cutaneous
Carboxyhemoglobin burns.196 Typically HbCO toxicity occurs when
Carbon monoxide (CO) is a colorless, odor- exposed to high levels of CO in a closed or
less, tasteless toxic gas that competes with oxy- poorly ventilated environment. Occasionally,
gen for the same molecular site on the however, high levels and even fatalities have
hemoglobin molecule. CO has almost 245 been reported outdoors following prolonged
times more affinity for hemoglobin than does use of gasoline- or oil-burning equipment.203
oxygen.230 Given 100 available molecules of Traditionally, HbCO has been considered to
hemoglobin in 21% oxygen and 0.01% CO, be harmful to cellular oxygenation in two
half of the molecules would combine with oxy- ways. First, hemoglobin combined with CO is
gen and half would combine with CO despite incapable of carrying oxygen at that molecular
the much lower concentration of CO. site. Second, HbCO shifts the oxyhemoglobin
Hemoglobin combined with CO forms the curve to the left and makes oxygen unloading
substance carboxyhemoglobin (HbCO). to the tissues more difficult. The leftward shift

A postoperative 55-year-old woman arrives in the recov- HR 90/min

ery room following cardiac surgery. She appears pale RR 25/min
and uncomfortable. Temp 37 C
ARTERIAL BLOOD GASES ASSESSMENT

FIO2 0.60 Abnormalities: List abnormal data and other noteworthy
SaO2 95% information. Classify ABG
pH 7.30 Explanation: List possible diseases, pathology, or
PaCO2 37 mm Hg other situations that may have led to this patients
PaO2 94 mm Hg condition.
[HCO3] 20 mEq/L Evaluation: Suggest additional data that would be useful
in helping understand the situation or in making a
LABORATORY WORK diagnosis.
[Hb] 5 g%
[WBC] 8000 mm3 INTERVENTION
Importance: Prioritize concern(s) of treatment in order
VITAL SIGNS of urgency and/or seriousness as you see the overall
BP 130/85 situation.
100 plasma rather than to the HbCO concentration

Available hemoglobin saturation (%)
HbCO Normal per se.198 The highly variable toxicity in patients

50% with comparable HbCO levels is consistent
80
with this theory.199 Some patients are severely
toxic at HbCO levels of only 20%, whereas
60
other patients are nearly asymptomatic (e.g.,
headaches) at levels as high as 50%.200
40 Regardless of the exact mechanism and in the
absence of a simple alternative, HbCO levels,
20 which are easily attained with CO-oximetry, still
probably provide the best markers of the degree
of CO toxicity.201 Notwithstanding, one should
0
0 20 40 60 80 100 always focus treatment on the total patient pic-
PO2 (mm Hg) ture versus simply the laboratory value.199
Administration of FIO2 1.0 is very effective
Figure 7-19. Effect of HbCO on oxyhemoglobin in the treatment of high HbCO levels. FIO2 1.0
affinity. In addition to occupying heme sites in place is effective because it reduces the half-life of
of oxygen, carboxyhemoglobin also increases HbCO from 5 hours and 20 minutes to approx-
the affinity of Hb for oxygen and shifts the
imately 1 hour and 20 minutes.202 In addition,
oxyhemoglobin curve to the left.
a secondary benefit is a slight increase in dis-
solved oxygen content because of the increased
PaO2. Hyperbaric oxygen, when available, is
of the curve is often depicted as shown in even more effective in the treatment of CO poi-
Figure 7-19; however, Figure 7-20 is probably soning because it reduces the half-life of HbCO
a better way to illustrate the decrease in oxy- to 23 minutes.202
genation because the available [Hb] is likewise
decreased with the formation of HbCO.197 Hemoglobin Variants
Although toxicity is typically measured as The hemoglobin described earlier is normal adult
HbCO%, substantial evidence suggests that hemoglobin (HbA). More than 120 variations
the toxicity of CO may be due primarily to the of hemoglobin, however, have been identified.
direct metabolic effects of dissolved CO in the Any small change in the sequence of amino
Normal
100
10% CO
80
30% CO
60
50% CO
40
20
0
0 20 40 60 80 100 120 140 600
PO2 (mm Hg)
Figure 7-20. Additive effect of left shift and increased HbCO% on oxyhemoglobin curve.
acids in the hemoglobin molecule results in a syndrome, it is lower still at nearly 16 mm Hg.232
different form of hemoglobin that may have Thus, through HbF, the fetus can attract oxy-
very different chemical properties. Originally, as gen from maternal HbA because of its greater
new forms of Hb were recognized, they were affinity. Furthermore, oxygen transport is fur-
named according to the letters of the alphabet ther enhanced in the infant because of a higher
(e.g., HbS, HbM, etc.). It soon became appar- hemoglobin concentration ([Hb] 18 g% in a
ent, however, that there would be more than term infant).
26 types of hemoglobin; therefore, new forms Ninety-five percent of hemoglobin present
of hemoglobin were named according to the in the fetus at 10 weeks gestation is HbF.231 At
geographic region where they were first dis- approximately 30 weeks gestation, the concen-
covered (e.g., Hb Kansas, Hb Beth Israel). tration of HbF begins to decline; and at term
Several hemoglobin variants have an altered the concentration of HbF is roughly 80%. HbF
affinity for oxygen. For example, Hb Kansas should continue to decline after birth, falling
has a P50 of 70 mm Hg, whereas Hb Rainier to 50% at 1 to 2 months and 5% at 6 months.
has a P50 of 12 mm Hg (Fig. 7-21). HbH has Often, HbF may even fall to normal adult
12 times more affinity for oxygen than HbA levels (<2%) after the first 6 months of life.233
and cannot release oxygen to the tissues. The Failure of HbF to decline has been observed
three hemoglobin variants of common clinical in certain pathologic conditions, such as beta
significance are HbF, HbM, and HbS. These thalassemia.231 More recently, elevated levels
species of hemoglobin are discussed in the of HbF have been shown in sudden infant
following sections. death syndrome and may help to shed some
light on this disorder, although the significance
Fetal Hemoglobin of this finding remains unclear.234
Fetal hemoglobin (HbF) is found in the fetus and
has a greater affinity for oxygen than HbA, Methemoglobin
presumably because it is less affected by DPG.81 A small portion of hemoglobin in the red blood
The P50 of normal HbF is about 20 mm Hg.231 cell normally undergoes a slight chemical change
In premature infants, P50 is approximately and forms methemoglobin (metHb). This change
18 mm Hg and in infant respiratory distress occurs when the ferrous ion loses an electron
and is thus transformed to the ferric state. In
this event, hemoglobin is oxidized (i.e., loss of
an electron) rather than oxygenated.
100 Methemoglobin is useless in the transport of
Hb Rainier oxygen. Normal metHb concentration is
80 approximately 1%.
Hb A Methemoglobinemia is defined usually as a
O2 saturation (%)
Hb Seattle metHb concentration exceeding 1% to 2%.

60
High levels of metHb may be acquired or con-
genital. Methemoglobinemia may be caused by
40 ingestion of amyl nitrate or nitroglycerin. Amyl
Hb Kansas
nitrite, snappers, and other volatile nitrites are
sometimes used as a recreational drugs for stim-
20
ulant, aphrodisiac, or psychedelic effects.204
These drugs may lead to rapid onset of severe
0 methemoglobinemia (30% to 70% metHb)
0 20 40 60 80 and an individual who presents to the emer-
O2 pressure (mm Hg) gency department incoherent and with severe
Figure 7-21. Hemoglobin variants with abnormal cyanosis.204,205
affinity. Hb Kansas has decreased oxygen affinity Topical anesthetics have frequently
and a P50 of 70 mm Hg. Hb Rainier has increased been implicated in the abrupt onset of methe-
affinity for oxygen and a P50 of 12 mm Hg. moglobinemia. Twenty-percent benzocaine
(e.g., Hurricaine spray) and prilocaine have been 100

implicated in several cases of acute onset severe SpO2
(Nellcor)
methemoglobinemia especially when the normal
dose is exceeded.209,210 80
Infants younger than 6 months of age are
particularly vulnerable to dietary methemoglo-
% Saturation
binemia, especially when exposed to well water
that contains nitrates.235 Nitrates may be con- 60
verted to nitrites by bacteria in the intestines,
thus leading to methemoglobinemia.204 Likewise,
infants exposed to topical anesthetics used as SaO2
40
teething gels for the relief of pain have also
developed severe methemoglobinemia.207,208 FIO2 = 1.0
Hemoglobin M is a congenital hemoglobin
variant that is functionally the same as 20
0 20 40 60 80
metHb in that it too is oxidized when exposed
% Met Hb
to oxygen.
Abrupt onset of severe cyanosis, especially Figure 7-22. Comparison of pulse oximetry read-
following administration of topical anesthetics, ings at various levels of metHb%. With increasing
should alert one to the possibility of methemo- concentrations of metHb, the pulse oximeter
globinemia. Cyanosis typically appears with readings tend to plateau around 85%.
metHb levels of approximately 15%.211 Other
researchers have described the clinical presen-
tation as cyanosis with a normal or high Sulfhemoglobin is present if oxyhemoglobin
PaO2206,211 or, in the case of inherited methe- combines with hydrogen sulfide. The blood may
moglobinemias, as being more blue than sick.236 also appear chocolate and measurements via
Another clue to the onset of methemoglo- co-oximetry may indicate high levels of methe-
binemia may be a modest decrease in SpO2 via moglobin because the absorption characteristics
pulse oximetry (e.g., 98% falling to 94%).212 are similar. Even low doses of sulfhemoglobin
Interestingly, however, with increasing levels of may cause severe cyanosis. Sulfhemoglobin
methemoglobin, the pulse oximeter tends to appears to be less toxic than methemoglobin
migrate towards an SpO2 reading of 85% probably because it shifts the oxyhemoglo-
(Fig. 7-22).213 Blood with elevated metHb will bin curve to the right. Sulfhemoglobin should
typically appear brown, rusty, or even black be suspected when the patient with presumed
and this too may be a useful clue to diagnosis. methemoglobinemia does not respond to
Ultimately, laboratory analysis via spectropho- methylene blue.214
tometry confirms the diagnosis.
Methylene blue accelerates the reduction of Hemoglobin S
metHb and may be useful in the treatment of Hemoglobin S is identical to HbA with the
some forms of this disorder. Methylene blue is exception that one of the 146 amino acids in the
usually administered intravenously at a rate of beta chains of globin is different. HbS results
1 to 2 mg/kg in adults and 2 mg/kg in infants; when glutamate is substituted for valine on
it should be administered slowly over 5 min- position 6 of the beta chain.215 This seemingly
utes and repeated if cyanosis persists for minute difference, however, is responsible for
1 hour.204 Often, relatively high levels of metHb the pathophysiology of sickle cell disease.
(i.e., >35%) are fairly well tolerated, and treat- Sickle cell anemia is an inherited disorder
ment may not be necessary. observed in patients who are homozygous
Although less common, another type of (i.e., inherited from both parents) for HbS. Sickle
abnormal hemoglobin, sulfhemoglobinemia, cell anemia is present in nearly 1% of African
may be mistaken for methemoglobinemia. Americans.215 The frequent painful episodes
A B C
Red cell
Polymorphonuclear
leukocyte
Intima
Endothelial cell
Platelet
D E
Figure 7-23. Pathophysiologic progression in sickle cell disease. A, Normal circulation. B, Red cell adher-
ence to vessel wall. C, Sickling of bound cell. D, Sickled red cells obstruct flow. E, Narrowing of vessel.
with sickle cell anemia is referred to in some Once the sickling phenomenon begins, addi-
African countries as the state of suffering,216 tional cells begin to sickle and obstruct blood
and the typical life span for these individuals is flow (see Fig. 7-23,D). Vaso-occlusion leads to
often less than 50 years.217 An individual expe- severe pain, destruction of endothelium, and ulti-
riencing one of the recurrent painful episodes mately narrowing of the vessel (see Fig. 7-23,E).
that affect almost every part of the body is said Vaso-occlusion often leads to cerebrovascular
to be in sickle cell crisis. accident, which is one of the most devastating
A purported sequence of vascular patho- consequences of the disease.220 Another very
physiology associated with sickle cell anemia is frequent occurrence in those with sickle cell
shown in Figure 7-23.216 Figure 7-23,A shows disease is acute chest syndrome. Acute chest
a normal vessel with circulating red blood
cells. Figure 7-23,B illustrates initial attach-
ment and lingering of a red blood cell to the
vascular internal (endothelial) wall.
This is followed by sickling of the red blood
cell as shown in Figure 7-23,C. Sickling occurs
because HbS has unique chemical properties
and is less soluble than HbA in the absence
of oxygen and tends to crystallize in the cells.
Figure 7-24 illustrates the characteristic
sickle shape of red blood cells observed under
microscope. Specifically, HbS is 50 times less
soluble than HbA in the deoxygenated
form.216 Low oxygen pressure, acidosis, and
hypothermia all tend to increase the sickling Figure 7-24. Sickle cell anemia. Note the presence
phenomenon.216 Interestingly, the presence of of abnormal sickle-shaped erythrocytes. These
increased HbF tends to diminish sickling and sickle cells are less pliable and are easily subject
enhance prognosis.218,219 to rupture (hemolysis).
syndrome is a term coined in 1979 to describe may be associated with an increased incidence
episodes of chest pain, fever, and leukocytosis of sudden unexplained death.223
(increased white blood cell counts).221 In addi-
tion, left heart enlargement is frequently seen
INTERNAL RESPIRATION
at a very young age in many individuals.216
The drug hydroxyurea is often used in the The final link in the transport of oxygen from
treatment of sickle cell disease. Hydroxyurea the atmosphere to the cells is referred to as inter-
increases the production of HbF which, in nal respiration (Fig. 7-25). Although internal
turn, appears to decrease sickling and vaso- respiration has been defined specifically as the
occlusion. Because the life span of these blood exchange of gases between the systemic capil-
cells is only approximately 10% as long as that laries and the cells, both cellular oxygen supply
for normal red blood cells, anemia is also a and cellular oxygen utilization are considered
common finding and transfusions may be a in this section.
mainstay of treatment. Although there is no cure
for sickle cell anemia, most individuals can Cellular Oxygen Supply
lead relatively normal lives. Although all arteries in the body carry virtually
When an individual is heterozygous (i.e., identical concentrations of oxygen, not all cells
inherited from only one parent), he or she pos- in the body are supplied with equal amounts of
sesses sickle cell trait. Nearly 10% of African oxygen, which is because not all cells in the
Americans possess sickle cell trait. Sickle cell body are exposed to the same amount of blood.
trait is not associated with anemia and is gen- Several factors determine the availability of
erally considered to be a benign condition. oxygen to a given cell (Fig. 7-26). Obviously,
Notwithstanding, the sickling phenomenon some cells are simply closer to capillaries than
may occur in these individuals in the presence others. Because movement of oxygen depends
of prolonged hypoxia. In addition, it has been on pressure gradients, the cells furthest away
suggested that the presence of sickle cell trait are most vulnerable to hypoxia.

A 62-year-old man appears in acute distress with short- HR 132/min

ness of breath and is cold and clammy. RR 22/min
Temp 37 C
FIO2 0.40 ASSESSMENT
SaO2 93% Abnormalities: List abnormal data and other noteworthy
pH 7.32 information. Classify ABG.
PaCO2 28 mm Hg Explanation: List possible diseases, pathology, or other
PaO2 74 mm Hg situations that may have led to this patients condition.
[HCO3] 18 mEq/L Evaluation: Suggest additional data that would be
useful in helping understand the situation or in making
LABORATORY WORK a diagnosis.
[Hb] 13 g%
[WBC] 9000 mm3 INTERVENTION
Importance: Prioritize concern(s) of treatment in order of
VITAL SIGNS urgency and/or seriousness as you see the overall
BP 85/P situation.

Figure 7-25. Three steps in oxygen delivery to the tissues.
A
Distance From Capillary
As previously described, the distance of a given
cell from a capillary is not constant. Many cap-
illaries are normally closed and open only when
gross perfusion to that particular region
increases. For example, actively contracting
muscle may have as many as 10 times more
open capillaries than resting muscle.81 The gate-
keeper of blood supply to a capillary network
is the local arteriole.
B
Arteriolar Constriction/Dilation
Arterioles may dilate or constrict in response to
the various factors that regulate them. Arterioles
are subject to both local and central influences.
Locally, arterioles dilate in response to decreased
oxygen supply, increased CO2, increased tem-
perature, and decreased pH. All these changes
C
are typically the result of increased metabolism
Figure 7-26. Cellular supply of oxygen. Schema
that necessitates increased oxygen supply.
showing intercapillary distances. Oxygen from blood The release of epinephrine is a central mech-
flowing through tissue capillaries must diffuse over anism that attempts to preferentially distribute
a longer path to reach cells A and C. Oxygen has a blood to the vital organs when oxygen is in short
short path to cell A when its capillary is open and supply in the body. When the body is confronted
a much longer one when it is closed. with an overall deficit in oxygen, both central
and local mechanisms are stimulated. In the the production of 36 adenosine triphosphate
short term, central effects tend to predominate. (ATP) molecules. ATP molecules, in turn, con-
If the oxygen shortage persists, however, local tain the high energy bonds that are so essential
effects ultimately override and generalized for life itself. The availability of oxygen is cru-
vascular dilation is seen. cial in the production of ATP from adenosine
diphosphate (ADP) in the Krebs cycle. The
Cellular Oxygen Utilization actual process of ATP formation is called
Variable Oxygen Extraction oxidative phosphorylation, because phosphate
Earlier in this chapter the normal C(a v)O2 was is added to ADP by using the energy from oxi-
calculated at about 5 vol%, which means that, dation.
on the average, about 5 mL O2 is taken up and
used by the tissues for every 100 mL of perfu- Anaerobic Glycolysis
sion. It should be noted, however, that the arte- In the absence of oxygen, metabolism is less
riovenous difference observed in specific organs efficient and only two molecules of ATP are
and tissues may vary considerably (Table 7-1). generated in the metabolism of glucose without
For example, the arteriovenous oxygen differ- oxygen (anaerobic glycolysis). Furthermore,
ence in the heart is about 11 vol% whereas anaerobic metabolism results in the produc-
the arteriovenous difference in the skin and tion of lactic acid, which may in turn lead to
kidneys is approximately 1 vol%. Apparently, metabolic acidemia.
tissues with high blood flow and low oxygen
requirements use the additional blood flow for Hypoxia
nonoxygenation processes, such as glomerular Tissue hypoxia exists when the cellular needs
filtration or temperature regulation. for oxygen are not met. Although isolated
To further complicate matters, some tissues mitochondria maintain oxidative phosphoryla-
are capable of increasing oxygen extraction tion with PO2 values less than 1 mm Hg,237
when additional oxygen is needed. Skeletal this probably does not occur in the intact
muscle can extract almost all of the blood oxy- organism. In humans, hypoxia probably occurs
gen during maximal exercise; however, heart when mitochondrial PO2 is less than approxi-
muscle is unable to increase oxygen extraction mately 7 mm Hg.238 Conversely, excessive tis-
despite its normally high extraction ratio.81 sue PO2 is also destructive to the cells. Thus,
one must carefully titrate oxygen to achieve
Biochemical Respiration optimal levels.
In biochemistry, respiration refers to the Cyanide or amobarbital may interfere with
oxidation of pyruvic acid in the Krebs cycle biochemical respiration and the normal use of
(Fig. 7-27). This series of reactions takes place oxygen in the cell. This form of hypoxia, com-
in the mitochondria of the cells and results in monly referred to as histotoxic hypoxia, is
Table 7-1. LOCAL VARIATIONS IN THE DISTRIBUTION OF BLOOD FLOW AND O2 UTILIZATION
Site Blood Flow (%) O2 Used (%) C(a v) O2 (vol%)

Pv O2 (mm Hg)
Heart 4 11 11 23
Skeletal muscle 21 30 8 34
Brain 13 20 6 33
Liver 24 25 4 43
Kidneys 19 7 1 56
Skin 9 2 1 60
Other 10 5 5 40
Total 100 100 5 40
Modified 2005 with permission from Finch, C.A., and Lenfant, C.: O2 transport in man. N. Engl. J. Med., 286:407,
1972. Copyright Massachusetts Medical Society. All rights reserved.
Anaerobic
glycolysis 2 ATP
Lactic acid
(No O2)
Cytoplasm
Glucose
Tissue
hypoxia O2
Cyanide Aerobic
(Histotoxic hypoxia) oxidative
phosphorylation 36 ATP
6 CO2 + 6 H2O
Biochemical (Krebs cycle)
respiration
Mitochondria
Figure 7-27. Aerobic metabolism via oxidative phosphorylation in the mitochondria produces 19 times
more energy (ATP) than anaerobic glycolysis. Normal aerobic metabolism decreases in the presence of
tissue hypoxia or cyanide poison. When aerobic metabolism cannot proceed, anaerobic metabolism
increases with the subsequent buildup of lactic acid.
unique because the primary defect occurs at Indeed, an RQ greater than 1.0 suggests
the site of internal respiration. lipogenesis secondary to excessive carbohy-
Another factor that may alter oxygen drate intake and conversion of carbohydrates
requirements is the patients temperature. into fat.240 Finally, the combined RQ of the
Oxygen consumption increases approximately body that reflects a composite of all types of
10% for each degree increase celsius.10 metabolism is normally approximately 0.8.
CO2 excretion via the lungs and oxygen
Respiratory Quotient uptake through the lungs may be measured as a
The respiratory quotient (RQ) quantitates the reflection of the RQ. The ratio of CO2 excretion
relationship between production of CO2 and to oxygen uptake is sometimes referred to as the
the consumption of oxygen. Specifically, it is the respiratory exchange ratio. During steady-state
ratio of CO2. produced
.
each minute to oxygen conditions, the respiratory exchange ratio is
consumed (VCO2/VO2). In pure carbohydrate equal to the respiratory quotient.
metabolism, the RQ is 1.0 because six molecules In critically ill patients in whom the work
of CO2 are produced for every six molecules of of breathing is a matter of concern, the RQ is
oxygen consumed (Equation 7-1). sometimes monitored by a device called an indi-
rect calorimeter or metabolic cart. The goal is to
Equation 7-1
C6H12O6 + 6 O2 6 H2O + 6 CO2 + energy
try to keep the RQ low via a low carbohydrate
diet, which, in turn, minimizes CO2 production
Fat metabolism, on the other hand, produces and diminishes the work required for CO2
less CO2 and the RQ is approximately 0.7. The excretion via ventilation. This technique may be
RQ of protein metabolism is near 0.8. The RQ useful when an attempt is made to decrease the
of alcohol is approximately 0.7 and the RQ work of breathing in patients who are being
during lipogenesis may be as high as 1.0 to 1.3. gradually weaned off mechanical ventilators.
EXERCISES
Exercise 7-1 Oxygen Transport

1. State the two forms in which oxygen is carried in the blood.

2. State the solubility coefficient for oxygen in blood at 37 C.
3. Milliliters of a substance in 100 mL of blood is usually referred to as ______.
4. Solubility of gases will (increase/decrease) as temperature increases.
5. The relationship between PO2 and the volume of dissolved oxygen is direct and
(logarithmic/linear).
6. Combined oxygen is carried in combination with ______.
7. A heme group is made up of ______ and ______.
8. Each molecule of hemoglobin is capable of combining with ______ molecules of oxygen.
9. The percentage of available hemoglobin molecules that are carrying oxygen in arterial
blood is symbolized as ______.
10. For all practical purposes, SaO2 refers to (combined/dissolved) oxygen.
Exercise 7-2 Oxyhemoglobin Dissociation Curve

1. The most important physiologic variable that determines SaO2 is the ______.
2. The relationship between PaO2 and SaO2 is direct and (linear/nonlinear).
3. What PaO2 values are normally associated with the following SaO2 values:
SaO2 (%) PaO2 (mm Hg)
50
90
100
4. At low PaO2 values, small changes in PaO2 are associated with (small/large) changes in SaO2.
5. On the flat upper portion of the curve, large changes in PaO2 values are associated with
(large/small) changes in SaO2 values.
6. The flat upper portion of the curve is known as the (association/dissociation) portion of
the curve.
7. The dissociation portion of the curve is so-named because the (beginning/end) of oxygen
unloading occurs on this portion of the curve.
8. Normal SaO2 is approximately ______%.
9. If PaO2 were to decrease from 100 to 60 mm Hg, SaO2 would decrease from 97%
to ______%.
10. The end of oxygen loading occurs on the (upper/lower) portion of the curve and the end
of oxygen unloading occurs on the (upper/lower) portion of the curve.
Exercise 7-3 Oxyhemoglobin Affinity

1. The standardized index of oxyhemoglobin affinity is ______.

2. Normal P50 is approximately ______ mm Hg.
3. List four factors known to alter the affinity of hemoglobin for oxygen (excluding PO2).
4. Increased PCO2 and temperature shift the oxyhemoglobin curve to the (right/left) because
Hb-O2 affinity is (increased/decreased).
5. The fact that increasing PCO2 decreases the affinity of oxygen for hemoglobin is known as
the ______ effect.
6. In humans with a normal PaO2, increased Hb-O2 affinity usually has a net
(beneficial/detrimental) effect.
7. A shift of the oxyhemoglobin curve to the right is usually beneficial because it enhances
oxygen (loading/unloading).
8. The oxyhemoglobin curve will shift to the left owing to a/an (increase/decrease)
in hydrogen ions; or stated another way, a/an (increase/decrease) in pH.
9. The P50 is measured at a pH of ______ and a PCO2 of ______ mm Hg.
10. The P50 is slightly lower in (men/women).
Exercise 7-4 2,3-Diphosphoglycerate

1. The presence of DPG (increases/decreases) the affinity of hemoglobin for oxygen.

2. The most important organic phosphate in the erythrocyte is DPG because it is the most
(diffusible/abundant).
3. DPG enhances oxygen (loading/unloading).
4. Anemia is associated with a/an (increase/decrease) in DPG.
5. Probably the most common cause of decreased DPG is
(hypoxemia/infusion of stored blood).
6. It is (possible/not possible) to restore DPG levels in stored blood.
7. DPG levels return to 50% of normal within ______ hours after the administration
of stored blood.
8. (Increased/decreased) pH tends to decrease DPG levels.
9. Changes in DPG levels tend to have a (short-term/sustained) effect on Hb-O2 affinity.
10. Blood DPG levels tend to decrease to approximately one-third that of normal after blood
storage for 1 week in the preservative ______.
Exercise 7-5 Oxygen Content

1. The symbol for the total volume of oxygen present in arterial blood is ______.
2. Calculate the volume of oxygen in the dissolved state (vol%) in the blood given the
following PaO2 values:
100 mm Hg
60 mm Hg
400 mm Hg
3. Calculate the volume of oxygen in the combined state (vol%) given the following:
[Hb] (g%) SaO2 (%)
15 95
12 90
10 80
4. Calculate CaO2 given:
[Hb] (g%) SaO2 (%) PaO2 (mm Hg)
10 94 70
14 98 65
7 97 80
5. The normal CaO2 is approximately ______ vol%.
6. Normal mixed venous PO2 is approximately ______ mm Hg, and normal mixed venous
oxygen saturation is approximately ______%.
7. Normal C(a v )O2 is approximately ______ vol%.
8. The relationship between the cardiac output, the oxygen consumption, and the difference
in arteriovenous oxygen content is expressed in the ______ equation.
9. When cardiac output decreases, C(a v )O2 (increases/decreases).
10. Normal oxygen consumption under basal metabolic conditions in a 70 Kg
young man is ______ mL/min.
Exercise 7-6 Cyanosis

1. The bluish color seen in certain oxygenation disturbances is called ______.

2. A bluish hue of the skin is called ______ cyanosis.
3. Central cyanosis may be observed on the ______.
4. When SO2 is 80%, the percentage of desaturated hemoglobin is ______%.
5. Cyanosis is usually evident when there is ______ g% average desaturated hemoglobin in
the (artery/capillary).
6. Normally, the average quantity of desaturated hemoglobin in the capillaries is
approximately ______ g%.
7. Cyanosis is unlikely in (anemia/polycythemia).
8. Cyanosis may be of less immediate concern in (anemia/polycythemia).

9. Calculate the average amount of desaturated hemoglobin given the following data, and
state whether this individual (would/would not) be cyanotic.
Given: [Hb] = 20 g%
SaO2 = 80%
Sv O2 = 60%
10. Calculate the average amount of desaturated hemoglobin given the following data, and
state whether this individual (would/would not) be cyanotic.
Given: [Hb] = 10 g%
SaO2 = 80%
SvO2 = 60%
Exercise 7-7 Oxygen Transport/HbCO/HbF

1. Dissolved oxygen transport is normally approximately ______ mL/min.

2. Normal total oxygen transport is approximately ______ mL/min.
3. Calculate total oxygen transport given: .
PaO2 (mm Hg) [Hb] (g%) SaO2 (%) Q(L/min)
70 12 92 5
100 15 98 2.5
80 6 97 5.2
4. CO has ______ times the affinity for hemoglobin compared with oxygen.
5. CO in chemical combination with hemoglobin is known as ______.
6. Classically, HbCO has been considered to be harmful to oxygenation by what two
mechanisms?
7. The P50 of HbF is approximately ______ mm Hg.
8. HbF has a (greater/lesser) affinity for oxygen than HbA within the body.
9. HbCO can be accurately measured with a (pulse oximeter/CO-oximeter).
10. The concentration of HbF in the term infant is approximately _____%.
Exercise 7-8 Methemoglobinemia and Sickle Cell Disease

1. When hemoglobin is oxidized rather than oxygenated, it is called ______.

2. Chocolate-colored blood is often seen with (hemoglobin S/methemoglobinemia).
3. Sulfhemoglobinemia may be mistaken for (methemoglobinemia/sickle cell disease)
4. Treatment for methemoglobinemia is intravenous (hydroxyurea/methylene blue).
5. Benzocaine spray for local anesthesia has been implicated in abrupt
(cyanosis/flushing of mucous membranes).
6. Sickling appears to decrease in the presence of (HbF/HbM).
7. State the three components of acute chest syndrome.
8. The SpO2 reading with severe methemoglobinemia tends to migrate toward ____%.
9. Amyl nitrate tends to cause increased (HbS/metHb).
10. Sickle cell trait is present in ___% of African Americans.
Exercise 7-9 Internal Respiration

1. State the four factors known to cause local vasodilation.

2. The normal arteriovenous oxygen content difference is ______ vol% in the heart
and ______ vol% in the skin.
3. Actual utilization of oxygen takes place in the (Golgi bodies/mitochondria) within the cells.
4. Oxygen consumption increases approximately ______% for every degree centigrade
increase in temperature.
5. The normal respiratory quotient for the entire body is ______.
6. The RQ of carbohydrate metabolism is ______.
7. Actively contracting muscle may have as many as ______ times the ordinary number of
open capillaries.
8. Most energy is produced in the cell during (glycolysis/the Krebs cycle).
9. Anaerobic metabolism results in the accumulation of ______ ______.
10. Concerning control of peripheral arterioles, (central/peripheral) effects predominate in the
short term.
11. Lipogenesis will result in an RQ as high as ___.

1. Visit www.austin.cc.tx.us/~emeyerth/hemoglob.htm. How many Hb molecules are in
100 mL of blood?
NBRC Challenge 7
1. A patient is treated with 20% benzocaine III. acidemia.
spray as a topical anesthetic prior to IV. abnormal Hb.
bronchoscopy. The patient becomes A) I and II only
suddenly very cyanotic. What laboratory B) I and IV only
test should be performed? C) II and III only
A) P50 D) II and IV only
B) Arterial blood gases E) II, III, and IV only
C) Serum electrolytes (RRT EXAMNBRC MATRIX I,C,2,b)
D) CO-oximetry
4. A (Ca v )O2 of 10 vol% suggests:
E) H&H
A) a high cardiac stroke volume.
(RRT CSE EXAMNBRC MATRIX
B) a low cardiac output.
III,B,1,h)
C) polycythemia.
2. The treatment of choice for D) methemoglobinemia.
methemoglobinemia is: E) sickle cell crisis.
A) Mechanical ventilation (RRT EXAMNBRC MATRIX
B) Methylene blue I.V. I,C,2,c)
C) Potassium I.V.
5. An RQ measurement of 1.2
D) Hyperbaric oxygenation
suggests:
E) Biphasic Positive Airway Pressure
A) technical error using indirect
(RRT CSE EXAMNBRC MATRIX
calorimetry.
I,C,1,b)
B) alcohol intoxication.
3. A patient with a pulse oximetry reading of C) excessive fat metabolism.
82% and a PaO2 of 60 mm Hg may have: D) diabetes mellitus.
I. hypothermia. E) lipogenesis.
II. hypercapnia. (RRT EXAMNBRC MATRIX I,C,2,g)
Chapter
8
Acid-Base Homeostasis
The bodys defenses against blood pH changes operate at different time rates. Chemical buffering is almost
instantaneous; pulmonary responses occur in minutes; renal responses in hours to days.
Giles F. Filley2
Acid-base physiology is inherently a slightly confusing subject, but clinical acid-base terminology makes it
very confusing.
Giles F. Filley2
Outline
Hydrogen Ions and pH, 196 Bicarbonate, 203
Free Hydrogen Ions, 196 Carbamino Compounds, 204
Clinical Significance, 196 Summary, 205
Description, 196 The Kidneys and Acid-Base Balance, 205
pH, 197 Regulation of Fixed Acids in the
Definition, 197 Blood, 205
Relationship Between pH and [H +], 197 Origin of Fixed Acids, 205
Acid-Base Balance, 197 Excretion of Fixed Acids, 206
Acids, 197 Regulation of Bicarbonate Concentration in the
Bases, 197 Blood, 206
pH Homeostasis, 197 Buffer Systems, 206
Acid Homeostasis, 197 Basic Chemistry, 207
Base Homeostasis, 198 Conjugate Acid-Base Pairs, 207
The Lungs and Regulation of Volatile Acid, 198 Degree of Dissociation, 207
Underlying Chemistry, 198 Buffer Solutions, 208
Chemical Equilibrium, 198 Chemical Components, 208
Law of Mass Action, 198 Buffering Reactions, 208
Hydrolysis Reaction, 199 Blood Buffers, 209
Direct Relationship between [CO2] and Buffer Effectiveness, 209
[H2CO3], 199 Buffer Interactions, 210
CO2 Homeostasis, 200 Henderson-Hasselbalch Equation, 210
CO2 Production, 200 Hendersons Equation, 211
CO2 Excretion, 201 Hasselbalchs Modification, 211
CO2 Transport, 203 Numeric Calculation, 211
Dissolved CO2, 203 Clinical Application, 212
Carbonic Acid, 203 Exercises, 218
HYDROGEN IONS AND pH

Description
Free Hydrogen Ions Only hydrogen in free ionic form, however,
Clinical Significance possesses this chemical potential and is part of
The free hydrogen ion concentration [H+] in the the measurement of free hydrogen ion concen-
blood must be maintained within very narrow tration. Hydrogen in chemical combination
limits to maintain life. Seemingly slight alter- with other elements (e.g., H2O, HCO3) is not
ations in the free [H+] may have profound, part of the free [H+].
life-threatening effects on the chemistry of the Technically, however, in an aqueous solution,
body. This unusual degree of reactivity is proba- even free hydrogen ions are combined chem-
bly related to the small size of the H+ that affords ically with water to form hydronium ions
it reaction sites unapproachable by larger ions. (e.g., H3O+, H5O+). Nevertheless, the distinction
196
Chapter 8 Acid-Base Homeostasis 197
between free hydrogen ions and hydronium Bases

ions is not important for clinical purposes. All hydrogen ions released in solution, however,
Sometimes, a comparison is also made do not remain free. Many hydrogen ions are
between H+ activity and H+ concentration. attracted to and combine with other chemical
Most hydrogen ion analyzers measure activity substances that are present in the blood. Any
rather than actual concentration. Here again, substance capable of combining with or accept-
however, there is little clinical significance to ing a hydrogen ion in solution is called a base.
this differentiation. Thus, the term hydrogen Thus, from a chemical standpoint, the blood
ion concentration is used to refer to hydrogen pH is a result of the balance of acids and bases
ion measurements throughout this text. (i.e., acid-base balance) at any given moment.
pH pH Homeostasis
Definition Human cells and organs function best under
The actual [H+] in the blood is very low, approx- constant internal conditions including normal
imately 0.00000004 equivalents per liter (Eq/L). pH. Maintenance of a constant internal envi-
Obviously, monitoring clinical changes using ronment is called homeostasis. Both acids and
these units would be a very difficult and cum- bases must be regulated closely to ensure sta-
bersome process. Therefore, it has become cus- ble levels and a normal pH. Maintenance of a
tomary to express [H+] as pH. The definition of constant pH may be called pH homeostasis.
pH is the negative log of the free [H +]. Although The dynamic regulation of blood pH is
this definition appears to be complex, pH is a accomplished through the interaction of the
less cumbersome method of assessing the amount lungs, the kidneys, and the blood buffers. The
of H+ present in a given fluid. The normal range lungs and kidneys precisely maintain levels
for pH in arterial blood is 7.35 to 7.45. of acids and bases present in the blood. The
blood buffers serve primarily a protective role,
Relationship Between pH and [H+] preventing large changes in pH when abnor-
It is important to understand the relationship mal conditions expose the blood to acid-base
between [H+] and pH, however, because it is abnormalities.
not a simple direct one. Because the pH is the
negative log of the free hydrogen ion concen- Acid Homeostasis
tration, the relationship between pH and [H+] Normal body metabolism tends to result in
is inverse. An increase in pH reflects a decrease an accumulation of excess acid. Thus, it is
in [H+], whereas a decrease in pH is associated important that the body excrete acid at a rate
with a increase of hydrogen ions. equivalent to its production to maintain pH
Also, because the relationship is logarithmic, homeostasis.
a relatively large change in hydrogen ion con-
centration only slightly alters the numeric value Acid Excretion
of pH. For example, doubling of the normal Two major organ systems are responsible for the
[H+] only results in a 0.3 unit decrease in pH.2 excretion of acids: the kidneys and the lungs.
Although the kidneys are often the first organs
Acid-Base Balance thought of when considering acid excretion,
Acids the lungs are actually the major organs of acid
Free hydrogen ions enter the blood on their excretion.
release from other chemical substances. Any In normal humans, the lungs excrete
chemical substance capable of releasing a H+ approximately 13,000 mEq/day of carbonic
into solution is defined as an acid. Therefore, acid.363 However, the kidneys of an average
the greater the number and quantity of acids American adult excrete only 40 to 80 mEq/day
present in solution, the higher the [H+] (and of acid.363 Thus, the lungs are the single most
lower the pH) will be. A variety of acids are important organs involved in the moment-
normally present in the blood, and these acids to-moment regulation of acid-base status
serve as the source of free hydrogen ions. and pH.
Acid Groups the reaction in one direction is equal to the rate

The kidneys and the lungs each excrete a dif- of the reaction in the opposing direction.
ferent general chemical group of acids. The Chemical equilibrium does not mean that the
lungs excrete volatile acid. Volatile acids are concentrations of constituents on both sides of
those that can be converted from a liquid form an equation are equal.
to a gaseous form to facilitate excretion. For A closed chemical system is one in which all
all practical purposes, carbonic acid (H2CO3) the reactants and products in a chemical reaction
is the only volatile acid excreted by the lungs must remain within that system. Once chemical
under ordinary conditions. equilibrium for a particular reaction is reached
The kidneys, on the other hand, excrete in a closed system, the concentrations of the var-
fixed acids such as sulfuric acid and phos- ious constituents do not change. The reaction
phoric acid. Fixed acids cannot be converted continues to proceed in both directions but a
into a gas and therefore must be excreted in a state of dynamic equilibrium is maintained.
fixed (liquid) state in the urine. When the concentration of the substances
on the left side of a chemical reaction at equi-
Base Homeostasis librium is greater than the concentration of the
Like acids, the bases in the bloodstream must constituents on the right side, the reaction is
also be maintained in a constant balance. The said to be shifted to the left. For example, the
organ responsible for the regulation of blood equation shown in Equation 8-1 is said to be
bases is the kidney. The plasma bicarbonate shifted to the left because the concentration of
concentration [HCO3] is the major blood base reactants on the left is greater than the con-
of clinical significance. The [HCO3] is care- centration of H2CO3. Nevertheless, the reac-
fully controlled in the nephron, which is the tion is still at equilibrium. Also note that the
functional unit of the kidney. arrow pointing to the left is longer than the
arrow pointing to the right. This designation
THE LUNGS AND REGULATION OF shows that the reaction is shifted to the left at
VOLATILE ACID equilibrium.
Underlying Chemistry Equation 8-1

H2O + CO2
H2CO3
The role of the lungs in human acid-base balance

(340) + (340)
and pH homeostasis is to maintain the concen- (1)
tration of carbonic acid [H2CO3] at constant
levels in the arterial blood. As described earlier, Law of Mass Action
the lungs are the major organs of volatile acid Once achieved, a reaction remains at equilib-
(i.e., H2CO3) excretion. Therefore, it is the rium in a closed system. If an additional
exclusive responsibility of the respiratory sys- amount of one of the constituents is added to
tem to excrete carbonic acid in quantities that the closed system from an external source,
are exactly in proportion to its production. however, a new equilibrium is established. This
Some fundamental principles and chemical new equilibrium partially counteracts the ini-
relationships must be grasped to fully under- tial imbalance in the equilibrium caused by the
stand the mechanisms involved in H2CO3 constituent that has been added. The change in
homeostasis. These basic chemical relation- equilibrium in response to a change in the
ships and principles include chemical equilib- amount of one of the reaction constituents is
rium, the law of mass action, the hydrolysis referred to as the law of mass action.
reaction, and the direct, linear relationship Thus, if there is an increase in one of the
between dissolved CO2 and H2CO3. reactants on the right side of the equation, the
law of mass action causes the equilibrium
Chemical Equilibrium point to shift to the left to partially counteract
A reversible chemical reaction can proceed in the disturbance. For example, in Equation 8-1,
either direction. In reversible chemical reactions, if 5 units of external H2CO3 were added to this
chemical equilibrium exists when the rate of equilibrium in a closed system, the equilibrium
would shift to the left to partially counteract CO2 and the concentration of carbonic acid
the alteration. The change in units shown in [H2CO3] in the blood. At 37 C, each H2CO3
Equation 8-2 shows the direction of changes molecule in solution is in equilibrium with
that would occur in response to the additional approximately 340 CO2 molecules, as shown
H2CO3 in the system. Conceptually, the in Equation 8-1.364 Earlier estimates reported
increase in mass on the right side of the equa- that the ratio was greater than 700 to 1; how-
tion pushes the reaction to the left side of the ever, improved methods suggest the ratio given
equation. here. When blood PCO2 levels increase, blood
levels of H2CO3 likewise increase. Thus, PCO2
Equation 8-2 can be used as a marker of blood volatile acid
H2O + CO2
H2CO3 (i.e., H2CO3) levels.

(343) + (343) (3)
Carbonic Acid Production
A similar phenomenon occurs if one of the Based on the law of mass action, the CO2 that
constituents is removed from the closed system. builds up at the tissues leads to a parallel
In this case, however, the change in equilibrium increase in carbonic acid and ultimately
is an attempt to restore the lost constituent. hydrogen ions (Fig. 8-1). Thus, there is an
If CO2 is removed from Equation 8-2, the increase in the amount of carbonic acid present
equilibrium would shift slightly to the left to in the blood as it passes the tissues and CO2
attempt to restore the lost CO2. The change in enters. Venous blood has more CO2 and car-
units in Equation 8-3 shows the general direc- bonic acid than arterial blood. In fact, that
tion of changes that would accompany the loss is why venous blood is slightly more acidic
of CO2. Note that the removal of CO2 from the (pH = 7.38) compared with arterial blood
system leads to a fall in H2CO3 concentration (pH = 7.40). Actually, the difference in pH
due to the law of mass action. would be more substantial were it not for the
many effective buffer systems in the blood.
Equation 8-3
H2O + CO2
H2CO3
Carbonic Acid Excretion

(344) + (340) (2) When the venous blood reaches the lungs, the
increased CO2 and carbonic acid that entered
Hydrolysis Reaction the blood at the tissues must be excreted. This
CO2 is produced continuously in the cells of is precisely the role of the lungs in acid-base
the body as an end product of aerobic metab- balance: to excrete CO2 and carbonic acid at the
olism. This CO2 then diffuses to the systemic
circulation where some of it reacts with water
to form carbonic acid. This reaction, shown
in Equation 8-4, is called the hydrolysis reac-
tion because water (hydro) is broken down Cell
CO2
(lysed) as it reacts with dissolved CO2 to form
carbonic acid. Because all acids are capable
of releasing hydrogen ions, the release of free
H+ from carbonic acid is also shown in
Equation 8-4. Blood
H2O + CO2 H2CO3 HCO3 + H+
Equation 8-4

H2O + CO2 H2CO3 HCO 3 + H
+
Direct Relationship between [CO2] and [H2CO3]

Figure 8-1. Carbonic acid production at the
Because of their common involvement in the tissues. Hydrogen ions are produced in the blood
hydrolysis reaction, there is a direct, linear rela- at the cells as CO2 reacts with water in the
tionship between the concentration of dissolved hydrolysis reaction.

Alveolus
and VA determines the arterial PaCO2 at any
CO2 given instant, which is shown in Proportion 8-1.
Proportion 8-1. CO2 HOMEOSTASIS

VCO 2
PaCO 2

VA
Blood
H2O + CO2 H2CO3 HCO3 + H+ CO2 Production
CO2 production depends on both the quantity
and the nature of metabolism. The quantity of
metabolism varies directly with body tempera-
Figure 8-2. Carbonic acid excretion in the lungs. ture. Metabolism increases as an individuals
Hydrogen ions are removed from the blood in the body temperature increases. The nature of
lungs as CO2 is excreted into the alveoli. metabolism depends on the type of foodstuff
(e.g., fat, protein, carbohydrate) being metabo-
lized. For example, carbohydrate metabolism
same rate that it is being produced. Figure 8-2 produces more CO2 than does fat metabolism.
shows that as CO2 diffuses into the alveoli, the In normal humans, increases in CO2 produc-
law of mass action forces the hydrolysis reaction, such as during exercise, are balanced phy-
tion to the left. The net effect of this action is siologically by increasing alveolar ventilation
a reduction in carbonic acid and a decrease in proportionately. Sometimes, however, increases
the number of hydrogen ions in the blood. in CO2 production cannot be offset by increased
Thus, as CO2 is excreted via the lungs, the ventilation. This finding may occur when CO2
body is functionally excreting H2CO3. production is high (e.g., patients with burns,
total parenteral nutrition, sepsis) or when the
CO2 Homeostasis ventilatory system is compromised.
It has been shown that carbonic acid levels in Large increases in metabolism and CO2
the blood closely parallel dissolved CO2 levels. production sufficient to result in PaCO2 eleva-
Dissolved CO2 is maintained at constant inter- tion may occur occasionally in patients with
nal levels both because of its direct effect on sepsis (blood infection) or massive burns. Also,
pH and for other physiologic reasons. The an increase in blood PaCO2 can occur after
maintenance of constant arterial blood PCO2 intravenous administration of the drug sodium
levels can also be called CO2 homeostasis. bicarbonate (NaHCO3) to a patient who is
The physiologic and metabolic processes that unable to increase alveolar ventilation.365
ultimately determine blood CO2 levels are Because bicarbonate is one of the factors in the
explored. hydrolysis reaction, its presence in increased
The arterial PCO2 at any given moment quantities pushes the reaction to the left, which,
depends on the quantity of CO2 entering the in turn, has the effect of increasing dissolved
blood from the tissues and the quantity of CO2 CO2 and H2CO3 levels in the blood.
leaving the blood via the lungs. The amount of The individual with a normal respiratory
CO2 entering the blood, in turn, depends on system responds to the increased CO2 with a
the metabolic rate and the substrate being parallel rise in alveolar ventilation and CO2
metabolized. The volume of CO2 produced per excretion. The inability to increase alveolar
minute (i.e., CO2 production) is designated as ventilation may be seen, however, when central

the VCO2. nervous system ventilatory control mechanisms
Excretion of CO2, on the other hand, are not intact or when the respiratory muscles
depends on alveolar ventilation. Alveolar are paralyzed. Paralysis of the ventilatory mus-
minute ventilation is the amount of fresh gas cles may occur after trauma or pharmacologic
that reaches functional (i.e., perfused) alveoli intervention for control of mechanical ventila-
each minute. The symbol for alveolar ventilation. Thus, in these situations the clinician

tion per minute is VA. The balance of VCO2 should try to minimize CO2 loading in the
blood or to provide the patient with some type in correct proportion to its production. To assess
of ventilatory support to aid in excretion of the the adequacy of ventilation one must get an
additional CO2 load. arterial blood gas and evaluate the PaCO2. The
PaCO2 is the best index available to assess the
CO2 Excretion adequacy of ventilation relative to CO2 produc-
In the clinical setting, increased CO2 production tion. If the lungs are maintaining CO2 home-
is usually balanced by increasing alveolar ven- ostasis, the PaCO2 is maintained within the
tilation. Furthermore, most clinical changes in normal range (i.e., PaCO2 35 to 45 mm Hg).
PaCO2 are a result of changes in alveolar ven-
tilation. Nevertheless, it is becoming increas- Alveolar Ventilation
ingly clear that changes in CO2 production can As shown in Proportion 8-2, PaCO2 is
also lead to PaCO2 alterations. inversely proportional to alveolar ventilation.
To show the inverse relationship between Alveolar ventilation differs from minute venti-
alveolar ventilation and PaCO2, Proportion 8-1 lation in that only the gas that reaches func-
is sometimes simplified to the form shown in tional (i.e., perfused) alveoli is considered

Proportion 8-2. In this proportion, VCO2 is alveolar ventilation; in other words, deadspace
considered to be a constant and the number volume (VD) (see Chapter 6) is subtracted
one is substituted in the numerator. The propor- from the tidal volume (VT) to determine alveo-

tion becomes simply an inverse relationship lar ventilation (VA). The formula for calcula-
between PaCO2 and alveolar ventilation. An tion of alveolar minute ventilation is shown in
increase in alveolar ventilation results in a Equation 8-6.
decreased PaCO2. Conversely, a decrease in
Equation 8-6
alveolar ventilation causes an increased PaCO2.
VA = (VT VD) RR
Proportion 8-2. SIMPLIFIED CO2 One can readily see that any increase in tidal
HOMEOSTASIS volume or RR (or a decrease in deadspace)
1 increases alveolar ventilation, assuming of
PaCO 2

VA course that all other variables remain constant.
An increase in alveolar ventilation, in turn,
Minute Ventilation lowers PaCO2. Conversely, a fall in RR or tidal
The amount of gas moving in and out of the volume (or an increase in deadspace) decreases
lungs with each breath is called the tidal volume alveolar ventilation and increases PaCO2.
(VT). The number of breaths taken each minute When a change in PaCO2 is seen clinically,
is often referred to as the frequency or respira- Equation 8-6 should be analyzed to determine

tory rate (RR). Exhaled minute ventilation (VE) what variable has resulted in the change in the
can be calculated as shown in Equation 8-5. patients ability to excrete CO2.
Equation 8-5
Minute Ventilation versus Alveolar Ventilation
VT RR = V E
Table 8-1 shows three sets of parameters where
Minute ventilation, however, is not a very the minute ventilation is the same (6000 mL/
reliable index of the adequacy of ventilation. min); however, alveolar ventilation and CO2
The drawback of minute ventilation is that it excretion are grossly different. Figure 8-3 sim-
does not tell us if the lungs are excreting CO2 ilarly illustrates how alveolar ventilation and
Table 8-1. MINUTE VENTILATION VERSUS ALVEOLAR VENTILATION

VT (mL) RR (bpm) VD (mL) V (mL/min) VA (mL/min) PaCO2 (mm Hg)
500 12 150 6000 4200 40

250 24 150 6000 2400 80
1000 6 150 6000 5100 30
6000
Minute ventilation
Minute alveolar
5000 ventilation
Minute deadspace
4000
3000
2000
1000
0
A. Normal B. Slow, deep C. Fast, shallow
Figure 8-3. Effect of breathing pattern on alveolar ventilation. A, Normal breathing pattern. B, Slow
deep breathing. C, Rapid shallow breathing.
deadspace ventilation would be impacted by breathing is very rapid and shallow, deadspace
the breathing patterns in Table 8-1. During nor- ventilation can actually exceed alveolar ventila-
mal breathing (see Fig. 8-3,A), most ventilation (see Fig. 8-3,C) despite a constant minute
tion is effective alveolar ventilation. If minute ventilation.
volume remains constant, alveolar ventilation Note likewise that the PaCO2 varies inversely
will increase with larger tidal volumes and a with the alveolar ventilation. The inadequacy of
slower respiratory rate (see Fig. 8-3,B). Finally, if minute ventilation as an index of the adequacy

A 52-year-old patient with acute respiratory distress syn- PaO2 52 mm Hg

drome is being mechanically ventilated in the control [HCO3] 16 mEq/L
mode in the critical care unit. The patient is being phar- FIO2 0.50
macologically paralyzed to facilitate mechanical ventilation.
Previous blood gases had shown a normal PaCO2 and ASSESSMENT
PaO2 with a severe metabolic acidosis (pH 7.12) second- Abnormalities: List abnormal data and other noteworthy
ary to renal failure. Two ampules of sodium bicarbonate information. Classify ABG.
are administered IV to correct the metabolic acidosis and Explanation: List possible diseases, pathology, or other
the following blood gas is obtained. situations that may have led to this patients condition.
ARTERIAL BLOOD GASES INTERVENTION

SaO2 70% Importance: Prioritize concern(s) of treatment in order
pH 7.10 of urgency and/or seriousness as you see the overall
PaCO2 56 mm Hg situation.
of ventilation is clearly shown in Table 8-1 and Carbonic Acid

Figure 8-3. The PaCO2 is the only reliable As shown previously in Equation 8-1, the con-
index of the adequacy of ventilation. centration of carbonic acid [H2CO3] in the
It should also be noted that in Table 8-1 and blood varies directly with the quantity of dis-
Figure 8-3, deadspace is considered a constant solved CO2, because these two substances are
150 mL/breath. In these sets, changes in alveo- related directly via the hydrolysis reaction. The
lar ventilation are due to alterations in VT and amount of actual H2CO3 in the blood, how-
RR. In many disease states, deadspace varies ever, is minute (0.006%) in comparison with
considerably from this value. Thus, even when total CO2 transport.
tidal volume and RR are known, the blood gas The reason for this unbalanced relationship
and specifically the PaCO 2 are necessary to is that the chemical equilibrium point of

assess the adequacy of VA and the ability of the reaction is such that the ratio of dissolved
the body to maintain CO2 homeostasis. [CO2] to [H2CO3] is approximately 340 to 1
(see Equation 8-1).364 In other words, the reac-
CO2 Transport tion is shifted far to the left. Thus, although
CO2 is transported in the blood in both the the quantitative relationship between dissolved
plasma and within the red blood cells (erythro- CO2 and H2CO3 is very important from an
cytes). The mechanisms by which CO2 is actually acid-base perspective, the volume of CO2
carried in these two compartments are reviewed. being transported in the form of H2CO3 is
The transport of CO2 in the blood is related inti- negligible.
mately to acid-base status and homeostasis. In some texts, H2CO3 is excluded as a mech-
CO2 is carried in the blood in four basic forms: anism of CO2 transport because of its nominal
dissolved CO2, carbonic acid (H2CO3), bicar- role. Nevertheless, it is included here for com-

bonate (HCO3), and carbamino compounds. pleteness and to reinforce understanding of the
direct relationship between the quantities of
Dissolved CO2 dissolved CO2 and H2CO3.
As described in Chapter 3, gases dissolve in
liquids in direct proportion to their partial Bicarbonate
pressures. Furthermore, the volume of gas dis- Plasma Bicarbonate Formation
solved in a given liquid depends on the solu- Equation 8-4 showed that not only is carbonic
bility coefficient of that gas in that particular acid in equilibrium with dissolved CO2, but
fluid. The solubility coefficient of CO2 in it is also in equilibrium with bicarbonate

blood is approximately 0.072 vol%/mm Hg, (HCO3 ). Thus, some of the CO2 that enters

which, of course, is much higher than the sol- the blood ultimately forms HCO 3 . The amount
ubility coefficient of O2 (0.003 vol%/mm Hg). of HCO3 formed in the plasma, however, tends
Given a normal PaCO2 of 40 mm Hg, the nor- to be very small for two reasons. First, the
mal volume of dissolved CO2 in the arterial accumulation of the products of the hydrolysis
blood is approximately 2.9 vol%. reaction tends to halt the reaction. Second, the
In comparison with O2, however, CO2 is hydrolysis reaction itself occurs at a very slow
sometimes reported in units of mEq/L. The sol- rate in the plasma, which is because there is
ubility coefficient of CO2 in units of mEq/L is no enzyme available to catalyze (speed up) the
0.03 mEq/L/mm Hg. Thus, given a normal arte- reaction.
rial PCO2 of 40 mm Hg, the normal volume of Thus, based on these limitations, one would
dissolved CO2 in the plasma is (40 mm Hg expect the amount of CO2 to be transported as
0.03 mEq/L/mm Hg) 1.2 mEq/L. Dissolved HCO3 to be very small. Surprisingly, HCO3 is
CO2 transport accounts for only approxi- actually the major mechanism of CO2 trans-
mately 8% of the total volume of CO2 transport and accounts for approximately 80% of
ported from the tissues to the lungs. The factor the CO2 transport from tissues to the lungs.
for converting CO2 in vol% to mEq/L is This is because of an interesting phenomenon
(vol%/2.23 = mEq/L). known as the chloride shift.
Chloride Shift Chloride Shift at the Tissues

As CO2 enters the blood from the tissues, it At the tissues, chloride enters the erythrocytes
accumulates in the blood plasma. Because CO2 as bicarbonate enters the plasma. Thus, the
readily diffuses through cell membranes, CO2 vast majority of CO2 transport is in the form

levels also increase within the erythrocytes. of HCO3. This HCO3 is produced in the ery-
Therefore, the hydrolysis reaction also takes throcytes but is transported from the tissues to
place within the erythrocyte. the lungs in the plasma.
Inside the erythrocyte, however, the hydro-
lysis reaction can occur at a much faster pace Chloride Shift in the Lungs
(13,000 times faster)81 than in the plasma As CO2 diffuses from the blood to the alveoli in
for two reasons. First, the presence of the the lungs, the chloride shift occurs in the oppo-
enzyme carbonic anhydrase speeds up the site direction (Fig. 8-5). In other words, Cl
hydrolysis reaction. Second, the products of returns to the plasma in exchange for the return

the hydrolysis reaction (i.e., HCO 3 and H+) of bicarbonate ions to the erythrocyte. Inside
are not permitted to accumulate within the the cells, HCO3 is converted back to dissolved
erythrocytes. Hydrogen ions promptly com- CO2. In this gaseous form, it can be excreted
bine with (are buffered by) desaturated hemo- from the plasma into the alveoli.
globin to prevent their accumulation and a
substantial change in intracellular pH. Simul- Carbamino Compounds
taneously, bicarbonate ions are transported Plasma Carbamino Compounds
through the erythrocyte membrane into the A small amount of CO2 is also transported in the
plasma. plasma in combination with protein. In this case,
The large quantity of bicarbonate (negative CO2 reacts with the amino acid groups present
anion) migrating from the erythrocyte to the on the protein molecule. Protein in combination
plasma sets up an electrostatic gradient with CO2 is called a carbamino compound.
between the intracellular fluid and the plasma. Carbamino compounds in the plasma account
This electrical gradient in turn results in the for only approximately 2% of CO2 transport.
movement of chloride anions into the ery-
throcyte from the plasma. This exchange of Carbamino-Hemoglobin
bicarbonate ions for chloride anions across Because the hemoglobin molecule contains the
the erythrocyte membrane is known as the protein globin, CO2 can combine with hemo-
chloride shift or the Hamburger phenomenon globin. The combined form of hemoglobin and
(Fig. 8-4). CO2 is called carbamino-hemoglobin. It should
be understood that the hemoglobin combina-
tion with CO2 does not occur at the same site

HHb Hb
Red blood cell
HHb Hb
c.a.
H2O + CO2 H2CO3 HCO3 + H+ Red blood cell
CO2 c.a.
H2O + CO2 H2CO3 HCO3 + H+
Cl
CO2 HCO3
Plasma Cl
Figure 8-4. Chloride shift at the tissues. Chloride
Plasma
enters the erythrocytes at the tissues in exchange
for the bicarbonate produced via the hydrolysis Figure 8-5. Chloride shift in the lungs. Chloride
reaction. The hydrolysis reaction is accelerated in returns to the plasma in exchange for bicarbonate.
the erythrocyte due to the presence of carbonic Bicarbonate is needed inside the cells to replenish
anhydrase. The hydrogen ion produced via the stores that are used up via the hydrolysis reaction
hydrolysis reaction is buffered by hemoglobin. as CO2 is excreted.
as the hemoglobin combination with O2. acids cannot be converted into gases and
Whereas O2 combines with hemoglobin at the excreted via the lungs. Therefore, the kidneys
heme site, CO2 combines with the amino groups are responsible for maintaining normal fixed
of proteins.81 It is indeed possible for the acid homeostasis.
hemoglobin molecule to carry O2 and CO2 at Furthermore, several conditions (e.g., dia-
the same time. Notwithstanding, however, the betes, hypoxia) can result in an abnormal
affinity of hemoglobin for CO2 is greater when increase in fixed acid production. In these situ-
it is not combined with O2. This result is the ations, the kidneys accelerate acid excretion
well-known Haldane effect. Conversely, when and attempt to maintain homeostasis.
hemoglobin is already carrying CO2, its affinity
for O2 decreases (i.e., Bohr effect). Origin of Fixed Acids
The percentage of CO2 transport in the form Metabolism
of carbamino-hemoglobin is approximately Fixed acids are a common product of metabo-
10%. Thus, the total amount of CO2 trans- lism. The specific fixed acid accumulating in
ported as carbamino compounds is 12%. the blood plasma at the tissues depends on the
type of substance being metabolized. The con-
Summary ditions surrounding metabolism (e.g., presence
A summary of quantitative CO2 transport is of O2) may also affect the products that result.
shown in Table 8-2.96 These percentages are The most common fixed acids that may accu-
based solely on CO2 added to the blood at the mulate in the blood are shown in Table 8-3.
tissue and transported to the lungs to be The type of substance that metabolizes into
excreted. The normal stores of CO2 continu- each specific acid is also shown.
ously present in the blood are not reflected in Protein metabolism results in the produc-
these numbers. Also, the percentage of CO2 tion of inorganic (not containing carbon)
transport in the chemical form of H2CO3 is so phosphoric and sulfuric acid. The incomplete
small that it is not included in Table 8-2. metabolism of lipids or carbohydrates results
in the accumulation of organic (containing car-
bon) acids. Specifically, lipid metabolism in the
THE KIDNEYS AND ACID-BASE
absence of insulin produces a buildup of aceto-
BALANCE
acetic and beta-hydroxybutyric acid. These
The kidneys (renal system) are second only to two acids are often referred to collectively as the
the lungs in their role of controlling blood pH. ketoacids. On the other hand, in the absence
The kidneys serve two major functions in of O2, carbohydrate metabolism produces an
acid-base homeostasis: fixed acid excretion accumulation of lactic acid.
and normal regulation of the bicarbonate con- Normally, the amount of fixed acid produced

centration [HCO3] in the blood. Bicarbonate is each day is small, approximately 50 to 60 mEq.
an important blood base.
Regulation of Fixed Acids in the Blood

Table 8-3. VARIOUS TYPES OF METABOLISM
Nonvolatile or fixed acids are produced WITH ASSOCIATED FIXED ACIDS
through normal body metabolism. These fixed Substance Fixed Acids
Protein catabolism Sulfuric acid (H2SO4)

Table 8-2. PERCENTAGES OF CO2 TRANSPORT
Phosphoric acid
FROM TISSUES TO LUNGS
(H3PO4)
Mechanism % Incomplete lipid (Ketoacids)
metabolism Acetoacetic acid
Bicarbonate 80 Beta-hydroxybutyric acid
Carbamino compounds 12 Carbohydrate Lactic acid
Dissolved 8 metabolism (in the
Total 100 absence of O2)
In the presence of disease (e.g., diabetic ketoaci- In any event, a large abnormal fixed acid load
dosis), however, fixed acid production may leads to an excess of hydrogen ions in the blood.
increase tremendously (e.g., 2000 mEq/day).366 This nonrespiratory (metabolic) acid-base dis-
turbance results in a decrease in blood pH.
Nonmetabolic Origin
Occasionally, an increase in fixed acids in the Regulation of Bicarbonate Concentration
blood may originate from a cause other than in the Blood
metabolism. This finding occurs typically when As is shown in the section on buffering, strong

a salt such as ammonium chloride (NH4Cl) is bases can be converted into the base (HCO3 )
administered intravenously to a patient, such in the blood. The bicarbonate concentration, in
as in the treatment of severe metabolic alkalosis. turn, is precisely regulated by the kidneys. The
Ammonium chloride is metabolized by the liver kidneys can both excrete excess bicarbonate
and results in the production of hydrochloric and produce bicarbonate when needed. Clear
acid (HCl). comprehension of the renal regulation of

[HCO3 ] is crucial to understanding the role of
Excretion of Fixed Acids the kidneys in acid-base balance.
Because the amount of fixed acid the kidneys The specific mechanisms through which the
must normally excrete is small, there is usually kidneys control bicarbonate are complex. These
no problem in maintaining homeostasis. mechanisms are affected by certain blood elec-
Nevertheless, in the presence of renal disease, trolytes, hormones, and drugs. Due to the
retention of fixed acids may occur. complex nature of this regulation, this subject
When the fixed acid load is unusually high, is discussed in more detail in Chapter 12.
even the normal kidney is unable to excrete
them over the short term. This finding may
BUFFER SYSTEMS
occur when large quantities of organic acids
are being produced due to incomplete metabo- Central features of the lungs and the kidneys
lism or when a chloride salt is administered. regarding acid-base homeostasis have been

A patient who has had cardiac surgery is being mechani- [HCO3] 22 mEq/L
cally ventilated in the assist/control mode following FIO2 0.4
surgery. Earlier blood gases had shown a significant
respiratory alkalosis (PaCO2 was 26 mm Hg / pH 7.54). ASSESSMENT
The physician overseeing the patient was concerned Abnormalities: List abnormal data and other noteworthy
about the respiratory alkalemia because the electrocar- information. Classify ABG.
diograph was very unstable. Therefore, the physician Explanation: List possible diseases, pathology, or other
added increased mechanical deadspace to try to situations that may have led to this patients condition.
increase the PaCO2. You go up to see the patient just Evaluation: Suggest additional data that would be useful in
as blood gases are reported after the mechanical helping understand the situation or in making a diagnosis.
deadspace had been applied.
INTERVENTION
ARTERIAL BLOOD GASES Importance: Prioritize concern(s) of treatment in order of
SaO2 98% urgency and/or seriousness as you see the overall situation.
pH 7.61 Objective: Specifically state the measurable or observable
PaCO2 20 mm Hg outcomes you would like treatment to accomplish.
PaO2 94 mm Hg Action: Describe your specific plan of action.
discussed. Another important aspect of acid- Equation 8-8

base homeostasis is the blood buffer system. HCl H+ + Cl

This remarkable system tends to stabilize the

bodys pH despite substantial alterations in the Degree of Dissociation
concentrations of acids or bases. Given an identical quantity of two different
acids in solution, however, the number of hydro-
Basic Chemistry gen ions that dissociate into a free state at equi-
A brief review of some additional chemical librium is not identical. Different acids have
fundamentals helps to ensure a solid theoreti- different degrees of dissociation. The greater
cal base for understanding the body buffers. the degree of dissociation of a given acid, the
stronger that acid is said to be. Strong acids have
Conjugate Acid-Base Pairs a high degree of dissociation, whereas weak
Acids, by definition, release hydrogen ions in acids have a low degree of dissociation.
solution. The hydrogen ions are said to disso- For example, Figure 8-6 compares the
ciate from the acid. The generic formula for dis- degree of dissociation between a strong acid
sociation of an acid is shown in Equation 8-7. (e.g., HCl) and a weak acid (e.g., H2CO3). The
Note that on dissociation, a hydrogen ion (H+) actual numbers used in this example are not
is released and a base (A) is present. Because all accurate but they are used only to show this
dissociation reactions are reversible equations, concept. Ten molecules of hydrochloric acid are
bases can combine (associate) with a hydrogen added to one solution, and 10 molecules of car-
ion to form the acid. bonic acid are added to the other. Most of the
HCl dissociates (eight of 10 molecules), and
Equation 8-7
HA
many free hydrogen ions are seen. However,
H +A
+
only two molecules of carbonic acid dissociate.
Thus, every acid must have a related base Thus, although both HCl and H2CO3 are
that will be present on dissociation of the hydro- acids, HCl is a stronger acid because it has a
gen ion. An acid in conjunction with its associ- higher degree of dissociation.
ated base is sometimes referred to as a conjugate Symbolically, the degree of dissociation is
acid-base pair. Equation 8-8 shows the dissocia- shown in the dissociation reaction by the size
tion reaction for hydrochloric acid. In this reac- or length of the arrows in the reversible reac-
tion, the conjugate acid-base pair is HCl and tion. A longer arrow in one direction indicates
Cl. In other words, the conjugate base of HCl that the concentrations of substances on that
is chloride (Cl). Similarly, the conjugate base of side of the equation are greater at equilibrium.

carbonic acid (H2CO3) is bicarbonate (HCO3). Note the length of the arrow to the right in
Hydrochloric acid
(strong acid)
H+ Cl H+ HCl
HCl Cl Cl H+ Cl
Cl
H+ +
Cl H
Figure 8-6. Comparison of strong and weak H
+
H+ Cl H+
Cl
acids. Although both containers are filled with 10
acid molecules, the HCl solution has many more
free hydrogen ions due to its degree of dissociation. Carbonic acid
Therefore, HCl is a much stronger acid. (weak acid)
H+ H2CO3 H2CO3
H2CO3
H2CO3 H2CO3
H2CO3
H2CO3 HCO3
HCO3 H2CO3 H+
Table 8-4. ACIDS IN DECREASING STRENGTH Therefore, buffer solutions do not prevent pH
Strength Acid change. Rather, buffer solutions minimize pH
change. Buffer solutions accomplish this by
Strongest HCl H+ + Cl converting strong acids into weaker acids or by

HHbO2 H+ + HbO2 converting strong bases into weaker bases.
HHb H + Hb
+

4 H+ + NH3 Chemical Components
Weakest H2O H + OH
+
Chemically, a buffer solution consists of two
substances in a common solution: a weak acid,
and a salt of its conjugate base. For example,
carbonic acid is a weak acid. The conjugate
Equation 8-8, denoting a high degree of disso- base of carbonic acid is bicarbonate (HCO3).
ciation and a strong acid. A salt of bicarbonate is sodium bicarbonate
Table 8-4 contains a list of some common (NaHCO3). Salts are completely dissociated
acids arranged in order of decreasing strength. into two charged ions (e.g., Na+ and HCO3).
The conjugate bases are shown in ascending Thus, a buffer solution could be prepared by
order of strength. In other words, the conju- placing carbonic acid in solution with NaHCO3,
gate base OH has the strongest affinity for the which is shown in Proportion 8-3.
H+, and the conjugate base Cl has the least
affinity for the hydrogen ion. Weak acids are Proportion 8-3. BICARBONATE BUFFER
associated with strong bases, whereas strong SYSTEM
acids are associated with weak bases. H2CO3
It may also be noted that hemoglobin may NaHCO3
function as an acid or a base in the blood. A
Buffering Reactions
substance that can act as either an acid or as
a base is sometimes referred to as an ampho- When a strong acid is introduced into the buffer
teric substance or an ampholyte.81 Also, both solution, it reacts with the conjugate base (salt)
oxygenated and deoxygenated hemoglobin are portion of the buffer pair. Equation 8-9 shows
included on the list. It can be seen, however, how the strong acid HCl would react with the
that the conjugate base of deoxygenated hemo- NaHCO3 in this buffer system. The result of
globin (Hb) is a stronger base than the conju- this reaction is that one molecule of the strong,

gate base of oxygenated hemoglobin (HbO2 ). highly dissociated acid HCl is converted to one
Thus, deoxygenated hemoglobin more readily molecule of the weak, poorly dissociated acid
picks up hydrogen ions than oxygenated H2CO3. In addition, one molecule of the salt
hemoglobin. NaCl is produced.
This characteristic of hemoglobin serves as an
Equation 8-9
advantage at the body tissues. After releasing
H2CO3
O2, hemoglobin more readily accepts the excess NaCl + H2CO3
HCl + NaHCO3
of hydrogen ions generated by the increased
CO2 levels and the hydrolysis reaction.
When a strong base such as sodium hydrox-
Buffer Solutions ide (NaOH) is added to a buffer solution, it
A buffer solution is a solution in which the pH reacts with the weak acid portion of the buffer
tends to be stable. The pH of a buffer solution pair as shown in Equation 8-10. In this reaction,
is less affected by the addition of acid or base the strong OH base is converted to the weaker
than a nonbuffer solution. If large quantities base bicarbonate (HCO3). Another product of
of acid are added to a nonbuffer solution, the this reaction is water (H2O).
pH decreases sharply. If the same amount of
acid is added to the same solution containing Equation 8-10
buffers, the pH does not fall to the same H2CO3
NaHCO3 + H2O
extent. Nevertheless, it would still decrease. NaOH + NaHCO3
Intracellular
Buffer Effectiveness
The effectiveness of a given buffer system
depends on three factors: the quantity of buffer
available, the pK of the buffer system, and
whether the buffer functions in an open or
Bicarbonate
Oxyhemoglobin closed system.
Inorganic phosphates
Hemoglobin Organic phosphates
Quantity
Obviously, the larger the quantity of a given
buffer that is available, the more acid or base
Inorganic it can buffer. Hemoglobin is the most impor-
Bicarbonate phosphates Protein
tant intracellular fluid buffer because of its
tremendous concentration.
Extracellular
pK of the Buffer System
Figure 8-7. Blood buffer compartments. The
A buffer functions best when the pH of the
various intracellular and extracellular buffers are
shown in their respective fluid compartments. solution is equal to the pK of the weak acid of
the buffer system. The pK of a weak acid is the
pH at which 50% of the acid is dissociated and
50% is undissociated. Figure 8-8 shows the pK
Blood Buffers of carbonic acid, which is approximately 6.1 in
The blood consists of many buffer systems the blood. Because strong acids are buffered by
including the bicarbonate buffer system. These the dissociated portion of the buffer pair (e.g.,
buffer systems constitute the first line of defense NaHCO3) and strong bases are buffered by the
against abrupt changes in blood pH. The blood undissociated portion (e.g., H2CO3), it follows
buffers work quickly and effectively to minimize that both bases and acids could be buffered
alterations in pH. equally well when the buffer system is at its pK.
The various blood buffers may be divided Buffers are generally considered to function
based on their physical location. Blood buffer well within 1 pH unit of their pK. Because the
systems exist both within cells (intracellular pK of the bicarbonate buffer system in blood is
fluid) and within the plasma (extracellular fluid). 6.1, this buffer functions best in the pH range
Figure 8-7 and Box 8-1 show the various buffers of 5.1 to 7.1. The blood, however, has a pH of
located in these two fluid compartments. Each 7.4. Thus, considering only the pK, the bicar-
buffer contains a weak acid and a salt of its bonate buffer is not particularly effective in the
conjugate base. blood. For reasons described in the following
section, however, the bicarbonate buffer is still
a very important blood buffer.
Box 8-1 Buffers in the Blood
Open versus Closed Buffer Systems
EXTRACELLULAR FLUID BUFFERS In a closed chemical system, a buffer becomes
Plasma bicarbonate less and less effective as the products of buffer-
Plasma proteins (e.g., albumin, globulin) ing accumulate, which is indeed the case for
Inorganic phosphates most of the blood buffers. Buffering effective-
ness is compared in an open versus a closed
INTRACELLULAR FLUID BUFFERS
system in Figure 8-9. The hemoglobin buffer
Bicarbonate
functions in a closed system. As hydrogen ions
Hemoglobin
are buffered by hemoglobin, acid hemoglobin
Oxyhemoglobin
Inorganic phoshates (HHb) accumulates. The buildup of HHb in
Organic phosphates turn slows the buffering reaction due to the
law of mass action.
Normal
operating point
in the body
4 5 6 7 8
0 100
25 75
associated form
dissociated form
Figure 8-8. The pK of carbonic acid. The pK is
% of acid in
% of acid in
the pH at which an acid is 50% dissociated. The
50 50 pK of carbonic acid in blood is 6.1.
pK
75 25
100 0
4 5 6 7 8
pH
This is not the case, however, for the bicar- that functions in an open system. For this
bonate buffer system. Due to the hydrolysis reason, the bicarbonate buffer system is the
reaction and the law of mass action, the bicar- most important extracellular fluid buffer.
bonate buffer system has the unique ability to
excrete carbonic acid via the lungs as it accu- Buffer Interactions
mulates through buffering. CO2 does not accu- Quantitatively, the extracellular and intracellu-
mulate in the blood; rather, any excess of CO2 lar fluids share the buffering of an acute acid
is excreted to maintain CO2 homeostasis. Thus, load almost equally, although the extracellular
the bicarbonate buffer is the only blood buffer buffering occurs more quickly. The bicarbonate
buffer system alone is responsible for more
than 50% of total buffering.367
Lungs The various blood buffers do not really
function independently in the blood. They are,
in fact, all chemically interdependent because
the hydrogen ion is common to all buffer
CO2 reactions. This principle of inter-relationship is
+
H2O sometimes referred to as the isohydric principle.
Guyton stated that the buffer systems actually
H2CO3 HHb
Open Closed buffer each other.173
+ system
HCO3 + + system H
H +H+ Hb
+
H+ HENDERSON-HASSELBALCH
EQUATION
CO2
cells A discussion of acid-base homeostasis would be
incomplete without some mention of the famous
Henderson-Hasselbalch equation. This chemical
Figure 8-9. Open versus closed system buffering.
equation provides the basis for determining
The bicarbonate buffer system is the most effective
many common blood gas measurements (e.g.,
extracellular buffer because it functions as an open
system. CO2, the product of acid buffering, does PCO2, [HCO3]). This equation describes the
not accumulate in the blood and slow the buffering fixed inter-relationships between PCO2, pH,
process. Also, CO2 that is used up when carbonic and [HCO3]. A brief historical perspective of
acid is consumed in buffering bases is replenished the development of this equation is presented,
easily through metabolism. followed by a mathematical calculation of
pH, and finally the clinical application of this in Equation 8-13. By using the negative log,
equation. the normal value for the free hydrogen ion
concentration (pH) in the arterial blood
Hendersons Equation becomes simply 7.35 to 7.45.
Chemists have known for a long time that
there was a constant mathematical relation- Equation 8-13
ship between the various substances present in [HCO 3 ]
pH = pKc + log
the dissociation reaction of an acid. If the con- [H 2 CO 3 ]
centration of the products of dissociation (right pKc = negative log of the dissociation
side of the dissociation reaction) is divided by constant of carbonic acid
the concentration of the undissociated acid
(left side of the equation), a constant number In practice, it is very difficult to measure
would always result for a given acid. This con- the [H2CO3] because it is so minute. An alter-
stant number is called the dissociation constant native, however, is to substitute the dissolved
of that particular acid, and each acid has its CO2 concentration in place of [H2CO3]
own distinctive constant. Calculation of the because the two are related directly and
dissociation constant for carbonic acid is linearly. The modified form of the Henderson-
shown in Equation 8-11. Hasselbalch equation that results is shown in
Equation 8-14.
Equation 8-11
[H + ] [HCO 3 ] Equation 8-14
Kc =
[H 2 CO 3 ] [HCO 3 ]
pH = pKc + log
[diss CO 2 ]
Kc = dissociation constant for carbonic acid
[diss CO2] = dissolved CO2 concentration
Henderson simply took this equation (see in mEq/L
Equation 8-11) and solved it for the [H+]
(Equation 8-12). The dissociation constant for Numeric Calculation
H2CO3 is a known value that can be substituted The normal blood pH can be calculated by
into the equation. If the [HCO3] and substituting the normal values for the factors
the [H2CO3] could then be measured, the equa- given in the modified Henderson-Hasselbalch
tion could be solved for the [H+]. Unfortunately, equation. Normal pKc within the blood is a

the normal hydrogen ion concentration in constant value of 6.1. The normal [HCO3 ] in
the blood is a very small and awkward num- the plasma is approximately 24 mEq/L.
ber (0.00000004 Eq/L). Therefore, a different The dissolved CO2 concentration in mEq/L
method of reporting this measurement was can be calculated by multiplying PaCO2
sought. (mm Hg) by the conversion factor (0.03 mEq/L/
mm Hg). Because the normal PaCO2 is
Equation 8-12 approximately 40 mm Hg, this value becomes
[H + ] =
Kc [H 2 CO 3 ] (40 mm Hg 0.03 mEq/L/mm Hg) 1.2 mEq/L
[HCO 3 ] of dissolved CO2. The result of substitution
of these values into Equation 8-14 is shown in
Hasselbalchs Modification Equation 8-15.
Hasselbalch addressed this problem by tak- One can see that the normal ratio of bicar-
ing the negative log of both sides of the bonate to dissolved CO2 in units of mEq/L is
Henderson equation. The symbol for the nega- approximately 20:1. Preservation of this ratio is
tive log of a substance is p. Thus, the negative essential to maintain a normal pH. Figure 8-10
log of the free hydrogen ion concentra- shows the effect that alterations in this ratio
tion becomes simply pH. The equation that have on the pH. Extreme alterations have a
results after this manipulation is called the substantial effect on pH and can ultimately
Henderson-Hasselbalch equation and is shown result in death.
pH 7.35 7.45
NORMAL
ACIDEMIA ALKALEMIA
20/1 25/1
12.5/116/1 32/1
10/1 40/1
8/1 7.4 7.5 50/1
7.2 7.3 7.6
6.3/1 7.1 7.7 60/1
7.0 7.8
Ratio 5/1 6.9 7.9 70/1 Ratio
6.8 8.0
DEATH DEATH
Dissolved CO2 HCO3
Figure 8-10. Normal 20:1 ratio of bicarbonate to dissolved CO2 in milliequivalents per liter. The normal
ratio of [HCO3] to dissolved CO2 in mEq/L is 20:1. Alteration of this ratio changes the pH and may lead
to death in severe cases.
Finally, Equation 8-15 shows that the log quantities are left in their normally recorded
of 20 is 1.3. Therefore, adding 1.3 to the nor- units. Using the normally reported units, the
mal pKc of 6.1 results in the normal arterial ratio is simply 24/40 ([HCO3] in mEq/L and
pH of 7.4. PaCO2 in mm Hg).
Equation 8-15 Proportion 8-4. [HCO3]/PaCO2 RATIO
24 mEq /L [HCO 3 ] kidneys
pH = (6.1) + log pH
1.2 mEq/ L PaCO 2 lungs
pH = (6.1) + log 20
pH = (6.1) + 1.3 The denominator in Proportion 8-4 (i.e.,
pH = 7.4 PaCO2) is, of course, primarily a product of res-
piratory lung function. The numerator, on the
Clinical Application other hand, [HCO3], is affected by buffering
and other nonrespiratory acid-base changes.
[HCO3]/PaCO2 Ratio
The organs with primary responsibility for
If all of the constants are eliminated from the [HCO3] regulation are the kidneys.
Henderson-Hasselbalch equation, it is reduced to
the simple relationship shown in Proportion 8-4. Metabolic Disturbances
The unit that [HCO3] is usually reported in Based on Proportion 8-4, an increase in the
is mEq/L. The unit that PaCO2 is typically numerator, [HCO3], tends to increase blood pH.
reported in is mm Hg. Technically, from a When analyzing blood gas data, a specific, meas-
mathematical standpoint, different units in ured acid-base condition that tends to increase
the numerator and denominator should not be blood pH may be called a laboratory alkalosis.
used. Rather, both should be converted to When the term alkalosis is used to infer a
mEq/L, which was described earlier. Neverthe- patients diagnosis, however, it should be used
less, the gross effect of a change in PaCO2 or only to indicate an abnormal, primary acid-base
[HCO3] on pH can still be appreciated if these condition and not compensatory responses.
Thus, a distinction should be made between a response to a change in the numerator within
laboratory alkalosis (e.g., increased [HCO3]), minutes. Nevertheless, the maximal respiratory
and an actual patients diagnosis of alkalosis response may take up to 24 hours.368,369
(e.g., vomiting that resulted in an increased In comparison, the compensatory response of
[HCO3]). the kidneys is slow. The kidneys require 48 to
On the other hand, a decrease in the numer- 72 hours to achieve maximal compensation.
ator tends to decrease blood pH. A specific, The initial, abnormal acid-base disturbance
measured acid-base condition that tends to that occurs in a particular patient is sometimes
lower blood pH may be called a laboratory referred to as the primary disturbance or
acidosis. Here again, the distinction should be problem. The acid-base change that occurs dur-
made between a laboratory acidosis (e.g., ing compensation for the primary problem is
decreased [HCO3]) and an actual patients sometimes referred to as a secondary or com-
diagnosis of acidosis (e.g., renal failure leading pensatory acid-base condition.
to a decreased [HCO3]). A more detailed dis-
cussion of this acid-base terminology appears Respiratory Disturbances
at the end of this chapter. Figure 8-11,A shows the normal [HCO3]/
The terms acidosis or alkalosis can be fur- PaCO2 ratio of 24/40. In ordinary circum-
ther clarified based on their origin. A condition stances this reflects a normal balance of acids
originating from the respiratory system is called and bases within the body and a normal pH.
a respiratory acid-base condition (acidosis/ Figure 8-11,B shows a primary respiratory
alkalosis). A nonrespiratory condition is called acidosis. This condition is associated with a rise
a metabolic acid-base condition. in PaCO2 and carbonic acid. A narcotic drug
overdose could lead to poor ventilation and to
Respiratory Disturbances this condition. Acute (abrupt onset) respira-
A change in the denominator of the [HCO3]/ tory acidosis increases the denominator of the
PaCO2 also tends to change blood pH. An ratio and decreases pH.
increase in the denominator (i.e., PaCO2) tends The kidneys, however, respond to this situa-
to decrease blood pH. In comparison, a decrease tion by increasing blood [HCO3] and thus
in PaCO2 tends to increase pH. increasing the numerator of the ratio. This result
The proportion points out that it is the ratio represents the secondary acid-base change.
of bicarbonate to PaCO2 that determines Figures 8-11,C and D show progressive com-
blood pH, not the absolute value of either of pensation. Ultimately, in Figure 8-11,D, com-
the factors. For example, if both [HCO3] and pensation is complete and the ratio is restored.
PaCO2 increase proportionately, the ratio and In patients, complete compensation to a pH
therefore blood pH will be normal. of 7.40 is probably never achieved. Complete
compensation is shown here, however, to show
Acid-Base Compensation the concept of progressive compensation. Also
When acid-base disturbances occur, the human remember that renal (kidney) compensation is
organism takes advantage of this ratio (i.e., not complete for 2 to 3 days. Figures 8-12,A to
[HCO3]/PaCO2) in an attempt to normalize D show the same chain of events that occur
pH. In other words, when the denominator in the development and compensation for a
increases, the body responds by increasing the primary respiratory alkalosis.
numerator, which has the effect of normalizing
the [HCO3]/PaCO2 ratio and pH. This process Metabolic Disturbances
of altering the unaffected component in the Figures 8-13,A to D show the onset and pro-
ratio in an attempt to normalize the overall gressive compensation of nonrespiratory
ratio is called acid-base compensation. (metabolic) acidosis. In this particular case,
The organs involved in acid-base compensa- metabolic acidosis is shown to have resulted
tion are the lungs and the kidneys. The lungs from a loss of blood base (i.e., HCO3). Meta-
regulate PaCO2, the denominator of the ratio. bolic acidosis may also develop due to an accu-
The kidneys regulate [HCO3], the numerator mulation of fixed acid in the blood. In either
of the ratio. The lungs can modify PaCO2 in event, however, bicarbonate (the numerator)
Normal acid-base status Uncompensated respiratory acidosis
7.3 7.4 7.5 7.3 7.4 7.5

7.2 7.6 7.2 7.6
7.1 7.7 7.1 7.7
7.0 7.8 7.0 7.8
6.9 7.9 6.9 7.9
6.8 8.0 6.8 8.0
A
AC BA C BA
ID SE I SE
D
pH pH

HCO 3 24 HCO 3 24
= = =
PaCO2 40 PaCO2 80
A pH = 7.40 B pH = 7.10
Partially compensated Completely compensated

respiratory acidosis respiratory acidosis
7.3 7.4 7.5 7.3 7.4 7.5

7.2 7.6 7.2 7.6
7.1 7.7 7.1 7.7
7.0 7.8 7.0 7.8
6.9 7.9 6.9 7.9
6.8 8.0 6.8 8.0
A BA A B
C C A
I SE I S
D D E
pH pH

HCO 3 36 HCO 3 48
= = = =
PaCO2 80 PaCO2 80
C pH = 7.30 D pH = 7.40
Figure 8-11. Compensation for respiratory acidosis. A, The normal [HCO3]/PaCO2 is associated with a
normal pH and acid-base balance. B, Increased PaCO2 is associated with an increase in volatile acid
[H2CO3] and a decreased pH. C, Renal compensation increases the blood [HCO3] and tends to normalize
the ratio. D, A normal pH would result if the ratio were restored to normal.
concentration decreases. In the case of increased acid-base problems is accomplished quickly via
fixed acids, bicarbonate is used up in the buffer- the lungs. Nevertheless, like the kidneys, the
ing reaction of the bicarbonate buffer system. lungs rarely achieve complete compensation
Finally, Figures 8-14,A to D show the onset back to a pH of 7.40.
and compensation for metabolic alkalosis. In clinical situations, what appears to be
Metabolic alkalosis is shown to result from the acid-base compensation may actually represent
accumulation of blood base, although theoreti- two distinct acid-base problems. These mixed
cally it could also result from the excessive loss acid-base disturbances are discussed in greater
of fixed acids. Compensation for metabolic detail in Chapter 14.
Normal acid-base status Uncompensated respiratory alkalosis
7.3 7.4 7.5 7.3 7.4 7.5

7.2 7.6 7.2 7.6
7.1 7.7 7.1 7.7
7.0 7.8 7.0 7.8
6.9 7.9 6.9 7.9
6.8 8.0 6.8 8.0
A B B
C A AC A
I S ID S
D E E
pH pH
24
HCO 3 HCO 3 24
= = =
PaCO2 40 PaCO2 20
A pH = 7.40 B pH = 7.70

respiratory alkalosis respiratory alkalosis
7.3 7.4 7.5 7.3 7.4 7.5

7.2 7.6 7.2 7.6
7.1 7.7 7.1 7.7
7.0 7.8 7.0 7.8
6.9 7.9 6.9 7.9
6.8 8.0 6.8 8.0
AC BA AC BA
ID SE ID SE
pH pH
HCO3 18 HCO3 12
= = = =
PaCO2 20 PaCO2 20
C pH = 7.55 D pH = 7.40
Figure 8-12. Compensation for respiratory alkalosis. A, The normal [HCO3]/PaCO2 is associated with a
normal pH and acid-base balance. B, Decreased PaCO2 is associated with a decrease in volatile acid
[H2CO3] and an increased pH. C, Renal compensation decreases the blood [HCO3] and tends to normalize
the ratio. D, A normal pH would result if the ratio were restored to normal.
Normal acid-base status Uncompensated metabolic acidosis

(loss of base)
7.3 7.4 7.5 7.3 7.4 7.5

7.2 7.6 7.2 7.6
7.1 7.7 7.1 7.7
7.0 7.8 7.0 7.8
6.9 7.9 6.9 7.9
6.8 8.0 6.8 8.0
A B A
C A C
I S I BA S
D E D E
pH pH
24
HCO 3 HCO 3 12
= = =
PaCO2 40 PaCO2 40
A pH = 7.40 B pH = 7.10

metabolic acidosis metabolic acidosis
7.3 7.4 7.5 7.3 7.4 7.5

7.2 7.6 7.2 7.6
7.1 7.7 7.1 7.7
7.0 7.8 7.0 7.8
6.9 7.9 6.9 7.9
6.8 8.0 6.8 8.0
AC
ID BA S A CI BA S
E D E
pH pH
HCO3 12 HCO3 12
= = = =
PaCO2 30 PaCO2 20
C pH = 7.20 D pH = 7.40
Figure 8-13. Compensation for metabolic acidosis. A, The normal [HCO3]/PaCO2 is associated with a
normal pH and acid-base balance. B, Decreased [HCO3] is associated with a decrease in blood base and a
decreased pH. C, Respiratory compensation decreases the blood volatile acid through hyperventilation and
tends to normalize the ratio. D, A normal pH would result if the ratio were restored to normal.
Normal acid-base status Uncompensated metabolic alkalosis
7.3 7.4 7.5 7.3 7.4 7.5

7.2 7.6 7.2 7.6
7.1 7.7 7.1 7.7
7.0 7.8 7.0 7.8
6.9 7.9 6.9 7.9
6.8 8.0 6.8 8.0
B
A
A CI BA S A CI S
D E D E
pH pH
24
HCO 3 HCO 3 48
= = =
PaCO2 40 PaCO2 40
A pH = 7.40 B pH = 7.70

metabolic alkalosis metabolic alkalosis
7.3 7.4 7.5 7.3 7.4 7.5

7.2 7.6 7.2 7.6
7.1 7.7 7.1 7.7
7.0 7.8 7.0 7.8
6.9 7.9 6.9 7.9
6.8 8.0 6.8 8.0
A B A B
C A C A
I S I S
D E D E
pH pH
HCO3 48 HCO3 48
= = = =
PaCO2 60 PaCO2 80
C pH = 7.50 D pH = 7.40
Figure 8-14. Compensation for metabolic alkalosis. A, The normal [HCO3]/PaCO2 is associated with a
normal pH and acid-base balance. B, Increased [HCO3] is associated with an increase in blood base and
an increased pH. C, Respiratory compensation increases the blood volatile acid through hypoventilation
and tends to normalize the ratio. D, A normal pH would result if the ratio were restored to normal.
Acid-Base Terminology for abnormal laboratory acid-base measure-

In 1964, the International Conference on ments (e.g., [HCO3], [BE], etc.). Conversely,
Acid-Base Terminology was sponsored by the the other school thought that the term acidosis
New York Academy of Sciences in an attempt should not represent a specific laboratory
to standardize acid-base terminology.370 Most measurement but rather a primary abnormal
of the controversy at that time (and I might acid-base process or condition.
add presently) surrounded the appropriate use Despite considerable disagreement,371 the
of the terms acidosis and alkalosis. One school conferees recommended in their report that the
thought that the term acidosis should be used terms acidosis and alkalosis be used only for
primary, abnormal acid-base processes, which is gas classification.371 The terms hyperbasemia
consistent with the usual use of the suffix osis and hypobasemia have been used by several
which means pathologic condition.372 Thus, authors,373375 but this terminology is cumber-
according to their recommendations, a compen- some and is not standard in the literature or in
satory increase in [HCO3] in a particular patient my clinic.
should not technically be called a metabolic alka- Therefore, in this text, I have chosen to use
losis because it is not a primary acid-base distur- the terms acidosis and alkalosis to indicate
bance. In the past (and in many circles in the measured laboratory changes in [HCO3] and
present), it was common to refer to a secondary PaCO2. I believe that naming abnormal labo-
increase in bicarbonate as a compensatory meta- ratory values in this manner greatly aids the
bolic alkalosis, which, of course, is inconsistent novice in blood gas classification.
with recommendations of the International When referring to the patient (compared
Conference on Acid-Base Terminology. with the blood gas), however, the terms acido-
Unfortunately, however, the committee did sis and alkalosis should be used only to indi-
not recommend an alternative terminology for cate primary, abnormal acid-base processes. In
what is sometimes referred to as a compen- comparison, a laboratory metabolic acidosis
satory or secondary acidosis/alkalosis, which, (e.g., decreased [HCO3]), may represent either
I might add, are often very useful terms in blood a primary or a secondary acid-base condition.
EXERCISES
Exercise 8-1 Hydrogen Ions and pH

1. Hydrogen in chemical combination with other elements (is/is not) part of the pH measurement.
2. The definition of pH is the ______.
3. The normal range for pH in arterial blood is ______.
4. The relationship between pH and [H+] is (direct/inverse) and (linear/logarithmic).
5. Doubling of the normal [H+] results in a (0.03/0.3) unit decrease in pH.
6. Any chemical substance capable of releasing a H+ into solution is defined as a/an ______.
7. Any substance capable of combining with or accepting a hydrogen ion in solution is
called a ______.
8. Maintenance of a constant internal environment is called ______.
9. State the two organs primarily responsible for acid-base balance.
10. Normal body metabolism tends to result in an accumulation of excess (acid/base).
11. The (kidneys/lungs) are the major organs of acid excretion.
12. The lungs excrete (volatile/fixed) acid.
13. Normally, ______ is the only volatile acid excreted by the lungs under ordinary conditions.
14. The organs responsible for the regulation of blood bases is the (lungs/kidneys).
15. The major blood base of clinical significance in blood gas interpretation is ______.
Exercise 8-2 Underlying Chemistry of H2CO3 Regulation

1. Chemical equilibrium (does/does not) mean that the concentrations of constituents on

both sides of an equation are equal.
2. A/an (open/closed) chemical system is one in which all the reactants and products in a
chemical reaction must remain within that system.
3. The chemical reaction below is said to be shifted to the (left/right).

H2O + CO2 H2CO3

(800) + (800) (1)
4. The change in equilibrium in response to a change in the amount of one of the reaction
constituents is referred to as the law of ______.
5. If there is an increase in one of the reactants on the right side of a reversible chemical
equation, the law of mass action causes the equilibrium to shift to the (right/left).
6. Write the hydrolysis reaction.
7. There is a (direct/inverse) and (linear/logarithmic) relationship between the concentration of
dissolved CO2 and the concentration of carbonic acid [H2CO3] in the blood.
8. ______ can be used as a marker of blood volatile acid (i.e., [H2CO3]) levels in the
arterial blood.
9. There is a/an (increase/decrease/no change) in the amount of carbonic acid present in the
blood as it passes the tissues.
10. Venous blood is slightly more (acidic/alkaline) compared with arterial blood.
Exercise 8-3 CO2 Homeostasis

1. The amount of CO2 entering the blood depends primarily on the ______.
2. The volume of CO2 produced per minute is designated as the ______.
3. ______ is the amount of fresh gas that reaches functional alveoli.
4. The symbol for alveolar ventilation per minute is ______.
5. State two conditions in which a large increase in metabolism and CO2 production may
result in increased PaCO2.
6. An increase in blood PaCO2 can occur after intravenous administration of the drug ______
to a patient unable to increase his or her alveolar ventilation.
7. An increase in alveolar ventilation results in a /an (increased/decreased) PaCO2.
8. The amount of gas moving in and out of the lungs with each breath is called the ______.
9. Write the formula for minute ventilation.
10. Minute ventilation (is/is not) a reliable index of the adequacy of ventilation.
11. The ______ is the best index available to assess the adequacy of ventilation.
12. Write the formula for alveolar minute ventilation.
13. Alveolar ventilation is (directly/inversely) proportional to PaCO2.
14. An increase in physiologic deadspace may (increase/decrease) PaCO2.
15. A decrease in respiratory rate or tidal volume (increases/decreases) alveolar ventilation.
Exercise 8-4 CO2 Transport

1. State the four mechanisms through which CO2 is carried in the blood.
2. In blood, the solubility coefficient of CO2 is (higher/lower) than the solubility
coefficient of O2.
3. The solubility coefficient of CO2 in blood is ______ mEq/L/mm Hg.
4. A PaCO2 of 80 mm Hg is equal to ______ mEq/L of CO2.
5. The volume of CO2 being transported in the form of H2CO3 (is/is not) negligible.
6. The hydrolysis reaction occurs at a very (slow/fast) rate in the plasma.
7. Of the CO2 transport from tissues to the lungs, 80% is in the form of (dissolved CO2/
carbonic acid/bicarbonate).
8. Inside the erythrocyte, the hydrolysis reaction occurs at a much (faster/slower) rate than in
the plasma.
9. The enzyme that speeds up the hydrolysis reaction is called ______.
10. Hydrogen ions generated by the hydrolysis reaction within erythrocytes are buffered by
(bicarbonate/hemoglobin).

11. Bicarbonate ions are transported through the cell membrane in exchange for (Cl/PO4 /K+).
12. The chloride shift is sometimes referred to as the ______ phenomenon.
13. Most of the HCO3 transporting CO2 from the tissues to the lungs originates in the
(erythrocytes/plasma).
14. Protein in combination with CO2 is called a /an ______.
15. The combined form of hemoglobin and CO2 is called ______.
16. Hemoglobin combination with CO2 (does/does not) occur at the same chemical site as
hemoglobin combination with O2.
17. The affinity of hemoglobin for CO2 is (greater/less) when it is combined with O2.
18. The decreased affinity of hemoglobin for CO2 when it is already carrying O2 is known as
the ______ effect.
19. The percentage of CO2 transport in the form of carbamino-hemoglobin is
approximately ______%.
20. Carbamino compounds in the plasma account for only approximately ______% of CO2
transport.
Exercise 8-5 The Kidney and Acid-Base Balance

1. State the two major acid-base functions of the kidney.

2. Fixed acids (can/cannot) be converted into gases and excreted via the lungs.
3. (Protein/carbohydrate/lipid) metabolism results in the production of inorganic phosphoric
and sulfuric acid.
4. (Protein/carbohydrate/lipid) metabolism in the absence of insulin produces a buildup of
acetoacetic and beta-hydroxybutyric acid.
5. Acetoacetic and beta-hydroxybutyric acid are often referred to collectively as the ______.
6. In the absence of O2, carbohydrate metabolism produces an accumulation of ______ acid.
7. Normally, the amount of fixed acid produced each day is small,
approximately ______ mEq.
8. Ammonium chloride is metabolized by the liver, resulting in the production of ______.
9. The kidneys can (excrete/produce/excrete and produce) bicarbonate ions.
10. The regulation of ([HCO3]/CO2) is the single most important role of the kidneys in
acid-base balance.
Exercise 8-6 Basic Chemistry Related to Buffers

1. Every acid must have a related ______ that is present on dissociation of the hydrogen ion.
2. An acid in conjunction with its associated base is sometimes referred to as a ______.
3. The conjugate base of H2CO3 is ______, and the conjugate base of HHb is ______.
4. All acids have (different/similar) degrees of dissociation.
5. Strong acids have a (high/low) degree of dissociation.
6. A longer arrow in one direction of a dissociation reaction indicates that the concentrations
of substances on that side of the equation are (greater/lower) at equilibrium.
7. In general, the stronger the acid, the (stronger/weaker) is its conjugate base.
8. (Deoxygenated/oxygenated) hemoglobin most readily picks up hydrogen ions.

9. The reaction: HCl H+ + Cl shows a (strong/weak) acid.
10. Hemoglobin may function as an (acid/base/acid or a base) in the blood and is sometimes
referred to as a /an ______ substance.
Exercise 8-7 Blood Buffer Systems

1. Buffer solutions (do/do not) prevent pH change.

2. Buffer solutions minimize pH change by converting strong acids into (bases/weaker acids).
3. State the two chemical substances that must be present in a buffer solution.
4. When a strong acid is introduced into the buffer solution, it reacts with the (salt/weak acid)
portion of the buffer pair.
5. State the two chemical components of the plasma bicarbonate buffer system in the blood.
6. If HCl is added to a bicarbonate buffer system, the results of the buffering are the
chemical substances ______ and ______.
7. Fill in the products of the following buffer reaction:
NaOH + H2CO3/NaHCO3 ______________.
8. State the three plasma buffers in the blood.
9. List the three factors that determine buffer effectiveness.
10. The pK of a weak acid is the pH at which ______% of the acid is dissociated.
11. (Open/closed) system buffers are most effective.
12. Buffers are generally considered to function well within (1/2/3) pH unit(s) of their pK.
13. The most important buffer system in the plasma is the (protein/bicarbonate) system.
14. The most important intracellular buffer is ______.
15. The principle of inter-relationship of the different buffer systems is sometimes referred to
as the ______ principle.
Exercise 8-8 Henderson-Hasselbalch Equation

1. State the name of the following equation:

[H+] = Kc [H2CO3]/[HCO3]
2. The symbol for the negative log of a substance is ______.
3. Write the formula for the Henderson-Hasselbalch equation.
4. Normal pKc is a constant value of ______.
5. The normal [HCO3] in the arterial plasma is ______ mEq/L.
6. The normal volume of dissolved CO2 in the arterial blood in mEq/L is ______.
7. The normal ratio of [HCO3]/dissolved CO2 in mEq/L is ______.
8. The log of 20 is ______.
9. Write the proportion that results if all constants are removed from the
Henderson-Hasselbalch equation.
10. Respiratory conditions alter the (numerator/denominator) of the Henderson-Hasselbalch

proportion.
11. The most important aspect of the Henderson-Hasselbalch proportion is the
(numerator/denominator/ratio between the numerator and denominator).
12. The process of altering the unaffected acid-base component in the Henderson-Hasselbalch
ratio in an attempt to normalize the overall ratio is called acid-base ______.
13. The normal [HCO3]/PaCO2 is ______.
Exercise 8-9 Acid-Base Physiology and Terminology

1. The primary organ system responsible for the [HCO3] is the (renal/respiratory) system.
2. A measured acid-base condition that tends to increase blood pH is termed a /an
____________.
3. A measured acid-base condition that tends to lower blood pH is termed a /an __________.
4. A nonrespiratory acid-base condition is called a /an ______ acid-base disturbance.
5. The kidneys require approximately ______ hours to achieve maximal compensation.
6. In actual patients, complete compensation to a pH of 7.4 is (usually/rarely) achieved.
7. Classify the laboratory acid-base status associated with the following [HCO3]/PaCO2 ratios
as (metabolic acidosis/metabolic alkalosis/respiratory acidosis/respiratory alkalosis):
a. 14/40
b. 24/80
c. 24/20
d. 36/40
8. According to the International Conference on Acid-Base Terminology, the term acidosis
should be reserved for (primary/compensatory) disturbances.
9. In this text, a compensatory increase in bicarbonate is called a /an ______ metabolic
alkalosis.
10. A term used by some authors to indicate decreased blood bicarbonate is ______.

1. Perform a web search using Clinical Acid-Base Balance. Visit sites listed under:
Acid Base Balance: Interactive teaching tools
Acid Base Balance: Introduction
Acid Base Balance: Clinical Considerations
pH of the Blood M.J. Bookallil
2. Write a summary of two new points regarding acid-base balance learned at each site.
NBRC Challenge 8
1. A 63-year-old man presents to the [HCO3] 48 mEq/L
emergency department with the following PaO2 71 mm Hg
arterial blood gases: You can conclude:
pH 7.35 A) the patient has COPD.
PaCO2 59 mm Hg B) the patient has mild hypoxemia
[HCO3] 30 mEq/L secondary to pneumonia.
PaO2 61 mm Hg C) the patient needs mechanical
The patient appears to have: ventilation.
I. chronic renal acid-base D) the hypoxemia indicates a
compensation. pulmonary problem.
II. COPD. E) the pulmonary changes suggest
III. acute respiratory acidosis. compensation for a metabolic
A) I only alkalosis.
B) II only (RRT EXAMINATION NBRC
C) I and II only MATRIX I,B,10,c)
D) II and III only
4. A burn patient is being mechanically
E) I, II, and III
ventilated with a minute ventilation
(CRT EXAMINATION NBRC
of 15 LPM and his PaCO2 is
MATRIX I,C,2,c)
52 mm Hg. A probable
2. In reviewing the patients chart you note explanation is:
that measured venous bicarbonate on the A) increased CO2 production.
electrolyte report is 28 mEq/L whereas B) decreased CO2 production.
the bicarbonate on the blood gas report C) the Haldane Effect.
is 25 mEq/L. You should conclude: D) the Bohr Effect.
A) there is a technical error on the E) excessive fat metabolism.
electrolyte report. (RRT EXAMINATION NBRC
B) there is a technical error on the MATRIX I,C,2,b)
blood gas report.
5. A patient is inadvertently given a
C) the lab tests must have been done
small amount of a strong acid
at different points in time.
intravenously. Blood gases are
D) the patient must have COPD.
immediately drawn and pH is 7.31.
E) these results are consistent and
A large swing in pH was most likely
expected.
prevented because of:
A) renal compensation.
MATRIX I,C,2,f)
B) hypoventilation.
3. A 40-year-old man presents to the emer- C) blood buffers.
gency department with the following arte- D) the hydrolysis reaction.
rial blood gases: E) carbamino compounds.
pH 7.56 (RRT EXAMINATION NBRC
PaCO2 52 mm Hg MATRIX I,B,10,c)
IV
UNIT
Clinical Oxygenation
225
Chapter
9
Assessment and Treatment of Hypoxemia
and Shunting
Hypoxemia...
...cardiac output, oxygen consumption, hemoglobin content, alveolar ventilation or lung disease can each
change, sometimes simultaneously and in opposite directions, so as to complexly alter the PaO2.
Peter D. Wagner243
Outline
Overview, 227 The PaO2/PAO2, 234
Assessment of Hypoxemia, 228 The PaO2/FIO2, 235
Effects of Cardiac Output on PaO2, 228 Summary, 236
Arterial Blood as a Mixture, 229 Differential Diagnosis of Hypoxemia, 236
Changes in Cardiac Output or Shunting, 229 Hypoventilation, 236
Decreased Cardiac Output with a Normal Evaluation, 236
Shunt, 229 Hypoventilation with Increased Shunting, 236
Increased Shunting with Normal Hypoventilation Secondary to Hemodialysis, 237
Cardiac Output, 229 Absolute Shunting, 237
Decreased Cardiac Output with an Capillary Shunting, 237
Increased Shunt, 230 Anatomic Shunting, 237
Increased Cardiac Output with an The 100% O2 Test, 237
Increased Shunt, 230 Relative Shunting, 238
Clinical Implications, 231 Diffusion Defects, 238
Other Mechanisms of Decreased PvO2, 231 Effects of Altitude and Air Travel in
Assessment of Physiologic Shunting, 232 Hypoxemia, 238
Introduction, 232 Summary, 239
Indices of Physiologic Shunting, 232 Clinical Appearance of the Patient with
Classic Shunt Equation, 232 Hypoxemia/Hypercapnia, 239
Estimated Shunt Equations, 232 Hyperoxemia, 239
The P(A a)O2, 233 Exercises, 240
OVERVIEW
words, Is the PaO2 appropriate for the given
The ability of the lungs to transfer oxygen from FIO2? Thus, the second part of oxygen transfer
the atmosphere to the pulmonary capillary blood evaluation is essentially an assessment of pul-
(i.e., external respiration) is the first critical step monary shunting.
in the overall process of oxygenation. The clin- The first section of this chapter briefly
ical assessment of oxygen transfer in the lungs describes the classification and assessment of
is a two-part evaluation. hypoxemia. Special reference is also made to
First, the adequacy of oxygen transfer must the effects of cardiac output and mixed venous
be evaluated. Assessment of the adequacy of blood on PaO2. The next portion of this chapter
oxygen transfer in the lungs is essentially hypo- addresses the evaluation and quantification of
xemic (i.e., PaO2) evaluation. An adequate PaO2 pulmonary shunting. The various clinical indices
is one that is sufficiently high so as not to suggest that have been used to estimate and quantify
the likelihood of tissue hypoxia. pulmonary shunting are surveyed. The use of
Second, the efficiency of oxygen transfer some of these indices in the differential diagnosis
through the lungs should be considered. In other of clinical hypoxemia is also discussed.
227
228 Unit IV Clinical Oxygenation
This is followed by a description of the clin- Box 9-1 Mechanisms of Hypoxemia

ical signs and symptoms associated with hypo-
1. Hypoventilation
xemia, hypercapnia, and hyperoxemia. Finally,
2. Absolute shunting
methods for treating hypoxemia are discussed. 3. Relative shunting
The value and clinical indications for oxygen 4. Diffusion defects
therapy, body positioning, mechanical ventila-
tion, and the use of positive end-expiratory
pressure (PEEP) are explored.
In the hospital, there are really only four
potential causes of hypoxemia (Box 9-1). These
ASSESSMENT OF HYPOXEMIA
causes include hypoventilation (see Fig. 9-1,C);
Hypoxemia is defined in this text as a below- absolute shunting (see Fig. 9-1,D); relative
normal PaO2 in the blood. The severity of shunting, commonly referred to as ventilation/
hypoxemia is an important indicator of the like- perfusion mismatch (see Fig. 9-1,E); and diffu-
lihood of hypoxia concomitant with the hypo- sion defects (see Fig. 9-1,F). Almost all hypo-
xemia. Table 2-7 is provided in Chapter 2 for xemia (excluding changes in cardiac output) in
classification of the severity of hypoxemia. the hospital setting may be presumed to be
Five mechanisms by which hypoxemia may due to one or more of these four mechanisms.
occur are shown in Figure 9-1. Hypoxemia may The differential diagnosis of hypoxemia is dis-
be due to a low partial pressure of inhaled oxy- cussed in a subsequent section of this chapter.
gen (PIO2) (which is present at high altitude),
when exhaled gas is rebreathed continuously
EFFECTS OF CARDIAC
in a confined area, or when a gas with less than
OUTPUT ON PaO2
21% oxygen is inspired (see Fig. 9-1,B). This
mechanism, however, is rarely responsible for A decrease in cardiac output is not generally
hypoxemia in the acute care setting. considered to be a primary cause of hypoxemia,
PACO2 PACO2
PAO2 PAO2 PAO2 PAO2
A. Normal gas exchange B. Decreased PIO2 C. Hypoventilation D. Absolute shunt
V/Q V/Q
E. Relative shunt F. Diffusion defect
Figure 9-1. Mechanisms of hypoxemia.

Chapter 9 Assessment and Treatment of Hypoxemia and Shunting 229
and no mention of cardiac output is made in oxygen content of mixed venous blood (CvO2)
Box 9-1 regarding the causes of hypoxemia. more accurately reflects the amount of oxygen
Notwithstanding, it is not correct to presume present in this blood and, therefore, how much
that the cardiac output has no effect on PaO2. it affects the arterial PO2. Nevertheless, PvO2 is
The relative influence of cardiac output on used here to illustrate this concept in the most
PaO2 in various clinical situations is explored. straightforward manner.
Arterial Blood as a Mixture Changes in Cardiac Output or Shunting

The clinician must always keep in mind that Decreased Cardiac Output with a Normal Shunt
arterial blood is a mixture of blood from two A decrease in PvO2 typically accompanies a
sources. Oxygenated blood is leaving func- decrease in cardiac output if oxygen consump-
tional alveolar-capillary units and entering the tion remains constant. Because tissues are
arteries. Also, some mixed venous blood is exposed to less blood, they must extract more
always entering the arterial circulation via the oxygen from available blood, which results in
normal anatomic shunt (Fig. 9-2). a lower PvO2. Thus, when cardiac output falls,
Note that, in a healthy individual breathing shunted blood entering the arterial circulation
room air, the PaO2 (100 mm Hg) is slightly will have a lower PvO2 than shunted blood
lower than the average partial pressure of when cardiac output is normal (Fig. 9-3).
oxygen in the average alveolus (i.e., PAO2 Nevertheless, it is important to note that in oth-
105 mm Hg) and significantly higher than the erwise normal lungs, a decrease in cardiac out-
mixed venous partial pressure of oxygen (i.e., put lowers PaO2 only slightly because shunted
PvO2, which is approximately 40 mm Hg). blood accounts for only 5% of the total arterial
Arterial PaO2 nearly approximates alveolar blood mixture. Thus, although PaO2 decreases
PAO2 because roughly 95% of arterial blood slightly with a decrease in cardiac output, the
originates from normally functioning alveolar- effect of a decreased cardiac output on PaO2 in
capillary units where the blood end-capillary the normal lung is minute.
PO2 (PcO 2 equilibrates with the PAO2). In con-
trast, less than 5% of the arterial mixture Increased Shunting with Normal Cardiac Output
is comprised of PvO2 contributed from the In the individual with an abnormally high
shunted blood. pulmonary shunt, the PvO2 of the shunted
Throughout the discussion regarding the blood has a more substantial impact on PaO2
effects of cardiac output on PaO2, the amount as shown in Figure 9-4. The low PaO2 that
of oxygen in the shunted blood is shown as a accompanies increased physiologic shunting
pressure measurement (e.g., PvO2). Actually, the is a result of the large percentage of venous
PAO2 PAO2
105
Hg
Hg
105
Pc
Pc
O 2
mm Hg mm Hg
O 2
m
m
m
10
10
Normally Normally
40
25
Normal anatomic
5
Normal anatomic
5
oxygenated
m
oxygenated
m
2
O
shunt 5%
O
shunt 5%
m
Pv
Pv
m
blood 95% blood 95%

Hg
Hg
PaO2 Arterial blood PaO2 Arterial blood

100 95
mm Hg mm Hg
Figure 9-2. Arterial blood is a mixture of Figure 9-3. Effects of decreased cardiac output on
oxygenated and shunted blood. PaO2 in humans with normal physiologic shunting.
Figure 9-5 shows how a decline in cardiac

output affects PaO2 in the patient compromised
PAO2 with preexisting pathologic shunting. Note the
105
mm Hg
Fluid lower PaO2 shown in Figure 9-5 compared
Hg
with Figure 9-4, despite identical shunt frac-
Pc
O 2
m
tions of 25%. Note also that a decrease in car-
m
10
Anatomic and
40
Normally diac output has a greater impact on PaO2 in the
5
pathologic
m
2
oxygenated O
Pv
individual with increased physiologic shunting
m
blood 75% capillary

Hg
shunt 25% (see Fig. 9-5), compared with the individual

PaO2
who has only a normal anatomic shunt (see
60 Arterial blood Fig. 9-3). It has in fact been shown that a
mm Hg decrease in PvO2 from 40 to 30 mm Hg with
a constant 30% shunt decreases PaO2 from
Figure 9-4. Effect of substantial physiologic 55 mm Hg to approximately 45 mm Hg.244
shunting on PaO2.
Increased Cardiac Output with an Increased Shunt
In the presence of a large physiologic shunt and
hypoxemia, cardiac output is more likely to
blood entering the arterial circulation. Note increase rather than decrease in the individual
that, in this case, the cardiac output and PvO2 with an intact cardiovascular system.245 The
are still normal. Increased shunting is the most increase in cardiac output is due at least partly to
common mechanism responsible for the devel- stimulation of the peripheral chemoreceptors sec-
opment of hypoxemia. ondary to the hypoxemia. Cardiac output tends
to increase quickly, due primarily to an increased
Decreased Cardiac Output with an Increased Shunt heart rate, and in a dose-response fashion.245
When substantial shunting is present, any In other words, the more severe the hypoxemia,
change in cardiac output has a more profound the greater the increase in cardiac output.
effect on PaO2. This is because changes in car- Increasing cardiac output tends to enhance
diac output affect the PO2 of the shunted blood, tissue oxygenation both by an increase in the
and the larger the physiologic shunt, the greater blood reaching the tissues and, to a lesser extent,
is the percentage of shunted blood entering the by increasing PaO2. The increase in cardiac
arterial circulation. output improves PaO2 by increasing PvO2,
PAO2 PAO2
105 105 Fluid
Fluid mm Hg
mm Hg
Hg
Hg
Pc
Pc
m
O 2
m
O 2
m
m
50
10
10
25
Anatomic and Normally Anatomic and

5
Normally
5
2
O
pathologic
2
m
m
pathologic
Pv
oxygenated
Pv
oxygenated
m
m
capillary blood 75% capillary

Hg
Hg
blood 75% shunt 25%

shunt 25%
PaO2 PaO2
Arterial blood 65 Arterial blood
50
mm Hg mm Hg
Figure 9-5. Effects of decreased cardiac output Figure 9-6. Effects of increased cardiac output
on PaO2 in the patient with increased physiologic on PaO2 in the patient with increased physiologic
shunting. shunting.
which is shown in Figure 9-6. This result is the observed in the critically ill patient with appar-
opposite effect to that shown in Figure 9-5 ently stable pulmonary status. Cardiac output
where cardiac output is decreased. can be measured directly in the patient with
a pulmonary artery catheter in place. In the
Clinical Implications absence of a pulmonary catheter, the patient
In clinical practice, the PaO2 is often used as a should be monitored for signs of low cardiac
crude index of pulmonary shunting. When the output, such as those described in Chapter 10.
fractional concentration of inspired oxygen
(FIO2) is held constant, an increase in PaO2 is Other Mechanisms of Decreased PvO2
usually attributed to an improvement in lung The clinician should understand that the preced-
function and the pulmonary shunt. Conversely, ing discussion about how cardiac output affects
a decline in PaO2 suggests further deteriora- PaO2 is really an oversimplification. First, as
tion in pulmonary gas exchange and worsen- stated previously, the actual PaO2 that results
ing of the pulmonary shunt. from the mixture of oxygenated and shunted
The logic of these assumptions is sound, and blood depends more on the oxygen content of
most often these assumptions prove to be cor- the two components than on their respective
rect. Sometimes, howeverparticularly in the oxygen tensions.
critically ill patient with substantial pulmonary Second, it should be understood that the
dysfunctiona change in PaO2 may be prima- mixed venous oxygen content or tension does
rily due to a nonpulmonary change.246 As has not depend solely on cardiac output. Anemia,
been shown, cardiac output has a notable increased metabolism, and abnormal distribu-
effect on PaO2 in patients with increased phys- tion of systemic perfusion are only some of the
iologic shunts. Furthermore, the influence of other factors that can significantly affect mixed
cardiac output on PaO2 is related directly to venous oxygen levels and, consequently, the
the size of the shunt. PaO2. It has been shown, however, that cardiac
It is wise to suspect a change in cardiac out- output is probably a primary factor in many
put when abrupt, unexplained hypoxemia is clinical situations.

Shortly before 11:00 AM, acute chest pain, shortness of PaO2 49 mm Hg

breath, frequent arrhythmias, and hypotension develop in [HCO3] 13 mEq/L
a 52-year-old woman with severe pneumonia. Interpret FIO2 0.50
the blood gases and patient condition at 11:00 AM.
ASSESSMENT
ARTERIAL BLOOD GASES 10:00 AM Abnormalities: List abnormal data and other noteworthy
SaO2 93% information. Classify ABG.
pH 7.37 Explanation: List possible diseases, pathology, or other
PaCO2 37 mm Hg situations that may have led to this patients condition.
PaO2 72 mm Hg Evaluation: Suggest additional data that would be
[HCO3] 25 mEq/L useful in helping understand the situation or in making
FIO2 0.50 a diagnosis.
ARTERIAL BLOOD GASES 11:00 AM INTERVENTION

SaO2 84% Importance: Prioritize concern(s) of treatment in order
pH 7.28 of urgency and/or seriousness as you see the overall
PaCO2 29 mm Hg situation.
ASSESSMENT OF PHYSIOLOGIC Box 9-2 Indices to Evaluate the

SHUNTING Physiologic Shunt
Introduction 1. Classic shunt calculation
2. Modified shunt equations
It is often useful in the clinic to quantitate the 3. P(A a)O2
efficiency of oxygen transfer in external respira- 4. PaO2/PAO2
tion. Analysis of oxygen-loading efficiency can 5. PaO2/FIO2
aid the clinician in the differential diagnosis of
lung disease and can provide valuable informa-
tion about severity or progression of pulmonary
disease. In addition, some indices of oxygen The physiologic shunt as calculated via the
loading can be useful in guiding oxygen therapy classic shunt equation is therefore the most
and related treatment of lung disorders. sophisticated and accurate measure of the effi-
The PaO2 alone provides little information ciency of the lungs to transfer oxygen. The
regarding the efficiency of oxygen loading into classic shunt equation and measurement is
the pulmonary capillary blood. The physiologic therefore the gold standard in the measurement
shunt, on the other hand, is the percentage of of the efficiency of oxygen uptake by the lungs.
the venous blood that remains unoxygenated Probably the most notable deterrent to rou-
after traveling from the right side of the heart tine measurement of the physiologic shunt is the
to the left side of the heart. It includes blood requirement for mixed venous blood samples.
that is absolutely shunted (i.e., anatomic shunts Mixed venous blood samples are available only
and true capillary shunts) and alveolar-capillary when a pulmonary artery (Swan-Ganz) catheter
units in which perfusion exceeds ventilation (i.e., is in place. . .
relative shunts). Thus, monitoring physiologic It should also be noted that Qsp/QT changes
shunting is an excellent way to quantitate the somewhat depending on the FIO2 at which it is
efficiency of oxygen uptake via the lungs. The measured. The pulmonary shunt tends to
indices that can be used to measure or to esti- decrease as FIO2 is increased from 0.21 to 0.40,
mate physiologic shunting are shown in Box 9-2. remains constant from FIO2 0.40 to 0.70, then
increases as FIO2 .moves.
above 0.70.253
Indices of Physiologic Shunting Nevertheless, Qsp/QT, which is calculated
Classic Shunt Equation through the classic shunt equation, is the meas-
The classic shunt equation. .
for calculation of urement of choice whenever a pulmonary artery
physiologic shunting (Qsp/QT) was described catheter is in place. Similarly, when precise
in Chapter 6 (Equation 6-3). It is noteworthy monitoring of pulmonary shunting is indicated,
that the classic shunt equation corrects for any such as in the patient with severe pulmonary
nonpulmonary (e.g., PvO2) mediated effects on shunting (e.g., PaO2 of 60 mm Hg on FIO2 of
arterial oxygenation, which have been described 0.60), some clinicians recommend pulmonary
earlier in this chapter. This is accomplished by catheterization to facilitate accurate monitoring
directly measuring mixed venous oxygen of the physiologic shunt.247
content and by using this value in the denomi-
nator of the equation. In fact, the classic shunt Estimated Shunt Equations
calculation is the only index of oxygen-loading When mixed venous blood is unavailable, a
efficiency of those shown in Box 9-2 that takes modified version of the classic shunt equation is
into account these .nonpulmonary
.
factors. sometimes used to estimate physiologic shunt-
Calculation of (Qsp/QT) via the classic shunt ing. Estimated shunt equations assume a given
equation is thus the only accurate way to meas- arteriovenous oxygen content difference
ure physiologic shunting when cardiac output (C[a v]O2) in their calculations. In some ver-
is unstable. Also, by using this index, the clini- sions of the equation, the difference is assumed
cian can distinguish between PaO2 disturbances to be the normal 5 vol%.248,249 Because it is
of pulmonary versus cardiovascular origin. common for critically ill patients to have
a higher cardiac output or lower oxygen Calculation

extraction than normal (and therefore a lower Obviously, only two measurements (PaO2 and
arteriovenous difference), in some versions, a PAO2) are needed to calculate the gradient.
difference of 3.5 vol% is deemed more accu- PaO2 is reported with the arterial blood gas
rate.250 A lower C(a v)O2 has also been demon- data. The PAO2 represents the ideal or mean
strated in patients with hepatopulmonary alveolar oxygen tension. Equation 9-2 is referred
syndrome and should be used when calculating to as the clinical alveolar air equation and repre-
estimated shunt in this group.282 sents the best formula to calculate clinical PAO2
An example of an estimated shunt equation when FIO2 is 0.6 or less.258 Other forms of this
using a C(a v)O2 difference of 3.5 vol% is equation have been shown to be less accurate
shown in Equation 9-1. Also note that the and should be avoided.258 Equation 9-2 roughly
equation has been rearranged to accommodate assumes a respiratory quotient (RQ) of 0.8,
inclusion of the arteriovenous difference. which has been shown to be a reasonable
clinical assumption.259,260
. .
Equation 9-1
Qsp/QT = (CcO
2 CaO2)/(CcO
2 CaO2) + 3.5 Equation 9-2
PAO2 = PIO2 1.2(PaCO2)
When mixed venous blood gases are
unavailable, the estimated shunt equation is When an individual is breathing an FIO2
probably the best alternative to the classic shunt greater than 0.6, the form of the clinical alveo-
formula.248,251 Notwithstanding, however, there lar air equation shown in Equation 9-3 should
are really no true substitutes for actually meas- be used for this calculation.258
uring mixed venous oxygen contents in criti-
Equation 9-3
cally ill patients.252 PAO2 = PIO2 PaCO2
The P(A a)O2 The PIO2 can be determined by multiplying
Normal Values the FIO2 by the barometric pressure minus water
The alveolar-arterial oxygen tension gradient, or vapor pressure (Equation 9-4). Equation 9-5
P(A a)O2, is a well-known noninvasive bedside shows that when breathing room air at sea
index that is used to quantitate the efficiency of level, PIO2 is approximately 150 mm Hg.
oxygen loading. If the blood and alveolar gas
Equation 9-4
were perfectly matched, the efficiency of oxygen PIO2 = (PB PH2O) FIO2
loading would be high and little or no difference
would exist between the mean alveolar PO2 where:
and the arterial PO2. On the other hand, an PB = barometric pressure, and
increase in P(A a)O2 suggests an increase in PH2O = water vapor pressure at 37 C.
the physiologic shunt.
Equation 9-5
The mean normal P(A a)O2 is approxi- PIO2 = (PB PH2O) FIO2
mately 10 mm Hg in adults younger than 60 = (760 mm Hg 47 mm Hg) 0.21
years of age breathing room air.254 Individual = 150 mm Hg
variations, however, may be great. The upper
limit of normal for adults younger than 60 years A shortcut that can be used to calculate
of age is approximately 20 mm Hg.254,255 P(A a)O2 is to subtract the sum of PaO2 and
Unfortunately, P(A a)O2 increases with PaCO2 from the normal sum of PAO2 and
advancing age and may be as high as 35 mm Hg PACO2 for the pertinent altitude.258 At sea level,
in the healthy individual older than 60 years the normal sum of alveolar PO2 and PCO2 is
of age.254 Furthermore, in some individuals, approximately 140 mm Hg. Thus, at sea level,
P(A a)O2 may also change with body posi- Equation 9-6 can be used to calculate P(A a)O2.
tion. In individuals older than 44 years of age,
P(A a)O2 increases with the assumption of Equation 9-6
the supine position.256,257 P(A a)O2 = 140 mm Hg (PaCO2 + PaO2)
Limitations with changing values of FIO2.261 Due to its

The P(A a)O2 is not particularly useful for increased stability, the PaO2/PAO2 appears
monitoring the progress of pulmonary dys- to have several advantages in clinical and
function at various values of FIO2.253 P(A a)O2 research application, compared with the
varies with both age and FIO2. In one study, the P(A a)O2.253,262
P(A a)O2 escalated with increasing FIO2 up
to 0.6. Above FIO2 of 0.6, no further increase Evaluation of Lung Function
in P(A a)O2 was observed.254 In the same Because, unlike P(A a)O2, the PaO2/PAO2 is
study, mean P(A a)O2 was 38 mm Hg for relatively constant with changes in FIO2, the
individuals 40 to 50 years old with FIO2 at progressive evaluation of lung function is more
0.4.254 At FIO2 of 0.6, the mean P(A a)O2 for readily accomplished. The PaO2/PAO2 has also
all age groups was 50 mm Hg. Most impor- been shown to parallel disease severity and shunt
tantly, P(A a)O2 correlates poorly with fraction in neonatal respiratory distress syn-
changes in pulmonary shunting.253 drome patients.263 Similarly, PaO2/PAO2 can be
Furthermore, the P(A a)O2 does not provide used to compare oxygen-loading efficiency in
the clinician with information regarding the patients on different FIO2 levels. The findings
selection of the most appropriate FIO2 level may have potential research application.
when treating the patient. Some indices dis-
cussed later in this chapter are purported to be Guide to Oxygen Therapy
valuable in this regard. Overall, the P(A a)O2 Under certain clinical conditions (see the fol-
has limited use when supplemental oxygen is lowing section on stability), the PaO2/PAO2
being administered. The normal P(A a)O2 does may also be useful to the clinician as a guide for
not remain constant at different FIO2 levels, nor selecting appropriate oxygen therapy. However,
is the normal range well established for many this method of selecting oxygen therapy is only
given FIO2 levels. accurate in the patient with unchanging car-
The P(A a)O2 may be somewhat useful in diopulmonary status.
evaluating pulmonary shunting in the patient When PaO2/PAO2 is calculated for a given
breathing room air who is also hypoventilating. patient at a given FIO2, the PaO2 that will
This application will be described later in this result from a change in FIO2 can be reasonably
chapter. approximated. Similarly, the FIO2 required to
achieve a specific target PaO2 can also be
The PaO2/PAO2 calculated if the initial PaO2/PAO2 is known.
Description In one study, a nomogram based on the
Limitations of the P(A a)O2 have led to the PaO2/PAO2 was shown to be quite accurate in
introduction of other indices to evaluate oxygen predicting the required FIO2 level to achieve a
transfer across the lungs. An alternative way to desired PaO2.264
look at the efficiency of pulmonary oxygena-
tion is to determine what percentage of the Normal Values
PAO2 that is delivered to the alveoli actually The lower limit of normal for PaO2/PAO2
reaches the arterial blood. Thus, instead of look- appears to be 0.75.261,265 In other words, 75%
ing at the absolute numeric alveolar-arterial of the oxygen partial pressure that is delivered
oxygen tension difference, one is evaluating to the alveoli normally reaches the arterial
the percentage of successful oxygen transfer. blood. Obviously, a low percentage (e.g., 0.30)
A clinical index that may be used for this indicates poor oxygen transfer and increased
purpose is the PaO2/PAO2. physiologic shunting. Generally, the lower
Theoretically, assuming constant lung func- the percentage, the greater the shunt. It must
tion, the percentage of the PAO2 that is success- always be remembered, however, that these
fully transferred across the lung should remain simplified indices of shunting do not take into
constant regardless of FIO2. Thus, as one might account changes in cardiac output and may be
expect, the arterial/alveolar PO2 ratio has been misleading in the patient with cardiovascular
shown to be more stable than the P(A a)O2 instability.
Stability of shunting that fails to account for cardiac

As the FIO2 is changed, the PaO2/PAO2 shows output and venous blood gas values is inher-
the most stability when the FIO2 is greater ently inaccurate.253,272 When a precise measure
than 0.3 and when the PaO2 is less than of shunting is indicated, the physiologic shunt
100 mm Hg.262 Therefore, the ratio is most accu- should be measured.
rate for predicting PaO2 for a given FIO2 when Surprisingly, several studies have suggested
values before and after the change fall within that the PaO2/FIO2 is actually more accurate
this range. The ratio also seems to be particu- than the PaO2/PAO2 as an index of pulmonary
larly constant in patients with fairly substan- shunting.247,248,273 A PaO2/FIO2 less than 200
tial shunts (i.e., those patients with ratios most often indicates a shunt greater than
<0.55).261,265 Interestingly, a large .relative
.
shunt 20%.247,270,272 Furthermore, a low PaO2/FIO2
component (many low but finite V/Q) seems to ratio on a relatively high FIO2 (e.g., PaO2/FIO2
diminish stability and is associated with an of 60 at FIO2 of 0.6) is clear evidence of a poor
abrupt increase in the ratio at some point as response to oxygen therapy and the presence of
the FIO2 increases.262 The precise FIO2 level at absolute shunting.
which this spike occurs is unpredictable; how-
ever, the more severe the ventilation/perfusion PaCO2 Changes
mismatch, the closer this FIO2 level is to 1.0.262 A notable limitation of the PaO2/FIO2 is that
it does not take into account changes in
The PaO2/FIO2 PaCO2. For example, if a patients PaO2 fell
The PaO2/FIO2, which is a simplified version of to 60 mm Hg due to hypoventilation (e.g.,
the PaO2/PAO2, has been used by many clini- PaCO2 = 80 mm Hg) while breathing room
cians as an index of pulmonary oxygen exchange air, the oxygenation ratio would decrease from
efficiency.266268 This index is easier to calcu- a normal value of 5.0 to approximately 3.0.
late because changes in arterial PaCO2 are dis- This oxygenation ratio implies that the intrin-
regarded and the clinical alveolar air equation sic ability of the lungs to transfer oxygen is
is not needed. Because normal PaO2 on room impaired. In fact, physiologic shunting is
air (0.2 FIO2) in adults is 80 to 100 mm Hg, normal; the hypoxemia is solely the result of
it follows that the normal PaO2/FIO2 is approxi- hypoventilation.
mately 400 to 500 mm Hg. Therefore, the oxygenation ratio should not
be used as an index of physiologic shunting with
Oxygenation Ratio low FIO2 levels (e.g., <0.3). At low FIO2 levels,
In 1972, Lecky and Ominsky reported the changes in PaCO2 tend to have a considerable
denominator of the PaO2/FIO2 ratio as a per- effect on the ratio. On the other hand, in many
centage (i.e., PaO2/%FIO2) and called this the clinical situations, and particularly in patients
oxygenation ratio.269 Using percentage in the receiving mechanical ventilation, the PaCO2
denominator, the normal range for the oxygena- does not usually change substantially between
tion ratio is simply 4.0 to 5.0. These workers blood gases,274,275 and the oxygenation ratio is
concluded that this index was the most simple, a useful gross indicator of pulmonary oxy-
understandable, and useful method for train- genation efficiency.
ing a novice to relate arterial to inspired oxygen The entire issue regarding the effects of
levels and to interpret this relationship.269 changes in PaCO2 is further clouded because
changes in PaCO2 directly influence cardiac
Index of Shunting output and PaO2.276 Decreases in PaCO2 levels
The PaO2/FIO2 and oxygenation ratio have been have been shown to significantly decrease
criticized because they do not always reflect cardiac output.277,278 Thus, changes in PaCO2
changes in shunting.270,271 However, in critically should be expected to alter oxygen-loading
ill patients with compromised cardiovascular efficiency. Because of the complex nature of
status, none of the shunt indices except the these interactions, high levels of precision
actual shunt measurement should be expected to in these clinical indices are difficult, if not
parallel closely the actual shunting. Any index impossible, to obtain.
Summary correct the problem, supportive therapy must be

provided to ensure adequate oxygen delivery
The search continues for a noninvasive index of true
to the tissues at minimum energy expense.
venous admixture. However, one may not exist.
Although it is desirable to try to isolate a
W. M. Granger253
single mechanism responsible for hypoxemia
in a given patient, this is often not possible.
The ideal method to assess the physiologic Frequently, hypoxemia is due to a combination
shunt is to measure the necessary values and of the four mechanisms shown in Box 9-1. For
calculate it. Mixed venous blood is essential to example, the patient with pneumonia typically
make these calculations; therefore, blood must has both true and relative shunting. In fact, it is
be sampled via a pulmonary artery catheter. unlikely that absolute capillary shunting is ever
The second best method to assess pulmonary present without some degree of relative shunt-
shunting is calculation of an estimated shunt, ing. Nonetheless, it is beneficial to determine the
based on an assumed arteriovenous oxygen major mechanism causing hypoxemia because
content difference. treatment that is focused on the primary prob-
All shunt calculations are rather cumbersome; lem is more likely to be effective.
however, a pocket computer can be programmed In approaching the differential diagnosis of
for easy calculation. When shunt calculations hypoxemia, each of the potential hypoxemic
are unavailable, other indices of pulmonary oxy- mechanisms shown in Box 9-1 should be respec-
genation efficiency, based on arterial PO2 and tively considered. Clinical evidence should then
alveolar PO2, are often used. All of these indices be sought to support or rule out the presence
may be somewhat inaccurate because PaO2, of that mechanism.
PAO2, and FIO2 values have similarly ques-
tionable precision. Hypoventilation
The PaO2 is the least accurate of blood gas Evaluation
measurements, and the oxygen electrode may be Alveolar hypoventilation while breathing room
especially inaccurate at high PaO2.279 Similarly, air leads to hypoxemia as carbon dioxide
the level of FIO2 that a given patient is presumed replaces oxygen in the alveoli. This mechanism
to be receiving is often very different from should be evaluated first because its presence or
the level that actual measurements have indi- absence can be determined quickly and accu-
cated.280,281 Finally, it has been shown that rately via PaCO2 assessment. Alveolar hypoven-
precise calculation of PAO2 is virtually impos- tilation is easily recognized as an arterial PCO2
sible, given the assumptions and inaccuracies higher than normal (i.e., PaCO2 > 45 mm Hg).
implicit in the clinical alveolar air equation. When hypoventilation is observed in an indi-
Despite these limitations, these indices are vidual with hypoxemia, the hypoventilation is
often useful as gross indicators of the efficiency responsible, at least in part, for the hypoxemia.
of pulmonary oxygen uptake. Using these
indices, impairment of pulmonary gas exchange Hypoventilation with Increased Shunting
can be tracked, and may provide crude guide- In disease states, other hypoxemic mecha-
lines to appropriate oxygen therapy. nisms commonly accompany hypoventilation.
Calculation of the alveolar-arterial oxygen
tension gradient (P[A a]O2) while the patient
DIFFERENTIAL DIAGNOSIS OF
is breathing room air is a useful tool for deter-
HYPOXEMIA
mining if the hypoxemia is due to hypoventila-
In the presence of clinical hypoxemia or tion alone or to hypoventilation in combination
increased physiologic shunting, the pathologic with increased physiologic shunting.283285
mechanism in gas exchange should be sought. In individuals younger than 60 years of age, a
Ultimately, the primary disease process or mech- P(A a)O2 less than 20 mm Hg while breathing
anism should be identified, and a comprehen- room air is indicative of relatively normal oxygen
sive care plan should be formulated. Until this uptake by the lungs. Conversely, a P(A a)O2 in
comprehensive treatment plan can completely excess of 20 mm Hg is abnormal and suggests
increased physiologic shunting. Some authors may result in profound improvement in arte-
consider 10 to 15 mm Hg to be a normal range rial oxygenation. Substantial anatomic shunt-
for P(A a)O2 while breathing room air.286 ing often requires surgical intervention.
A normal gradient of up to 20 mm Hg is used
here because this includes approximately The 100% O2 Test
2 standard deviations from the mean of the adult The 100% O2 test, which compares the
population.287 P(A a)O2 of an individual breathing room
air with the P(A a)O2 on FIO2 of 1.0, is use-
Hypoventilation Secondary to Hemodialysis ful in differentiating true capillary shunting
Somewhat surprisingly, hemodialysis has been from relative capillary shunting.262 Both
associated with the development of hypoventi- absolute and relative capillary shunting will
lation and hypoxemia. Apparently, the dialysis show an increased P(A a)O2 on room air;
acts like a second set of lungs in that carbon however, when FIO2 1.0 is administered for
dioxide is excreted. The pseudo-hypoventilation approximately 20 minutes, the P(A a)O2
that ensues reduces ventilation to the actual remains abnormal only if absolute shunting is
lungs with resultant hypoxemia although present.
actual PaCO2 remains normal.290 Hypoxemia due to relative capillary shunt-
ing is caused by an inadequate oxygen supply . .
Absolute Shunting in the poorly ventilated alveoli (i.e., low V/Q).
Blood passing from the right side to the left Administration of FIO2 of 1.0 provides suffi-
side of the heart without being exposed to cient oxygen to all alveoli regardless of the actual
alveolar oxygen constitutes an absolute shunt. volume of ventilation. Thus, FIO2 of 1.0 totally
Absolute, or true, shunts may be anatomic or corrects hypoxemia due to relative capillary
capillary in nature (see Chapter 6). Absolute shunting.
shunting responds poorly to administration of The normal P(A a)O2 at FIO2 of 1.0 is less
supplemental oxygen, because the oxygen does than 50 mm Hg. Therefore, at FIO2 of 1.0, a
not come in contact with the shunted blood. P(A a)O2 greater than 50 mm Hg indicates the
presence of absolute shunting; conversely, when
Capillary Shunting it is less than 50 mm Hg, there is no abnormal
Absolute capillary shunting results from alveolar absolute shunt component. In this case, shunting
consolidation (filling with fluid) or collapse. observed on room air must be due to the
Alveolar consolidation appears as a white-out relative shunt effect.
on the chest radiograph. Conditions known to Actual performance of the 100% O2 test is
be associated with absolute capillary shunting presently rarely done because it has been shown
should alert the clinician to its likelihood. These that breathing FIO2 of 1.0 leads in itself to
include acute respiratory distress syndrome, absorption atelectasis and to increased true cap-
left-sided heart failure, pneumonia, and atelec- illary shunting.288 The absolute shunt measured
tasis. Pulmonary edema, whether cardiogenic in normal individuals may even exceed 10%
(left-sided heart failure) or noncardiogenic, is after breathing FIO2 of 1.0. This shunt induc-
probably the single greatest cause of severe, ing effect is undesirable, particularly in patients
absolute capillary shunting in critical care units. already compromised by increased physiologic
shunting.
Anatomic Shunting Nevertheless, the basic theory underlying
Congenital cardiovascular anomalies are often the 100% O2 test may be clinically useful.
accompanied by increased anatomic shunting. That is, the general degree of PaO2 responsive-
Similarly, newborn infants with persistent ness to oxygen therapy may help to differentiate
fetal circulation also have anatomic shunts. true from relative shunting.286 A substantial
Generally, pulmonary intervention is ineffec- increase in PaO2 after elevation of FIO2 sug-
tive in the treatment of these problems. In the gests relative shunting, whereas a poor response
case of persistent fetal circulation, however, to oxygen therapy is typical of absolute
decreasing the pulmonary vascular resistance shunting.
Relative Shunting some degree in all patients who manifest

Relative shunting is often referred to as hypoxemia.
ventilation-perfusion mismatch or simply per-
fusion in excess of ventilation. Hypoxemia is Diffusion Defects
observed on room air when a substantial quan- A diffusion defect is a structural impedance to
tity of pulmonary. .
perfusion is to areas with oxygen transfer in the lungs, due to a thick-
below-normal V/Q. In contrast to absolute ened alveolar-capillary membrane. However, it
shunting, relative shunting is characterized by is unlikely that diffusion defects alone result in
a good PaO2 response to small increments of hypoxemia at sea level in humans with normal
oxygen therapy. cardiac output. Most of the hypoxemia at rest
Relative shunting in the clinic is most often observed in patients with diffusion defects is
the result of uneven distribution of ventilation believed to be mainly a result of concurrent
secondary to increased pulmonary secretions. It relative shunting.288 These patients may, how-
represents the major hypoxemic mechanism in ever, manifest hypoxemia during exercise, which
uncomplicated chronic obstructive pulmonary may facilitate the diagnosis.
disease. A relatively abrupt onset of rela- In any event, hypoxemia associated with dif-
tive shunting and increased hypoxemia often fusion defects responds to oxygen therapy. Thus,
accompanies hemodialysis (see discussion regarding supportive treatment, it is reasonable
under hypoventilation) or the administration of to include these patients under the category of
bronchodilators (e.g., albuterol, levalbuterol, relative shunting.
salmeterol, isoproterenol) or nitrates (e.g.,
nitroprusside, nitroglycerin).289 Effects of Altitude and Air
Increased relative shunting and hypoxemia Travel in Hypoxemia
may also be seen in patients with chronic As previously described, the partial pressure
liver disease or cirrhosis.291 The hypoxemia of of inspired oxygen will decrease as altitude
liver disease appears to be due to ascites, increases. Likewise, the partial pressure of arte-
which may alter the distribution of ventilation, rial oxygen will decrease in a corresponding
and abnormalities in pulmonary perfu- manner with increasing altitude.
sion.291,292 Overall, relative shunting is, in all Not surprisingly, the converse is also true; that
likelihood, the most common clinical hypox- is, PaO2 will tend to increase as one descends
emic mechanism and is probably evident to below sea level (760 mm Hg). Indeed, individuals

A 28-year-old woman is admitted semi-comatose due to ASSESSMENT

a drug overdose and possible aspiration. Abnormalities: List abnormal data and other noteworthy
SaO2 86% situations that may have led to this patients condition.
pH 7.22 Evaluation: Suggest additional data that would be useful in
PaCO2 50 mm Hg helping understand the situation or in making a diagnosis.
PaO2 62 mm Hg
[HCO3] 20 mEq/L INTERVENTION
FIO2 room air Importance: Prioritize concern(s) of treatment in order of
urgency and/or seriousness as you see the overall situation.
with end-stage lung disease manifested an is to enhance our understanding of the patho-
increase in PaO2, increased exercise capability, logic mechanisms that predominate in a given
and felt better subjectively after descent to patient, which, in turn, should assist us in the
a barometric pressure of 798 mm Hg at the development of a sound therapeutic plan.
Dead Sea, the lowest altitude on earth.293
Because air travel occurs at a high altitude,
CLINICAL APPEARANCE OF THE
airplane cabins are pressurized to equate to an
PATIENT WITH HYPOXEMIA/
altitude of approximately 5000 ft. In some cases,
HYPERCAPNIA
cabin pressures may equate to even higher alti-
tudes but the Federal Aviation Administration The clinical appearance of the patient may be
requires equilibration to no higher than 8000-ft the first clue with regard to the onset or wors-
altitude.695 At 8000 ft, even healthy people will ening of hypoxemia or hypercapnia. Some of
likely have PaO2s less than 60 mm Hg and the most important signs and symptoms com-
SaO2s less than 90%. Roughly, one can expect monly associated with hypoxemia or hyper-
a PaO2 decrease of approximately 4 mm Hg per capnia are shown in Box 9-3. The body will
1000-ft increase in elevation.695 typically respond to hypoxemia with increased
The decrease in PaO2 associated with air cardiac output in a dose-response manner,301
travel is of particular concern to the individual but cardiac output may sometimes decrease
with chronic lung disease, decreased ventilatory with severe hypoxemia.
reserve, and chronic hypoxemia. Therefore, Sometimes the hypoxemic patient is relatively
oxygen supplementation should be adminis- asymptomatic, and hypoxemia can only be
tered in these individuals especially if the PaO2 determined by blood gas analysis or pulse
is expected to fall below 50 mm Hg.295,296 oximetry. In the acute emergency, the patients
airway, respiratory, and circulatory status must
Summary be quickly evaluated and, if necessary, corrective
Methods for differentiation of the four mech- action should be undertaken.
anisms of hypoxemia have been discussed.
Application of P(A a)O2 in making the differ-
HYPEROXEMIA
ential diagnosis has also been presented. The
role of P(A a)O2 in the differential diagnosis Not only hypoxemia but also hyperoxemia
of hypoxemia is summarized in Table 9-1. (an excessive amount of oxygen in the blood)
Limitations of the P(A a)O2 have also been dis- is undesirable. When the PaO2 exceeds 100
cussed. The purpose of the differential diagnosis mm Hg, very little benefit is accrued in terms
Table 9-1. DIFFERENTIAL DIAGNOSIS OF HYPOXEMIA

Alveolar-Arterial PO2 Difference
Abnormality Arterial PO2 Arterial PCO2 Room Air 100% O2
Hypoventilation Decreased Increased Normal Normal

Absolute shunt Decreased Normal or decreased* Increased Increased
Relative shunt Decreased Normal, increased, or Increased Normal
decreased*
Diffusion defect Normal at rest Normal or decreased* Normal at rest Normal
Decreased during Increased during
exercise exercise
*Attributable to hyperventilation from secondary causes.

From Hinshaw, H.C., Murray, J. F.: Diseases of the Chest, 4th ed. Philadelphia, W. B. Saunders, 1980, p. 960.
Box 9-3 Signs and Symptoms of additional blood oxygen content, whereas
of Hypoxemia and the risk of complications increases.
Hypercapnia Excluding mild elevations of PaO2 (up to a
maximum of about 130 mm Hg),81 hyperox-
Hypoxemia
emia is always the result of excessive FIO2.
Muscular incoordination
Confusion
Occasionally unexpectedly high PaO2 levels
Loss of judgment may provide the first clue of erroneous labora-
Extreme restlessness, combative behavior tory data or technical error.
Tachycardia In certain cases in which the patient is believed
Mild hypertension to be hypoxic from nonpulmonary factors,
Peripheral vasoconstriction hyperoxemia may be used therapeutically. For
Cyanosis example, tissue oxygenation may improve
Bradycardia* slightly when there is severe anemia or cardio-
Bradyarrhythmias* vascular failure. Hyperoxemia is particularly
Hypotension* valuable in the treatment of carboxyhemoglo-
Hypercapnia
binemia (carbon monoxide poisoning) because
Progressive somnolence
Disorientation
it accelerates the destruction of the pathologic
Mucosal, scleral, conjunctival hyperemia carboxyhemoglobin.
Diaphoresis In general, the clinician should realize that
Tachycardia the gain in blood oxygen content with hyper-
Hypertension oxemia is only modest and that this measure is
only a stopgap to mitigate the impact of severe
*Associated with severe hypoxemia.
From Glauser F. L., Polatty R.C., and Sessler C.N.:
hypoxia in the short term. Ultimately, therapy
Worsening oxygenation in the mechanically ventilated must address the actual cause of the hypoxia.
patient. Am. Rev. Resp. Dis., 138:458465, 1988.
EXERCISES
Exercise 9-1 Hypoxemia and the Role of Cardiac Output

1. The PaO2 is a measure of oxygen-loading (adequacy/efficiency) in the lungs, whereas the

P(A a)O2 is a measure of oxygen-loading (adequacy/efficiency).
2. State the four mechanisms of hypoxemia usually observed in the hospital setting.
. .
3. (Relative shunting/absolute shunting) is commonly referred to as V/Q mismatch.
4. Venous blood (sometimes/always) mixes with oxygenated blood to form arterial blood.
5. In the patient with a normal shunt, changes in cardiac output will have
(no/minimal/substantial) effects on PaO2.
6. The PaO2 is always slightly (higher/lower) than the average PcO
2 from well-oxygenated
alveolar-capillary units.
7. A decrease in cardiac output is associated typically with a (rise/fall) in Pv O2.

8. In a patient with normal cardiac output and a substantial shunt, PaO2 decreases because
of (low Pv O2/a large percentage of venous blood entering the arteries).
9. When
. .
PaO2 decreases from 55 to 45 mm Hg in a patient with a previously measured
Qsp/QT of 30%, it (can/cannot) be presumed that shunting has increased.
10. Cardiac output affects PaO2 levels most in the individual with (normal/increased)
physiologic shunting.
Exercise 9-2 Alveolar-Arterial O2 Gradients

1. The symbol for the alveolar-arterial oxygen tension gradient is ______.

2. The mean normal P(A a)O2 in adults breathing room air is approximately ______ mm Hg,
and the upper limit of normal is ______ mm Hg.
3. The P(A a)O2 reflects primarily (ventilation-perfusion mismatch/cardiac output).
4. The PAO2 calculated in the alveolar air equation represents the (actual/mean) PAO2 in all
alveoli.
5. Write the clinical form of the alveolar air equation that should be used when FIO2 is less
than or equal to 0.60.
6. Write the formula for calculation of PIO2.
7. Normal maximum P(A a)O2 while breathing FIO2 of 1.0 in adults is ______ mm Hg.
8. Administration of 100% O2 may lead to increased true shunting through the
development of ______.
9. The P(A a)O2 (increases /decreases /does not change) with advancing age.
10. Write the clinical form of the alveolar air equation that should be used to calculate PAO2
when FIO2 is greater than 0.6.
Exercise 9-3 Oxygenation Ratios

1. The PaO2/PAO2 is (more/less) stable than the P(A a)O2 at varying FIO2 levels.
2. The lower limit of normal for PaO2/PAO2 in adults is a value of ______.
3. The PaO2/PAO2 is most stable in critically ill patients when FIO2 is in the range
of ______ to ______.
4. The PaO2/PAO2 is most stable in critically ill patients when the PaO2
is less than ______ mm Hg.
5. The normal PaO2/FIO2 is a value greater than ______.
6. The PaO2/%FIO2 is called the ______ ratio.
7. A PaO2/FIO2 of 200 is equivalent to an oxygenation ratio of ______.
8. The PaO2/FIO2 (does/does not) account for changes in PaCO2.
9. The (PaO2/PAO2 or P[A a]O2) may be useful to the clinician as a guide for selecting
appropriate oxygen therapy.
10. Changes in PaCO2 (do/do not) influence cardiac output and PaO2.
Exercise 9-4 Indices of Physiologic Shunting

1. The classic shunt equation (corrects/does not correct) for any nonpulmonary (e.g., Pv O2)
mediated effects on arterial oxygenation.
. .
2. Calculation of Qsp/QT via the (classic/estimated) shunt equation is the only
accurate measurement of physiologic shunting when cardiac output is
unstable.
3. The most notable deterrent to routine measurement of the physiologic shunt is the
requirement for (arterial oxygen content/mixed venous blood).
. .
4. The Qsp/QT, as calculated through the classic shunt equation, is the
measurement of choice whenever a /an (arterial catheter/pulmonary artery catheter)
is in place.
5. Estimated shunt equations assume a given ______ in their calculations.
6. The
.
gold
.
standard in evaluation of shunting is the measurement of the
(Qsp/QT or P[A a]O2).
7. The best index to use to differentiate simple hypoventilation from hypoventilation
with increased physiologic shunting is the ______ with the patient breathing
room air.
8. The oxygenation index used in the 100% O2 test is the ______ with FIO2 of 1.0.
9. The simplest oxygenation index to use that does not require calculation of the alveolar PO2
is the ______.
10. A PaO2/FIO2 of less than 200 almost always indicates a shunt greater
than ______%.
Exercise 9-5 Differential Diagnosis of Hypoxemia and

Effects of Altitude on Hypoxemia
1. In most clinical situations, (a single mechanism is/multiple mechanisms are) responsible for
a given decrease in PaO2.
2. The first mechanism to rule out in the presence of hypoxemia is
(absolute shunting/hypoventilation).
3. Absolute shunting is characterized by a (poor/good) response to oxygen
therapy.
4. Absolute shunting is characterized by a (white-out/darkening) of the chest
radiograph.
5. Pulmonary (embolus/edema) is probably the single most common cause of severe
absolute shunting in critical care units.
6. It is wise to suspect (diffusion defect/decreased cardiac output) when there is abrupt onset
of hypoxemia in a critically ill patient with apparently stable lungs.
7. State the two potential causes of hyperoxemia.
. .
8. The (relative/absolute) shunt phenomenon is commonly referred to as V/Q
mismatch.
9. The maximum PaO2 attainable on room air is approximately (130/150) mm Hg.
10. Name two general groups of drugs that have been associated with the onset of relative
shunting after their administration.
11. A form of pseudo-hypoventilation may occur in the patient with
(hemodialysis/nitrate therapy).
12. Hypoxemia is often seen in conjunction with chronic (renal /liver) failure.
13. PaO2 will tend to (increase/decrease) at the Dead Sea.
14. Airplane cabins tend to be pressurized equivalent to approximately
(5000/12,000) feet.
15. PaO2 will typically decrease approximately _____ mm Hg per 1000-ft. elevation.
Exercise 9-6 The P(A a)O2 in Differential Diagnosis

Determine whether the hypoxemia in the following cases (1 to 5) is due to simple
hypoventilation or hypoventilation with increased physiologic shunting. All blood gases
were drawn at FIO2 of 0.21.
Case PaO2 (mm Hg) PaCO2 (mm Hg)

1. 40 60
2. 62 50
3. 68 60
4. 40 80
5. 59 55
Assuming an abnormal P(A a)O2 on room air and given the P(Aa)O2 at FIO2 of 1.0,
determine whether the primary hypoxemic mechanism is true or relative shunting.
Case P(A a)O2 (mm Hg)
6. 360
7. 47
8. 240
9. 30
10. 90

1. Search the web by entering arterial-alveolar oxygen gradient. List two sources that provide
useful information or examples and critique them.
NBRC Challenge 9
1. A 45-year-old patient has a P(Aa)O2 of D) PaO2.
35 on room air. This value is consistent E) tidal volume.
with a diagnosis of: (RRT EXAMINATION NBRC
A) deadspace disease. MATRIX I,C,2,c)
B) pneumonia.
4. A patient with a normal physiologic shunt
C) low cardiac output.
has a sudden decrease in cardiac output.
D) high cardiac output.
One would expect PaO2 to:
E) acute renal failure.
A) increase sharply.
B) increase slightly.
MATRIX I,B,10,c)
C) increase substantially over the
2. A patient has an increased PaCO2, next few hours.
a normal P(A a)O2, and hypoxemia. D) decrease sharply.
The hypoxemia is due to: E) decrease very slightly or
A) hypoventilation.
. .
not at all.
B) V/Q mismatch. (RRT EXAMINATION NBRC
C) absolute shunting. MATRIX I,B,9,c)
D) diffusion defect.
5. If the PaO2/PAO2 decreased, P(A a)O2
E) high altitude exposure. . .
would ________ and Qsp/QT would
____________.
MATRIX I,C,2,c)
A) increase, increase
3. A patient with a pulmonary shunt fraction B) increase, decrease
of 30% has a sudden decrease in Pv O2. C) decrease, increase
This will result in a decrease in: D) decrease, decrease
A) physiologic deadspace. E) decrease, not change
B) physiologic shunting. (RRT EXAMINATION NBRC
C) potassium. MATRIX III,A,1,m,1)
Chapter
10
Treatment of Hypoxemia and Shunting
I believe the frequent forceful encouragement to cough and raise sputum supplemented by a degree of
bullying and buffeting is often more relevant than all the paraphernalia of O2 masks, intubation, ventilators,
and blood gas measurements put together.
E. J. Campbell297
Outline
Treatment, 246 Equipment Systems, 259
Acute Hypoxemia, 247 Indications, 260
Oxygen Therapy, 247 Mechanism of Effectiveness, 260
Mechanism of Effectiveness, 247 Complications, 260
Relative Shunting, 247 Decreased Cardiac Output, 260
Diffusion Defects, 248 Pulmonary Barotrauma, 262
Hypoventilation, 248 Deterioration of Ventilation-Perfusion
Absolute Shunting, 248 Ratio, 262
Oxygen Administration Devices, 248 Miscellaneous Complications, 262
High-Flow Systems, 248 Clinical Approach, 263
Low-Flow Systems, 249 AutoPositive End-Expiratory Pressure, 263
Oxygen Therapy in the Spontaneously Predisposing Factors, 263
Breathing Patient, 250 Effects, 263
Goals in Oxygen Therapy, 250 Detection, 263
Clinical Approach to Oxygen Therapy, 250 Management, 264
Excessive Oxygen Therapy, 254 Positive End-Expiratory Pressure on
High FIO2 Levels, 255 AutoPositive End-Expiratory Pressure, 264
High PaO2 Levels, 255 Body Positioning, 264
Mechanical Ventilation, 256 Factors in Gas Exchange, 264
Introduction, 256 Cardiac Output, 265
Acute Lung Injury/Acute Respiratory Distress Airway Closure, 265
Syndrome, 256 Gravity, 266
Acute Respiratory Distress Syndrome/Net, 257 Clinical Application, 266
Open Lung Approach, 257 Diffuse Lung Disease, 266
Permissive Hypercapnia, 257 Unilateral Lung Disease, 266
PaO2 Targets and Permissive Hypoxemia, 258 Summary, 266
Positive End-Expiratory Pressure, 258 Nitric Oxide, 266
Overview, 258 Long-Term Oxygen Therapy, 267
Definition and Waveforms, 258 Exercises, 267
or palliative, treatment. Supportive treatment

TREATMENT
does not aim to correct the underlying prob-
There are two primary objectives in the treat- lem; rather, its aim is to support the patient
ment of hypoxemia (i.e., decreased PaO2) and until correction of the underlying problem can
increased pulmonary shunting. Foremost is the take place.
maintenance of an adequate PaO2 to prevent Equally important, albeit less urgent, is the
hypoxia (decreased cellular oxygenation). When reversal or correction of the underlying defect.
the presence of hypoxia is likely, such as in Thus, the initial priority is to ensure an ade-
severe hypoxemia, this objective requires imme- quate PaO2 and to prevent tissue hypoxia.
diate attention. The maintenance of adequate The long-term focus is correction or control of
oxygenation is considered to be supportive, the basic pathologic insults.
246
Chapter 10 Treatment of Hypoxemia and Shunting 247
Acute Hypoxemia
Box 10-1 Options for Treatment of
The management and control of acute hypo- Hypoxemia
xemia and chronic hypoxemia are different.
Oxygen therapy
Obviously, the goals and objectives of oxygen
Mechanical ventilation
therapy in the chronic patient are less urgent PEEP/CPAP
and focused more on the long term. The man- Alveolar recruitment maneuvers
agement of acute hypoxemia certainly has a Body positioning
more emergent focus and will be discussed first. Nitric oxide
As stated previously, the prevention of tissue
hypoxia is foremost. A precise PaO2 that will
result in hypoxia in all individuals cannot be Finally, with substantial absolute capillary
identified, because various factors (e.g., hemo- shunting, therapy with positive end-expiratory
globin concentration, oxyhemoglobin affinity, pressure or continuous positive airway pressure
cardiac output) interrelate in a complex manner (PEEP/CPAP) and/or alveolar recruitment
to deliver oxygen to the tissues. Nevertheless, maneuvers will probably be necessary.
it is prudent to make a few clinical assumptions Frequently, a combination of these therapies is
based solely on the PaO2. administered to a given patient. This is simply
Tissue hypoxia is likely in the presence of because most cases of hypoxemia will have
severe hypoxemia (i.e., PaO2 < 45 mm Hg). more than one mechanism. The optimal sup-
Therefore, severe hypoxemia must be corrected portive plan for each patient must be individu-
immediately. Moderate hypoxemia (PaO2 45 to alized, based on the pulmonary pathology
59 mm Hg) may be associated with hypoxia if present and a thorough understanding of the
the cardiovascular system is unable to compen- value and role of each supportive modality.
sate. Thus, the likelihood of hypoxia in con-
junction with moderate hypoxemia depends OXYGEN THERAPY
primarily on the integrity of the cardiovascular
system. Mechanism of Effectiveness
In clinical practice, moderate hypoxemia is Relative Shunting
usually corrected, which minimizes the com- The effectiveness of oxygen therapy in relieving
pensatory stress placed on the cardiovascular hypoxemia depends primarily on the nature of
system and ensures that hypoxia does not the mechanism responsible for the hypoxemia
occur. Although mild hypoxemia (PaO2 60 to in the first place. For example, oxygen therapy
79 mm Hg) is generally not associated with is very effective in reversing the hypoxemia
hypoxia, oxygen therapy may be used to min- caused by relative shunting. As illustrated in
imize the strain on the cardiopulmonary system Figure 10-1, relative shunts are alveolar-capillary
and to make the patient more comfortable. units that have low but finite ventilation-
Notwithstanding, liberal use of oxygen ther- perfusion ratios. The gas exchange problem in
apy has recently been challenged.696 It has these units is that the quantity of oxygen avail-
been purported that oxygen administration able is insufficient (i.e., decreased partial pressure
may delay application of appropriate respira- of alveolar oxygen [PAO2]) to oxygenate com-
tory care.696 pletely the volume of blood perfusing them.
The types of palliative therapy commonly The effectiveness of oxygen therapy is related
used for acute PaO2 support are shown in to its effects on alveolar-capillary units with low
Box 10-1. The most appropriate measures for a V/Q ratios. Administration of oxygen increases
particular patient depend on the specific nature the alveolar oxygen supply and partial pressure
of the oxygen-loading problem. For example, in these units (see Fig. 10-1). It should be under-
when hypoxemia results from severe hypoven- stood that the administration of oxygen does
tilation, mechanical ventilation will likely be not change the ventilation-perfusion ratio or
necessary. On the other hand, when the hypox- improve lung function. Nevertheless, despite
emic mechanism is predominantly relative shunt- low ventilation with respect to perfusion, alveo-
ing, oxygen therapy may be all that is needed. lar oxygen delivery and PaO2 are increased.
Room air FIO2 1.0 Venturi mask
Exhalation port
V/Q V/Q
PAO2 PAO2
2
PcO 2
PcO
PaO2 PaO2
Room air
Figure 10-1. Response of relative shunting to
O2 therapy. O2 therapy increases the
. . PAO2 of the
alveolar-capillary units with low V/Q and thus cor-
rects this form of hypoxemia.
O2
()
Diffusion Defects ()
Room Room
Oxygen therapy is also effective in the presence air
(+) air (+)
of diffusion defects. The increased PAO2 associ-
ated with oxygen therapy increases the driving
Venturi mask
pressure of oxygen across the alveolar-capillary principle Oxygen
membrane and thereby speeds up equilibration.
Pulmonary diffusion is discussed in detail in Figure 10-2. Air-entrainment mask. The air-
Chapter 6. entrainment mask is a high-flow oxygen adminis-
tration system that makes use of the Venturi
Hypoventilation principle.
Oxygen therapy corrects the hypoxemia asso-
ciated with hypoventilation by replenishing
the alveolar oxygen supply. Oxygen therapy Oxygen Administration Devices
alone in the treatment of hypoventilation, how- There are two general types of oxygen adminis-
ever, is inadequate, because it does not correct tration devices: low-flow systems and high-flow
the hypercarbia and acidemia that are also systems.
present.
High-Flow Systems
Absolute Shunting High-flow systems, sometimes referred to
Oxygen therapy is generally ineffective in reliev- as fixed performance systems, are defined as
ing hypoxemia resulting from true capillary oxygen administration devices that provide gas
shunting. This finding should not be surprising, flow rates that are high enough to completely
because the increased partial pressure of inhaled satisfy the patients inspiratory demand.298
oxygen (PIO2) associated with oxygen therapy Ventilators and low fraction of inspired oxygen
never reaches blood that is perfusing consoli- (FIO2) air-entrainment masks (Fig. 10-2)
dated or collapsed alveoli. Despite its relative are examples of high-flow systems. High-flow
ineffectiveness, however, oxygen therapy is systems offer the advantage of delivering accu-
administered to all patients with hypoxemia, rate, controlled levels of FIO2. Furthermore,
because there is probably some relative shunt they often provide control of temperature and
component in all hypoxemia and oxygen ther- humidity of the inspired gas. A disadvantage of
apy is likely too add some additional volume of high-flow systems is that they are often noisy,
oxygen to the blood. bulky, and uncomfortable.
Inhalation port
Exhalation ports
From
oxygen source
Head
strap
A
Inhalation port
(one-way valve)
Exhalation ports
(one-way valve)
Reservoir
Figure 10-3. Nasal cannula. The nasal cannula is bag
a low-flow system for delivering oxygen.
Low-Flow Systems
Low-flow systems, sometimes referred to as
variable performance systems, supply oxygen
Head From
at flow rates that are less than the patients strap oxygen source
B
inspiratory flow demand. The specific level of
FIO2 delivered may be high or low. Examples Figure 10-4. Types of oxygen masks.
include the nasal cannula (Fig. 10-3), the A, A simple oxygen mask delivers an FIO2 of
simple mask (Fig. 10-4,A), and partial and approximately 0.5. B, Partial and rebreathing
non-rebreathing masks. A non-rebreathing masks tend to provide an FIO2 of approximately
0.40 to 0.70.
mask is shown in Figure 10-4,B. Advantages of
low-flow systems include simplicity and
patient tolerance. A disadvantage is that con-
trol of FIO2 levels with low-flow systems is less normal, the actual FIO2 level delivered is less
precise, because levels may vary with changes than that shown in Table 10-1. Conversely, with
in ventilatory pattern. slow, shallow ventilation, FIO2 levels may be
Low-flow systems that use reservoir bags much higher than those shown in Table 10-1.
(e.g., partial rebreathing masks and non- Non-rebreathing masks that incorporate
rebreathing masks) allow for some rebreathing one-way valves to prevent inspiration of room
of the first portion of exhaled gas and delivery air have been traditionally thought to provide
of higher rates of FIO2. With the partial a higher FIO2 (i.e., 0.6 to 0.8) than partial
rebreathing mask, the first one-third of rebreathing masks (i.e., 0.4 to 0.7).302 There is
exhaled gas is captured in the reservoir bag some evidence to suggest only very minimal FIO2
during expiration and is re-inhaled on the fol- differences between these two types of masks
lowing breath. Because this gas is rich in oxy- under normal clinical circumstances.303,698,699
gen, FIO2 levels increase. It is interesting to note that, as a variable
The approximate levels of FIO2 that are system, FIO2 delivered via a nasal cannula
delivered with a specific apparatus set on a could theoretically increase from 0.44 at a tidal
given flow rate are shown in Table 10-1. One volume of 500 mL, to 0.68 if tidal volume fell
must remember, however, that these approxima- to 250 mL.10 Therefore, it must not be assumed
tions apply only to individuals with a normal that low flow rates of oxygen from devices such
breathing pattern (e.g., tidal volume 500 mL, as nasal cannulas always deliver low FIO2
respiratory rate 12 breaths per minute). When levels. One must always keep in mind the effects
a patient breathes more rapidly or deeper than of breathing pattern on FIO2 when using
Table 10-1. APPROXIMATE FIO2 LEVELS WITH factors to consider when applying oxygen ther-
LOW-FLOW DEVICES apy in preterms and neonates.302,304
Device Flow (L/min) FIO2
Goals in Oxygen Therapy
Nasal Cannula 1 0.24 The traditional goals of oxygen therapy are to
2 0.28 maintain an adequate PaO2, to minimize car-
3 0.32 diopulmonary work, and to prevent or allevi-
4 0.36 ate hypoxia. Although PaO2 has historically
5 0.40
been the single most important parameter used
6 0.44
to gauge the appropriateness of oxygen ther-
Simple mask 6 0.40
7 0.50 apy, it should not be the sole criterion. Vital
8 0.60 organ function, general clinical appearance of
Partial rebreathing mask 610 0.60 the patient, and indices of cardiovascular stress
such as heart rate and arterial blood pres-
Adapted from Ziment, I.: Respiratory Pharmacology and sure must also be incorporated into decision
Therapeutics. Philadelphia, W.B. Saunders, 1978.
making.
For example, oxygen therapy may be deemed
beneficial if it is accompanied by an improving
low-flow oxygen administration systems. To blood pressure or heart rate even if the PaO2
further complicate matters, there is evidence failed to increase significantly. As stated by
to suggest that oxygen concentration may be Campbell, Oxygen therapy is too serious to be
higher during nasal breathing versus mouth left to electrodes alone.297 Evaluation of the
breathing when using nasal cannulas,315 need for oxygen must include an assessment of
although this finding is controversial.302 the entire cardiopulmonary system as well as
Despite the fact that high-flow systems are complete hypoxic assessment as discussed in
more accurate and that their use is advocated by Chapter 11.
some clinicians,300 low-flow systems have more It is noteworthy that analysis of arterial blood
widespread use because of their simplicity and gases is not always indicated simply because
comfort. oxygen is being briefly administered. The cost of
arterial blood analysis may outweigh its benefit,
Oxygen Therapy in the Spontaneously particularly in short-term therapy.298 The price
Breathing Patient of one blood gas analysis may exceed the cost of
Since the early nineteenth century, when 24 to 48 hours of oxygen therapy. In many cases,
Thomas Beddoes opened the Pneumatic pulse oximetry can serve as a cost-effective alter-
Institute of Bristol, oxygen therapy has played native to arterial blood gas analysis for moni-
a vital role in healthcare. Without exception, toring oxygen therapy.
oxygen therapy is the first-line clinical treat-
ment for acute hypoxemia regardless of the Clinical Approach to Oxygen Therapy
mechanism or underlying cause. Immediate The first step before the actual administra-
application of oxygen therapy is essential in tion of oxygen is to classify each patient into
the treatment of severe hypoxemia or when one of two groups: oxygen-sensitive or non
there is a high probability of tissue hypoxia. oxygen-sensitive. This is important because the
Recommendations by the American Associ- approach to therapy in each group is markedly
ation for Respiratory Care302 as well as the different. Verification of the presence or
American College of Chest Physicians and the absence of oxygen sensitivity can usually be
National Heart and Blood Institute state that accomplished through a physical examination
oxygen therapy should be used when PaO2 is and review of the patients medical record.
less than 60 mm Hg or SaO2 is less than
90%.298 A summary of key recommendations NonOxygen-Sensitive Patients
for oxygen therapy in the acute care hospital In the absence of chronic obstructive pulmonary
are shown in Box 10-2. Box 10-3 outlines key disease (COPD), chronic CO2 retention, or acute
Box 10-2 AARC Clinical Practice GuidelineOxygen Therapy in the Acute Care
Hospital: Nuts & Bolts
INDICATIONS: PaO2 <60 mm Hg
SpO2 <90%
Acute Potential for Hypoxia
Severe Trauma
M.I.
Postoperative Status
OBJECTIVE: PaO2 >60 mm Hg
SpO2 >90%
COMPLICATIONS: Acute Hypercapina in COPD
PaO2 > or = 60 mm Hg may cause
Absorption altectasis
Leukocyte/ciliary depression
Oxygen toxicity
More vulnerable with
Paraquat poisoning or Bleomycin Rx
FIO2 > or = 0.50 may cause
EQUIPMENT: Nasal Cannula
Flows up to 6 LPM
Humidification unnecessary <4 LPM
Simple Oxygen Mask
Flows 510 LPM
Always >5 LPM to prevent rebreathing
Partial Rebreathing Mask
Flows 610 LPM
Always >5 LPM to prevent rebreathing
Non-Rebreathing Mask
Flows 1015 LPM
Venti-Masks
Accurate FIO2 at recommended flows
May not meet flow needs with >35% settings
MONITORING: COPD <2 hrs
FIO2 >0.40 <8 hrs
FIO2 <0.40 <12 hrs
Check system daily
Acute M.I. <72 hrs
Reference: Oxygen therapy for adults in the acute care facility2002 revision and update. AARC Clinical Practice
Guideline. Respir. Care 47:717720, 2002.
Box 10-3 AARC Clinical Practice GuidelinesOxygen Therapy in Acute Setting

Preterms/Neonates: Nuts & Bolts
INDICATIONS: Hypoxemia
Acute Potential for Hypoxia
OBJECTIVE: PaO2 5080 mm Hg
SpO2 >88%
Capillary O2 >40 mm Hg
COMPLICATIONS: Retinopathy of Prematurity
Persistent Fetal Circulation
Irregular breathing if cool flow on
trigeminal
Potential for tracheal ignition during laser
bronchoscopy
EQUIPMENT: Nasal Cannula
Variable FIO2 performance
Humidification not necessary
Maximum flow <2 LPM
Use low increment flowmeters (0200 mL/min)
Flowrate increments <0.125 LPM
Simple Oxygen Mask
Variable FIO2 performance
Approximate FIO2 = 0.35 0.50
Primary use emergency transport
Poorly tolerated by infants
Interfere with feeding
Oxygen hoods
Fixed FIO2 performance
Set air entrainment devices to FIO2 1.0
Control FIO2 with oxygen blenders
Flow >7 LPM to wash out deadspace
Maintain temperature to neutral thermal environment
High flow may produce harmful noise exposure
Non-isotonic in nebulizers may cause airway hyperactivity
O2 Administrative Devices to Avoid
Incubators
Primary purpose to control temperature
High risk of infection if use incubator humidifier
Partial Rebreathing Masks
Non-Rebreathing Masks
Naso-pharyngeal catheters
MONITORING: Check all equipment at least daily
Reference: Selection of an Oxygen Delivery Device for Neonatal and Pediatric Patients2002 Revision and Update.
AARC Clinical Practice Guideline. Respir. Care, 47:707716, 2002.
severe asthma,700 oxygen therapy may be guards against hypoxia and is unlikely to cause
administered without concern for inducing substantial hypercapnia and acidosis.
hypoventilation. It has been said that the brain
softens before the lung hardens, in reference to FIO2 Selection
the reluctance of clinicians to administer oxy- A useful guideline for FIO2 selection in acute
gen for fear of oxygen toxicity. Oxygen therapy exacerbation of COPD is the fact that PaO2
must not be withheld in the case of a patient increases approximately 3 mm Hg for each 0.01
who may be hypoxic. increase in FIO2.300,309 Thus, if a patient with
When PaO2 falls below 55 mm Hg acutely, COPD is seen in the emergency department dur-
short-term memory is altered and euphoria ing an acute exacerbation with a PaO2 of 39
or impaired judgment may be observed.298 mm Hg on FIO2 of 0.21, the FIO2 level indicated
Therefore, in most clinical situations the PaO2 to achieve a PaO2 of 60 mm Hg is 0.28. In other
should be targeted to 60 to 80 mm Hg. words, an FIO2 increase of 0.07 should increase
PaO2 approximately 21 mm Hg (7 3 mm Hg).
Oxygen-Sensitive Patients The formula shown in Equation 10-1 may be
The approach to oxygen therapy in the patient used to determine the appropriate percentage
with COPD, acute severe asthma,700 or chronic of oxygen to be applied in acute exacerbation of
hypercapnia is completely different. In these COPD, assuming a target PaO2 of 60 mm Hg.
individuals, caution is the byword. Excessive Of course, this is just a guideline, and individual
oxygen therapy administered to these oxygen- cases may vary considerably. It must also be
sensitive patients could potentially have fatal remembered that this guideline applies only to
consequences. Nevertheless, even in these the patient with COPD in acute exacerbation.
patients, when hypoxia is suspected, oxygen It should also be noted that when in doubt it is
therapy should never be withheld simply probably wise to administer more oxygen rather
because the patient may be sensitive to oxygen. than less.
Correction of hypoxia is always the first priority.
Equation 10-1
Specifically, the first line of supportive treat- 60 mm Hg room air PaO2/3 = required % FIO2
ment in acute exacerbation of COPD is low increase
FIO2 therapy. Typically, the patient with COPD
in acute respiratory failure has blood gases Following the initial application of oxygen
approximating those shown in Example 10-1.300 therapy and after allowing 30 minutes to
obtain a steady state, therapy should be titrated
Example 10-1 to achieve an SpO2 of 90%. It is noteworthy
Typical Blood Gases during Acute that arterial oxygen saturation also increases
Respiratory Failure in Patients with Chronic on average 3% to 4% per 0.01 increase in FIO2
Obstructive Pulmonary Disease in acute COPD.300 This substantial increase
pH 7.237.39 shows the tremendous value of oxygen therapy
PaCO2 6080 mm Hg in acute COPD. Because these patients are
PaO2 40 mm Hg often on the steep portion of the oxyhemoglo-
bin curve, the amount of oxygen actually pres-
Despite PaCO2 levels in excess of 60 to ent in the blood rises sharply with only a small
65 mm Hg, many patients with COPD can be increase in PaO2.
treated without mechanical ventilation.306
In general, mechanical ventilation should not Progressive Hypercapnia
be initiated unless pH falls below 7.20297,306 and One must always keep in mind that increases
after all else fails.297,307 The decision to insti- in PaO2 in patients with COPD may also
tute mechanical ventilation in COPD is always be accompanied by increases in PaCO2.
difficult and requires consideration of a host of Although a slight increase in PaCO2 is incon-
variables. sequential, a large increase with a concomitant
A reasonable target PaO2 in acute exacerba- acidosis must be avoided. There is increasing
tion of COPD is 60 mm Hg.308 This level evidence, however, that it is not the hypercapnia
per se that results in deleterious effects316 but PaCO2 levels in some patients with COPD seem
rather the progressive acidemia, muscle weak- to decrease during acute exacerbation of the dis-
ness, and exhaustion, which must be carefully ease (see Chapter 14).10 Thus, when blood gases
monitored. are first sampled in the hospital, PaCO2 levels
The patient is more likely to have an increase could appear lower than their normal baseline.
in PaCO2 in response to O2 administration when In other words, chronic CO2 retention may
initial PaCO2 is greater than 70 mm Hg,309,700 go unrecognized during acute exacerbation
or when the initial PaO2 is very low.310 Also, because PaCO2 is within the normal range.
the clinician should be aware that worsening In any event, it appears prudent to approach
hypercarbia may be observed several hours oxygen therapy cautiously in all patients with
after the onset of oxygen therapy.306 COPD, regardless of PaCO2 levels.
The increase in PaCO2 also tends to be pro- Recently, it has been shown that patients with
portional to the level of FIO2 delivered. In one acute, severe asthma often develop acute hyper-
study, PaCO2 increased on average 5 mm Hg capnia when 100% oxygen is administered.700
with administration of FIO2 0.24 and 8 mm Hg In addition, they also respond with a decreased
on FIO2 0.28.307 In another study, modest FIO2 peak expiratory flow rate. This is in marked con-
levels of 0.35 to 0.40 substantially aggravated trast to the response when 0.28 FIO2 is adminis-
hypercapnia.311 When excessive oxygen ther- tered. These patients typically responded with
apy appears to be responsible for progressive a decreased PaCO2.700
hypercapnia, FIO2 should be reduced gradually, The device selected for the administration
because abrupt cessation of oxygen may result of oxygen is somewhat a matter of personal
in further deterioration of the patient. preference. High-flow systems such as air-
The buildup of CO2 to high levels in the entrainment masks with low FIO2 levels have
blood gives rise to the syndrome known as the advantage of accurate FIO2 rates regardless
CO2 narcosis. This syndrome, which may be a of breathing pattern and are advocated by
misnomer,316 is characterized by increasing some as the safest, most effective method
PaCO2 levels, acidemia, stupor, and coma.310 to deliver oxygen.308 However, the patients
Additional clinical signs suggestive of mild-to- comfort and compliance with these devices are
moderate hypercarbia include decreased cerebral not good. In addition, these masks are often
function, headache, drowsiness, lethargy, and unsightly, awkward, and noisy.
asterixis.312 See Box 9-3 for a more complete list Low-flow systems (e.g., nasal cannula) are
of the signs and symptoms associated with more often used. They are less obtrusive, quieter,
hypercapnia, although it is difficult to differen- and better tolerated. For more precise FIO2 con-
tiate some of these symptoms from acidemia. trol, however, flowmeters marked in flow incre-
Sometimes, severely hypercapnic patients ments less than 1 L/minute may be required.314
(i.e., PaCO2 150 mm Hg) may be relatively Furthermore, one must always remember that a
asymptomatic. Nevertheless, the clinician must nasal cannula is a low-flow system and, as such,
be continuously on guard for any signs or symp- may allow considerable FIO2 variation with
toms of hypercapnia and progressive acidosis changes in ventilatory pattern.
while administering oxygen to the patient with
COPD. Excessive Oxygen Therapy
Some authors suggest that high doses of Few clinicians feel the fear of oxygen toxicity is
oxygen therapy may be safely administered greater than the concern for tissue hypoxia.
to patients with COPD if hypercapnia is not D.R. Hess, R.B. Kacmarek305
present initially.298,313 In my experience, I have
observed increasing PaCO2 levels after oxygen Excessive oxygen therapy may produce conse-
therapy in COPD despite the absence of preex- quences similar to the symptoms of hypoxia
isting hypercarbia. and is also dangerous.317 The net potential for
The phenomenon of normal PaCO2 levels in harm depends on the net interaction of three
a patient who actually has chronic hypercap- critical variables: FIO2, PaO2, and duration of
nia could be explained by the observation that exposure.
High FIO2 Levels at FIO2 greater than or equal to 0.60 should

High FIO2 levels (i.e., 0.60) for extended peri- be avoided whenever possible for greater than
ods ultimately cause some cytotoxic and func- 48 hours.305
tional damage. In animals, FIO2 of 1.0 has Nonetheless, whenever oxygen status or car-
caused death within 48 to 72 hours due to diopulmonary integrity are in doubt, oxygen
non-cardiogenic pulmonary edema.305 should be administered.305 This is especially
In humans, the precise onset of oxygen toxic- true during suctioning, bronchoscopy, trans-
ity is somewhat controversial.305 Signs of oxygen port, periods of instability, and during initia-
toxicity in the form of substernal distress have tion of mechanical ventilation. Many believe it
been observed within 6 hours after the onset of is also true during mechanical ventilation in
1.0 FIO2 administration.318 In other cases, FIO2 ARDS where the fear of high alveolar pressures
resulted in inflammatory airway changes and and volutrauma often supersede the fear of
bronchitis within 24 hours.305 In contrast, no oxygen toxicity.305
striking effects while breathing 1.0 FIO2 were
observed in postoperative open heart patients High PaO2 Levels
after 24 to 48 hours of therapy.318 Nonetheless, High PaO2 levels similarly may cause harm to
it seems prudent to minimize the exposure time a patient and must be avoided. Notable is the
to high levels of FIO2 in all patients. phenomenon of retrolental fibroplasia, more
High FIO2s also result in the development recently referred to as diffuse retinopathy of
of oxygen free radicals (superoxide, hydrogen prematurity. In this disorder, high PaO2 levels
peroxide, hydroxyl ion) that result in structural in the retinal arteries cause vasoconstriction,
lung changes.305 Various drugs and chemicals which may, in turn, result in permanent blind-
may enhance this effect. These include the ness. This disorder is primarily a disease of pre-
chemotherapeutic agent Bleomycin, the anti- mature infants with poorly developed retinal
arrhythmic agent Amiodarone,319 and poisons vessels.
such as paraquat. Indeed, it has been suggested As described previously, in some COPD and
that clinicians target a PaO2 of only 50 mm Hg asthma patients, high PaO2 levels may lead to
and avoid an FIO2 over 0.4 during the admin- the development of progressive hypoventilation
istration of Bleomycin.305 In contrast, in the and hypercarbia. Occasionally, a dramatic
severely damaged lung, antioxidants are pres- increase in PaO2 levels in these oxygen-sensitive
ent that help minimize lung damage despite individuals may result in apnea.81 Again, despite
high FIO2.305 these caveats, oxygen therapy should never be
High FIO2 levels (particularly FIO2 = 1.0) withheld from any patient when the presence of
also predispose individuals to the development hypoxia is likely.81,305
of absorption atelectasis. Gas trapped in an alve- Finally, a PaO2 greater than 150 mm Hg may
olus is absorbed more quickly when the oxygen cause coronary vasoconstriction and lead to
concentration is high. This is observed even in arrhythmias in susceptible individuals with coro-
healthy individuals, who may develop up to nary disease.320,321 In summary, oxygen should
a 10% shunt after breathing an FIO2 of 1.0. always be administered in the lowest dose pos-
Consequently, high FIO2 levels are particularly sible. However, hypoxia, when suspected, must
worrisome in patients with shunt-producing always be treated.
disease, because they can ill afford a further Nothwithstanding the clear focus of this text
reduction in gas exchange. on insuring sufficient oxygen is administered, a
Arguments have been presented that hyper- controversial opposing view has been presented
oxemia, even for short periods, is not innocuous in a recent article.696 John B. Downs, a well-
and should be avoided. Indeed, hyperoxemia respected critical care physician, purports that
has been associated with worsening oxygen our excessive use of oxygen may, indeed, delay
consumption,348 muscle fatigue, and ventilation- appropriate respiratory care. This provocative
perfusion mismatch. Overall, although the clin- article is worth reading and challenges many
ical evidence is conflicting, as a general rule of our long-held notions regarding oxygen
most clinicians believe oxygen administration therapy.696

A patient with a history of 50-pack years of smoking ASSESSMENT

presents with a barrel chest, flattened diaphragms Abnormalities: List abnormal data and other noteworthy
on chest radiography, and pursed lip breathing to the information. Classify ABG.
emergency department. He has had a recent upper Explanation: List possible diseases, pathology, or other
respiratory infection and is now congested with situations that may have led to this patients condition.
shortness of breath. Evaluation: Suggest additional data that would be useful in
helping understand the situation or in making a diagnosis.
SaO2 75% INTERVENTION
pH 7.32 Importance: Prioritize concern(s) of treatment in order of
PaCO2 65 mm Hg urgency and/or seriousness as you see the overall situation.
PaO2 42 mm Hg Objective: Specifically state the measurable or observable
[HCO3] 31 mEq/L outcomes you would like treatment to accomplish.
FIO2 room air Action: Describe your specific plan of action.
MECHANICAL VENTILATION 3.0, the patient is classified as having ALI.322

Based on chest radiography, ALI/ARDS was
Introduction previously believed to be a diffuse lung disease
Mechanical ventilation is generally not a first- that impacted the entire lung in a uniform man-
line treatment for oxygenation disturbances. ner. However, it has become increasingly clear
Specifically, mechanical ventilation is reserved with the use of computed tomography that this
for the treatment of ventilatory problems, evi- syndrome affects the microscopic lung in a het-
denced by an increased PaCO2 and a low pH. erogeneous manner. Some alveolar-capillary
Sometimes, however, oxygenation disturbances units are edematous and collapsed whereas
may be so severe that cardiopulmonary col- others are normal. The overall lung is function-
lapse seems eminent or the work of breathing is ally small.
exhaustive. In these situations, mechanical ven- The heterogeneous nature of this disorder
tilation may be useful to help the patient to rest leads to the overfilling of normal alveoli during
and to allow for more effective breathing. traditional mechanical ventilation and volu-
trauma. Volutrauma is an iatrogenic problem
Acute Lung Injury/Acute Respiratory that refers to lung damage similar in nature to
Distress Syndrome
Probably the most common clinical use of
mechanical ventilation is in the treatment of Box 10-4 ARDS Definition
acute lung injury (ALI) and the acute respira- Criteria
tory distress syndrome (ARDS). ALI/ARDS may
1. Acute onset
be caused by a direct lung insult (e.g., pneumo- 2. Bilateral infiltrates
nia, aspiration) or an indirect lung insult (e.g., 3. No evidence of congestive heart failure
transfusion, diffuse inflammatory response). (pulmonary wedge pressure <18 mm Hg)
Regardless of the cause, the ultimate result is 4. Oxygenation ratio <2.0
altered capillary permeability and pulmonary
edema. From Brower, R.G., Matthay, M.A., Morris, A., et al:
Ventilation with lower tidal volumes as compared with
The American-European Consensus Confer- traditional tidal volumes for acute lung injury and the
ence in 1994 defined ARDS using the criteria acute respiratory distress syndrome. N. Eng. J. Med. 342:
in Box 10-4. If the oxygenation ratio is 2.0 to 13011308, 2000.
ARDS but caused by excessive pressure and/or Alveolar recruitment maneuvers and higher
stress in lung units. The injury is sometimes levels of PEEP are used to maximize alveolar
referred to as volume-induced lung injury recruitment.
(VILI) and is likely to occur when plateau pres- Presently, the ARDS/Net approach seems to
sures measured in the lungs exceed 30 cm be gaining increasing popularity. However, the
H2O.305 VILI leads to inflammation, repair, modes and methods of mechanical ventilation
and remodeling of the lung. continue to evolve, and the specific characteris-
It has also been known for years that many tics of future approaches are certain to change.
patients with ARDS do not die because of pul- The myriad details of mechanical ventilation
monary dysfunction but rather due to the and application of PEEP and positive pressure
onset of multiple organ dysfunction syndrome is beyond the scope of this text.
(MODS). This syndrome is characterized by tis-
sue injury secondary to inflammatory mediators/ Permissive Hypercapnia
cells, bacteremia, and/or tissue hypoxia. Many Application of the open lung approach or the
clinicians currently believe that VILI may facil- ARDS/Net technique for mechanical ventilation
itate the release of inflammatory mediators and often results in the development or worsening of
contribute to MODS. The ARDS/Net study hypercapnia. It is a common belief, however,
discussed in the following section supports this that hypercapnia may be acceptable as long as
hypothesis. pH can be maintained within an acceptable
range. Arterial pH is typically maintained above
Acute Respiratory Distress 7.20 through the use of increased respiratory
Syndrome/Net rates or bicarbonate infusion if necessary.305
Traditional application of mechanical ventila- Notwithstanding, even small increases in
tion in ARDS involved the use of tidal volumes PaCO2 will increase cerebral perfusion; there-
of 10 to 15 mL/kg of body weight. In the ARDS/ fore, permissive hypercapnia should be avoided
Net study, it was hypothesized that these high when intracranial pressure is increased.
volumes could induce VILI, exacerbate MODS, Hypercapnia also stimulates ventilation; how-
and contribute to mortality. Therefore, patients ever, patients are often heavily sedated or
in the experimental group were mechanically paralyzed for controlled ventilation. Also,
ventilated with a tidal volume target of 6 mL/kg hypercapnia usually results in an increased car-
of ideal body weight with plateau pressures of diac output and pulmonary hypertension,
30 cm H20 or less.323 The intent was to reduce although results may be variable.
injurious lung stretch and the release of inflam- Most often, the primary limiting factor in per-
matory mediators. PEEP was applied in the missive hypercapnia is pH. Gradual pH change
range of 10 to 20 cm H2O to maintain alveolar is better tolerated than abrupt pH change and
recruitment. younger patients seem to tolerate pH change
The results were striking and, in fact, better than the elderly. Administration of buffers
the ARDS/Net study was prematurely termi- (e.g., sodium bicarbonate) to protect pH is con-
nated based on the clear superiority of the troversial. Sodium bicarbonate is also known
low tidal volume technique.323 Application of to cause intracellular acidosis, which may have
the ARDS/Net technique resulted in significant adverse effects.
decreased mortality (22%) and fewer patient The open lung approach and the ARDS/Net
days on the ventilator.323 These results occurred technique represent a radical departure in
despite higher FIO2s and PEEP levels used in priorities and focus as compared to traditional
the low tidal volume group. mechanical ventilation. Whereas, maintenance
of a normal PaCO2 was traditionally consid-
Open Lung Approach ered prerequisite to alveolar pressure, it is con-
The open lung approach to mechanical venti- sidered secondary to alveolar pressure with the
lation is an alternative to the ARDS/Net newer ventilation strategies. Thus, hypercapnia,
approach. In the open lung approach, the although undesirable, represents a trade-off
focus is on maintaining a low plateau pressure for minimizing alveolar pressure and lung stress
while using pressure controlled ventilation. exposure.
PaO2 Targets and Permissive POSITIVE END-EXPIRATORY

Hypoxemia PRESSURE
In the healthy adult lung, PaO2 will exceed 80
mm Hg. Mild hypoxemia (>60 mm Hg) is gen- Overview
erally considered acceptable in mild-to-moder- Absolute shunting responds poorly to all of the
ate lung disease, particularly when there is palliative measures discussed previously. In par-
concern for VILI or oxygen toxicity. In severe ticular, oxygen therapy is ineffective because the
lung disease, or during Bleomycin therapy, inspired oxygen cannot enter collapsed or fluid-
PaO2 may be consciously allowed to remain as filled alveoli. Furthermore, increasing the
low as 50 mm Hg provided no other serious inspired oxygen concentration in itself tends to
side effects are manifested.305 In permissive accentuate the capillary shunting process.324
hypercapnia, PaCO2 may be allowed to increase Because the rudimentary problem in absolute
to 80, perhaps 100, mm Hg in the presence of capillary shunting is loss of functional alveoli,
severe lung disease provided acidosis is not effective treatment should aim towards restoring
severe.305 Likewise, mild acidosis may be toler- these alveoli to a functional state. The efficacy
ated during ALI/ARDS, provided pH does not of PEEP lies in its ability to prevent or reverse
fall below 7.20.305 alveolar collapse, increase lung volume, and thus
The idea of permissive hypoxemia (i.e., con- reduce the capillary shunt.
sciously allowing PaO2 to remain at levels below PEEP was first used in clinical medicine in
60 mm Hg) is gaining increased interest with approximately 1938 by Alvan Barach.325 Later,
some very prominent physicians.696,701 As in a classic paper published in 1967, PEEP was
Dr. Downs argues in a compelling manner, described by Ashbaugh and Petty as an effec-
there is little evidence to support the idea of tive therapeutic modality for the treatment of
maintaining a normal PaO2. Indeed, it is his ARDS.294 Previously, PEEP was often charac-
belief that by doing so, we are masking the real terized as the mainstay or cornerstone in the
pulmonary problems and delaying appropriate treatment of ARDS.335 Although ARDS/Net
treatment. has changed our focus somewhat, PEEP remains
He argues systematically that oxygen a key component in the treatment of arterial
consumption remains normal down to PaO2 hypoxemia.
<30 mm Hg. He asserts that saturation is A technique with a similar goal to PEEP is
surely more important than PaO2, and it is known as the alveolar recruitment maneuver
likely that the body could sustain arterial (ARM). The intent here is to apply an increased
saturations below 50%. If one considers inflation pressure to the lung (typically 30 to
the ability of the body to withstand falls in 45 cm H2O) and hold it to recruit collapsed alve-
cardiac output or [Hb] of a similar magnitude, oli. The maneuver typically lasts for approxi-
why should the body be in such peril with mately 1 minute, is done periodically, and has
only a 10% to 15% decline in SpO2 down been shown to improve gas exchange. One must
below 90%? be cautious to avoid significant decreases in
The editor of Respiratory Care, David cardiac output during the maneuver.
Pierson, MD, asks a similar question regard- Despite improvement during and immedi-
ing treatment in ARDS.701 Does it really make ately after the maneuver, gas exchange has
a difference if the PaO2 is 50 mm Hg or 100 been shown to deteriorate again within 15
mm Hg? Perhaps not, and the patient may be minutes.347 The use of PEEP in conjunction
paying a great physiological price for us to with ARM helps to avoid de-recruitment or
keep it near 100 mm Hg. These questions re-collapse of alveoli. This represents one of
are far from resolved and, for now, it is pru- the prime goals of PEEP in the management
dent to follow traditional guidelines. Never- of ALI/ARDS.
theless, just as permissive hypercapnia would
have been unheard of 15 years ago, permis- Definition and Waveforms
sive hypoxemia may be the norm in years to PEEP is defined as a pressure above atmospheric
come. at the airway opening at the end of expiration.326
Most often, PEEP is applied in conjunction with

mechanical ventilation. Continuous positive air- Controlled mechanical ventilation (CMV)
way pressure (CPAP) is a form of PEEP that is
applied to spontaneously breathing patients.
CPAP may be defined as a system for applying
PEEP to spontaneously breathing patients, in
which the applied pressure remains positive
Pressure
throughout the breathing cycle.327 Although it is
a spontaneously breathing modality, many ven-
tilators are also capable of providing CPAP.
When the pressure in a PEEP system is
allowed to fall below ambient pressure during
spontaneous inspiration, the breathing system/ 0
A Time
mode does not meet the criteria for CPAP.
A system that would allow this to occur is some-
times referred to simply as PEEP with sponta-
Continuous positive airway pressure (CPAP)
neous breathing or expiratory positive airway
pressure (EPAP). It has been shown that EPAP is
associated with a greater work of breathing than
Pressure
is CPAP; therefore, PEEP is best applied in the

form of CPAP in the spontaneously breathing
individual.
Figure 10-5 shows pressure tracings during 0
controlled mechanical ventilation (CMV), B Time
CPAP, and PEEP with CMV. An EPAP tracing
would be similar to that in Figure 10-5,B, with
one important difference: during inspiration, Controlled mechanical ventilation (CMV) with
positive end-expiratory pressure (PEEP)
the tracing would fall below the zero baseline.
Equipment Systems
Figure 10-6 shows one of the earliest systems
Pressure
used to administer CPAP. In this system, the

depth of the underwater seal determines the
CPAP level administered to the patient.
When selecting equipment to be used for the
administration of PEEP or CPAP, there are sev- 0
eral important considerations. First, the PEEP/ C Time
expiratory valve assembly that is used should Figure 10-5. Various modes of ventilation.
provide only minimal resistance to expiratory Pressure tracings for (A) controlled mechanical
flow. Valves associated with increased flow ventilation; B, continuous positive airway
resistance increase the mean airway pressure and pressure; and C, controlled mechanical
the risk of complications. Another important ventilation with positive end-expiratory
consideration related to CPAP equipment is pressure.
the use of a system that minimizes the work of
breathing. It is becoming increasingly clear that
deleterious consequences are associated with force against expiratory flow and abruptly
increased work of breathing. close when flow stops. Flow resistors, on the
Basically two types of valves have been other hand, do not in themselves maintain pos-
used to maintain PEEP within breathing sys- itive pressure; rather, they limit expiratory flow
tems: threshold resistors and flow resistors. to the point that the pressure does not have suf-
Threshold resistors apply a relatively constant ficient time to fall to zero. Threshold resistors
Figure 10-6. Continuous positive O2

source
airway pressure system. Schematic
diagram of system to provide con- Air
tinuous positive airway pressure in source
a spontaneously breathing person. O2 blender
Airway and alveolar pressures PEEP
throughout the respiratory cycle are
set by submerging the expiratory Patient
tube in a water reservoir to achieve
Humidifier Water
the desired amount of PEEP.
reservoir
generally are better than flow resistors for the decreased venous return associated with PEEP
application of PEEP because they have a lower (described in the section on complications)
potential for cardiovascular side effects. may actually enhance cardiac performance.
It is certainly reasonable to attempt a trial of
Indications PEEP therapy in most patients with a substantial
The primary indication for PEEP therapy is the true capillary shunt. Of course, the potential
presence of substantial absolute shunting. The complications of PEEP must also be considered
classic indication for PEEP is a diagnosis of in this decision. In the patient with absolute
idiopathic respiratory distress syndrome shunting who does not require ventilatory sup-
(IRDS) in newborns or ALI/ARDS in adults. port, the CPAP mode should be used.
These diseases are associated with progressive,
often severe, true capillary shunting that is Mechanism of Effectiveness
potentially fatal if left untreated. The use of The effectiveness of PEEP is related to its ability
10 to 20 cm H2O of PEEP is used in ARDS to to increase the FRC, recruit alveoli, and improve
prevent alveolar collapse. the ventilation-perfusion match. Figure 10-7
PEEP has been used in many conditions that shows how PEEP applied via an endotracheal
are not related to increased capillary shunting tube helps to reverse low ventilation-perfusion
(e.g., obstructive sleep apnea, neonatal apnea, ratios and capillary shunting.
chest trauma, control of mediastinal bleeding PEEP may also have a desirable effect
after open heart surgery).332 Most of these other through the redistribution of lung water. Several
applications are controversial; however, CPAP studies suggest that PEEP shifts water from
therapy is widely accepted in the treatment of alveoli to the perivascular space, where it does
obstructive sleep apnea. not impair gas exchange.333,334
It is also known that the insertion of an arti-
ficial airway decreases the functional residual Complications
capacity (FRC). Therefore, in intubated infants The two most widely recognized complications
and adults, 3 to 5 cm H2O of PEEP or CPAP is of PEEP therapy are decreased cardiac output
typically applied. and pulmonary barotrauma.
PEEP has also been applied to various other
capillary shunt disorders besides ARDS. CPAP Decreased Cardiac Output
has been applied intermittently and continuously Decreased cardiac output is probably the most
to reverse or minimize the incidence of post- commonly cited complication of PEEP or CPAP
operative atelectasis.331 The major drawback therapy.335 This side effect is dose-related, and
to this application appears to be its questionable hypovolemic patients are especially susceptible
cost-effectiveness.331 to this problem.336
PEEP is often effective in the treatment of Two mechanisms that have been postulated
cardiogenic pulmonary edema.331 PEEP would to explain the PEEP-induced decrease in cardiac
seem to help these patients in two ways: (1) it output are shown in Figure 10-8. Decreased
tends to reverse the capillary shunt, and (2) the venous return (see Fig. 10-8,A) secondary to
Bilateral disease
ATEL
Two lung
. . PEEP
V/Q
Figure 10-7. Mechanism of PEEP effectiveness. Application of PEEP to both lungs through a single-lumen
tube in patients with bilateral lung disease usually results in a reversal
. . of low ventilation-to-perfusion
relationships and atelectasis in both lungs. (ATEL, atelectasis; V/Q low ventilation-perfusion ratio.)
compression of the great veins that results in a through which some of these factors may
decreased venous return gradient is probably decrease the cardiac output are explored.
the most important mechanism.335 In addition,
increased pulmonary vascular resistance may Compliance
cause right ventricular dysfunction due to disten- Presumably, when lung compliance is low, such
tion and decreased contractility (see Fig. 10-8,B). as in ARDS, pressure in the lungs is poorly
Surprisingly, many patients who receive transmitted to the intrapleural space, and there-
PEEP therapy do not have a decrease in car- fore, cardiac effects are diminished. On the
diac output. The cardiac effects resulting from other hand, in an individual with healthy lungs,
a given dose of PEEP depend on the interaction alveolar pressure is more readily transmitted to
of many different variables, including lung the pleural space, and cardiac output is more
compliance, functional residual capacity (FRC), likely to decrease. Thus, cardiac output is more
mean airway pressure, blood volume, and likely to decrease with application of PEEP
pulmonary wedge pressure. The mechanisms in the patient with healthy lungs. One study
Decreased venous return

Increased pulmonary vascular resistance
and right ventricular dysfunction
+ + PEEP
+ +
PEEP
+ + PVR
+ +
cr
In
ea re
se s su
d p l e ral pre
+ u +
Distended
RV
Contractility
D ec t
re ased di e n
venous return gra
A B
Figure 10-8. Mechanisms of PEEP-induced decreased cardiac output. Two of the mechanisms responsible
for the decrease in cardiac output associated with PEEP are shown. A, Intrathoracic pressure increases as
the lung expands. The positive intrathoracic pressure compresses the great veins and decreases the venous
return gradient. B, PEEP also compresses the pulmonary vasculature which, in turn, distends the right
ventricle and decreases contractility.
confirmed that pressure transmission is related PEEP. It seems probable that the higher the level
to compliance; however, it failed to support the of PEEP, the greater is the tendency for baro-
presumption that this in turn leads to hemody- trauma. Also, as stated previously, barotrauma
namic consequences.337 is more likely when FRC is above normal.
Functional Residual Capacity Deterioration of Ventilation-Perfusion Ratio

Theoretically, the administration of PEEP does Occasionally, the administration of PEEP leads
not adversely affect cardiac output unless nor- to a paradoxical fall in PaO2. This phenomenon
mal FRC is exceeded. Therefore, administration is most likely to occur when PEEP is applied to
of PEEP to individuals with below-normal FRC an individual with unilateral lung disease.305
should not substantially decrease cardiac output. Presumably, PEEP preferentially inhibits perfu-
Conversely, if PEEP is administered in doses suf- sion to the healthy lung because of the normal
ficient to increase the FRC above normal limits, compliance. Thus, as shown in Figure 10-9,
depression of cardiac output is likely. Because more blood is routed through the diseased lung
lung compliance is best at normal FRC, some with subsequent worsening hypoxemia.
clinicians had used compliance measurements Sophisticated application of PEEP to only the
as an indicator of the ideal PEEP level. If pro- diseased lung has been carried out with apparent
gressive PEEP levels increase compliance, the success.339,340 To apply differential lung PEEP,
assumption is that FRC is moving closer to nor- a double-lumen tube must be placed in the lungs.
mal. On the other hand, if progressive PEEP lev- Different levels of PEEP can then be applied to
els are associated with a decrease in compliance, each lung as needed. Figure 10-10 shows
the assumption is that the lungs or alveoli are schematically the application of differential lung
overdistended. However, because it has been PEEP through a double-lumen catheter.
demonstrated that ARDS is not homogeneous
throughout the lung, this approach to determin- Miscellaneous Complications
ing ideal PEEP levels may result in VILI. The administration of PEEP may lead to neu-
Furthermore, it has more recently been shown rologic and renal complications. Like any clin-
that if PEEP is applied in ARDS to prevent alve- ical application of positive pressure, PEEP may
olar collapse, compliance may actually decrease
despite an improvement in gas exchange.305
Similarly, because patients with COPD already
have an increased FRC, PEEP should be used in Diseased lung Normal lung
this group with extreme caution.
Mean Airway Pressure

Finally, the tendency of PEEP to decrease the
cardiac output is directly proportional to the PEEP
mean airway pressure rather than to the peak
airway pressure. For this reason, flow resistors
have a greater tendency than threshold resistors
to decrease cardiac output because flow resis-
tors maintain a higher mean airway pressure. PVR
When high levels of PEEP must be administered, Blood flow Compressed
every effort should be made to keep mean air- diversion to intra-alveolar
way pressure at the lowest possible level. diseased lung vessels
. .
Figure 10-9. Worsening V/Q with PEEP applica-
Pulmonary Barotrauma
tion. PEEP preferentially inhibits perfusion to the
Pulmonary barotrauma (e.g., pneumothorax, normal lung because of the normal compliance,
subcutaneous emphysema, pneumomediasti- which leads to increased perfusion of the diseased
num) may occur with the administration of lung and decreased PaO2.
AutoPositive End-Expiratory Pressure

The phenomenon termed auto-PEEP has been
found to be very prevalent in mechanically ven-
tilated patients (i.e., 39%).343,344 In auto-PEEP
positive pressure remains in the alveoli at the
end of expiration, although it is not reflected
on the pressure manometer of the ventilator.
15 5
This covert form of PEEP has also been referred
to as inadvertent PEEP, occult PEEP, or pul-
monary gas trapping.
Predisposing Factors
Figure 10-10. Differential lung PEEP. By using a It appears that the prolonged expiratory time
double-lumen endotube, different levels of PEEP required by patients with COPD predisposes
are applied independently to each lung in propor- them to the auto-PEEP effect. Nevertheless,
tion to their needs. this phenomenon is not exclusive to patients
with COPD. It has also been observed in
newborns and patients who are on controlled
increase intracranial pressure and reduce cere- ventilation with high minute volumes.344,345
bral perfusion pressure.341 This change may be
a serious complication in the patient with Effects
neurologic disease. Auto-PEEP may have deleterious conse-
PEEP may impair renal function due to quences. It may substantially diminish venous
decreased perfusion or by increasing antidiuretic return and decrease cardiac output and blood
hormone. Also, an increase in the amount of pressure. It can hamper monitoring because it
fluid present in the lungs with PEEP application distorts static compliance measured at the
has also been reported.342 As described previ- bedside. Also, in the presence of auto-PEEP,
ously, however, PEEP probably improves the spontaneous inspiration requires greater effort
distribution of lung water from the alveoli to the to decrease alveolar pressure below atmos-
perivascular space, which actually enhances gas pheric pressure, which is associated with a
exchange.333,334 substantial increase in the work of breathing.
Finally, it may increase peak airway pressure
Clinical Approach and lead to barotrauma.
There is no question that PEEP is beneficial in On the other hand, because auto-PEEP is
the patient with profound ARDS. PEEP should indeed true PEEP, it may be responsible for
be applied at the minimum level necessary for improved PaO2 levels. In this case, a reduction
adequate gas exchange and to prevent alveolar in auto-PEEP may improve the cardiac output
collapse. This is typically approximately 10 to but, at the same time, may lead to worsening
20 cm H2O. PEEP should always be adjusted hypoxemia.
in small increments and decrements.
During withdrawal, FIO2 should first be Detection
reduced to 0.50, then PEEP should be reduced Because normal passive monitoring of airway
very gradually to 5 cm H2O. If SpO2 decreases pressure does not reflect auto-PEEP, the clini-
when PEEP is decreased, the previous level of cian must actively detect this phenomenon. The
PEEP should be re-established. After PEEP is following procedure may be used to evaluate
reduced to 5 cm H2O, FIO2 can be reduced a patient for auto-PEEP. At the end of exhala-
to 0.40. If the patient is stable at 5 cm H2O tion (immediately before the next ventilator
and FIO2 0.40, mechanical ventilation can be inspiratory phase), the expiratory valve is
discontinued. manually occluded. The pressure manometer
A There are several ways that auto-PEEP can be

decreased when it is considered to be hazardous.
Increasing the inspiratory flow rate in patients
15 2 0
with COPD has been shown to improve oxy-
genation and decrease FRC.328,329 Aggressive
bronchodilation helps to control airway resist-
ance. Normalization of the pH in acidemia helps
B to minimize minute volume requirements (i.e.,
respiratory compensation for metabolic acidosis
increases minute ventilation). Use of lower
15 15 15 compressible volume ventilator circuits may
also decrease the auto-PEEP effect.330
Positive End-Expiratory Pressure on AutoPositive

Figure 10-11. Detection of auto-PEEP. The End-Expiratory Pressure
auto-PEEP effect. During mechanical ventilation Interestingly, the application of very low
of a patient with airflow obstruction, expiratory levels of applied external PEEP superimposed
flow is too slow to allow complete deflation of the on auto-PEEP has been advocated to decrease
lung to its normal relaxed state before the ventilator the work of breathing.343,346 With only auto-
delivers another breath. Slow flow continues until
PEEP, the patient must exert a tremendous
interrupted by the next inflation. Alveolar pressure
remains positive at end-exhalation but is not
amount of effort to establish the negative pres-
measured by the ventilator manometer located sure necessary for inspiration. This situation is
downstream of the site of flow limitation (A). similar to inspiration with an EPAP system.
Alveolar pressure at end-exhalation can be quanti- The use of PEEP on auto-PEEP tends to
fied by stopping flow transiently at the end of the minimize the effort required, much as CPAP
set exhalation period (B). improves the work of breathing compared
with EPAP. Nevertheless, this form of therapy
(i.e., PEEP on auto-PEEP) should be applied
is then observed until pressure equilibrium is cautiously. In particular, the untoward effects
established. The pressure equilibrium point of excessive PEEP must be avoided. The peak
reflects the level of auto-PEEP. Respiratory inspiratory pressure may serve as a crude index
movements by the patient during this meas- of appropriate PEEP levels, because the peak
urement distort the readings and nullify the pressure should not increase with proper
findings. application of PEEP on auto-PEEP.346
The phenomenon of auto-PEEP is shown in
Figure 10-11. Note that the auto-PEEP effect is
BODY POSITIONING
not detected at the proximal airway pressure
monitor unless the expiratory valve is occluded Often, a simple change in a patients body posi-
immediately before the ventilator inspiratory tion may substantially alter PaO2. Despite the
phase. wealth of documentation available to support
Measurement of auto-PEEP is often difficult this, little emphasis is usually placed on this
or awkward at the bedside. New ventilation subject. Positioning can be a practical, effective
technologies and devices such as the Braschi clinical tool in PaO2 management.
valve have simplified the process and improved
accuracy of measurements. Factors in Gas Exchange
At least three factors may alter pulmonary gas
Management exchange when body position is changed.351
The first step in the management of auto-PEEP First, a change in cardiac output may occur,
is to evaluate whether it is beneficial or detri- with subsequent effects on PaO2, such as those
mental to the patient. In some cases, it may described in Chapter 9. Second, airway closure
indeed be beneficial. may develop or may be accentuated during tidal

A patient is hypotensive and septic in the ASSESSMENT

critical care unit. The following day the patient is on Abnormalities: List abnormal data and other noteworthy
a high-flow aerosol FIO2 1.0 system and blood gases information. Classify ABG.
are drawn. The chest radiograph shows a diffuse Explanation: List possible diseases, pathology, or other
white-out and the pulmonary wedge pressure is situations that may have led to this patients condition.
normal. Evaluation: Suggest additional data that would be useful in
pH 7.20 Importance: Prioritize concern(s) of treatment in order of
PaCO2 52 mm Hg urgency and/or seriousness as you see the overall situation.
PaO2 54 mm Hg Objective: Specifically state the measurable or observable
[HCO3] 19 mEq/L outcomes you would like treatment to accomplish.
FIO2 1.0 Action: Describe your specific plan of action.
breathing by assumption of the supine posi- a decrease in cardiac output and development or
tion.351 Third, gravity alters the distribution of worsening of pulmonary edema. Here, assump-
ventilation and perfusion. The net interaction of tion of the sitting position, with the concomitant
these effects as well as the effect of body posi- decrease in venous return and enhanced cardiac
tion on the work of breathing determines the performance, may be life-saving. In the presence
optimal position for each patient. of cardiovascular disease, the primary goal of
positioning the patient is to optimize cardiac
Cardiac Output function and the patients comfort.
One should first consider the effect that a
change in body position has on cardiac output Airway Closure
because cardiac output is a critical factor in tis- In patients likely to have high closing volumes,
sue oxygen delivery. Healthy individuals tend to as described in Chapter 6, (e.g., the elderly,
have an increase in cardiac output in the supine obese patients, smokers), PaO2 is usually higher
position compared with the sitting position. in the sitting versus the supine position.351 The
Venous return is enhanced in the supine posi- increase in FRC associated with the sitting posi-
tion because blood does not have to be pumped tion is probably the major reason why PaO2 is
uphill back to the heart. improved. This may help to explain why PaO2
In the presence of disease, one must carefully levels observed in patients with cystic fibrosis
consider whether the patient would benefit from are slightly higher in the sitting position com-
more or less venous return. In hypovolemic pared with the supine position.354
shock, in which venous return is diminished, An additional consideration in patients
the patient will likely have an improved cardiac with COPD or obese patients is the work of
output when supine. The improvement in car- breathing associated with body position. In
diac status in the supine position may also be these individuals, the work of breathing may
accompanied by an increase in PaO2.352 be considerably higher in the supine position
Congestive heart failure, on the other hand, due to the difficulty in displacing the abdomi-
may be aggravated by assumption of the supine nal contents with the diaphragm. Thus, when
position. In this case, the failing heart is unable airway closure or chronic obstructive pul-
to pump the increase in venous return. The monary disease is suspected, the patient should
supine position may predispose the patient to most often be placed in the sitting position.
Surprisingly, however, some patients with patient is breathing spontaneously or is being

COPD show an improvement in PaO2 with mechanically ventilated.
recumbency.355 One study, in which the patient population
was small, reported a mean PaO2 improve-
Gravity ment of 121 mm Hg when mechanically venti-
As described in Chapter 6, ventilation and per- lated patients with unilateral lung disease were
fusion are generally distributed to the most positioned with the diseased lung up versus
gravity-dependent areas of the lungs. The down.358 Increased distribution of ventilation
application of positive pressure ventilation dis- and perfusion to normal lung regions theoreti-
rupts this pattern slightly and relatively more cally explains this vast improvement in oxygen
ventilation enters the nongravity-dependent loading.
regions. Thus, the ventilation-perfusion match Surprisingly, there is some evidence to sug-
is not quite as good during mechanical ventila- gest that, in infants and young children with
tion compared with spontaneous breathing. unilateral lung disease, gas exchange is actu-
ally better with the diseased lung down.359 In
Clinical Application addition there have been reports in adults as
Diffuse Lung Disease well where gas exchange improved with the
In the presence of diffuse lung disease, patients diseased lung down, in particular with pul-
are most often placed in the supine position monary embolus.360,361 Further studies are
unless cardiac output or airway closure con- necessary, however, before application of this
siderations dictate otherwise. Assumption of finding becomes standard clinical practice.
the prone position has been shown to substan-
tially increase PaO2 (approximately 40 mm Summary
Hg) in most ALI/ARDS patients, compared Patients with abnormal pulmonary status
with the supine position.353 Three possible . . should not be subjected to positioning that
mechanisms for this include: improved V/Q, could potentially lower their PaO2 or cardiac
changes in lung mass and shape, and alter- output to dangerous levels which could, in turn,
ations in chest wall compliance. compromise tissue oxygenation. Because body
Although prone positioning improves oxy- position may substantially affect PaO2, it is wise
genation, it has not been shown to improve to record body position at the time of blood gas
survival. Side effects are uncommon but include analysis. The patients position should be an
dislodgment of endotracheal and other tubes integral part of the therapeutic plan.
or lines. The prone position may also present a
considerable problem regarding patient access
NITRIC OXIDE
and care. Thus, although prone positioning is
still being implemented in some places and it Inhaled nitric oxide has also been employed as
does indeed increase oxygenation in most cases, a therapeutic agent to enhance gas exchange in
enthusiasm for its use seems to be waning.305 ALI/ARDS.350 Nitric oxide is a selective pul-
In patients with diffuse lung disease, there is monary vasodilator and small airway dila-
also some evidence to suggest that lying on the tor.349 Other pulmonary vasodilators may also
right side may result in a higher PaO2 than lying cause systemic hypotension which is undesir-
on the left side.356 This may be related to the able. In contrast, the short half-life and rapid
greater surface area present in the right lung. absorption by hemoglobin ensures nitric oxide
has no systemic effects.
Unilateral Lung Disease Potential side effects include development of
In the presence of unilateral lung disease, cor- methemoglobinemia or formation of nitric or
rect body position may be very beneficial. nitrous acid, although this has not been com-
Patients with unilateral lung disorders should mon. The other significant deterrent to nitric
normally be positioned with the healthy lung oxide use is cost which is substantial for
down.352,356,357 This is true whether the a patient population with a high mortality.
LONG-TERM OXYGEN THERAPY

Continuous long-term oxygen therapy
Combined results of the Nocturnal Oxygen appears to benefit individuals by: (1) increased
Therapy Trial (NOTT)692 and the Medical survival, (2) decreased pulmonary vascular
Research Council Working Party693 demon- resistance, (3) increased exercise capacity,
strated that survival in COPD patients was (4) improved oxygenation during sleep, and
greatest with continuous oxygen use. (5) increased neuro-psychological performance.
The classic indication for long-term oxygen Oxygen therapy should likewise be consid-
use is the presence of COPD and a PaO2 less ered in COPD patients when traveling by
than or equal to 55 mm Hg or SaO2 less than airplane. One can expect a 4-mm Hg decrease
or equal to 88%. If the PaO2 is less than or in PaO2 for each 1000-ft elevation.695
equal to 59 mm Hg, the patient may be eligi- Airplanes are required by the Federal Aviation
ble if any of the following other criteria are Administration to maintain cabin pressures at
present: (1) hematocrit greater than or equal to least equivalent to 8000-ft elevation.694 Thus,
55%, (2) p pulmonale on electrocardiography, or one might expect PaO2 to decrease a maxi-
(3) peripheral edema secondary to right-heart mum of 32 mm Hg during flight.
failure. This needs to be demonstrated two times Because long-term hypoxia is tolerated
in the patient who is medically stable and seated. slightly better, these recommendations state
Desaturation to SaO2 less than 88% following a that chronic oxygen therapy may not be neces-
6-minute walk or during sleep also suggests the sary unless PaO2 is less than 55 mm Hg with
need for oxygen therapy. It is not uncommon for the patient in the recumbent position. Oxygen
individuals with COPD to have a 10 mm Hg or therapy may also be required if PaO2 falls
more decrease in PaO2 during sleep. below 55 mm Hg during sleep or exercise.
EXERCISES
Exercise 10-1 Oxygen Therapy

1. The first line of treatment for all oxygen-loading disturbances is ______.

2. Tissue hypoxia is likely when (mild/moderate/severe) hypoxemia is present.
3. ACCP recommendations state that oxygen therapy is indicated when PaO2 is less
than ______ mm Hg, or SaO2 is less than ______%.
4. Oxygen therapy increases (ventilation-perfusion ratios/alveolar oxygen supply).
5. Oxygen therapy is most effective when hypoxemia is caused by (relative/true) shunting.
6. Oxygen therapy can be most precisely delivered with (low-flow/high-flow) administration
devices.
7. In an individual with a normal breathing pattern, a nasal cannula set at 1 L /minute delivers
an FIO2 of approximately ______.
8. If the patients tidal volume is less than normal while breathing via a low-flow oxygen
administration system, the FIO2 is (lower/higher) than Table 10-1 indicates.
9. (High-flow/Low-flow) oxygen administration systems have the most widespread use
because of their simplicity and patient comfort.
10. Partial rebreathing masks tend to deliver an FIO2 of about ________.
Exercise 10-2 Hazards and Guidelines in Oxygen Therapy

1. When PaO2 falls below ___ mm Hg acutely, short-term memory is altered and euphoria or
impaired judgment may be observed.
2. In general, mechanical ventilation should not be initiated in COPD unless pH falls below
______ and all else fails.
3. A reasonable target PaO2 in acute exacerbation of COPD is ____ mm Hg.
4. State the three critical variables that determine the potential for physiologic harm when
administering oxygen therapy.
5. A PaO2 of greater than ______ mm Hg may lead to arrhythmias in patients with coronary
disease.
6. In most cases, _________ __________ can serve as a cost-effective alternative to blood
gases for monitoring oxygen therapy.
7. The first priority in clinical oxygenation is always (minimizing FIO2 /correction of hypoxia).
8. Oxygen therapy must be administered with extreme caution in the presence of
(COPD/heart failure).
9. PaO2 usually increases approximately ______ mm Hg for every 0.01 increase in FIO2 in
acute exacerbation of COPD.
10. The syndrome that may be a misnomer characterized by increasing PaCO2, acidemia,
stupor, and coma is known as ______.
Exercise 10-3 General Treatment and Positioning in

Oxygen-Loading Problems
1. State the three primary goals of oxygen therapy.

2. List at least four general types of therapy that can be used in the supportive treatment of
oxygen-loading disturbances.
3. State the three factors that may alter PaO2 when body position is changed.
4. In hypovolemic shock, cardiac output is likely best in the (sitting/supine) position.
5. In acute congestive heart failure, cardiac output is likely best in the (sitting/supine) position.
6. In the elderly or obese patient, PaO2 is usually highest in the (sitting/supine) position.
7. Adult patients with unilateral lung disease tend to have improved PaO2 levels when the
diseased lung is placed (up/down).
8. Infants with unilateral lung disease may have improved PaO2 levels when the diseased lung
is (up/down).
9. Ventilation/perfusion balance (is/is not) improved during mechanical ventilation compared
with spontaneous breathing.
10. Studies have shown that the (supine/prone) position has been associated with a higher
PaO2 level in ARDS.
Exercise 10-4 Oxygen Toxicity/ALI/ARDS

1. The chemotherapeutic agent _________ may accelerate oxygen toxicity.

2. The anti-arrhythmic agent ___________ may contribute to the progression of oxygen toxicity.
3. Poisons such as ________ may also contribute to oxygen toxicity.
4. It has been suggested that clinicians target a PaO2 of only ___ mm Hg and avoid an FIO2
over 0.4 during the administration of Bleomycin.
5. ALI and ARDS stand for ___________ and ________.
6. ALI is (more/less) severe than ARDS.
7. ARDS affects the lung in a (homogeneous/heterogeneous) manner.
8. It is believed that lung damage tends to occur when the alveolar pressure
exceeds ___ cm H2O.
9. VILI is the symbol for ______ ________ ________ _______.
10. MODS is the symbol for _____ ________ ________ ________.
11. The study that dramatically changed the mechanical ventilation approach to ARDS was
called _________.
12. Tidal volumes using the ARDS/Net approach are limited to ____ mL/Kg.
13. Allowing the PaCO2 to increase, as a consequence of ventilating with low tidal volume and
alveolar pressures, is referred to as __________ _____________.
14. Mortality was significantly (increased/decreased) in ARDS using the ARDS/Net approach.
15. The pH should not be allowed to fall below ____ even with permissive hypercapnia.
Exercise 10-5 PEEP/CPAP

1. PEEP has often been referred to as the cornerstone in the treatment of the pulmonary
disorder called ______.
2. (PEEP/CPAP) is the therapy best suited for the spontaneously breathing patient.
3. (Oxygen/PEEP) therapy is the most effective treatment for absolute shunting.
4. When PEEP applied to a spontaneously breathing patient falls below ambient pressure
during inspiration, the system is referred to as (CPAP/EPAP).
5. A (flow/threshold) resistor applies a relatively constant force against expiratory flow and
abruptly closes when flow stops.
6. (Continuous/Noncontinuous) flow CPAP systems are associated with the least work of
breathing.
7. The use of ______ cm H2O of PEEP is used in ARDS to prevent alveolar collapse.
8. The use of PEEP (is/is not) effective in the treatment of sleep apnea.
9. PEEP usually (improves/worsens) ventilation-perfusion matching.
10. PEEP most likely has a (beneficial/detrimental) effect on the distribution of lung water.
Exercise 10-6 Complications of PEEP

1. List the two most commonly cited complications associated with PEEP therapy.
2. (Hypervolemic/Hypovolemic) patients are especially susceptible to a decreased cardiac
output after the initiation of PEEP.
3. PEEP therapy is most likely to decrease cardiac output when pulmonary compliance is
(high/low).
4. PEEP therapy tends to have adverse effects on cardiac output when FRC is (above/below)
normal.
5. The tendency of PEEP to decrease cardiac output is directly proportional to the
(peak/mean) airway pressure.
6. PEEP therapy may be associated with a fall in arterial PO2 when administered to an indi-
vidual with (diffuse/unilateral) lung disease.
7. PEEP devices that create only (flow/threshold) resistance are associated with lower mean
airway pressures.
8. The major mechanism responsible for the decrease in cardiac output associated with PEEP
is (decreased venous return/right ventricular dysfunction).
9. PEEP may (decrease/increase) intracranial pressure.
10. A specialized form of PEEP used in unilateral lung disorders is ______ lung PEEP.
Exercise 10-7 Auto-PEEP

1. Inadvertent PEEP during mechanical ventilation is referred to as ______.

2. Patients with (COPD/ARDS) are especially susceptible to auto-PEEP.
3. Auto-PEEP is very common during mechanical ventilation at (low/high) minute ventilation.
4. Auto-PEEP (increases/decreases) the work of breathing.
5. Auto-PEEP (is/is not) reflected on the pressure manometer of a ventilator without
intervention.
6. Auto-PEEP can be detected by performing an (inspiratory/expiratory) pressure hold.
7. Auto-PEEP can be treated by (increasing/decreasing) ventilator flow rate.
8. (High/Low) compressible ventilator circuits tend to increase auto-PEEP.
9. Low doses of applied PEEP may (increase/decrease) the work of breathing associated
with auto-PEEP.
10. Peak pressure on the ventilator (should/should not) increase with proper application of
applied PEEP to auto-PEEP.

1. Go to http://www.emedicine.com/radio/Topic770.htm.
A. Describe the incidence of ARDS in the United States.
B. List at least five possible etiologies of ARDS.
NBRC Challenge 10
1. A known COPD patient arrives in the A) PEEP
emergency department in acute exacer- B) Nitric oxide
bation. Blood gases are drawn and the C) Prone position
PaO2 is 51 mm Hg. Which of the follow- D) Trendelenburg position
ing oxygen set-ups would be most likely E) Increased fluids intravenously
to result in a PaO2 of 60 mm Hg for him? (CRT EXAMINATION NBRC
A) Simple oxygen mask at 6 LPM MATRIX III,C,2,a)
B) Partial rebreathing oxygen mask at
4. What clinical recommendations could be
7 LPM
made
. . for an ARDS patient to improve
C) Vent-mask at FIO2 0.30
V/Q matching?
D) Nasal cannula 1 LPM
I. Decrease alveolar ventilation
E) Nasal cannula 3 LPM
II. Prone positioning
III. Nitric oxide
MATRIX II,A,1.a.1)
A) I only
2. In attempting to ventilate an ARDS B) II only
patient using the ARDS/Net approach, C) I and II only
which of the following guidelines would D) II and III only
be adhered to? E) I, II, and III
I. Tidal volume 6 mL/kg ideal body (RRT EXAMINATION NBRC
weight MATRIX III,B,4,c)
II. Maximum alveolar pressure of
5. A patient with ALI is being ventilated at
30 cm H2O
an FIO2 of 0.50 and 10 cm H2O of PEEP.
III. PEEP of 5 cm H2O
If oxygenation is quite good, the next
A) I only
move would be to:
B) II only
A) discontinue mechanical
C) I and II only
ventilation.
D) I and III only
B) decrease FIO2 to 0.35.
E) II and III only
C) decrease PEEP to 5 cm H2O.
D) extubate the patient.
MATRIX III,C,1,d)
E) change to intermittent mechanical
3. Which of the following therapies may be ventilation mode.
beneficial in the patient on a ventilator (RRT EXAMINATION NBRC
with cardiogenic pulmonary edema? MATRIX III,B,4,a)
Chapter
11
Hypoxia: Assessment and Intervention
Hypoxia not only breaks the machine, it wrecks the machinery.

T. S. Haldane376
Clearly, the process of tissue oxygen delivery is a complex one and unlikely to be easily defined by the
measurement of simple parameters.
David R. Dantzker377
Outline
Overview, 272 Sensitivity, 290
Oxygen Supply Variables, 273 Specificity and the Lactate/Pyruvate Ratio, 291
Arterial Oxygenation, 273 Creatine Kinase Reaction, 291
PaO2, 273 Cyanide in Smoke Inhalation, 291
SaO2, 274 Summary, 291
Blood Hemoglobin Concentration, 276 Mixed Venous Oxygenation Indices, 291
Anemia, 276 Measurement, 291
Laboratory Diagnosis of Anemia, 276 Mixed Venous Oxygen Saturation, 292
Types of Anemia, 278 Mixed Venous Oxygen Partial Pressure, 292
Anemia and Hypoxia, 280 Clinical Oxygenation Disturbances and PvO2, 293
Blood Transfusions, 280 Clinical Application, 294
Circulatory Status, 281 Oxygen Uptake and Utilization, 294
Cardiac Output, 281 Normal Oxygen Uptake, 294
Shock, 281 Normal Supply-Independent Oxygen
Hemodynamic Monitoring, 285 Uptake, 295
Treatment, 289 Covert Hypoxia, 295
Key Indicators of Hypoxia, 290 Gastric Tonometry, 297
Lactate, 290 Vital Organ Function, 297
Mortality, 290 Exercises, 298
First, as a matter of routine, one should evalu-

OVERVIEW
ate the three essential components of oxygen
The prevention, detection, and treatment of supply shown in Box 11-1. The ABCs of tissue
hypoxia must be foremost in the minds of cli- oxygen supply are Arterial oxygenation assess-
nicians treating cardiopulmonary patients. The ment, Blood hemoglobin concentration, and
ultimate goal in the management of oxygena- Circulatory status. A deficiency in any one of
tion is the prevention of tissue hypoxia. When these components may compromise oxygena-
hypoxia is present, the goal is immediate recog- tion of the tissues.
nition and intervention to minimize untoward Although evaluation of oxygen supply com-
effects. ponents is a logical starting point, in many
There is no single, simple index or way to cases, it is still difficult to conclude whether
quickly and accurately assess tissue oxygenation. tissue hypoxia is, indeed, present. Therefore,
Rather, tissue oxygenation status is best assessed when more definitive information is needed,
by systematically analyzing the various com- the clinician may look to specific indices
ponents of the oxygenation system and by eval- that suggest oxygenation failure and tissue
uating related laboratory data. I have divided hypoxia. Potential markers of tissue hypoxia
tissue hypoxic assessment into two phases. are listed in Box 11-2. These include lactate
272
Chapter 11 Hypoxia: Assessment and Intervention 273
Box 11-1 Tissue Oxygen Supply Hypoxia is unlikely in mild hypoxemia, possi-
Assessment ble in moderate hypoxemia, and likely in
severe hypoxemia. In moderate hypoxemia,
Arterial oxygenation assessment
development of hypoxia depends mainly on
SpO2
PaO2
the integrity of the cardiovascular system.
Blood hemoglobin concentration These guidelines represent clinical rules of
Circulatory status (cardiac output) thumb. There are, of course, exceptions to
B/P every rule. It has been shown that under cer-
Heart rate tain conditions, hypoxia does not occur despite
Arrhythmias the presence of severe hypoxemia.378380 For
Blood volume example, mountain climbers at the summit of
Vascular tone Mt. Everest had PaO2 levels below 30 mm Hg
without apparent adverse consequences.378
Similarly, patients with congenital heart dis-
measurement, indices of mixed venous oxy- ease had PaO2 levels averaging 37 mm Hg
genation, oxygen uptake and utilization, and without notable physiologic impairment.380
gastric mucosal acidosis. Furthermore, these patients were capable of
some exercise, during which PaO2 levels
decreased further to 28 mm Hg.380
OXYGEN SUPPLY VARIABLES
Finally, despite the fact that a PaO2 of less
Each of the oxygen supply variables as shown than 20 mm Hg is generally considered to be
in Box 11-1 will be described in detail. incompatible with life, 13 of 22 patients in one
study recovered without permanent physiologic
Arterial Oxygenation impairment despite PaO2 levels of less than
There are two primary indicators of arterial 21 mm Hg.379 Thus, PaO2 alone, even when
oxygen supply: PaO2 and SaO2. An approxi- extremely low, is inadequate as an index of
mate gauge of SaO2 is often reflected by pulse tissue hypoxia.
oximetry and in this case may be referred to as Also, one must not rely too heavily on PaO2
SpO2. The student should understand that true alone because measurements in stable critically
SaO2 can only be measured by CO-oximetry as ill patients in one study varied as much as 13%
described later in this chapter and Chapter 15. from one reading to another.381 This consti-
Nevertheless, SpO2 provides a crude index of tutes an average variance of about 16 mm Hg
SaO2 in the absence of abnormal Hb species. in PaO2 measurements without a noticeable
change in patient condition.
PaO2
PaO2 as an Index of Hypoxia Prevention of Hypoxemic Hypoxia
When available, the partial pressure of oxy- The guidelines presented previously, notwith-
gen in the arterial blood (PaO2) is a logical standing the exceptions, represent a prudent
starting point in tissue oxygenation assess- approach to the classification of hypoxemia and
ment. As described in previous chapters, the the prevention of hypoxia. One must remember
degree of hypoxemia in a given individual is a that in normal persons, when PaO2 decreases
simple indicator of the likelihood of hypoxia. to about 55 mm Hg, judgment and short-term
memory may be impaired, presumably due to
hypoxia.382 Therefore, in all but unusual circum-
stances, it is unacceptable to allow moderate or
Box 11-2 Markers of Tissue
severe hypoxemia (i.e., PaO2 < 60 mm Hg)
Hypoxia
to persist.382 This is true even in patients
Lactate accumulation with chronic obstructive pulmonary disease
Decreased mixed venous oxygen (COPD), because a PaO2 of 60 mm Hg is not
Oxygen uptake and utilization
associated with a great risk of increasing
Gastric mucosal acidosis
hypercarbia.382
As described in Chapter 10, there are some wavelengths are used, abnormal forms of
circumstances (e.g., paraquat poisoning, Hb such as HbCO and MetHb cannot be
ARDS) when moderate degrees of hypoxemia detected.383 Second, SaO2 measured in this
may be considered acceptable or permissive. way is the percentage of HbO2 compared with
Indeed, a rebuttal of the traditional approach to the sum of HbO2 and desaturated Hb only.
treatment of hypoxemia has been presented.696 Because this measurement does not include
Nevertheless, treatment of moderate hypoxemia abnormal forms of Hb, it is sometimes referred
seems prudent until clear evidence suggests to as functional SaO2.383 Functional SaO2 is
otherwise. the percentage of HbO2 compared with the
Methods available to treat hypoxemia have quantity of Hb capable of carrying O2. MetHb
been discussed in detail in Chapter 10. Although and HbCO are not capable of carrying O2;
the PaO2 is a useful starting point in clinical therefore, they are not specifically considered
hypoxic assessment, it is foolhardy to equate in this measurement.
a normal PaO2 with normal tissue oxygenation. Pulse oximetry, as described subsequently,
The myriad other factors that may influence is used routinely to evaluate oxygen satura-
O2 transport and internal respiration must also tion. Since pulse oximeters use only two wave-
be evaluated. lengths, they may likewise provide incorrect
information when substantial MetHb or HbCO
SaO2 is present. It is imperative that we always
SaO2 Determination keep these important issues in mind and do not
The SaO2 is the percentage of hemoglobin that routinely assume a normal pulse oximeter
is carrying oxygen in the arterial blood. It reading always indicates adequate oxygen
should be remembered that 98% of oxygen is saturation.
carried in arterial blood combined with Hb. CO-oximetry. Functional SaO2, as described
Regarding saturation, it is important for the previously, is in contrast with SaO2 measure-
clinician to note the technique that is being ment using a CO-oximeter. As the name implies,
used to determine SaO2, because the values this instrument can measure HbCO% in addi-
obtained by different techniques may vary. tion to the SaO2. Also, methemoglobin levels
Saturation may be calculated via a nomogram may be measured as a percentage of total Hb
or measured by oximetry, CO-oximetry, or with this unit.384
pulse oximetry. In CO-oximeter measurements, all forms of
Calculated SaO2 Using a Nomogram. Some Hb are included in the calculation of the total
laboratories use a nomogram to predict the Hb concentration. Thus, with this instrument,
SaO2, based on the PaO2 and pH.383 This cal- SaO2 is the percentage of HbO2 compared with
culated SaO2 does not account for factors all forms of Hb (including abnormal forms of
other than the pH that may alter HbO2 affin- Hb). SaO2 measured in this way is sometimes
ity. Furthermore, this methodology assumes referred to as fractional SaO2, which may be
that no abnormal forms of Hb are present, substantially different from functional SaO2 in
such as HbCO or MetHb. Obviously, calcu- certain situations.
lated SaO2 provides little more information In review, the percentage of HbO2 com-
than PaO2 and may sometimes lead to a false pared with the sum of Hb and HbO2 is called
sense of security. Some laboratories label cal- functional SaO2; the percentage of HbO2 com-
culated saturation as SO2. pared with all forms of Hb is called fractional
Oximetry. SaO2 may be measured more SaO2.
accurately via oximetry. Oximeters are two- Pulse Oximetry. The saturation as measured
wavelength spectrophotometers. The specific by pulse oximetry (SpO2) is a functional SaO2
technique underlying two-wavelength oxime- measurement as described earlier. As a two-
try is discussed in Chapter 15. wavelength device, the pulse oximeter cannot
It is important to understand two essential distinguish between HbO2 and HbCO; there-
points when SaO2 is measured with the two- fore, SpO2 is equal to the sum of HbO2 and
wavelength method. First, when only two HbCO percentages.385
Other factors that have been thought to alter in the blood, it is inferior to PaO2 as a sensitive
pulse oximetry readings include hypothermia, index of pulmonary deterioration, mild hypox-
dark fingernail polish, vasoconstriction asso- emia, and/or hyperoxemia. Because the normal
ciated with shock, and infusion of dyes.386 individual has an SaO2 on the flat portion of
Interestingly, SpO2 readings may be slightly the oxyhemoglobin dissociation curve, rela-
higher if the finger being used for the test is tively large changes in PaO2 result in minimal
elevated, presumably because of changes in or no change in SaO2.
venous congestion.387 Newer pulse oximeter
technology tends to eliminate many potential SpO2 and Abnormal Hb Species
measurement errors (see Chapter 15). As described earlier, SpO2 measures functional
saturation, not fractional saturation. Thus,
SaO2 as an Index of Hypoxia abnormal Hb species (e.g., HbCO, MetHb) are
SaO2 is a better indicator of arterial oxygen not reflected. HbCO is recorded as HbO2
content than is the PaO2. Approximately 98% because only two wavelengths of light are being
of blood oxygen is carried in the combined state measured. This could lead to a false sense of
(e.g., HbO2); therefore, SaO2 more accurately security regarding the patient with significant
reflects the quantity of oxygen in the blood levels of abnormal Hb species. If, for example,
than the PaO2. Clinically, as long as SaO2 an individual has an HbCO level of 20% and
exceeds 90%, most clinicians are confident that a fractional HbO2 level of 70%, SpO2 will read
the patient is not hypoxic. Usually a red flag is approximately 90%.
raised, however, when SaO2 falls below 90%. Thus, pulse oximetry may be misleading in
Furthermore, with the advent of routine the patient with recent exposure to carbon
SpO2, understanding of the oxyhemoglobin monoxide. With increased methemoglobine-
curve assumes greater clinical importance. mia, SpO2 readings tend to migrate toward
Important relationships between PO2 and SO2 85%. As always, one cannot depend too heav-
must be committed to memory (i.e., PO2 of ily on any single technology as a replacement
60 mm Hg = SO2 of 90%; PO2 of 40 mm Hg = for thorough clinical evaluation.
SO2 of 75%). The clinician must be able to Although pulse oximetry has some short-
mentally equate and interchange these two comings as a true measure of oxygen satura-
important parameters of oxygenation. tion, it is useful particularly as a monitor of
The PO2SO2 relationships described earlier desaturation. In other words, when there is a
hold true given normal oxyhemoglobin affin- fall in oxygen saturation from previous levels,
ity. A change in this relationship (e.g., PO2 = it will usually be reflected. For this reason, pulse
60 mm Hg; SO2 = 80%) is indicative of a change oximetry is an excellent method to monitor
in HbO2 affinity (i.e., shift in oxyhemoglobin oxygen status on a real-time basis.
curve) that may be clinically important to rec-
ognize. For example, in the presence of alka- Maintenance of an Adequate SaO2
lemia and hypocarbia, SpO2 may remain above In summary, SaO2 values may vary substan-
90% even when PaO2 is much lower than tially depending on the technique of measure-
60 mm Hg. ment. The clinician must understand the method
There is sometimes concern that a left-shifted being used and its implications regarding patient
oxyhemoglobin dissociation curve may cause management. When abnormal forms of Hb are
tissue hypoxia because the hemoglobin will not suspected, SaO2 should always be measured by
release oxygen to the tissues. This phenomenon using CO-oximetry.
alone, especially in chronic conditions, is prob- When fractional SaO2 is low, as determined
ably unlikely to cause tissue hypoxia as a patient by CO-oximetry, therapy is focused on decreas-
with a P50 of 11 mm Hg did not appear to ing the amount of any abnormal Hb species
show any evidence of hypoxia.436 present in the blood and increasing blood oxy-
Finally, the relative insensitivity of SaO2 gen content to satisfactory levels.
must also be recognized. Although SaO2 is a High levels of HbCO are treated with frac-
superior index of quantitative oxygen content tion of inspired oxygen (FIO2) of 1.0 and, when
available, hyperbaric oxygen. The half-life of 120

HbCO is approximately 5 hours on room air.
Thus, it takes the body about 5 hours to elim-
inate 50% of HbCO while breathing room air. 100
Breathing 100% O2 decreases the half-life to
about 1 hour. Furthermore, the high levels of
inspired oxygen maximally saturate available
Oxygen transport % normal

Hb and enhance dissolved O2 concentration. 80
In the case of very high MetHb levels, methylene
blue is often useful to accelerate the reduction
of MetHb to Hb. 60
In most clinical situations, conventional wis-
dom is simply to maintain the fractional SaO2
above 90% to 92%. This usually equates to a
40
PaO2 > 60 mm Hg. When SaO2 falls below this
point, however, immediate action is usually
indicated to restore SaO2 to safer levels. One
must remember that below 90% saturation, 20
SaO2 will fall precipitously with further PaO2
reductions. Although this approach has been
recently challenged,696 presently it is probably
0
best to adhere to conventional wisdom. 10 20 30 40 50 60 70
Hematocrit
Blood Hemoglobin Concentration
Anemia Figure 11-1. Hematocrit and oxygen transport.
Not only is the SaO2 important in tissue oxy-
genation, but the absolute quantity of hemoglo-
bin present in the patient must be adequate to
carry and deliver oxygen throughout the body. is known as the hematocrit (Hct). Hematocrit
The normal red blood cell concentration (abbre- is normally approximately 47% in men and
viated [RBC]) is 5 million/mm3 (700,000) for approximately 42% in women. Because the
men and 4.5 million/mm3 (500,000) for RBCs make up the major portion of the hema-
women. The normal Hb concentration (abbre- tocrit, it is also a useful indicator of anemia.
viated [Hb]) is 15 g% (15 g/100 mL of blood) In a sense, hematocrit is a double-edged
in men and 13 to 14 g% in women. sword. If Hct is extremely low, arterial oxygen
A reduction in the amount of circulating content and oxygen transport will be compro-
RBCs or Hb is termed anemia. In general, the mised. Conversely, when Hct is excessive, blood
classic criterion for an individual to be consid- viscosity is increased and again, oxygen trans-
ered anemic is if [RBC] is less than 4 million/ port may be diminished due to a fall in cardiac
mm3 or if [Hb] is less than 12.5 g%.702 Actual output (Fig. 11-1). The optimal clinical Hct is
normal values vary with age and sex. Anemia likewise controversial and, in different patient
may greatly diminish the ability of the blood populations, has been shown to be as low as
to transport oxygen because hemoglobin is 30% or as high as 45%.437
responsible for approximately 98% of oxygen
transport. Laboratory Diagnosis of Anemia
When blood is centrifuged or allowed to When anemia is observed, the cause should be
stand, it separates into two layers: (1) a layer investigated. A thorough discussion of the var-
of formed elements that includes RBCs, white ious types of anemia and differential diagnosis
blood cells (WBCs), and platelets; and (2) a is beyond the scope of this book; however,
layer of straw-colored fluid called plasma. some fundamentals and terminology involved
The percentage of formed elements by volume in anemia are reviewed.
Figure 11-4. Iron deficiency anemia with

hypochromia and microcytosis. Note the presence
of many small (microcytic) cells and the decreased
amount of hemoglobin pigment (hypochromia)
within the cells.
Figure 11-2. Mature erythrocytes, peripheral

blood (1000, Wrights stain).
The presence of great numbers of large (>10 m)
RBCs is called macrocytosis. This condition is
Anemia is generally classified and diagnosed also seen in Figure 11-3. Conversely, the pres-
based on the characteristics of the RBCs ence of great numbers of small (<5 m) RBCs
observed and the number of immature RBCs is called microcytosis (Fig. 11-4).
seen. In particular, the size, shape, and amount Cell size is measured in the clinical labora-
of Hb have diagnostic significance. tory using the mean corpuscular volume
(MCV) index. Normal MCV is 90 (8) femp-
Mean Corpuscular Volume toliters (fL).388 Decreased [Hb] associated with
Normal RBCs are, for the most part, approxi- an MCV less than 82 fL is called microcytic
mately 7 m in diameter. Figure 11-2 shows a anemia; decreased [Hb] associated with an
normal RBC film magnified 1000 times. MCV greater than 98 fL is called macrocytic
Anisocytosis is said to exist when there are anemia.
abnormal variations in cell size (Fig. 11-3).
Red Blood Cell Shape
Abnormalities in the shape of RBCs are called
poikilocytosis. An example of a cell with an
abnormal shape is the megaloblast. These cells
are large (11 to 20 m), nucleated RBCs that
are oval and slightly irregular in shape (see
Fig. 11-3). Megaloblasts are found in anemia
due to vitamin B12 deficiency (i.e., pernicious
anemia) or in folic acid deficiency.
Immature Red Blood Cells

The presence of large numbers of immature
RBCs in the blood suggests that anemia may
be due to acute blood loss. Under normal con-
Figure 11-3. Megaloblastic anemia with anisocy- ditions, between 0.5% and 1.5% of RBCs are
tosis and macrocytosis. Abnormal variation in cell in the immature form known as reticulocytes
size (anisocytosis) is evident. Large, nucleated, (Fig. 11-5).389 The presence of increased retic-
oval-shaped megaloblasts can also be seen. ulocytes in the blood is called reticulocytosis.
<32%) is seen commonly in iron deficiency

anemia (see Fig. 11-4).
Summary
Table 11-1 compares MCV and MCHC.
Table 11-2 summarizes many of the terms used
in describing RBCs when diagnosing anemia.
Common types of anemia associated with each
laboratory finding are also shown in Box 11-3.
Types of Anemia
Some of the more common types of anemia are
briefly discussed here to acquaint the reader
with the variety of potential anemic mecha-
nisms (see Table 11-2). The presence of anemia
means either (1) that there is a decrease in the
production of RBCs or hemoglobin or (2) that
RBCs or Hb is being lost or destroyed at an
Figure 11-5. Reticulocyte(s), peripheral blood
(1000, new methylene blue stain). accelerated rate.
Decreased production may be due to a prob-
lem at the production site (i.e., bone marrow)
or to a deficiency in one of the necessary con-
Reticulocytosis leads to rapid oxygen constituents for RBC/Hb production. On the other
sumption in acquired blood samples and may hand, accelerated loss or destruction may be
lower blood PaO2 if not measured promptly. due to excessive rupture (hemolysis) of RBCs
Another type of immature RBC, the normoblast, or to excessive blood loss.
is not normally found in the blood but may be
observed in anemia secondary to acute blood Bone Marrow Failure
loss. A normoblast is a nucleated RBC similar Abnormal development (aplasia) of the bone
in size to a normal RBC. marrow may occur without apparent cause, but
more commonly this condition follows exposure
Mean Corpuscular Hemoglobin Concentration to some chemical or physical agent. Chemical
The percentage of the RBC volume occupied agents known to be associated with aplastic
by Hb is another useful diagnostic aid in anemia include the drug chloramphenicol, insec-
anemia. Normally, approximately one-third ticides such as DDT, and arsenic. Physical causes
of the RBC consists of Hb. The clinical labo- include excessive exposure to radiation.
ratory test used to evaluate RBC [Hb] is the
mean corpuscular hemoglobin concentration Inadequate Hemoglobin Synthesis
(MCHC). Normal MCHC is 34 2%388 and The most common problem in Hb synthesis
is called normochromia. Hyperchromia (MCHC is iron deficiency. Iron supply is normally not
>36%) is rare; however, hypochromia (MCHC a problem, because iron is recycled following
Table 11-1. RED BLOOD CELL INDICES

Mean Corpuscular Volume (MCV) Mean Corpuscular Hemoglobin Concentration (MCHC)
Measurement of average size or volume of Measurement of average [Hb] in 100 mL of

individual RBCs packed RBCs
Normal value: 90 8 fL Normal value: 34 2%
MCV <82 fL indicates microcytosis MCHC <32% indicates hypochromia
MCV >98 fL indicates macrocytosis MCHC >36% indicates hyperchromia
Table 11-2. ERYTHROCYTE ABNORMALITIES

Terminology Description Types of Anemia
Anisocytes Abnormal variations in cell size Nonspecific

Hypochromia Pale cells due to decreased [Hb] within cell Iron deficiency
Macrocytes Large cells greater than 10 Pernicious anemia and folic
acid deficiency
Megaloblasts Large, oval, irregular, nucleated cells Pernicious anemia and folic
acid deficiency
Microcytes Small cells less than 5 Iron deficiency, thalassemia
Normoblasts Immature, nucleated red blood cells of normal size Acute blood loss
Poikilocytes Abnormal variations in cell shape Nonspecific
Reticulocytes Immature red blood cells containing Acute blood loss
a network of granules or filaments
Sickle cells Crescent or sickle-shaped cells Sickle cell anemia
the destruction of old RBCs. However, when Thus, we must continue to be vigilant in its
iron is lost from the body, as in hemorrhage, or identification and prevention.
when additional iron is required, such as in Production of Hb may be abnormal in a
pregnancy, it may be in short supply for Hb genetic disorder called thalassemia. Thalassemia,
production. also known as Cooleys anemia or Mediter-
Probably the most common cause of iron ranean disease, may manifest itself in one of two
deficiency anemia is chronic blood loss. It may forms: thalassemia major is a severe form of
also be seen in infants or in mothers during the disease that may be associated with severe
pregnancy. An interesting diagnostic character- anemia; thalassemia minor is a milder form.
istic observed in some individuals with iron Inadequate production of Hb is associated
deficiency is pagophagia.438 Pagophagia is a with hypochromia and the presence of small
type of pica or craving for unusual sub- RBCs (microcytosis).
stances. Pagophagia is a strong craving for ice
and is the most common type of pica seen in Inadequate Red Blood Cell Formation
iron deficiency anemia. Pica occurs in up to Production of RBCs depends on an adequate
58% of patients with iron deficiency.438 supply of folic acid, vitamin B12, and the hor-
In recent years, severe iron deficiency has mone erythropoietin. Folic acid is plentiful
become relatively uncommon. Nevertheless, in green leafy vegetables. Alcohol, however,
mild iron deficiency is still far too common and interferes with the metabolism of folic acid.
can have damaging long-term consequences.439 Therefore, poor diet or alcoholism may lead to
folic acid deficiency.
Vitamin B12, sometimes referred to as extrin-
sic factor, is normally absorbed in the stomach.
Box 11-3 Common Types of Anemia This absorption is facilitated through a sub-
Small Red Blood Cells (Microcytic) stance that has been labeled intrinsic factor.
Iron deficiency (chronic hemorrhage) Individuals lacking in this intrinsic factor may
Thalassemia develop anemia due to vitamin B12 deficiency.
Large Red Blood Cells (Macrocytic) Anemia that develops by this mechanism is
Folic acid deficiency known as pernicious anemia.
Vitamin B12 deficiency (pernicious anemia) Anemia is also common in chronic renal
Normal-sized Red Blood Cells (Normocytic) failure and is due at least in part to decreased
Hemolytic erythropoietin. Some loss of RBCs into the
Aplastic
urine may also occur due to increased perme-
Acute hemorrhagic
ability of the diseased glomerulus.
Anemia due to folic acid or vitamin B12 defi- The presence of normoblasts in the blood is
ciency leads to a high number of large RBCs abnormal and a sign of accelerated RBC pro-
(i.e., macrocytosis). In addition, megaloblasts duction. Anemia secondary to the loss of RBCs
may be observed in the blood of these individ- is typically normocytic in laboratory analysis.
uals.
Anemia and Hypoxia
Red Blood Cell Loss/Hemolysis Surprisingly, mild anemia (i.e., [Hb] 10 g%)
Immediately after acute blood loss, [RBC] may usually will not result in hypoxia. The large
be normal. Soon after, however, fluid enters the reserve of O2 normally present in the blood and
blood from the interstitial space and thus leads the bodys compensatory mechanisms both
to anemia. tend to ensure adequate tissue oxygenation. As
Hemolysis is usually the result of the pres- discussed previously, usually only about 25%
ence of toxins in the blood. Toxins may origi- of the oxygen in arterial blood is extracted by
nate from infectious processes or may directly the tissues; therefore, mild anemia does not
enter the blood, such as in poisonous snake- substantially affect tissue O2 supply.
bites. Many chemical agents may be associated Furthermore, the body responds to anemia
with hemolysis. Finally, chronic hemolysis with by increasing cardiac output and increasing
acute exacerbation may occur in disorders 2,3-diphosphoglycerate (DPG) levels. In healthy
such as sickle-cell disease (see Chapter 7) or individuals, mild, acute normovolemic anemia
thalassemia. is compensated for by increases in cardiac
The pain rate (episodes per year) is a useful output up to 50%.391 Within 2 weeks the car-
measure of the severity of sickle cell disease.440 diac output returns to preanemic levels, with
Treatment, which has been discussed briefly an increase in DPG accounting for the com-
in Chapter 7, may include bone marrow trans- pensation. Thus, the major compensatory
plant, or more commonly, administration of mechanism in acute anemia is an increased
pharmacological agents (e.g., hydroxyurea) cardiac output, whereas in chronic conditions,
aimed at increasing the amount of fetal Hb increases in DPG prevail.
(HbF).441 Increases in HbF have an ameliorat- In moderate to severe anemia (i.e., [Hb] = 6
ing effect on the disease and symptoms. Many to 9 g%) hypoxia may occur, depending on
of these chemotherapeutic agents, however, the cardiac reserve and the acuteness of onset.
may cause adverse effects and drugs with less Anemic hypoxia in all likelihood will be seen
potential of side effects (e.g., butyrate) continue when [Hb] falls below 6 g% and the capa-
to be explored.441 bilities of compensatory mechanisms are
Reticulocyte levels typically are increased in exceeded.392
conditions associated with hemolysis or blood
loss. In most long-term hemolytic anemias, Blood Transfusions
reticulocytes exceed 5%.390 When evaluating Blood transfusion is the treatment of choice for
the reticulocyte levels, however, one must keep severe anemia; however, this therapy may be
in mind that reticulocytes are usually expressed associated with substantial risk. Some adverse
as a percentage of total RBCs. effect to blood transfusion may occur in as many
It is probably better to think in terms of the as 20% of recipients.442 Immune side effects are
actual count of reticulocytes rather than the seen in approximately 3% of all transfusions.393
percentage. The normal actual count of retic- Typically these are mild allergic reactions,
ulocytes is about 50,000 cells/mm3 or 1% of although potentially fatal hemolytic reactions
[RBC]. If [RBC] decreases from 5 million to are observed in approximately one of 6000
2.5 million/mm3, and the reticulocyte count transfusions.393
remains constant (i.e., 50,000 cells), the per- In addition, anaphylactic reactions may
centage of reticulocytes would be 2%. If the occur, and not infrequently patients contract
actual reticulocyte count is not considered, this post-transfusion hepatitis.393 Finally, blood is a
could be wrongly interpreted as an increase in complex substance and may carry with it addi-
RBC production. tional risk factors not yet clearly identified. The
acquired immunodeficiency syndrome has intensive care unit who require precise moni-
been a painful lesson in this regard. toring of fluid balance and function of the left
The ideal hematocrit and [Hb] in critically side of the heart.
ill patients are also a matter of some contro- In recent years, noninvasive cardiac output
versy. Certainly, Hct need not be within the monitors have become available that facilitate
normal range in order to ensure adequate measurement of cardiac output in the absence
oxygenation. Optimal levels are probably of a Swan-Ganz catheter.445 These devices,
somewhere between 30% and 45% depending which make use of the Fick equation, have
on the individuals particular pathology.394,437 been shown to be reasonably accurate in clini-
There is some evidence to suggest that the cal situations.
optimal hematocrit in critically ill patients is
about 33% (see Fig. 11-1), because further Clinical Assessment
increases do not result in increased cellular O2 Notwithstanding, in many clinical situations,
availability.395 Obviously, low Hct levels are cardiac output must be assessed indirectly.
associated with decreased ability of the blood This assessment is accomplished through eval-
to carry oxygen. In contrast, high Hct levels uation of a host of clinical signs and symptoms.
increase blood viscosity and thereby dampen Urine output, neurologic status, blood pressure,
cardiac output. pulse, capillary refill (i.e., the speed at which
A [Hb] blood transfusion trigger of less color returns to the skin after it is depressed),
than 7.0 g/dL has been recommended and is cyanosis, and warmth of extremities all pro-
probably a useful guideline.444 Nevertheless, at vide clues about the adequacy of circulation.
high altitude, or for patients with brain injury, a Although all these indicators provide useful
much higher trigger (e.g., 10 g/dL) is probably information, they cannot replace actual meas-
appropriate.443 urement of cardiac output when it is in serious
question.
Circulatory Status Even when cardiac output is measured,
Cardiac Output however, complete cardiovascular assessment
The cardiovascular system is the core of the must include sequential evaluation of the three
human oxygenation system.
. The cardiac minute basic components of the cardiovascular system:
output (abbreviated Q or sometimes CO) is the (1) the pump (heart), (2) the fluid (blood), and
volume of blood ejected from the left side of the (3) the tubules (blood vessels). The interaction
heart each minute. Cardiac output is a crucial of these three components determines the
index concerning tissue oxygenation. Cardiac important cardiovascular parameters of cardiac
output is approximately 5 L /min in normal output and arterial blood pressure. Further-
individuals. The cardiac index (CI) relates car- more, this chronologic assessment aids in deter-
diac output to body size and expresses cardiac mining the root cause of any cardiovascular
output as liters per minute per body surface area disturbance.
in square meters (m2). Thus, the cardiac index
should be the same in all individuals regardless Shock
of size or weight. The normal cardiac index is Shock is a state of collapse of the cardiovascu-
3.5 0.7 L/min/m2. lar system usually associated with a loss of
arterial blood pressure. The signs and symp-
Measurement toms of shock are a result of inadequate perfu-
The cardiac output can be measured easily by sion to a particular organ or may be due to the
thermodilution technique or can be calculated compensatory response of the central nervous
using the Fick equation if a pulmonary artery system to the shock state. The sympathetic
(Swan-Ganz) catheter is in place. Placement of portion of the autonomic nervous system is
a pulmonary artery catheter is an invasive pro- typically stimulated in shock, resulting in the
cedure with potentially serious complications. release of epinephrine and norepinephrine.
Therefore, insertion of these catheters is usu- These substances, in turn, lead to an increased
ally restricted to critically ill patients in the heart rate and constriction of peripheral blood
vessels, which represents an attempt of the body Conversely, high cardiac rates tend to
to preserve cardiac output and arterial blood increase cardiac output. When the heart rate
pressure. increases to approximately 2 to 21/2 times nor-
mal, however, cardiac output tends to drop.
Clinical Symptoms This occurs because the rapid heart rate does
Restlessness, anxiety, or alteration in con- not allow for appropriate filling of the heart
sciousness may be early signs of shock caused between beats. Therefore, cardiac output actu-
by decreased cerebral perfusion. Cyanosis, ally decreases in severe tachycardia due to the
decreased urine output, and lactic acidosis may simultaneous fall in stroke volume.
likewise suggest poor perfusion status. Rapid Congestive Heart Failure. Pump effectiveness
breathing and respiratory alkalosis are often may be diminished acutely when heart muscle is
observed with shock, presumably as a secondary not adequately perfused or oxygenated, as in
response to hypoperfusion mediated through myocardial infarction (heart attack). A similar
the peripheral
. . chemoreceptors or as a result of situation may occur in chronic hypertension
high V/Q in the lungs. where the heart is faced with relentless pumping
Vasoconstriction secondary to the release of against substantial resistance. When the heart is
norepinephrine and, to a lesser extent, epineph- unable to pump the blood within it, congestion
rine may also lead to cold, pale extremities. of blood occurs in the heart; thus, the name
Sympathetic stimulation of the sweat glands in congestive heart failure (CHF). CHF may be
conjunction with the peripheral vasoconstric- the result of a faulty heart valve, inadequate
tion tends to make the skin appear cold and oxygenation of heart muscle (e.g., in myocar-
clammy. dial infarction), fluid overload of the heart, or
prolonged stress on the heart from pump-
Etiology ing against high resistance (e.g., in chronic
Shock may occur due to failure of the heart as hypertension).
a pump; failure to maintain an adequate blood When CHF originates from the left side of the
volume, as in hemorrhage; or failure of the heart, congestion also accumulates in the lungs
blood vessels to maintain adequate muscular (i.e., pulmonary edema). Symptoms of acute
tone, as in vasodilation with subsequent loss left-sided heart failure include edema, jugular
of pressure. Systematic evaluation of the car- vein distention, hypoxemia, shortness of breath,
diovascular system in shock should proceed abnormal heart sounds, and fine crackles in the
by individually assessing each of these three lung fields. The diagnosis is confirmed when
components. the chest radiograph shows increased hilar
markings and lung fluid. Also, hemodynamic
Pump Effectiveness measurements typically display high pressures
Cardiac output is the product of heart rate and in the heart.
stroke volume. Thus, pump effectiveness Optimal management of severe left-sided
depends on the frequency of beats (heart rate) heart failure often includes insertion of a
and the volume of blood ejected with each beat Swan-Ganz catheter in the pulmonary artery.
(stroke volume). Presence of this catheter allows for monitoring
Heart Rate and Stroke Volume. Normal of the pulmonary wedge pressure, as described
heart rate is approximately 70 beats per minute. later. Pulmonary wedge pressure is an excellent
Slower rates tend to reduce cardiac output unless index of the function of the left side of the
they are accompanied by a concurrent increase heart and congestive heart failure. Further-
in stroke volume. Well-trained athletes often more, it is a very useful index to follow in fluid
manifest bradycardia (decreased heart rate) but management and the treatment of left-sided
maintain a normal cardiac output. In this case, heart failure.
cardiac output remains normal because of the Cardiogenic Shock. Cardiovascular collapse
enhanced stroke volume performance of the due to failure of the heart as a pump is called
conditioned heart muscle. cardiogenic shock, because its origin is the
BV
CVP
BP CI
Art blood lactate
A-VO2 Hct normal
difference Art: PO2
Art: pH
Art: PCO2
P Figure 11-6. Cardiogenic shock. The
principal hemodynamic and metabolic
abnormalities seen in cardiogenic shock.
Urine flow
PR
heart itself. Figure 11-6 shows some of the hypovolemia and maintain an adequate car-
principal hemodynamic and metabolic changes diac output.
that are associated with cardiogenic shock. When a central venous pressure line is in
place, low central venous pressure readings
Blood Volume are a good indication of hypovolemia. In the
The output of the heart as a pump can never absence of invasive monitoring, however, the
exceed its input; thus, cardiac output volume patient should be evaluated for clinical signs
cannot exceed venous return volume. Venous of hypovolemia. These include dried mucous
return is the amount of blood returning to the membranes, tachycardia, postural hypotension
right side of the heart. Inadequate venous return, (falling arterial pressure upon assumption of
regardless of cause, results in a decreased cardiac the standing position), high specific gravity of
output. The loss of 20% of total blood volume the urine, and poor skin turgor.
may reduce arterial pressure by 15% and cardiac Hypovolemic Shock. Cardiovascular col-
output by 41%.446 lapse secondary to inadequate blood volume is
Hypovolemia. A decrease in blood volume termed hypovolemic shock. When the shock
is called hypovolemia. Hypovolemia may be is due to actual internal or external bleeding,
absolute, such as in the case of hemorrhage it may also be termed hemorrhagic shock.
with the actual loss of blood; alternatively, Hemorrhagic shock is commonly observed fol-
hypovolemia may be relative, as in the case of lowing trauma or surgery. Figure 11-7 shows
systemic vasodilation and pooling of blood some of the principal hemodynamic and meta-
in the extremities. Relative hypovolemia also bolic changes seen in hypovolemic or hemor-
may result from loss of intravascular fluid to rhagic shock.
the interstitial space, which can occur in burn The long-term intensive care unit (ICU)
injuries. Regardless of whether hypovolemia population often requires transfusion due to
is relative or absolute, fluids must be admin- the excessive loss of blood used for laboratory
istered in sufficient quantities to reverse the diagnosis. In one example, 85% of all patients
CVP
BP CI
Art blood lactate
A-VO2 Hct
difference Art: PO2
Art: pH
Figure 11-7. Hypovolemic shock. The Art: PCO2
P
principal hemodynamic and metabolic
abnormalities seen in hypovolemic or
traumatic shock.
Urine flow
PR
who were in ICU for more than 7 days Psychogenic shock (fainting) is a similar albeit
required blood transfusions.453 Therefore, less serious phenomenon in which transient
decreasing phlebotomy blood loss is an impor- vasodilation results from an emotional stimulus
tant goal in ICU patient management. or because of extreme heat or exhaustion.
Septic Shock. Profound vasodilation may
Vascular Tone also result from a chemical origin. This may be
Maintenance of arterial blood pressure and secondary to the presence of some toxin in the
cardiovascular integrity requires the presence blood, as in septic shock, or to administration of
of some muscle tone (vasoconstriction) in the a foreign substance into the body, with a subse-
peripheral circulation. If all peripheral arterioles quent severe allergic reaction. Septic shock is a
were to dilate simultaneously, arterial pressure condition caused by infection or an inflamma-
would fall to dangerous levels.396 Vascular tone tory reaction in the blood. In septic shock, car-
throughout the body is an important factor diac output is usually quite high. Nevertheless,
that affects blood pressure, heart work, and blood pressure may still be low and tissue per-
the allocation of perfusion. The muscular tone fusion may not be adequate because of the
of peripheral vessels must be carefully controlled profound vasodilation. The principal hemody-
to minimize cardiac stress while providing namic and metabolic changes seen in septic
optimal cardiac output, blood pressure, and shock are shown in Figure 11-8. It is becoming
cellular perfusion. increasingly clear that increases in cardiac out-
Neurogenic Shock. There are several types put are not always distributed ideally through-
of shock in which there is a loss of vascular tone out the body and that the distribution of blood
with a subsequent decrease in blood pressure. may be a critical, yet often neglected variable.
In neurogenic shock, nervous system control of Anaphylactic Shock. When severe vasodi-
vascular tone is lost and may result in profound lation is secondary to an allergic reaction,
vasodilation. This may occur after an injury the condition is termed anaphylactic shock.
such as a fractured spine or after cardiac arrest. Anaphylactic shock is mediated by the release
CVP
BP CI
Art blood lactate
A-VO2 Hct normal
difference Art: PO2
Art: pH
Art: PCO2
P Figure 11-8. Septic shock. The principal
hemodynamic and metabolic abnormalities
seen in hyperdynamic septic shock.
Urine flow
PR
of histamine, which is a potent vasodilator. congestive heart failure. Therefore, the clinician
Anaphylaxis may be responsible for as many should be familiar with some of the basic
as 500 deaths each year.447 terminology, techniques, and values used in
Even when anaphylaxis is anticipated and hemodynamic evaluation. Just as the term
rapidly treated by experienced personnel, severe implies, hemodynamic refers to blood move-
reactions may not respond. The treatment of ment and to the various pressures generated
choice in anaphylactic shock is the administra- throughout the cardiovascular system because
tion of epinephrine (a sympathomimetic drug) of this movement.
to maintain cardiac output and increase vas-
cular tone. It is also probably best to hospital- Arterial Blood Pressure
ize all patients with serious anaphylaxis for Historically, arterial blood pressure has been
24 hours because relapses may occur.447 the clinicians primary hemodynamic measure-
ment. In the past, priority was placed on the
Summary maintenance of arterial blood pressure. Drugs
It is evident that the presence of shock or a were liberally administered to ensure that arte-
decrease in cardiac output may originate from rial blood pressure remained at a satisfactory
the heart, the blood, or the tone of the periph- level. Unfortunately, cardiac output was some-
eral blood vessels. Clinical evaluation of the times adversely affected by efforts that were
cardiovascular system requires that each of focused solely on the blood pressure. It is now
these three components be considered as a pos- recognized that the maintenance of cardiac
sible source of cardiovascular disturbance. output is of greater importance than the main-
tenance of the blood pressure per se.
Hemodynamic Monitoring Arterial blood pressure is usually measured
As alluded to previously, it is common to per- indirectly using a blood pressure cuff and pres-
form hemodynamic monitoring in the critical sure gauge (sphygmomanometer). When con-
care setting, particularly in the management of tinuous monitoring of arterial blood pressure
is desirable, insertion of an arterial line may be

useful. Newer, noninvasive devices are also
available for continuous monitoring.
Upon insertion, an arterial line allows for
(1) continuous monitoring of blood pressure,
(2) arterial blood gas sampling, and (3) more
precise measurement of arterial blood pres-
sure than possible with indirect assessment.
Although useful, arterial blood pressure moni-
toring provides only limited information about
overall cardiovascular status. Furthermore, it
is an invasive monitor that increases the risk of
infection.
Central Venous Pressure

A central venous pressure (CVP) line is a more
sophisticated form of hemodynamic assess-
ment. A CVP line is a catheter placed in a
peripheral vein and threaded into the superior
vena cava or the right atrium of the heart. Thus,
the CVP reflects the right atrial pressure (RAP).
Normal CVP is 2 to 10 mm Hg. A high CVP
Figure 11-9. Pulmonary artery catheter.
(>20 mm Hg) suggests congestive heart failure
or fluid overload with subsequent backup of
fluid in the heart. An extremely low CVP, on
the other hand, may indicate hypovolemia.
Pulmonary Artery Pressure

Pulmonary Artery Catheter. A more accurate mmHg
technique with which to evaluate hemodynamic 30
status is the Swan-Ganz pulmonary artery
catheter. An illustration of a pulmonary artery 0
catheter is shown in Figure 11-9. This multi-
30
lumen catheter is inserted similarly to the CVP
A
catheter. Insertion differs, however, in that the
catheter actually passes through the right side 0
of the heart and into the pulmonary circula- 30 B
tion. Figure 11-10 shows how the catheter
moves through the heart and the correspon-
0
ding pressure tracings that are normally found
as it passes through the heart. 30
Pulmonary Artery Catheter Insertion.
C
Movement of the catheter through the heart is 0
accomplished by inflating a small balloon on
the catheter tip, which allows the catheter to D
float through the heart chambers. Thus, the
Figure 11-10. Pulmonary catheter insertion.
pulmonary artery catheter is often referred to Insertion of a Swan-Ganz balloon flotation
as a balloon flotation catheter. As illustrated in catheter into the pulmonary artery with accompa-
Figure 11-10, the catheter is actually inserted nying pressure tracings at each step. A, Right
until it wedges in a pulmonary artery, where- atrium. B, Right ventricle. C, Pulmonary artery.
upon the balloon is deflated. D, Pulmonary artery wedge position.
While the balloon is deflated, the pressure Starlings curve shows that normally the
measured through the catheter is the pulmonary heart muscle increases its force of contraction in
artery pressure (PAP) (see Fig. 11-10,C). Normal response to an increase in preload. Therefore,
PAP is 25 mm Hg systolic and 10 mm Hg dias- as preload increases, myocardial performance
tolic. Increases in pulmonary vascular resist- and cardiac output likewise increase. When
ance (PVR), such as may occur with pulmonary pulmonary wedge pressure exceeds 18 to
emboli or severe hypoxemia or acidemia, are 20 mm Hg, however, the left ventricle is unable
reflected by an increase in PAP. Pulmonary to handle the increased filling pressure, and
vascular resistance may also increase with left-sided heart failure ensues.399
positive end-expiratory pressure (PEEP) ther- At this point, therapeutic measures must
apy. Left-sided heart failure also increases be undertaken to reduce the pressure. Therapy in
the PAP. CHF typically includes digitalis to improve the
force of ventricular contraction and furosemide
Pulmonary Wedge Pressure (Lasix) to reduce the filling pressure of the heart.
Technique. Insertion of a Swan-Ganz catheter These measures allow the heart to function more
also allows for measurement of the pulmonary effectively and thereby reduce the buildup of
wedge pressure (PWP). PWP is the pressure pulmonary edema.
obtained when the balloon on the catheter is Thus, PWP serves as an excellent means to
inflated and forward blood flow cannot pro- monitor left-sided heart function or failure. It
ceed past the catheter tip. Therefore, the pres- has been shown that PWP is a more accurate
sure being measured is actually a measure of indicator of left-sided heart failure than is
backpressure from the left side of the heart. In CVP.399
most clinical situations, PWP closely parallels
the left ventricular end-diastolic filling pressure Pulmonary Artery Catheter and
(LVEDP), which is very informative regarding Differential Diagnosis
function of the left side of the heart. Normal When the Swan-Ganz catheter is properly
PWP is approximately 5 to 12 mm Hg.397,398 positioned, both CVP readings and PWP read-
Increased Pulmonary Wedge Pressure. The ings can be obtained through different ports in
concept of preload refers to the filling volume the catheter. The availability of both measure-
within the ventricles of the heart before con- ments allows for further clarification of the car-
traction. Clinically, the pressure within the diovascular status. For example, cardiogenic
ventricles (rather than the volume) before con- shock can be differentiated from hypovolemic
traction is used as an indicator of preload. shock. Shock of cardiac origin is associated
Pressure is used because it is easier to measure with an increased PWP, whereas hypovolemic
than volume and because normally there is a shock shows a relatively normal PWP and a
good relationship between preload pressure low CVP.
and volume. The CVP is an indicator of right Various different hemodynamic values either
ventricular preload, whereas the PWP is an can be directly measured or can be calculated
index of left ventricular preload. with a pulmonary artery catheter in place.
In contrast to preload, the concept of after- Table 11-3 gives normal ranges for various
load refers to the resistance or impedance that hemodynamic measurements and calculations.
the heart must pump against. Diastolic blood Table 11-4 lists typical hemodynamic and
pressure and vascular resistance contribute to metabolic findings observed in various types
the afterload. High pulmonary vascular resist- of shock.
ance contributes to a high afterload for the The PWP is especially useful in differentiating
right side of the heart. Similarly, arterial hyper- cardiogenic from noncardiogenic pulmonary
tension suggests increased afterload for the left edema. Cardiogenic pulmonary edema is asso-
side of the heart. High afterload contributes to ciated with an increased PWP. Figure 11-11
increased heart work. (The pulmonary artery illustrates the various hemodynamic changes
catheter, however, is used primarily to evaluate associated with cardiogenic shock and
preload.) CHF. Conversely, if the pulmonary edema is
Table 11-3. NORMAL RANGES OF why PWP readings cannot be obtained (e.g.,
HEMODYNAMIC VALUES cannot get catheter to wedge), diastolic pul-
Pressures Normal Range monary artery pressure readings could be sub-
Central venous pressure 210 mm Hg stituted in the patient with normal pulmonary
(CVP) status. On the other hand, the presence of
Right ventricle increased pulmonary vascular resistance is
Systolic 1530 mm Hg characterized by an increased PAP with no
Diastolic 05 mm Hg increase in PWP. This could be the result of a
Pulmonary artery
pulmonary embolus or of pulmonary vasocon-
Systolic 1530 mm Hg
striction secondary to severe hypoxemia or
Diastolic 512 mm Hg
Mean 1118 mm Hg acidemia.
Pulmonary wedge 512 mm Hg
Cardiac Output/Pv O2
Hemodynamics
Cardiac output 4.48.9 L /min Catheters equipped with thermistors (tempera-
Cardiac index 3.5 0.7 L /min/m3 ture sensors) near their tips permit easy determi-
Stroke volume 60129 mL /beat nation of cardiac output via the thermodilution
Stroke volume index 46 3/beat/m3 technique. Furthermore, mixed venous blood
Pulmonary vascular 70 20 dyn/sec/cm-5 gas samples can be acquired through these
resistance catheters. Mixed venous gases can provide still
Arteriovenous O2 4.0 0.6 mL /100 mL more information regarding the status of tissue
difference oxygenation.
Modified from Cherniak, R.M., and Cherniak, L.: Some pulmonary artery catheters can also
Respiration in Health and Disease, 3rd ed. Philadelphia, measure mixed venous oxygen saturation con-
W. B. Saunders, 1983, p. 59. tinuously; others are equipped with cardiac
pacemakers. The use of pulmonary artery
catheters in the critical care setting remains
noncardiogenic (e.g., acute respiratory distress somewhat controversial due to the lack of data
syndrome [ARDS]), then the PWP is relatively on mortality and complications. Nevertheless,
normal. Characteristics of these two entities most believe the development of pulmonary
are compared in Table 11-5. artery catheters has been a valuable break-
through in critical care medicine.
Pulmonary Artery Diastolic Pressure
It is noteworthy that the pulmonary artery Left Atrial Pressure
diastolic pressure is close to the PWP in the In some institutions, a catheter may be placed
absence of pulmonary disease (i.e., normal directly into the left atrium to monitor left ven-
PVR). Thus, if there is some technical reason tricular function. Normal values for left atrial
Table 11-4. HEMODYNAMIC AND METABOLIC DIFFERENCES IN VARIOUS TYPES OF SHOCK

Arterial Response Aterial
Blood Pulse PWP/ Cardiac Urine to Volume Blood
Type of Shock Pressure Rate CVP Index Flow Load PaO2 C (a v )O2 Lactate
Hypovolemic
Cardiogenic or
Neurogenic
Septic
(hyperdynamic)
= decreased.
= increased.
From Sabiston, D.C., Jr.: Davis-Christopher Textbook of Surgery, 11th ed. Philadelphia, W. B. Saunders, 1977, p. 73.
PAP PWP
RAP
CO
CVP
Figure 11-11. Hemodynamic changes associated with congestive heart failure and pulmonary edema.
CVP, central venous pressure; RAP, right atrial pressure; PAP, pulmonary artery pressure; PWP, pulmonary
artery wedge pressure; CO, cardiac output.
pressure are essentially the same as for PWP. Optimization of Venous Return
Obviously, this is a more direct measurement Venous return is most readily manipulated via
and may be more accurate; however, it is unclear intravenous infusions or alteration of body
whether this degree of precision is really neces- position. Venous return should be enhanced in
sary. Certainly Swan-Ganz catheters are more noncardiogenic shock by elevating the feet and
widely used and accepted. increasing the volume of intravenous therapy.
A fluid challenge of 50 to 200 mL until
Treatment PWP increases by at least 3 mm Hg may be
A detailed discussion of treatment of cardio- a useful approach to the treatment of relative
vascular disorders is beyond the scope of this hypovolemia.10
text. Nevertheless, a brief description of some Conversely, venous return should be
of the fundamentals of treatment of cardio- decreased in the treatment of cardiogenic shock
vascular disorders is appropriate. Two major and heart failure. This can be accomplished by
aspects of treatment are considered: (1) opti- having the patient assume a sitting position
mization of venous return, and (2) drug inter- and by positive pressure breathing, adminis-
vention. tration of diuretics, and/or fluid restriction.
Table 11-5. CATEGORIES OF PULMONARY EDEMA

Feature Cardiogenic Noncardiogenic
Major etiologies Left ventricular failure, Mitral stenosis ARDS

Pulmonary wedge pressure Increased Normal
Pulmonary capillary permeability Normal Increased
Protein content of edema fluid Low High
ARDS = acute respiratory distress syndrome.

From Weinberger, S.E.: Principles of Pulmonary Medicine. Philadelphia, W. B. Saunders, 1986, p. 301.
Precise regulation of fluids may require inser- Mortality

tion of a pulmonary artery catheter. Elevated blood lactate concentration (hyper-
lactatemia) is most often the result of tissue
Drug Intervention hypoxia. In addition, the severity of hyper-
In a very simplistic approach, cardiovascular lactatemia correlates with mortality in lactic
drugs generally affect one of the following: acidosis and shock and, as such, is a useful
heart rate (chronotropic effect), arrhythmia prognostic index.401,402 In particular, there is
(abnormal heart beat) control, vascular tone, or a striking increase in mortality as lactate
the force of cardiac contraction (i.e., ejection increases above 2.5 mM/L403; thus, lactate val-
volume). A general pharmacology text or publi- ues greater than this should be clearly consid-
cation should be consulted for a more detailed, ered clinically significant. Furthermore, when
current review. blood lactate concentration increases to a level
greater than 8 mM/L and remains there for
KEY INDICATORS OF HYPOXIA more than 2 hours, mortality increases to
90%.401
Lactate
The cells have a remarkable ability to with- Sensitivity
stand challenges in oxygen supply. Indeed, it Although blood lactate elevation is usually
requires only a PO2 of 1 mm Hg to maintain observed in severe shock, lactate is not a highly
cellular respiration at maximal levels.437 The sensitive indicator of hypoxia.400,404,405 This is
immediate response of the cell to hypoxia is because lactic acid levels do not rise linearly
the onset of anaerobic (without O2) metabo- with progressive hypoxia; rather, they rise
lism. The two major anaerobic pathways are rapidly in the first few minutes of hypoxia,
glycolysis and the creatine kinase reaction. with production falling off as energy stores are
In glycolysis, pyruvate becomes the terminal depleted.406 Blood lactate levels may also be 10
electron acceptor; in the process, pyruvate is times higher inside the cell than in the blood
reduced to lactate and lactic acid accumulates. immediately outside the cell where it is typi-
The excess lactic acid in the blood may serve as cally measured.405 Indeed, in animal models,
an indirect measure of hypoxia. Because lactic lactate doesnt increase until perfusion is
acid is almost completely dissociated at the restored.436 Obviously, lactate may be a late
physiologic pH of the blood, the lactate anion marker of tissue hypoxia.
is measured as an index of lactic acid in the Furthermore, the normal liver takes up excess
blood (blood lactate concentration). At rest, lactate quickly in the presence of normal per-
normal blood lactate concentration is 0.9 to fusion.407 In addition, it is generally assumed
1.9 mM/L.400 In milligram per deciliter units, that the ability of the liver to remove lactate is
normal blood lactate concentration is 8 to several-fold greater than the ability of the
17 mg/dL (conversion factor is 9 mM/L = tissues to produce it.437 Therefore, elevated
mg/dL). In the past, lactate measurements were blood lactate levels are transient unless circu-
of little use because the laboratory turnaround latory failure or liver impairment is also
time was nearly 2 hours. Presently, lactate can present.405
be measured within 90 seconds, which makes Variations in blood lactate measurements
it considerably more useful.459 also may occur related to the site of measure-
Often, a patient with marginal oxygenation ment. Arterial blood is better suited than
status will not have a lactate level on the labo- peripheral venous blood as an indicator of
ratory report but will have an unexplained generalized hypoxia because arterial blood is
metabolic acidosis. The combination of meta- representative of the whole body. Venous
bolic acidosis and marginal oxygenation status, blood sampled from a pulmonary artery
and especially when the cardiac output is in catheter or a central venous catheter (not
question, is highly suggestive of tissue hypoxia peripheral venous blood), however, yields
and lactic acidosis. lactate concentrations essentially equivalent
to those in arterial blood.402 In clinical prac- important to recognize that the presence of
tice, a reasonable expectation is that [HCO3] hydrogen cyanide is also a major concern
should decrease approximately 1 mEq/L for in many cases of smoke inhalation.460,461
every 1 mEq/L of lactate accumulation.436 Residential fires may produce cyanide toxicity,
One mEq/L is equal to one mM/L in univalent which leads to problems with cellular use of
ions. oxygen.
In addition, cyanide toxicity is difficult to
Specificity and the Lactate/Pyruvate Ratio recognize because cyanide disappears relatively
Another major drawback of blood lactate as an quickly from the blood. Diagnosis is further
indicator of hypoxia is its lack of specificity.405 complicated because laboratory measurement
An increase in lactate levels may occur in two of cyanide may take up to 5 hours.460
ways. First, increased lactate is associated with Increased lactate in victims of smoke inhala-
any rise in blood pyruvate (e.g., infusion of pyru- tion and in the absence of high HbCO levels
vate, glucose, or bicarbonate). Second, blood may suggest cyanide toxicity. Indeed, lactate
lactate levels may increase independent of pyru- has been shown to correlate better with cyanide
vate, as in hypoxia, liver disease, or during levels than HbCO levels in some cases. Early
exercise. recognition of cyanide toxicity is important
The lactate/pyruvate (L/P) ratio is useful for because the patient can be treated with mechan-
differentiating lactate elevations that are due to ical ventilation, FIO2 1.0, and nitrites. Nitrites
primary hyperlactatemia (e.g., hypoxia) from facilitate the formation of methemoglobin,
elevations that are simply due to increased which, in turn, rapidly absorbs cyanide.461
metabolism of pyruvate (secondary hyperlac-
tatemia). When the L/P ratio is normal (i.e., Summary
10:1), the elevation in lactate level is due to Based on the complex interrelationships in
secondary hyperlactatemia. anaerobic metabolism, it is not surprising that
An L/P ratio in excess of 10:1 is called clinical studies have often failed to show a good
primary hyperlactatemia or excess lactate. correlation between decreased oxygen trans-
Primary hyperlactatemia is most commonly port or low mixed venous oxygen levels and
the result of hypoxia; however, other causes the onset of increased blood lactate levels.411
have been identified, including liver disease, On new frontiers, magnetic resonance spec-
leukemia, beta-adrenergic drugs,408 and con- troscopy (MRS) is a technique that holds great
genital defects.409 promise for measuring intracellular metabolic
activity and variables such as phosphocreatine
Creatine Kinase Reaction levels and pH.412
In some organs (e.g., heart, brain, muscle), the Although measurement of blood lactate
creatine kinase reaction provides an anaerobic provides us with valuable information regard-
alternative to glycolysis.410 In this reaction, ing hypoxia and prognosis, it is not a suffi-
stored phosphocreatine transfers a high-energy ciently sensitive or specific index of hypoxia
phosphate bond to adenosine diphosphate when used alone.
(ADP), converting it to adenosine triphosphate
(ATP). This anaerobic pathway actually con- Mixed Venous Oxygenation Indices
sumes hydrogen ions, in direct contrast to Measurement
glycolysis, which produces lactic acid. This Mixed venous blood must be distinguished from
metabolic pathway is limited, however, by the peripheral venous blood. Blood gases from
supply of phosphocreatine. peripheral venous blood provide us with limited
information because they reflect only local con-
Cyanide in Smoke Inhalation ditions. Conversely, mixed venous gases provide
The importance of recognition of HbCO in us with a more global picture of oxygena-
smoke inhalation victims has been described tion because mixed venous blood is an average
earlier. In evaluating internal respiration, it is of all venous blood returning to the heart.
Table 11-6. NORMAL MIXED VENOUS

BLOOD VALUES Mixed Venous Oxygen Partial Pressure
PvO2 35 45 mm Hg Mixed venous PO2 and, to a lesser extent, SvO2
SvO2 75% have been advocated as useful indicators of
CvO2 15 vol% hypoxia. The value of mixed venous blood in the
pH 7.38 assessment of hypoxia lies in the fact that it is a
PvCO2 46 48 mm Hg reflection of the interaction of the pulmonary
and cardiovascular systems. The oxygenation
status of arterial blood, on the other hand, is
Unfortunately, mixed venous blood samples primarily a reflection of only the pulmonary
are available only when the patient has a pul- system. Arterial blood provides information
monary artery catheter in place. Furthermore, regarding oxygen supply to the tissues, whereas
the catheter must be in the proper position if mixed venous blood provides information
samples are to truly represent mixed venous regarding the balance of oxygen supply and
blood. Normal values for mixed venous blood demand.
are shown in Table 11-6. Mixed venous PO2 has received consider-
able attention as an index of hypoxia because
Mixed Venous Oxygen Saturation it seems to represent the average end-capillary
The oxygen saturation of mixed venous blood oxygen-driving pressure. It is also well known
(SvO2) can be measured using a single blood that the body attempts to maintain the end-
sample or can be monitored continuously using capillary PO2 in a variety of hypoxic threats,
a fiber-optic catheter. Continuous monitoring of presumably in an attempt to preserve tissue
SvO2 provides a useful way to monitor circula- oxygenation.414 Mixed venous PO2 has been
tory changes, because SvO2 usually decreases purported to be the best single index of tissue
with deterioration of cardiovascular status. In hypoxia,415,416 although other reports dispute
addition, cardiovascular drugs or PEEP therapy this claim.410,417 A major shortcoming of mixed
may be titrated to optimal dosage through venous oxygen values is that venous blood is
continuous SvO2 monitoring.413 In general, an heterogeneous and mixed venous samples
increase in SvO2 is a positive response, whereas depend on the distribution of the cardiac
a decrease is undesirable. Figure 11-12 illus- output.
trates several conditions that may result in a Although it is now clear that mixed venous
decreased SvO2. PO2 is not always a reliable indicator of
Figure 11-12. Causes of decreased

SvO2. Potential sources of decreased SvO2
include increased oxygen consumption Decreasing SvO2 due to:

(VO2), decreased arterial oxygen satura-
VO2 SaO2
tion (SaO2), anemia (decreased Hb), and
decreased cardiac output (CO).
Hb CO
Cell Cell Cell Cell PaO2 55 mm Hg PvO2 30 mm Hg

Cell
Cell Cell Cell Cell Cell Systemic capillary
Figure 11-15. Moderate hypoxemia without an

Cell Cell
Cell Cell Cell increased cardiac output.
PaO2 100 mm Hg PvO2 40 mm Hg
Systemic capillary If we further assume that this cell is just

barely oxygenated at normal PvO2, it follows
Figure 11-13. Normal precapillary and post- that any decrease in PvO2 will prohibit oxy-
capillary PO2.
genation of this cell and thus lead to hypoxia.
If PvO2 continues to fall, more and more cells
are affected and hypoxia increases in severity.
hypoxia or cardiac output,418 it is important to Therefore, as a general guide, hypoxia is prob-
understand why it was initially considered to able when PvO2 is less than 35 mm Hg.415
be the ideal hypoxic index. Whether a given
cell in the body receives sufficient oxygen to Clinical Oxygenation Disturbances and PvO2
meet metabolic requirements depends essen- Hypoxemia
tially on two factors: (1) the driving pressure The body responds to moderate hypoxemia by
propelling oxygen from the capillaries to the increasing cardiac output and thus by main-
cells, and (2) the distance of the cell from the taining PvO2 (Fig. 11-14). Thus, tissue oxygena-
capillary itself. tion (PvO2) is preserved despite the fall in
oxygen content. The increased cardiac output
Driving Pressure allows the blood to traverse the capillary more
Figure 11-13 illustrates the average normal quickly and minimizes the decrease in PO2.
precapillary and post-capillary PO2. As the In patients unable to increase cardiac output,
blood traverses the normal (average) capillary, PvO2 may decrease (Fig. 11-15).
the PaO2 decreases from approximately 100 to
40 mm Hg. The driving pressure that moves Decreased Cardiac Output and Anemia
oxygen from the capillaries to the tissues is the In circulatory shock, PaO2 remains relatively
difference between the capillary PO2 and the normal; however, PvO2 decreases (Fig. 11-16).
cellular PO2. Therefore, the oxygen-driving A similar relationship between PaO2 and PvO2
pressure is lowest at the end of the capillary. is observed in hypoxia due to severe anemia or
carbon monoxide poisoning.
Distance of the Cell from
the Capillary High PvO2 and Hypoxia
Also, the pressure of oxygen (PO2) tends to be In septic shock, hypoxia is not due to the
lowest in those cells that are farthest away oxygen-driving pressure; rather, it is the result of
from the capillary. Thus, in the theoretical shunting of blood past the tissues or of cellu-
model shown in Figure 11-13, the specific cell lar metabolic dysfunction. Thus, PvO2 in this
that would have the lowest PO2 would be the disorder may actually be increased although
cell in the upper right-hand corner. the patient still has hypoxia (Fig. 11-17).
Interestingly, however, short-term instability
Systemic capillary
Systemic capillary
Figure 11-14. Moderate hypoxemia with an
increased cardiac output. Figure 11-16. Circulatory shock.
as a good sign indicating a return of local

vascular control.437 Notwithstanding, clinical
Systemic capillary studies seem to indicate that a mixed venous
PO2 less than 28 mm Hg is associated with a
Figure 11-17. Septic shock. poor prognosis.437
In clinical practice, saturation is most often
monitored because this value can be routinely
may still be recognized in these individuals by monitored with a special Swan-Ganz catheter
acute declines in mixed venous oxygenation in place. Monitoring of SvO2 is especially use-
from baseline.454 ful when trending patients. Abrupt changes
A similar paradoxical increase in PvO2 is certainly suggest a more thorough evaluation
also seen in cyanide poisoning, again because of the cardiopulmonary system.
of the inability of the cell to utilize oxygen.
PvO2 has also been shown to be misleading Oxygen Uptake and Utilization
in various conditions associated with supply- Normal Oxygen Uptake
dependent oxygen consumption to be described Oxygen uptake by the tissues normally remains
in the following section. relatively constant despite variations in O2 trans-
port (O2 delivery), because oxygen transport
Clinical Application usually far exceeds tissue O2 requirements. If
In summary, the theory behind changes in O2 transport decreases substantially, however,
mixed venous oxygenation is very useful to a critical point is eventually reached at which
understand. Changes in mixed venous oxygen O2 transport is insufficient to meet tissue
saturation should essentially parallel changes demands. Below this critical oxygen delivery
in mixed venous PO2. Nevertheless, changes in point, hypoxia develops and the accumulation
mixed venous oxygenation must always be of lactic acid is likely. This is called physiologic
treated with some degree of suspicion since it is oxygen supply dependency and can be demon-
a composite measurement from all organs and strated in all people.
tissues. Indeed, some have speculated that a The critical O2 delivery point has been shown
decline in mixed venous PO2 may be interpreted to be about 8 to 10 mL/kg/min in critically

A 43-year-old female patient with severe cardiogenic ASSESSMENT

pulmonary edema is being mechanically ventilated with Abnormalities: List abnormal data and other noteworthy
10 cm H2O PEEP. Despite being on FIO2 0.70, her PaO2 is information. Classify ABG.
only 65 mm Hg and her mixed venous PO2 is 35 mm Hg. Explanation: List possible diseases, pathology, or other
The PEEP is increased to 15 cm H2O and arterial and situations that may have led to this patients condition.
mixed venous blood gases are drawn 30 minutes later. Evaluation: Suggest additional data that would be useful in
BLOOD GASES
pH 7.36 Importance: Prioritize concern(s) of treatment in order
PaCO2 38 mm Hg of urgency and/or seriousness as you see the overall
PaO2 74 mm Hg situation.
[HCO3] 22 mEq/L Objective: Specifically state the measurable or observ-
FIO2 0.70 able outcomes you would like treatment to accomplish.
PvO2 27 mm Hg Action: Describe your specific plan of action.
ill patients.419,420 In a normal 70-kg individual, O2 transport increases even beyond normal
this would correspond to an O2 transport of levels. The presumed reason for this deviation
approximately 550 to 700 mL O2/min. When O2 from the norm is that there is some form of O2
transport falls below this level, tissue hypoxia debt present in these individuals428 and that
should be assumed. It has been shown that when even with normal O2 transport, they may be
oxygen transport falls below 8 mL/kg/min, hypoxic. This covert (or occult) hypoxia pre-
blood lactate greatly increases and survival is sumably is due to a derangement in internal
poor.420 Oxygen transport may indeed be one respiration. The term covert hypoxia should be
of the most sensitive indicators of hypoxia at used with great caution, however, because the
our disposal, although further study of this reason for this increased O2 consumption is
notion is necessary. unclearit could be due simply to an aberra-
Thus, maintenance of O2 transport in excess tion in metabolism. Nevertheless, it could also
of the critical delivery point is crucial in the represent a need for life-sustaining O2.
management of critically ill patients. This is Figure 11-18 depicts graphically the normal
particularly true when PEEP is being used relationship between O2 transport and uptake
because PEEP may be associated with a fall in (see Fig. 11-18, solid line). The normal critical
O2 transport despite improvement in PaO2. O2 delivery point (see Fig. 11-18, solid circle) is
The clinician should also be aware of those approximately 8 mL/kg/min. Note that, nor-
conditions that may increase O2 consumption mally, higher levels of O2 transport have no
and elevate the critical oxygen delivery point. effect on O2 uptake. In so-called covert hypoxia,
These conditions include shivering, convulsions, there continues to be increased O2 uptake with
sepsis, and fever. A higher minimum level of progressive increases in O2 transport.
O2 delivery is indicated in these circumstances. The exact mechanism responsible for covert
hypoxia is not known. It has been postulated
Normal Supply-Independent Oxygen Uptake that the hypoxia and lactic acidosis associated
As described in the previous section, attain- with septic shock are due to some derangement
ment of O2 transport levels markedly higher of O2 use in the cell.429 Some studies, however,
than the critical delivery point is probably not
necessary because this does not lead to greater
oxygen use. Thus, maintenance of normal O2
transport is probably not an appropriate or
necessary clinical goal.
Another way of describing the relationship
O2 uptake
between O2 transport and uptake is to say that

above the critical O2 delivery point, there is a
plateau in O2 uptake. Above the critical point,
O2 uptake is independent of O2 transport. The
tissues apparently have no need for an addi-
tional supply of O2.
5 10 15 20 25 30
Covert Hypoxia O2 transport (ml/kg)
It has been observed that O2 uptake may Critical O2 delivery point Normal O2 transport
increase with O2 transport in some individuals Covert hypoxia
with septic shock,421 ARDS,422 acute liver fail-
Figure 11-18. Covert hypoxia. In normal humans,
ure,423 congestive heart failure,424 COPD,425
oxygen consumption decreases when oxygen deliv-
increased pulmonary vascular resistance,426 and ery falls below the critical point. However, increases
respiratory failure in general.427 This phenome- in oxygen delivery above the critical O2 delivery
non has also been described as pathological point do not ordinarily increase oxygen uptake.
oxygen supply dependency. In covert hypoxia, progressive increases in oxygen
In other words, O2 uptake does not plateau delivery result in progressive increases in oxygen
as in normal individuals; rather, it increases as uptake.
suggest that a decline in nutrient blood flow have shown that the phenomenon is due to
rather than cellular dysfunction is the predomi- some artifact. The apparent increase in oxygen
nant mechanism.421,429 Microemboli and release consumption may be due to a drug effect (i.e.,
of various vasoactive substances have been prostacyclin), temperature variances,450 or, as
shown in supply-dependent oxygen uptake and many believe, it is simply a mathematical error
could explain the mechanism responsible for due to the method of calculation.451,452
the circulatory disturbance and the so-called
covert hypoxia. Multiple Organ Dysfunction Syndrome
The same pathologic entities that manifest sup-
Vasodilator Effects ply-dependent O2 uptake (septic shock, ARDS,
Prostacyclin is a potent vasodilator that also COPD) are often associated with the disorder
tends to increase O2 transport and prevent known as multiple organ dysfunction syn-
formation of microemboli in the systemic drome (MODS). This phenomenon is often
capillaries.428 Administration of prostacyclin observed in critically ill patients in whom sev-
to critically ill patients may help to identify eral organ systems fail (e.g., respiratory, renal,
individuals with covert hypoxia, because these hepatic, circulatory, central nervous system).
patients show an increase in O2 uptake after Multiple organ failure is the most common
the administration of this drug.428 Administra- cause of death in patients with ARDS.
tion of dobutamine has been associated with It is unclear whether multiple organ dys-
similar effects.430 function syndrome is caused by hypoxia or by
some other mechanism. Although earlier the
Prognosis presence of hypoxia was considered to be
Patients whose O2 uptake increases in response unlikely, the discovery of covert hypoxia sug-
to increased O2 transport and tissue perfusion gests that hypoxia may indeed be present in
are more likely to die.428 Use of prostacyclin or these individuals and may be responsible to a
a similar drug may therefore help the clinician great extent for the deterioration often
to recognize the presence of covert hypoxia and observed.431 In particular, death from septic
to provide a prognostic indicator. Perhaps in shock seems to be related more to persistent
the future this drug or a similar vasodilator will peripheral vascular changes than to cardiac
prove to be beneficial in the management of output problems.432
covert hypoxia.
Recognition of supply-dependent O2 uptake Summary
may be important in the approach to manage- Studies have shown a poor correlation between
ment of the critically ill. First, the notion that PvO2 and other measures of hypoxia such as
tissue oxygenation is always acceptable when lactic acid and oxygen consumption.433
O2 transport is in the acceptable range must be Despite its theoretical attractiveness, PvO2 has
re-evaluated. Some patients may benefit from not proved to be the perfect index of hypoxia.
further increases in O2 transport beyond nor- As stated previously, there is no perfect index
mal. In addition, understanding that the con- of hypoxia.
dition of an individual with covert hypoxia is Notwithstanding, PvO2 and lactate are use-
probably in a downward spiral suggests that ful variables to follow in the critically ill
aggressive attempts to maintain oxygenation patient with potential hypoxia. Changes in
may be warranted. PvO2 provide valuable information regarding
changes in the patients cardiovascular status
Pathological Supply Dependency and are particularly useful in understanding
Controversy concurrent changes in PaO2.410 From a practi-
This concept of pathological supply depend- cal standpoint, venous oxygenation values are
ency is very controversial. Some studies have relatively sensitive indicators of the oxygenation
demonstrated very beneficial positive out- disturbances that accompany routine bedside
comes by increasing oxygen transport in these procedures such as endotracheal suctioning434
patients,448,449 whereas other investigators451,452 and positioning of the patient.435

A patient with sepsis and ARDS is in the critical ASSESSMENT

care unit. Abnormalities: List abnormal data and other noteworthy
BLOOD GASES
pH 7.25
PaO2 68 mm Hg Importance: Prioritize concern(s) of treatment in order of
[HCO3] 16 mEq/L urgency and/or seriousness as you see the overall situation.
FIO2 0.60 Objective: Specifically state the measurable or observ-
PvO2 47 mm Hg able outcomes you would like treatment to accomplish.
Lactate 9 mEq/L
Gastric Tonometry Measuring gut pH is also useful as poor per-

Gastric tonometry is a relatively new technique fusion of the gut may causes life-threatening
for evaluating tissue oxygenation and hypoxia. stress bleeding and release of toxins into the
It is well known that when the body has a lim- bloodstream. Gastric tonometry has been shown
ited supply of oxygen, blood will be distrib- to be a sensitive and reproducible method for
uted to the vital organs (e.g., heart, brain, evaluation of blood flow to the gut.456,457
kidneys) at the expense of the gastrointestinal Gastric pH has also been shown to correlate
tract and less vulnerable organs. Therefore, the with mortality in critically ill patients.458 Despite
gut should be one of the first organs to be these promising results, further studies are
affected by a hypoxic crisis.455 Furthermore, needed to demonstrate its safety and value.
the unique microvasculature of the gut make it
especially sensitive to local hypoxia.459 Vital Organ Function
Tonometry is a technique that makes use of In the face of hypoxic threats, the body tries to
the principle that fluid or air in contact with maintain oxygenation of the vital organs such as
tissue can be used to estimate conditions within the brain and the heart. It follows that if com-
the tissue. With gastric tonometry, air or fluid, pensatory mechanisms are effective, normal
within a special nasogastric tube is equilibrated organ function is preserved. Therefore, the mon-
with the gastric mucosa. Following equilibra- itoring of vital organ function is another useful
tion, the PCO2 is measured from this air or fluid. tool in oxygenation assessment. Unfortunately,
The [HCO3] from a concurrent arterial blood organ failure may occur rather abruptly and
gas is then used to calculate the local tissue without warning. Thus, we finish where we
pH.459 The technique is also of interest since it is began, in the realization that there is no single,
essentially a noninvasive measure of tissue simple, accurate index of the adequacy of tissue
oxygen status. oxygenation.
EXERCISES
Exercise 11-1 Hypoxic Assessment

1. State the three main components (ABCs) to be evaluated in oxygen supply assessment.
2. The ultimate goal in the management of oxygenation is the prevention of
(hypoxemia /hypoxia).
3. There (is/is not) a simple, single index of hypoxia.
4. The best place to begin in hypoxic assessment is ____________ ___________.
5. PaO2 less than 45 mm Hg is (usually/always) associated with hypoxia.
6. PaO2 (is/is not) a highly stable measurement in critically ill patients.
7. In general, PaO2 should be maintained above ______ mm Hg in most clinical situations.
8. Normal PaO2 (ensures/does not ensure) adequate tissue oxygenation.
9. Judgment and short-term memory are usually impaired in normal individuals when PaO2
falls below ______ mm Hg.
10. In moderate hypoxemia, the development of hypoxia depends mainly on the integrity
of the ______.
Exercise 11-2 SaO2

1. Calculated SaO2 (is /is not) an accurate, reliable way to measure SaO2.
2. Oximeters that use two wavelengths to measure SaO2 (do/do not) measure the quantity of
MetHb present.
3. SaO2 determined by two-wavelength oximetry measures (fractional/functional) saturation.
4. The concentration of HbCO (is/is not) directly measured with functional saturation.
5. The CO-oximeter measures (functional/fractional) SaO2.
6. All forms of Hb are included in the calculation of total Hb in the measurement of
(fractional/functional) SaO2.
7. Pulse oximeters measure (functional/fractional) SaO2.
8. Pulse oximeters are most useful for (trending of/accurate measure of ) SaO2.
9. SaO2 measurements by two-wavelength oximetry and by CO-oximetry (are/are not) always
identical.
10. Pulse oximeters use (two-/four-) wavelength oximetry.
Exercise 11-3 Laboratory Diagnosis of Anemia

1. State the normal [RBC] and [Hb] in the blood.

2. A reduction in the number of circulating RBCs or [Hb] is called ______.
3. The percentage of formed elements in the blood is called ______.
4. When there are abnormal variations in cell size, ______ is said to be present.
5. The presence of many cells larger than 10 m in diameter is called ______.
6. Cell size is indicated by the (MCHC /MCV ).
7. Abnormality in the shapes of RBCs is called ______.
8. Normally, there are 1.0% to 1.5% immature RBCs present in the blood, which are
called ______.
9. Normal MCHC is ______%.
10. Iron deficiency anemia is typically associated with (hyperchromia /normochromia /
hypochromia).
Exercise 11-4 Types of Anemia and Treatment

1. Inability of the bone marrow to produce RBCs secondary to exposure to some chemical or
physical agent is called ______ anemia.
2. Chronic blood loss may lead to a form of anemia associated with microcytosis and
hypochromia that is called ______ anemia.
3. A genetic disorder that may hamper Hb production and lead to anemia is called ______.
4. State the three substances besides Fe needed for normal RBC production.
5. Individuals unable to absorb vitamin B12 owing to the absence of intrinsic factor may have
______ anemia.
6. The presence of megaloblasts and macrocytosis is common in (Cooleys anemia /folic acid
deficiency).
7. The major compensatory mechanism in acute anemia is ______, whereas the major
compensatory mechanism in chronic anemia is ______.
8. The optimal Hct may be anywhere from _____% to ____%.
9. Snake venoms may lead to ______ anemia.
10. Mediterranean disease is another name for ______.
Exercise 11-5 Cardiovascular System/Shock

1. The volume of blood ejected from the left side of the heart each minute is called
the ______.
2. The symbol for cardiac minute output is ______.
3. When cardiac output is adjusted for body size by dividing it by body surface area, the
resultant value is called the ______.
4. State two methods that can be used to measure cardiac output invasively.
5. There (is/is not) a technique to measure cardiac output noninvasively.
6. List at least five ways in which cardiac output can be assessed indirectly.
7. List the three basic components of the cardiovascular system.
8. Collapse of the cardiovascular system associated with a decrease in blood pressure is
called ______.
9. In shock, stimulation of the sympathetic nervous system leads to (vasodilation/
vasoconstriction).
10. List at least five signs and symptoms that are associated with shock.
Exercise 11-6 Types of Shock

1. Write the formula for cardiac output.

2. Cardiac output generally (increases/decreases) with slight decrease in heart rate.
3. Cardiac output generally (increases/decreases) with a slight increase in heart rate and
(increases/decreases) with extreme increases in heart rate.
4. Cardiovascular collapse due to failure of the heart as a pump is called ______ shock.
5. A decrease in blood volume is called ______.
6. A useful indicator of hypovolemia is a (low/high) CVP.
7. Jugular vein distention, hypoxemia, fine crackles in the lungs, and abnormal heart sounds
are found in the cardiovascular problem known as ______.
8. Cardiovascular collapse secondary to inadequate blood volume is called ______ shock.
9. In ______shock, cardiac output is usually high and profound vasodilation and blood
infection are present.
10. Shock secondary to a profound allergic reaction and vasodilation is called ______ shock.
Exercise 11-7 Hemodynamic Monitoring

1. Central venous pressure (CVP) is measured in the ______.

2. Normal CVP is ______ mm Hg.
3. A high CVP suggests (heart failure/hypovolemia).
4. The balloon-tipped, multilumen catheter that is inserted into the pulmonary artery for
hemodynamic monitoring is called the ______.
5. Normal PAP is ______ mm Hg.
6. PWP is normally about ______ mm Hg.
7. A PWP of 25 mm Hg suggests (left-sided heart failure /pulmonary emboli).
8. Pulmonary edema associated with a PWP of 10 mm Hg is consistent with the diagnosis of
(congestive heart failure/ARDS).
9. In the patient with normal pulmonary vascular resistance, a reasonable substitute for the
PWP, when there is a technical problem in trying to get the catheter to wedge, is the
(diastolic/systolic) PAP.
Exercise 11-8 Cardiovascular Treatment

1. In the presence of left-sided heart failure and acute pulmonary edema, the patient usually
benefits from assumption of the (feet-up/sitting) position.
2. In the presence of blood loss and shock, the patient usually benefits by assumption of the
(feet-up/sitting) position.
3. Positive pressure breathing is usually (beneficial/detrimental) in hypovolemic shock; it is
usually (beneficial/detrimental) in cardiogenic shock.
4. A drug that increases heart rate is said to have a positive (chronotropic/inotropic) effect.
Exercise 11-9 Blood Lactate

1. Anaerobic metabolism leads to an excess of ______ acid.

2. The ______ anion is measured as a reflection of lactic acid levels.
3. Normal blood lactate in mM/L is ______.
4. Blood lactate concentration in mg/dL is approximately ______ times higher than lactate
concentration in mM/L.
5. Hyperlactatemia (correlates/does not correlate) with mortality.
6. Normally, the (kidney/liver) takes up lactate from the blood (slowly/quickly).

7. Blood lactate (is/is not) a sensitive indicator of hypoxia.
8. The normal blood lactate/pyruvate ratio is ______.
9. In hypoxia, the blood lactate/pyruvate ratio is (normal/increased/decreased).
10. Blood lactate (is/is not) a highly specific indicator of hypoxia.
Exercise 11-10 Mixed Venous Oxygenation Indices

1. Mixed venous blood can be obtained only when a ______ is in place.

2. Normal SvO2 is ______%.
3. A fiber-optic catheter can be used to measure (SvO2/PvO2).
4. As a general guide, hypoxia is likely when PvO2 is less than ______ mm Hg.
5. SvO2 and PvO2 are affected by (pulmonary changes only/cardiovascular changes only/both
pulmonary and cardiovascular changes).
6. A PaO2 of 55 mm Hg and a PvO2 of 40 mm Hg are indicative of (increased/decreased)
cardiac output.
7. A PaO2 of 95 mm Hg and a PvO2 of 25 mm Hg are indicative of (decreased/increased)
cardiac output.
8. Severe anemia or carboxyhemoglobinemia results in a relatively (low/high/normal) PaO2
and a (low/high/normal) PvO2.
9. PvO2 levels may be surprisingly (high/low) in septic shock.
10. Low levels of PvO2 (usually/always) indicate hypoxia.
Exercise 11-11 Oxygen Uptake/Utilization

1. In healthy individuals, a slight increase or decrease in O2 transport (is/is not) associated

with a similar change in O2 consumption.
2. The point at which O2 transport is inadequate to meet tissue O2 demands is called
the ______.
3. The critical oxygen delivery point in critically ill patients is about ______ mL /kg /min.
4. Maintenance of normal values of O2 transport in critically ill patients is usually
(necessary/unnecessary).
5. In septic shock, ARDS, and acute liver failure, it has been shown that O2 uptake (is always
constant /may be increased) when O2 transport increases even beyond normal levels.
6. The presence of hypoxia despite apparently normal O2 transport is called ______ hypoxia.
7. Patients who display covert hypoxia have a (good/poor) prognosis.
8. Covert hypoxia may be responsible for a common cause of death in ARDS due to ______.
9. A potent vasodilator that may be useful in demonstrating covert hypoxia is ______.
10. In normal persons, O2 uptake is (increased/unchanged) with an increase in O2 transport
beyond normal; in individuals with septic shock, O2 uptake (may be increased/
is unchanged) with an increase in O2 transport beyond normal.
11. The apparent (physiologic/pathologic) oxygen supply dependency may simply be due to
a mathematical error.

1. Go to internet site: http://www.mtsinai.org/pulmonary/books/physiology/chap6_1.htm.
A. List 3 to 5 clues suggesting tissue hypoxia.
B. Determine which patient has the lowest CaO2 in clinical problem 2.
NBRC Challenge 11
1. Given the following, which diagnosis is D) Septic shock

most likely? E) Anaphylactic shock
CVP = 1 mm Hg PWP = 5 mm Hg (RRT EXAMINATION NBRC MATRIX
BP = 90/P I,B,10,e)
A) Cardiogenic shock
4. A patient with left heart failure is admitted
B) ARDS
to the critical care unit on FIO2 0.60 via
C) Hypovolemic shock
face mask. The patient should be placed
D) Left heart failure
in the _______________ position.
E) Mitral valve failure
A) sitting
(RRT EXAMINATION NBRC MATRIX
B) Trendelenburg
I,B,9,e)
C) prone
2. Which of the following techniques or D) supine
measurements might assist in determin- E) reverse Trendelenburg
ing if a patient has tissue hypoxia? (RRT EXAMINATION NBRC MATRIX
A) Blood pyruvate III,B,1,d)
B) Tensilon test
5. An abrupt decrease in cardiac output
C) Gastric tonometry
might be identified by evaluating:
D) Blood chloride levels
I. SpO2.
E) Serum magnesium
II. [Hb].
III. C(av)O2.
I,A,1,i)
IV. SvO2.
3. Given the following, which diagnosis is A) I and II only
most likely?: B) I and III only
CVP = 15 mm Hg PWP = 25 mm Hg C) I and IV only
BP = 90/P D) II and IV only
A) Cardiogenic shock E) III and IV only
B) ARDS (CRT EXAMINATION NBRC MATRIX
C) Hypovolemic shock III,D,2)
V
UNIT
Clinical Acid Base
305
Chapter
12
Regulation of Acids, Bases, and Electrolytes
Regulation of Volatile Acid (Ventilation)

One might guess that respiration would increase whenever cells of the body use more O2 and form more CO2
and would decrease whenever they need less O2 and form less CO2. This, indeed, is the case.
Julius H. Comroe81
Regulation of Fixed Acids, Bases, and Electrolytes

It cannot be stated too often that neither the water, nor the electrolytes, nor the acid-base balance may be
studied individually because of the strong interaction between them.
Gosta Rooth462
Outline
Overview, 307 Sodium Regulation in the Kidney, 317
Regulation of Ventilation, 308 Chemical Mechanisms, 317
Chemoreceptors, 308 NaCl Mechanism, 317
Central Chemoreceptors, 308 NaHCO3 Mechanism, 318
Peripheral Chemoreceptors, 309 Renin-Angiotensin System, 319
Chemoreceptor Interactions, 310 Total Sodium Reabsorption, 320
Reflexes, 312 Regulation of [HCO3], 321
Hering-Breuer Reflex, 312 Diuretics, 321
J Receptors, 312 Interference with NaCl Reabsorption, 321
Renal Function, 313 Interference with NaHCO3 Reabsorption, 321
Macroscopic Anatomy and Hyperaldosteronism, 321
Physiology, 313 Secondary Hyperaldosteronism, 321
Microscopic Anatomy and Physiology, 313 Primary Hyperaldosteronism, 322
Urine Formation, 314 Urinary Buffers and H+ Excretion, 322
Glomerular Filtration, 314 Ammonia, 322
Tubular Reabsorption, 314 Phosphate, 323
Tubular Secretion, 314 Plasma pH and [K+], 323
Body Fluids and Electrolytes, 314 Law of Electroneutrality, 324
Fluid Compartments, 314 Principle of Electroneutrality, 324
Electrolytes, 315 Hypochloremic Metabolic Alkalosis, 324
Electrolyte Distribution, 315 Anion Gap, 324
Plasma Electrolytes, 316 Hyperchloremic Metabolic Acidosis, 325
Major Plasma Cations, 316 High Anion Gap Acidosis, 325
Sodium, 316 Summary, 325
Potassium, 316 Hypoalbuminemia and the Anion Gap, 326
Calcium, 317 Stewarts Strong Ion Difference, 326
Magnesium, 317 Exercises, 327
OVERVIEW
regulate ventilation in health and disease are
The prominent roles of the lungs and the reviewed.
kidneys in acid-base homeostasis were des- This is followed by a review of kidney
cribed in Chapter 8. In this chapter, we take a (renal) function. Processes used by the kidneys
more in-depth look at precisely how the lungs to excrete wastes and to maintain fluid and
and the kidneys perform these functions. electrolyte balance are examined. In particular,
Regarding the regulation of volatile acid, sodium regulation and its effect on blood bicar-
some of the major factors that control and bonate are explored.
307
308 Unit V Clinical Acid Base
The effects of certain therapeutic interven- Reflexes and chemoreceptors serve to meas-
tions, such as diuretics and steroids, are also ure the output of the system and provide feed-
considered. In addition, the value of the serum back loops back to the medulla. As such,
electrolyte profile in evaluating acid-base distur- reflexes and chemoreceptors play a vital role in
bances is discussed. the regulation of ventilation. Although a detailed
analysis of all the factors that mediate ventila-
tion is beyond the scope of this text, a basic
REGULATION OF VENTILATION
review of the chemoreceptors and a few promi-
As described earlier, the volume of carbon nent reflexes is important to understand arterial
dioxide (and, therefore, volatile acid) excretion blood gas application.
varies directly with the quantity of alveolar ven-
tilation. The amount of alveolar ventilation, in Chemoreceptors
turn, depends on the mechanisms responsible for The chemoreceptors are probably the single
the control and regulation of ventilation. Thus, most important mechanism by which ventilation
a brief review of the major factors that regulate is regulated. Two basic groups of chemo-
ventilation in health and disease is in order. receptors influence ventilation: (1) the central
The control of ventilation is a complex chemoreceptors, located within the central nerv-
physiologic process. The major factors that ous system; and (2) the peripheral chemorecep-
play a role in the regulation of ventilation are tors, located within the cardiovascular system.
shown in Figure 12-1. The primary respiratory
center (generator) is located in the medulla of Central Chemoreceptors
the brain (medullary center). Output of the Location and Response
medullary center is influenced by several other The central chemoreceptors are chemosensitive
centers in the brain that affect respiration. The areas located on the medulla of the brain. These
apneustic and pneumotaxic centers in the pons chemoreceptors in the medulla should not be
tend to modify the ventilatory pattern, and the confused with the medullary respiratory center,
cerebral cortex may participate in voluntary because they are distinctly separate entities. The
input into the system. chemoreceptors are bathed in cerebrospinal fluid
Higher centers in CNS

(cerebral cortex, pons)
Respiratory generator
(medulla)
Receptor reflexes
(pulmonary, chest Inspiratory muscles
wall, airway)
Chemoreceptors
Expansion of chest wall;

inspiratory airflow into lungs
PCO2
PO2
Gas exchange
Figure 12-1. Regulation of ventilation. Organization of the respiratory control system. The dashed lines
show feedback loops affecting the respiratory generator.
Chapter 12 Regulation of Acids, Bases, and Electrolytes 309
(CSF) and respond directly to the pH of the the time when the alveolar PCO2 changes until
cerebrospinal fluid. When the hydrogen ion this change is reflected in the CSF. This time
concentration of the CSF increases (i.e., pH delay explains why the ventilatory response
decreases), an increase in ventilation is triggered. to increased or decreased alveolar PCO2,
Conversely, when the pH of the CSF increases, although highly sensitive, is not instantaneous.
the ventilatory drive and the volume of ventila- Furthermore, if circulation is impaired, such as
tion are diminished. The central chemoreceptors in congestive heart failure, this delay may be
do not respond to oxygen levels in the blood. exaggerated because it takes longer for blood
from the lungs to reach the medulla. In theory,
Blood-Brain Barrier this circulatory delay may explain the Cheyne-
The CSF is separated from the blood by the Stokes breathing that is sometimes observed in
blood-brain barrier, which is readily permeable congestive heart failure.
to gases but relatively impermeable to ions. Cheyne-Stokes breathing is a recurrent pat-
Gases equilibrate quickly across the blood-brain tern of ventilation characterized by a progressive
barrier. Some ions, such as bicarbonate, may rise and fall of tidal volume (Fig. 12-2). A period
tend to equilibrate across the barrier, but the of apnea may sometimes occur between cycles.
exchange process is active transport rather than The related alveolar and central chemoreceptor
simple diffusion. The active transport of ions PCO2 levels at different points in the breathing
across the blood-brain barrier may take a con- cycle are also shown in Figure 12-2.
siderable time (i.e., hours to days)81 compared
with the immediate diffusion of gases. Peripheral Chemoreceptors
Thus, when the PaCO2 increases, PCO2 in Location
the CSF immediately follows suit. This, in turn, The second group of chemosensitive cells
lowers the pH of the CSF, and the ventilatory (chemoreceptors) that affects ventilation is
drive is augmented within minutes. In meta- located adjacent to the walls of certain arterial
bolic acidosis, however, the bicarbonate ion is blood vessels. These peripheral chemorecep-
transported slowly out of the CSF. Therefore, tors are located in two distinct anatomic areas:
it takes longer for the pH of the CSF to decrease, the carotid and aortic bodies.
and consequently the ventilatory response is The carotid bodies are a group of cells located
delayed. near the bifurcation of the common carotid
artery into the internal and external carotid arter-
Cheyne-Stokes Ventilation ies. They appear as small, pink nodules, approx-
It is noteworthy that even with respiratory (i.e., imately 3 to 5 mm in diameter.81 The aortic
PCO2) gas changes, there is some delay from bodies are located within the arch of the aorta.
Hyperpnea
Apnea
Ventilation
Alveolar PCO2
PCO2 at
chemoreceptor
Delay
Time
Figure 12-2. Cheyne-Stokes breathing. Cheyne-Stokes breathing, showing a cyclic pattern of ventilation.
In patients with a prolonged circulation time, the delay between the signal to the central chemoreceptor
(PCO2 at the chemoreceptor) and ventilatory output (reflected by alveolar PCO2) is shown.
The two sets of cells, which are referred to The number of peripheral chemoreceptor
collectively as the peripheral chemoreceptors, impulses sent to the brain to stimulate ventila-
serve to chemically monitor the blood passing by tion in hypoxemia may increase greatly. Initially,
them. To perform this function, the peripheral ventilatory impulses increase only slightly as
chemoreceptors receive a relatively large blood PaO2 falls slightly below the normal range.
flow in proportion to their size. When PaO2 falls below 60 mm Hg, however,
there is a dramatic increase in impulse produc-
Responsiveness tion and ventilation.
Unlike the central chemoreceptors, the periph- Not only do the peripheral chemoreceptors
eral chemoreceptors respond to several differ- greatly stimulate ventilation when PaO2 falls
ent blood gas stimuli: the PaO2, arterial pH, below this critical point; they also stimulate
and PaCO2. In addition, when blood flow past the cardiovascular system. Clinically, this is
the peripheral chemoreceptors is diminished manifested by a rise in heart rate and arterial
(e.g., in shock), an increase in ventilation is blood pressure. Restoration of PaO2 to normal,
also stimulated. The peripheral chemoreceptors however, allows ventilation, heart rate, and
generally do not respond to anemia (e.g., methe- blood pressure to return to normal levels.
moglobinemia, HbCO poisoning), although
there is some response when anemia is severe. Chemoreceptor Interactions
Interestingly, the peripheral chemoreceptors The breathing pattern observed at any given
stimulate severe hyperpnea (increased tidal time is the net result of the integration of vari-
volume) in cyanide poisoning.81 ous different inputs. As stated earlier, messages
may originate from brain centers, chemorecep-
PaCO2 /pH tors, reflexes, or even voluntary commands.
Although both the peripheral and central Notwithstanding, the chemoreceptors are often
chemoreceptors respond to increased PaCO2 the most dominant forces that control ventila-
and decreased pH, they are not equally sensitive tion. In some situations, the peripheral and
to these stimuli. Specifically, a relatively large central chemoreceptors work together for a
increase in PaCO2 or a decrease in pH potentiated response. In other circumstances,
(e.g., PaCO2 increase = 10 mm Hg; pH they tend to antagonize each other and blunt
decrease = 0.1)81 is necessary before a notable individual responses. A few examples of
increase in ventilation will be triggered via the chemoreceptor interactions follow.
peripheral chemoreceptors. Conversely, the
central chemoreceptors respond to very slight Normal Ventilation
changes in PaCO2. In a normal young man, The regulation of ventilation in normal indi-
minute ventilation increases approximately 2.5 L viduals is primarily under the control of the
with only a 1-mm Hg increase in PaCO2.81 central chemoreceptors; however, as previously
mentioned, the peripheral chemoreceptors
PaO2 send weak messages to the brain to ventilate
The response of the peripheral chemoreceptors and have some, albeit small, influence on the
to a low PaO2 sets them apart from the central ventilatory pattern. Thus, the ventilatory pat-
chemoreceptors and is their most important tern is the net result of the integration of the
mechanism clinically. Even in normal humans, two sets of chemoreceptors.
some, albeit few, impulses are sent to the brain
from the peripheral chemoreceptors stimulating Acute Hypoxemia
ventilation. PaCO2 and the central chemo- In the presence of disease, the peripheral
receptors are the primary mechanisms of venti- chemoreceptors may take the dominant role in
latory control during normal ventilation. the regulation of ventilation. For example, in
Regulation of ventilation in pulmonary dis- acute, severe hypoxemia, the peripheral
ease is often in marked contrast. Here, the chemoreceptors send a powerful message to
peripheral chemoreceptors often play the domi- the brain to increase ventilation and generally
nant role in determining the ventilatory pattern. will override the central chemoreceptors.
Subsequently, the increased ventilation that Progressive Pulmonary Deterioration

accompanies severe, acute hypoxemia lowers Lung diseases, such as emphysema, chronic
PaCO2. The decreased PaCO2, in turn, has the bronchitis, and chronic asthma, are often
effect of making the CSF alkalotic and depress- grouped into a single category called chronic
ing ventilation via the central chemoreceptors. obstructive lung disease (COLD), chronic
Thus, in acute hypoxemia, two conflicting obstructive pulmonary disease (COPD), or
messages are sent to the brain. The severe chronic airflow obstruction (CAO). A common
hypoxemia requires an increase in ventilation via denominator of these diseases is that they may
the peripheral chemoreceptors, whereas the low lead to a progressive inability of the lungs to nor-
PaCO2 depresses the central chemoreceptors. mally exchange gases and maintain ventilation.
Because the number of impulses resulting from
severe hypoxemia is large and the decrease in Normal Lung Function
impulses resulting from the falling PaCO2 is The effects of progressive pulmonary deteriora-
small, the individual will display a net increase tion on the chemoreceptors and blood PaCO2
in ventilation. It is important to recognize, and PaO2 levels are shown in Table 12-1.
however, that the central chemoreceptors tend Normal lung function is associated with normal
slightly to blunt the hyperventilation. blood gases and ventilation is primarily under
the control of the central chemoreceptors.
Chronic Hypoxemia
In chronic hypoxemia, PaCO2 also remains Mild Disease
low. After a few hours, however, the pH of the The initial blood gas abnormality associated
CSF, made alkalotic by the hypocarbia, begins with mild pulmonary disease is mild hypoxemia
to return to normal as bicarbonate ions are with a normal PaCO2 (see Table 12-1). In this
actively transported out of the blood-brain early stage, the increase in peripheral chemo-
barrier. When the pH of the CSF returns to receptor stimulation is so minute that it is not
normal, it no longer depresses ventilation via clinically detectable. The central chemorecep-
the central chemoreceptors. At this point, the tors maintain primary control over ventilation.
individual actually begins to hyperventilate to
a greater degree. It is, in fact, well known that Moderate Disease
the ventilatory response to chronic hypoxemia As deterioration in external respiration contin-
is greater than the ventilatory response to ues, PaO2 continues to decline. At a PaO2 level
acute hypoxemia because of this mechanism.81 of approximately 60 mm Hg (although there
Again, the ventilatory pattern at any point in may be considerable individual variation with
time depends on the interaction of the regard to the specific PaO2 when this occurs), a
chemoreceptors. dramatic increase in peripheral chemoreceptor
Table 12-1. REGULATION OF VENTILATION AND BLOOD GASES IN PROGRESSIVE

PULMONARY DISEASE
Progressive Disease
Normal Mild Moderate Severe
Blood gases
PaO2 100 mm Hg 65 mm Hg 55 mm Hg 50 mm Hg
PaCO2 40 mm Hg 40 mm Hg 34 mm Hg 50 mm Hg
Central chemoreceptors ++++ ++++ ++ +
Peripheral chemoreceptors + ++ +++ ++++
Control C C P P
C = central chemoreceptors.
P = peripheral chemoreceptors.
stimulation is seen, and the peripheral chemo- ventilation-perfusion alterations than a result of
receptors assume primary control of ventilation. a decrease in ventilatory drive.463 Furthermore,
The strong peripheral chemoreceptor drive usu- the Haldane effect (release of CO2 from Hb into
ally results in an increase in alveolar ventilation the blood in the presence of increased oxygen)
and a fall in the PaCO2 (see Table 12-1). may be responsible for some of the ensuing
It is important to note that, during this phase, hypercarbia.464 The precise mechanism responsi-
the cardiovascular system is also required to ble for this hypoventilation remains a controver-
increase the heart rate and to elevate the blood sial issue and multiple factors may be influencing
pressure. From a teleologic perspective, because ventilation simultaneously. Regardless of the
O2 levels are falling to a critical point on the exact mechanism, worsening hypercarbia must
oxyhemoglobin curve, the cardiovascular system be recognized as a possible consequence of oxy-
appears to be trying to ensure sufficient tissue gen therapy in chronic lung disease.
O2 delivery.
Reflexes
Severe Disease At least six different reflexes have been described
If external respiration continues to deteriorate, in relation to the regulation of ventilation.81
CO2 excretion is ultimately impaired and The precise role of many of these reflexes must
PaCO2 levels begin to increase. Furthermore, still be defined. Nevertheless, two reflexes may
PaO2 levels continue to fall (see Table 12-1). be useful in helping the clinician to understand
Indeed, the classic definition of acute respira- the origin of respiratory alkalosis in certain
tory failure is a PaCO2 greater than 50 mm Hg pulmonary conditions.
and/or a PaO2 less than 50 mm Hg.
The same pattern of progressive pulmonary Hering-Breuer Reflex
deterioration can also occur over a short time The Hering-Breuer reflex, or stretch reflex, is
(days or hours) in acute pulmonary disease. This probably the most widely known of the
pattern may be observed in pneumonia, postop- reflexes involved in the regulation of ventila-
erative respiratory failure, or acute asthma. It tion. This reflex appears to regulate tidal volume
is always important to identify patients with and respiratory rate to minimize the muscular
moderate impairment (i.e., moderate disease as work of breathing.
described in Table 12-1), because further deteri- The Hering-Breuer reflex is not usually active
oration leads to hypercarbia. The classic exam- during normal breathing. Rather, it is activated
ple of this is the patient in status asthmaticus when the lung is overinflated or underinflated.
(sustained unresponsive asthma) whose condi- The Hering-Breuer reflex is often described as
tion deteriorates progressively over a period of two separate reflexes: an inflation reflex, which
days, leading ultimately to exhaustion and to the inhibits inspiration, and a deflation reflex,
abrupt onset of respiratory acidemia. which stimulates inspiration when the lung
In patients with severe chronic lung disease, volume is low.
administration of oxygen may lead to progres- The deflation reflex may be responsible, at
sive hypercapnia and occasionally even to least in part, for the hyperventilation observed
apnea. For years, it was believed that this in restrictive lung diseases. The ventilatory pat-
occurred because these patients were breathing tern commonly observed in these patients is
exclusively in response to the so-called hypoxic characterized by a rapid respiratory rate and a
drive of the peripheral chemoreceptors. It was low tidal volume. This pattern, although benefi-
assumed that the central chemoreceptors had cial in terms of the work of breathing, may lead
become dulled because of the chronic hyper- to respiratory alkalosis.
carbia; it followed, then, that oxygen therapy
increased the PaO2 and knocked out the drive J Receptors
to breathe. The juxtapulmonary capillary receptors (J recep-
Other studies have shown that the worsen- tors) are located in the interstitial tissue of the
ing hypercarbia associated with oxygen ther- alveolar-capillary membrane. It is believed that
apy in these patients is more likely a result of these receptors are stimulated by an increased
thickness of the alveolar-capillary membrane. Microscopic Anatomy and Physiology

Stimulation of these receptors could then The functional unit of the kidney is the
explain the tachypnea and hyperventilation seen nephron. Each kidney contains approximately
with pulmonary edema, congestion, or fibrosis. 1 million nephrons. A schematic drawing of the
Certainly alveolar hyperventilation is common functional nephron is shown in Figure 12-4.
in these conditions. Blood enters the nephron through the afferent
arteriole, which in turn enters an enclosed cap-
sule. This capsule, called Bowmans capsule, is
RENAL FUNCTION
actually the first portion of the renal tubular
The renal system has essentially three primary system.
functions. First, the kidneys are responsible for Encased within the capsule, the afferent arte-
excreting nonvolatile waste products, includ- riole branches into a capillary network and
ing fixed acids. Second, the kidneys are respon- then leaves Bowmans capsule through the
sible for the regulation of blood volume. efferent arteriole. The capillary tuft or network
Third, the kidneys must regulate blood concen- within the capsule is called the glomerulus. The
trations of various electrolytes (e.g., HCO3) capillaries that make up the glomerulus are
and other blood constituents. very porous, and much of the plasma is filtered
into Bowmans capsule. The fluid that accumu-
Macroscopic Anatomy and Physiology lates within the capsule is called the glomerular
The gross anatomy of the kidney is shown in filtrate, which begins its journey through the
Figure 12-3. Each of the two kidneys consists nephron.
of an outer cortex and an inner medulla. Urine The tubule that the glomerular filtrate passes
formed in the functional units of the kidney through immediately upon leaving Bowmans
gathers in the renal pelvis and then flows capsule is called the proximal tubule, because
through the ureters down to the urinary bladder, it is close (proximal) to the capsule. Actually,
where it is stored. Ultimately, urine is excreted this tubule follows a very convoluted path, and
through the urethra. it is sometimes referred to as the proximal
Cortex Glomerulus
Renal vein Medulla Bowmans capsule
Renal Afferent
arteriole Proximal tubule
artery
Efferent
arteriole Distal
Pelvis tubule
Collecting
tubule
Right kidney Left kidney Peritubular
(cut surface) capillaries
Venules Loop of
Henle
Ureters
Arcuate Thin
vein segment
Vasa recta
Urinary bladder
Direction of Pelvis
urine flow
Figure 12-3. Gross anatomy of the renal system. Figure 12-4. The functional nephron.
convoluted tubule. The glomerular filtrate Tubular Reabsorption

then travels through the loop of Henle, the dis- Approximately 99% of all the fluid that passes
tal convoluted tubule, and, ultimately, the col- into the glomerular filtrate is reabsorbed. As
lecting duct. The fluid that accumulates in the the filtrate passes through the nephron, vari-
collecting duct is essentially urine, which then ous electrolytes and substances are reabsorbed
flows to the renal pelvis en route to be in proportion to the bodys needs. As shown in
excreted. Figure 12-4, a rich supply of capillaries (i.e.,
peritubular capillaries and vasa recta) is imme-
Urine Formation diately adjacent to the renal tubules that facil-
Three processes are involved in the formation of itate reabsorption of many of these electrolytes
urine: (1) glomerular filtration, (2) tubular reab- back into the bloodstream.
sorption, and (3) tubular secretion. Through
these processes, the kidney can accomplish its Tubular Secretion
functions, which are described at the beginning The cells that line the renal tubules are also capa-
of this section. ble of secreting certain electrolytes into the fil-
trate in exchange for the reabsorption of other
Glomerular Filtration electrolytes that the body seeks to recapture.
The glomerulus functions as a semi-permeable This process of exchanging one electrolyte for
membrane that allows for the diffusion of fluid another in the filtrate is called tubular secretion.
similar in ionic concentration to plasma into
the filtrate. Cells and proteins do not normally BODY FLUIDS AND ELECTROLYTES
pass through the glomerulus into the filtrate.
In fact, proteinuria (protein in the urine) and Fluid Compartments
hematuria (blood in the urine) may be impor- Approximately 60% of the bodys weight is
tant findings that suggest renal disease. made up of water. This water is separated by
The volume of glomerular filtrate formed membranes into various body fluid compart-
depends on the volume of renal perfusion. ments (Fig. 12-5). As further shown in Figure
Normally, the kidneys receive approximately 12-6, approximately two-thirds of the water
20% of the cardiac output. The amount of this (approximately 65%) is located in the intracel-
volume that is filtered out into the glomerular lular fluid space, or within cells. The remaining
filtrate is also large. A volume roughly equiva-
lent to the entire extracellular fluid volume
(i.e., 15 L) passes through the glomeruli every
2 hours.465 In the patient with reduced volume TOTAL BODY FLUIDS
and metabolic alkalosis, glomerular filtration (40 liters)
is likewise reduced. This perpetuates the syn-
drome of metabolic alkalosis as excess [HCO3] Plasma volume Red cell volume
cannot be excreted.480 Thus, correction of (3 liters) (2 liters)
metabolic alkalosis is dependent on adequate
renal perfusion and glomerular filtration.
Any drug that increases cardiac output (e.g., EXTRACELLULAR INTRACELLULAR VOLUME
epinephrine, digitalis) or preferentially increases (15 liters) (25 liters)
renal perfusion (e.g., aminophylline) tends to Interstitial
increase urine formation. A diuretic is any volume
substance that increases urine flow. Therefore, (12 liters)
in a broad sense, these drugs may be consid- Blood volume
ered to be mild diuretics, although they are (5 liters)
not generally administered primarily for this Figure 12-5. Body fluid compartments.
purpose. An increase in the amount of urine Diagrammatic representation of the body fluids,
excreted is called polyuria; a decreased urine showing the extracellular fluid volume, intracellular
output is called oliguria. fluid volume, blood volume, and total body fluids.
2/3 of
TOTAL BODY WATER
Body weight =
1/3 =
Extracellular fluid
2/3 = Intracellular fluid
3/4 =
1/4 =
Interstitial
Plasma
fluid
Na
+
HCO3 Prot

HCO 3
Mg++ Prot Na+ Na+

Cl Cl
K+ Phos
Figure 12-6. Composition of body fluid compartments. Percentage of total body water and approximate
electrolyte composition of various compartments is shown.
35% exists in the extracellular fluid compart- Electrolyte Distribution

ment or outside the cells. Each of the body fluid compartments contains
The body fluids can also be categorized con- electrolytes. However, each compartment has its
cerning whether they exist within the vascular own unique electrolyte composition. Often there
system (i.e., intravascular fluid or blood volume) may be a striking contrast from one compart-
or outside it (i.e., extravascular fluid). The por- ment to another in electrolyte concentration, as
tion of the extracellular fluid that exists within shown in Figures 12-6 and 12-7. For example,
the vascular space is the plasma. If plasma is potassium is the most abundant intracellular
allowed to coagulate and the coagulated fluid cation, with a concentration of approximately
is centrifuged, the clear fluid that remains is 141 mEq/L. In sharp contrast, the potassium
called serum. concentration in the plasma is only approxi-
The portion of the extracellular fluid that mately 4 mEq/L.
exists outside the vascular space is also called Similarly, the major intracellular anion is
the interstitial fluid, because it lies in the spaces phosphate, with a concentration of approxi-
between the various cells throughout the body. mately 75 mEq/L; on the other hand, the plasma
As graphically shown in Figures 12-5 and 12-6,
most of the extracellular fluid consists of inter-
stitial fluid.
EXTRACELLULAR INTRACELLULAR
FLUID FLUID
Electrolytes +
Na 142 mEq/L 10 mEq/L
Two types of chemical substances are found in K+ 4 mEq/L 141 mEq/L
body water: non-electrolytes and electrolytes. Ca++ 5 mEq/L <1 mEq/L
Non-electrolytes are uncharged substances Mg++ 2 mEq/L 58 mEq/L
Cl 103 mEq/L 4 mEq/L
that remain intact. Urea, creatinine, and glucose
HCO3 27 mEq/L 10 mEq/L
are examples of non-electrolytes. Electrolytes, Phosphates 2 mEq/L 75 mEq/L
on the other hand, dissociate and carry electrical SO4 1 mEq/L 2 mEq/L
charges. Electrolytes that carry a positive charge
are called cations; those that carry a negative Figure 12-7. Intracellular versus extracellular
charge are called anions. electrolyte composition.
phosphate level is near 2 mEq/L. Clearly, the tends to follow Na+. Therefore, excessive loss
concentration of an electrolyte in one compart- of Na+ into the urine is associated with polyuria
ment does not always mirror the concentration and potentially with hypovolemia. Most diuret-
of that electrolyte in other compartments. The ics inhibit Na+ reabsorption in the nephron, thus
values for intracellular electrolytes shown in causing diuresis by allowing Na+ to be excreted
Figure 12-7 are only approximate; actual intra- in the urine.
cellular electrolyte concentrations may vary High concentrations of sodium seen in the
substantially from one type of cell to another. plasma (e.g., Na > 158 mEq/L) generally indi-
cate a water or volume deficit. This is sometimes
Plasma Electrolytes referred to as an extracellular volume contrac-
Clinical measurements of electrolyte concen- tion that may lead to metabolic alkalosis as
trations are most often made from intravascu- the kidneys attempt to retain sodium bicar-
lar fluid samplesspecifically, the plasma or bonate. Conversely, low sodium concentrations
serum. The plasma closely reflects the elec- (Na < 120 mEq/L) indicate water excess and
trolyte composition of the entire extracellular may cause what is referred to as a dilution aci-
fluid compartment; however, it does not reflect dosis. Severe hyponatremia may also be caused
the intracellular fluid composition. by the administration of diuretics, especially
thiazides.469 Insuring a normal sodium concen-
Major Plasma Cations tration is critical to maintenance of fluid and
As shown in Table 12-2, there are essentially acid-base balance.
four important cations in the plasma: sodium
(Na+), potassium (K+), calcium (Ca2+), and Potassium
magnesium (Mg2+). In general, the kidney In contrast to Na+, the normal plasma concen-
more precisely regulates the concentrations of tration of K+ is within the range of 3.5 to
cations than anions, because even small abnor- 5 mEq/L. Potassium must be precisely main-
malities in the concentrations of most cations tained within this narrow range in the extra-
have adverse effects on the patient. In contrast, cellular fluid or serious adverse consequences
small abnormalities in the concentrations of may occur. In particular, K+ is closely related to
most anions are usually inconsequential. neuromuscular activity.
Both plasma hypokalemia (i.e., low [K+]) or
Sodium plasma hyperkalemia (i.e., increased [K+]) may
As shown in Table 12-2, sodium (Na+) is the lead to abnormalities in muscle contractility
most abundant extracellular cation, with a and life-threatening arrhythmias. Because the
concentration of 142 mEq/L. As such, Na+ reg- normal plasma concentration of this cation is
ulation is related intimately to osmosis and so low, there is very little margin for deviation
fluid balance. Generally speaking, body water without untoward effects.
Potassium imbalances are also associated
with abnormal ECG tracings. The characteristic
Table 12-2. PLASMA ELECTROLYTES
ECG changes associated with both hypokalemia
Cation Anion and hyperkalemia are shown in Figure 12-8;
Charges (mEq/L) Charges (mEq/L) however, ECG changes may not be seen in mild
imbalances. Knowledge and recognition of these
Na+ 142 Cl 103
abnormal tracings may be useful in helping to
K+ 4 HCO3 27
Ca2+ 5 HPO42 2 identify serious potassium disturbances.
Mg2+ 2 SO42 1 Serious hyperkalemia is most often due to
Others (trace 1 Organic acids 5 renal failure or metabolic acidosis. In contrast,
Elements) Protein 16 hypokalemia, which is probably the most com-
mon electrolyte disturbance, may be caused by
154 154 diuretics, steroids, or beta agonist drugs.478
From Tietz, N.W.: Fundamentals of Clinical Chemistry, Hypokalemia may also be associated with mus-
3rd ed. Philadelphia, W. B. Saunders, 1987. cle weakness or cramps. Severe hypokalemia
Magnesium
NORMOKALEMIA
The magnesium cation is predominantly an
U wave shallow intracellular cation. It is involved in many
Normal PR if present enzyme reactions within the body and plays a
interval
role in neuromuscular functions. It is also
important in normal central nervous system
Normal P wave Rounded normal-
function.
sized T wave
Normal QRS SODIUM REGULATION IN THE
KIDNEY
HYPOKALEMIA
Sodium regulation by the kidney is intimately
ST depressed related to acid-base balance. A complex inter-
Slightly prolonged and prolonged
PR interval
relationship is involved in the renal regulation
of blood [Na+], [HCO3], [K+], and [H+]. For
this reason, the specific chemical mechanisms
Prominent
Slightly U wave
related to Na+ reabsorption from the glomerular
peaked P wave filtrate are reviewed here. These same mecha-
Depressed T wave
(may be inverted) nisms also help to explain renal regulation of
the other important acid-base electrolytes.
HYPERKALEMIA Narrow, Chemical Mechanisms
peaked
Decreased R
T wave Most of the Na+ that enters the glomerular fil-
wave amplitude
trate is recaptured by the renal tubular cells by
two different chemical mechanisms: the NaCl
mechanism and the NaHCO3 mechanism.
Wide flat Depressed
P wave ST segment NaCl Mechanism
Prolonged
PR interval
Widened QRS Ions that move across cell membranes may do so
by diffusion or by active transport. Diffusion is
Figure 12-8. ECG changes seen in potassium a passive process by which molecules move
imbalances. from a high concentration to a low concentra-
tion. In contrast, active transport requires the
expenditure of cellular energy to move a sub-
(K < 3.0) has been implicated as a potential stance across a membrane, often against a con-
cause of ventricular arrhythmias and cardiac centration gradient. Much of the electrolyte
arrest.478,479 reabsorption and secretion that occurs in the
nephron is through active transport.
Calcium The NaCl mechanism of Na+ reabsorption is
Calcium is important to the body for several shown in Figure 12-9. The Na+ cation is actively
reasons. It is important in the initiation of transported from the glomerular filtrate into the
muscular contraction and in maintaining nor- renal tubular cell. To maintain electroneutrality,
mal neuromuscular irritability. Calcium is also the Cl anion passively accompanies Na+. Both
essential for normal blood coagulation and for Na+ and Cl are then transported from the renal
maintaining normal structural integrity of tubular cell to the extracellular fluid immedi-
bones and teeth. ately outside the renal tubular cells and ulti-
Calcium is normally present in approximately mately to the plasma.
equal amounts as ionized Ca2+ and un-ionized Thus, each time this complete reaction takes
Ca. Alkalemia decreases the concentration of place, both a Na+ cation and a Cl anion are
ionized Ca2+, which results in increased neuro- recaptured from the glomerular filtrate back
muscular irritability and possible tetany. into the extracellular fluid (blood). All through
EXTRACELLULAR
FLUID TUBULE
Na+ + Cl
Figure 12-9. Sodium reabsorption via

the NaCl mechanism. Sodium is actively Active transport Active transport
+
transported from the filtrate to the renal Na Na+ Na+
tubular cell and then to the extracellular Cl Cl Cl
fluid and blood. Chloride passively
accompanies sodium to maintain
electroneutrality.
the renal tubule (i.e., proximal tubule, loop of Carbonic anhydrase, the enzyme that acceler-
Henle, distal tubule) Na reabsorption occurs ates the hydrolysis reaction, is available within
via this mechanism. the renal cells.
After the Na+ enters the renal cell from the fil-
NaHCO3 Mechanism trate, it is then actively transported to the extra-
The other reaction by which Na+ is recaptured cellular fluid. In the NaCl mechanism described
from the filtrate is slightly more complex. In this earlier, Cl was available inside the renal cell to
reaction, an H+ ion is secreted from the renal accompany the Na+ into the extracellular fluid.
tubular cell by active transport into the filtrate In this reaction, the anion HCO3, which was
in exchange for Na+ cation, which enters the generated via the hydrolysis reaction, accompa-
renal cell as shown in Figure 12-10. Hydrogen nies the Na+ into the extracellular fluid.
ions are made available within the renal tubu- As shown in Figure 12-10, the H+ secreted
lar cells through the hydrolysis reaction. into the filtrate fuels the hydrolysis reaction
EXTRACELLULAR
FLUID TUBULE
Figure 12-10. Sodium reabsorption via Na+ + HCO3

H+ secretion and the NaHCO3 reaction.
Hydrogen ions, available through the
hydrolysis reaction, are secreted into Active transport
Na+ Na+ Na+
the filtrate in exchange for sodium. The + Active transport
sodium is then transported from the renal HCO3 HCO3 + H+ H+ HCO3
cell to the extracellular fluid and ultimately H2CO3
to the plasma. Bicarbonate, also available H2CO3
from the hydrolysis reaction, accompanies H2O (Carbonic
+ anhydrase)
sodium into the extracellular fluid to CO2 CO2 CO2 + H2O
maintain electroneutrality.
EXTRACELLULAR
FLUID TUBULE
Na+
Figure 12-11. Sodium reabsorption via
K+ secretion and the NaHCO3 reaction.
Active transport
Na+ +
Na Na
+ Potassium ions are secreted into the fil-
+ Active transport trate in exchange for sodium. The sodium
HCO3 HCO3 + H+ K +
K+ is then transported from the renal cell
H2CO3 to the extracellular fluid and ultimately
to the plasma. Bicarbonate accompanies
H2O (Carbonic
+ anhydrase) sodium into the extracellular fluid to
CO2 CO2 CO2 maintain electroneutrality.
and leads to increased dissolved CO2. The reaction is used to reabsorb Na+, an HCO3
increased dissolved CO2, in turn, diffuses from anion enters the extracellular fluid. It follows
the filtrate into the renal cell to fuel the hydroly- that any condition that increases this reaction
sis reaction in the intracellular space. It has been may cause metabolic alkalosis (i.e., increased
postulated that carbonic anhydrase is also avail- blood [HCO3]). Conversely, any condition that
able along the border of the renal cell to acceler- decreases this reaction tends to cause metabolic
ate the hydrolysis reaction within the filtrate. acidosis (i.e., decreased blood [HCO3]).
There is another important variation of the
NaHCO3 reaction. In some cases, a K+ cation Renin-Angiotensin System
rather than an H+ ion is secreted into the filtrate One of the primary ways that the body regu-
in exchange for the Na+ cation (Fig. 12-11). lates sodium reabsorption and ensures an ade-
In fact, because most K+ that enters the filtrate in quate blood volume and renal perfusion is
the glomerulus is totally reabsorbed in the prox- through the renin-angiotensin-aldosterone sys-
imal tubule, it is only through this NaHCO3 tem. An integral part of this system is a group
reaction in the distal tubule that excess K+ can of cells in the walls of the afferent arterioles
be excreted. immediately adjacent to the glomerulus, which
The renal cells can selectively secrete K+ or have the ability to detect decreased renal per-
H+ into the glomerular filtrate, depending on fusion. These cells, because they lie close to the
the bodys needs. For example, in the presence of glomeruli, are called the juxtaglomerular cells.
alkalemia, H+ ions are retained because of their When blood flow through the renal arterioles
relative shortage. This, in turn, leads to selective is decreased, the juxtaglomerular cells secrete
K+ loss and, potentially, to hypokalemia. Thus, renin into the bloodstream.
alkalemia tends to cause hypokalemia. Immediately after renin enters the blood-
Abnormalities in potassium concentration stream, it reacts with angiotensinogen in the
have a similar effect. Intracellular hypokalemia plasma and forms the substance angiotensin I
(low [K+]) results in increased H+ secretion. (Fig. 12-12). Within minutes, angiotensin I is
This condition is often difficult to recognize converted to angiotensin II by an enzyme pres-
because measurements of serum potassium may ent in the lungs. Angiotensin II has effects that
be normal even when intracellular potassium is tend to elevate blood pressure and increase
depleted. renal perfusion.
Regardless of whether an H+ ion or a K+ Angiotensin II causes systemic vasoconstric-
cation is secreted, each time the NaHCO3 tion, which in turn increases the blood pressure.
Blood pressure Renin Table 12-3. SITE AND MECHANISM OF

Angiotensinogen
SODIUM REABSORPTION
Site in Tubule
Angiotensin I
Mechanism Proximal Loop Distal % Total
Kinase II
% Total
Angiotensin II Vasoconstriction
reabsorption
as NaCl 47 25 8 80
% Total
Aldosterone reabsorption
as NaHCO3 18 2 20
% Total
Na+, HCO3 Blood pressure reabsorption 65 25 10 100
Figure 12-12. The renin-angiotensin-aldosterone Modified from Frazier, H.S., and Yager, H.: The clinical
mechanism. use of diuretics (Pt. I). N. Engl. J. Med., 288: 246, 1973;
Frazier, H.S., and Yager, H.: The clinical use of diuretics
(Pt. II). N. Engl. J. Med., 288: 455, 1973.
Angiotensin II also stimulates increased pro- Total Sodium Reabsorption

duction of the hormone aldosterone by the In Table 12-3, total Na+ reabsorption is broken
adrenal cortex. Aldosterone, in turn, stimulates down according to its site in the tubule, and
NaHCO3 reabsorption in the distal tubule of the respective percentages reabsorbed by each
the nephron. Because water reabsorption fol- of the two mechanisms are shown.466,467 Note
lows Na reabsorption, blood volume increases that most Na+ is reabsorbed in the proximal
and perfusion to the kidney should also tubule (65%), approximately 25% in the loop,
improve. Some physiologic results of aldos- and only 10% in the distal tubule. Also note
terone secretion are shown in Figure 12-13. that 80% of total Na+ reabsorption is in the
Aldosterone
Renal reabsorption Increased renal excretion

of sodium of potassium
Hypokalemia
Water Bicarbonate Hydrogen Muscle paralysis

reabsorption retention secretion
Alkalosis
Increased extracellular Increased Increased

fluid volume blood volume cardiac output
Increased arterial pressure
Figure 12-13. Physiologic results of aldosterone secretion.

form of NaCl; only 20% normally is reab- metabolic alkalosis and hypokalemia. However,
sorbed as NaHCO3. it is not the diuretic itself that causes these
effects. Rather, these effects are mediated
Regulation of [HCO3] through the renin-angiotensin system because
The NaHCO3 reaction is also the mechanism of the loss of Na+ and decreased renal perfu-
by which tubular reabsorption of the HCO3 sion. It is, in fact, the compensatory response
anion is accomplished. Technically speaking, to the loss of fluid imposed by the diuretic that
HCO3 is not reabsorbed; rather, it is leads to high aldosterone levels and excessive
reclaimed, because it must be transformed into NaHCO3 reabsorption. The magnitude of the
dissolved CO2 before it can cross from the fil- aldosterone response is related directly to the
trate into the renal tubular cells. Table 12-3 strength of the diuretic and to the degree of
shows that 90% of HCO3 reabsorption occurs concomitant renal hypoperfusion.
in the proximal tubule.466 The final 10% is
reabsorbed in the distal tubule. Interference with NaHCO3 Reabsorption
Because HCO3 is actually generated in this A few types of diuretics interfere directly with
reaction, any increase in this reaction will ele- NaHCO3 reabsorption. These diuretics include
vate blood [HCO3]. At least three factors carbonic anhydrase inhibitors, such as acetazo-
are known to stimulate HCO3 production468: lamide (Diamox), and drugs that compete with
(1) increased blood PCO2 stimulates increased aldosterone for distal tubule chemical sites such
bicarbonate reabsorption as an acid-base com- as spironolactone (Aldactone). In contrast to
pensatory mechanism; (2) low serum potassium NaCl-inhibiting diuretics, these diuretics tend
stimulates bicarbonate reabsorption and tends to cause metabolic acidosis because they inhibit
to cause metabolic alkalosis; and (3) decreased NaHCO3 reabsorption. Aldactone also tends
blood volume stimulates bicarbonate reabsorp- to cause hyperkalemia, because the NaHCO3
tion through the renin-angiotensin mechanism. absorption mechanism per se is blocked.
Diamox, on the other hand, may actually
Diuretics increase potassium excretion because it only
Diuretics (drugs which can increase the urine inhibits the formation and availability of H+
output) commonly have important effects on ions via the hydrolysis reaction.
acid-base balance. The specific effect of a given Diuretics that interfere with NaHCO3 reab-
diuretic depends on its mechanism of action. sorption are the diuretics of choice in the patient
From an acid-base perspective, diuretics that with metabolic alkalosis. However, these diuret-
interfere with Na reabsorption can be classi- ics generally are not very potent and, when
fied as (1) those that interfere with NaCl reab- given alone, are often inadequate to obtain
sorption and (2) those that interfere with satisfactory levels of diuresis.
NaHCO3 reabsorption.
Hyperaldosteronism
Interference with NaCl Reabsorption Normally, some aldosterone circulates in the
Most of the commonly used diuretics act by bloodstream; however, when aldosterone
this mechanism. These include thiazide (e.g., levels are excessive (i.e., hyperaldosteronism),
Diuril, Hydrodiuril) and loop diuretics such NaHCO3 reabsorption (and H+ excretion) is
as furosemide (Lasix) and ethacrynic acid also excessive, and metabolic alkalosis results.
(Edecrin). Thiazide diuretics interfere with Na+ Hyperaldosteronism likewise tends to cause
reabsorption in the distal tubule. Because the hypokalemia. The administration of diuretics
amount of Na+ reabsorption in the distal that interfere with NaCl reabsorption may cause
tubule is not large (see Table 12-3), thiazides the triad of hyperaldosteronism, hypokalemia,
are not particularly potent. Loop diuretics, as and metabolic alkalosis.
their name implies, act in the loop of Henle
and are much stronger diuretics. Secondary Hyperaldosteronism
Both types of diuretics (i.e., thiazides, loop Hyperaldosteronism that occurs as a result of
diuretics) may lead to the development of the renin-angiotensin system (e.g., diuretic- or
hypoperfusion-induced), is termed secondary buffers. Secretion of H+ ions into the filtrate

hyperaldosteronism, because the high aldos- occurs only until the pH falls to approximately
terone levels are secondary to the decreased 4.5. Therefore, it is important that the tubular
renal perfusion. fluid can accept a large number of hydrogen
Chemically, aldosterone is classified as a ions without allowing the pH to fall to this
mineralocorticoid. Therefore, high aldosterone point. This process is accomplished in health
levels are also sometimes referred to as miner- and disease through the urinary buffers.
alocorticoid excess. The term secondary min- There are three important urinary buffers:
eralocorticoid excess is analogous to secondary bicarbonate, ammonia, and phosphate. The
hyperaldosteronism. buffering of H+ ions in the tubule by the bicar-
bonate buffer system has been illustrated in
Primary Hyperaldosteronism Figure 12-10. The other two urinary buffers
High aldosterone levels may also be the result of are briefly described here.
some abnormality in adrenal cortex secretion
such as an adrenocortical tumor or Cushings Ammonia
syndrome. This form of aldosteronism is called As shown in Figure 12-14, ammonia (NH3) is
primary hyperaldosteronism. Primary hyperal- generated in the renal tubule cells from glut-
dosteronism may cause metabolic alkalosis. amine and other amino acids. Being a gas,
Steroids (glucocorticoids), which are com- ammonia then diffuses into the tubular fluid
monly administered therapeutically, are chem- where it can combine with an H+ ion and min-
ically similar to the mineralocorticoids and imize the fall in pH. The new substance
have similar properties. Thus, steroids in rela- formed, ammonium (NH 4+), cannot diffuse
tively large doses may cause metabolic alkalosis. back into the tubule cell because it is ionized.
Surprisingly, licorice also has a similar chemical Hence, ammonium (and an H+ ion) is excreted
component. In relatively high doses, licorice in the urine.
may also lead to metabolic alkalosis. The conjugate bases associated with the
accumulation of fixed acids (e.g., Cl) can be
excreted with any cation (e.g., Na+, K+). In
URINARY BUFFERS AND H+
normal individuals, most of the H+ ions asso-
EXCRETION
ciated with fixed acid excretion are disposed of
The excretion of fixed acids (e.g., phosphoric, by NH3. Furthermore, in the presence of
sulfuric, hydrochloric acid) by the kidney acidemia, there is increased ammonia produc-
depends on the availability of the urinary tion and H+ excretion. The kidney can increase
EXTRACELLULAR
FLUID TUBULE
Na+ + Cl
Figure 12-14. Ammonia and urinary Active transport

buffering. Ammonia is generated in the Na+ Na+ Na+
+ Active transport
+
renal tubule cell and then diffuses into the HCO3 HCO3 + H H
+
filtrate. Within the filtrate, ammonia com-

bines with a H+ and forms ammonium.
H2CO3 NH4+ + Cl
Diffusion
Ammonium is excreted in the urine. H2O NH3 NH3
+
CO2 CO2 Glutamine

A 54-year-old man with CHF is being chronically treated CO2 42 mEq/L

with digitalis and thiazide diuretics. He arrives in the Cl 79 mEq/L
emergency department complaining of weakness, K 2.6 mEq/L
lethargy, and muscle cramps. ECG demonstrates an
inverted T wave and a prominent U wave. Blood gases ASSESSMENT
and electrolytes are drawn. Abnormalities: List abnormal data and other noteworthy
ARTERIAL BLOOD GASES Explanation: List possible diseases, pathology, or other
SaO2 97 situations which may have led to this patients condition.
pH 7.54
INTERVENTION
PaCO2 48 mm Hg
[HCO3] 40 mEq/L
situation.
FIO2 0.21
Objective: Describe the specific goal or target of treatment.
Na 133 mEq/L
PLASMA pH AND [K+]

acid excretion by as much as fourfold by this
mechanism.480 The clinician should also be aware of the
important relationship between the pH of the
Phosphate plasma and the potassium ion concentration of
The other major buffer in the filtrate is the plasma ([K+]). In acidemia, for example,
++
phosphate. As shown in Figure 12-15, Na + the plasma [K+] usually increases. Conversely,
HPO4 ++, which is present in the filtrate, can in respiratory or metabolic alkalemia, the
exchange an Na+ for an H+ ion from the renal plasma [K+] decreases.
tubular cell, as described earlier in the Apparently, when plasma H+ levels are high,
NaHCO3 mechanism for reabsorption of Na. some of the excess H+ is actively transported to
The H+ that enters the filtrate can immediately the intracellular space (Fig. 12-16,A). This may
combine with HPO42 to form H2PO4. represent an attempt by the body to spread out
Therefore, the phosphate buffer also facilitates the H+ load to a larger fluid space, perhaps
increased H+ excretion. Acidemia increases as an intracellular-extracellular fluid buffer
phosphate excretion and thereby enhances the mechanism. In any event, in exchange for the
ability of the kidneys to excrete H+. H+ that enters the cells, K+ is released to the
EXTRACELLULAR TUBULE
FLUID
Na + Na+ + HPO4
+
Figure 12-15. Phosphate and urinary

Na+ Na+ + Na+ + HPO4 buffering. Phosphate in the filtrate can
Na+ + HCO3

accept an H+ and minimize the fall in pH.
HCO3 + H+

H+

H2CO3 H2PO4
H2O
+
CO2 CO2
Na+ + H2PO4

A. Acidemia per liter, the concentration of cations is equal to

the concentration of anions in any specific fluid
compartment. Table 12-2 demonstrates that
Plasma K+ the total concentration of cations in the plasma
hyperkalemia (154 mEq/L) is equal to the total concentration
Intracellular of anions in the plasma (154 mEq/L). Thus, the
H+ fluid
law of electroneutrality is maintained.
As stated earlier in this chapter, the kidneys
more precisely control the concentration of
B. Alkalemia plasma cations than anions. This probably
occurs because alterations in major cations are
generally more detrimental. Conversely, the
Plasma concentration of the most abundant anion,
hypokalemia K+
chloride, can change appreciably with almost
Intracellular
H+ fluid no clinical consequences.
Thus, the body allows the concentration of
chloride to vary in a somewhat passive manner.
The serum chloride concentration generally
Figure 12-16. pH and plasma potassium.
A, Plasma acidemia tends to cause hyperkalemia as
varies in response to the need for electroneu-
hydrogen ions from the plasma exchange with potas- trality. For example, if the body has lost another
sium ions from the intracellular fluid. B, Plasma anion (e.g., bicarbonate) and has a total anion
alkalemia tends to cause plasma hypokalemia as deficiency, the chloride concentration increases.
potassium ions from the plasma move into the intra-
cellular fluid in exchange for hydrogen ions. Hypochloremic Metabolic Alkalosis
The law of electroneutrality helps to explain
the inverse relationship between chloride and
plasma. Plasma potassium rises approximately bicarbonate anions in metabolic alkalosis. If
0.5 mEq/L for every 0.1 decrease in pH.470 the total cation concentration is normal, an
In organic acidemia (e.g., lactic acidosis, increase in bicarbonate (i.e., metabolic alkalo-
ketoacidosis), the inverse relationship between sis) is always associated with hypochloremia
pH of the plasma and [K+] does not always hold (i.e., decreased chloride), which must inevitably
true.471473 The reasons for this are unclear but occur if electroneutrality is to be maintained.
perhaps they are related to the fact that organic Patients with chronic obstructive pulmonary
acidosis typically originates in the intracellular disease and chronic hypercarbia often selec-
fluid. tively retain the base bicarbonate in order to
In alkalemia, the exchange of hydrogen ions normalize pH. These patients also manifest
and potassium ions is in the opposite direction hypochloremia to maintain electroneutrality.
(see Fig. 12-16,B). Hydrogen ions leave the The phrase hypochloremic metabolic alkalo-
intra-cellular space to replenish the deficiency in sis is sometimes used to refer to metabolic alka-
the plasma space.474 Conversely, potassium ions losis that originated as a result of a loss of
enter the cells in exchange for hydrogen ions. chloride (e.g., due to diuretics, loss of gastroin-
Thus, alkalemia leads to plasma hypokalemia testinal secretions). This terminology is not rec-
because of the migration of potassium to the ommended here, however, because metabolic
intracellular space. alkalosis of any origin is likely to be associated
with a low serum chloride (i.e., hypochloremia)
LAW OF ELECTRONEUTRALITY regardless of the mechanism of its origin.
Principle of Electroneutrality Anion Gap

The law of electroneutrality states that in a The anion gap is an index that can be used to
volume of fluid, the total positive charges of the aid in the diagnosis of metabolic acidosis.
cations are equal to the total negative charges Figure 12-17,A shows the balance between
of the anions. Thus, in units of milliequivalents sodium, which is the major cation, and chloride
NORMAL ACIDOSIS bicarbonate from the body, or it may be caused

Without With by the accumulation of some fixed acid. Based
Increase Increase on the law of electroneutrality, if excessive
in unmeasured in unmeasured
anions anions bicarbonate were to be lost from the body
(e.g., renal tubular disease, diarrhea), the chlo-
A 12 A 12
A 27 ride concentration would have to increase to
HCO3 10
HCO 3 maintain sufficient anions for electroneutrality.
27 Thus, metabolic acidosis caused by a loss of
HCO3 10
base is often called hyperchloremic metabolic
acidosis, because it is typically associated with
Na+ Na+ Na+ hyperchloremia.
142 140 140 Figure 12-17,B shows that, in metabolic aci-
Cl
Cl 118 Cl dosis caused by the loss of base (i.e., hyper-
103 103 chloremic metabolic acidosis), the anion gap is
normal. Because the chloride anion (a meas-
ured anion) increases to replace the bicarbon-
ate anion, the number of unmeasured anions
remains constant.
A B C
Figure 12-17. The anion gap and metabolic High Anion Gap Acidosis
acidosis. A, The normal anion gap. B, Normal Metabolic acidosis (i.e., decreased [HCO3]) is
anion gap in metabolic acidosis due to loss of more commonly due to the abnormal accumu-
base, so-called hyperchloremic metabolic acidosis. lation of fixed acids (e.g., lactic acid, keto
C, Increased anion gap in metabolic acidosis acids). Referring back to Table 12-2, it can be
due to increased fixed acid. seen that the unmeasured anions that make up
the anion gap include anions from fixed acids
and bicarbonate, which are the two most (e.g., lactate, sulfate, phosphate). Therefore,
abundant (major) anions. The mathematical when there is excessive accumulation of these
difference between sodium (Na+) and the sum acids, the anion gap increases.
of chloride and bicarbonate (HCO3 and Cl) In the presence of increased fixed acids in
represents the anion gap (A), or unmeasured the blood, the bicarbonate concentration
anions. decreases due to buffering. Thus, in the pres-
Because total CO2 rather than bicarbonate ence of increased fixed acids, plasma bicar-
is often reported with serum electrolytes, it is bonate decreases but chloride does not
acceptable to substitute total CO2 for bicar- increase. Rather, the increase in anions neces-
bonate in the anion gap formula, as shown in sary for electroneutrality occurs in the unmea-
Equation 12-1. The normal anion gap, which sured anions. Figure 12-17,C shows the
is calculated in Equation 12-1, is approxi- electrolyte pattern that is seen with metabolic
mately 12 mEq/L (see Fig. 12-17,A). The nor- acidosis secondary to increased accumulation
mal anion gap range is 12 to 14 mEq/L. An of fixed acids.
increased anion gap usually represents an
increase in blood fixed acids. A low anion gap Summary
is uncommon, although it may be observed as The anion gap is a useful index for differenti-
a result of hypoalbuminemia. ating the general causes of metabolic acidosis.
When metabolic acidosis is caused by a loss of
Equation 12-1
[Na+] ([Cl ] + [TCO2]) = A
base (so-called hyperchloremic metabolic acido-
142 (103 + 27) = 12 sis), the anion gap is normal. Conversely, when
increased fixed acids are present in the blood,
the anion gap increases.
Hyperchloremic Metabolic Acidosis Notwithstanding, the anion gap is not a par-
Metabolic acidosis (i.e., decreased [HCO3]) ticularly sensitive index, and mild A elevations
may be caused by a loss of base such as (e.g., to 1416 mEq/L) may be seen in some
conditions other than metabolic acidosis. In Table 12-4. ANION GAP ADJUSTED FOR
particular, alkalosis and hyperalbuminemia HYPOALBUMINEMIA
tend to increase the anion gap. Nevertheless, Albumin (g/dL) Maximum A (mEq/L)
an anion gap above 16 mEq/L strongly sug-
gests increased fixed acids in the blood. 4.4 16
Furthermore, the higher the anion gap, the 4.0 15
greater is the likelihood of increased fixed 3.6 14
acids and metabolic acidemia. Therefore, the 3.2 13
2.8 12
anion gap is a useful diagnostic index in the
assessment and the differential diagnosis of Reference: Figge, J. et al: Anion gap and hypoalbumine-
metabolic acidosis. mia. Crit. Care Med. 26:18071810, 1998.
Hypoalbuminemia and the Anion Gap of metabolic acidosis and should be afforded a
As mentioned previously, the protein concen- high index of suspicion.
tration has a significant impact on the anion
gap. The most abundant protein is albumin,
STEWARTS STRONG ION
therefore the clinician should realize that
DIFFERENCE
changes in albumin will substantially change
the anion gap. Normal albumin is approxi- In 1981, Peter Stewart advocated a new
mately 4.4 g/dL in the blood. approach to acid-base diagnosis475 that contin-
For every 0.4 g/dL drop in albumin, the ues to be espoused by some clinicians.477
anion gap will decrease 1 mEq/L.481 Because Through a series of complex mathematical cal-
hypoalbuminemia is quite common in the crit- culations, Stewart concluded that there are only
ical care setting, the normals for anion gap three independent variables that determine pH.
should be adjusted for each patient accordingly The three independent variables are PCO2, the
as shown in Table 12-4. Using Table 12-4 will strong ion difference (SID), and total concen-
help identify those patients with increased tration of the nonvolatile weak acids [ATOT].
fixed acids that may go unrecognized. Again, The strong ion difference can be calculated as
increased fixed acid is the most common cause SID = ([Na] + [K] + Ca2+ + Mg2+ + [other strong

A 62-year-old man with a history of chronic anemia K 5.2 mEq/L

arrives in the emergency department short of breath. Albumin 3.2 g/dL
Blood gases and electrolytes are drawn.
ASSESSMENT
ARTERIAL BLOOD GASES Abnormalities: List abnormal data and other noteworthy
SaO2 97 information. Classify ABG.
PaCO2 20 mm Hg situations which may have led to this patients condition.
PaO2 84 mm Hg
[HCO3] 8 mEq/L
a diagnosis.
FIO2 0.21
Na 135 mEq/L INTERVENTION
CO2 10 mEq/L
Importance: Prioritize concern(s) of treatment in order of
Cl 109 mEq/L urgency and/or seriousness as you see the overall situation.
anions]).477 Stewart advocates disregarding [Na], [Cl], and [protein] is of great value in
[HCO3] because it is a dependent variable and understanding how changes in these values
not one of the three key independent variables. impact acid-base and fluid balance. In particu-
Despite the precision of this approach, its lar, careful analysis of electrolytes and protein
cumbersome and technical nature make it dif- can assist in understanding the nature of extra-
ficult to understand and apply in clinical prac- cellular fluid contraction alkalosis, dilution
tice.476 Notwithstanding, I believe its focus on acidosis, and protein disturbances.
EXERCISES
Exercise 12-1 Regulation of Ventilation

1. The primary respiratory center (generator) located in the central nervous system
is in the ______.
2. The central chemoreceptors respond directly to the pH of the (blood/CSF).
3. The blood-brain barrier is readily permeable to (ions/gases) but is relatively impermeable
to (ions/gases).
4. The circulatory delay has been suggested to explain the breathing pattern sometimes
observed in congestive heart failure called ______ respiration.
5. The peripheral chemoreceptors are located in two distinct anatomic areas:
the ______ and ______ bodies.
6. Designate which of the following may stimulate the peripheral chemoreceptors:
a. Mild anemia
b. Hypoxemia
c. Cyanide poisoning
d. Hypercarbia (PaCO2 70 mm Hg)
e. Cardiogenic shock
f. pH 7.32
7. The (central/peripheral) chemoreceptors respond to low oxygen levels in the blood.
8. When PaO2 falls below ______ mm Hg, there is a dramatic increase in impulse production
and ventilation.
9. The regulation of ventilation in healthy individuals is primarily under the control of the
(central/peripheral) chemoreceptors.
10. In acute hypoxemia, the central chemoreceptors are (stimulated/depressed).
11. The ventilatory response to chronic hypoxemia is (less/greater) than the ventilatory
response to acute hypoxemia.
12. The initial blood gas abnormality associated with mild pulmonary disease is mild
(hypoxemia/hypercarbia).
13. In severe pulmonary disease, blood gases typically show (hypocarbia/hypercarbia).
14. Administration of oxygen to individuals with chronic pulmonary disease may result in
progressive (hypercarbia/hypocarbia).
15. The (J receptor/Hering-Breuer) reflex is located in the interstitial tissue of the
alveolar-capillary membrane.
Exercise 12-2 Renal Function

1. Each of the two kidneys consists of an outer ______ and an inner ______.
2. Urine gathers in the renal pelvis and then flows through the ______ down to the urinary
bladder, where it is stored.
3. The functional unit of the kidney is the ______.
4. The capillary network within Bowmans capsule is called the ______.
5. Blood enters the nephron through the (afferent/efferent) arteriole.
6. The tubule that the glomerular filtrate passes through immediately after leaving Bowmans
capsule is called the ______ ______ ______.
7. Cells and proteins (can/cannot) normally pass through the glomerulus into the filtrate.
8. Decreased urine output is called ______.
9. The process of exchanging one electrolyte for another in the filtrate is called tubular
(absorption/secretion).
10. The fluid that accumulates within Bowmans capsule is called the ______.
Exercise 12-3 Body Fluids and Electrolytes

1. Most body water is located in the (extracellular/intracellular) fluid space.

2. Fluid within the vascular system is called the ______ fluid.
3. If plasma is allowed to coagulate and the coagulated fluid is centrifuged, the clear fluid
that remains is called ______.
4. The portion of the extracellular fluid that exists outside the vascular space is
called the ______ fluid.
5. Glucose is an example of a/an (electrolyte/non-electrolyte).
6. Electrolytes that carry a positive charge are called (cations/anions).
7. (Sodium/potassium) is the most abundant intracellular cation.
8. List the four major cations in the plasma with their normal concentrations.
9. The most abundant extracellular cation is (potassium/sodium).
10. (Na+ /K+) is intimately related to osmosis and fluid balance.
Exercise 12-4 Chemical Mechanisms of Sodium Reabsorption

and the Renin-Angiotensin System
1. State the two different chemical mechanisms by which Na+ is reabsorbed from the
glomerular filtrate.
2. To maintain electroneutrality, the anion ______ passively accompanies Na+ from the filtrate
to the renal tubular cell in the NaCl mechanism.
3. State the two possible cations that can be secreted into the filtrate in exchange for a Na+
in the NaHCO3 reaction.
4. Carbonic anhydrase (is/is not) present in the renal tubular cells.
5. Hydrogen ions available to be secreted in the NaHCO3 reaction are produced as a result of
the (NaCl/hydrolysis) reaction.
6. In the presence of alkalemia, (H+/K+) is selectively secreted in the NaHCO3 reaction and
(H+/K+) is retained.
7. The group of cells that are located in the walls of the afferent arterioles of the nephrons
immediately adjacent to the glomerulus and that have the ability to detect decreased renal
perfusion are called the ______ cells.
8. The juxtaglomerular cells secrete (angiotensin/renin) into the bloodstream.
9. Angiotensin II stimulates the production of ______ from the adrenal cortex.
10. Aldosterone stimulates (NaCl/NaHCO3) reabsorption.
Exercise 12-5 Total Sodium Reabsorption and Diuretics

1. Most Na+ is reabsorbed in the (proximal/distal) tubule.

2. Normally, (20%/80%) of Na+ reabsorption is in the form of NaCl.
3. Na+ reabsorption in the distal tubule is primarily in the form of (NaCl/NaHCO3).
4. Technically speaking, HCO3 is (reabsorbed/reclaimed) from the filtrate.
5. About 90% of bicarbonate reabsorption occurs in the (proximal/distal) tubule.
6. Most of the commonly used diuretics interfere with (NaCl/NaHCO3) reabsorption.
7. (Thiazide/Loop) diuretics are quite potent.
8. Loop and thiazide diuretics may lead to the development of metabolic (acidosis/alkalosis)
and (hypokalemia/hyperkalemia).
9. The metabolic alkalosis seen with administration of loop diuretics (is/is not) due to an
aldosterone response.
10. The diuretic of choice in metabolic alkalosis is (thiazide/acetazolamide).
Exercise 12-6 Hyperaldosteronism, Urinary Buffers,

and Potassium
1. Hyperaldosteronism leads to metabolic (acidosis/alkalosis).

2. Hyperaldosteronism leads to (increased/decreased) H+ excretion and
(hyperkalemia/hypokalemia).
3. Hyperaldosteronism that occurs as a result of the renin-angiotensin system (e.g.,
diuretic- or hypoperfusion-induced) is called (primary/secondary) hyperaldosteronism.
4. Aldosterone is classified chemically as a (mineralocorticoid/glucocorticoid).
5. Cushings syndrome is an example of (primary/secondary) hyperaldosteronism.
6. Steroids administered therapeutically are classified chemically as
(glucocorticoids/mineralocorticoids).
7. Secretion of H+ ions into the filtrate occurs only until the pH of the filtrate falls to
approximately ______.
8. Name the three urinary H+ buffer systems.
9. In acidemia, the serum [K+] usually (increases/decreases).
10. The increased K+ observed in the plasma in acidemia originates from the
(interstitial/intracellular) space.
Exercise 12-7 Law of Electroneutrality, Anion Gap, and

Stewarts Strong Ion Difference
1. Because of the law of electroneutrality, metabolic alkalosis is usually associated with

(hypochloremia/hyperchloremia).
2. The anion gap is an index that can be used to help to determine the cause of metabolic
(alkalosis/acidosis).
3. Write the formula for calculation of the anion gap using serum electrolytes.
4. The normal anion gap range is about ______ mEq/L.
5. Metabolic acidosis with a normal A is called (hypochloremic/hyperchloremic) metabolic
acidosis.
6. In the presence of increased fixed acids in the blood, the anion gap (increases/decreases).
Calculate the anion gap, given the following electrolytes, and indicate whether the metabolic
acidosis is due to increased fixed acids or to a decreased base (assume normal albumin).
Na+ Cl TCO2
7. 140 98 14
8. 142 105 15
9. 135 115 10
10. 134 102 17
11. Low albumin tends to (increase/decrease) the anion gap.

12. According to Stewarts strong ion difference, [HCO3 ] is a/an (dependent/independent)
acid-base variable.
13. State the three independent variables in Stewarts strong ion difference approach to
acid-base analysis.

1. Search the internet for Stewarts Strong ION Difference. Suggested site:
http://ccforum.com/content/4/1/6.
A. List the bodys strong ions.
B. State the purported advantage of using Stewarts strong ion difference.
2. Search the internet for increased anion gap metabolic acidosis.
A. What does the acronym MUDPILES stand for?
NBRC Challenge 12
1. A blood gas on a patient reveals a pri- A) the patients anion gap.

mary metabolic acidosis. One of the first B) serum potassium.
tests you would consider to determine C) PaO2.
the primary diagnosis would be: D) PaCO2.
A) chest radiograph. E) [Hb].
B) pulmonary function studies. (RRT EXAMINATION NBRC
C) serum electrolytes. MATRIX I,A,2,a)
D) 12 lead ECG.
4. In critically ill patients, the anion gap
E) fluid I&0.
should be interpreted in light of the
(RRT-CSE EXAMINATION NBRC
________ level.
MATRIX I,A,1,c)
A) albumin
2. Following administration of KCl I.V. for a B) hemoglobin
patient with metabolic alkalosis, the C) magnesium
serum potassium level is 4.0 mEq/L. You D) ionized calcium
would recommend: E) non-ionized calcium
A) increasing the dosage of potassium (RRT EXAMINATION NBRC
chloride. MATRIX III,A,1,g)
B) calculation of the anion gap.
5. After administration of FIO2 1.0, the
C) obtaining a chest radiograph.
patients anion gap moves from 23 to
D) holding the administration of KCl.
12 mEq/L, one can conclude the patient
E) obtaining an ECG.
most likely:
A) had ketoacidosis.
MATRIX III,A,1,g)
B) was hypokalemic.
3. An ECG tracing of a patient with chronic C) had lactic acidosis.
renal failure manifests a prolonged PR D) had hyperchloremic acidosis.
interval, a widened QRS, and a narrow E) had cyanide toxicity.
peaked T wave. It would be important to (RRT-CSE EXAMINATION NBRC
evaluate: MATRIX III,B,1,h)
Chapter
13
Differential Diagnosis of Acid-Base
Disturbances
it should be emphasized that a given set of acid-base values is never diagnostic of a particular acid-base
disorder, but rather consistent with a wide range of acid-base abnormalities.
J.A. Kraut and N.E. Madias540
For each class of disorders (i.e., metabolic acidosis, respiratory alkalosis, etc.), a wide range of possibilities
exists When the diagnosis is not immediately apparent from the history or clinical setting, however,
laboratory data can be extremely helpful.
Jordan J. Cohen and
Jerome P. Kassirer483
As with all acid-base disorders, analysis of arterial blood gas samples and serum electrolytes provide the
quantitative basis for diagnosis and treatment.
Erik Swenson484
The value of establishing a diagnosis is to provide a logical basis for treatment and prognosis.
Clayton L. Thomas482
Outline
Introduction, 333 Overall Appearance, 341
Complete Picture, 333 Common Causes of Respiratory Alkalosis, 341
Classification versus Diagnosis, 333 Hypoxemia, 341
Support Information, 333 Overzealous Mechanical Ventilation, 342
Definitive Acid-Base Diagnosis, 333 Restrictive Lung Disease, 342
General versus Definitive Diagnosis, 333 Neurologic Disorders, 342
Common Causes of General Disturbances, 334 Shock/Decreased Cardiac Output, 343
Respiratory Acidosis, 334 Metabolic Acidosis, 343
Physiologic Response to Respiratory Acidosis Physiologic Response to Metabolic Acidosis, 343
(Hypercapnia), 334 Common Causes of Metabolic Acidosis, 343
Common Causes of Respiratory Acidosis, 334 High Anion Gap Metabolic Acidosis, 344
Chronic Obstructive Pulmonary Disease, 335 Normal Anion Gap Metabolic Acidosis, 348
Oxygen Excess in Chronic Obstructive Metabolic Alkalosis, 350
Pulmonary Disease, 336 Physiologic Response to Metabolic Alkalosis, 351
Drugs, 336 Common Causes of Metabolic Alkalosis, 351
Extreme Ventilation-Perfusion Mismatch, 336 Hypokalemia, 352
Exhaustion, 337 Ingestion of Large Amounts of Alkali or
Neuromuscular Disorders, 337 Licorice, 352
Iatrogenic Respiratory Acidosis, 338 Gastric Fluid Loss, 353
Neurologic Disorders, 339 Hyperaldosteronism Secondary to Nonadrenal
Excessive CO2 Production, 339 Factors, 353
Respiratory Alkalosis, 340 Bicarbonate Administration, 354
Physiologic Response to Respiratory Alkalosis Adrenocortical Hypersecretion, 354
(Hypocapnia), 340 Steroids, 355
Neurologic Response, 340 Eucapnic Ventilation Posthypercapnia, 355
Cardiovascular Response, 340 Exercises, 356
332
Chapter 13 Differential Diagnosis of Acid-Base Disturbances 333
abnormal patient process (i.e., perhaps it is due

INTRODUCTION
to compensation). Thus, the clinician must seek
A systematic method for classification of additional evidence that supports the presence
acid-base status, based on the arterial blood gas of a primary abnormal acid-base process.
report, was described in Chapter 2, and limits,
rules, and steps in classification were clearly Support Information
delineated. Application of these principles leads Additional information that must be used to sup-
to consistent results regardless of the back- plement and modify blood gas findings includes
ground of the interpreter. In fact, these limits drug therapy, vital signs, chest radiograph, elec-
and steps can be programmed into a computer trocardiography, pulmonary function studies,
that will provide reproducible classifications. and physical assessment. Assessment of various
There is no question that blood gas classifi- blood tests is also important. Measurement of
cation is useful in the clinical assessment of electrolytes, blood glucose, blood urea nitrogen
acid-base status. It is an excellent way to sum- (BUN), creatinine, red blood cell count, and
marize the blood gas report and to focus atten- white blood cell count provides valuable insight
tion on important problem areas. However, into the patients acid-base status, particularly in
many acid-base disorders go unrecognized if the critical care setting. Indeed, many blood gas
only the blood gas report is considered. machines now include many of these measure-
Furthermore, general acid-base diagnoses such ments along with blood gases.
as metabolic acidosis or respiratory alkalosis
do not provide a great deal of information Definitive Acid-Base Diagnosis
about the underlying disorder. Optimal patient General versus Definitive Diagnosis
treatment and follow-up requires a more spe- An acid-base diagnosis based on blood gas
cific, in-depth, understanding of the nature of classification alone lacks specificity. Even after
the problem. complete acid-base assessment, a diagnosis of
respiratory acidosis or metabolic acidosis is a
Complete Picture general acid-base diagnosis. A general acid-base
Just as the PaO2 is only one piece in the puzzle diagnosis does not reveal the patients underlying
of tissue oxygenation, the blood gas is similarly disease or problem.
only one piece in the puzzle of acid-base balance. Examples of more definitive acid-base diag-
All laboratory tests should be interpreted within noses are lactic metabolic acidosis secondary to
the context of the patient as a whole. The effec- hypoxia or respiratory alkalosis secondary to
tive clinician considers more than numbers from hypoxemia. Compared with a general acid-base
a solitary test. The conglomerate of pre-existing diagnosis, a definitive diagnosis provides the
disease, knowledge of physiology and pathology, clinician with a much clearer understanding
effects of therapeutic interventions, and integra- of the acid-base pathophysiology. Furthermore,
tion of historical data must all be considered. depiction of the specific root problem in a given
The ability to integrate these myriad consider- acid-base disturbance is a prerequisite to optimal
ations is indeed the art of acid-base diagnosis. treatment and therapy.
Thus, the clinician should not conclude
Classification versus Diagnosis acid-base assessment with only a blood gas
The clinician must keep in mind that when the classification or a general acid-base diagnosis
terms acidosis or alkalosis are applied to a (e.g., respiratory acidosis, metabolic alkalosis).
patient, they reflect a pathologic acid-base A more descriptive etiology (i.e., definitive diag-
process, and not simply an isolated laboratory nosis) must be determined after careful analy-
finding. It is technically incorrect to state that sis of physical findings, symptoms, history, and
the patient has a metabolic acidosis simply supplemental laboratory data. Furthermore,
because the bicarbonate or base excess on the identification of the specific acid or base that has
blood gas report is low. A low base excess rep- caused the disturbance (e.g., increased carbonic
resents a laboratory measurement (laboratory acid, increased lactic acid, loss of bicarbonate)
metabolic acidosis) and not necessarily an also helps to clarify thinking and understanding.
Common Causes of General Disturbances hypercapnia, cerebral blood flow may more
In this chapter, some of the more common causes than double while, conversely, it will decrease
of respiratory and metabolic acid-base distur- by more than 50% when PaCO2 falls by about
bances are briefly discussed. The novice clinician 10 mm Hg.496 This may be especially impor-
is encouraged to review this information before tant in the patient with CNS trauma or fol-
he or she attempts to make a definitive acid-base lowing CNS surgery where low intracranial
diagnosis at the bedside. A diligent attempt has pressure is a goal in patient treatment. In
been made to include all the common causes of chronic hypercapnia, cerebral blood flow is nor-
these general acid-base disorders and some mal and responsiveness to changes in PaCO2 is
causes that are less common. Obviously, it is reduced. It appears that interstitial acidosis is
impossible to list every possible cause. really the primary regulator of cerebral dilation
In general, the boxes have been constructed and perfusion.497
as functional groupings of acid-base disorders. Cardiovascular effects in mild to moderate
Problems with similar mechanisms (e.g., neuro- hypercapnia typically include an increased car-
muscular problems) have been clustered diac output and tachycardia mediated through
together rather than trying to list every specific an adrenergic response. On clinical examina-
disease that could cause a particular type of tion, the skin may be flushed and warm. The
acid-base disorder. patient may also be diaphoretic and demon-
It is noteworthy that often more than one strate a bounding pulse. In severe hypercapnia,
root problem is responsible for a general hypotension and/or arrhythmia may occur as a
acid-base diagnosis. A patient may have meta- direct effect of PaCO2 on the myocardium and
bolic alkalosis due to a combination of factors. vasculature.485
For example, it is not uncommon for a patient to Physiologic changes may be more related to
be receiving both diuretics and steroids and, in concurrent acidemia and hypoxia than hyper-
addition, to manifest hypokalemia. In this case, capnia. Certainly there is a less dramatic response
three different underlying factors could be con- when hypercapnia develops slowly. The some-
tributing to a metabolic alkalosis. Therefore, it is what innocuous nature of hypercapnia has
advisable to review and consider all possibilities, lead to the therapeutic approach of permissive
even if one mechanism is already evident. hypercapnia498 where hypercapnia is tolerated
in an effort to avoid excessive alveolar volume
and pressure (see Chapter 10). Many believe
RESPIRATORY ACIDOSIS
that substantial hypercapnia is likely associated
Respiratory acidosis may result from a variety with very few adverse effects.498
of acute and chronic causes. It threatens
acid-base balance through the accumulation of Common Causes of Respiratory Acidosis
carbonic acid. Furthermore, it compromises As discussed previously, it is important to
oxygenation via decreased alveolar delivery identify the underlying cause of the acid-base
and hypoxemia. disorder to optimize management. Some com-
mon causes of respiratory acidosis are shown
Physiologic Response to Respiratory in Box 13-1.
Acidosis (Hypercapnia) Some may find it easier to think of the
The clinical manifestations of acute hypercapnia potential origins of the various fundamental
are predominantly neurologic.485 Symptoms acid-base disturbances. For example, as shown in
may vary from anxiety and irritability to Figure 13-1, eight common sources of primary
lethargy and somnolence. Pulmonary symptoms respiratory acidosis are: the lungs (e.g., chronic
may include dyspnea and distress. Stupor and obstructive pulmonary disease [COPD]), drugs
coma appear to be rare but may occur when (e.g., anesthetics/narcotics), mechanical ven-
PaCO2 exceeds 70 mm Hg.485 tilation (e.g., iatrogenic hypoventilation),
It is also important to remember that hyper- muscle fatigue (e.g., status asthmaticus),
capnia causes increased cerebral perfusion and central nervous system (CNS; e.g., central alveo-
intracranial pressure. Indeed, during acute lar hypoventilation), neuromuscular junction
Chronic Obstructive Pulmonary Disease

Box 13-1 Causes of Respiratory
Acidosis The most common cause of chronic respira-
tory acidosis is COPD. Emphysema, chronic
Chronic obstructive pulmonary disease (COPD)
bronchitis, and asthma are the major sub-
Oxygen excess in COPD
Drugs
groups of COPD. COPD is characterized by
Barbiturates progressive airway disease that leads to gas
Anesthetics trapping, uneven distribution of ventilation,
Narcotics hypoxemia, and, ultimately, in severe disease,
Sedatives respiratory acidosis.
Extreme ventilation-perfusion mismatch The patient with COPD is readily recog-
Exhaustion nized on physical examination by the presence
Neuromuscular disorders of a barrel chest, adventitious (abnormal)
Poliomyelitis breath sounds, labored breathing, and forced
Amyotrophic lateral sclerosis expiration. Hyperaeration and flattened
Guillain-Barr syndrome
diaphragm are present on the chest radio-
Electrolyte deficiencies (K+, PO4)
Myasthenia gravis
graph. Pulmonary function studies show a
Iatrogenic respiratory acidosis diminished forced expiratory flow (FEF) in
Neurologic disorders the mid-expiratory flow in moderate disease,
Excessive CO2 production progressing to a decreased forced expiratory
Total parenteral nutrition volume in 1 second (FEV1) in more severe
Sepsis disease.
Severe burns Chronic respiratory acidosis is only seen in
NaHCO3 administration approximately 25% to 33% of patients with
significant chronic airflow obstruction.499
Chronic hypercapnia appears to be a mecha-
(e.g., Guillain-Barr syndrome), increased nism whereby some patients avoid excessive
metabolism in cells/tissues (e.g., burn patients), respiratory muscle fatigue. Indeed, because
and oxygen excess depressing ventilatory drive of the hypercapnia, these patients can elimi-
(e.g., in COPD). nate CO2 with far less ventilatory effort.499,500
CNS
Neuromuscular
Muscle fatigue
junction
Mechanical Respiratory Metabolism

ventilation acidosis (tissues/cells)
Drugs O2 excess
Lungs O2
Figure 13-1. Potential sources of respiratory acidosis.

Therefore, hypercapnia appears to be a useful FIO2, it is logical to assume that oxygen therapy
strategy for avoiding inspiratory muscle over- was excessive.
loading and failure.499 Notwithstanding, Interestingly, oxygen therapy may worsen
due to their limited ventilatory reserve, acute hypercapnia in other chronic disorders as well.
pneumonia can and frequently does lead to Although the mechanism is unclear, these
a superimposed acute ventilatory failure in these include patients with neuromuscular disease,
individuals.501 asthma, diaphragmatic dysfunction, or obesity
hypoventilation syndrome.485
Oxygen Excess in Chronic Obstructive
Pulmonary Disease Drugs
As described previously, chronic respiratory Depressant drugs such as morphine may dimin-
acidosis is common in end-stage COPD. In ish respiratory drive,492 with resultant hypercar-
addition, when high concentrations of oxygen bia and acidosis. The response of a given patient
are administered to patients with end-stage depends on the individual, the drug, and the
COPD (especially those with hypercarbia), dosage. Barbiturates, anesthetics, narcotics, and
they may manifest an acute rise in PaCO2 lev- sedatives may cause this effect. Narcotic over-
els above their chronically elevated baseline dose characteristically manifests itself in a slow
PaCO2. This acute respiratory acidosis is most respiratory rate in the spontaneously breathing
apt to occur when PaCO2 levels are very high patient.
and/or when PaO2 levels are very low at the Individuals with COPD are particularly
time when the oxygen is administered.486,487 vulnerable to the respiratory effects of seda-
Actually, baseline hypoxia and acidosis are tives and narcotics and may exhibit further
better predictors of those patients likely to CO2 retention even at normal dosages. Although
have worsening respiratory acidosis than base- the usual setting for drug-induced hypoventila-
line PaCO2.485 tion is the emergency room, respiratory acido-
Even slight elevations in FIO2 may cause sis secondary to drug effects may also be seen
this effect.488,489 The acute hypercarbia may be in the postoperative or critical care milieu.
progressive and may occasionally result in res- Neuromuscular blocking agents may also be
piratory arrest. The rise in PaCO2 may be used to control ventilation in the ICU. This is
caused by obliteration of the hypoxic drive of particularly true with many of the new ventila-
the peripheral chemoreceptors; however, some tory techniques such as inverse I:E ratios and
evidence suggests that it is due primarily to permissive hypercapnia, which may render
a worsening of ventilation-perfusion match- the patient uncomfortable or anxious. Barring
ing.490 In all likelihood, it is a multi-factorial the obvious problem of potential ventilator dis-
response. connect, one must be careful to avoid paralysis
Regardless of the potential for acute respira- without adequate sedation. The terror of con-
tory acidosis, when hypoxia is suspected, oxy- scious paralysis is unthinkable.
gen must be administered in doses sufficient to
relieve it. The target of oxygen therapy in COPD Extreme Ventilation-Perfusion Mismatch
is typically a PaO2 of approximately 60 mm Hg, As stated earlier, the mechanism that ultimately
although not higher.486,491 When acute respira- leads to respiratory acidosis in COPD is most
tory acidosis is observed in a patient with COPD likely deterioration in the ventilation-perfusion
who has a PaO2 level greater than 60 mm Hg, match. Regardless of the disease, whenever gas
the FIO2 may be excessive. The higher the PaO2 exchange capabilities of the lung become
and FIO2 level, the more likely that the respi- extremely compromised, the ability of the lungs
ratory acidosis is at least in part related to the to excrete CO2 may become impaired. This may
oxygen therapy. occur in severe lung cancer, pneumonia, or any
A trial of decreased FIO2 followed by arte- other severe pulmonary parenchymal disease.
rial blood gases should reveal whether excess In summary, any acute or chronic disease that
oxygen was in fact the cause of the acute respi- results in severe lung damage may ultimately
ratory acidosis. If PaCO2 improves at a lower lead to respiratory acidosis.
Exhaustion and respiratory acidosis. Some of the more

Acute respiratory acidosis may likewise occur common disorders that may affect neuromus-
as a result of simple exhaustion due to exces- cular integrity include myasthenia gravis,
sive work of breathing over an extended poliomyelitis, amyotrophic lateral sclerosis,
period. This mechanism may explain the and the Guillain-Barr syndrome.
sudden onset of respiratory acidosis that has Guillain-Barr syndrome is characterized by
been observed in patients with status asth- loss of reflexes and symmetric paralysis, typically
maticus after a sustained period of laborious beginning in the legs, with eventual nearly com-
breathing. plete or complete recovery.502 Acute Guillain-
In progressive pulmonary disease of any Barr usually begins with fine paresthesias in
origin, there appears to be some point at which the toes or fingertips, followed within days by
the work of breathing is so great that adequate leg weakness that makes walking and climbing
ventilation can no longer be maintained. The stairs difficult. Weakness usually ascends and
patient may respond to this scenario with pro- pain is common. Approximately two-thirds of
gressive hypercapnia or even with respiratory cases follow an infection. Increased protein in
arrest due to extreme fatigue. Mechanical ven- the cerebrospinal fluid is a valuable diagnostic
tilation is indicated at this point to give the marker. Patients with very low (i.e., < 18 mL/kg)
patient a rest. or rapidly declining vital capacities should be
There is also some evidence to suggest that transferred and observed in ICU.
the onset of exhaustion is related to the degree The trend of neuromuscular dysfunction on
of lactic acidosis that develops as a result of ventilation can be observed at the bedside
the extreme workload.447 through serial measurements of vital capacity.
A falling vital capacity may indicate progres-
Neuromuscular Disorders sive hypoventilation and perhaps the onset of
Neuromuscular Disease respiratory acidosis. Figure 13-2 designates
Diseases that affect the neuromuscular junc- suggested clinical management of the Guillain-
tion or the function of the respiratory muscles Barr syndrome based on progressive deterio-
themselves may progress to hypoventilation ration of the vital capacity.
VITAL CAPACITY
(mL/kg)
RESPIRATORY PATHOPHYSIOLOGY Normal VENTILATORY MANAGEMENT

65
45
Poor cough secretions accumulate 30 Chest physical therapy
25
Sigh mechanism compromised Incentive spirometry and deep breathing
atelectasis and hypoxemia begin 20 to minimize ongoing atelectasis
15 Elective intubation for positive-pressure

Sigh lost atelectasis and shunting ventilation; several high-volume breaths
per minute
Hypoventilation 10 Positive-pressure ventilation to aid gas
exchange and prevent fatigue
Hypercapnia Full ventilation
5
Figure 13-2. Vital capacity in management of Guillain-Barr syndrome.

Normal Myasthenia gravis
Synaptic
space
Acetylcholine
receptors
Muscle
Figure 13-3. Neuromuscular junction in myasthenia gravis. (Note the decreased acetylcholine receptors
and the widened synaptic space.)
Myasthenia gravis affects approximately in the apneic or paralyzed patient in whom the
25,000 people each year in the United States. rate and volume of ventilation is exclusively a
The basic abnormality in myasthenia gravis is a result of the ventilator settings. Thus, especially
decrease in the number of acetylcholine receptors in the patient on mechanical ventilation, there
in the neuromuscular junction.503 Figure 13-3 is always the possibility of therapy-induced
illustrates the decreased number of acetylcholine (iatrogenic) respiratory acidosis.
receptors and the widened synaptic space in Inappropriately low ventilator settings for
myasthenia gravis as compared to the normal tidal volume or respiratory rate results in an ele-
neuromuscular junction. The clinical result of vated PaCO2 and a blood gas classification of
this disease is neuromuscular weakness and respiratory acidosis. Thus, insufficient mechan-
fatigue. ical ventilation may induce respiratory acidosis,
particularly when drugs have been administered
Electrolyte Deficiencies to facilitate control of the patients ventilation.
Hypokalemia, a common electrolyte disorder in Subsequent manipulation of ventilatory set-
the critical care setting, is also associated with tings corrects only the iatrogenic respiratory
muscle weakness and even paralysis. The clini- acidosis. These ventilator changes cannot, of
cian must be particularly alert to this problem course, correct the underlying condition (e.g.,
when trying to wean patients from mechanical respiratory acidosis secondary to CNS depres-
ventilation. The presence of hypokalemia may sion) that was responsible for the initiation of
result in unsuccessful weaning attempts. Low mechanical ventilation in the first place.
phosphate levels, although less common, may
similarly impede normal neuromuscular control. Permissive Hypercapnia
In most applications of mechanical ventilation,
Iatrogenic Respiratory Acidosis the goal is to normalize PaCO2. Notwithstand-
During mechanical ventilation, some aspects of ing, in contrast to traditional mechanical ven-
the ventilatory pattern (e.g., tidal volume, res- tilation, it is now common in acute lung injury
piratory rate) may not be under the direct con- and acute respiratory distress syndrome (and
trol of the patient; rather, they are a product of some other disorders) to allow respiratory aci-
the machine settings. This is particularly true dosis to develop in an effort to avoid excessive
alveolar pressure or volume. This so-called production (RQ of 0.7) than carbohydrate
permissive hypercapnia is considered to be metabolism (RQ of 1.0).
potentially less harmful than using higher lung Total Parenteral Nutrition and the Respira-
inflation pressures to ensure a normal PaCO2. tory Quotient. Total parenteral nutrition (TPN)
Nevertheless, severe hypercapnia should still is a nutritional support formula administered
be avoided, even in this population, and even intravenously to critically ill patients to avoid
mild hypercapnia may be harmful if there is the adverse effects of malnutrition.493 TPN
concern regarding excessive cerebral perfusion consists of a mixture of glucose and amino
or when there is substantial acidemia. acids. As such, TPN is high in carbohydrates
and increases the RQ and the production of
Neurologic Disorders CO2 after administration. In the patient unable
Neurologic disease or trauma (including spinal to meet the increased ventilatory requirement
cord injury) may also lead to hypoventilation necessary to excrete this additional CO2, respi-
and respiratory acidosis. The mechanism by ratory acidosis may ensue.
which this effect occurs is via depression or Specifically, acute respiratory acidosis has
malfunction of the respiratory centers or an been observed in patients with chronic lung
increased intracranial pressure. Similarly, CNS disease in response to the administration of
dysfunction is probably responsible for the TPN.494 This effect may occur both in nonintu-
respiratory acidosis that commonly follows bated patients and in patients on mechanical
cerebral hypoxia and cardiac arrest. ventilation.494,495 During mechanical ventilation,
The CNS is also responsible for the respira- the risk of TPN-induced respiratory acidosis is
tory acidosis that occurs during sleep in patients reduced if the minute volume of the ventilator
with central sleep apnea. In addition, central is increased just before TPN administration.495
mechanisms may play a role in the chronic res- In addition, the development of hypercapnia
piratory acidosis associated with obesity that is has been reported in two young patients without
known as the Pickwickian syndrome. Finally, COPD during weaning from mechanical ventila-
Ondines curse, a condition characterized by tion while receiving TPN.338 Furthermore, when
unexplained hypoventilation, most likely has the number of carbohydrate calories given to
a neurologic origin. these patients was decreased, CO2 production
likewise dropped, and the respiratory acidosis
Excessive CO2 Production was corrected.338 In summary, a high RQ may
As described in Chapter 8 in the section on CO2 contribute to the onset or maintenance of
homeostasis, the PaCO2 depends not only on respiratory acidosis.

the quantity of CO2 leaving the blood (i.e., VA),
but also on metabolism and CO2 production Quantity of Metabolism: Thermic Effect

(VCO2). The significance and effects of CO2 Just as a high RQ can increase CO2 production,
production on ventilation and acid-base status a general increase in the quantity of energy
in critically ill patients have only recently been metabolism (thermic effect), such as may occur
appreciated. Carbon dioxide production with fever, will also increase CO2 production
depends on both the type and the quantity of and may contribute to respiratory acidosis.
metabolism. Malignant hyperthermia (MH) is an inher-
ited condition in which some medications
Type of Metabolism (especially anesthetics) trigger sustained skeletal
The Respiratory Quotient and CO2 Production. muscle contraction and hypermetabolism.504
As described in Chapter 7, the respiratory Symptoms include rapid, acute severe respi-
quotient (RQ) relates CO2 production to oxy- ratory acidosis; hyperthermia; ventricular

gen consumption (VCO2/ VO2). The numeric dysrhythmias; hyperkalemia; and muscular
value of the RQ, in turn, depends on the rigidity.505 The clinical course of the disorder is
type of body fuel being metabolized. Fat short, usually 1 to 3 days. Untreated, MH may
metabolism for example, results in less CO2 have a 70% mortality.504 Treatment includes
termination of the triggering agent, and control tissue PCO2 and thus exacerbate the tissue
of pH, temperature, and potassium.505 acidosis. This issue is discussed in greater detail
Patients with severe burns also have an in Chapter 14 in the section on treatment of
increase in total body metabolism secondary to metabolic acidosis.
tissue destruction and the reparative process.
This response is greater than the hypermetab-
RESPIRATORY ALKALOSIS
olism seen in sepsis or other forms of trauma.
The magnitude and duration of the metabolic Respiratory alkalosis, like respiratory acidosis,
response parallel burn severity with metabo- may result from a variety of acute and chronic
lism doubling in a 60% total body burn.506 causes. It disrupts acid-base balance by deplet-
Other causes of hypermetabolism include ing the normal blood stores of carbonic acid.
sepsis, fever, thyrotoxicosis, and trauma.485 In Respiratory alkalosis is a very common acid-
fever, CO2 production will increase approxi- base disorder.
mately 13% for each degree centigrade eleva-
tion in body temperature. TPN is associated not Physiologic Response to Respiratory
only with a high RQ; it also has a thermic effect Alkalosis (Hypocapnia)
secondary to the protein component of the solu- Patients with respiratory alkalosis often pres-
tion.550 Consequently, TPN tends to increase ent with dyspnea and chest pain or tight-
CO2 production through changes in both the ness.512 In addition to renal compensation (i.e.,
type and quantity of metabolism.550 decreased [HCO3]) for respiratory alkalosis,
Indeed the thermic effect appears to have an hypocapnia will decrease cerebral blood flow,
even stronger impact on CO2 production than alter some electrolyte concentrations, and
the type of substrate used for metabolism. The increase the production of lactic acid.
administration of excess calories will also lead Regarding potassium, there is an initial
to increased CO2 production through lipogen- abrupt onset of hyperkalemia. This is rapidly
esis, which has an RQ of nearly 8.0.507 followed by the development of hypokalemia.508
Thus, the number of calories, the percent- Typically, serum potassium will decrease
age of carbohydrate, and the nature of the 0.3 mEq/L for each 0.1 unit increase in pH.508
patients illness must all be considered regard- Occasionally, electrolyte disturbances will be
ing the CO2 production load. In contrast, CO2 associated with muscle spasm. In addition,
production may sometimes be reduced by respiratory alkalosis increases production and
decreased glucose intake, cooling, or paralyz- decreases the clearance of lactic acid; however,
ing the patient.498 the increase in lactic acid levels is only
modest.508
Sodium Bicarbonate Administration
Administration of sodium bicarbonate Neurologic Response
(NaHCO3) intravenously also increases blood Hypocarbia has been associated with painful
CO2 levels via the hydrolysis reaction. In spon- tingling in the hands and feet and numbness
taneously breathing individuals who are capa- and sweating of the hands. Dizziness is also
ble of increasing alveolar ventilation, this excess sometimes observed. Typically, these symp-
CO2 is immediately excreted. However, in the toms require PaCO2 to decline approximately
patient unable to excrete the additional blood 20 mm Hg. As described previously, decreased
CO2 (e.g., because of neurologic disease or con- cerebral perfusion has also been associated
trolled mechanical ventilation), hypercarbia and with hypocarbia; however, this effect appears
acute respiratory acidosis develop.365 to be mediated by acidosis.
Severe hypercapnia and respiratory acidosis of
mixed venous blood has been shown to accom- Cardiovascular Response
pany resuscitation during cardiac arrest.567 Cardiovascular effects of hypocarbia include
It is presumed that these mixed venous gases peripheral vascular constriction, tachycardia,
reflect tissue conditions. The administration of and increased cardiac output. Hypocarbia
NaHCO3 in this setting may further elevate the may also decrease coronary blood flow and
potentially induce arrhythmias. The patient Box 13-2 Causes of Respiratory

may sometimes complain of palpitations, chest Alkalosis
pain, or tightness.
Hypoxemia (moderate to severe)
Overall Appearance Overzealous mechanical ventilation
Restrictive lung disorders
In patients admitted to the emergency depart- Fibrosis
ment, one hospital found the most common Ascites
presenting complaints with substantial hypocap- Scoliosis and thoracic cage deformities
nia were dyspnea (61%), chest pain or tightness Third trimester of pregnancy
(43%), paresthesias (35%), panic (30%), dizzi- Pneumonia
ness (13%), palpitations (13%), and muscle Acute respiratory distress syndrome
spasm (9%).512 Finally, acute respiratory alka- Congestive heart failure
losis may be associated with nausea, vomiting, Emboli in pulmonary circulation
or changes in gastrointestinal motility.508 Neurologic origin
Fever
Common Causes of Respiratory Anxiety
Cerebrospinal fluid acidosis
Alkalosis
Trauma
Although mild hypocapnia may be seen in Severe pain
females and children younger than the age of Shock/decreased cardiac output
3 years, most often respiratory alkalosis is not
normal. Some of the most common causes of
respiratory alkalosis are shown in Box 13-2. Six
possible origins of primary respiratory alkalosis Hypoxemia
are shown in Figure 13-4. These include the Hypoxemia is one of the most common
lungs (e.g., pulmonary fibrosis), drugs (e.g., and important causes of hyperventilation and
salicylate toxicity), mechanical ventilation, the respiratory alkalosis. Moderate hypoxemia
CNS (e.g., tumor), the cardiovascular system (PaO2 < 60 mm Hg) stimulates the peripheral
(e.g. cardiogenic shock), and thoracic cage chemoreceptors causing increased alveolar venti-
abnormalities (e.g., scoliosis). lation and respiratory alkalosis. For this reason,
CNS
Mechanical Respiratory Cardiovascular

ventilation alkalosis system
Drugs
Thoracic cage
Aspirin O.D.
Lungs
Figure 13-4. Potential sources of respiratory alkalosis.

whenever a PaO2 less than 60 mm Hg is seen in affect the alveolar-capillary membrane, including
conjunction with respiratory alkalosis, a cause- congestive heart failure, acute respiratory
and-effect relationship should be presumed. distress syndrome, fibrosis, pneumonia, and
Normalization of the PaO2 is often all that is pulmonary emboli.
necessary to restore a normal PaCO2. In some
patients, multiple mechanisms will be present. Neurologic Disorders
Therefore, when normalization of PaO2 fails to There are a variety of conditions that may cause
correct respiratory alkalosis, other underlying respiratory alkalosis via the central nervous
causes should be sought (see Box 13-2). system stimulation. These conditions include
chemical stimuli, acidosis of the cerebrospinal
Overzealous Mechanical Ventilation fluid, and physical and emotional stimuli.
The application of mechanical ventilation may
lead to iatrogenic respiratory alkalosis.509 Chemical Stimuli
Respiratory alkalosis may be the result of an Infection/Toxins. Although some neurologic
excessive tidal volume or respiratory rate setting. disturbances cause respiratory acidosis, many
At times, hyperventilation to a PaCO2 of 25 to neurologic problems may result in hyperven-
30 mm Hg is used therapeutically to decrease tilation. The respiratory alkalosis may be chem-
intracranial pressure in head trauma or CNS ically induced by an infectious condition such
disorders. as meningitis or septicemia. Presumably, the
infection produces a chemical that crosses the
Restrictive Lung Disease blood-brain barrier and stimulates the central
When expansion of the lungs, thoracic cage, or chemoreceptors. The accumulation of other
alveoli is restricted, certain reflexes are activated chemicals or toxins may similarly stimulate
(e.g., Hering-Breuer, J receptors) that stimulate hyperventilation. In hepatic (i.e., liver) encepha-
hyperventilation and respiratory alkalosis (see lopathy, for example, ammonia accumulates in
Chapter 12). The various disorders shown under the blood and stimulates ventilation via the CNS.
restrictive lung disease in Box 13-2 all have in
common some restriction of lung or alveolar Salicylates
expansion. Salicylates (e.g., aspirin) in large doses also
The Hering-Breuer reflex may play a role in stimulate the respiratory centers and cause
the hyperventilation of thoracic cage problems. hyperventilation. Therefore, a respiratory alka-
The hyperventilation of ascites (accumulation losis usually accompanies salicylate poisoning
of fluid in the peritoneal cavity), thoracic cage or overdose. For unknown reasons, adults seem
deformities, and the third trimester of preg- to display respiratory alkalosis as the dominat-
nancy could be, at least in part, a reflex reaction ing acid-base disturbance in salicylate intoxi-
to the mechanical restriction of inspiration. cation, whereas children more often have
It is known, however, that the respiratory metabolic acidosis due to the accumulation of
alkalosis of pregnancy is also related to the hor- salicylic acid as the dominant disturbance.
mone progesterone, which stimulates ventila-
tion.510 During pregnancy, especially the third Acidosis of the Cerebrospinal Fluid
trimester, PaCO2 is usually approximately 28 to Acidosis of the cerebrospinal fluid (CSF) leads
32 mm Hg.510 Furthermore, most women also to hyperventilation through stimulation of the
experience dyspnea even in the first two central chemoreceptors. The change in pH
trimesters of pregnancy.508 of the CSF most often parallels the change
The exact role of the J receptor reflex has not in pH of arterial blood. However, because of
been clarified. These receptors, situated within the relative impermeability to ions of the
the alveolar-capillary membrane, have been pos- blood-brain barrier, occasionally a change in
tulated to respond to thickening of or edema pH in the blood is not immediately reflected in
within the alveolar-capillary membrane. This is the CSF.
a feasible explanation for the hyperventilation CSF acidosis without blood acidemia is
commonly noted in various disorders that may likely to occur (1) after the correction of blood
acidemia with bicarbonate, (2) following descent respiratory alkalosis, however, it is likely that
from acclimatization to a high altitude, or (3) these individuals have high venous PCO2 levels
during weaning from mechanical ventilation and tissue respiratory acidosis. As described in
when a patient has had sustained hyperventila- detail in Chapter 14 in the section on the
tion while on the ventilator. Although these venous paradox, arterial blood gases may reflect
situations are not seen frequently, the clini- poorly the overall acid-base status in these
cian should always keep these possibilities in patients.
mind when hyperventilation cannot be easily
explained.
METABOLIC ACIDOSIS
Physical/Emotional Stimuli Metabolic acidosis occurs in a variety of dis-
In addition to chemical stimuli, the respiratory eases and even during normal heavy exercise.
centers may be stimulated by physical changes
in the CNS. Physical changes may result from Physiologic Response to Metabolic
CNS trauma with resultant increased intracra- Acidosis
nial pressure, or from a disease process such as Probably the most serious consequences of
a CNS tumor. Fever is also known to be asso- metabolic acidosis are on the cardiovascular
ciated with hyperventilation. system. Metabolic acidosis directly suppresses
Emotional stimuli may likewise lead to sub- myocardial contractility and vascular smooth
stantial hyperventilation during extreme stress muscle. This, in turn, may lead to a decreased
or severe pain. It is not uncommon for patients cardiac output and blood pressure. Concurrent
to present with respiratory alkalosis in the sympathetic nervous system stimulation may
emergency room or physicians office due to somewhat counteract the direct effects of aci-
hysteria, panic, or anxiety. dosis on the cardiovascular system when meta-
The term hyperventilation syndrome was bolic acidosis is mild.
first used in 1938 to describe patients who pre- Metabolic acidosis may also result in hyper-
sented with hypocapnia and anxiety.511 kalemia as potassium migrates from the intra-
Hyperventilation syndrome is purported to cellular space to the plasma (see Chapter 12) in
affect nearly 10% of the population.508 It affects exchange for hydrogen ions. This effect is most
predominantly females and occurs most often in prominent in non-organic types of acidosis.
the third or fourth decade of life.508 One must Finally, as previously described, respiratory
be careful, however, to rule out a compensatory acid-base compensation will lead to hyperven-
response to other acid-base disturbances such tilation and often dyspnea. Similarly, when pos-
as ketoacidosis or myocardial infarction.512 sible, renal compensation will include increased
acid excretion and bicarbonate absorption.
Shock/Decreased Cardiac Output In metabolic acidosis of non-renal origin, the
Finally, shock and decreased perfusion may lead kidney can increase hydrogen ion excretion
to respiratory alkalosis. It is not uncommon to three- to fourfold.484
see patients in profound hypotension and low
cardiac output states manifesting substantial Common Causes of Metabolic Acidosis
arterial hyperventilation. The hyperventilation Respiratory acid-base disturbances always
is probably due in part to peripheral chemo- reflect a change in blood volatile acid concen-
receptor stimulation secondary to diminished tration, specifically carbonic acid. Clinical
perfusion. metabolic acidosis, on the other hand, may be
Perhaps more importantly, the low cardiac the result of either the accumulation of some
output contributes to arterial hyperventilation fixed acid in the blood or the loss of normal
by another mechanism. The fall in pulmonary blood base.
perfusion associated with this state may lead to After a general acid-base diagnosis of meta-
a relative hyperventilation of the lungs due to bolic acidosis (primary) has been established,

many high alveolar V/Q units and despite nor- the patients biochemical profile should be eval-
mal minute ventilation. In contrast to the arterial uated. Typically, the biochemical profile consists
of electrolyte concentrations (Na+, K+, Cl, and a normal anion gap. Again, it is sometimes
HCO3 or total CO2), blood glucose, and an useful to think of the various potential sources
index of renal function (BUN or creatinine). of general acid-base disturbances. Figure 13-5
Using the electrolytes from the biochemical illustrates common sources of high anion gap
profile, the first step in determining a specific metabolic acidosis. High anion gap acidosis
acid-base diagnosis is calculation of the anion may occur as a result of: toxins (e.g., methanol
gap [Na (TCO2 + Cl) = A]. The anion gap poisoning), the kidneys (e.g., azotemic renal
(A) is helpful particularly in the diagnosis of failure), metabolism (e.g., lactic acidosis/
metabolic acidosis because it allows us to dif- ketoacidosis), or, less commonly, the liver (e.g.,
ferentiate conditions associated with increased cirrhosis).
fixed acids in the blood from conditions asso-
ciated with the loss of blood base. High Anion Gap Metabolic Acidosis
As described in Chapter 12, when the anion Box 13-3 lists the most common causes of high
gap exceeds 16 mEq/L, an increase in blood anion gap metabolic acidosis and the specific
fixed acids is highly probable. Furthermore, the acids that tend to accumulate with each disor-
higher the anion gap, the greater is the confi- der. Other data reported on the biochemical
dence in this conclusion. Conversely, when the profile (e.g., BUN, glucose) and the oxygena-
anion gap is normal (i.e., 12 to 14 mEq/L), a tion indices on the blood gas report are useful
loss of blood base is more likely the cause of the in making a definitive acid-base diagnosis.
metabolic acidosis. Like all laboratory data, Probably the three most common types of
marginal findings indicate the need for a more metabolic acidosis are ketoacidosis, azotemic
comprehensive evaluation of the patient and renal failure, and lactic acidosis.
his or her overall status. In addition, we must
always be cognizant of the effect of albumin Toxins
concentrations on the anion gap (hypoalbu- Aspirin Overdose. Salicylate toxicity may fol-
minemia decreases the anion gap) especially in low aspirin overdose, ingestion of oil of win-
critical care. The anion gap may be corrected tergreen (methyl salicylate), or ingestion of
for albumin levels as described in Chapter 12. other salicylate products. It should be noted that
The potential causes of metabolic acidosis one teaspoon of oil of wintergreen is equivalent
can thus be separated into two groups: (1) to approximately 21 regular strength aspirin
those associated with the accumulation of fixed tablets.513 The high anion gap acidosis is a
acids and therefore with a high anion gap, and result of the accumulation of salicylic acid, lactic
(2) those associated with the loss of base and acid, and ketoacids. Salicylate toxicity is most
Toxins
Metabolic
Liver acidosis Kidneys
High A
Metabolism
(tissues/cells)
Figure 13-5. Potential sources of high anion gap metabolic acidosis.

Box 13-3 Causes of High Anion Poisons/Drug Effects

Gap Metabolic Acidosis Wood Alcohol (Methanol). Ingestion of wood
alcohol leads to inebriation and metabolic
Etiology Accumulated Acid(s)
acidosis. It is also characterized by engorged
Toxins retinal vessels and blurred vision. There may be
Aspirin overdose Salicylic, lactic, a profound elevation of the anion gap. This
ketoacids
type of poisoning is most likely to be seen in
Wood alcohol Formic, lactic
(methanol)
the alcoholic.
Ethylene glycol Glycolic, oxalic, Ethylene Glycol. Ethylene glycol is the active
lactic ingredient of antifreeze. It has a sweet, pleasant
Paraldehyde Formic, lactic taste, and it may be accidentally ingested by chil-
Toluene Benzoic dren because of its taste and appearance (i.e.,
Azotemic renal failure Phosphoric, sulfuric color). Ethylene glycol has euphoric effects and
Lactic acidosis Lactic may be substituted for ethanol by alcoholics or
Hypoxia ingested in an attempt at suicide. Ethylene glycol
Ethanol ingestion causes an estimated 60 deaths each
Liver failure year; as little as 100 mL may be lethal.517
Poisonings
Notwithstanding, with early diagnosis and
(e.g., methanol)
Ketoacidosis Acetoacetic, beta-
effective treatment, mortality is close to zero.514
Starvation hydroxybutyric The clinical features of ethylene glycol inges-
Alcoholic tion occur in three distinct phases.518 Within
Diabetic 30 minutes to 12 hours, neurologic symptoms
are observed (e.g., hallucinations, stupor, coma).
In 12 to 24 hours, cardiovascular complications
may occur (e.g., heart failure, arrhythmia).
often seen in children less than 1 year old but Finally, the breakdown of ethylene glycol results
is also relatively common in adults. in oxalic acid, which crystallizes in the kidney.
Early clinical manifestations of salicylate Thus, acute renal failure constitutes the third
toxicity include hyperventilation, mild confu- stage of toxicity.
sion, tinnitus, and decreased auditory acuity. Treatment of ethylene glycol poisoning
These mild symptoms can rapidly progress to focuses on preventing its metabolism and on
seizures, coma, and death.513 The presence of facilitating its excretion. Because it helps to
fever is a particularly ominous sign.513 prevent the metabolism of ethylene glycol,
The metabolic acidosis of salicylate poison- ethanol is usually administered intravenously.
ing is usually accompanied by a primary respi- The drug 4-methylpyrazole has been reported
ratory alkalosis, particularly in adults.515 to be even more effective than alcohol in this
Frequently in adults, the pH is near 7.40 or regard, however it is very expensive514,519 at
slightly alkaline despite an anion gap near approximately $4000/case.514 Hemodialysis is
20 mEq/L.513 Salicylate poisoning may be con- also recommended to facilitate the removal of
fused with ketoacidosis because the acid-base ethylene glycol.518
and clinical picture is similar in both problems Paraldehyde. Paraldehyde (Paral) is a
(i.e., hyperglycemia, ketosis). The diagnosis sedative/hypnotic drug sometimes used during
can be confirmed, however, based on a history delirium tremens in alcoholics or as an analgesic
of salicylate ingestion and high blood salicylate in obstetrics. Paraldehyde intoxication may
concentration, usually greater than 30 mg/dL; cause high anion gap metabolic acidosis.
however, it may be much higher.516 The clini- Toluene. Toluene is the active ingredient in
cian should also be aware that salicylate levels transmission fluid and paint thinner. Social
may continue to increase following admission abuse of this drug has been reported. Sniffing
especially with ingestion of enteric coated or inhaling toluene may cause lightheadedness
aspirin.513 For this reason, serial salicylate and euphoria and may lead to high anion gap
levels are imperative. acidosis.520
Azotemic Renal Failure Clinical Picture. Azotemic renal failure may

Many different types of renal disease may be be acute or chronic. The clinical course of acute
seen clinically. Renal failure associated with a renal failure is characterized by an oliguric phase
high anion gap and the inability to excrete followed by a polyuric phase. Because erythro-
fixed acids is called azotemic renal failure. poietin is produced in the kidneys, anemia is
Other types of renal disease may be associated common in renal disease, especially chronic
with a normal anion gap acidosis (e.g., renal renal failure. The anemia is typically normo-
tubular acidosis) secondary to the loss of blood chromic and normocytic. In addition, the
base (see discussion of normal anion gap aci- anemia is remarkably asymptomatic even at
dosis later in this chapter). The specific acids hematocrit levels of 15% to 20%.523 Therefore,
that accumulate in azotemic renal failure are transfusions are generally withheld until the
phosphoric and sulfuric acid. patient is symptomatic.523
Azotemia. Azotemia is the accumulation of Uremia is a toxic clinical condition associated
nitrogenous wastes in the blood from protein with azotemia and renal failure. Uremia affects
metabolism. The specific blood values that are a variety of body systems and causes a host of
elevated in azotemia are BUN and creatinine. symptoms (e.g., somnolence, depression, nausea
Blood Urea Nitrogen. Normal BUN is less and vomiting, and circulatory disturbances).
than 23 mg/dL. The BUN in a given patient
depends on the balance between the amount Lactic Acidosis
of urea being produced and the amount being Lactic acidosis is probably the most common
excreted. Urea production depends on the quan- cause of high anion gap acidosis. As such, it
tity of protein metabolism, and urea excretion should be afforded a high index of suspicion.
depends on renal function. In addition to As described in Chapter 11, lactic acid concen-
impaired renal function, certain drugs and tration is reflected by measurement of the lactate
upper gastrointestinal bleeding may also elevate concentration in the blood. Blood lactate meas-
the BUN. urement may not be routinely included on the
Creatinine. Normal blood creatinine is 0.5 biochemical profile; therefore, the diagnosis of
to 1.5 mg/dL. Creatinine formation is deter- lactic acidosis is often made after other causes of
mined only by body muscle mass and is there- high anion gap acidosis have been ruled out.
fore relatively constant. Creatinine excretion is However, lactic acidosis can be confirmed by
determined by renal function. Because creati- actually measuring blood lactate concentration.
nine is less affected by diet, it is a more reliable Normal blood lactate levels are about 1.8
indicator of renal function than is BUN. mM/L (18 mg/dL). Slight elevations in blood
Azotemia and Decreased pH. The pH typi- lactate concentration, up to about 3 mM/L,
cally does not begin to decrease until azotemia are fairly common (e.g. stress, respiratory alka-
is fairly substantial (e.g., BUN > 40 mg/dL and losis) and generally are not associated with
creatinine > 4 mg/dL).521 acidemia.521 Further elevations, however, tend
Etiology. Azotemic renal failure may be due to lower the pH. Typically, in lactic acidosis,
to the nephrotoxic effects of certain drugs (e.g., blood lactate exceeds 5 to 7 mM/L and may be
antibiotics) or heavy metals. Alternatively, three or four times higher.484,521 Lactic acidosis
azotemic renal failure may be caused by poor is most often due to tissue hypoxia. However,
renal perfusion and ischemia or hypertension. several other causes have been reported.
Prerenal azotemia is a condition in which Hypoxia. The assessment of hypoxia has
azotemia is due to inadequate renal perfusion. been described in detail in Chapter 11. Hypoxia
In prerenal azotemia, restoration of adequate may be secondary to anemia, cardiovascular fail-
renal perfusion corrects the azotemia. More ure, or pulmonary decompensation. Indices of
severe or protracted renal hypoperfusion may oxygen supply and indicators of tissue hypoxia
cause acute tubular necrosis and dysfunction. (PaO2, SaO2, [Hb], Pv O2, Sv O2, cardiac out-
This true form of acute renal failure cannot be put) are particularly useful in this evaluation.
reversed immediately by restoration of normal Lactic acidosis has been reported immediately
renal perfusion. after grand mal seizures (pH of 7.14).484,524
In blood gases performed 60 minutes later, not elevated. In alcoholic ketoacidosis, the pri-
however, the pH had returned to normal.524 mary acid disturbance is elevation of beta-
Other Causes. Causes of lactic acidosis not hydroxybutyric acid and this is not reflected
related to tissue hypoxia include excessive by the routine Acetest (measurement of aceto-
ethanol intake, methanol ingestion, leukemia, acetate). The Acetest is a qualitative Na nitro-
neoplasms, drugs,525 and congenital heart prusside reaction in which acetoacetate bodies
defects.526 Also, when pH falls below 7.10, manifest a purple color.519
regardless of the initial cause, lactic acid begins Dextrose and water is the treatment of choice
to accumulate.523 in alcoholic ketoacidosis.523,528 Dextrose con-
Any condition that elevates pyruvate (e.g., verts beta-hydroxybutyrate into acetoacetate
intravenous glucose administration) causes a and serves as a source of carbohydrate.
rise in blood lactate levels. These conditions Diabetes Mellitus. The Greek term diabetes,
are known collectively as secondary hyperlac- which means passing through, is used to describe
tatemia (see Chapter 11). those diseases characterized by excessive urina-
In the presence of oxygen, the liver rapidly tion. The term mellitus means sweet, which is in
converts lactate in the blood back to glucose contrast to the term insipidus, which means
or CO2 and, in the process, produces bicar- uninteresting or insipid. In acute diabetes mel-
bonate in the blood. Both acute and chronic litus, there is increased urination, and the urine
hepatic insufficiency can, therefore, lead to is sweet due to high levels of glucose (glycosuria).
lactic acidosis.527 Early physicians tasted the urine in order to
differentiate this disorder from diabetes
Ketoacidosis insipidus, a very different pathologic condition
When glucose is unavailable within the bodys in which urination is also excessive but the
cells, fat is metabolized at an accelerated rate. urine is not sweet.
Fat metabolism, in turn, leads to the accumu- Pathology. The common pathologic defect in
lation of acetoacetic and beta-hydroxybutyric patients with diabetes mellitus is insulin defi-
acid. These two acids are known collectively as ciency. Insulin is necessary to transport glucose
ketoacids; their increased production may lead from the extracellular fluid to the intracellular
to ketoacidosis with a high anion gap. fluid. When insulin is not available, glucose lev-
The anions associated with these acids are els rise in the plasma (hyperglycemia) and fat
acetoacetate and beta-hydroxybutyrate. A small metabolism increases with resultant ketoacido-
portion of acetoacetate is converted to acetone. sis. Adult-onset (type II) diabetics produce
Acetone is responsible for the characteristic insulin but their cells are unable to use it fully.
fruity odor of the patients breath in ketoacido- The high levels of plasma glucose, in turn,
sis. Acetone, acetoacetate, and beta-hydroxybu- lead to increased urine output (hyperosmolar
tyrate are known collectively as ketone bodies. diuresis) in an effort to maintain blood osmolar-
Their accumulation in the blood is referred to as ity. The loss of fluids may also lead to dehydra-
ketosis. Ketosis and ketoacidosis may be seen in tion. In addition, the compensatory response to
starvation, alcoholism, and diabetes mellitus. acidemia results in a characteristic deep, gasping
Starvation. Ketosis may occur if carbohy- type of ventilation called Kussmauls breathing.
drates are severely restricted in the diet. Laboratory Findings. The average plasma
Ketoacidosis generally is not severe unless glu- glucose level in diabetic ketoacidosis is approx-
cose stores are severely depleted, such as in imately 500 mg/dL.518 The severity of the hyper-
starvation. Fortunately, starvation is rare in the glycemia depends primarily on the degree of
United States, although it may be seen in con- volume depletion from the diuresis and vomiting
ditions such as anorexia nervosa. that is often present. There are increased levels
Alcoholic Ketoacidosis. Alcoholics may of blood ketones, which are shown by a positive
present in the emergency room with a normal or Acetest. Hyperkalemia secondary to acidemia
slightly elevated blood glucose (i.e., <250 mg/dL) is also common. The urine shows increased
and ketoacidosis. Interestingly, when acetoac- levels of glucose (glycosuria) and ketones
etate levels are measured in the blood, they are (ketonuria).
Intestines
Metabolic acidosis Surgery

Drugs
Normal A-
Kidneys
Figure 13-6. Potential sources of normal anion gap metabolic acidosis.
Normal Anion Gap Metabolic Acidosis Renal Tubular Acidosis

Normal anion gap acidosis (i.e., hyper- Description. Renal function may be impaired
chloremic metabolic acidosis) is due to the loss secondary to diminished glomerular filtration
of base. The two major organs usually respon- or renal tubular dysfunction. Azotemic renal
sible for the body losing or excreting bases are failure (i.e., associated with a high anion gap and
the kidneys and the intestine (Fig. 13-6). The high BUN and creatinine levels) is due to dimin-
intestinal secretions are very high in bicarbon- ished glomerular function. When renal acidosis
ate concentration. Thus, in the differential is caused specifically by the failure of the renal
diagnosis of normal anion gap acidosis, it is tubules to absorb bicarbonate, it is termed renal
wise to suspect a loss of intestinal secretions tubular acidosis (RTA). From an acid- base per-
(e.g., diarrhea) or bicarbonate excretion via spective, azotemic renal failure is due to the accu-
the kidneys (e.g., renal tubular acidosis). Other mulation of acids, whereas RTA is due to a loss
causes may include drugs (e.g., carbonic anhy- of base (i.e., HCO3). In contrast to azotemic
drase inhibitors) or intestinal surgical proce- renal failure, glomerular filtration is typically
dures (e.g., ileostomy). A variety of potential adequate in RTA, and therefore azotemia is mild
causes of normal anion gap metabolic acidosis or absent. In addition, the plasma bicarbonate in
are shown in Box 13-4. RTA is usually only mildly decreased and is
most often greater than 15 mEq/L.484
Urine pH. The compensatory response of the
kidney to acidemia is acidification (i.e., excretion
Box 13-4 Causes of Normal Anion of H+ ions) of the urine. In hydrogen ion excess,
Gap Metabolic Acidosis H+ ions are secreted into the filtrate, and urine
Renal tubular acidosis pH is typically quite low (pH 4.50). In RTA,
Enteric drainage tubes urine pH is inappropriately high (pH of 6.00 to
Diarrhea 7.00) despite blood acidemia. This is a result of
Urinary diversion the increased bicarbonate content of the urine.
Carbonic anhydrase inhibitors Other Findings. Other findings in RTA
Early renal disease include hypokalemia, hypophosphatemia,
Dilution acidosis and nephrocalcinosis. Nephrocalcinosis is the
Biliary or pancreatic fistulas deposit of calcium phosphate in the renal
Acidifying salts tubules. Serum chloride characteristically is
Sulfur, hydrogen sulfide, drugs
between 110 and 120 mEq/L (i.e., hyper-
Eucapnic ventilation posthypocapnia
chloremic metabolic acidosis).
Causes. RTA may be a component of an leads to mild metabolic acidosis.529 Carbonic

inherited defect (e.g., Lowe syndrome, Fanconi anhydrase is, of course, important in the renal
syndrome). Alternatively, it may be drug-induced tubular cells in order to facilitate NaHCO3 reab-
(e.g., outdated tetracycline, sulfonamides) or a sorption. When carbonic anhydraseinhibiting
result of some metabolic disorder (e.g., vitamin agents are administered, the effect on renal
D deficiency, secondary hyperparathyroidism). tubules is similar to that of RTA, in that bicar-
bonate is poorly reabsorbed and is therefore
Enteric Drainage Tubes excreted in the urine.
The bicarbonate concentration of secretions in Acetazolamide (Diamox) is a carbonic
the small intestine is higher than in plasma anhydrase inhibitor that is used sometimes as a
(e.g., 70 mEq/L in the small intestine versus diuretic. This drug may, in fact, be the diuretic
24 mEq/L in arterial blood).529 The pancreas, of choice in metabolic alkalemia because of its
biliary tree, and duodenal glands all produce tendency to promote bicarbonate excretion.
and secrete alkaline secretions. Therefore, surgi- Acetazolamide is not often used alone for
cal conditions that necessitate enteric drainage diuresis, however, because it is only a moder-
tubes may lead to a loss of bicarbonate. In par- ately potent diuretic. Administration of this
ticular, ileostomy may be complicated by a high drug may lead to metabolic acidosis, particu-
volume of fluid and electrolyte loss. larly in patients with renal failure.
Mafenide acetate (Sulfamylon acetate cream),
Diarrhea also a carbonic anhydrase inhibitor, is a broad-
Diarrhea is probably the most common cause spectrum bacteriostatic agent that may be
of hyperchloremic metabolic acidosis in the applied topically in the treatment of burns.
intensive care unit.484 The mechanism of meta- Sulfamylon is absorbed easily through heat-
bolic acidosis in diarrhea is exactly the same as damaged skin, and repeated use may result in
in excessive drainage through enteric tubes. metabolic acidosis.
Large quantities of base are excreted along
with fluid and electrolytes in the stool. The Early Renal Disease
prototype of metabolic acidosis associated Azotemic acidosis may accompany end-stage
with diarrhea is seen in cholera, in which stool renal disease; in early renal disease (e.g., intersti-
volume can exceed 15 L/day. Severe hyper- tial nephropathy, diabetic nephropathy), hyper-
chloremic metabolic acidosis may also occur. chloremic metabolic acidosis may be seen.515
Hypovolemia and hypokalemia resulting from This disturbance is probably related to the
the excessive loss of intestinal secretions are diminished ability of renal cells to secrete ammo-
also critical problems in severe diarrhea. nia, a major urinary buffer. Because ammonia
Laxative abuse should also be suspected in the accounts for more than 50% of buffering, its
patient with unexplained hyperchloremic absence greatly limits hydrogen ion excretion
metabolic acidosis.484 and HCO3 reabsorption.
Urinary Diversion Dilution Acidosis

In certain urinary disorders (e.g., tumors, con- Sudden, rapid infusion of a sodium chloride
genital anomalies), the ureters may be surgically solution may dilute the blood sufficiently to
diverted to the intestine to allow for urine excre- lead to metabolic acidosis. Dilution acidosis due
tion (uretero-enterostomy). Uretero-enterostomy to expansion of the fluid space has caused hyper-
may be associated with severe hyperchloremic chloremic metabolic acidosis in children.529 In
metabolic acidosis. Uretero-ileostomy appears contrast, dilution acidosis is rare in adults.
to cause fewer acid-base and electrolyte prob-
lems than uretero-sigmoidostomy.516 Biliary or Pancreatic Fistulas
A fistula is an abnormal connection from a
Carbonic Anhydrase Inhibitors normal cavity or tube to another cavity or free
Chronic administration of drugs that act by inhi- surface. Fistulas may be congenital or may be
bition of carbonic anhydrase almost invariably caused by trauma, abscess, or inflammation.
Fistulas can develop in the gastrointestinal sys- In patients with sustained hypocarbia (e.g., dur-
tem from the biliary tree or the pancreas directly ing mechanical ventilation or during prolonged
to the intestine and thus lead to the loss of pan- hyperventilation associated with asthma), the
creatic secretions or bile. The bicarbonate base bicarbonate is excreted by the kidneys as a
concentration of bile may be 60 mEq/L and as compensatory mechanism. If hypocarbia is
high as 100 mEq/L in pancreatic secretions.529 quickly corrected to eucapnic ventilation (nor-
Obviously, a large loss of these secretions may mal PaCO2), the blood gas may appear as a
lead to hyperchloremic metabolic acidosis. hyperchloremic metabolic acidosis. This acid-
base condition has been commonly observed in
Acidifying Salts patients with severe, acute asthma.530
Acidifying salts (e.g., ammonium chloride, HCl, It may be argued that the resultant metabolic
arginine hydrochloride) that are sometimes acidosis is not a true acidosis at all, because it
used in the treatment of severe alkalemia have really originates from a compensatory mecha-
the potential to cause normal anion gap acidosis. nism. Nevertheless, at a given point in time,
Ammonium chloride intoxication has a similar the blood gas appears as a primary metabolic
effect. acidosis, and this must be recognized. The
issue is not whether this abnormality should be
Sulfur, Hydrogen Sulfide, Drugs called a metabolic acidosis; rather, it is impor-
Elemental sulfur and hydrogen sulfide have been tant that the chain of events that has caused
implicated as unusual causes of normal anion this problem is understood.
gap acidosis.529 Other uncommon causes of
metabolic acidosis include intravenous tetra-
METABOLIC ALKALOSIS
cycline and carbenicillin; however, the mecha-
nism responsible for the acidosis is unclear.529 Metabolic alkalosis is very common in acute
illness.480 In a study of more than 13,000 hos-
Eucapnic Ventilation Posthypocapnia pitalized patients, metabolic alkalosis was the
Eucapnia is the presence of normal amounts of most frequent acid-base disturbance encoun-
CO2 (i.e., PaCO2 35 to 45 mm Hg) in the blood. tered and was present in more than half of all
Hypocarbia, is the presence of low levels of patients with abnormal acid-base status.531
CO2 in the blood (i.e., PaCO2 < 35 mm Hg). Furthermore, more than half of the surgical

A 50-year-old woman arrives in the emergency depart- Cl 104 mEq/L

ment after ingesting an unknown quantity of enteric- K 5.2 mEq/L
coated aspirin. She appears relatively normal. Blood Salicylate level 22 mg/dL
gases and electrolytes are drawn.
ASSESSMENT
SaO2 97 information. Classify ABG.
PaO2 114 mm Hg
FIO2 0.35 Importance: Prioritize concern(s) of treatment in order
Na 142 mEq/L of urgency and/or seriousness as you see the overall
CO2 15 mEq/L situation.
Stomach
Mechanical
Oral bases
ventilation
Metabolic
Drugs NaHCO3
alkalosis
Hypokalemia Fluid loss

Adrenal
cortex
K
Figure 13-7. Potential sources of metabolic alkalosis.
patients who have blood gas determinations of the patient with chronic respiratory acidosis
are likely to be alkalemic at some point during (e.g., posthypercapnic respiratory acidosis) may
their hospitalizations.532 also be causative. In addition, the excessive
fluid loss and hypokalemia from any cause will
Physiologic Response to Metabolic stimulate bicarbonate retention. Finally, exces-
Alkalosis sive secretion of the adrenal cortex (e.g., hyper-
Metabolic alkalosis may have serious conse- aldosteronism) will also result in renal retention
quences in the central nervous and cardiovas- of bicarbonate.
cular systems. Mild-to-moderate metabolic Unlike metabolic acidosis, the potential
alkalosis may cause lethargy and confusion, causes of metabolic alkalosis may be listed in a
whereas severe alkalemia may lead to seizures single box (Box 13-5).
and/or coma. Neuromuscular irritability may
cause spasm, twitching, or tetany. Depressed
myocardial contractility and arrhythmias may
Box 13-5 Causes of Metabolic
occur. Severe alkalemia has been associated
Alkalosis
with increased mortality and should be avoided.
Hypokalemia
Common Causes of Metabolic Alkalosis Ingestion of large amounts of alkali or licorice
Gastric fluid loss
Metabolic alkalosis may be caused by an
Vomiting
abnormal loss of fixed acid from the body or
Nasogastric drainage
by the abnormal accumulation or production Hyperaldosteronism secondary to nonadrenal
of blood base. Most often, a loss of acid (e.g., factors
renal H+ excretion, loss of HCl from the stom- Bartters syndrome
ach) is accompanied by concurrent production Inadequate renal perfusion
of blood bicarbonate. Diuretics (inhibiting NaCl reabsorption)
The more common origins of metabolic Bicarbonate administration
alkalosis are shown in Figure 13-7. Drugs may Sodium bicarbonate overcorrection
be responsible (e.g., diuretics, steroids), or the Blood transfusions
administration of excessive sodium bicarbon- Adrenocortical hypersecretion (e.g., tumor)
Steroids
ate or oral bases. Loss of gastric secretions (e.g.,
Eucapnic ventilation posthypercapnia
vomiting), or excessive mechanical ventilation
Hypokalemia tend to vary inversely with pH. Indeed, serum

Metabolic AlkalosisHypokalemia Syndrome potassium levels may increase with acidemia
In the presence of an intracellular potassium despite a moderate total potassium deficit.
deficit, the renal tubular cells preferentially, Similarly, serum hypokalemia in alkalemia is
although not exclusively, secrete hydrogen ions in part due to the migration of extracellular
(acid) into the urine in exchange for sodium potassium into the intracellular fluid space.
(see Chapter 12). In addition, the kidneys can- Nevertheless, regarding acid-base balance, the
not conserve potassium. Therefore, some clinician must be sure that there is not a true
potassium continues to be excreted in the urine potassium deficit that will hamper the ability of
even with the depletion of normal body stores. the kidney to correct the metabolic alkalosis.
Furthermore, when serum potassium levels are As a general rule, potassium should be admin-
low or when alkalemia is present, total bicar- istered slowly when the patient manifests a low
bonate reabsorption via the NaHCO3 reaction serum [K+] with a target serum potassium in the
is stimulated.533 All of these processes together low normal range.
tend to foster a syndrome of metabolic alkalo- It should also be remembered that hypo-
sis and hypokalemia. Hypokalemia causes kalemia tends to cause muscle weakness and
metabolic alkalosis and metabolic alkalosis may impair a marginal patients ability to ven-
tends to perpetuate hypokalemia. tilate adequately. Furthermore, extracellular
potassium ion concentration is the single most
Incidence of Hypokalemia important determinant of myocardial membrane
Hypokalemia is common in hospitalized stability.541
patients. Many pharmacologic agents may
cause an increased loss of potassium into the Ingestion of Large Amounts of Alkali or Licorice
urine and, thus, hypokalemia. These agents Alkali Loading
include NaCl-inhibiting diuretics and steroids. The kidney readily excretes single doses of alkali,
Inhaled beta 2 agonists can also cause signifi- which may transiently elevate blood bases.
cant hypokalemia.541 When large amounts of base are administered
It is noteworthy that any condition that results over a long period, however, renal excretion may
in loss of fluids and volume contraction may be unable to keep pace with the alkali load.
lower serum potassium. Thus, loss of gastroin- This is particularly true in patients with low
testinal secretions may lead to hypokalemia (e.g., extracellular fluid volumes or impaired renal
vomiting, nasogastric suction, biliary fistulas). function.529
The milk-alkali syndrome is an example of
Serum Potassium this phenomenon. This syndrome is sometimes
The serum potassium concentration is not a par- seen in patients with peptic ulcer disease who
ticularly sensitive indicator of the total potas- ingest large quantities of milk and absorbable
sium content in the blood. The percentage of alkaline medications during a sustained period.
total blood potassium in the intracellular fluid The syndrome consists of metabolic alkalosis,
(i.e., 98%) far exceeds its percentage in the hypercalcemia, and renal impairment.529
plasma (2%). Fortunately, serum hypokalemia Ingestion by infants of large quantities of
usually reflects total body potassium deficits. bicarbonate or soy-protein formula has simi-
However, the degree of serum hypokalemia does larly resulted in metabolic alkalosis due to
not reflect accurately the magnitude of the total ingestion of excessive base. These conditions
body potassium deficiency. Therefore, plasma or can be readily recognized by a history of inges-
serum [K+] must be interpreted carefully. tion of large quantities of base and the presence
The assessment of potassium status is further of alkaline urine.529
clouded by the intracellular-extracellular shifts
in potassium that accompany changes in pH Excessive Licorice Ingestion
and the administration of catecholamines. As The agent glycyrrhizic acid, which is present in
described in Chapter 12, serum potassium levels licorice, certain medicines, candies, and chewing
tobacco, is similar structurally and chemically The presence of carbonic anhydrase in the
to aldosterone.529 Therefore, when ingested in gastric cells facilitates the hydrolysis reaction.
large quantities (e.g., 20 to 40 g of licorice),523 it In turn, the hydrogen ion generated via the
has effects similar to those of hyperaldostero- hydrolysis reaction is secreted into the stomach
nism and may lead to metabolic alkalosis. along with chloride from the blood. In
Recently, it has been argued that glycyrrhizic exchange for the chloride anion that has left the
acid may not actually be the active ingredient blood, the bicarbonate anion, present in the
that causes metabolic alkalosis.542 Nevertheless, gastric cells from the hydrolysis reaction, enters
it still appears that licorice does indeed cause the blood. Thus, the regeneration of HCl tends
metabolic alkalosis. to cause metabolic alkalosis by increasing
blood bicarbonate.
Gastric Fluid Loss Loss of Fluid and Electrolytes. The loss of
The loss of large quantities of gastric secretions gastric secretions may lead to hypovolemia
is probably the most common cause of severe and stimulation of aldosterone. The effect of
metabolic alkalosis (i.e., plasma [HCO3] 50 to increased aldosterone is, as discussed earlier,
60 mEq/L).529 A large volume of gastric secre- stimulation of NaHCO3 reabsorption in renal
tions may be lost by severe and prolonged tubules accompanied by increased potassium
vomiting or in the presence of nasogastric secretion.
suctioning. Other electrolytes are also lost with the gas-
tric secretions. Sodium is often slightly depleted,
Mechanism of Alkalosis and potassium and chloride may be substantially
Loss of Acid. Gastric secretions are very depleted. The potassium concentration of gastric
acidic. They contain hydrochloric acid (HCl), secretions is approximately 20 mEq/L.529 The
and the pH may be close to 1.0 (i.e., [H+] of anion gap may be elevated owing to contraction
100 mEq/L). When the HCl in these secretions of the extracellular fluid space, which causes an
is lost, new HCl must be generated by the cells increased protein concentration.534
in the gastric mucosa. The chemical process by
which this occurs is shown in Figure 13-8. Chloride Replacement
Administration of chloride permits gradual cor-
rection of the alkalemia. The presence of chlo-
ride facilitates increased renal NaCl retention
and, therefore, a diminished need for renal
Blood Gastric cell Stomach
NaHCO3 retention and hydrogen ion secretion.
CO2 + H2O
Hyperaldosteronism Secondary to Nonadrenal Factors
Carbonic Secondary hyperaldosteronism is the condition
anhydrase of increased blood aldosterone levels secondary
H2CO3 to some stimuli outside the adrenal gland itself.
Typically, secondary hyperaldosteronism is due
to increased renin-angiotensin activity triggered
HCO3 HCO3 + H+ H+ by diminished renal perfusion (see Chapter 12).
Conditions and drugs that may lead to secondary
Cl Cl hyperaldosteronism include Bartters syndrome,
inadequate renal perfusion, and diuretics.
Figure 13-8. Production of HCl in gastric cells.
Hydrogen ions generated in the gastric cells via the Bartters Syndrome
hydrolysis reaction are secreted into the stomach Bartters syndrome is a relatively rare disorder
with chloride. The bicarbonate produced via the that can cause hyperaldosteronism second-
hydrolysis reaction enters the blood in exchange ary to high levels of renin. The hyperaldos-
for the chloride. teronism, in turn, leads to hypokalemia and
metabolic alkalosis. Arterial blood pressure it depends on the patients total extracellular
is typically normal or low. The unique com- fluid volume as well as on the rate and type of
ponent of this disease is hyperplasia (i.e., abnormal acid production. Second, there is an
excess proliferation of normal cells) of the elevation of bicarbonate produced within the
juxtaglomerular cells. body (endogenous production) during liver
Gitelman syndrome, which is even more metabolism of the conjugate bases in lactic and
rare, is a similar disorder that is typically seen ketoacidosis. Lactate can be broken down only
in late childhood or early adulthood.480 in the presence of a sufficient quantity of
oxygen.
Inadequate Renal Perfusion The breakdown of anions, such as lactate,
When perfusion to the kidney is diminished, citrate, and acetate, generates blood bicarbon-
the renin-angiotensin system is activated, and ate. In fact, lactate was used in the past for the
metabolic alkalosis may develop. Conditions treatment of metabolic acidosis due to its abil-
that decrease cardiac output, blood volume, or ity to generate blood bicarbonate.
selective renal perfusion may have this effect.
Cardiac output may be low in diseases such as Blood Transfusions
congestive heart failure. Low functional blood During storage of blood, the pH tends to
volume (hypovolemia) may accompany dehy- decrease.535,536 Indeed, administration of
dration or migration of fluid to the interstitial massive blood transfusions over a short
space. A selective decrease in renal perfusion period may cause a transient metabolic
may occur in renal artery stenosis or in renal acidosis that clears up rather quickly.535 More
disease secondary to hypertension. important, metabolism of citrate, the anticoag-
ulant most commonly used for storage of
Diuretics blood, leads to the gradual onset of metabolic
Most diuretics facilitate urinary excretion alkalosis after massive transfusions. Metabolic
of NaCl by impeding its reabsorption in the alkalosis tends to peak about 24 hours after
renal tubules. The transient blood volume transfusion.535
loss may lead to secondary hyperaldostero- A unit of whole blood contains approxi-
nism, hypokalemia, and metabolic alkalosis. mately 17 mEq of citrate, whereas a unit of
Generally, the more potent the diuretic, packed cells contains only 5 mEq.515 For each
the greater is its potential to cause metabolic mole of citrate metabolized, 3 moles of bicar-
alkalosis. bonate are produced.537 Thus, the potential
for citrated blood transfusions to cause meta-
Bicarbonate Administration bolic alkalosis is apparent. It is important to
Sodium Bicarbonate Overcorrection recognize metabolic alkalosis resulting from
Sodium bicarbonate (NaHCO3) is sometimes massive blood transfusions in the critical care
used in the treatment of metabolic acidemia. setting, because this condition has been
Presently, the use of sodium bicarbonate in reported to complicate weaning from mechan-
some types of metabolic acidosis (e.g., lactic ical ventilation.538
acidosis during cardiac arrest) is controversial.
(This controversy is addressed in Chapter 14 Adrenocortical Hypersecretion
regarding treatment of acid-base disorders.) Excessive secretion of aldosterone directly by
Nevertheless, sodium bicarbonate continues the adrenal cortex leads to metabolic alkalosis
to be the treatment of choice for metabolic through renal potassium excretion and bicar-
acidosis, and the development of metabolic bonate retention. This mechanism is often
alkalosis secondary to overcorrection is not referred to as primary hyperaldosteronism or
uncommon. primary mineralocorticoid excess. It is most
Overcorrection of metabolic acidosis occurs often due to a tumor of the adrenal cortex
frequently for two reasons. First, the appropri- (aldosteronoma). In primary hyperaldos-
ate dose of sodium bicarbonate that should be teronism, aldosterone secretion cannot be
administered in a given situation is not clear-cut; suppressed by volume expansion.

You are the only person available to care for this patient. You must assess the patient /situation and act accordingly.
A 55-year-old man arrives in the emergency department Cl 61 mEq/L

comatose following severe sustained vomiting. Blood K 2.2 mEq/L
gases and electrolytes are drawn.
ASSESSMENT
SaO2 86% information. Classify ABG.
PaO2 54 mm Hg
FIO2 0.21 Importance: Prioritize concern(s) of treatment in order
Na 135 mEq/L of urgency and/or seriousness as you see the overall
CO2 54 mEq/L situation.
Steroids is decreased abruptly toward normal laboratory

Glucocorticoids, commonly called steroids, have values (which may occur during mechanical
a large and varied application in medicine. The ventilation), the blood gas picture may appear
chemical structure of glucocorticoids is very sim- as metabolic alkalosis.
ilar to that of mineralocorticoids such as aldos- Although in a sense this is not a true pri-
terone; as a result, glucocorticoids show similar mary metabolic alkalosis, an understanding of
properties. Therefore, steroid therapy, especially its origin is nevertheless important. This is espe-
in large doses, may cause metabolic alkalosis. cially true because adequate chloride intake is
essential for its correction. Furthermore, the
Eucapnic Ventilation Posthypercapnia high incidence of posthypercapneic metabolic
Chronic hypercapnia is associated with renal alkalosis (40% in one study539) makes it an
bicarbonate retention as a compensatory important consideration in acid-base assessment
mechanism. In chronic hypercapnia, if PaCO2 in critical care.
EXERCISES
Exercise 13-1 Respiratory Acidosis

1. Respiratory acidosis threatens acid-base balance through the (accumulation/loss) of

carbonic acid.
2. The most common cause of chronic respiratory acidosis is ____________________.
3. The presence of a barrel chest, adventitious (abnormal) breath sounds, labored breathing,
and forced expiration suggests that the patient has ____________________________.
4. When a patient with COPD is likely to be hypoxic, oxygen therapy (should/should not) be
withheld because of the risk of acute respiratory acidosis.
5. Individuals with COPD (are/are not) particularly vulnerable to the respiratory effects of
sedatives and narcotics.
6. Exhaustion may explain the sudden onset of respiratory acidosis that has been observed
in patients with ________________________ after a sustained period of laborious breathing.
7. The progress of neuromuscular function can be monitored at the bedside through serial
measurements of (blood gases/vital capacity).
8. (Hyperkalemia/Hypokalemia), a common electrolyte disorder in the critical care setting, is
associated with muscle weakness and even paralysis.
9. Fat metabolism results in (less/more) CO2 production than carbohydrate metabolism.
10. Administration of sodium bicarbonate (NaHCO3) intravenously also (decreases/increases)
CO2 production via the hydrolysis reaction.
11. The thermic effect is a change in the (type/quantity) of metabolism.
12. Total parenteral nutrition is generally associated with a/an (increased/decreased)
need for ventilation.
13. Central mechanisms may play a role in the chronic respiratory acidosis observed in obese
individuals, which is called the ________________________ syndrome.
14. A condition characterized by unexplained hypoventilation is sometimes referred
to as ____________________ curse.
15. List eight major causes of respiratory acidosis.
Exercise 13-2 Respiratory Alkalosis
1. Respiratory alkalosis disrupts acid-base balance by (increasing/depleting) blood

carbonic acid.
2. The single most common and important cause of hyperventilation and respiratory
alkalosis is _________________________.
3. The (Hering-Breuer/J-receptor) reflex is also known as the stretch reflex.
4. The (Hering-Breuer/J-receptor) reflex provides a feasible explanation for the
hyperventilation commonly noted in various disorders that may have an impact
on the alveolar-capillary membrane.
5. Ammonia may (stimulate/depress) ventilation.
6. CSF (alkalosis/acidosis) stimulates hyperventilation.
7. (Increased/Decreased) perfusion of the peripheral chemoreceptors may also lead
to respiratory alkalosis.
8. In adults, (respiratory alkalosis/metabolic acidosis) appears to be the dominating
acid-base disturbance in salicylate intoxication.
9. Individuals with severe shock and arterial respiratory alkalosis probably have venous
respiratory (alkalosis/acidosis).
10. List the five major general causes of respiratory alkalosis.
Exercise 13-3 High Anion Gap Metabolic Acidosis: Toxins and

Azotemic Renal Failure
1. When the anion gap exceeds 16 mEq/L, (decrease in base/increase in fixed acids) in the
blood is highly probable.
2. The metabolic acidosis of _______________________ intoxication is usually accompanied
by a primary respiratory alkalosis.
3. Symptoms from ingestion of ___________________________ include engorged retinal
vessels and blurred vision.
4. The active ingredient in antifreeze is _____________________________.
5. The active ingredient in transmission fluid and paint thinner is _____________________.
6. Renal failure associated with a high anion gap and the inability to excrete fixed acids is
called (renal tubular acidosis/azotemic renal failure).
7. The specific blood values that are elevated in azotemia are the ___________________
and ________________________.
8. _________________________ azotemia is a condition in which azotemia is due to
inadequate renal perfusion.
9. The toxic clinical picture associated with azotemia and renal failure is called
_____________________________.
10. The pH typically does not begin to decrease until azotemia is fairly substantial and
creatinine exceeds at least ____________ mg/dL.
Exercise 13-4 High Anion Gap Metabolic Acidosis: Lactic
Acidosis and Ketoacidosis
1. Lactic acidosis is probably the most (common/uncommon) cause of high anion gap
metabolic acidosis.
2. Both acute and chronic (hepatic/renal) insufficiency may lead to lactic acidosis.
3. Fat metabolism leads to the accumulation of which two ketoacids?
4. ________________________ is responsible for the characteristic fruity odor of the patients
breath in ketoacidosis.
5. Acetone, acetoacetate, and beta-hydroxybutyrate are known as the _________________
bodies.
6. State three conditions that may cause ketoacidosis.
7. The _______________________ is a qualitative Na nitroprusside reaction in which
acetoacetate bodies manifest a purple color.
8. Diabetes (insipidus/mellitus) is associated with (hypoglycemia/hyperglycemia).
9. __________________________ must be present to transport glucose from the extracellular
fluid to the intracellular fluid.
10. Diabetes mellitus is associated with (hypoglycemia/hyperglycemia).
11. (Edema/Dehydration) is common in diabetic ketoacidosis.
12. The average plasma glucose level in diabetic ketoacidosis is approximately
(200/500) mg/dL.
13. The compensatory response to ketoacidosis results in a characteristic deep, gasping type
of ventilation known as ______________________ breathing.
14. The increased glucose in the urine associated with diabetic acidosis is
called _____________________.
15. State the four major causes of high anion gap metabolic acidosis.
Exercise 13-5 Normal Anion Gap Metabolic Acidosis

1. Normal anion gap acidosis is also called (hypochloremic/hyperchloremic) metabolic acidosis.

2. State the two major organs capable of losing/excreting base from the body.
3. When renal acidosis is caused specifically by the failure of the renal tubules to absorb
bicarbonate, it is called __________________________.
4. In renal tubular acidosis, urine pH is surprisingly (high/low).
5. Surgical conditions that necessitate (gastric/enteric) drainage tubes may lead to a loss of
bicarbonate.
6. Metabolic acidosis may result from excessive (vomiting/diarrhea).
7. (Acetazolamide/Furosemide) may lead to metabolic acidosis.
8. Dilution acidosis is most common in (adults/children).
9. The bicarbonate concentration of bile and pancreatic juice is very (low/high).
10. State 11 major causes of normal anion gap acidosis.
Exercise 13-6 Metabolic Alkalosis

1. The kidneys (can/cannot) conserve potassium.

2. Most potassium is in the (intracellular/extracellular) fluid.
3. Probably the most common cause of metabolic alkalosis is (gastric fluid loss/primary
hyperaldosteronism).
4. In the generation of gastric HCl, an (H+ ion/HCO3 anion) enters the blood.
5. Hyperplasia of the juxtaglomerular cells is associated with _____________________
syndrome.
6. The immediate response to blood transfusion may be metabolic (acidosis/alkalosis),
whereas the delayed response may be metabolic (acidosis/alkalosis).
7. Excessive secretion of aldosterone by the adrenal cortex (e.g., tumor) that leads to
metabolic alkalosis is called (primary/secondary) hyperaldosteronism.
8. Steroids commonly used therapeutically in medicine are (mineralocorticoids/
glucocorticoids).
9. Metabolism of citrate or lactate leads to metabolic (acidosis/alkalosis).
10. State eight major causes of metabolic alkalosis.

1. Search the Internet for acid base cases and bring in five cases for classroom discussion.
2. Find cases with the five types of acid-base disturbances: respiratory acidosis, respiratory
alkalosis, high anion gap metabolic acidosis, hyperchloremic metabolic acidosis, and
metabolic alkalosis.
NBRC Challenge 13
1. A hypokalemic, CHF patient with a pH of D) [Cl]

7.54 is in need of a diuretic. Which of the E) [Mg+]
following would you recommend? (CRT EXAMINATION NBRC MATRIX
A) Lasix I,A,1,c)
B) Hydrodiuril
C) Diamox 4. A known COPD patient is admitted with
D) Mannitol an acute exacerbation. He is placed on
E) Edecrin a 2 LPM nasal cannula and given a
(CSE-RRT EXAMINATION NBRC narcotic to calm him and blood gases
MATRIX III,D,13) and electrolytes are drawn. What would
you recommend at this time?
2. A patient is in profound cardiogenic shock. A) Include a lactate measurement.
A blood gas is drawn and the PaCO2 is B) Include a glucose measurement.
25 mm Hg. What would you conclude C) Include a magnesium measurement.
regarding the status of the tissues? D) Discontinue the oxygen until the
A) Tissues are most likely alkalotic. blood gas is done.
B) Tissues are well oxygenated. E) Discontinue the narcotic.
C) Tissues are likely acidotic. (CSE-RRT EXAMINATION NBRC
D) Tissue pH is probably near normal. MATRIX III,D,13)
E) Tissues are not undergoing
anaerobic metabolism. 5. A patient has a primary metabolic acidosis
(RRT EXAMINATION NBRC and an anion gap of 25 mEq/L. What lab-
MATRIX I,B,9,c) oratory information would you find useful?
I. Blood glucose
3. A patient has a lactate level of 8 mM/L, an II. BUN
anion gap of 24 mEq/L, a blood glucose III. Lactate
of 123 mg/dL, a BUN of 21 mg/dL, and IV. Urinary Cl
no evidence of poisoning or salicylate A) I and II only
toxicity. What information may be useful B) I and III only
in making a diagnosis? C) II and IV only
A) [Hb] D) I, II, and III only
B) [Ca++] E) II, III, and IV only
C) [Na+] (NBRC RRT CSE MATRIX I,A,2.a)
Chapter
14
Mixed Acid-Base Disturbances
and Treatment
One must develop a clear understanding of the pathophysiologic principles which underlie simple disorders
before a comfortable approach to diagnosis and therapy of mixed disorders can be developed.
Robert G. Narins, Michael Emmett 515
The principal reason that one seeks an accurate assessment of acid-base equilibrium is to obtain an
appropriate guide to therapy.
Jordan J. Cohen, Jerome P. Kassirer 483
Outline
Overview, 361 Respiratory Acidosis, 371
Factors That May Complicate Clinical Acid-Base Spontaneous Breathing, 371
Data, 362 Mechanical Ventilation, 372
Respiratory/Renal Pathology, 362 Respiratory Alkalosis, 373
Chronic Obstructive Pulmonary Disease, 362 Spontaneous Breathing, 373
Chronic Renal Failure, 364 Mechanical Ventilation, 373
Therapeutic Intervention, 364 Metabolic Acidosis, 374
Mixed Acid-Base Disturbances, 364 Sodium Bicarbonate Administration, 374
Definition, 364 Cardiac Arrest and Sodium Bicarbonate
Recognition of Mixed Disturbances, 365 Therapy, 374
Acid-Base Map, 365 Complications of Sodium Bicarbonate
Compensatory Patterns, 367 Therapy, 375
Alerts to Mixed Disturbances, 368 Alternatives to Sodium Bicarbonate Therapy, 376
Acid-Base Treatment, 369 Metabolic Alkalosis, 377
Overview, 369 Mild-to-Moderate Metabolic Alkalosis, 377
Supportive versus Corrective Treatment, 370 Severe Metabolic Alkalemia, 378
Focus of Supportive Treatment, 370 Exercises, 379
OVERVIEW
simple acid-base disturbances are described.
Three final aspects of clinical acid-base man- In addition, common settings and clues that
agement are explored in this chapter. First, may suggest a mixed acid-base disturbance are
some of the major diseases and factors that presented.
tend to complicate the interpretation of clinical The final portion of this chapter deals with
acid-base data are discussed. These factors the supportive treatment of the four general
include chronic lung disease, chronic renal dis- acid-base disorders: respiratory acidosis, respi-
ease, and therapeutic intervention. Blood gas ratory alkalosis, metabolic acidosis, and meta-
and acid-base interpretation under these cir- bolic alkalosis. General guidelines are presented
cumstances often requires special attention regarding the management of these generic
and skill. disorders.
Second, methods that can be used to differ- In addition, venous paradox during
entiate simple (single) acid-base problems from cardiopulmonary resuscitation or severe
mixed (complicated, multiple) acid-base distur- shock is described under metabolic acidosis.
bances are reviewed. In particular, the acid-base This phenomenon has important implica-
map and rules of thumb for compensation of tions regarding blood gas interpretation as
361
well as the most appropriate use of NaHCO3 of COPD. Nevertheless, blood gases in this
therapy. group are often confusing and complex.
Furthermore, they may be misleading if they are
FACTORS THAT MAY COMPLICATE not clearly understood. Abnormal baseline val-
CLINICAL ACID-BASE DATA ues, unpredictable acute ventilatory changes,
and the potential coexistence of lactic acidosis
Respiratory/Renal Pathology may all interact in a complex manner. The result
The primary organ systems involved in the may be misleading data when a single blood gas
maintenance of acid-base balance are the respi- is considered in isolation. Some examples are
ratory and renal systems. Disease, and in par- given of how this result may occur.
ticular chronic disease, in either of these body
systems can directly impair acid-base conditions Relative Hyperventilation
or hamper the ability of the affected organ It is not uncommon for a patient with COPD
system to compensate for another acid-base to lower PaCO2 in response to acute hypo-
disturbance. Thus, blood gas and acid-base xemia arising from an acute lung infection.
interpretation in these chronic diseases Superimposing this acute change on the chronic
requires special attention and understanding. (normal hypercapnic baseline) values shown in
Example 14-1 results in blood gases approxi-
Chronic Obstructive Pulmonary Disease mating those shown in Example 14-2.
Chronic obstructive pulmonary disease (COPD)
is the classic example of a chronic respiratory Example 14-2
disease. The typical acid-base picture in COPD is Relative Hyperventilation in COPD
well known to most clinicians. Although respi- pH 7.52
ratory alkalosis may possibly be seen at an early PaCO2 40 mm Hg
stage of the disease and in acute asthma, the [BE] 5 mEq/L
characteristic picture in long-standing, severe, [HCO3] 31 mEq/L
pulmonary disease is hypercapnia (e.g., PaCO2 PaO2 52 mm Hg
> 50 mm Hg) with metabolic compensation
(increased [BE], [HCO3]). Example 14-1 shows Similar results could occur if a patient with
typical blood gases in long-standing COPD. COPD were placed on a mechanical ventilator
and ventilated to a PaCO2 of 40 mm Hg.
Example 14-1 Classification of this blood gas in isolation
Typical End-Stage COPD Blood Gases could result in the diagnosis of metabolic alka-
pH 7.38 losis. The underlying cause is, in fact, eucapnic
PaCO2 55 mm Hg (normal PaCO2) ventilation posthypercapnia.
[BE] 5 mEq/L Treatment for simple metabolic alkalemia
[HCO3] 31 mEq/L here, however, would be inappropriate; opti-
PaO2 55 mm Hg mal management requires an understanding of
the disease process and the likely chain of
The pH is often within the normal range events that have led to this point. It is probably
(i.e., completely compensated) and may even more desirable to return this patients PaCO2
be on the alkalotic side of the normal range.10 to their baseline level.
This finding is not consistent with rules that
apply to compensation (i.e., overcompensation Relative Hyperventilation with Lactic Acidosis
should not occur), however, and may be Another important consideration in the patient
related to a mild concurrent primary metabolic with COPD is the potential for hypoxia and
alkalosis. The administration of steroids and lactic acidosis. Individuals with COPD often
diuretics with concomitant hypochloremia or have increased heart rates and elevated arterial
hypokalemia is common in severe COPD. blood pressure under chronic normal conditions
Arterial blood gases are critical in the diag- to maintain adequate tissue oxygenation. In
nosis and management of acute exacerbations addition, right-sided heart failure is common
Chapter 14 Mixed Acid-Base Disturbances and Treatment 363
in COPD secondary to increased pulmonary This particular blood gas picture is a com-
vascular resistance. When the acute stress of mon finding in acute exacerbation of COPD in
pneumonia and increasing hypoxemia is super- the emergency department. The hallmark to
imposed on an already compromised cardio- recognition of this situation (acute exacerba-
vascular system, hypoxia may develop. tion of COPD) is the surprisingly normal pH
If lactic acidosis compounds the blood gas despite severe hypercapnia.
shown in Example 14-2, the result may appear Patients with COPD who present with blood
as shown in Example 14-3. The net effect of gas results such as those shown in Example 14-4
these interactions is a relatively normal blood can often be treated successfully with low
gas acid-base picture despite a severely com- concentrations of oxygen therapy, noninvasive
promised patient. Thus, serial blood gas meas- ventilation, and bronchial hygiene.543,544 Thus,
urements and other clinical findings are essential mechanical ventilation, with related discomfort
in understanding the significance of any isolated and the potential for complications, can often
blood gas report. be avoided. Furthermore, a blood gas such as
this may be the first clue that the patient has
Example 14-3 COPD. This finding, in turn, alerts the clinician
Relative Hyperventilation with Lactic to the potential for increasing hypercapnia with
Acidosis in COPD excessive oxygen therapy. Therefore, recogni-
pH 7.38 tion of this situation may have great clinical
PaCO2 40 mm Hg importance.
[BE] 1 mEq/L
[HCO3] 24 mEq/L Acute Hypercapnia with Lactic Acidosis
PaO2 44 mm Hg If lactic acidosis develops coincidentally with the
acute hypoventilation shown in Example 14-4
Acute Hypercapnia (not an unlikely situation), COPD blood gases
Many patients with severe COPD respond may appear as shown in Example 14-5.
paradoxically to acute hypoxemia or oxygen
therapy in that their PaCO2 increases instead Example 14-5
of decreases. Reasons for this are unclear Acute Hypercapnia with Lactic Acidosis
but are most likely related to worsening in COPD
ventilation-perfusion mismatch and exhaus- pH 7.20
tion secondary to the work of breathing. In PaCO2 75 mm Hg
addition, as described previously, excessive [BE] 2 mEq/L
oxygen therapy may similarly precipitate acute [HCO3] 28 mEq/L
hypercarbia. This affect has also recently been PaO2 44 mm Hg
shown to occur during acute asthma exacerba-
tions and the administration of FIO2 1.0.700 When considered in isolation, this blood gas
Excessive oxygen therapy may also be recog- appears to show an acute hypoventilation (res-
nized by the concurrent presence of a PaO2 in piratory acidosis). Actually, this individual has
excess of 60 mm Hg. When acute hypercapnia two primary acid-base problems: respiratory
is superimposed on typical COPD chronic acidosis and metabolic acidosis. Rather than
blood gases, the result may appear as shown in immediately starting mechanical ventilation,
Example 14-4. a short, carefully controlled (and monitored)
trial of oxygen therapy might mitigate gas
Example 14-4 exchange problems and obviate the need for
Acute Hypercapnia in COPD mechanical ventilation. If this is unsuccessful,
pH 7.30 noninvasive ventilation should be attempted
PaCO2 75 mm Hg prior to full-blown mechanical ventilation.
[BE] 8 mEq/L Again, interpretation and treatment must be
[HCO3] 33 mEq/L tailored to the specific case. These various
PaO2 48 mm Hg examples have been provided to emphasize the
complexity and the need for careful serial generated as a compensatory mechanism to the
analysis of blood gases in COPD. acidosis, in conjunction with the delivery of
large tidal volumes via mechanical ventilation,
Chronic Renal Failure has caused the apparent alkalosis. It would be
Just as COPD can distort blood gas values, inappropriate, however, to attempt to treat the
renal failure or disease may affect baseline respiratory alkalosis. The only true primary
data. These disorders impair the renal ability acid-base problem in this patient is metabolic
to manipulate and control bicarbonate concen- acidosis. Mechanical ventilation has created
tration and various electrolytes and body flu- the false impression of respiratory alkalosis.
ids. In severe stages of disease, metabolic If this same degree of metabolic acidosis
acidosis with acidemia may be present. The developed in this individual during spontaneous
presence of chronic renal disease must be con- breathing (i.e., not during mechanical ventila-
sidered when arterial blood gases and tion), the blood gas picture might more closely
acid-base status are evaluated. resemble Example 14-7. Thus, the potential
impact of respiratory assistance on the blood
Therapeutic Intervention gas findings can be appreciated. The clinician
Therapy given to a patient may sometimes dis- must be mindful of the mode of mechanical ven-
tort the blood gas findings and may complicate tilation and whether it may influence blood gas
the interpretation. The administration of patterns.
diuretics, steroids, electrolytes, oxygen, bicar-
bonate, or mechanical ventilation may cause Example 14-7
primary acid-base disturbances or may alter Metabolic Acidosis During Spontaneous
compensatory patterns. These factors must all Breathing
be considered carefully during acid-base diag- pH 7.32
nosis, particularly in the critical care setting. PaCO2 25 mm Hg
A specific area of application where blood [BE] 10 mEq/L
gases may be measured frequently is during [HCO3] 13 mEq/L
mechanical ventilation. The clinician must PaO2 64 mm Hg
realize, however, that mechanical ventilation, by
its very objective, controls at least a portion of The potential for mechanical ventilation to
ventilation in a set pattern. Therefore, compen- camouflage acid-base events has been described.
sation for metabolic acid-base disturbances can- Similarly, many of the other therapeutic meas-
not occur in exactly the same manner as it would ures mentioned earlier can lead to iatrogenic
in the patient who breathes spontaneously. acid-base disturbances. Arterial blood gases and
acid-base disturbances must always be inter-
Example 14-6 preted within the context of therapeutic measures
Metabolic Acidosis During Mechanical and long-standing pulmonary or renal disease.
Ventilation
pH 7.44 MIXED ACID-BASE DISTURBANCES
PaCO2 18 mm Hg
[BE] 12 mEq/L Definition
[HCO3] 12 mEq/L The natural tendency of the body to compensate
PaO2 64 mm Hg for primary acid-base disturbances was dis-
cussed in Chapter 8. Because of this natural phe-
Example 14-6 shows blood gases that may nomenon, whenever opposing respiratory and
be seen during mechanical ventilation in a metabolic conditions were present, compensa-
patient with a metabolic acidosis. Note that tion was assumed. Although this initial assump-
this blood gas in isolation appears to be a com- tion is logical, it may be incorrect. It is not
pletely compensated respiratory alkalosis. uncommon to have two opposing primary acid-
Actually, this patient has only a metabolic aci- base disturbances that give the surface appear-
dosis. Nevertheless, the rapid respiratory rate ance of simple compensation. The coexistence
of two primary acid-base disturbances is called When a patients values fall outside these
a mixed acid-base disturbance. bands, it is very unlikely that the patient has
just one disturbance. On the other hand, when
Recognition of Mixed Disturbances a patients values fall within one of these bands
Acid-Base Map it does not ensure that the patient has a single
How can simple compensation be differenti- acid-base disturbance, it simply means that the
ated from a mixed acid-base disturbance? data are compatible with this conclusion.
Probably the most useful aid in this regard is the Figure 14-2 shows how the acid-base map
acid-base map that is shown in Figure 14-1. can be used by simply aligning the two adjacent
The labeled areas encompass with 95% confi- sides of a piece of paper with the patients
dence the range of pH, PaCO2, and bicarbonate respective PaCO2 (horizontal axis) and pH (ver-
that one would expect to find in patients who tical axis). The corner point of the paper repre-
have only one simple acid-base disturbance. sents where the values intersect on the map. The
Separate bands are also given for both acute data in Figure 14-2,A are consistent with chronic
and chronic acid-base problems. simple respiratory acidosis. Remember, this does
100 7.0
90 6 9 12 15 18 21 24
80 7.1
27
70 is 30
os
cid
.a
sp 33 7.2
re
Mecidos
60 e
ut
a
Ac 36
tab is
olic
39
H+ 50 cido
sis
7.3 pH
re sp. a 42
nM/L ronic 45
Ch
48
40 N 51 7.4
57
Chronic .
63
resp. alk Metabolic
7.5
30 alk. alkalosis 69
p. 75
es
ut er 7.6
20 Ac
7.7
7.8
10 m HC 8.0
Eq O3
/L
8.5
0
10 20 30 40 50 60 70 80 90 100
PCO2 mm Hg
Figure 14-1. Acid-base map. N indicates the area of normal values. The numbered diagonal lines give the
bicarbonate concentrations in milliequivalents per liter. The confidence bands for the expected range of values
of the six common acid-base disturbances are illustrated. The map has several potential uses. First, it can
serve in place of a pocket calculator and allow the clinician to check, for example, if a patients reported
venous serum bicarbonate concentration is in accord with the measured values for the PCO2 and pH of his
or her arterial blood. Second, it may provide assistance in distinguishing between compensatory responses
and mixed disturbances. If the point corresponding to a patients values falls outside the 95% confidence
bands, it is likely that a mixed disturbance exists. The reverse is not necessarily true, however. A point falling
within a confidence band does not necessarily mean the presence of a single disorder, because there are
several ways to arrive at the same point. Finally, sequential plotting of a patients values for several hours
to days may greatly simplify the understanding and management of complex acid-base disturbances.
100 7.0 100 7.0
90 6 9 12 15 18 21 24 90 6 9 12 15 18 21 24
80 7.1 80 7.1
27 27
s is sis
70 ido
30 70 ido
30
c c
.a .a
sp 33 7.2 sp 33 7.2
re re
Mecido
Mecido
60 e 60 e
a
a
ut ut
tab sis
tab sis
36 36
Ac Ac
olic
olic
H+ 50 H+ 50
39 39
osis osis
. acid 42 7.3 pH . acid 42 7.3 pH
nic resp nic resp
nM/L Chro
45 nM/L Chro
45
48 48
51 51
40 N 7.4 40 N 7.4
57 57
Chronick. 63 Chronick. 63
resp. al . Metabolic
7.5 resp. al . Metabolic
7.5
30 . alk alkalosis 69 30 . alk alkalosis 69
sp 75 sp 75
re 7.6 re 7.6
te te
20 cu 20 cu
A 7.7 A 7.7
[H
7.8 [H
7.8
10 m CO
Eq 3 ] 8.0 10 m CO
Eq 3 ] 8.0
/L /L
8.5 8.5
0 0
10 20 30 40 50 60 70 80 90 100 10 20 30 40 50 60 70 80 90 100
PCO2 mm Hg PCO2 mm Hg
PaCO2 60 mm Hg PaCO2 30 mm Hg
pH 7.35 pH 7.60
The blood gas is consistent with simple chronic Because these values fall outside the bands
respiratory acidosis (e.g., COPD). for simple acid-base problems, a mixed (combined)
A B respiratory and metabolic alkalosis are present.
100 7.0 100 7.0
90 6 9 12 15 18 21 24 90 6 9 12 15 18 21 24
80 7.1 80 7.1
27 27
70 sis 70 sis
ido ido
30 30
c c
.a .a
sp 33 7.2 sp 33 7.2
re re
Mecido
Mecido
60 e 60 e
a
t t
cu cu
tab sis
tab sis
36 36
A A
olic
olic
H+ 50 H+ 50
39 39
osis osis
. acid 42 7.3 pH . acid 42 7.3 pH
nic resp nic resp
nM/L Chro
45 nM/L Chro
45
48 48
51 51
40 N
7.4 40 N 7.4
57 57
Chronick. 63 Chronick. 63
resp. al lk . Metabolic
7.5 resp. al lk . Metabolic
7.5
30 .a alkalosis 69 30 .a alkalosis 69
sp 75 sp 75
re 7.6 re 7.6
te te
20 cu 20 cu
A 7.7 A 7.7
[H
7.8 [H
7.8
10 m CO
Eq 3 ] 8.0 10 m CO
Eq 3 ] 8.0
/L /L
8.5 8.5
0 0
10 20 30 40 50 60 70 80 90 100 10 20 30 40 50 60 70 80 90 100
PCO2 mm Hg PCO2 mm Hg
PaCO2 70 PaCO2 30
pH 7.38 pH 7.35
Because these values fall outside the bands The blood gas is consistent with simple metabolic
for simple acid-base problems, a mixed respiratory acidosis.
acidosis and metabolic alkalosis are present.
C D
Figure 14-2. Application of acid-base map.
not mean that the elevated bicarbonate cannot primary acid-base disturbances, although in this
be due to a primary problem, but only that the case they are in opposite directions (i.e., respira-
data are consistent with usual compensation tory acidosis and metabolic alkalosis). Without
for chronic respiratory acidosis. an acid-base map, one might assume that these
Figure 14-2,B does not fall within any band, blood gas results are due to complete compensa-
therefore the clinician can be relatively certain tion. Finally, Figure 14-2,D is consistent with
that there are two separate, primary, acid-base a simple metabolic acidosis.
disturbances (respiratory alkalosis and metabolic The acid-base map is a simple, useful tool for
alkalosis). Figure 14-2,C similarly represents two the evaluation of mixed acid-base disturbances.
Pocket versions of this map are available for discussed in Chapter 8 and it does not repre-
use at the bedside. sent renal compensation.
After maximal renal compensation (several
Compensatory Patterns days later), however, the pH returns approxi-
The degree of compensation observed in the four mately halfway back to normal (i.e., 7.31).
simple primary acid-base disturbances, although Thus, complete compensation (i.e., pH in nor-
quite similar, is not identical. For reasons that mal range) is not usually seen when respiratory
are unclear, some types of acid-base problems acidosis is quite severe. Complete compensation
(e.g., metabolic alkalosis) result in more com- for respiratory acidosis occurs only when the
plete compensation than others. Nevertheless, respiratory acidosis is not severe (i.e., PaCO2 <
in the absence of an acid-base map, it is useful 60 mm Hg). In addition, because the mechanism
to have some idea of the typical compensatory of renal compensation for respiratory acidosis is
patterns that should accompany the four simple bicarbonate retention, the chloride anion is
acid-base disturbances. This can help the clini- typically low to preserve electroneutrality.
cian to evaluate the appropriateness of the degree
of compensation observed in a given individual. Respiratory Alkalosis
Compensation for respiratory alkalosis is similar
Respiratory Acidosis in magnitude to compensation for respiratory
The pH falls approximately 0.06 unit for an acidosis. In general, the pH should return at least
acute 10-mm Hg increase in PaCO2. After max- halfway back toward normal. Again, an exam-
imal renal compensation, the change in pH ple is shown in Table 14-1. Surprisingly, how-
associated with an increase of 10 mm Hg in ever, when the respiratory alkalosis persists for
PaCO2 is approximately 0.03 unit. Thus, the pH weeks, the pH may actually return completely
returns approximately 50% of the way back to normal in some cases.515 Renal compensation
toward normal after maximal compensation. for respiratory alkalosis requires the excretion of
Table 14-1 shows the typical compensatory bicarbonate; therefore, hyperchloremia often
response to respiratory acidosis. This table shows develops to preserve electroneutrality.
that when the PaCO2 increases to 70 mm Hg
acutely, the pH drops immediately to approxi- Metabolic Acidosis
mately 7.22 (0.06 decrease/10 mm Hg PaCO2 The major portion of the ventilatory response
increase). The immediate increase in bicarbon- to metabolic acidosis usually begins quickly;
ate is a result of the hydrolysis effect that was however, the maximal compensatory response
Table 14-1. COMPENSATORY PATTERNS

Hypothetical Cases
(initial PaCO2 = 40 mm Hg, [HCO3] = 24 mEq/L
Chronic Response
Primary Insult Initial Effects (Several Days)
Metabolic Acidosis [HCO3] to 15 mEq/L PaCO2 = 40 mm Hg PaCO2 = 30 mm Hg

pH = 7.20* pH = 7.30
Metabolic Alkalosis [HCO3] to 40 mEq/L PaCO2 = 40 mm Hg PaCO2 = 51 mm Hg
pH = 7.62* pH = 7.51
Respiratory Acidosis PaCO2 to 70 mm Hg [HCO3] increases to 27 mEq/L [HCO3] = 33 mEq/L
pH = 7.22 pH = 7.31
Respiratory Alkalosis PaCO2 to 20 mm Hg [HCO3] decreases to 20 mEq/L [HCO3] = 15 mEq/L
pH = 7.60 pH = 7.50
*In comparing metabolic acidosis and alkalosis, note that to produce the same acute change in pH (0.2 unit),
a much larger change in [HCO3 ] is necessary in metabolic alkalosis (HCO3 = 16 mEq/L) than in metabolic acidosis
(HCO3 = 9 mEq/L).
Modified from Kokko, J.P., and Tennen, R.L.: Fluids and Electrolytes, Philadelphia, W. B. Saunders, 1986, p. 386.
may take up to 24 hours.545, 546 When metabolic Box 14-1 Alerts to Mixed Acid-Base
acidosis develops in the plasma, it takes some Disturbances
time for the pH to fall in the cerebrospinal
Absence of compensation
fluid owing to the limited permeability of ions
Long-standing pulmonary or renal disease
across the blood-brain barrier. Lactic acidosis, Excessive compensation
however, may actually develop within the Respiratory assistance
brain cells, and it is therefore associated with Temporal inconsistencies
a more rapid ventilatory response.515 Settings conducive to mixed disturbances
A very useful rule of thumb when an
acid-base map is not at hand is that after max-
imal compensation, the PaCO2 generally acid-base problems are camouflaged in mixed
approximates the last two digits of the pH.515 disturbances, they may easily be missed. In this
Thus, in simple chronic metabolic acidosis with setting, covert acid-base problems are untreated
a pH of 7.30, the PaCO2 is usually approxi- and are likely to lead to progressive deteriora-
mately 30 mm Hg (see Table 14-1). tion. Furthermore, even use of the acid-base
map does not identify those mixed disturbances
Metabolic Alkalosis that result in blood gas data that coincide
The respiratory compensatory response to with findings that normally accompany simple
metabolic alkalosis is hypoventilation with disturbances.
retention of carbonic acid. It has long been Therefore, the clinician must look for clues
assumed, however, that this response was lim- that suggest the presence of multiple (mixed)
ited by the onset of hypoxemia. Therefore, it is acid-base disorders. Box 14-1 suggests some
often stated that compensation for metabolic situations that should alert the clinician to the
alkalosis will not allow the PaCO2 to exceed likelihood of a mixed acid-base disturbance.
55 to 60 mm Hg.515
More recent reviews have shown that Absence of Compensation
hypoventilation is not limited by hypoxemia.547 Compensation is the normal response of the
Progressive, linear hypoventilation accompanies body to a primary acid-base problem. When
progressive, simple, metabolic alkalosis when it compensation is absent, given sufficient time for
is not associated with other acid-base prob- its development, suspicion should be aroused.
lems.547 As shown in Table 14-1, compensation This may, in fact, be the first clue that the organ
may sometimes also allow the pH to return system that should be compensating (i.e., lungs,
halfway back to normal; however, a lesser com- kidneys) is itself impaired.
pensatory response is more common. In one report, the absence of compensation
in ketoacidosis of diabetes mellitus served to
Summary alert the clinicians to the presence of a primary
In the absence of an acid-base map, it is useful respiratory problem.548 The patients who did
to know that maximal compensation for most not compensate (display hypocapnia) had occult
simple acid-base disturbances is approximately mucous plugging of major bronchi.548 After
50%. Compensation for respiratory alkalosis this problem was corrected, these individuals
is usually slightly greater than this, whereas responded appropriately.
compensation for metabolic alkalosis is usu-
ally slightly less. Knowledge of compensatory Long-Standing Pulmonary or Renal Disease
patterns can alert the clinician to the presence When chronic pulmonary or renal disease is
of a mixed disturbance even when an acid-base present, the body should not be expected to
map is not available. compensate normally for other primary distur-
bances. In addition, diseases of these systems
Alerts to Mixed Disturbances in and of themselves are often associated with
Mixed acid-base disturbances are far from chronically abnormal blood gases and simple
uncommon in the hospital setting. When primary acid-base disorders. Thus, the abnormal
baseline values in these individuals must be Box 14-2 Common Settings of

appreciated. Furthermore, the ability of these Mixed Acid-Base
systems to respond to other acid-base insults is Disorders
compromised.
METABOLIC ACIDOSIS/
Excessive Compensation
It has been shown that maximal compensation Cardiopulmonary arrest
Severe pulmonary edema
for simple acid-base disorders is rarely complete,
Poisonings
particularly when the primary acid-base insult
is substantial. The appearance of complete METABOLIC ACIDOSIS/
compensation for a relatively severe acid-base RESPIRATORY ALKALOSIS
problem should be viewed with skepticism. For Salicylate intoxication
example, the likelihood of complete compen- Sepsis
sation in chronic respiratory acidosis is less Severe liver disease
than 15% when PaCO2 exceeds 60 mm Hg.549
METABOLIC ACIDOSIS/
Furthermore, the likelihood is less than 1%
METABOLIC ALKALOSIS
when the chronic PaCO2 exceeds 70 mm Hg.549
The presence of complete compensation in fairly Renal failure with vomiting
Alcoholic ketoacidosis with vomiting
substantial acid-base alterations more than likely
represents a mixed acid-base disturbance. METABOLIC ALKALOSIS/
Respiratory Assistance COPD with vomiting or diuretics
When ventilation is being assisted artificially
(e.g., mechanical ventilation), the rate and vol- METABOLIC ALKALOSIS/
ume of ventilation are not exclusively under the RESPIRATORY ALKALOSIS
patients control. Therefore, these situations com- Critically ill patients
plicate acid-base analysis and often appear as Severe liver disease with vomiting
mixed, albeit partially iatrogenic, disturbances. From Kokko, J.P., and Tannen, R.L.: Fluids and
Electrolytes, Philadelphia, W. B. Saunders, 1986, p. 392.
Temporal Inconsistencies
Maximal renal compensation takes 2 to 3 days.
When maximal compensation appears to have here is not new. Laboratory data cannot be inter-
occurred almost instantaneously, the explana- preted in a vacuum. All available information
tion is more likely to be a mixed acid-base must be assimilated into a meaningful whole.
disturbance. Also, as described previously,
the absence of compensation despite sufficient ACID-BASE TREATMENT
elapsed time should also arouse suspicion.
Previous blood gas findings should always be Overview
taken into account when interpreting current Clearly, the work and time committed to the
information. pursuit of an accurate acid-base diagnosis will
have been in vain if the treatment is inappro-
Settings Conducive to Mixed Disturbances priate. Effective treatment must be aimed at
Various clinical settings are commonly associated specific objectives. The development of these
with mixed acid-base disturbances (Box 14-2). objectives is predicated on the determination
The effective diagnostician is continually on of potentially reversible problems. The poten-
the alert for clues that may unveil or further tial for success with a given therapy must be
clarify pathologic disturbances. A barrel chest, weighed judiciously against concomitant risks
an elevated blood sugar, hypokalemia, or hypo- and the urgency of action required. The ques-
xemia, for example, may be the first clues to an tions of whether to treat and how best to
unidentified acid-base problem. The message treat a problem are often complex and are

A 56-year-old woman with long-standing COPD and ASSESSMENT

CHF presents to the emergency department with Abnormalities: List abnormal data and other noteworthy
dyspnea and weakness. She has been taking digitalis information. Classify ABG.
and Lasix for control of her CHF and corticosteroids for Explanation: List possible diseases, pathology, or other
her long-standing COPD. situations that may have led to this patients condition.
Evaluation: Suggest additional data that would be
pH 7.45
FIO2 0.21 situation.
Na 140 mEq/L Objective: Specifically state the measurable or observable
CO2 48 mEq/L outcomes you would like treatment to accomplish.
Cl 70 mEq/L Action: Describe your specific plan of action.
K 3.1 mEq/L
complicated by many variables. One goal in (notable exception ARDS). Clinicians are occa-
this chapter is to provide the clinician with sionally distracted from this theme when base
basic guidelines that may improve the quality excess, bicarbonate, or PaCO2 are significantly
of these therapeutic decisions. abnormal. Erroneously, therapy may be directed
primarily toward normalization of these other
Supportive versus Corrective Treatment indices. Although these indices may provide
The general thrust of therapeutic endeavors guidelines for treatment, therapy should not be
may be in one of two possible directions. focused primarily on these lesser sub-indices of
Supportive or palliative treatment focuses acid-base status. Rather, the primary focus
on the preservation of an acceptable pH and of supportive acid-base treatment must be on
on the prevention of life-threatening changes the pH.
in pH. In Example 14-8, supportive treatment is not
Corrective treatment, on the other hand, indicated. Although the PaCO2 is significantly
aims to actively reverse the underlying acid-base elevated, the pH, which is more important
disorder and thus to preclude any further from an acid-base standpoint, is within accept-
acid-base deviation. In the case of drug-induced able limits. In this example, treatment should
hypoventilation, this would include flumazenil be focused on correction rather than on
for benzodiazepines and naloxone for narcotics. support. The clinician should attempt to iden-
Nevertheless, the broad and diverse nature of tify fully the underlying cause and to initiate
corrective treatment prohibits a detailed review corrective action when possible.
of this topic in this text. Rather, basic principles
in the application of supportive treatment are Example 14-8
explored. pH 7.35
PaCO2 60 mm Hg
Focus of Supportive Treatment [BE] 5 mEq/L
When considering supportive treatment, it is
wise to remember that normalization of the pH A similar distraction often occurs when the
is usually the primary objective of intervention [BE] is very low. Example 14-9 depicts a situation
in which the [BE] is 13 mEq/L. However, to considering treatment because it emphasizes

correct the metabolic acidosis in this example the specific defect, that is, a failure of the lungs
would likely put the patient into alkalemia. to adequately excrete CO2 through ventilation.
Appropriate therapy would include identifica- When spontaneous breathing cannot preclude
tion and correction of the underlying acid-base significant respiratory acidemia, mechanical
defect. Supportive therapy is not indicated ventilation is likely indicated.
because the pH is in the normal range. In acute respiratory acidemia, the severity of
the acidemia is in all likelihood a more sensitive
Example 14-9 indicator of the need for mechanical ventilation
pH 7.38 than is the severity of the hypercarbia. Some
PaCO2 20 mm Hg have suggested that mechanical ventilation
[BE] 13 mEq/L be considered when pH falls below 7.25 or
hypercapnia exceeds PaCO2 of 80 mm Hg,485
Regarding treatment, it also should be although this is currently controversial.498
emphasized that therapy should be focused Thus, it is a reasonable guide to seriously con-
only on primary acid base problems (e.g., true sider mechanical ventilation when the pH is less
respiratory acidosis, true metabolic alkalosis). than 7.25 in respiratory acidemia. The presence
Secondary changes in acid-base parameters are of progressive respiratory acidemia, regardless
compensatory by definition and reverse them- of the specific pH level, is often a stronger indi-
selves in the absence of primary problems. For cation of the need for mechanical ventilation
example, a laboratory metabolic acidosis (e.g., than is an isolated pH measurement.551
[HCO3] 19 mEq/L) may be compensatory and, Obviously, anything that might diminish
as such, may not need to be treated. muscle strength should be avoided in primary
Information has been provided in this chap- respiratory acidosis. Thus, hypokalemia and
ter and in this text to aid the clinician in veri- hypophosphatemia should be corrected in the
fying the presence of primary acid-base patient with respiratory acidosis. Also, in some
disturbances and in identifying their origin. cases (e.g. obesity hypoventilation syndrome,
Also, regarding treatment, intervention should COPD), respiratory stimulants or proges-
be considered for all primary disturbances, terone510 may be effective.
even when these disturbances are relatively
minor. Optimal patient treatment should not Guidelines in Chronic CO2 Retention
await a crisis. Although acute respiratory acidemia with a
In very unusual situations, therapeutic com- pH of less than 7.25 may suggest the need for
pensation may be indicated. For example, if mechanical ventilation, there are exceptions.
metabolic acidemia during mechanical ventila- The most notable of these is the acute exacer-
tion is resulting in severe strain on the respira- bation of COPD associated with chronic hyper-
tory system in order to maintain compensation, carbia. Initiation of mechanical ventilation is
it is probably in the patients best interest to often riddled with complications in patients
provide iatrogenic hyperventilation that may with COPD.552 They are difficult to wean, and
diminish work and may further normalize iatrogenic pulmonary infection is common.
the pH. The clinician must keep in mind, how- In further support of withholding mechanical
ever, that therapeutic compensation should be ventilation, many patients with COPD in acute
reserved only for exceptional and often dire pulmonary exacerbation manifest improved
circumstances. The main objective is to treat acid-base status after the administration of a
the primary acid-base problem. controlled low concentration of O2 (i.e., FIO2
0.24 to 0.40). Administration of low doses of O2
Respiratory Acidosis in COPD is sometimes referred to as low-flow
Spontaneous Breathing O2 therapy.
General Guidelines Low-flow O2 therapy is a more appro-
Respiratory acidemia is often called ventila- priate therapeutic starting point than expen-
tory failure.10 This term is attractive when sive and invasive mechanical ventilation.553,554
Low-flow O2 may be effective despite high in determining minute ventilation and alveolar
initial PaCO2 (e.g., PaCO2 > 65 mm Hg). The ventilation. It therefore follows that respira-
patient must be monitored continuously with tory acidosis in this group may be, in a sense,
this therapy, however, and if hypercapnia iatrogenic, that is, caused by treatment (e.g.,
increases or acidemia is not relieved with this ventilator settings). Indeed, we have discussed
conservative management, noninvasive venti- earlier the use of permissive hypercapnia as a
lation or intubation and mechanical ventila- therapeutic strategy in ALI/ARDS.
tion may still be required. In the patient in whom we choose to correct
Noninvasive pressure support ventilation respiratory acidosis, the ventilator settings
has been shown to be a good alternative to may need to be adjusted. The PaCO2 level can
mechanical ventilation in some patient popula- be lowered by increasing alveolar ventilation.
tions.558 Noninvasive ventilation (Nasal mask Alveolar ventilation, in turn, may be increased
ventilation with Positive Pressure Ventilation) during mechanical ventilation by three possi-
has also been shown to be a very effective ble methods: increased tidal volume, increased
method to treat patients with chronic hypoven- respiratory rate, or decreased mechanical
tilation syndromes556 and COPD.557 deadspace. The specific changes to make will
In recent years, it has been suggested that, in depend on the ventilator mode as well as the
some patients, hypercapnia may actually be therapeutic objectives and priorities.
viewed as a desirable patient response. For

example, it may represent decreased ventilatory Decreasing VCO2
work (rather than exhaustion or fatigue) and a Finally, in some cases of respiratory acidosis, it
positive adaptation in COPD.499,500 Some have may be more desirable to attempt to decrease
even gone so far as to suggest that administra- CO2 production rather than to increase alveo-
tion of oxygen with subsequent worsening lar ventilation.494 The CO2 production can be
hypoxemia may actually enhance survival in retarded by altering nutrition (e.g., discontinue
COPD.555 total parenteral nutrition and reduce the respi-
Likewise, with the advent of permissive ratory quotient) or by decreasing the work of
hypercapnia, hypoventilation may be viewed breathing (e.g., paralysis).
as clearly more desirable than high lung infla-
tion pressures and volutrauma in acute lung Guidelines in Chronic CO2 Retention
injury/acute respiratory distress syndrome Normally, the goal of mechanical ventilation is
(ALI/ARDS) during mechanical ventilation. to restore normal eucapnic ventilation (i.e.,
The decision to intubate and initiate mechani- PaCO2 35 to 45 mm Hg) and normal pH.
cal ventilation in the patient with COPD is In patients with COPD and chronic hypercap-
never easy. All subjective and objective infor- nia, however, the goal is to carefully return the
mation should be incorporated into the analy- arterial PCO2 to the chronic normal level for
sis of the problem. that patient.
Large, abrupt decreases in arterial PCO2 in
Mechanical Ventilation the patient with chronic CO2 retention should
be avoided because this reduction may poten-
Teaching the fundamentals of ventilator care to tially lead to cerebral alkalosis, vasoconstric-
medical house staff is the most challenging aspect tion, and ischemia.560 In addition, generalized
that I acknowledge in their ICU curriculum. seizures, decreased cardiac output, or cardiac
R.D. Hubmayer562 arrhythmias may occur. Arterial PCO2 should
be lowered slowly and progressively in these
General Guidelines patients. In the past, some authors had sug-
The patient already receiving mechanical ven- gested rates as low as 10 mm Hg per hour,561
tilation constitutes a special diagnostic and although this would seem hard to achieve in
therapeutic situation. During the application the clinical setting.
of mechanical ventilation, the mode and set- Again, the target of arterial PCO2 reduction
tings on the mechanical ventilator play a role in the patient with chronic CO2 retention is the
patients chronic normal value. When patients exercises or diaphragmatic retraining.559,563

with COPD and chronic hypercarbia are Nevertheless, in severe hysteria or pain, phar-
mechanically ventilated to eucapnic ventilation macologic sedation or analgesia may be neces-
(i.e., laboratory normal arterial PCO2 35 to sary. Most often, supportive treatment of
45 mm Hg) for sustained periods (i.e., 2 to respiratory alkalemia is minimal. Identification
3 days), the kidneys excrete the excess bicar- and treatment of the underlying cause (correc-
bonate that is normally present in the blood. tive treatment) is usually the primary focus of
When weaning from mechanical ventilation is attention in this acid-base disorder.
then attempted through trials of spontaneous
breathing, arterial PCO2 increases to chronic Mechanical Ventilation
normal levels and acute uncompensated res- Severe respiratory alkalemia may occur during
piratory acidemia appears. The result is an mechanical ventilation and may diminish
additional obstacle to successful weaning cerebral perfusion.564 This may lead to shock,
in patients for whom weaning is already very seizures, and coma.564 Thus, severe respiratory
difficult. alkalemia must be avoided during mechanical
ventilation.
Respiratory Alkalosis In the patient with increased intracranial
Spontaneous Breathing pressure (ICP), hyperventilation is sometimes
As discussed in Chapter 13, the most common maintained therapeutically to lower ICP.
cause of respiratory alkalemia is moderate- Nevertheless, ideally the PaCO2 should proba-
to-severe hypoxemia. Although listed as a poten- bly not be allowed to fall below 30 mm Hg,508
tial underlying cause of respiratory alkalemia, and it should only be used for the short term
hypoxemia is not truly a root problem because as prolonged hyperventilation may be asso-
it is a nonspecific symptom of some other ciated with cerebral vasoconstriction and
cardiopulmonary pathology. Thus, in a very ischemia.565
practical sense, the prevention of hypoxemia Respiratory alkalemia with associated
may be considered as supportive treatment of hypocarbia is most often the result of increased

respiratory alkalemia. alveolar ventilation (VA). Therefore, treatment
In general, ventilation is increased of respiratory alkalemia during mechanical

greatly when PaO2 falls below approximately ventilation is accomplished by reducing VA.
60 mm Hg. Thus, a good starting point in the There are three general approaches to reducing

supportive management of respiratory alka- VA: by the reduction of tidal volume, the addi-
lemia is to ensure that PaO2 is equal to or tion of mechanical deadspace, or the reduction
exceeds 60 mm Hg. This, of course, normally of the respiratory rate. Sometimes, it is neces-
equates to an SpO2 of 90%. Of course, a PaO2 sary to administer drugs or to change the mode
of 60 mm Hg should not be exceeded in the of mechanical ventilation to achieve better con-
patient with COPD. trol of alveolar ventilation. An important con-
Some patients who present with respiratory cern regarding the use of muscle relaxants is the
alkalemia do not have hypoxemia or their res- potential for extreme patient anxiety. Extreme
piratory alkalemia fails to improve after the anxiety is particularly likely when the adminis-
restoration of a normal PaO2. In these cases, tration of muscle relaxants is not accompanied
further clarification of the underlying problem by the administration of sedatives or anal-
is necessary to determine the best course of gesics. Finally, whenever muscle relaxants are
treatment. administered, the effects of the drug should be
For example, acute anxiety may be accom- explained fully to the patient in advance.
panied by respiratory alkalemia, paresthesias, Notwithstanding the preceding caveats,
and dizziness. Here, simple rebreathing into a there are times when controlled ventilation via
bag or tubing may alleviate the respiratory the administration of skeletal muscle relaxants
alkalemia and may diminish symptoms. or sedatives is indicated. To allow a patient in
Some patients with chronic hyperventilation severe distress with extreme work of breath-
verging on panic seem to benefit from breathing ing and borderline hypoxia to breathe rapidly
and, paradoxically, ineffectively is certainly not excretion (e.g., salicylate or phenobarbital toxic-
optimal patient treatment. ity) or combat life-threatening hyperkalemia.484
Administration of sodium bicarbonate should
Metabolic Acidosis probably not be considered in metabolic aci-
The need for therapeutic intervention in meta- dosis unless pH is less than 7.10 and even then
bolic acidemia is gauged primarily by the it may not be beneficial.484 Indeed, in the most
severity of the acidemia. Mild-to-moderate severe cases of metabolic acidosis (e.g., lactic,
metabolic acidemia (pH > 7.10) is usually best ketoacidosis), alkalizing agents have shown the
left untreated with supportive measures.484 least efficacy.484
Currently, many would make an argument for Administration of oral bicarbonate may be
rarely using buffer treatments to support the useful in chronic metabolic acidosis. In cases of
pH in acute metabolic acidosis.484 chronic renal failure it may increase exercise tol-
A major problem with traditional therapy erance, prevent growth retardation, and reduce
for metabolic acidosis (i.e., intravenous sodium protein wasting and osteoporosis.484
bicarbonate) is that therapy simply corrects the
acidosis of the extracellular fluid and may, Dosage
in fact, acutely worsen the intracellular acidosis. Equation 14-1 shows the traditional method
It is becoming increasingly clear that many crit- for calculating the intravenous bicarbonate
ical organs (e.g., heart, brain, liver, respiratory dose in those rare cases where it may be neces-
muscles) have a remarkable intrinsic ability to sary. Nevertheless, all formulas are estimates
defend against intracellular acidosis. because dynamic physiologic acid-base changes
Therefore, treatment of the underlying discontinue during the therapeutic period, and dif-
ease and renal physiologic replenishment of ferent types of metabolic acidosis (e.g., lactic aci-
depleted bicarbonate most often negate the dosis, poisonings) respond to varying degrees.
need for supportive treatment. Occasionally, After administration of the initial dose, blood
therapeutic intervention may be necessary to gases should be analyzed and any additional
treat moderate acidemia if the patient is in a bicarbonate therapy should be guided based
precarious clinical state with cardiovascular on these results.
instability or if compensatory work of breath-
ing is exhaustive.484 Equation 14-1
Historically, lactate was a drug used to coun- [BE] 0.3 weight in kg/2 = HCO3 dose
teract metabolic acidemia. After administration,
lactate is converted to bicarbonate through the Cardiac Arrest and Sodium Bicarbonate Therapy
process of oxidation. However, lactate is rela- Venous Paradox
tively ineffective in the absence of oxygen, and Sodium bicarbonate has generally not been
even in its presence, the full alkalizing effect may shown to improve survival in cardiac arrest,
take 1 or 2 hours to achieve. For these reasons, and it is not recommended for routine initial
lactate is a poor alkalizing agent and is almost cardiac arrest management by the American
never used presently. Citrate, which has a similar Heart Association (AHA).703 Sodium bicar-
alkalizing mode of action, is also poorly suited bonate appears to correct extracellular fluid
for the clinical treatment of acidemia. acidosis at the expense of intracellular acidosis.
It does not appear to reduce and may in fact
Sodium Bicarbonate Administration exacerbate intramyocardial acidosis.
Indications In addition, there is considerable evidence
In the past, intravenous sodium bicarbonate that hypertonic buffer solutions may compro-
has been the drug most often used for the treat- mise cardiac resuscitation by reducing coro-
ment of severe metabolic acidosis in critical nary perfusion pressure.566 The importance of
care and during cardiopulmonary resuscitation coronary perfusion pressure in successful
(CPR). Presently, there is strong evidence to resuscitation has been widely acknowledged.
avoid the use of sodium bicarbonate in acute Studies have shown that during cardiopul-
conditions unless there is a need to assist toxin monary resuscitation, central venous PCO2
(average of 54 mm Hg) is about 34 mm Hg Complications of Sodium Bicarbonate Therapy

higher than the arterial PCO2 (average of Intracellular Hypercapnia, Cerebrospinal Fluid
21 mm Hg).567 Furthermore, central venous pH Acidosis, and Coma
had an average of 7.15, whereas arterial pH The administration of NaHCO3 will result in
had an average of 7.41.567 This phenomenon a further increase in intracellular and cerebro-
of venous acidosis with arterial alkalosis has spinal PCO2 as it is produced via hydrolysis.
been called the venous paradox. These findings Because CO2 is more permeable through cell
are in sharp contrast to the normal difference membranes and the blood-brain barrier than are
between arterial and venous PCO2 of approxi- bicarbonate ions, the immediate consequence of
mately 7 mm Hg and the normal difference in sodium bicarbonate therapy is a paradoxic intra-
pH of only about 0.02. cellular acidosis and rise in cerebrospinal fluid
Probably the most effective method to com- PCO2.570 Several detrimental consequences asso-
bat the metabolic acidosis during cardiac ciated with CPR have been attributed to this
arrest is with hyperventilation and vigorous effect. Specifically, rapid administration of exces-
cardiac compression.575 sive amounts of bicarbonate may precipitate
coma or arrhythmia.571
Value of Arterial Blood Gases in Cardiopulmonary
Resuscitation Bicarbonate Overcorrection Alkalosis
These findings strongly suggest that during There are also other complications associated
cardiopulmonary resuscitation (CPR), severe with sodium bicarbonate administration.
venous hypercapnia and acidosis often coexist Iatrogenic alkalemia after bicarbonate therapy
with simultaneous arterial hypocapnia and is relatively common. This may occur by two
alkalosis.567 It follows then that arterial blood mechanisms. First, hyperventilation may persist
gases generally fail to reflect systemic tissue or even increase due to continued cerebrospinal
acid-base status and are poorly suited for mon- fluid acidosis despite correction of plasma
itoring systemic acid-base conditions.567 This is acidemia. Second, as the body metabolizes
probably true both during CPR and during anions associated with organic acidosis (e.g.,
other low cardiac output states. lactate, acetoacetate, 3-hydroxybutyrate),
Thus, the value of arterial blood gases in endogenous bicarbonate is produced. The triad
CPR is cloudy. Mixed venous gases probably of endogenous bicarbonate, exogenous bicar-
provide a better indication of tissue acid-base bonate, and persistent hyperventilation may
status. Nevertheless, some measure of arterial thus lead to significant alkalemia.
oxygenation may still be important in the
assessment of the adequacy of tissue oxygen Hypokalemia
delivery.568 Acidemia is associated with the migration of
Arterial PCO2 is typically quite low during potassium (K+) from the intracellular fluid to
CPR,567 which is probably related to the rela- the plasma. During bicarbonate therapy, a rapid
tive hyperventilation of the lung secondary elevation of pH may result in serious hypo-
to the poor perfusion and decreased cardiac kalemia as K+ returns to the intracellular space.
output.569 This is particularly of concern during digitalis
The venous hypercapnia, on the other hand, therapy, because hypokalemia may predispose
is undoubtedly associated with an extremely to digitalis toxicity and arrhythmia. When
high tissue intracellular PCO2. It is known that hypokalemia is present with severe acidemia,
during anaerobic metabolism, cellular PCO2 bicarbonate must be administered with
increases more rapidly than in the blood. This extreme caution.
finding is particularly worrisome because an
intramyocardial PCO2 in excess of 475 mm Hg Fluid Overload
contributes to electromechanical dissociation. Another potential complication of bicarbonate
Electromechanical dissociation occurs when therapy is the precipitation of fluid overload or
the electrical activity of the heart continues but hypernatremia. Because sodium bicarbonate is
the mechanical pump does not function. dispensed as a hypertonic solution, fluid overload
may occur in the patient who is sensitive to in correcting acidosis in the cerebrospinal fluid
fluid. For example, this may be of considerable and intracellular compartment.573 It has been
concern in the patient with congestive heart later shown, however, that neither carbon diox-
failure. Even more important is the high risk ideproducing or carbon dioxideconsuming
of intra-cranial hemorrhage associated with buffers improved intracellular myocardial aci-
the administration of sodium bicarbonate dosis or resuscitatibility574; therefore, the use
in neonates. Special precautions should be of THAM is not recommended.
followed when sodium bicarbonate is used in It has also been argued that the effect of
neonates. introduction of carbon dioxide from buffer
therapy is relatively small and that the endoge-
Arterial Hypercapnia nous carbon dioxide production may be of
There is an immediate increase in plasma dis- much greater significance.574
solved CO2 after the administration of bicar- Furthermore, THAM is not without com-
bonate. In most cases, this additional CO2 is plications; it may cause spasm, phlebitis, or

excreted rapidly through increased VA; however, thrombosis at the site of administration

in the patient who is unable to increase VA because of its alkaline pH. Moreover, THAM
(e.g., neurologic disorder, controlled ventilation), is stored in a powder form and must be mixed
arterial PCO2 may increase appreciably.365 immediately before being administered to a
patient. This procedure may delay and compli-
Alternatives to Sodium Bicarbonate Therapy cate administration during cardiac arrests or
Tris-hydroxymethyl-aminomethane (THAM) other emergencies.
has been suggested as being a superior alkaliz- Carbicarb, a 1:1 mixture of disodium car-
ing agent to bicarbonate with less potential for bonate and sodium bicarbonate has also been
complications and increased therapeutic effec- purported to be more beneficial than sodium
tiveness. These claims are based on the follow- bicarbonate in hypoxic lactic acidosis.576
ing purported advantages: the intracellular Notwithstanding, Carbicarb has not been shown
buffering capability of THAM, the absence of to be more effective in follow-up studies.484
sodium, and the ability to buffer carbonic acid. The most disturbing aspect of the use of alka-
In early studies, THAM was shown to be a linizing agents for the treatment of metabolic
more effective buffer than sodium bicarbonate acidosis is the observation that re-oxygenation

A patient with chronic renal failure is admitted to the ASSESSMENT

hospital. Abnormalities: List abnormal data and other noteworthy
Explanation: List possible diseases, pathology, or
SaO2 91% other situations that may have led to this patients
pH 7.18 condition.
PaCO2 21 mm Hg Evaluation: Suggest additional data that would be
PaO2 78 mm Hg useful in helping understand the situation or in making
[HCO3] 8 mEq/L a diagnosis.
FIO2 0.21
Na 142 mEq/L INTERVENTION
CO2 15 mEq/L Importance: Prioritize concern(s) of treatment in order
Cl 101 mEq/L of urgency and/or seriousness as you see the overall
K 6.7 mEq/L situation.
of hypoxic cells is associated with increased cell onset of metabolic alkalosis in patients prone
death when the pH is normal or alkaline. to its development (e.g., receiving loop diuretics,
Indeed, this seems to indicate that acidosis may gastric fluid loss).
have a protective effect.484 Nevertheless, it is The drugs cimetidine or ranitidine may be
premature to assume that this is undoubtedly useful in patients at risk for metabolic alkalo-
true until further evidence is acquired. For sis secondary to stomach drainage because
now, we must continue to attempt to maintain they reduce gastric fluid secretion and acid
what we feel is a minimally acceptable pH, loss.529 Likewise, potassium-sparing diuretics
keeping in mind the clearly controversial role may be useful to avoid renal loss of potassium.
of buffer therapy.
Potassium
The attempt to restore homeostasis in the presence Mechanism of Potassium Loss. Patients with
of an acid-base disturbance is not a precise science metabolic alkalosis often also present with
when it comes to the metabolic component. hypokalemia. The hypokalemia may be due to
J. Morfei477 the mechanism responsible for the alkalosis
(e.g., renal NaHCO3 reabsorption, loss of gas-
Metabolic Alkalosis tric contents) or it may develop as the kidney
Metabolic alkalosis is one of the most common attempts to compensate for alkalemia. In alka-
simple acid-base disturbances in the critical lemia, the renal tubular cells selectively secrete
care environment. In one report, more than potassium into the urine while retaining
half of surgical patients who had blood gas hydrogen ions.
determinations were reported to be alkalemic Failure to correct potassium deficits will
at some point during their hospitalization.577 perpetuate the alkalemia or increase its sever-
Several authors have suggested that metabolic ity. Furthermore, low body potassium may
alkalosis accounts for about one-third of all lead to other adverse effects, such as arrhyth-
acid-base disturbances.480 mias in the patient receiving digitalis.
Metabolic alkalosis may be associated with Potassium Deficit. In general, the severity of
CNS dysfunction and hypokalemia, which may the potassium deficit is proportional to the
lead to serious arrhythmia. Moreover, severe severity of the metabolic alkalosis.529 Moderate
alkalemia (pH > 7.55) has been associated with metabolic alkalosis (plasma bicarbonate 30 to
a steep increase in mortality.579 A mortality rate 40 mEq/L) is accompanied typically by potas-
of 41% has been reported for pH values in sium deficits of 200 to 500 mEq.529 In severe
excess of 7.55 and 80% mortality may be asso- metabolic alkalosis (i.e., plasma bicarbonate of
ciated with values greater than 7.64.578 Timely 40 to 60 mEq/L), the deficit may be as high as
management of metabolic alkalemia may mini- 1000 mEq.529 Replenishment of these deficits
mize the incidence and severity of these unto- can be in the range of 100 to 150 mEq/day for
ward effects. Furthermore, in patients with several days in moderate alkalosis and may
mixed respiratory acidosis and metabolic alka- increase to 200 to 300 mEq/day in the most
losis, correction of the alkalosis may reduce severe cases.529
hypercapnia.583 Potassium Objective. KCl is most often indi-
cated in metabolic alkalemia in doses sufficient
Mild-to-Moderate Metabolic Alkalosis to replace body potassium stores, while avoid-
There are three important elements in the suc- ing plasma hyperkalemia. A reasonable clinical
cessful management of mild-to-moderate target is a low normal serum potassium ([K+]
metabolic alkalemia: potassium replacement, 3.5 to 4.0 mEq/L). Maintenance of higher levels
chloride replacement, and fluid volume may result in dangerously high levels of serum
replacement. Indeed, diminished intravascular potassium after the pH returns to normal,
volume and hypokalemia have been purported because potassium moves from the intracellular
to be responsible for the maintenance of 95% fluid to the plasma as the pH is decreased.
of cases of metabolic alkalosis.581 Control of Serum Potassium. One must always keep
these three ingredients can likewise prevent the in mind that potassium is measured in the
extracellular fluid. Extracellular potassium reabsorption, such as acetazolamide (Diamox),

levels may not always precisely reflect total is often beneficial in these patients.
body potassium, because most potassium In summary, treatment of mild-to-moderate
resides in the intracellular space. Furthermore, metabolic alkalosis requires appropriate replace-
in the presence of alkalemia, potassium ment of potassium, chloride, and body fluids. In
migrates from the plasma to the intracellular selected cases, acetazolamide may be useful, and
fluid. This is an important reason why therapy cimetidine may be used in a preventative fashion.
should be targeted for a low normal serum
potassium. A low normal target also seems Severe Metabolic Alkalemia
reasonable because most people actually have As mentioned earlier, severe metabolic alkalemia
serum potassium concentrations toward the (pH > 7.55) has been associated with a steep rise
upper limits of normal (4.0 to 4.7 mEq/L).580 in mortality. Patients with a pH between 7.60
The relatively low serum concentration also and 7.64 had a mortality of 65%, whereas a
dictates that potassium be administered slowly. higher pH was associated with even a higher
Slow administration allows the potassium to mortality (i.e., 90%).579 Acute severe alkalemia
move gradually to the intracellular space and often reduces cerebral blood flow and may cause
helps to avoid dangerous variations in extra- seizures and coma.533
cellular fluid concentrations. Relatively minor The treatment described earlier for metabolic
changes in serum potassium may be very detri- alkalosis (i.e., potassium chloride and fluid
mental. For example, hyperkalemia of 6.0 may replacement) is a slow process dependent on
lead to serious consequences, and values of 6.5 renal mechanisms that may require several days.
may likely cause potentially fatal arrhythmias. In severe metabolic alkalemia, more aggressive
In summary, potassium replacement is critical in therapy may be indicated to restore the pH to
the management of metabolic alkalosis; never- safe levels.
theless, it must be accomplished slowly, care- Administration of dilute hydrochloric acid
fully, and systematically. into a central vein is probably the best and
safest treatment for severe metabolic alka-
Chloride and Fluid Volume Replacement lemia.583585,587 Interestingly, some reports have
Ninety percent of metabolic alkalosis seen clin- also reported improved oxygenation following
ically is associated with depletion of chlo- administration but this remains to be substanti-
ride.582 This may result from diuretic therapy ated.583,587 A central vein must be used because
or from a loss of excessive gastric fluid. Blood of the corrosive nature of this strong acid.
bicarbonate is generated in these circum- Extravasation of HCl has been associated with
stances as the kidney attempts to correct fluid severe soft tissue necrosis.586 An estimation of
volume deficiencies. Correction of alkalemia the amount of hydrochloric acid to be initially
here can only occur if sufficient fluid volume administered can be calculated in the same way
and NaCl are available to the kidneys. that the dose of bicarbonate was calculated in
The amount of NaCl that is necessary Equation 14-1.584
depends on the degree of fluid volume depletion. The solution should contain 100 mEq of
The amount can be evaluated through central HCl/L of NaCl. This solution is typically infused
venous pressure measurements or, in the absence at a rate of 1 liter for 4 to 6 hours. Further
of a central venous pressure line, through clinical therapy must be guided by arterial blood gas
assessment. It is not uncommon for patients measurements after the initial dose.
with excessive gastric fluid loss to need several Other acidifying agents (e.g., ammonium
liters of fluid replacement. chloride or arginine monohydrochloride) may
Some patients have inadequate NaCl and be used, but they require proper metabolism by
fluid perfusing the kidneys, despite abundant the liver and may be associated with complica-
body stores (e.g., congestive heart failure, tions. Ammonium chloride should be avoided
ascites). Sodium chloride and fluid therapy in in patients with liver disease. Administration of
these patients would be totally inappropriate.533 arginine monohydrochloride may precipitate
A diuretic that selectively depresses bicarbonate dangerous hyperkalemia.
High doses of acetazolamide may likewise be forms of aggressive acid-base management

useful in helping to reverse metabolic alkalemia (e.g., acetazolamide, hypoventilation) may
in the patient who can tolerate diuresis. also be appropriate. Some authors suggest
Acetazolamide is particularly useful in patients that treatment for severe metabolic alkalosis
with posthypercapnic metabolic alkalosis with should be reserved for only experts in acid-base
normal volume status.480 Nevertheless, it is not management because indications for treatment
recommended for routine use because its admin- are limited and therapy is potentially haz-
istration is associated with increased renal excre- ardous.480 Probably most importantly, both
tion of water, sodium, and potassium, all of moderate and severe metabolic alkalemia ulti-
which are undesirable in metabolic alkalosis. mately require potassium, chloride, and fluid
In addition, patients who are being mechan- maintenance.
ically ventilated may be hypoventilated during Many cases of metabolic alkalosis can be
severe metabolic alkalemia in an effort to pro- prevented. This can be accomplished by main-
tect the pH (therapeutic compensation). This taining a high index of suspicion in situations
maneuver is only a stopgap, however, until that are commonly associated with metabolic
other treatment can become effective. alkalosis (i.e., diuretic therapy, gastric
In summary, acidifying agents may be drainage) and through prompt attention to
indicated in severe metabolic alkalemia. Other fluid and electrolyte balance.
EXERCISES
Exercise 14-1 Factors Complicating Acid-Base Disturbances

1. State the two organ systems involved in the compensation of acid-base disturbances.
2. Indicate with an arrow whether the following blood gas parameters are typically above or
below normal in severe COPD.
PaCO2 _________
[HCO3] _________
[BE] _________
3. The finding of metabolic alkalosis and a normal PaCO2 on the blood gas report of a patient
with severe COPD is likely to be the result of (bicarbonate treatment/compensation for
previous hypercapnia).
4. It is not uncommon for (lactic acidosis/ketoacidosis) to complicate the blood gas finding in
acute exacerbation of COPD.
5. The hallmark of acute exacerbation of COPD is the presence of a surprisingly normal
(PaO2/pH) despite severe hypercarbia.
Questions 6-8: Given the following blood gas:
pH 7.30
PaCO2 75 mm Hg
[BE] 8 mEq/L
[HCO3] 35 mEq/L
PaO2 48 mm Hg
6. The patient most likely has (COPD/renal failure).

7. The patient should be treated initially with (low-flow O2 therapy/mechanical ventilation).
8. The high bicarbonate is probably a result of (a primary metabolic problem/compensation).
9. Compensation for metabolic acidosis during mechanical ventilation may appear
(more/less) complete than during spontaneous breathing.
10. Chronic renal failure most often presents with metabolic (acidosis/alkalosis).
Exercise 14-2 Mixed Acid-Base Disturbances

1. The coexistence of two primary acid-base disturbances is called a ___________ acid-base

disturbance.
2. The percentage of patients with simple acid-base disturbances that fall within the bands
seen on the acid-base map is ______%.
3. When a patients values fall within one of the bands on the acid-base map, it
(does/does not) ensure that he or she has a single acid-base disturbance.
4. Given a patient with a simple, primary, acute respiratory acidemia resulting in a PaCO2
of 70 mm Hg and pH of 7.22, state the approximate pH that results after maximal
compensation.
5. Given a patient with a simple, primary, acute respiratory alkalosis resulting in a PaCO2 of
20 mm Hg and a pH of 7.60, state the approximate pH that results after several days of
compensation.
6. List the approximate PaCO2 values that will accompany maximum compensation for simple,
primary metabolic acidosis given the following pH values: 7.18, 7.30, and 7.22.
7. Compensation for respiratory acidosis usually leads to (hypochloremia/hyperchloremia).
8. Compensation for respiratory alkalosis usually leads to (hypochloremia/hyperchloremia).
9. The maximal compensatory response to metabolic acidosis may take up to 1 (hour/day).
10. State six situations that should alert the clinician to the likelihood of a mixed acid-base
disturbance.
Exercise 14-3 Respiratory Acid-Base Treatment

1. State the two general directions or thrusts of therapeutic (treatment) interventions in

acid-base disturbances.
2. The primary focus of treatment in acid-base disturbances is stabilization of the
(pH/PaCO2/[BE]).
3. Ventilatory failure is a term used to designate what primary acid-base disturbance?
4. In respiratory acidemia, the most sensitive indicator of the need for mechanical ventilation
is the (PaCO2/pH).
5. In general, mechanical ventilation should be considered in respiratory acidosis in the

patient who does not have COPD when the pH falls below ______.
6. Before initiating mechanical ventilation in patients with COPD and with respiratory
acidosis, it is wise to attempt __________ therapy.

7. List three variables that may be changed to alter VA and correct respiratory acidemia or
respiratory alkalemia during mechanical ventilation.
8. Acute, severe hypercapnia in patients with COPD should ideally be corrected
(gradually/quickly).
Exercise 14-4 Treatment of Metabolic Acidosis

1. Primary metabolic acidosis with a pH of 7.23 generally (is/is not) treated with NaHCO3.
2. Lactate and citrate, after passing through the ______, produce bicarbonate.
3. The drug most commonly used in the treatment of severe primary metabolic acidosis
is ___________.
4. In general, sodium bicarbonate may be indicated when the pH falls below ______ due to
metabolic acidosis.
5. Bicarbonate administration may lead to plasma (hypokalemia/hyperkalemia).
6. A serious potential complication of bicarbonate therapy in neonates that is related to the
hypertonicity of sodium bicarbonate is ______ hemorrhage.
7. If bicarbonate is administered to a patient who cannot alter alveolar ventilation, ______
may result.
8. Administration of sodium bicarbonate (has/has not) been associated with coma and
decreased central nervous system function.
9. Two drugs purported to have advantages over sodium bicarbonate are ______ and ______.
10. Write the formula for estimating the dose of bicarbonate to be administered in metabolic
acidemia.
11. Sodium bicarbonate (is/is not) indicated in metabolic acidosis associated with
hyperkalemia or salicylate toxicity.
12. Sodium bicarbonate (is/is not) recommended for routine initial cardiac arrest management
by the AHA.
13. During cardiopulmonary resuscitation, central venous PCO2 may be (slightly/much) higher
than arterial PCO2.
14. The phenomenon of venous acidosis with arterial alkalosis has been called
the ____________.
15. The administration of NaHCO3 results initially in a (fall/rise) in intracellular and
cerebrospinal pH.
16. Calculate the dose of bicarbonate indicated for the treatment of metabolic acidemia when
the [BE] is 20 mEq/L and the patient weighs 80 kg.
Exercise 14-5 Treatment of Metabolic Alkalosis

1. State the three important elements in the treatment of mild-to-moderate metabolic alkalosis.
2. A drug that is useful in controlling the development of metabolic alkalosis secondary to
gastric drainage by decreasing gastric secretion is ______.
3. A reasonable target of potassium replacement in metabolic alkalosis is a serum value
above ______.
4. Potassium deficits must be replaced (slowly/quickly).
5. A useful diuretic that decreases blood bicarbonate level in metabolic alkalosis is ______.
6. Severe metabolic alkalemia is defined as a pH equal to or in excess of ______.
7. The treatment of choice in severe, sustained metabolic alkalemia is ________________.
8. Dilute HCl should be administered through a (peripheral/central) vein.
9. The concentration of dilute HCl should be ______ mEq/L.
10. Metabolic alkalosis is (common/uncommon) in the hospital setting.

1. Go to the American Heart Association site and describe current recommendations for the
use of sodium bicarbonate during cardiac arrest.
NBRC Challenge 14
1. An ICU patient with apparent hypo- You would recommend:

volemia has blood gases with electrolytes A) increased FIO2.
drawn. Results include: pH 7.53, PaCO2 B) noninvasive positive pressure
50 mm Hg, [K] 3.1 mEq/L. Which of the ventilation.
following would be useful? C) mechanical ventilation.
A) Acetazolamide D) serum electrolytes.
B) Mechanical ventilation E) sodium bicarbonate I.V.
C) Dilute HCl I.V. (CRT EXAMINATION NBRC
D) KCl I.V. MATRIX III,D,12,d)
E) Carbicarb
4. Arterial blood gases drawn during a car-
(CSE-RRT EXAMINATION NBRC
diac arrest show the following results: pH
MATRIX III,D,13)
7.45 and PaCO2 30 mm Hg. Based on
2. An ICU patient with ARDS is being these results, it is reasonable to assume
mechanically ventilated in the ICU in the that myocardial and tissue pH is:
control mode at 6 mL/Kg. Blood gases A) normal.
are drawn with the following results: pH B) most likely alkalotic.
7.32, PaCO2 62 mm Hg, PaO2 68 mm Hg. C) most likely acidotic.
You are asked for recommendations D) in need of HCl acid I.V.
regarding mechanical ventilation. You E) in need of sodium bicarbonate.
would recommend: (CSE-RRT EXAMINATION NBRC
A) increased tidal volume. MATRIX I,C,2,e)
B) increased respiratory rate.
5. Blood gases are drawn on a patient in
C) elimination of all mechanical
ICU with the following results: pH 7.61
deadspace.
and PaCO2 55 mm Hg. Despite various
D) KCl I.V.
attempts to correct acid-base status, it
E) leave the patient on the current
has remained essentially the same for the
settings.
past 2 days and the physician is con-
cerned about the potential for arrhyth-
MATRIX III,E,3)
mias. At this time you might suggest:
3. A patient with acute exacerbation of A) KCl I.V.
COPD is being treated with low-flow B) NaCl I.V.
oxygen therapy but appears to be C) NaHCO3.
worsening with increased dyspnea D) dilute HCl acid I.V.
and a mild increase in hypercapnia E) Carbicarb therapy.
despite a PaO2 of 62 mm Hg. pH (CSE-RRT EXAMINATION NBRC
has fallen slightly to 7.30. MATRIX III,D,13)
VI
UNIT
Noninvasive Techniques and

Case Studies
385
Chapter
15
Noninvasive Blood Gas Monitoring
Pulse oximetry is arguably the most significant technological advance ever made in monitoring the well-being
and safety of patients during anesthesia, recovery, and critical care.
J.W. Severinghaus and P.B. Astrup588
Monitors, of themselves, never improve patient outcome because they do not do anything. They provide
information that must be interpreted. The decision to act (or not to act) must be made by a clinician.
Charles G. Durbin, Jr.618
Pulse oximetry and capnography are not replacements for arterial blood gas analysis, but rather serve as
adjunctive monitoring tools.
J. Prouix589
Outline
Introduction, 388 Limitations, 402
Oximetry, 388 Transcutaneous PO2 /PCO2 Monitoring, 403
Historical Development, 388 Introduction, 403
Spectrophotometry, 389 Anatomy of the Skin, 403
Qualitative Analysis, 389 Factors Determining PtcO2, 403
Quantitative Analysis, 390 PtcO2PaO2 Agreement, 404
Oximeters, 390 Placement, 404
Transmission Oximetry, 390 Calibration, 405
Hemolysis, 391 Response Time, 405
Backscatter Oximetry, 391 Perfusion and Drugs, 405
Functional Saturation, 392 Temperature, 405
CO-Oximetry, 392 Clinical Application, 405
Ear Oximetry, 392 Limitations, 405
Background, 392 Transcutaneous PO2 versus Pulse Oximetry, 405
Hewlett-Packard Ear Oximeter, 393 Capnometry, 406
Pulse Oximetry, 393 Introduction, 406
Overview, 393 Measurement Techniques, 407
Diagnosis versus Monitoring, 393 Infrared Absorption Capnometers, 407
Conventional Underlying Technologies, 394 Mainstream versus Sidestream Sampling, 408
Historical Development, 394 Colorimetric CO2 Analysis, 408
Photoelectric Plethysmography, 394 Capnograms, 408
Pulse/Circulation Dependency, 396 Normal Capnogram, 408
Two-Wavelength Methodology, 396 Abnormal Capnograms, 409
Technical Limitations, 397 Volumetric Capnograms, 410
Accuracy, 397 PetCO2 as an Indicator of PaCO2, 410
Technical Error, 398 P(aet)CO2, 412
Advances in Technology, 401 Usefulness of PetCO2, 413
Signal Extraction Technology, 401 Verification of Intubation, 413
Other New Methods, 401 PetCO2 during Cardiopulmonary
General Application, 401 Resuscitation, 413
Usefulness, 401 Summary, 414
SpO2 Targets, 402 Exercises, 415
387
388 Unit VI Noninvasive Techniques and Case Studies
INTRODUCTION
delayed information about a single previous
The assessment of blood oxygenation, carbon point in time. Unfortunately, this is the case
dioxide levels, and pH is crucial in the man- with arterial blood gases.
agement of critically ill patients. Arterial blood Monitoring techniques such as pulse oxime-
gases remain the gold standard of evaluation try, on the other hand, are generally used con-
in these areas. Nevertheless, acquisition of an tinuously. Measurement techniques are used
arterial blood sample for analysis is an invasive primarily to evaluate the patient during a specific
procedure in which a foreign object (needle) point in time or during an acute cardio-
penetrates the protective barrier of the skin pulmonary crisis. Conversely, monitoring
and directly enters the bloodstream. techniques are used more often in an ongoing
The use of invasive procedures is associated fashion to indicate potentially harmful condi-
with an increased potential for complications, tions for the patient. Monitoring techniques
such as infection or trauma. In addition, invasive generally provide real-time information.
procedures generally cause increased discomfort In this chapter, the traditional tech-
and pain for the patient. Furthermore, invasive niques of oximetry and CO-oximetry are
procedures are usually costly. Changes in reviewed and compared with noninvasive pulse
governmental reimbursement policies have oximetry. A brief review of transcutaneous gas
exerted considerable pressure on hospitals to measurement techniques is also included.
use less expensive assessment techniques. Finally, capnometry and capnography are
Finally, acquired immunodeficiency syndrome discussed. Throughout these discussions, the
has vastly increased our awareness regarding clinician should always keep in mind the
the potential hazards to health care workers in quote by Charles Durbin at the beginning
handling blood or blood products. of this chapter. Monitors do not do anything,
Emphasis and attention in recent years has it is the clinician who must act and respond
been focused on the development of noninva- appropriately.
sive techniques and methods for patient moni-
toring, treatment, and evaluation. The pulse OXIMETRY
oximeter is an example of a device developed
for the noninvasive assessment of oxygenation. Historical Development
In view of the first quotation used at the begin- The technique of measuring the oxygen satu-
ning of this chapter, it is not surprising that ration of blood hemoglobin was described in
pulse oximetry has caused a virtual revolution 1932.590 Use of the term oximeter to describe
in the way that we approach the assessment of the particular measurement device, however,
oxygenation. was not introduced until 10 years later in
Another trend has been the movement away 1942.591 Millikan (1906 to 1947) coined the
from measurement devices and techniques term oximeter for the device that he invented
toward monitoring devices and techniques. to measure ear oxygen saturation.591 At that
Measurement techniques, such as arterial time, Millikan was working on the problem of
blood gases, provide us with static information aviators losing consciousness while at high
or data about a single, isolated point in time, a altitude during battle. He solved this problem
snapshot if you will. Often, these static meas- by inventing a servo-controlled oxygen supply
urements do not reflect the moment-to-moment system attached to an ear oximeter.
changes in oxygenation and trends that occur Earlier, however, in 1860, invention of
within the body. Oxygenation is in reality the spectroscope by Bunsen and Kirchhoff
a continuously changing, dynamic process. actually paved the way for the development of
Measurement techniques may be subdivided oximetry.591 The spectroscope was a device
further into those that provide immediate that was used initially to measure the exact
real-time information, such as a pulmonary wavelengths of light emitted after introducing
wedge pressure or an arterial blood pressure. elements into the flame generated by a Bunsen
Alternatively, measurements may provide us with burner.
Chapter 15 Noninvasive Blood Gas Monitoring 389
Spectrophotometry an unknown substance.591 As such, colorimetry

Qualitative Analysis depended on visual acuity and perception and,
Interestingly, each substance studied with the consequently, was not highly exact. The current
spectroscope had its own unique light emission measurement technique of spectrophotometry
spectrum. Apparently, each substance absorbed is sometimes referred to incorrectly as a colori-
and therefore emitted light of different wave- metric method. This term is technically incorrect
lengths in its own unique manner much like because color per se is not actually evaluated.
each individual has his or her own distinct
fingerprints. The particular pattern of light Photoelectric Effect
absorption/emission at sequential light wave- Discovery of the photoelectric effect and devel-
lengths can be graphed, and this pattern is opment of practical photoelectric cells (photo
known as the absorption spectrum of that par- detectors) paved the way for spectrophoto-
ticular substance. The absorption spectra of metry as it is used today. The photoelectric
some of the more common forms of hemoglo- effect is the ability of light to release electrons
bin that may be present in the body are shown from metals in proportion to the intensity of
in Figure 15-1. Measurement of the light spec- the light (Figure 15-2). A photodetector can
trum of an unknown substance may thus serve use this principle to measure light intensity and
as a useful technique for qualitative analysis. to convert it into electrical energy.
In spectrophotometry, light is passed through
Colorimetry a filter and is thus converted into a specific
Early techniques for actually measuring light wavelength. This light is then passed through a
intensity over sequential light wavelengths were cuvette that contains the substance being ana-
difficult. For this reason, colorimetry, a simpli- lyzed. The amount of light that passes through
fied measurement technique that did not actu- the cell is detected on the opposite side of the
ally require measurement of light intensity, was cuvette by a photo detector and is reflected on
often used in qualitative analysis. Colorimetry a meter (Figure 15-3). Thus, measurement of
was a methodology wherein the color of a light emission at different wavelengths can be
known substance was compared with that of readily accomplished by using the technology
535 560 577 622 636 670

25
20
Hb
Absorbance
HbO2
15 HbCO
MetHb
SHb
10
0
500 550 600 650 700
nm
Figure 15-1. Absorption spectra of common forms of hemoglobin. Absorption spectra of oxyhemoglobin,
deoxyhemoglobin, methemoglobin, carboxyhemoglobin, and sulfhemoglobin.
ns k = a constant (characteristic of the substance

ro
e ct ed and wavelength of the incident light)
El ject c = concentration of the absorbing substance
e
d = pathlength in the absorbing medium
Li
gh
(usually expressed in centimeters)

t
The Lambert-Beer law shows that light

absorption of a substance depends not only on
the substance per se but also on the concentra-
tion (c) of the substance present.
Surface of a metal
such as sodium Optical Density
Figure 15-2. Photoelectric effect. Light releases One of three things can happen to light as it
electrons from metals in proportion to the intensity enters a blood sample: (1) light may be
of the light. absorbed by the solution; (2) it may be trans-
mitted through the solution; or (3) it may be
reflected from the solution.
of spectrophotometry. The term spectrophoto- During analysis of a substance, the ratio of
metry (spectro-photo-metry) is based on the light intensity incident on the substance (Io) is
measurement (-metry) of light (-photo-) spec- compared with the light intensity of the trans-
trums (spectro-). mitted light (Ix). The ratio of Io/Ix is sometimes
referred to as the optical density. Plotting out the
Quantitative Analysis optical density at various wavelengths leads to
Interestingly, spectrophotometry can be used for a graphic representation of the light absorption
quantitative analysis as well as for qualitative spectrum of a substance (see Fig. 15-1).
analysis; that is, the amount or concentration of When c in the Lambert-Beer law is expressed
a particular substance can also be evaluated by in moles per liter, k is then referred to as the
using the principles of spectrophotometry. molar extinction coefficient.
Lambert-Beer Law Oximeters

Quantitative spectrophotometry is made possi- An oximeter is an instrument that measures the
ble by application of the Lambert-Beer law. amount of light transmitted through, or reflected
from, a sample of blood at two or more specific
log10 Io/Ix = kcd
wavelengths.592 Thus, oximetry is a light meas-
Io = intensity of light incident on the specimen urement (photometric) technique that uses
Ix = intensity of the transmitted light two or more specific wavelengths of the light
spectrum to differentiate oxygenated from
unoxygenated hemoglobin and to quantitate
their relative concentrations. In other words,
an oximeter is a dedicated spectrophotometer
that is designed specifically to measure oxygen
saturation (SO2).
Transmission Oximetry
Because hemoglobin is a colored substance, it
absorbs some of the light that is passed through
a blood sample. Furthermore, according to the
A B C D E Lambert-Beer law, the amount of light absorbed
Figure 15-3. Components of a spectrophotometer. at a particular wavelength (i.e., optical density)
A simplified diagram of a spectrophotometer. depends on the concentration of hemoglobin
Components include (A) lamp, (B) filter, (C) cuvette, present.591 Similarly, the amount of light trans-
(D) photocell, and (E) meter. mitted through the blood sample at a given
Relative absorbance
Hb
Isobestic point
HbO2
600 700 800 900 1000

Wavelength (nm)
Figure 15-4. Light absorption spectra of oxygenated and deoxygenated hemoglobin. At a wavelength of
805 nm, an isobestic point exists. At 650 nm, there is a large difference in absorption between oxyhemoglobin
and deoxyhemoglobin.
wavelength is related inversely to the amount Hemolysis

of light absorbed. Because the presence of cells in the blood tends to
Each form of hemoglobin (e.g., HbO2, Hb, scatter light, measurements of SaO2 by oximetry
HbCO, metHb) has its own unique absorption/ in the laboratory are made usually after break-
transmission spectrum (see Fig. 15-1). The SaO2 ing down the red blood cells (i.e., hemolysis).
level can be measured because oxyhemoglo- Typically, red blood cells are hemolyzed ultra-
bin and desaturated hemoglobin absorb light sonically within the oximeter to make the
equally at some wavelengths, whereas they sample more homogeneous and to increase the
absorb light differently at other wavelengths. accuracy of the measurement. Transmission
For example, at a wavelength of 805 nm in the oximeters that use hemolyzed blood are gener-
near infrared region, oxyhemoglobin and ally accurate, stable, and precise.595
desaturated hemoglobin have identical light
absorption properties (Fig. 15-4).593 When two Backscatter Oximetry
substances absorb light equally at a given wave- As an alternative to transmission oximetry, one
length, an isobestic point is said to exist.594 can measure the amount of light reflected at
On the other hand, at a wavelength of certain wavelengths and likewise determine the
650 nm in the red region of the spectrum, there SaO2 value. Each species of hemoglobin has its
is a large difference in light absorption prop- own unique reflection spectrum, just as each
erties between oxyhemoglobin and desatu- species has its own unique absorption spectrum.
rated hemoglobin (see Fig. 15-4). The total Figure 15-5 illustrates the location of the
hemoglobin can be determined at 805 nm major components used in transmission oxime-
and the amount of HbO2 can be found at try compared with backscatter (reflection)
650 nm. Thus, the difference in light absorp- oximetry. Multiple (two) wavelength oximeters
tion at these two wavelengths can be used to are shown in both examples that use red and
calculate SaO2. infrared light sources. The major difference in
IR
IR
Photodetector Photodetector
Red
Red
Transmission oximetry Reflection oximetry
Figure 15-5. Location of major components of transmission and reflection oximeters.
the two techniques is simply the location of the species are included in the determination of
photodetector. In transmission oximetry, the total hemoglobin and therefore the calculation
photo detector is opposite the light source, of saturation.596
whereas in reflection oximetry it is on the same Thus, with this instrument, SaO2 is the per-
side as the light source. centage of HbO2 compared with all measured
forms of hemoglobin (including dyshemoglo-
Functional Saturation bin species) in the arterial blood. SaO2 measured
Regarding interpretation of data, it is important in this way is sometimes referred to as fractional
to understand two essential points when SaO2 is SaO2 and may, at times, differ substantially
measured using the two-wavelength method. from functional SaO2.
First, when only two wavelengths are used, con- The clinician should be aware that a poten-
centrations of abnormal forms of hemoglobin tial error may occur when CO-oximetry is used
(e.g., HbCO, metHb) cannot be detected.594 in neonatal/premature infant SaO2 assessment.
Second, the SaO2 value measured in this way is Erroneously high HbCO% and erroneously
the percentage of HbO2 compared with the sum low SaO2 levels may be reported if substantial
of HbO2 and desaturated Hb only (however, quantities of fetal hemoglobin are present. The
HbCO and generally metHb will be picked up error is introduced because the absorption
by the oximeter as HbO2). Because this meas- properties of fetal oxyhemoglobin are similar to
urement does not include abnormal forms of those of HbCO at the light wavelengths used.597
hemoglobin, it is sometimes referred to as func- In review, the percentage of HbO2 compared
tional SaO2.594 Functional SaO2 is the percent- with the sum of desaturated hemoglobin and
age of HbO2 compared with the quantity of HbO2 in arterial blood is called functional SaO2,
hemoglobin capable of carrying oxygen. whereas the percentage of HbO2 compared with
MetHb, HbCO, and sulfhemoglobin are all forms (including dyshemoglobin species) of
incapable of carrying oxygen and are some- hemoglobin in arterial blood is called fractional
times referred to as dyshemoglobin species. SaO2. The presence of substantial quantities of
Dyshemoglobin species are not directly consid- fetal hemoglobin may distort HbCO% and
ered in the measurement of functional saturation SaO2 readings obtained via CO-oximetry.
via oximetry. Notwithstanding, the presence of
significant dyshemoglobin species may lead to Ear Oximetry
erroneous functional saturation. Background
Unfortunately, conventional measurement of
CO-Oximetry saturation via oximetry or CO-oximetry
Functional SaO2 is in contrast with the SaO2 requires the acquisition of a blood sample. In
measurement resulting from use of a CO- other words, both of these measurements are
oximeter (i.e., cuvette oximeter).591 As the name invasive. Obviously, measurement of saturation
implies, this instrument can measure HbCO% noninvasively would be an attractive alternative.
in addition to SaO2. In addition, the percentage As early as 1935, Matthes showed how
of methemoglobin is usually measured as well. transmission oximetry could be applied to the
With this instrument, major dyshemoglobin external ear.598 Throughout the years, however,
the major problem with noninvasive oximetry being manufactured.603 Pulse oximeters are
has been the inability to differentiate light typically being used in its place.
absorption due to arterial blood from that due
to all other blood and tissues in the light path. PULSE OXIMETRY
Two techniques were developed in an attempt
to isolate arterial blood and to get a more Overview
accurate SaO2 reading. The phenomenal growth and acceptance of pulse
First, attempts were made to arterialize the oximetry since the mid-1980s has made it the
ear by enhancing local perfusion. Arterialization preeminent noninvasive monitor of oxygenation.
could be accomplished by one or more of the G.H. Hicks628
following: heating the ear, applying a chemical
vasodilator (e.g., nicotine cream),599 or briskly The simplicity and ready availability of pulse
rubbing the ear for about 15 seconds. oximetry has literally revolutionized clinical
Second, a sensor was developed that incor- oxygenation monitoring. Currently, blood
porated a bladder that could be used to com- oxygenation can easily be monitored continu-
press the earlobe and to render it bloodless. ously and noninvasively at the bedside or in
Thus, the optical properties of the bloodless ear the office or home. Application of this tech-
could be compared with the optical properties nology requires minimal technical skill and
of the perfused ear. This information could knowledge regarding the assembly, applica-
then be used to cancel out individual variations tion, and maintenance of equipment. Pulse
in skin pigmentation or ear characteristics. oximeters are typically calibrated at the fac-
tory and undergo a self-diagnostic check
Hewlett-Packard Ear Oximeter when powered up.628 Furthermore, arterial
In 1976, Hewlett-Packard incorporated these blood gases with related risks, complications,
principles into the development of the model and costs can often be avoided by using pulse
47201A ear oximeter. This device used the oximetry.289
aforementioned principles and measured Indeed, pulse oximetry is currently a stan-
light transmission at eight different equally dard of care in the operating room and is
spaced wavelengths from 650 to 1050 nm. probably soon to become a standard of care
Measurements at all eight wavelengths were in critical care and other healthcare settings. It
incorporated into a complex formula that has already been referred to as a standard of
corrected for light absorption due to skin pig- care for nearly all patients in neonatal and
mentation and provided a measure of func- pediatric intensive care.628 No other medical
tional saturation. This clinical instrument device has achieved such widespread accept-
was accurate over a saturation range of 65% ance and implementation.610
to 100%.600 A MEDLINE (National Library of Medicine)
The original Hewlett-Packard ear oximeter search of the term pulse oximetry in 2003
was used widely in pulmonary function labora- yielded more than 2300 citations,628 and the
tories, cardiac catheterization laboratories, and list is growing rapidly. Furthermore, pulse
physiologic research. Furthermore, the fact that oximetry has been demonstrated to be the sin-
ear oximetry could measure oxygen saturation gle most important identifier of critical mishap
under both stable and rapidly changing condi- events.611 Capnography is second, with ECG a
tions rendered it a very useful diagnostic tool.601 distant third. The value of pulse oximetry is
Simple ear oximetry has not, however, proved such that it has often been referred to as a fifth
accurate enough to be used for determining the vital sign.612,628
appropriate oxygen prescription for patients
requiring supplemental oxygen during exer- Diagnosis versus Monitoring
cise.602 Ear oximetry has never achieved promi- Historically, arterial blood gas assessment was
nence as a clinical bedside monitor because of commonly used for diagnostic purposes. On
its bulky nature and relatively high cost. The the other hand, arterial blood gases are limited
Hewlett-Packard ear oximeter is no longer in patient oxygenation monitoring because
they represent a single, past moment in time. of small light-emitting diodes (LEDs) and
In contrast, pulse oximetry is much better microprocessors have made the production of
suited for patient oxygenation monitoring than pulse oximeters both feasible and relatively
diagnosis. economical.
The term monitoring is derived from the
Latin word monere, which means to warn. Historical Development
Although the accuracy of pulse oximetry may Although photoelectric plethysmography (to be
make it suspect in certain diagnostic applica- described in the next section) and spectrophoto-
tions, its value in patient surveillance is unques- metry have been available for decades, not
tionable. Pulse oximetry may help us identify until 1972 did the Japanese biochemical engi-
potentially lethal oxygenation disturbances neer Takuo Aoyagi591 successfully combine
while we still have time to respond. these techniques in the development of the
It has been estimated that more than one- pulse oximeter. Also, the development of
third of patients are admitted to intensive care microprocessors and LEDs paved the way for
units primarily for the purpose of monitor- clinical pulse oximetry by providing lightweight,
ing.613,614 The essence of monitoring is contin- stable light sources and bedside computer-
uous trending with concurrent alarms and ization of complex mathematical formulas.
signals of critical situations. The Japanese firm Nihon Kohden developed
The true value of any alarm, however, relies Aoyagis instrument and received a Japanese
on the ability of the clinician to recognize its patent in 1974.615
significance and act upon it. He or she must be By 1988, the number of companies that sold
readily aware of clinical signs such as cyanosis pulse oximeters under their own brand names
or tachypnea, which are essential signs warn- increased to 29; 45 different oximeter models
ing of impending distress. Indeed, the clinician were available.607 This relatively new technol-
remains the ultimate and most important ogy had grown exponentially in just a few years.
patient monitor. Furthermore, based on the expanding applica-
tions of pulse oximetry, it appears that this
Conventional Underlying Technologies trend is likely to continue.
Three technologies have been cleverly blended
into the development of the pulse oximeter. Photoelectric Plethysmography
Photoelectric plethysmography is used to deter- A plethysmograph is a device for meas-
mine the patients pulse. Spectrophotometry is uring and recording changes in volume of a part
applied to determine the ratio of oxygenated to of the body or an organ. Photoelectric plethys-
reduced hemoglobin. Finally, the development mography, originally described in 1937,604
Beers Law: Part 2
Thick
Thin
Dim Bright Dim Bright
0% 100% Detector 0% 100% Detector

Meter Meter
Figure 15-6. Thickness of the solution and light transmission. All other things being equal, a red light
appears dimmer as the thickness of the solution increases.
Photodetector Light source is a technology that makes use of light trans-

mission properties to detect the changes from
one moment to another in blood volume that
occur in a finger or toe. These changes are pre-
sumably due to the pulsating arterial vascular
bed. Thus, this technology may be used to detect
the presence or magnitude of a pulse.605
As you may recall from the Lambert-Beer
formula, the pathlength in an absorbing
medium affects the amount of light absorption/
transmission at a given wavelength. Simply,
decreased light passes through the medium as
the thickness (volume) increases (Fig. 15-6). If a
vascular bed (e.g., finger) is positioned between
a light source and a photo detector, pulsatile
blood flow can be detected because the amount
of light absorbed is in proportion to the volume
Figure 15-7. Photoelectric plethysmography of blood present (Fig. 15-7). The pulse oximetry
and pulse detection. The increased blood sensors can be placed on a variety of sites as
volume during systole results in decreased light shown in Fig. 15-8.
transmission. The graphic representation of the pulse can
also be displayed and is known as a plethysmo-
gram (Fig. 15-9). Constant (static) light absorp-
tion occurs due to tissue and venous blood,
whereas variable (dynamic) absorption occurs
Adults or childs nger Childs toe
Infants or childs foot Infants hand
Figure 15-8. Sites for pulse oximetry sensors.

zero out constant sources of interference and to
Dynamic
Variable absorption calculate baseline absorption. Changes in light
of arterial blood
absorption during systole can therefore be pre-
Absorption due
sumed to be due to the addition of pulsatile
to venous blood arterial blood in the light path (see Fig. 15-9).608
Absorption
Pulse/Circulation Dependency
Static
Absorption due In pulse oximetry, identification of the pulse
to tissue
facilitates comparison of the difference in light
absorption in the two phases and thus isolates
arterial blood from all other factors in the
Time light path. Consequently, a measurable pulse
is essential in the noninvasive assessment of
Figure 15-9. Plethysmogram. Pulse oximetry
oxygen saturation.
waveform illustrating static and dynamic
absorption components.
The mere functioning of a pulse oximeter,
however, should not be interpreted as evidence
of adequate perfusion or tissue oxygenation.606
due to pulsatile arterial blood. Photoelectric It is also wise to question pulse oximetry read-
plethysmography has been used to monitor the ings when the heart rate of the oximeter differs
hemodynamic status of patients after surgery. greatly from other indicators and measurements
In general, when blood pressure or local blood of heart rate. Newer pulse oximeter designs
flow is high, the pulse amplitude is high. (e.g., signal extraction technology [SET])
Conversely, in the presence of vasoconstriction actually calculate oxygen saturation as meas-
or hypotension, pulse amplitude decreases ured with pulse oximetry (SpO2) through com-
(Fig. 15-10). Changes in the plethysmogram plex algorithms without first referencing the
may indicate the onset of hemodynamic prob- pulse rate.629
lems and may suggest the need for prompt
intervention. More important, detection of the Two-Wavelength Methodology
pulse allows for the noninvasive determination The schematic illustration of two-wavelength
of oxygen saturation. transmission oximetry shown in Figure 15-5 is
In pulse oximetry, baseline absorption is the closely parallel to the structure and function of
amount of light that is absorbed during dias- most pulse oximeters. On one side of the fin-
tole in the measured pulse cycle. The availabil- ger are two LEDs that transmit light alternately
ity of the pulse allows light absorption due to through the tissue to the photodetector (light
tissue, bone, and venous blood to be canceled detector) on the other side. Both the LEDs and
out. In addition, any ambient light that reaches the photodetector are aligned directly opposite
the photo detector is likely canceled out. Thus, each other and are encased within the probe.
detection of the pulse and diastole allows us to One LED emits light at a wavelength of 660 nm
Pulse amplitude
Red wavelength
Pulse amplitude
Red wavelength
a b
Time (sec) Time (sec)

Vasodilation or high Vasoconstriction or low
blood pressure blood pressure
Figure 15-10. Effects of hemodynamics on pulse amplitude.

Red Infrared computed through the ratio of light absorption

changes (red/infrared) that occurs during systole
20,000 (see Fig. 15-9; Fig. 15-12). The photodetector
10,000 actually measures light during three modes:
5,000 the red light mode, the infrared light mode,
Molar extinction coefficient
and when both lights are off.616,630 The third

1,000 mode (i.e., when both lights are out) helps
insure that light (or noise) from any other
500
source that may be reaching the detector is
also canceled out.
100 Photodetectors may sample light as frequently
50 as 480 times per second.616 Although technol-
ogy continues to improve, a reading should be
attainable within at least 2 minutes.617 The
10 response time to actual arterial oxygenation
changes also depends on the location of the
550 650 750 850 950 1000 probe.630 Probes placed on the ear respond
Wavelength (nanometers) quickest whereas finger probes may take up to
Hemoglobin 12 seconds longer. Probes placed on the toes
Oxyhemoglobin show an even greater lag time for response.
In summary, pulse oximeters are two-
Figure 15-11. Light wavelengths used in pulse wavelength oximeters that measure light
oximetry. Light absorption characteristics of
transmission both before and during a pulse by
oxyhemoglobin and deoxyhemoglobin.
incorporating the principles of photoelectric
plethysmography.609 The difference in transmis-
in the red range, whereas the other LED emits sion at both wavelengths during a pulse pro-
light at 940 nm in the infrared range.608 vides a measure of blood oxygen saturation. If
These two wavelengths are used because they a pulse cannot be detected with traditional tech-
facilitate differentiation of oxyhemoglobin from nology, oxygen saturation cannot be measured.
deoxygenated hemoglobin (Fig. 15-11) and cal-
culation of saturation. At 660 nm in the red Technical Limitations
range, light absorption of deoxygenated hemo- Accuracy
globin is 10 times higher than light absorption The accuracy of pulse oximeters in measuring
by oxygenated hemoglobin. However, at a wave- exact saturation has been shown to be about
length of 940 nm in the infrared range, light 4% as compared to blood oximetry measure-
absorption by oxygenated hemoglobin is sub- ments.619,628 There is a general tendency to be
stantially higher than light absorption by deoxy- less accurate (i.e., 6%628) as saturation falls
genated hemoglobin. Thus, saturation can be particularly to less than 70%. The readings are
100% Saturation
Pulse amplitude
Red
Pulse amplitude
Infrared
a b
Time (sec) Time (sec)
Figure 15-12. Calculation of saturation is based on the ratio of pulse amplitudes. The ratio of pulse
amplitude is defined as a/b = R.
most often falsely high at true low readings but Methemoglobin may likewise alter pulse
some may actually be falsely lower.620,621 This oximetry readings. The clinician should be mind-
is not particularly surprising because different ful that nitrites, benzocaine (local anesthetic), or
instruments use different pulse detection and dapsone (antibiotic used in the treatment of
SaO2 calculation algorithms.621 Furthermore, malaria or Pneumocystis carinii infection) may
most of these algorithms were developed based cause serious methemoglobinemia. There is rea-
on saturations of normal volunteers and there- sonable evidence to suggest that the readings tend
fore correlate better with high or normal satu- to migrate toward 85% (see Chapter 7). Thus,
rations. One early study reported in 1991 found lower than expected pulse oximetry readings
that only 10% of pulse oximetry readings in would occur when true saturation exceeded 85%
patients with poor perfusion were actually whereas higher readings would occur in severe
accurate to within 4%,631 but newer models methemoglobinemia. Like carboxyhemoglo-
and technology have improved accuracy binemia, the clinician should always be alert to
substantially. the potential causes and possibility of methemo-
Some guidelines recommend comparing globinemia especially when cyanosis is observed
directly measured simultaneous saturations without substantial decreases in SpO2. Like car-
(i.e., CO-oximetry readings) with various pulse boxyhemoglobinemia, sampling of blood via
oximeter readings to get a baseline relation- CO-oximetry is necessary for confirmation.
ship.622 These same guidelines also recom- Surprisingly, fetal hemoglobin seems to
mend periodic comparisons as the patients behave very similar to adult hemoglobin despite
condition changes. These comparisons would its increased affinity for oxygen. Pulse oximetry
also help the clinician understand the standard seems to agree very well with directly measured
biases of the specific devices being used. arterial saturation in newborns despite high
Notwithstanding, this is generally not practical fetal hemoglobin levels (60% to 90%).
or cost-effective. Most importantly, the clini-
cian should understand that arterial blood Dyes and Pigments
gases are superior for diagnostic purposes Vascular dyes administered during cardiac
whereas pulse oximetry is most beneficial as catheterization (i.e., methylene blue, indocya-
a real-time monitoring device. nine green, and indigo carmine) may similarly
affect pulse oximetry readings. In particular,
Technical Error methylene blue, which is also used in the treat-
Hemoglobin Variants ment of methemoglobinemia, may lead to a
It is well known that high carboxyhemoglobin spurious severe decrease in SpO2.616
levels [HbCO] will falsely elevate SpO2 read- Others have reported that brown, blue, and
ings. This is extremely important to remember green nail polish may substantially affect read-
since a high saturation reading in a patient ings and suggest routine removal.616,619,632 If
with carboxyhemoglobinemia may lead to a this problem is suspected, the probe can be
false sense of security regarding oxygenation placed on the lateral aspects of the digit instead
in the unsuspecting clinician. In any patient of over the nail.630,670
who is suspect for elevated HbCO (e.g., smoke Skin pigmentation may also be a factor as
inhalation, etc.), saturation should always an SpO2 less than 85% was shown to be less
be measured via arterial blood samples with accurate in African Americans in some investi-
CO-oximetry. gations.619,627 Others have reported that skin
Interestingly, in one study of postoperative pigmentation does not affect accuracy628;
open-heart surgery patients, pulse oximetry therefore, this remains controversial.
seemed to cause slight elevations in readings as Finally, there has been some discussion
compared to saturations measured in the regarding the impact of hyperbilirubinemia on
blood.623 The authors suggested that perhaps pulse oximetry readings. AARC guidelines
slight elevations in HbCO secondary to hemo- state the hyperbilirubinemia does not affect the
lysis or infusion of stored blood may have been accuracy of pulse oximetry readings.622 This
responsible for the elevated readings. is most likely because the absorption peak of
bilirubin is below that used in pulse oximetry. on the same hand). Cross-talk error as well as
It is interesting to note, however, that the other forms of optical shunting can easily be
patients in some of these studies may also have eliminated by covering each sensor with
had slight (i.e., 5% to 6%) elevations in HbCO opaque material.
secondary to heme metabolism.618
Decreased Perfusion
Optical Interference For years, low perfusion states have been recog-
Although this remains controversial, bright nized as a source of pulse oximeter malfunction
external ambient lights may impact oxygen satu- or error.622 Indeed, decreased perfusion and
ration measured by pulse oximetry (SpO2).622 motion artifact (to be discussed in next section)
Typically, in the presence of optical interference have been cited as the two most common
(bright external lights), the pulse search alarm problems responsible for inaccurate SpO2
flashes and the digital display is blank. In one readings.628 A variety of factors may lead to
unusual anecdotal case that occurred in 1987 decreased perfusion including decreased cardiac
with an older model pulse oximeter, an ambient output, decreased arterial blood pressure, hypo-
light in the operating room caused the SpO2 thermia, hypovolemia, or vasoactive drugs.
display to remain at 100% even though the Under vasoconstrictive conditions, the ear lobe
patient had cyanosis and was in distress.624 This appears to be the site least altered by compro-
apparently occurred because the light had an mised perfusion.633
unusual pulsatile quality, and the photodetector When perfusion is insufficient, most monitors
was sensing this quality as a pulse. As always, display a message indicating inadequate pulse
one cannot depend too heavily on any single signal or provide only intermittent readings. As
technology as a replacement for a thorough stated earlier, most early pulse oximeters did not
clinical evaluation. provide a measurement within 4% of blood
The potential for various forms of ambient saturation measurements under conditions of
light to affect pulse oximetry readings has been decreased perfusion.631 Early pulse oximeters
studied in more detail recently.616 The findings amplified the pulse when it was weak. This,
of this study suggest that ambient light has no in turn, amplified the background noise which
significant effect on SpO2 and that exposure to resulted in decreased accuracy.628 Monitors are
ambient light is clinically unimportant. In all available that measure blood pressure and pulse
likelihood, any light without a pulsatile quality oximetry independently and simultaneously.
should be automatically factored into baseline
measurements and, therefore, should not affect Motion Artifact
readings. Historically, motion of the probe (e.g., shivering)
has likewise been a common source of error.
Optical Shunting Motion may cause decreased accuracy, loss of
Use of a sensor that is inappropriate for the signal, desaturation alarms, or missed hypox-
patient or for the clinical setting may lead to emic events. It was believed that erroneous
optical shunting. This phenomenon occurs when signals could be reduced by synchronizing
part of the light emitted from the LED reaches signals with electrocardiograph (ECG) signals.
the photo detector without passing through the Notwithstanding, oximeters using ECG syn-
finger. Optical shunting tends to bias the reading chronization did not display increased accu-
toward the 81% to 85% level.625 Selecting the racy.634 Probably the best way to identify
appropriate size of sensor and applying it cor- motion artifact is via pulse wave analysis
rectly generally eliminates this problem. In (i.e., false or erratic pulse display), but this is
particular, digit sensors should not be applied also difficult and tedious. One method to mini-
to fingers with long nails.626 mize motion artifact was to attach the probe to
Another potential type of optical interference an alternate site such as the ear or toe.619
is optical cross-talk. Optical cross-talk is a form It is not uncommon for hypoxemic patients
of interference that may occur when multiple to be agitated and move violently. Therefore,
sensors are placed in proximity (e.g., two sensors failure of the pulse oximeter to provide an
accurate signal during motion could mean fail- which, in turn, may cause additional errors of
ure of the monitoring device when the patient 1% to 4%.628
is at greatest risk of hypoxia. Furthermore, Furthermore, because different pulse oxime-
motion artifact is probably the most common ters use different algorithms and, in some
reason for abandoning the use of pulse oxi- cases, different technology, readings between
meter monitoring.636 Indeed, motion artifact different brands and models of pulse oximeters
may also cause both false-positive (false alarm) are likely to differ. When practical, it may be
and false-negative (missed hypoxemic event) useful to get a concurrent blood saturation to
alarms.637 serve as a baseline for future changes.
False Alarms Hazards and Complications

False alarms present a huge problem and obsta- Hazards or complications associated with the
cle particularly in intensive care. Nearly 90% of use of pulse oximeters are rare. Complications
ICU alarms are false, while another 5% are true of a relatively minor nature have been reported
but irrelevant.638 Furthermore, experienced occasionally in children. These complications
nurses were unable to identify nearly 40% of include a localized skin burn due to a malfunc-
critical alarms.639 This may not be particularly tioning probe that heated to more than 70 C,
surprising to anyone who has been subjected skin erosion after a probe had been left on an
to the data overload present in critical care. ear of a 4-month-old infant for longer than
Pulse oximetry is especially prone to false 48 hours, and localized tanning of the skin.705
alarms in the neonatal intensive care units. Devices may overheat in the unusual event of
Approximately half of neonatal/pediatric alarms cracking of the LED casing.641 In general, pulse
were due to pulse oximetry. Furthermore, 70% oximetry is a safe technology. A summary of
were false alarms and nearly 95% were consid- some key points and issues detailed in the AARC
ered clinically unimportant.640 Clinical Practice Guideline for Pulse Oximetry
Probably the most troubling issue related to is shown in Box 15-1.671
false alarms is the impact on bedside clinicians,
patients, and families. In addition to increased
stress and inefficiencies, the numbing effect of Box 15-1 AARC Clinical Practice
alarm overload inevitably leads to a less than GuidelinePulse
urgent response when true critical events occur. Oximetry: Nuts & Bolts
Furthermore, patients and families are subjected Indications
to additional stress and concern when alarms Prolonged continuous oxygen monitoring
sound and especially when clinicians do not Spot-check of oxygenation
react expediently. In short, excessive false alarms Diagnosis of moderate to severe hypoxemia
subject everyone to unnecessary stress and (Best to correlate with directly
strain in addition to the increased likelihood of measured SaO2)
true disaster. Any and all attempts to increase Limitations
No ventilation (PaCO2) evaluation
the accuracy and specificity of these monitors
No acid-base pH evaluation
and alarms would certainly result in enhanced
Poor in detection of hyperoxemia
patient care. The new SET technology described Potential Errors
subsequently in this chapter represents a Motion artifact
welcome addition to current monitoring Dyshemoglobin species
technology. Intravascular dyes / pigments
Ambient light
Other Sources of Error Skin pigmentation
Other factors that may affect readings include Nail polish
temperature variances above or below body Degree of severe hypoxemia or hyperoxemia
temperature. These temperature changes can Reference: AARC Clinical Practice Guideline: Pulse
cause LEDs to shift their spectral outputs oximetry. Respir. Care, 36:14061409, 1991.
Advances in Technology number of false alarms while also purporting

Signal Extraction Technology nearly 100% detection of true alarms with
SET is a term coined by Masimo Inc. describing application of SET.628,635,642,647,648
new methods, algorithms, and probes used to
(seemingly) more accurately determine SpO2 Other New Methods
during patient motion or decreased perfusion. Other manufacturers and technologies have
SET was unveiled in 1998 and by 1999, there also been developed and some studies have
were many independent research studies claim- purported their superiority to the SET tech-
ing this technique to be more specific and sen- nology.649 Clearly, all current technology is
sitive than traditional pulse oximetry.642 improving as all new models outperform old
Most importantly, SET functions better than models.637 It is likely that the future will be
conventional pulse oximeters during motion or even brighter than the remarkable past regard-
poor perfusion,628,645,646 the two most common ing pulse oximetry.
technical limitations in pulse oximetry. In 2000, Despite some conflicting reports, at this
it was the only technology cleared by the point in time, there is a preponderance of evi-
US Food and Drug Administration to make dence to support the superiority of the SET
claims regarding accuracy during motion or low technology in reducing false alarms, particu-
perfusion.642 Due to its rather unique approach larly during motion and low perfusion states.
to SpO2 and pulse measurement, some key prin- Most of these studies do not directly
ciples in its application will be discussed. evaluate total cost. There have been reports of
According to product literature,629 the two decreased sensor expense when using SET
keys to this new process for obtaining SpO2 sensors650; however, to my knowledge, no clear
are the discrete saturation transform algorithm comparisons of total cost. As times goes on,
and the low noise optical probe. The discrete we will have to continue to monitor advances
saturation transform algorithm in conjunction in this rapidly changing technology.
with special adaptive filters allows for the
identification of the SpO2 without first refer- General Application
encing the pulse rate. This algorithm attempts Usefulness
to identify and ignore sources of pulse rate Pulse oximetry probably does offer a significant step
interference.643,644 at detecting hypoxemia while theres still something
The SET system also uses a special low we can do about it.
noise optical probe (Fig. 15-13). Unlike con- C. Durbin (discussion)618
ventional sensor design, the photo detector is
recessed in a cavity to act like a shock absorber Pulse oximetry is, in all likelihood, our most
and minimize optical pathlength changes valuable patient monitor. As described earlier,
during motion.629 the pulse oximeter can be applied noninvasively
Studies have also demonstrated a substan- and continuously to monitor oxygen satura-
tial (7-fold or higher)635,647 decrease in the tion or more correctly desaturation. Handheld
devices weighing as little as 1.3 oz without
batteries651 can be carried to the bedside for
oxygenation assessment.
rd ir The true value of pulse oximetry is in sur-
veillance and trending rather than for diagnosis,
and it can be a valuable indicator of hypoxic cri-
sis. Nevertheless, at times, pulse oximetry can
also be a crude diagnostic index of benefit in the
Recessed physicians office or the patients home. In these
photodetector
scenarios, changes in the patients SpO2 follow-
Figure 15-13. Low noise optical probe. Low noise ing simple manipulations in patient position can
optical probe design shows recessed photo detector. sometimes aid in diagnosis.652
In critical care, another potential application that saturation is a much less sensitive indica-
for pulse oximetry is its use in conjunction with tor of blood oxygenation than PaO2, especially
continuous in vivo (within the body) measure- when saturation is near or above 90% on
ment of oxygen saturation in the pulmonary the flat upper portion of the oxyhemoglobin
artery by using a fiber-optic catheter. This dual curve.
oximetry can be used to monitor cardiac out- Finally, one must always remember that
put continuously via the Fick equation. pulse oximetry reveals absolutely nothing
Finally, when applied appropriately, pulse about ventilation, electrolyte changes, or acid-
oximetry may result in cost savings. For exam- base balance. An arterial blood gas, despite its
ple, the use of pulse oximetry instead of arterial drawbacks concerning time and its invasive
blood gases during mechanical ventilation or nature, provides the most complete picture of
oxygen therapy protocols can be cost-effective. oxygenation and acid-base status.
SpO2 Targets Functional versus Fractional Saturation

In most spontaneously breathing and mechan- Pulse oximetry will indeed be misleading in
ically ventilated patients, an SpO2 of 92% to the patient with carboxyhemoglobinemia or
94% is a reasonable goal for FIO2 titration.619 methemoglobinemia. The clinician must always
Some have suggested a slightly higher goal of be cognizant of the fact that SpO2 does not
95% in African-American patients.619 Similarly, measure or indicate these conditions. Indeed,
a target of 93% may be best when prescribing pulse oximetry will be normal and misleading in
oxygen during exercise for patients with the presence of severe carboxyhemoglobinemia.
COPD.654 Therefore, the clinician must maintain a high
In premature infants at risk of retinopathy of index of suspicion of these problems especially
prematurity, one should keep the high alarm in when the history of the patient suggests
the range of 92% to 95% or lower because this their presence (e.g., smoke inhalation). Most
SpO2 is on the flat portion of the oxyhemoglo- importantly, when cyanosis is present with
bin dissociation curve and the actual PaO2 may normal SpO2, these conditions should be ruled
be excessive.628,618 Setting the alarm at 95% out through arterial blood sampling and
provides a 95% probability that the PaO2 does CO-oximetry.
not exceed 80 mm Hg; however, in this range,
more than half of the alarms may be false.655 Accuracy of Pulse Oximetry
At high altitude (e.g., Denver), normal new- The accuracy of pulse oximetry in reflecting
borns to the first 4 months of life may have PaO2 is not good on the flat upper portion of
SpO2s that are considerably low (i.e., as low as the oxyhemoglobin curve. In other words, if
80%); therefore, lower SpO2s may be accept- the SpO2 is 92%, and given a 4% accuracy,
able.653 Finally, in the critically ill, it may be the actual PaO2 could be anywhere from 55 to
argued that SpO2s as low as 75% to 80% may 80 mm Hg. If the SpO2 were 97%, the PaO2
be less harmful than high alveolar pressures or might be anywhere from 65 to 500 mm Hg.
excessive levels of positive end-expiratory pres- These relationships also assume a normal
sure.618 Precise targets for SpO2 will remain an pH, which is unlikely in the critical care setting.
important issue to study for years to come. It has been suggested by some that the limits
of precision are more like 5%, and that a read-
Limitations ing of 95% could reflect a PaO2 as low as
Despite its benefit, it is important to understand 55 mm Hg and as high as 600 mm Hg.618
what pulse oximetry is not. First, the clinician Regardless of the exact ranges, the salient point
must understand that pulse oximetry measures is that a given pulse oximetry reading may be
functional saturation and not fractional satu- associated with a wide range of PaO2.
ration. Secondly, it is essential to realize that When it is essential to know the actual PaO2,
pulse oximetry is only 4% accurate and even such as during oxygenation of the premature
less accurate when saturation is less than 70% infant (with concern of hyperoxemia and
to 80%. Therefore, the clinician should realize retinopathy of prematurity), pulse oximetry does
not provide sufficient accuracy. Similarly, a pulse Transcutaneous PO2 monitors are most
oximeter reading of 90% may be viewed as often used in neonatal intensive care units
satisfactory when, in fact, it may represent clini- owing to the thin skin layer in these patients
cally significant hypoxemia. and their special needs for oxygen monitoring.
Similarly, pulse oximetry should be used very Transcutaneous PO2 monitors are slightly
carefully in determining the need for chronic more sensitive than pulse oximeters; however,
oxygen therapy in the home. First, use of only they require a much greater degree of care and
pulse oximetry could disqualify a significant maintenance to ensure proper function.
number of patients truly in need of home Improvements have been made in terms of ease
oxygen therapy. Only 80% of patients with of application and comfort, but other technical
a resting PaO2 of less than 55 mm Hg had a issues still complicate routine use.669
concomitant SpO2 of less than 85%.656 Thus,
20% of these patients would have been inap- Anatomy of the Skin
propriately denied home oxygen therapy based The top three layers of the skin are important
on pulse oximetry assessments alone. In addi- in the function of transcutaneous PO2 moni-
tion, many patients could be deprived of neces- tors. The outermost layer (stratum corneum) is
sary oxygen therapy or reimbursement perhaps actually dead tissue, and it behaves function-
based on HbCO artifact. ally like a diffusion membrane (Fig. 15-14).
Another issue that has surfaced with the The next layer is known as the epidermis. The
routine use of continuous pulse oximetry has epidermis does not contain blood vessels but
been the identification of striking desaturation consumes oxygen at a very high rate. The next
(<80%) in otherwise healthy, elderly post- layer of skin is called the dermis. The dermis
operative patients.657 Indeed, episodic severe consumes little oxygen in itself, but its capil-
hypoxemia may be normal in some patients laries provide the blood supply and oxygen for
and not associated with any adverse conse- the epidermis as well.
quences. Please refer to the discussion on
permissive hypoxemia in Chapter 10. Factors Determining PtcO2
Arterial PO2 represents the pressure of oxygen
Ventilation and Acid-Base Balance as blood enters the various tissues throughout
Again, the clinician must always keep in mind the body. Obviously, the PO2 normally falls as
that pulse oximetry provides no information blood traverses the tissue capillaries because
regarding the status of ventilation and acid- some oxygen is released to the tissues. The PO2
base balance. The subtle clues to developing does not fall as much in skin capillaries as in
and progressive acid-base disturbances are other capillaries because perfusion to the skin
absent with pulse oximetry. Arterial blood is far in excess of metabolic requirements.
gases are necessary when there is any question Furthermore, if perfusion is further increased
regarding these issues. due to heating the skin, capillary PO2 begins to
approach PaO2. In fact, PtcO2 may even
TRANSCUTANEOUS PO2/PCO2 exceed PaO2 (measured at body temperature
MONITORING and pressure saturated [BTPS]) if it is meas-
ured at a higher temperature. If perfusion is
Introduction diminished (e.g., in shock), capillary PO2 is
A relationship between blood PO2 and skin much lower than PaO2 due to increased O2
PO2 was shown in 1951.658 In 1967, the PO2 extraction by the cells. Conversely, PtcCO2 will
was measured on the skin surface by using a increase with decreased perfusion.
Clark electrode, and this measurement was PO2 decreases still more as the tissue dis-
correlated with PaO2.659 The PO2 measured by tance increases from the capillary. The thicker
using a modified Clark electrode applied the skin, the greater is the difference between
directly to the skin is called transcutaneous capillary PO2 and skin surface PO2, which
PO2 (PtcO2). Most current transcutaneous explains why PtcO2 more nearly equals PaO2
monitors also measure PtcCO2 concurrently.619 in newborns than in adults. Furthermore, the
Cutaneous sensor
Stratum
corneum
Figure 15-14. Skin layers and transcutaneous

PO2. The transcutaneous oxygen sensor detects
oxygen that diffuses from the dermal capillary Epidermis
bed below the skin surface.
Dermis
Hypodermis
epidermis in preterms lacks a keratinized stra- adults, PtcO2 is generally about 20% less than
tum corneum that is the main barrier to diffu- PaO2.662 In infants, though, PtcO2 is actually
sion.660 Therefore, PtcO2 in the preterm will approximately 5% to 15% higher than PaO2
be higher than PtcO2 in the term infant despite because of the direct effects of the high tem-
the same PaO2 in both.660 perature at the measurement site.662
All these factors help to explain why PO2
tends to be lower on the skin surface compared PtcO2PaO2 Agreement
with intra-arterial readings. Another impor- Placement
tant physical law must also be remembered, Because function of the electrode depends greatly
however, in understanding PtcO2 as measured on the nature of the skin on which it is placed,
in the clinic. Gay-Lussacs law states that, given the selection of an appropriate site is important
a constant gas volume, as temperature increases to obtain PtcO2 values that are approximate to
so does pressure. Transcutaneous PO2 electrodes PaO2 values. Generally, one should choose
heat the skin to about 43.5 C. The direct phys- a site where capillary pressure is high and vaso-
ical effect of this heating is to increase PO2 constriction is usually minimal. The chest near
through stimulation of brownian movement of the clavicles, the head, or the lateral sides of the
the gas molecules. Increasing the temperature abdomen are sites often used. The buttocks or
from 37 to 44 C would have the direct physical inside upper thighs may also be used.
effect of increasing a PO2 of 100 to 140 Some locations may show a very low
mm Hg.661 Of course, any local increase in tem- PtcO2 that fails to increase promptly when the
perature also tends to increase local meta- microelectrode is applied. If this occurs, a dif-
bolism. Nevertheless, this effect is less than the ferent location should be tried. Placement of
direct physical effects on the skin. Unlike oxy- the electrode properly on the skin surface is
gen, PtcCO2 correlates well with PaCO2 at body also important. The electrode should be flat
temperature. against the skin but should not indent or
Thus, one can see that the value for PtcO2 compress the skin.
depends on various factors. Most of these The skin should be prepared by wetting it.
factors tend to make PtcO2 lower than PaO2, Wet skin is more permeable than dry skin. Gels
whereas the direct physical effect of an increase or glycerol are sometimes used and have the
in temperature actually tends to make PtcO2 advantage of adhering to the skin better than
higher. The actual PtcO2 that is observed in water in some locations. Nevertheless, oxygen
a given patient, however, depends on the net diffuses through the water more quickly than
interaction of all of these factors. In normal through gel.
Calibration The major complication associated with the

Transcutaneous PO2 electrodes must be cali- application of transcutaneous PO2 electrodes
brated before being used. After initial applica- is burns to the skin. This complication can
tion to the patient, PtcO2 readings are low generally be avoided by rotating the electrode
because the skin is cool. During the next 5 to placement every 2 to 6 hours.630
15 minutes as the skin warms, PtcO2 increases
and reaches a plateau. Clinical Application
Drift, or a change in the baseline with time, Transcutaneous PO2/PCO2 most often varies
may also occur in these electrodes. Drift may be closely with arterial blood gases in infants and
positive or negative and is usually approximately is a useful way to continuously monitor new-
1% to 5%. If the electrode is left in place for borns and premature infants. In particular,
more than 6 hours, PtcO2 usually decreases.663 transcutaneous PO2 may be a sensitive indica-
This problem can be discovered only by peri- tor of hyperoxemia immediately following sur-
odic recalibration. Transcutaneous PO2 elec- factant replacement therapy. Transcutaneous
trodes should be repositioned and calibrated PO2/PCO2 may help guide application of spe-
every 2 to 6 hours, and more frequently in cial ventilator strategies such as high-frequency
newborns.630 jet ventilation. They may also help to avoid
infant stress and blood loss associated with
Response Time excessive blood gas sampling. Finally, PtcCO2
The response time of the electrode depends on may assist in monitoring hypercapnia and the
the age of the patient and more specifically on potential for increased intracranial perfusion
the skin thickness. In infants, the skin is thin and hemorrhage. Despite its numerous limita-
and response time has been reported as 10 to tions, transcutaneous monitoring still seems to
15 seconds.662 In adults, the skin is thick and have a place in NICU monitoring.
response time is 45 to 60 seconds.662 In gen-
eral, the older the individual, the longer is the Limitations
response time. Other studies have shown Despite its value, in some situations, transcu-
response times that were considerably longer taneous gas measurement is still plagued
for oxygen (90% response took 5 minutes); with a host of limitations. Box 15-2 provides a
however, CO2 response times (90% response) brief summary of some of the key points
occurred in one-third of this time.669 from the AARC Clinical Practice Guideline
related to Transcutaneous Blood Gas Monito-
Perfusion and Drugs ring for Neonatal/Pediatric Patients.672 Further-
Transcutaneous PO2 does not agree well with more, Box 15-3 likewise summarizes many of
PaO2 when perfusion is poor. The lower the the overall limitations of transcutaneous mon-
arterial pressure, the lower is the correlation itoring. The clinician should always keep in
between PaO2 and PtcO2. Similarly, shock and mind that transcutaneous gas measurement is
acidosis may decrease the correlation. Drugs far from a direct process and many factors can
and anesthetics that decrease the blood pres- disturb the delicate balance of measurement
sure or alter the distribution of perfusion may that ultimately is expected to accurately reflect
also disrupt the correlation. arterial conditions.
Temperature Transcutaneous PO2 versus

Even one degree of difference in the temperature Pulse Oximetry
at which skin PO2 is measured can have a Several early studies compared the clinical value
profound effect on the value obtained. When of PtcO2 with SpO2 as measured via pulse
PO2 is greater than 100 mm Hg, PO2 increases oximetry.664,665 The SpO2 has been shown to
6 mm Hg/C increase.661 When PO2 is less than be a more sensitive indicator of severe hypox-
100 mm Hg, it increases 6%/C increase.661 emia.666,667 Furthermore, the response time of
The temperature of the PtcO2 electrode should pulse oximetry is about five times faster than
be set at 43.5 C. that for transcutaneous PO2.
Box 15-2 AARC Clinical Practice GuidelinesTranscutaneous Blood Gas

(O2/CO2) Monitoring for Neonatal and Pediatric Patients: Nuts & Bolts
Indications
Continuous monitor of oxygenation and ventilation
Quantify response to interventions (validate with ABGs initially and periodically)
Technical Limitations
Labor intensive
Prolonged stabilization time
Oxygen electrode requires heating skin surface
Calibration error potential
Clinical Limitations (i.e., decreased correlation with ABG)
Hyperoxemia (PaO2 > 100 mm Hg)
Hypoperfusion and acidosis
Electrode placement integrity
Vasoactive drugs
Skin injury or burns
Reference: AARC Clinical Practice Guideline: Transcutaneous blood gas monitoring for neonatal & pediatric patients.
Respir. Care, 39:11761179, 1994.
From a practical standpoint, pulse oximetry of oxygenated blood is relatively constant when
offers several additional advantages when PaO2 is above 90 mm Hg, SpO2 is not a sensitive
compared with transcutaneous PO2 monitor- indicator of hyperoxemia. Thus, PtcO2 is the pre-
ing. Pulse oximetry requires no heating; there- ferred index in infants at risk of retinopathy of
fore, there is essentially no risk of complication prematurity secondary to excessive oxygenation.
from burns. Conversely, the potential for burns
is a major concern with PtcO2 monitoring.
CAPNOMETRY
Transcutaneous PO2 monitoring requires
skin preparation, calibration of the electrode, Perhaps the most important thing to realize about
technical warm-up time, and periodic rotation PetCO2 is that it is not PaCO2.
of the electrode site. Pulse oximetry, on the other D. Hess673
hand, requires no skin preparation, no calibra-
tion, no warm-up, and no periodic movement Introduction
of the probe. In the intensive monitoring of Capnometry is the measurement of carbon diox-
oxygenation in the adult, pulse oximetry is ide (CO2) in the exhaled gas. Capnography is
generally a superior technology. the technique of displaying CO2 measurements
The PtcO2 is, however, a better index of hyper- as waveforms (capnograms) throughout the
oxemia than SpO2.668 Because the saturation respiratory cycle. Capnography is a standard
Box 15-3 Limitations of Transcutaneous Monitoring

Frequent calibration required
Frequent position changes of electrode required
Relatively long equilibration time following electrode placement
Insufficient electrode temperature may adversely affect performance
Performance may be suboptimal over poorly perfused areas
PtcO2 tends to underestimate PaO2 and PtcCO2 tends to overestimate of PaCO2
Compromised hemodynamic status causes an underestimate of PaO2 and an overestimate PaCO2
Heated electrode may cause skin to blister
PtcO2 may underestimate PaO2 during hyperoxemia
Frequent membrane/electrolyte changes, and electrode maintenance required
Performance more reliable in neonates than adults (at least for PtcO2)
From Hess, D.R., Kacmarek, R.M.: Essentials of Mechanical Ventilation, 2nd ed. New York, McGraw-Hill, 2002.
of care for general anesthesia.704 The end-tidal Patient Pump

CO2, which is the maximum partial pressure of r
i rro
CO2 exhaled during a tidal breath (just before M
the beginning of inspiration), is designated
Photodetector
Sample chamber
PetCO2. Although technology associated with
capnography continues to develop, clinical Infrared lamp Filter
understanding of the meaning and limitations
of this measurement lags behind.
Measurement Techniques M
irr
Carbon dioxide analyzers may use infrared, or
Reference chamber
mass spectrometry, Raman spectra analysis, or
a photoacoustic spectra technology.674 The two Figure 15-15. Schematic representation of a
methods most commonly employed are mass double-beam infrared capnometer.
spectrometry and infrared analysis. Mass spec-
trometers are extremely precise instruments
that can perform various functions including 0.25 seconds. Carbon dioxide has an absorp-
simultaneous measurement of several or all of tion peak at 4250 nm. Nitrous oxide and water
the constituents of a gas mixture. They are have absorption peaks close to this area. Thus,
accurate to within two decimal points within there is potential for the introduction of error
0.1 second of the actual event. They are often with these substances; however, most analyzers
used to monitor a large number of mechanical have safeguards to minimize or prevent these
ventilators in the operating room. Nevertheless, technical errors. The units take advantage of
mass spectrometers are labor-intensive, cum- the fact that CO2 absorbs infrared radiation in
bersome, costly systems and are not practical in proportion to its concentration (spectropho-
most critical care situations. Interestingly, the tometry). The accuracy of most capnometers is
presence of Freon (used as a propellant in about 12% or 4 mm Hg.673
metered dose inhalers) may artificially increase Infrared analyzers may be double-beamed,
CO2 reading in mass spectrometers.674 positive-filter models (which include a reference
chamber) as shown in Figure 15-15. In contrast,
Infrared Absorption Capnometers they may be single-beam, negative-filtered as
Capnography is most often accomplished with shown in Figure 15-16. In both models, a spin-
free-standing infrared absorption capnometers. ning wheel (chopper), improves the accuracy
The infrared absorption technique is simpler of the sensor by periodically obstructing and
and less expensive than mass spectrometry. opening the light channel(s). Older models
Traditional response time is approximately required frequent calibration but some newer
Chopper
Recorder/display
Infrared
light source
Airway sample chamber Photodetector
Figure 15-16. Single-beam infrared capnography. The basic components of a single-beam, negative-filter
infrared carbon dioxide detector used in some mainstream sampling systems.
Tracheal tube Tracheal tube

Sample
chamber
Sample To remote analyzer

Infrared light adapter
source
To microprocessor
Photodetector
Ventilator circuit
wye connectors
A B
Figure 15-17. Mainstream vs. sidestream CO2 sampling. A, Mainstream CO2 sampling. B, Sidestream
CO2 sampling.
models perform self-calibration, have no gas, which will distort function and accuracy.
moving parts, and respond in approximately Special water traps and foam barriers and, in
100 milliseconds.656 some units, back-flushing systems have been
designed to deal with this problem. In addi-
Mainstream versus Sidestream Sampling tion, aspiration flowrate must be set carefully
There are two general sampling techniques (e.g., 150 mL/min) to avoid significant distor-
employed by the various capnometers: main- tions in the waveform. At times, the continu-
stream and sidestream analysis. ous aspiration of gases causes some dampening
or smoothing of CO2 waveforms. In addition,
Mainstream Analyzers if a leak is present in the system, PCO2 read-
Mainstream analyzers measure CO2 directly in ings decrease due to air dilution. Finally, side-
the airway (Fig. 15-17,A). Mainstream analyzers stream analyzers usually have slower response
provide a very rapid, crisp, and accurate times than do mainstream analyzers.625
response. Early mainstream analyzers were criti-
cized for their weight, fragile nature, or the addi- Colorimetric CO2 Analysis
tion of mechanical deadspace, however, newer Simple colorimetric techniques for evaluating the
designs have essentially eliminated these prob- presence of CO2 in exhaled gas have been avail-
lems. The issue of water or sputum in the system able for many years. In 1916, Marriott described
contaminating readings, however, still remains. the use of a material that changed color in the
Most mainstream analyzers use a heating device presence of CO2.675 More recently, an end-tidal
to eliminate moisture accumulation. Mainstream CO2 detector has been described which is pur-
designs are best suited for artificial airways. ple when CO2 is less than 0.5%, then turns
tan up to 2% CO2, and finally becomes yellow
Sidestream Analyzers when CO2 exceeds 2%. The detector is said to
Sidestream analyzers aspirate the gas sample be reliable and easy to use.676 These devices are
through a small bore tubing for analysis within reliable and inexpensive and especially useful
a chamber (see Fig. 15-17,B). Sidestream analy- for detection of successful intubation.
zers can be used in the nonintubated patient by
placement of the sampling tubing at the exter- Capnograms
nal nares or through a specially designed nasal Normal Capnogram
cannula.673 A normal single breath capnogram is shown
Unfortunately, mucus or moisture may be in Figure 15-18. The partial pressure of expired
aspirated into the tubing along with exhaled CO2 is plotted vertically against time on the
CO2 38 C
E
A B
0
Time
Zero baseline (A-B) End-tidal value (D)

Rapid, sharp rise (B-C) Rapid, sharp downstroke (D-E)
Alveolar plateau (C-D)
Figure 15-18. Essentials of the normal capnographic waveform.
horizontal axis. At the very onset of expiration, The clinician should also be aware that the
no CO2 is observed because the first gas to graph paper may be run at a slow or fast
leave the lungs comes from the anatomic dead- speed. In the initial portion of the graphs in
space (see Fig. 15-18,A,B). The anatomic dead- Figure 15-19, the paper is being run at a fast
space is, of course, filled with fresh gas (PCO2 speed. Thus, fine details in the shape of the
0 mm Hg) from the previous inspiration. capnogram can be specifically analyzed. High-
As exhalation continues, some alveolar gas speed capnometry can often provide useful
begins to be exhaled along with the anatomic diagnostic information and fine detail of each
deadspace, and an upward movement of the breath.
capnogram is observed. As the gas becomes The final portion of the graphs is being
proportionally more alveolar and less anatomic run at slow speed. Slow-speed capnography
deadspace, there is a corresponding rise in the essentially provides a running monitor of the
exhaled PCO2 (see Fig. 15-18,B,C). Then, when end-tidal CO2 (PetCO2) level. Some monitors
essentially all of the gas being exhaled is coming display both slow and fast speed graphics.
from alveoli, an alveolar plateau (see Fig. 15-8, Slow-speed capnography is sometimes referred
C,D) is observed. to as a CO2 trend.
Finally, when expiration is complete and
inspiratory flow begins, CO2 decreases quickly Abnormal Capnograms
to zero (see Fig. 15-18,D,E). The PCO2 level The alveolar plateau will demonstrate an
attained immediately before descent in the curve increased slope in the presence of ventilation-
occurs is referred to as the end-tidal partial perfusion mismatch (e.g., COPD/ARDS).680
pressure of CO2 (PetCO2). This point is also Likewise, the alveolar plateau may flatten in a
shown in Figure 15-18,D. more normal manner following treatment of
Simultaneous capnograms produced by early reversible ventilation-perfusion mismatch.
model sidestream capnometer and a mainstream Figure 15-20 illustrates capnographic improve-
capnometer are shown in Figure 15-19. The ment in a 2-year-old boy with severe croup fol-
smoothing of the waveform due to the old side- lowing administration of racemic epinephrine.
stream analyzer compared with the mainstream The capnogram may also alert the clinician
analyzer is readily apparent. Smoothing of the to rebreathing if the baseline continues to esca-
waveform occurs when the aspiration flow rate late as shown in Figure 15-21. Finally, the onset
is too low. Newer sidestream analyzers eliminate of patient spontaneous inspiration can be iden-
this problem and demonstrate a waveform sim- tified when sharply decreasing CO2 is observed
ilar to that shown for the mainstream analyzer. during the alveolar plateau. This phenomenon
B
Figure 15-19. Comparative tracings from mainstream and sidestream analyzers. Simultaneous tracings
from a mainstream analyzer (A) and a sidestream analyzer (B). The first portion of each graph represents
fast-speed capnography, whereas the latter portion represents slow-speed capnography. Note the smooth-
ing of the waveform with sidestream analysis during fast speed.
has been termed the curare cleft (Fig. 15-22) to noninvasively measure cardiac output. A
when observed in patients recovering from modified form of the Fick equation is used for
neuromuscular blockade. this determination. This technique seems very
promising as a method to determine the valu-
Volumetric Capnograms able cardiac output measurement without the
The partial pressure of carbon dioxide can be need for invasive catheters.
plotted against volume instead of time utiliz-
ing some recent technology (Fig. 15-23). The PetCO2 as an Indicator of PaCO2
volumetric capnogram provides additional As described previously, the PetCO2 repre-
information regarding deadspace and CO2 sents the end-tidal pressure of carbon dioxide.
production heretofore not readily available In spontaneously breathing normal individu-
at the bedside. Specifically, anatomical dead- als, the PetCO2 varies in concert with the
space, alveolar deadspace, and CO2 production PaCO2. This fact, although true, is probably
per minute may be determined. This informa- the origin of an abundance of confusion sur-
tion can be particularly useful in evaluation of rounding capnography. Only in the healthy
PaCO2 changes during mechanical ventilation. spontaneously breathing individual does this
It is also valuable when rapid increases in CO2 fact hold true. Indeed, in sick individuals, the
production may indicate malignant hyper- PetCO2 and PaCO2 are distinctly different
thermia in the operating room. Given stable entities that may, in fact, change in opposite
metabolism and alveolar ventilation, flattening directions. Although PetCO2 is inviting as a
of phases II and III may indicate decreased pul- simple, noninvasive, reflection of PaCO2, it is
monary perfusion in volumetric capnography not. Time and time again, this has been shown.
as shown in Figure 15-24. Use of PetCO2 as a predictor of PaCO2 is
Technology has also become recently avail- deceiving and incorrect, and should be used
able that allows for the volumetric capno- with great caution for this purpose in mechan-
gram in conjunction with partial rebreathing ically ventilated patients.619 Indeed, 73% of
Paper speed 25 mm/sec Paper speed 25 mm/sec

90 90
80 80
70 70
60 60
50 50
40 40
30 30
20 20
10 10
Before racemic EPI EtCO2 = 61-63 After racemic EPI EtCO2 = 50

aerosol aerosol
A B
Figure 15-20. Evaluating drug effectiveness with capnography. Capnograms of 2-year-old boy with severe
croup before (A) and after (B) administration of racemic epinephrine by aerosol.
50
PCO2 (torr)
40
30 Figure 15-21. Capnogram produced with
20
rebreathing.
10
0
Time
50
40
PCO2 (torr)
30 Figure 15-22. Capnogram produced with

20 curare cleft.
10
0
Time
Arterial CO2
Alveolar deadspace volume

Exhaled CO2 (%)
Figure 15-23. Volumetric capnogram. Note that

q End-tidal the area under the capnogram is carbon dioxide
CO2 production. Also note that the volume-based capno-
Exhaled CO2 volume gram allows determination of anatomic dead space,
alveolar volume, and alveolar deadspace.
p
Airway Alveolar volume

deadspace Exhaled tidal volume
Normal
FECO2
Figure 15-24. Volumetric capnogram with Decreased
decreased pulmonary perfusion. perfusion
Exhaled volume
the variability in PetCO2 has absolutely noth- Indeed, capnography has been identified as a
ing to do with changes in PaCO2.677 Thus, valuable indicator of patient mishaps, second
more than half of the time it can be misleading only to pulse oximetry, but more valuable than
if simply viewed, even as a trend monitor, in ECG tracings.611
this manner. Changes in PetCO2 may be the result of
There are two situations in which PetCO2 changes in carbon dioxide production, alveo-
may be considered to reflect PaCO2. First is the lar ventilation, or equipment malfunctions.
patient with normal lungs, such as a patient Potential causes of increased PetCO2 are shown
being hyperventilated secondary to head trauma. in Box 15-4. Causes of decreased PetCO2 are
Second, sudden substantial change in PetCO2 shown in Box 15-5.
has been shown to be of benefit in identifying
mishaps.678 This could be a ventilator disconnect P(aet)CO2
or some other potentially catastrophic event. If PaCO2 and PetCO2 are known, the gradient
can be calculated. Normally, the gradient is less
Box 15-4 Causes of Increased

PetCO2 Box 15-5 Causes of Decreased
INCREASED CO2 PRODUCTION AND
PetCO2
DELIVERY TO THE LUNGS DECREASED CO2 PRODUCTION AND
Fever DELIVERY TO THE LUNGS
Sepsis Hypothermia
Bicarbonate administration Pulmonary hypoperfusion
Increased metabolic rate Cardiac arrest
Seizures Pulmonary embolism
Hemorrhage
DECREASED ALVEOLAR Hypotension
VENTILATION
Respiratory center depression INCREASED ALVEOLAR VENTILATION
Muscular paralysis Hyperventilation
Hypoventilation
COPD EQUIPMENT MALFUNCTION
Ventilator disconnect
EQUIPMENT MALFUNCTION Esophageal intubation
Rebreathing Complete airway obstruction
Exhausted CO2 absorber Poor sampling
Leak in ventilator circuit Leak around endotracheal tube cuff
From Hess, D.: Capnometry and capnography: Technical From Hess, D.: Capnometry and capnography: Technical
aspects, physiological aspects, and clinical applications. aspects, physiological aspects, and clinical applications.
Respir. Care, 35(6):562, June 1990. Respir. Care, 35(6):562, June 1990.
than 5 mm Hg; however, it can be increased with movement of the patients head. Assessment of
deadspace disease such as pulmonary embolism PetCO2 is the most reliable way to insure cor-
or decreased cardiac output.674 The presence of rect placement of an endotracheal tube.
increased deadspace may also have some signi- Occasionally PetCO2 may be high because of
ficance as a prognostic indicator in surgical other reasons. Esophageal gas may be quite high
patients, although further research is needed in CO2 following ingestion of carbonated bever-
to confirm this.681 Interestingly, P(aet)CO2 ages, or antacids. Nevertheless, the PCO2 will
measured after forced exhalation seems to decrease rapidly following 10 to 15 seconds of
be best for evaluation of acute pulmonary bag-resuscitator ventilation.
embolism,679 although this is not always prac- One must also keep in mind, however, that
tical in the clinic. in the absence of circulation, as during cardiac
Occasionally, PetCO2 may actually be arrest or very low perfusion states, PetCO2
higher than PaCO2. The reasons for this are may be very low or absent. Notwithstanding,
unclear but are most likely due to emptying of the American College of Emergency Physicians,

low V/Q units with long time constants at the as well as the International Guidelines for
end of expiration. Emergency Cardiovascular Care recommend
use of CO2 detection to verify endotracheal
Usefulness of PetCO2 tube placement.674 Furthermore, new American
Verification of Intubation Heart Association guidelines require secondary
As stated earlier, PetCO2 is useful as a general confirmation of proper tube placement in all
indicator of PaCO2 in the patient with normal patients by exhaled CO2 immediately after intu-
lungs and has some value as a gross indicator of bation and during transport.682 Colorimetric
patient mishaps. detectors are adequate for this purpose.674
Monitoring of PetCO2 via colorimetry is also
clearly a valuable adjunct to assessing success- PetCO2 during Cardiopulmonary Resuscitation
ful endotracheal intubation. Intubation of the PetCO2 appears to be useful in the evalua-
esophagus is a serious problem that may occur tion of cardiopulmonary resuscitation (CPR).
during attempted intubation, during manip- First, the PetCO2 increases with restoration
ulation of the endotracheal tube, or during of artificial circulation and correlates with

A 26-year-old woman is being mechanically ventilated ASSESSMENT

following cranial surgery. She is being intentionally Abnormalities: List abnormal data and other noteworthy
hyperventilated via mechanical ventilation to minimize information. Classify ABG.
intracranial pressure. She is also being monitored contin- Explanation: List possible diseases, pathology, or other
uously via capnometry. situations that may have led to this patients condition.
Evaluation: Suggest additional data that would be useful in
SaO2 98%
pH 7.54 INTERVENTION
PaCO2 27 mm Hg Importance: Prioritize concern(s) of treatment in order
PaO2 94 mm Hg of urgency and/or seriousness as you see the overall
[HCO3] 23 mEq/L situation.
FIO2 0.40 Objective: Specifically state the measurable or observ-
PetCO2 21 mm Hg able outcomes you would like treatment to accomplish.
Suddenly, her PetCO2 increases to 35 mm Hg. Action: Describe your specific plan of action.

A 64-year-old man is being mechanically ventilated in ASSESSMENT

the surgical intensive care unit following heart surgery. Abnormalities: List abnormal data and other noteworthy
pH 7.36 Evaluation: Suggest additional data that would be useful in
PaCO2 37 mm Hg helping understand the situation or in making a diagnosis.
PaO2 74 mm Hg
FIO2 0.50 Importance: Prioritize concern(s) of treatment in order of
PetCO2 27 mm Hg urgency and/or seriousness as you see the overall situation.
The patient appears uncomfortable and short of Objective: Specifically state the measurable or observ-
breath and a later ABG reveals a PaCO2 of 50 mm Hg. able outcomes you would like treatment to accomplish.
Nevertheless, the PetCO2 continues to read at Action: Describe your specific plan of action.
approximately 27 mm Hg.
cardiac output and coronary perfusion pres- cardiopulmonary resuscitation. Capnography is

sure.683,684,686 Perhaps most important, an a beneficial way to evaluate PaCO2 in the patient
abrupt increase (within 30 seconds) in PetCO2 with normal lungs. In addition, capnography
may be the earliest sign indicating that sponta- and PetCO2 are useful as indicators of patient
neous circulation has been restored in the mishaps.
patient being resuscitated.689 Thus, the (PaCO2 PetCO2) or the slope of the capno-
PetCO2 may be a very useful quantitative indi- gram may be beneficial in many other situations
cator of pulmonary perfusion and cardiac out- to evaluate deadspace, equipment malfunctions,
put during cardiac arrest.689 Higher PetCO2s and response to therapy and ventilation-
were likewise observed when fatigued rescuers perfusion mismatch. Its benefit in assessing for
were relieved by fresh rescuers.687 In addition, pulmonary embolus and optimal positive end-
higher PetCO2s were observed during suc- expiratory pressure is less convincing. Likewise,
cessful resuscitation of animals than during its benefit in infants and children needs
unsuccessful resuscitation.685 Likewise, PetCO2 additional verification.673 Most importantly, it
may be useful in identifying patients who were should not be assumed to reflect PaCO2 in most
likely to be successfully resuscitated as those mechanically ventilated patients. Its use in this
with a PetCO2 of 15 mm Hg were more likely manner is misleading and dangerous.
to be successfully resuscitated than those with Volumetric CO2 analysis is useful for evaluat-
a PetCO2 of 7 mm Hg.688 Administration of ing carbon dioxide production from metabolism
bicarbonate during CPR may negate the use- and alveolar deadspace changes. Its use as a
fulness of PetCO2 as an indicator of blood method to noninvasively monitor cardiac output
flow during CPR because it will artifactually is very promising and likely to expand.
increase carbon dioxide levels. Box 15-6 reviews key points from the
AARC Clinical Practice Guideline regarding
Summary use of capnography during mechanical ventila-
Clearly, colorimetric CO2 analysis is useful to tion.674 Notably, at this time, capnography is
help verify endotracheal intubation. PetCO2 also not held to the quality assurance standards
appears beneficial in tracking cardiac output imposed on invasive tests such as arterial
(i.e., pulmonary perfusion) and response to blood gas analysis.
Box 15-6 AARC Clinical Practice GuidelinesCapnography/Capnometry

during Mechanical Ventilation, 2003 Revision and Update:
Nuts & Bolts
Indications: Conventional Capnometry/Capnography
Verification endotracheal intubation
Monitoring V/Q especially VD/VT
Slope phase III capnograph
PaCO2 PetCO2 trends
Assessment pulmonary embolus
Indications Volumetric Capnometry
Assess CO2 production per minute
Assess alveolar deadspace
Clinical Limitations
PetCO2 is not a replacement for PaCO2
Technical Error
Oxygen, water, or nitrous oxide in light path
Carbonated beverages or antacids in stomach
Leaks in ventilator circuitry
Reference: AARC Clinical Practice Guideline. Capnography/capnometry during mechanical ventilation. (2003 update).
Respir. Care, 48:534539, 2003.
EXERCISES
Exercise 15-1 Basic Principles of Oximetry

1. The gold standard test in the evaluation of acid-base balance and oxygenation is ______.
2. (Monitoring/Measurement) techniques provide the clinician with static information about
a single point in time.
3. Measurement of the light spectrum of an unknown substance is a useful method of
(quantitative/qualitative) analysis.
4. The ability of light to release electrons from metals in proportion to the intensity of the light
is known as the ______.
5. Quantitative spectrophotometry is made possible through application of the______ law.
6. The ratio of light intensity at a given wavelength incident on a substance compared with
the intensity of light transmitted through the substance is called its______.
7. An instrument that measures the amount of light transmitted through (or reflected from)
a sample of blood at two or more specific wavelengths to assess O2 levels is called
an ______.
8. An oximeter is a dedicated ______ specifically designed to measure SaO2.
9. When two substances have identical light absorption properties at a given wavelength,
an ______ point is said to exist.
10. In reflection oximetry, the photo detector is on the (same/opposite) side of the blood
sample as the light source.
11. Transmission oximeters are more accurate if (hemolyzed/nonhemolyzed) blood is used.
12. When using two wavelength oximetry, abnormal forms of hemoglobin, such as
methemoglobin, (are/are not) identified.
13. State the four hemoglobin species that are usually measured by a CO-oximeter.
14. SaO2 measured via CO-oximetry is sometimes called (fractional/functional) saturation.
15. The ______ ear oximeter measured light at eight different wavelengths.
Exercise 15-2 Pulse Oximetry

1. Blood oxygen saturation can be monitored continuously and noninvasively at the bedside
with the technology of ______.
2. A device for measuring and recording change in the volume of a part of the body or an
organ is called a ______.
3. Photoelectric plethysmography is used in pulse oximeters to measure the ___________.
4. In pulse oximetry, baseline absorption is the amount of light absorbed during
(systole/diastole) of the heart cycle.
5. Pulse oximeters are generally (accurate/inaccurate) when large amounts of fetal
hemoglobin are present.
6. Pulse oximeters use ______ wavelengths of light.
7. Pulse oximeters use light from what two light ranges?
8. When part of the light being emitted by a pulse oximeter reaches the photo detector by
passing around rather than passing through the finger, ____________ is said to exist.
9. Pulse oximetry (does/does not) measure carboxyhemoglobin levels.
10. Continuous simultaneous measurement of saturation through a fiber-optic pulmonary
artery catheter and a pulse oximeter is called ______.
Exercise 15-3 Transcutaneous PO2/PCO2

1. The symbol for transcutaneous PO2 is ______.
2. Transcutaneous PO2 monitors require (more/less) maintenance and care than do pulse
oximeters.
3. The PtcCO2 electrode requires (more/less) skin heating than the PtcO2 electrode.
4. State the three layers of the skin from the outermost layer inward.
5. The epidermis consumes oxygen at a (high/low) rate and contains (many/no) blood vessels.
6. Transcutaneous PO2 electrodes heat the skin to approximately ______ C.
7. In the normal adult, PtcO2 is approximately 20% (greater/less) than PaO2.
8. In the normal infant, PtcO2 is approximately 5% to 15% (higher/lower) than PaO2.
9. (Wetting/Drying) the skin increases permeability.
10. Transcutaneous PO2 electrodes (do/do not) require a warm-up period and calibration.
11. The major complication associated with PtcO2 is skin ______.
12. It is usually recommended that electrode placement be rotated every ______ hours.
13. Transcutaneous PO2 closely varies with PaO2 in (adults/infants).
14. Between SpO2 and PtcO2, the better index of hyperoxemia is ______.
15. Which of the following is the most sensitive indicator of severe hypoxemia: SpO2, PtcO2.
Exercise 15-4 Capnometry Technique

1. The technique of displaying CO2 measurements as waveforms throughout the respiratory

cycle is called ______.
2. State the two most common types of machines that can be used to perform capnography.
3. (Mass spectrometers/Infrared capnometers) are often used to monitor a large number of
mechanically ventilated patients simultaneously in the operating room.
4. Carbon dioxide absorbs (red/infrared) radiation in proportion to its concentration.
5. Radiation beams in infrared CO2 analyzers are interrupted periodically by devices called
______ in order to increase accuracy and prevent electronic drift.
6. State the two general types of infrared CO2 analyzers that are available depending on their
actual measurement site.
7. (Sidestream/Mainstream) analyzers aspirate the gas into the sample chamber.
8. Mainstream designs are best suited for (artificial airways/spontaneously breathing patients).
9. Sidestream analyzers traditionally have (slower/faster) response times than do mainstream
analyzers.
10. Problems with secretions and moisture are diminished with (sidestream/mainstream)
CO2 analyzers.
Exercise 15-5 Capnograms

1. The CO2 concentration of the gas exhaled at the beginning of expiration is (high/almost zero).
2. The flat upper portion of the single breath capnogram is called the (anatomic
deadspace/alveolar plateau).
3. Smoothing of the CO2 waveform may occur with the (sidestream/mainstream) analyzer.
4. (Fast/Slow) speed capnography is essentially just a running monitor of end-tidal CO2.
5. PetCO2 (is/is not) a reliable indicator of PaCO2 in most mechanically ventilated patients.
6. After ingestion of a carbonated beverage, PetCO2 may be falsely (low/elevated) when
evaluating the patient for correct placement of the endotracheal tube.
7. After a pulmonary embolus, one would expect PetCO2 to (rise/fall).
8. At the onset of cardiac arrest, PetCO2 (falls/rises).
9. An abrupt (rise/fall) in PetCO2 may be the first sign of the restoration of spontaneous
circulation after resuscitation for cardiac arrest.
10. A relatively large slope of the alveolar plateau is indicative of a /an (obstructive/restrictive)
lung problem.
11. Volumetric CO2 analysis is useful for evaluating (carbon dioxide production/PaCO2).
12. Volumetric CO2 analysis with a partial rebreathing technique may be useful for
noninvasively monitoring (RQ/cardiac output).

1. Search the web for noninvasive measurement of cardiac output and report on its validity
compared to measurement of cardiac output by thermal dilution and the Fick method.
NBRC Challenge 15
1. A patient with arrhythmias experiences important in follow-up is:

a sudden, substantial decrease in cardiac A) PtcO2.
output. One would expect the following B) PtcCO2.
monitor change: C) pulse oximetry.
A) increased PetCO2. D) conventional capnography.
B) decreased PetCO2. E) volumetric capnography.
C) increased PtcO2. (RRT EXAMINATION NBRC MATRIX
D) increased metHb%. I,B,9,a)
E) increased HbCO%.
4. Following administration of benzocaine
(CRT EXAMINATION NBRC MATRIX
before a bronchoscopy, a patient appears
I,B,10,a)
very cyanotic. At this point, you would
2. A surgical patient is on mechanical venti- recommend patient evaluation via:
lation and is also being monitored with A) PtcO2.
capnography. There is a sudden decrease B) PtcCO2.
in PetCO2 without a change in PaCO2; C) pulse oximetry.
and there is a strong suspicion that the D) conventional capnography.
patient has recently had a pulmonary E) CO-oximetry.
embolus. What is a logical cause for the (CSE EXAMINATION NBRC MATRIX
decreased PetCO2? I,C,2,e)
A) The patient is hypoventilating.
5. In order to maximize safety and prevent
B) The patient is hyperventilating.
patient mishaps, rank the following
C) The patient has increased
monitors in order of their usefulness:
shunting.
I) ECG
D) The patient has increased
II) Pulse oximetry
deadspace.
III) Capnography
E) There is a likely ventilator
A) I, II, III
disconnect.
B) I, III, II
C) II, I, III
I,B,10,a)
D) II, III, I
3. A premature newborn patient has recently E) III, II, I
been treated with surfactant therapy. (CSE EXAMINATION NBRC MATRIX
The monitor that would likely be most I,C,1,a)
Chapter
16
Arterial Blood Gas Case Studies
Outline
Narcotic Overdose, 419 Acute Exacerbation of Chronic Obstructive
Unexplained Acidemia, 420 Pulmonary Disease, 425
Gastrointestinal Disturbance, 420 Mitral Valve Replacement, 426
Status Asthmaticus, 421 Patient with Burns, 427
Acute Respiratory Acidemia, 422 Chronic Obstructive Pulmonary Disease
Nasogastric Suction, 422 and Congestive Heart Failure, 429
Unexplained Alkalemia, 423 Pulmonary Edema, 430
Oxygenation Disturbance, 423 Answers to Arterial Blood Gas
Diabetic Patient, 424 Case Studies, 432
Case 1 NARCOTIC OVERDOSE

Repeat blood gases are as follows:
A 25-year-old man residing at sea level is
brought to the emergency department after a Arterial Blood Gases
narcotic overdose and possible aspiration. He FIO2 0.21
is placed on a pulse oximeter, and arterial pH 7.21
blood gases are drawn. PaCO2 64 mm Hg
[HCO3] 24 mEq/L
Arterial Blood Gases PaO2 48 mm Hg
FIO2 0.21
pH 7.45 Vital Signs
PaCO2 36 mm Hg Pulse 55/min
[HCO3] 23 mEq/L BP 100/60
PaO2 145 mm Hg Temperature 37 C
RR 8/min
Vital Signs
Pulse 55/min Pulse Oximetry
Blood pressure (BP) 100/60 SpO2 80%
Temperature 37 C
Respiration rate (RR) 8/min 1B Questions
1. Classify the arterial blood gas.
Pulse Oximetry 2. What are the four common causes of
SpO2 80% hypoxemia in hospitalized patients?
3. Hypoventilation (is/is not) a cause of
1A Questions hypoxemia in this patient.
1. Is the pulse oximeter reading congruent 4. What index can be used to differentiate
with the PaO2? simple hypoventilation from hypoven-
2. Which of the two readings must be tilation in conjunction with increased
wrong? physiologic shunting?
3. (Air in the sample/Venous sampling) 5. Write the clinical form of the alveolar air
could explain these results. equation while breathing room air.
419
6. What is this patients P(Aa)O2 on 9. What is the cause of the metabolic

room air? acidosis?
7. This patient (does/does not) have 10. The hypocapnia appears to be
abnormal increased physiologic shunting. (compensatory/a primary acid-base
8. Treatment of this patients acid-base problem).
status may require (sodium bicarbonate/
mechanical ventilation).
Case 3 GASTROINTESTINAL
DISTURBANCE
Case 2 UNEXPLAINED ACIDEMIA
A woman is admitted to the hospital with sal-
A 46-year-old woman who is comatose and monella enteritis and a history of severe diar-
has an unknown history is admitted to the rhea for about 10 days before admission. Vital
emergency department. Arterial blood gases signs, blood gases, and electrolytes taken at
and laboratory data are as follows: admission are shown below:
Arterial Blood Gases Arterial Blood Gases

FIO2 0.21 FIO2 0.21
pH 7.22 pH 7.15
[HCO3] 10 mEq/L [HCO3] 5 mEq/L
PaO2 96 mm Hg PaO2 96 mm Hg
SaO2 96% SaO2 93%
Vital Signs Vital Signs

Pulse 118/min Pulse 112/min
BP 170/110 BP 100/70
Temperature 37 C Temperature 37 C
RR 18/min RR 24/min
Plasma Electrolytes Plasma Electrolytes

Na+ 137 mEq/L Na+ 134 mEq/L
CO2 12 mEq/L CO2 7 mEq/L
Cl 104 mEq/L Cl 113 mEq/L
K+ 5.5 mEq/L K+ 3.2 mEq/L
Bloodwork 3 Questions
Glucose 110 mg/dL 1. Classify the arterial blood gas.
Creatinine 11 mg/dL 2. The anion gap is (high/low/normal).
BUN 130 mg/dL 3. The plasma chloride is (high/low/normal).
Lactate 12 mg/dL 4. What is the cause of the metabolic
acidosis?
2 Questions 5. The plasma [K+] is (high/low/normal).
1. Classify the arterial blood gas. 6. What is the likely cause of the potassium
2. The anion gap is (high/low/normal). disturbance?
3. The patient (appears/does not appear) to 7. The diuretic (Lasix/acetazolamide) could
be hypoxic. cause an acid-base disturbance similar
4. The lactate is (normal/increased). to this, but the acidemia is usually less
5. The glucose is (normal/increased). severe.
6. The creatinine is (normal/increased). 8. (Azotemic renal failure/Renal tubular
7. The BUN is (normal/increased). acidosis) may cause a normal anion gap
8. The [K+] is (normal/increased). metabolic acidosis.
Chapter 16 Arterial Blood Gas Case Studies 421
Case 4 STATUS ASTHMATICUS

[HCO3] 16 mEq/L
A 17-year-old boy with a history of asthma has PaO2 55 mm Hg
been continuously short of breath for approx- SaO2 92%
imately 2 days. He enters the hospital wheez-
ing and with air hunger. Arterial blood gases Vital Signs
and vital signs are as follows: Pulse 120/min
BP 140/90
Arterial Blood Gases Temperature 37 C
FIO2 0.21 RR 22/min
pH 7.35
PaCO2 22 mm Hg 4B Questions
[HCO3] 12 mEq/L 1. Classify the arterial blood gas.
PaO2 41 mm Hg 2. Lactate (can/cannot) be quickly metabo-
SaO2 77% lized in the presence of adequate oxygen.
3. The low bicarbonate concentration at
Vital Signs this point is most likely due to
Pulse 132/min (compensation/lactic acidosis).
BP 150/90 4. The current values (do/do not) fall within
Temperature 37 C the band for simple respiratory alkalosis
RR 28/min on the acid-base map.
4A Questions The patients wheezing continued to be severe

1. Classify the blood gas according to the for the next 48 hours. He looked very tired
basic rules for blood gas classification at this point, and arterial blood gases were as
discussed in Chapter 2. follows:
2. Are there any signs to suggest that this is
a mixed acid-base disturbance? Arterial Blood Gases
3. Do these values fall under the band on FIO2 0.5
the acid-base map for simple metabolic pH 7.32
acidosis? (See acid-base map in PaCO2 35 mm Hg
Chapter 14.) [HCO3] 17 mEq/L
4. Reclassify the acid-base status. PaO2 52 mm Hg
5. What is the cause of the respiratory SaO2 83%
alkalosis?
6. What is the probable cause of the Vital Signs
metabolic acidosis? Pulse 135/min
7. What therapy is indicated? BP 150/100
8. Is it important to administer a low Temperature 37 C
concentration of oxygen to this patient? RR 18/min (wheezing is less
9. What could explain the elevated blood audible)
pressure, pulse, and RR in this patient?
4C Questions
Oxygen therapy and aerosol therapy with 1. Classify the arterial blood gas.
bronchodilators are administered, and the 2. It (can/cannot) be assumed that the
following blood gases are obtained about patient has almost completely recovered.
3 hours later: 3. The decreased wheezing (is/is not) clearly
a positive sign.
FIO2 0.5 The next day, the patient appears to be more
pH 7.47 comfortable and under much less stress.
PaCO2 24 mm Hg Arterial blood gases are as follows:
Arterial Blood Gases 3. Do these blood gas values fall in the band
FIO2 0.28 for acute respiratory acidosis on the
pH 7.32 acid-base map?
PaCO2 40 mm Hg 4. Does the plasma bicarbonate concen-
[HCO3] 20 mEq/L tration of 29 mEq/L represent renal
PaO2 90 mm Hg compensation?
SaO2 96% 5. Is it possible for a blood gas to be correct
when the base excess of the blood is
Vital Signs decreased and the actual bicarbonate is
Pulse 90/min increased?
BP 120/80 6. How much will the plasma bicarbonate
Temperature 37 C increase acutely for every 10-mm Hg
RR 14/min increase in PaCO2 due to the hydrolysis
effect?
4D Questions 7. What supportive treatment is
1. Classify the arterial blood gas. indicated for this patients acid-base
2. What is the most likely cause of the status?
metabolic acidemia at this time?
Case 6 NASOGASTRIC
Case 5 ACUTE RESPIRATORY
SUCTION
ACIDEMIA
A 34-year-old man involved in an automobile A nasogastric tube was placed in a 32-year-old
accident arrives in the emergency department woman with intestinal obstruction. For several
with severe head trauma. Arterial blood gases, days, large amounts of fluid were suctioned
vital signs, and pulse oximetry readings are as from the nasogastric tube. Arterial blood gases
follows: and electrolytes were as follows:
Arterial Blood Gases Arterial Blood Gases

FIO2 0.21 FIO2 0.21
pH 7.10 pH 7.53
[BE] 5 mEq/L [HCO3] 39 mEq/L
[HCO3] 29 mEq/L PaO2 92 mm Hg
PaO2 60 mm Hg SaO2 98%

BP 100/50 BP 110/70
RR 12/min RR 18/min
Pulse Oximetry Plasma Electrolytes

SpO2 78% Na+ 142 mEq/L
CO2 42 mEq/L
5 Questions Cl 86 mEq/L
1. What is the normal SaO2 at a PaO2 of 60 K+ 3.2 mEq/L
mm Hg?
2. Why is the SpO2 only 78% in this 6 Questions
patient despite a PaO2 of 60 mm Hg? 1. Classify the arterial blood gas.
Case 8 OXYGENATION
2. Do the values fall within the band on
DISTURBANCE
the acid-base map for simple metabolic
alkalosis? A 4-month-old infant is admitted to the emer-
3. What is the cause of the metabolic gency department with cyanosis and mild
alkalosis? cardiopulmonary distress. The family was from
4. Metabolic alkalosis is usually associated a rural area, and the infant had been receiving
with (hyperchloremia/hypochloremia). formula prepared with water taken from a
5. Hypokalemia (is/is not) common with a well. Arterial blood gases, before the infant
loss of gastric fluid. was given oxygen, were drawn and the blood
6. Loss of body fluids (is/is not) an important specimen was noted to be dark. The blood gas
aspect of this type of metabolic alkalosis. results, pulse oximetry readings, and vital signs
7. What is the appropriate treatment for were as follows:
this type of metabolic alkalosis?
FIO2 0.21
Case 7 UNEXPLAINED ALKALEMIA
pH 7.30
A 28-year-old woman in her eighth month of PaCO2 28 mm Hg
pregnancy is admitted to the hospital after [BE] 12 mEq/L
having severe vomiting for several days. PaO2 105 mm Hg
Arterial blood gases, vital signs, and elec-
trolytes are as follows: Vital Signs
Pulse 140/min
Arterial Blood Gases BP 140/100
FIO2 0.21 Temperature 37 C
pH 7.58 RR 40/min
PaCO2 31 mm Hg
[HCO3] 28 mEq/L Pulse Oximetry
PaO2 65 mm Hg SpO2 94%
SaO2 96%
8A Questions
Vital Signs 1. Does the pulse oximeter reading and
Pulse 110/min PaO2 concur with the clinical picture of
BP 130/80 cyanosis and the appearance of a dark
Temperature 37 C blood sample?
RR 18/min 2. Should another blood gas sample be
drawn?
Plasma Electrolytes
Na+ 130 mEq/L The child is then placed on oxygen and repeat
CO2 32 mEq/L arterial blood gases are drawn. Surprisingly,
Cl 86 mEq/L when a small amount of the sample acciden-
K+ 3.1 mEq/L tally escapes from the syringe, the blood
appears rusty brown or chocolate in color.
7 Questions Blood gas results and vital signs are as follows:
2. What is the likely cause of the metabolic Arterial Blood Gases
alkalosis? FIO2 0.5
3. What is the likely cause of the pH 7.28
respiratory alkalosis? PaCO2 28 mm Hg
4. What mechanisms are responsible for [HCO3] 13 mEq/L
hyperventilation during late pregnancy? PaO2 240 mm Hg

BP 130/90 BP 90/50
RR 38/min RR 32/min
Pulse Oximetry Plasma Electrolytes

SpO2 90% Na+ 136 mEq/L
CO2 7 mEq/L
8B Questions Cl 95 mEq/L
1. What is the predicted normal PaO2 on K+ 6.3 mEq/L
FIO2 of 0.5?
2. Does the infant appear to have abnormal Bloodwork
shunting? Glucose 750 mg/dL
3. Could the cyanosis and metabolic Acetoacetic acid 250 mg/dL
acidosis be due to hypoxia? Blood urea nitrogen (BUN) 38 mg/dL
4. What type of oxygenation disturbance Lactate 30 mg/dL
could be associated with cyanosis
despite a normal PaO2 and rust- 9A Questions
colored blood on exposure of the 1. Classify the arterial blood gas.
blood to air? 2. Why is the PaO2 greater than
5. Is there normally any methemoglobin 100 mm Hg on room air?
present in the blood? 3. What is the maximum PaO2 that can be
6. What is the normal percentage of achieved during hyperventilation while
methemoglobin in the blood? breathing room air?
7. Are infants more likely to have this 4. This is a (high/normal) anion gap
particular disorder? metabolic acidosis.
8. How can the level of methemoglobin be 5. The primary cause of the metabolic
reduced? acidosis is (lactic acidosis/
9. Why is the pulse oximeter reading in ketoacidosis).
the normal range? 6. It is (expected/unexpected) to have some
10. Methemoglobin is (oxygenated/ accumulation of lactic acid during
oxidized). ketoacidosis.
11. The definitive diagnosis would be made 7. State the two ketoacids.
via (CO-oximetry, electrolytes)? 8. The concentration of acetoacetic acid is
(normal/high).
9. Severe (hyperglycemia/hypoglycemia)
Case 9 DIABETIC PATIENT
is common during diabetic
A 32-year-old woman with a history of dia- ketoacidosis and causes
betes mellitus is admitted to the hospital with (polyuria/oliguria).
lethargy and confusion. Current arterial blood 10. Hyperkalemia is (unexpected/expected)
gases, laboratory data, and vital signs are in ketoacidosis.
shown below: 11. Dehydration is (common/uncommon) in
ketoacidosis. Explain this.
Arterial Blood Gases 12. The deep, rapid, breathing pattern
FIO2 0.21 observed in ketoacidosis is called
pH 7.04 ______ breathing.
PaCO2 15 mm Hg 13. Due to hypovolemia in ketoacidosis,
[HCO3] 10 mEq/L blood pressure is frequently (high/low),
PaO2 125 mm Hg and BUN is frequently
SaO2 95% (decreased/increased).
14. Ketosis and ketoacidosis are a result of [HCO3] 34 mEq/L

increased (carbohydrate/protein/fat) PaO2 39 mm Hg
metabolism. SaO2 52%
15. The fruity odor often present on the
breath during ketoacidosis is a result of Vital Signs
(acetone/urea). Pulse 130/min
16. Sodium bicarbonate treatment (is/is not) BP 130/110
recommended for this patient. Temperature 38.5 C
RR 35/min
Follow-up
The patient was treated with bicarbonate, Bloodwork
insulin, and fluids. Blood gases and electrolytes White blood cell [WBC] 17,000 mm3
were drawn 6 hours later and were as follows: [Hb] 17 g%
Hct 51%
FIO2 0.21 Plasma Electrolytes
pH 7.54 Na+ 139 mEq/L
PaCO2 32 mm Hg CO2 36 mEq/L
[BE] 4 mEq/L Cl 89 mEq/L
PaO2 97 mm Hg K+ 4.1 mEq/L
SaO2 98%
10A Questions
Plasma Electrolytes 1. Classify the arterial blood gas.
Na+ 136 mEq/L 2. In general, what first-line supportive
CO2 33 mEq/L treatment is usually indicated when a
Cl 90 mEq/L normal patient presents with acute severe
K+ 3.1 mEq/L respiratory acidosis and hypoxemia?
3. Is intubation and mechanical ventilation
9B Questions indicated in this patient? Why? What
1. Classify the arterial blood gas. special form of mechanical ventilation
2. What mechanisms may be responsible for might be useful?
the metabolic alkalosis? 4. What is the most important priority in
3. What mechanism is most likely responsible the treatment of this patients blood
for the continued hyperventilation? gas? What treatment is indicated for
supportive therapy?
5. What is the target PaO2 in the clinical
Case 10 ACUTE EXACERBATION
management of COPD associated with
OF CHRONIC OBSTRUCTIVE
chronic hypercapnia?
PULMONARY DISEASE
6. In an acute exacerbation of COPD,
A 62-year-old (60 kg) man with a history of how much does the PaO2 usually
chronic bronchitis is examined in the emer- increase for a 1% increase in inspired
gency department for shortness of breath and oxygen concentration?
expectoration of large amounts of yellow spu- 7. What FIO2 should be administered to
tum. The following blood gases, vital signs, this patient?
bloodwork, and electrolytes were drawn in the 8. Is the plasma [HCO3] in the laboratory
emergency department: normal range?
9. Why is the plasma [HCO3] elevated in
Arterial Blood Gases this patient? Is this an acute process?
FIO2 0.21 10. Is the plasma [HCO3] consistent with
pH 7.23 the total CO2 finding on the electrolyte
PaCO2 80 mm Hg report?
11. Is the chloride normal in this patient? surgery, he becomes disoriented. Arterial blood
Explain. gases are drawn:
12. Are the values for [Hb] and Hct
normal? Explain. Arterial Blood Gases
13. Is the WBC count normal? Explain. FIO2 0.21
14. Is the temperature normal? pH 7.20
15. Are the pulse and blood pressure readings PaCO2 22 mm Hg
within normal limits? Explain. [BE] 18 mEq/L
PaO2 82 mm Hg
The patient was treated with low-flow oxy- SaO2 92%
gen therapy and aerosol bronchodilators.
Nevertheless, his condition did not improve. Vital Signs
He showed progressive hypercapnia, acidemia, Pulse 141/min
and a diminished level of consciousness. The BP 75/P*
patient was therefore intubated and was placed Temperature 37 C
on mechanical ventilation. Approximately RR 24/min
1 hour after the initiation of mechanical venti- (P* = diastolic BP cannot be measured.)
lation, the patient manifested seizures and
arrhythmias. Arterial blood gases were drawn: Bloodwork
Hct 44%
Arterial Blood Gases [WBC] 9000 mm3
FIO2 0.4
pH 7.68 Plasma Electrolytes
PaCO2 35 mm Hg Na+ 140 mEq/L
[HCO3] 40 mEq/L CO2 11 mEq/L
PaO2 120 mm Hg Cl 108 mEq/L
SaO2 99% K+ 5.1 mEq/L
10B Questions 11A Questions

1. Classify the arterial blood gas. 1. The patient appears to have gone into
2. What is the probable cause of the (lactic acidosis/ketoacidosis).
metabolic alkalosis? 2. The patient is most likely in
3. What is a possible reason for the seizures (hypovolemic/septic/cardiogenic) shock.
and arrhythmias? 3. The anion gap is
4. The PaCO2 should be lowered (rapidly/ (normal/decreased/increased).
slowly) via mechanical ventilation in 4. Hypoxia (can/cannot) be present without
acute exacerbation of COPD. hypoxemia.
5. The target PaCO2 during mechanical 5. Classify the blood gas.
ventilation of this patient is approxi- 6. Is the degree of compensation typical for
mately (40 mm Hg/50 mm Hg or a simple metabolic acidosis?
higher).
6. This patients response to oxygen therapy The patient is stabilized and later goes to
was (poor/good). the operating room. After surgery, the patient
7. The response to oxygen therapy suggests is put on a mechanical ventilator and the
(absolute/relative) shunting. following arterial blood gases, vital signs,
laboratory data, and hemodynamic data are
obtained:
Case 11 MITRAL VALVE
REPLACEMENT Arterial Blood Gases
A 53-year-old man is admitted to the hospital FIO2 1.0
for mitral valve replacement. While awaiting pH 7.42
PaCO2 32 mm Hg day, arterial blood gases and vital signs were as

[BE] 4 mEq/L follows:
PaO2 240 mm Hg
SaO2 99% Arterial Blood Gases
FIO2 0.5
Vital Signs pH 7.57
Pulse 110/min PaCO2 32 mm Hg
BP 130/80 [BE] 6 mEq/L
Temperature 37 C PaO2 90 mm Hg
RR 12/min SaO2 98%
Bloodwork Vital Signs

Hct 22% Pulse 110/min
[Hb] 5 g% BP 130/80
[WBC] 14,000 mm3 Temperature 37 C
RR 12/min
Plasma Electrolytes
Na+ 140 mEq/L 11C Questions
CO2 12 mEq/L 1. Classify the arterial blood gas.
Cl 105 mEq/L 2. What is the probable cause of the
K+ 5.3 mEq/L metabolic alkalosis?
3. The oxyhemoglobin curve in this patient
Hemodynamic Profile is likely shifted to the (left/right).
Central venous 7 mm Hg
pressure (CVP)
Case 12 PATIENT WITH BURNS
Pulmonary artery 28/12 mm Hg
pressure (PAP) A 28-year-old man is trapped in a fire in the
Pulmonary wedge 9 mm Hg hospital laundry room and has an inhalation
pressure (PWP) injury and burns over 35% of his body. As
Cardiac output (CO) 4.8 L/min oxygen is being initiated in the emergency
Sv O2 60% department, he is placed on a pulse oximeter
Pv O2 32 mm Hg and arterial blood gases are drawn. Blood
gases, electrolytes, pulse oximetry, and vital
11B Questions signs show the following:
2. The mixed venous oxygen values are Arterial Blood Gases
(less/greater) than normal. FIO2 0.21
3. What is the major problem in tissue pH 7.29
oxygenation at this time? PaCO2 28 mm Hg
4. This patient is presently (well/poorly) [BE] 12 mEq/L
oxygenated. PaO2 72 mm Hg
5. What treatment does this patient need to SaO2 (calculated) 95%
improve oxygenation?
6. What is the likely cause of the Vital Signs
respiratory alkalosis? Pulse 118/min
7. At this time, the metabolic acidosis is BP 130/90
most likely (primary/compensatory). Temperature 38 C
8. The FIO2 should be (reduced/left as is). RR 32/min
The patient was given many units of blood Pulse Oximetry

and the [Hb] was stabilized. The following SpO2 94%
Plasma Electrolytes CO-oximetry

Na+ 136 mEq/L HbCO% 12%
CO2 16 mEq/L
Cl 102 mEq/L Bloodwork
K+ 4.6 mEq/L Hct 52%
[WBC] 14,000 mm3
12A Questions Lactate 6 mM/L
1. Is the PaO2 a value that is usually
considered clinically acceptable? Plasma Electrolytes
2. Is the calculated SaO2 in the acceptable Na+ 128 mEq/L
range? CO2 12 mEq/L
3. Is the SpO2 acceptable? Cl 98 mEq/L
4. Classify the patients blood gas. K+ 5.8 mEq/L
5. The anion gap is (high/low/normal).
6. Is there any reason to believe that this Hemodynamic Profile
patient is hypoxic? CVP 1 mm Hg
7. What measurement device would provide PAP 20/8 mm Hg
a true measurement of fractional PWP 4 mm Hg
oxygen saturation? CO 2.8 L/min
8. The oxygen saturation as measured via Sv O2 54%
pulse oximetry represents (functional/ Pv O2 30 mm Hg
fractional) saturation.
9. Carboxyhemoglobin is read as 12B Questions
(oxygenated/desaturated) hemoglobin 1. Tissue hypoxia and lactic acidosis
via pulse oximetry. (do/do not) appear to be present in the
10. The metabolic acidosis on the admission follow-up patient data.
blood gas is most likely a result of 2. The lactic acidosis (is/is not) due to
(HbCO/decreased PaO2). HbCO on this blood gas. Explain.
3. The half-life of HbCO on FIO2 1.0 is
The HbCO% is measured via a CO-oximeter approximately (1/5) hour(s).
and is 40%. Therefore, FIO2 1.0 is adminis- 4. The type of hypoxia that seems to be
tered to the patient. A pulmonary artery present is (hypoxemic/circulatory/
catheter is inserted because the fluid balance is anemic/histotoxic) hypoxia.
an important aspect of severe burn manage- 5. This patient appears to be in
ment. Three hours later, arterial and mixed (cardiogenic/hypovolemic)
venous blood gases are drawn, and pulmonary shock.
hemodynamics are measured: 6. The Hct is usually (low/high) in the
first few hours after severe burns.
Arterial Blood Gases 7. Why is the [K+] increased?
FIO2 1.0 8. The Sv O2 and Pv O2 are
pH 7.23 (normal/increased/decreased).
PaCO2 25 mm Hg 9. The FIO2/PaO2 relationship
[BE] 16 mEq/L suggests (absolute/relative)
PaO2 68 mm Hg shunting.

SaO2 88% 10. VCO2 in burn patients is often
(increased/decreased).
Vital Signs
Pulse 135/min After progressive hypoxemia and hypercapnia,
BP 75/P* 4 days later he is on a mechanical ventilator
Temperature 38 C and 15 cm H2O positive end-expiratory pres-
RR 35/min sure (PEEP). Blood gas and hemodynamic
(P* = diastolic BP cannot be measured.) data are as follows:
Arterial Blood Gases 12D Questions

FIO2 0.8 1. Did the PaO2 and SaO2 improve with the
pH 7.34 higher level of PEEP?
PaCO2 38 mm Hg 2. At this point PEEP should be
[BE] 5 mEq/L (increased/left as is/decreased).
PaO2 58 mm Hg
SaO2 88%
Case 13 CHRONIC OBSTRUCTIVE
Mechanical Ventilation PULMONARY DISEASE AND
CONGESTIVE HEART FAILURE
PEEP 15 cm H2O
This patient is a 53-year-old woman with
Hemodynamic Profile emphysema and congestive heart failure. She is
CVP 8 mm Hg on a chronic regime of digitalis, Lasix, and
PAP 32/12 mm Hg steroids. She presents to the emergency depart-
PWP 12 mm Hg ment with weakness and shortness of breath.
CO 3.7 L/min The following blood gases, vital signs, blood-
Sv O2 60% work, and electrolytes were reported in the
Pv O2 30 mm Hg emergency department:
12C Questions Arterial Blood Gases

1. Is the absolute capillary shunting at FIO2 0.21
this point due to congestive heart pH 7.43
failure? PaCO2 78 mm Hg
2. This patient most likely has [HCO3] 50 mEq/L
(a pulmonary emboli/acute respiratory PaO2 51 mm Hg
distress syndrome [ARDS]). SaO2 88%
3. The Pv O2 suggests that tissue
oxygenation is (good/less than Vital Signs
optimal). Pulse 126/min
BP 110/80
After an increase in PEEP to 20 cm H2O, the Temperature 37 C
following blood gas and hemodynamic data RR 26/min
are obtained:
Bloodwork
Arterial Blood Gas WBC 8000 mm3
FIO2 0.8 [Hb] 16 g%
pH 7.35 Hct 48%
PaCO2 36 mm Hg
[BE] 5 mEq/L Plasma Electrolytes
PaO2 77 mm Hg Na+ 142 mEq/L
SaO2 91% CO2 51 mEq/L
Cl 80 mEq/L
Mechanical Ventilation K+ 2.6 mEq/L
PEEP 20 cm H2O
13A Questions
Hemodynamic Profile 1. Classify the arterial blood gas based on
CVP 16 mm Hg the simple principles of classification that
PAP 35/14 mm Hg are described in Chapter 2.
PWP 14 mm Hg 2. State any conditions that are present
CO 3 L/min that might alert the clinician to the
Sv O2 50% potential that a mixed disturbance
Pv O2 25 mm Hg exists.
3. Is the plasma [HCO3] consistent with the 5. Pulmonary artery diastolic pressure
total CO2 reported on the electrolyte is sometimes used as a substitute for
report? PWP. Is this practice acceptable in
4. Is the patient receiving any drugs that this patient if the wedge balloon
could cause metabolic alkalosis? If so, malfunctions?
name them.
5. Are there any electrolyte abnormalities
Case 14 PULMONARY EDEMA
that could contribute to metabolic
alkalosis in this patient? Explain. This 50-year-old patient was recently transferred
6. Is it possible that congestive heart failure to the intensive care unit from the emergency
(disease itself) can cause metabolic department after progressive cardiopulmonary
alkalosis? Explain. distress that culminated in a cardiac arrest. The
7. What drugs that this patient is receiving patient is presently intubated and receiving
could lead to hypokalemia? mechanical ventilation. Current arterial blood
8. How should the metabolic alkalosis be gases, laboratory data, and vital signs are shown
treated in this patient? below:
9. Is oxygen therapy indicated? If so, what
is the target PaO2? Arterial Blood Gases
10. What FIO2 is indicated? FIO2 0.7
11. What could explain the weakness in this pH 7.20
patient? PaCO2 50 mm Hg
[BE] 9 mEq/L
Because of cardiac arrhythmias and this PaO2 64 mm Hg
patients marginal cardiovascular status, she SaO2 85%
was admitted to the hospital. A pulmonary
artery catheter was inserted to evaluate more Vital Signs
accurately her cardiac function and fluid sta- Pulse 100/min
tus. Hemodynamic findings and mixed venous BP 70/P
oxygenation values are shown below: Temperature 37 C
RR 20/min
Hemodynamic Profile and Mixed Venous
Oxygenation Bloodwork
CVP 15 mm Hg WBC 11,000 mm3
PAP 45/25 mm Hg BUN 25 mg/dL
PWP 9 mm Hg Glucose 120 mg/dL
Sv O2 74% Lactate 75 mg/dL
Pv O2 38 mm Hg
CO 5.4 L/min Plasma Electrolytes
Na+ 140 mEq/L
13B Questions CO2 15 mEq/L
1. Does the pulmonary wedge Cl 105 mEq/L
pressure indicate left-sided heart K+ 5.4 mEq/L
failure?
2. Is the CVP pressure normal? 14A Questions
3. The pulmonary vascular resistance 1. Classify the PaO2.
appears to be (normal/above normal/ 2. Is mild hypoxemia associated with
below normal) in this patient. hypoxia in normal individuals?
4. Increased pulmonary vascular resistance 3. The PaO2 is a direct measure of
is common in chronic obstructive (combined/dissolved) oxygen.
pulmonary disease (COPD) because of 4. What percentage of arterial blood oxygen
(low alveolar PO2/alkalemia). is usually in the dissolved state?
5. The PaO2 provides (no/some indirect) 27. State the two major categories of
information about the amount of pulmonary edema.
combined oxygen.
6. The relationship between PaO2 and Invasive Monitoring
SaO2 is expressed in the (shunt equation/ The patients chest radiograph showed diffuse
oxyhemoglobin dissociation curve). lung infiltrates consistent with cardiogenic pul-
7. The normal SaO2 expected at a PaO2 of monary edema or ARDS. A pulmonary artery
approximately 60 mm Hg is ______ %. catheter was inserted, and the following read-
8. As seen in this patient, an SaO2 of only ings were obtained:
85% with a PaO2 of 64 mm Hg means
that oxyhemoglobin affinity is Hemodynamic Profile and Mixed Venous
(increased/decreased/normal). Oxygenation
9. In this patient, the oxyhemoglobin CVP 10 mm Hg
curve is shifted to the (left/right). PAP 50/20 mm Hg
10. What could explain the change in PWP 22 mm Hg
oxyhemoglobin affinity in this patient? Sv O2 40%
11. Does this patient appear to have Pv O2 28 mm Hg
adequate tissue oxygenation? CO 2.4 L/min
12. What vital sign information may suggest
that this patient has tissue hypoxia? 14B Questions
13. Classify this patients acid-base status 1. What is the most important
based on the blood gas report. hemodynamic index to differentiate
14. What underlying cause is probably cardiogenic pulmonary edema from
responsible for the respiratory acidosis? noncardiogenic pulmonary edema?
15. The first step in determining the cause 2. (Left-sided heart failure/ARDS) is
of a metabolic acidosis is to calculate responsible for the pulmonary edema in
the ______ . this patient at this time.
16. This patients anion gap is ______. 3. Is the CVP usually high in left-sided
17. This anion gap suggests (increased heart failure?
fixed acids/decreased bases) in the 4. Why is the CVP not excessively high in
blood. this patient?
18. State four general causes of increased 5. What type of supportive pulmonary
fixed acids. treatment is often effective in the
19. What is the most likely cause of treatment of absolute pulmonary
metabolic acidosis in this patient? shunting disorders?
20. Is the lactate level normal? 6. Is PEEP contraindicated in this patient
21. What is the most likely explanation for because of the low blood pressure?
why the potassium concentration has 7. Should this patients feet be elevated
increased? because his blood pressure is low?
22. What are the four general mechanisms 8. What type of drug can be given to
of hypoxemia in the acute care setting? this patient to decrease blood
23. What is the normal PaO2 when volume?
breathing FIO2 of 0.7? 9. What drug is usually indicated to
24. This patient (must/does not) have improve cardiac contractility and
increased shunting. function in congestive heart failure?
25. This patient has predominantly (absolute/ 10. The mixed venous oxygenation values
relative) shunting because the response are (low/high/normal) and suggest that
to oxygen therapy is (good/poor). the patient (is/is not) hypoxic.
26. State at least three common cardio-
pulmonary disorders that can cause The patient was managed aggressively with
increased absolute shunting. digitalis, diuretics, and fluid restriction. The next
day, blood gases, hemodynamic measurements, Both of these measurements cannot be

and electrolytes were as follows: correct.
2. The PaO2 cannot be correct. A PaO2 of
Arterial Blood Gases 145 mm Hg cannot be achieved by
FIO2 0.5 breathing room air. Furthermore, the
pH 7.54 patients vital signs are not congruent
PaCO2 39 mm Hg with the blood gas report.
[BE] 9 mEq/L 3. Air in the sample could explain these
PaO2 74 mm Hg results because it would increase the
SaO2 95% PaO2 and decrease the PaCO2.
Vital Signs CASE 1B

Pulse 110/min 1. Uncompensated respiratory acidosis with
BP 75/P moderate hypoxemia.
Temperature 37 C 2. Hypoventilation, relative shunting,
RR 25/min absolute shunting, diffusion defect.
3. Hypoventilation is present (PaCO2 of
Plasma Electrolytes 64 mm Hg), which is responsible, at least
Na+ 135 mEq/L in part, for the hypoxemia.
CO2 30 mEq/L 4. The P(Aa)O2 on room air can be used to
Cl 90 mEq/L make this differentiation. When the
K+ 2.5 mEq/L P(Aa)O2 is less than 20 mm Hg, simple
hypoventilation is the cause; however,
Hemodynamic Profile when the value exceeds 20 mm Hg,
CVP 2 mm Hg increased physiologic shunting is also
PAP 20/8 mm Hg present.
PWP 7 mm Hg 5. PAO2 = (PBPH2O) 0.21 1.2 (PaCO2).
CO 3.1 L/min 6. P(Aa)O2 = 25 mm Hg.
7. Does have increased physiologic
14C Questions shunting, which may be due to
1. Classify the blood gas. pulmonary aspiration.
2. Classify the blood gas based on the new 8. Mechanical ventilation.
base excess (see answer to question 1).
3. What factors may contribute to the CASE 2
metabolic alkalosis at this time? 1. Partially compensated metabolic acidosis
4. Is this patient still in shock? with normoxemia.
5. Should it be assumed that the patient is 2. The anion gap is high
still in cardiogenic shock? (i.e., A = 21 mEq/L).
6. At this point in time the patient may Na (TCO2 + Cl) = A
benefit from being in the (sitting/supine) (normal 1214 mEq/L)
position. 3. There is no evidence to support
7. What acid-base/electrolyte factors would hypoxia.
contraindicate weaning the patient from 4. The lactate concentration is in the normal
the mechanical ventilator at this time? range (<18 mg/dL). Note that the units
are mg/dL. Normal values are much
ANSWERS TO ARTERIAL BLOOD lower in mM/L or mEq/L.
GAS CASE STUDIES 5. The glucose concentration is normal
(normal fasting glucose,
CASE 1A 70 to 150 mg/dL).
1. A saturation of 80% does not make 6. The creatinine is greatly increased
sense with a PaO2 of 145 mm Hg. (normal < 1.5 mg/dL).
7. The BUN is greatly increased asthma may also contribute to the

(normal < 23 mg/dL). hyperventilation.
8. The [K+] is increased (normal < 5 mEq/L). 6. The most likely explanation for the
9. The metabolic acidosis is due to azotemic metabolic acidosis is lactic acidosis as
renal failure. a consequence of severe hypoxemia and
10. The hypocapnia appears to be com- tissue hypoxia.
pensatory; it is consistent with expected 7. The most important treatment at this
compensation because the PaCO2 time is oxygen therapy to relieve the
(25 mm Hg) approximates the last two severe hypoxemia.
digits of the pH (0.22). Furthermore, 8. Recent evidence suggests it is best to
these values fall within the band first attempt low-flow (concentration)
for simple metabolic acidosis on the oxygen during acute exacerbation.700
acid-base map. Nevertheless, higher FIO2 may be
required and it is imperative to correct
CASE 3 the apparent lactic acidosis.
1. Partially compensated metabolic acidosis 9. The increased blood pressure, heart
with normoxemia. rate, and respiratory rate are all
2. The anion gap is normal (14 mEq/L). normal physiologic responses to
3. The plasma chloride concentration is severe hypoxemia. These effects
high (hyperchloremia). It is normally at may be mediated via the peripheral
a concentration of about 103 mEq/L. chemoreceptors.
4. The probable cause of the hyperchloremic
(normal anion gap) acidosis in this CASE 4B
patient is the history of severe diarrhea. 1. Partially compensated respiratory alkalosis
5. The potassium concentration is low with moderate hypoxemia. The clinician
(<3.5 mEq/L). should keep in mind that a mixed
6. Potassium is lost secondary to GI fluid disturbance may still be present.
loss dehydration with the diarrhea. 2. Lactate can be metabolized quickly by
7. Acetazolamide (Diamox) can cause the liver in the presence of adequate
hyperchloremic metabolic acidosis because oxygen. This may explain some
it is a carbonic anhydrase inhibitor. improvement in [HCO3].
8. Renal tubular acidosis leads to normal 3. Compensation alone may explain these
anion gap metabolic acidosis. results but lactic acidosis is also common
in severe asthma. A lactate measurement
CASE 4A would aid in diagnosis.
1. Compensated metabolic acidosis with 4. The current values fall within the band
severe hypoxemia. for chronic respiratory alkalosis.
2. Yes, the presence of excessive (i.e.,
complete) compensation suggests a mixed CASE 4C
acid-base disturbance. In addition, the 1. Uncompensated metabolic acidosis with
history of asthma and the presence of moderate hypoxemia.
severe hypoxemia should be considered 2. It cannot be assumed that the patient is
in the acid-base evaluation. better. He may have reached the point of
3. No, therefore we can be virtually sure that exhaustion and may be headed toward
a mixed acid-base disturbance is present. ventilatory failure. The continued
4. Mixed respiratory alkalosis and worsening of vital signs and PaO2
metabolic acidosis (two primary are highly suggestive of this common
acid-base problems). phenomenon in status asthmaticus. The
5. The severe hypoxemia is responsible for patient should be watched closely to
part, if not all, of the hyperventilation. determine if mechanical ventilation
Perhaps the restrictive component of the is required.
3. Is not. Decreased and inaudible wheezing CASE 7

may indicate decreased air flow and 1. Mixed respiratory and metabolic
patient deterioration. alkalosis with mild hypoxemia.
2. Severe vomiting can cause metabolic
CASE 4D alkalosis.
1. Uncompensated metabolic acidosis with 3. Respiratory alkalosis is common in the
normoxemia. third trimester of pregnancy.
2. Eucapnic ventilation after hypocapnia; 4. Hyperventilation is common in the third
the bicarbonate was low earlier owing trimester of pregnancy owing to:
to a compensatory mechanism. Now (1) mechanical difficulty (i.e., upward
that the respiratory alkalosis has been displacement of the diaphragm), and (2)
corrected, the low bicarbonate appears progesterone stimulates ventilation.
as a primary metabolic acidosis.
Nevertheless, other potential causes of CASE 8A
primary metabolic acidosis should be 1. No, cyanosis and a sample of dark
considered and ruled out. blood (suggesting poor oxygenation and
possible methemoglobinemia) are
CASE 5 incongruent with the PaO2 and pulse
1. The SaO2 at a PaO2 of 60 mm Hg is oximeter readings (suggesting good
normally 90%. oxygenation).
2. The oxyhemoglobin curve has shifted 2. Yes, a repeat blood gas would be
to the right owing to acidemia and appropriate because of the incongruencies.
hypercapnia. It should also be analyzed via
3. Yes. CO-oximetry.
4. No, the increased bicarbonate is simply a
result of the acute hypercapnia and the CASE 8B
effect of hydrolysis (see Chapter 5). 1. (Four to five the percentage of oxygen
5. Yes, in acute hypercapnia the base excess inspired) 5 50 = 250 mm Hg.
of the blood gives falsely low values due 2. No, 240 mm Hg is within the expected
to in vivo/in vitro effects, and the actual range.
bicarbonate reads falsely high owing to 3. Yes, the cyanosis suggests an
the hydrolysis effect (see Chapter 5). oxygenation disturbance; however, an
6. The plasma [HCO3] increases explanation of why this would occur
approximately 1 mEq/L for every must be sought. Remember, hypoxia
10 mm Hg increase in PCO2 acutely. can exist without hypoxemia.
7. Intubation and mechanical ventilation is 4. Methemoglobinemia.
indicated. Hyperventilation may be 5. Yes.
indicated to decrease ICP. 6. (<1%1.5%).
7. Yes, infants younger than 6 months
CASE 6 of age are particularly vulnerable to
1. Partially compensated metabolic alkalosis methemoglobinemia, especially when
with normoxemia. exposed to water from a well, because
2. Yes. it contains nitrates.
3. Loss of excessive gastric secretions. 8. Administration of methylene blue
4. Hypochloremia. accelerates the reduction of
5. Hypokalemia is common. methemoglobin.
6. Loss of fluids is important 9. A pulse oximeter cannot detect
(see Chapter 13). methemoglobin but in its presence SpO2
7. Appropriate treatment must include migrates toward 85%.
replacement of fluids, chloride, and 10. Oxidized.
potassium. 11. CO-oximetry.
CASE 9A CASE 10A

1. Partially compensated metabolic 1. Partially compensated respiratory
acidosis with hyperoxemia. acidosis with severe hypoxemia.
2. Hyperventilation on room air can cause 2. Intubation and mechanical
hyperoxemia (i.e., PaO2 > 100 mm Hg). ventilation.
3. The maximum PaO2 that can be achieved 3. No, because this patient has COPD.
during hyperventilation by breathing Intubation and mechanical ventilation
room air is approximately 130 mm Hg. should be avoided in these patients if at
4. This is a very high anion gap metabolic all possible, and low-flow oxygen therapy
acidosis (A = 34 mEq/L). has worked well in many cases. Bronchial
5. Ketoacidosis. hygiene is also a very important part of
6. Some buildup of lactic acid is expected therapy. Noninvasive positive pressure
during ketoacidosis. ventilation has also been shown to be
7. Acetoacetic acid and beta-hydroxybutyric effective.
acid. 4. Increasing the PaO2 is the utmost
8. The concentration of acetoacetic acid is priority. Low-flow oxygen therapy is
high (normal < 10 mg/dL). indicated.
9. Hyperglycemia is seen in diabetic 5. 60 mm Hg.
ketoacidosis because the glucose cannot 6. As a crude rule of thumb, in acute
enter the cells in the absence of insulin. exacerbation of COPD, PaO2 typically
Hyperglycemia also causes hyperosmolar increases 3 mm Hg/0.01 FIO2 increase
diuresis (polyuria secondary to the high (see Chapter 10).
osmotic pressure). 7. The FIO2 should be 0.28. (This is based
10. Hyperkalemia is expected owing to on an expected 3-mm Hg increase/0.01
intracellular/extracellular hydrogen FIO2 increase and a target PaO2 of
ionpotassium exchanges. In addition, 60 mm Hg.) Pulse oximetry should be
the general tissue breakdown that occurs used to titrate therapy to 90% SpO2.
in ketoacidosis releases intracellular 8. No. Normal plasma bicarbonate is
potassium to the plasma. 24 2 mEq/L. The plasma [HCO3] is
11. Dehydration is common in diabetic keto- elevated in this patient.
acidosis due to polyuria and vomiting. 9. The plasma [HCO3] probably increased
12. Kussmauls breathing. as a compensatory mechanism for the
13. Blood pressure is frequently low, and chronic respiratory acidosis and because
BUN is slightly increased. of the hypercapnia and hydrolysis.
14. Fat metabolism. In fact, if lactic acidosis is also present
15. Acetone. (a distinct possibility with a PaO2 of
16. Sodium bicarbonate treatment is 39 mm Hg), the plasma [HCO3] may
recommended because the pH is less than actually be lower than this patients
7.10 and, most importantly, because the chronic normal baseline level.
potassium is substantially elevated. 10. Yes. The total CO2 and [HCO3] should
be very close, and they are. It is also
CASE 9B common for the TCO2 to be slightly
1. Mixed respiratory and metabolic higher because it is measured in venous
alkalosis with normoxemia. blood.
2. Factors that may contribute to metabolic 11. No. The patient has hypochloremia.
alkalosis include overcorrection with This finding is expected in chronic
NaHCO3, the conversion of ketones into respiratory acidosis. When the
bicarbonate by the liver, and hypokalemia. bicarbonate anion increases as
3. Persistent hyperventilation is common a compensatory mechanism, the
after metabolic acidosis, probably chloride anion decreases to maintain
secondary to CSF acidosis. electroneutrality (see Chapter 12).
12. No. They are both elevated. The finding 2. Cardiogenic shock is likely based on the
of secondary polycythemia is common patients cardiovascular history.
in COPD, especially in chronic 3. Anion gap increased (A = 23 mEq/L).
bronchitis. This is a compensatory (Normal 1214 mEq/L)
mechanism to increase oxygen transport 4. Hypoxia can be present without
in the presence of hypoxemia. hypoxemia.
13. No. The WBC count is elevated (normal 5. Partially compensated metabolic acidosis
< 10,000 cells/mm3). This finding and with normoxemia.
the finding of yellow sputum suggest a 6. Yes, the last two digits of the pH
bacterial infection/pneumonia. approximate the PaCO2, and the values
14. The temperature is elevated, which is fall within the band for simple metabolic
also consistent with infection or acidosis on the acid-base map.
pneumonia.
15. The pulse and blood pressure are both CASE 11B
slightly elevated. Again, this is the 1. Completely compensated respiratory
normal response to hypoxemia. alkalosis with hyperoxemia.
2. The mixed venous oxygen values are less
CASE 10B than normal. Normal Pv O2 is greater
1. Uncompensated metabolic alkalosis with than 35 mm Hg and normal Sv O2 is
hyperoxemia; however, it is known that greater than 75%. This suggests
the patient has COPD and is being hypoxia.
mechanically ventilated. Therefore, these 3. Severe anemia ([Hb] 5 g%).
factors must be kept in mind. 4. Poorly oxygenated due to the severe
2. The metabolic alkalosis is most likely due anemia despite a normal PaO2 and
to eucapnic ventilation posthypercapnia. cardiac output.
In other words, the patient is being 5. Blood transfusion.
ventilated at a lower PaCO2 than is his 6. Overzealous mechanical ventilation
normal chronic value. Therefore, the (or perhaps the mechanical ventilator is
bicarbonate that was retained as exaggerating the respiratory compensatory
compensation for both the acute and response to a primary metabolic acidosis).
chronic respiratory acidosis now appears 7. Primary, based on the severe anemia and
as a primary metabolic alkalosis. probable lactic acidosis.
3. Severe metabolic alkalemia may cause 8. The FIO2 should probably be left as is
these effects. The CSF may be even more until the severe anemia is treated; it
alkalotic than the blood because the CSF should then be reduced because of the
has less buffering capacity. Furthermore, hyperoxemia.
seizures have been reported after the
rapid reversal of hypercapnia in CASE 11C
exacerbation of COPD. 1. Combined respiratory and metabolic
4. Slowly. alkalosis with normoxemia.
5. 50 mm Hg or higher because this is 2. The blood transfusions (citrate preserva-
probably near this patients normal tive) may be completely or partially respon-
chronic baseline. sible for the delayed metabolic alkalosis
6. Good response to oxygen therapy (see Chapter 13).
(i.e., PaO2 of 120 mm Hg on FIO2 of 0.4). 3. The curve would be shifted to the left
7. Relative shunting, which is typical in because of the decreased [H+] (alkalemia)

COPD and V/Q mismatch. and hypocapnia. Stored blood transfusions
may also shift the curve to the left because
CASE 11A of decreased DPG. However, DPG levels
1. Lactic acidosis is likely with a BP are usually back to normal 24 hours after
of 75/P. transfusion.
CASE 12A 5. The patient appears to be in hypo-

1. Yes. A PaO2 of 72 mm Hg, although volemic shock, which is shown by the
mildly hypoxemic, is usually considered low CVP and low sodium. Furthermore,
to be clinically acceptable. it is well known that sodium and fluids
2. Yes. An SaO2 of 95% is acceptable. generally move to the extravascular space
Nevertheless, use of a calculated SaO2, after severe burns. Cardiogenic shock is
especially in a patient with burns, is not not present, which is substantiated by
reliable. the low PWP.
3. The saturation reading on the pulse 6. The Hct is usually high in the first few
oximeter (SpO2) is also acceptable. Here hours after severe burns because of
again, however, this reading is not hemoconcentration secondary to the
reliable in the patient with burns and loss of intravascular fluid to the
smoke inhalation. extravascular space.
4. Partially compensated metabolic acidosis 7. The potassium concentration is usually
with mild hypoxemia. elevated in burns due to the destruction
5. The A is high (18 mEq/L). of cells and to the release of intracellular
6. Yes. Carboxyhemoglobinemia is common potassium into the plasma. Also, the
after smoke inhalation, and metabolic exchange of intracellular potassium ions
acidosis may suggest lactic acidosis. for hydrogen ions in acidemia increases
7. A CO-oximeter could measure fractional the serum potassium.
saturation as well as HbCO%. 8. Sv O2 and Pv O2 are decreased and,
8. Oxygen saturation measured by pulse because of the relatively normal PaO2,
oximetry represents functional saturation. this is highly suggestive of hypoxia of
Functional saturation does not reflect circulatory origin.
abnormal Hb species such as metHb 9. Absolute shunting. Oxygenation
or HbCO. ratio <1.0.
9. HbCO will be read as oxygenated Hb 10. CO2 production is often increased in
via pulse oximetry. burn patients.
10. HbCO is most likely to be responsible
for the metabolic acidosis on the blood CASE 12C
gas when the patient was admitted to 1. No. Congestive heart failure would be
the hospital. associated with a high pulmonary wedge
pressure (e.g., PWP > 18 mm Hg).
CASE 12B 2. ARDS is common after severe burns with
1. Lactic acidosis is apparently still present inhalation injury and is characterized by
and is shown by a high anion gap acidosis severe hypoxemia despite increased FIO2.
and increased lactate (normal < 2 mM/L). 3. Less than optimal.
The low mixed venous oxygen values
also suggest tissue hypoxia. CASE 12D
2. The current lactic acidosis is not due to 1. The PaO2 and SaO2 are both improved.
HbCO because it has fallen from 40% 2. The PEEP should be decreased. Although
to 12%. The hypoxia appears to be due the PaO2 and SaO2 have improved, the
to a low cardiac output (i.e., BP 75/P) mixed venous oxygen indices and the
and CO 2.8 L/min. cardiac output have deteriorated. The
3. The half-life of HbCO on FIO2 of 1.0 is gains in reversing the pulmonary shunt
approximately 1 hour. While the patient are offset by an apparent decrease in
is breathing room air, the half-life of cardiac output. Often these cases are
HbCO is 5 hours. further clouded as peripheral shunting
4. Circulatory hypoxia because the cardiac in sepsis leads to higher mixed venous
output is only 2.8 L/min and BP is oxygen indices. This may occur despite
very low. patient deterioration.
CASE 13A 4. 1% to 2% of CaO2 is in the dissolved

1. Compensated metabolic alkalosis with state.
moderate hypoxemia. 5. Some indirect.
2. Long-standing pulmonary disease 6. Oxyhemoglobin dissociation curve.
(i.e., COPD) and excessive compensation 7. 90% SaO2 at a PaO2 of 60 mm Hg.
(more than 50% compensation). Also, 8. Decreased.
the administration of Lasix and steroids 9. Shifted to the right.
and the presence of serum hypokalemia. 10. The increased PaCO2 and the
3. Yes. The [HCO3] and total CO2 are increased hydrogen ion concentration
very close. (i.e., decreased pH) both shift the curve
4. Yes. Both Lasix and, to a lesser extent, to the right.
steroids can cause metabolic alkalosis. 11. No; cardiovascular status is poor
5. Yes. Hypokalemia and hypochloremia (low B/P).
may lead to metabolic alkalosis. 12. BP of 70/P is indicative of shock
6. Yes. Poor renal perfusion may lead to and severely compromised cardio-
secondary hyperaldosteronism. vascular function (i.e., circulatory
7. Lasix, and to a lesser extent steroids, hypoxia).
may cause hypokalemia. 13. Mixed respiratory and metabolic
8. Potassium replacement is indicated acidosis.
perhaps in the form of KCl. Fluids should 14. Extreme ventilation-perfusion mismatch
not be administered because of the CHF. (suggested by the severe shunt) or
Perhaps the diuretic acetazolamide would exhaustion (suggested by the history) is
help to counteract the metabolic acidosis likely to be responsible for the respiratory
while still providing some diuresis. acidosis. Alternatively, cerebral hypoxia
9. Yes. Oxygen therapy is indicated to try associated with the cardiac arrest may
to achieve a target PaO2 of 60 mm Hg. be causing a neurologic deficit or
10. The FIO2 indicated is 0.24 (i.e., assume inadequate mechanical ventilation may
3-mm Hg increase in PaO2/0.01 FIO2 be a factor (see Chapter 13).
increase in acute exacerbation of COPD). 15. Anion gap.
Oxygen should be titrated to SpO2 90%. 16. A = 20 mEq/L.
11. Hypokalemia causes muscular weakness 17. Increased fixed acids in the blood are
and, if severe, may cause hypoventilation. suggested by the high anion gap.
18. Toxins, azotemic renal failure, lactic
CASE 13B acidosis, ketoacidosis.
1. No. A PWP of 9 mm Hg is normal. 19. Lactic acidosis secondary to circulatory
2. No. The CVP pressure is elevated hypoxia.
(normal < 10 mm Hg). 20. No. Normal lactate is only up to
3. Above normal as indicated by a normal 18 mg/dL.
PWP and an increased PAP. 21. Acidemia often causes plasma
4. Low alveolar PO2. hyperkalemia owing to an intracellular-
5. No. The use of pulmonary artery diastolic extracellular exchange of K+ for H+.
pressure in place of wedge pressure is Although plasma hyperkalemia is not
acceptable only when the pulmonary always seen in organic acidosis, it is still
vascular resistance is normal, which is fairly common.
not the case here. 22. Hypoventilation, absolute shunting,
relative shunting, diffusion defects.
CASE 14A 23. Normal PaO2 is approximately
1. Mild hypoxemia. 45 percent inspired oxygen. Thus,
2. No. Oxygen content is still good at 280350 mm Hg.
a PaO2 greater than 60 mm Hg. 24. The patient must have increased
3. Dissolved oxygen. shunting (oxygenation ratio <1.0).
25. The patient has predominantly absolute positioning for the patient. In hypo-
shunting because the response to oxygen volemic shock, the feet should be
therapy is poor. elevated. The sitting position is more
26. Pneumonia, atelectasis, pulmonary appropriate for cardiogenic shock.
edema, etc. 8. Diuretics (e.g., Lasix).
27. Cardiogenic (congestive heart failure) 9. Digitalis.
and noncardiogenic pulmonary edema 10. The mixed venous oxygenation indices
(ARDS). are low and suggest hypoxia.
CASE 14B CASE 14C

1. Pulmonary wedge pressure (PWP). 1. This blood gas is not internally consistent
2. Left-sided heart failure is responsible for and is therefore not possible. It is impos-
the pulmonary edema, which is indicated sible to have alkalemia without either a
by a wedge pressure of 22 mm Hg respiratory or metabolic alkalosis. In this
(normal <12 mm Hg). case, a transcribing error occurred. The
3. Yes. This is how left-sided heart failure base excess should have been 9 mEq/L.
was usually monitored before the routine 2. Uncompensated metabolic alkalosis with
availability of pulmonary artery catheters. mild hypoxemia.
4. The CVP does not always closely parallel 3. Factors that may contribute to the
the pulmonary wedge pressure, which is metabolic alkalosis in this patient
one of the important reasons why include diuretic therapy, hypokalemia,
pulmonary artery catheters are more hypochloremia, and hyperaldosteronism
accurate than CVP lines. secondary to poor renal perfusion.
5. PEEP therapy and ARDS/net protocol. 4. Yes. The patient is still in shock, which is
6. No. Although PEEP should always be shown by the BP 75/P.
applied carefully when the cardiac output 5. No. The wedge pressure is too low for
or BP is low. Nevertheless, PEEP may cardiogenic shock. The low CVP and other
actually improve the cardiac output in hemodynamic pressures suggest hypo-
left-sided heart failure by decreasing volemic shock, probably as a result of the
venous return and by easing the aggressive diuresis and fluid restriction.
workload on the heart. Furthermore, PEEP 6. The patient may benefit from being
has been shown to be effective in the placed in the supine position, which
treatment of cardiogenic pulmonary would enhance venous return.
edema. Nevertheless, this should be approached
7. Definitely not! This would increase the cautiously in the patient with CHF.
venous return to a heart that is already 7. There are two areas that need to be cor-
failing. Patients in acute congestive heart rected before weaning the patient: (1) meta-
failure are best placed in the sitting bolic alkalosis that causes hypoventilation
position. This position helps to decrease as a compensatory mechanism must be
venous return, to minimize heart strain, reversed, and (2) the hypokalemia that
and perhaps to improve cardiac output. causes muscle weakness must be corrected.
It is important to understand the origin Potassium chloride would correct the
of hypotension before determining optimal hypokalemia and hypochloremia.
References
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document C46-A [ISBN 1-56238-444-9]. NCCLS, 940 Blood, 3rd ed. Philadelphia, W.B. Saunders, 1985.
West Valley Road, Suite 1400, Wayne, PA 19807-1898, 19. Centers for Disease Control. Update: Universal pre-
2001. cautions for prevention of transmission of human
2. Filley, G. F.: Acid-Base and Blood Gas Regulation. immunodeficiency virus, hepatitis B virus, and other
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pulmonary dysplasia. Adv. Exp. Med. Biol., 220: pulmonary resuscitation: A preliminary report. Crit.
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667. Bossi, E., Meister, B., and Pfenninger, J.: Comparison 685. Sanders, A. B., Ewy, G. A., Bragg, S. Atlas, M., et al:
between transcutaneous PO2 and pulse oximetry for Expired PCO2 as a prognostic indicator of successful
monitoring O2 treatment in newborns. Adv. Exp. resuscitation from cardiac arrest. Ann. Emerg. Med.,
Med. Biol., 220:171176, 1987. 14:948952, 1985.
668. Baeckert, P., Bucher, H. U., Fallenstein, F., et al: Is 686. Garnett, A. R., Ornato, J. P., Gonzalez Johnson, B.:
pulse oximetry reliable in detecting hyperoxemia in End-tidal carbon dioxide monitoring during cardio-
the neonate? Adv. Exp. Med. Biol., 220:165169, pulmonary resuscitation. J.A.M.A., 257:512515,
1987. 1987.
669. Kesten, S., Chapman, K. R., and ReBuck, A. S.: 687. Kalenda, Z.: The capnogram as a guide to the effi-
Response characteristics of a dual transcutaneous cacy of cardiac massage. Resuscitation, S6:259263,
oxygen/carbon dioxide monitoring system. Chest, 1978.
99:12111215, 1991. 688. Sanders, A. B., Kern, K. B., Otto, C. W., Milander,
670. Chan, M. M.: What is the effect of fingernail M. M., et al: End-tidal carbon dioxide monitoring
polish on pulse oximetry? Chest, 123:21632164, during cardiopulmonary resuscitation: A prognostic
2003. indicator for survival. J.A.M.A., 262:13471351,
671. AARC Clinical Practice Guideline: Pulse oximetry. 1989.
Respir. Care, 36:14061409, 1991. 689. Falk, J. L., Rackow, E. C., and Weil, M. H.: End-tidal
672. AARC Clinical Practice Guideline: Transcutaneous carbon dioxide concentration during cardiopul-
blood gas monitoring for neonatal & pediatric monary resuscitation. N. Engl. J. Med., 318:607611,
patient. Respir. Care, 39:11761179, 1994. 1988.
673. Hess, D.: Capnometry and capnography: Technical 690. National Committee for Clinical Laboratory
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674. AARC Clinical Practice Guideline. Capnography/ (Proposed guideline). NCCLS publication C27P.
capnometry during mechanical ventilation (2003 Villanova, PA, N.C.C.L.S., 1985.
update). Respir. Care, 48:534539, 2003. 691. National Committee for Clinical Laboratory
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the surgical ICU: A meta-analysis of the arterial and xemic chronic obstructive lung disease: A clinical
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Literary Award, 1992. Also presented at the AARC 693. Report of the Medical Research Council Working
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694. Code of Federal Regulations, Title 14 CFR, Part 700. Rodrigo, G. J., et al: 100% oxygen can be harmful
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Office, 1986. 701. Pierson, D. J.: The future of respiratory care. Respir.
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cardiopulmonary patients. Chest, 101:11041113, 702. Lyght, C. E.: The Merck Manual, 11th ed. West
1992. Point, PA, Merck, Sharpe and Dohme, 1966.
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Answers
CHAPTER 1 PaCO2 (very mild)

Standard procedure for selecting the opti-
ON-CALL CASE 1-1 ABGs and Critical mal site for drawing an arterial blood gas was
Thinking not followed. The radial artery (preferably
Assessment in the non-dominant hand) is the first artery
Abnormalities: of choice for arterial blood gas sampling. A
Blood gases were not drawn during a steady state. modified Allen test should also be performed
Only a few minutes elapsed since O2 was placed to ensure sufficient collateral circulation to the
on the patient. hand through the ulnar artery; this should be
ABGs should not be drawn for 30 minutes as documented. The blood gas values reflect
a general rule. normal oxygenation and acid-base balance
A repeat sample should be drawn. with the exception of mild hyperventilation
Repeat sample on room air. (hypocarbia).
Assessment Explanation:
Abnormalities: The pain and decreased mobility of the right
Normal pH hand could be a result of injury to the median
PaCO2 (hypocapnia) nerve when attempting arterial puncture of the
PaO2 brachial artery (see Fig. 1-11). The course of the
[HCO3] median nerve closely parallels that of the brachial
artery. Cases have been described in which
Explanation: median nerve damage followed brachial artery
One must keep in mind that blood gas values puncture. Furthermore, selection of the brachial
are different in Denver than they would be at artery in the dominant hand as a first choice is
sea level (i.e., PaO2 will be lower due to high somewhat controversial and could lead to undue
altitude). See Chapter 2. harm and potential litigation (see Legal Issues in
One should also note that the patient is 70 the section on Common Sample Sites). The mild
years old. The lower normal limit of PaO2 in the hyperventilation may have been a result of pain,
elderly is approximately 75 mm Hg at sea level. which accompanied the arterial puncture.
One should also remember that it is com-
mon for normal females to have slightly lower
PaCO2 values than males. When PaCO2 is low EXERCISES
for a prolonged period, the bicarbonate will
tend to decrease as explained in Chapter 2. EXERCISE 1-1 Blood Gas Values
It appears that the blood gas is generally nor- 1. pH 7.357.45
mal for a female of 70 years old in Denver, CO. PaCO2 3545 mm Hg
[BE] 0 2 mEq/L
Evaluation: PaO2 80100 mm Hg
Additional useful information would be a [HCO3] 24 2 mEq/L
patient history and physical examination, SaO2 97%98%
including vital signs. 2. PaO2
SaO2
ON-CALL CASE 1-2 ABGs and Critical 3. [HCO3]
Thinking [BE]
Assessment 4. False. Either of these metabolic indices
Abnormalities: alone is sufficient for interpretation provided
Normal blood gas oxygenation and acid-base that the metabolic index is completely
status understood.
460
Answers 461
5. 95% EXERCISE 1-4 Arterial Blood Sampling

6. Lower 1. Radial
7. Age PaO2 Brachial
84 10 mm Hg at age 58 Femoral
78 10 mm Hg at age 72 2. Ulnar
Formula PaO2 = 109 (0.43 age) Axillary
8. 97% to 98% Dorsalis pedis
9. 5 Temporal
10. 90, 75 3. Thrombus (clot) formation with possible
11. Kilopascal (kPa) dislodgement
12. 13.3 kPa Hemorrhage
13. 2 Infection
14. 7.5 mm Hg Pain
15. 8 kPa = 60 mm Hg Arteriospasm
16. Level off Peripheral nerve damage
Vasovagal response
EXERCISE 1-2 Arterial versus 4. Vasovagal
Venous Blood 5. Modified Allen test
1. Arteries are blood vessels that carry 6. 5 to 15 sec
blood away from the heart. Veins 7. Median
are blood vessels that carry blood to 8. Femoral
the heart. 9. 30
2. Arterial 10. 45
3. Arterial 11. A flashing pulsation of blood upon entry
4. Localized tissue into the vessel and auto-filling of the
5. Arterial pH syringe with blood
12. 35 min
EXERCISE 1-3 Preparation for 13. a. Readily available source for serial or
Arterial Sampling emergency blood gases
1. Heparin b. Accurate, continuous monitor of blood
Coumadin pressure
Aspirin 14. Closed
Dipyridamole 15. Non-dominant
Streptokinase 16. Should not
2. Hemophilia
3. Steady state
NBRC Challenge 1
4. 30 min
5. Should 1. C) The modified Allen test evaluates radial
6. 20 to 25 gauge artery collateral circulation and should be
7. 25 gauge performed before radial artery puncture.
8. Plastic 2. C) Inadvertent venous puncture is most
9. Lithium heparin (sodium common when attempting femoral artery
heparin, 1000 U/mL was the puncture due to proximity of vein.
previous standard and may still 3. D) An arterial blood gas is the gold standard
be used) to evaluate the combination of oxygen-
10. 1000 U/mL ation, acid-base, and ventilation.
11. 0.05 mL 4. E) Mild hypoxemia is common in the eld-
12. Continue erly and a PaO2 of 75 mm Hg is the lower
13. Aseptic limit of normal at the age of 70.242
14. Nosocomial 5. E) Low PaCO2 values are common in
15. Optional young females.
462 Answers
(The multiple-choice questions given initially [HCO3]

are less complex than those typically on NBRC Moderate hypoxemia (very near severe)
exams because they are intended for the novice PaO2
as an introduction to NBRC job-related format.) SaO2
ABG classification: Partially compensated
respiratory acidosis with moderate
CHAPTER 2 hypoxemia.
Barrel chest, smoking history, age, and
ON-CALL CASE 2-1 ABGs and Critical pulmonary secretions all suggest chronic lung
Thinking disease. The mild pH disturbance despite sub-
Assessment stantial hypercapnia also suggests some
Abnormalities: chronic compensation secondary to chronic
pH respiratory acidosis.
PaCO2
Normal [HCO3] Explanation:
Mild hypoxemia ( PaO2) This ABG would likely represent an acute
SaO2 exacerbation of chronic obstructive pulmonary
ABG classification: Uncompensated respiratory disease (COPD).
acidosis (acute ventilatory failure) with mild
hypoxemia. Evaluation:
A young person with slow respiratory rate A chest radiograph could further clarify the
and comatose in the emergency department. presence of chronic lung disease. One might
also evaluate the patient for the presence of an
Explanation: acute bacterial infection. Fever, increased
Unexplained acute respiratory acidosis in the white blood cell count (leukocytosis), and the
emergency department and a very slow respi- presence of purulent secretions would help
ratory rate could likely be a narcotic or other confirm this. Pulmonary function studies
drug overdose. Mild hypoxemia is likely sec- would also help confirm pulmonary disease
ondary to hypoventilation. and impairment.
Evaluation: Intervention
Patient history and physical might unveil the Importance:
events that led up to the condition. A drug First priority is to get oxygenation to an
screen would also be useful. acceptable level while always keeping in
mind that patients with COPD may hypo-
Intervention ventilate in response to oxygen therapy
Importance: (i.e., they are oxygen sensitive). Excessive
First priority is to get ventilation at an accept- oxygen therapy in these patients may be very
able level. dangerous and should be avoided unless
Because the patient is comatose, she is likely absolutely necessary. It is common practice
to have obtunded reflexes and is at risk for to try to get the PaO2 to approximately
aspiration. Thus, the patient should be intu- 60 mm Hg by using low-flow oxygen. Low-
bated and placed on mechanical ventilation to flow oxygen is really low oxygen concentra-
normalize PaCO2. tions as administered by nasal cannula (e.g.,
13 L/min) or Venti-masks. This is an impor-
ON-CALL CASE 2-2 ABGs and Critical tant group of patients that we must recognize
Thinking have chronic lung disease and in whom
Assessment oxygen should be administered sparingly.
Abnormalities: Notwithstanding, oxygen must be adminis-
pH tered in quantities sufficient to preclude
PaCO2 hypoxia.
Answers 463
EXERCISES 5. a. Normal [HCO3]

b. Metabolic alkalosis
EXERCISE 2-1 pH Assessment c. Metabolic acidosis
1. pH 6. a. Decrease
2. Extracellular b. Increase
3. Overall c. Decrease
4. 6.80 to 7.80 7. [HCO3] and [BE]
5. Depressive 8. 0 2 mEq/L
6. Alkalemia 9. Base deficit
7. Does not 10. a. Metabolic acidosis
8. Acidemia b. Metabolic alkalosis
9. Acidosis c. Metabolic alkalosis
10. Acid-base status d. Metabolic acidosis
Basic (primary) acid-base disturbance(s) e. Normal [BE]
Compensation assessment f. Metabolic alkalosis
11. pH
PaCO2 EXERCISE 2-4 Compensation
[HCO3] Assessment
PaO2 1. Compensation
12. a. Acidosis 2. Respiratory
b. Acidosis 3. Renal
c. Alkalosis 4. Hypocarbia
d. Normal pH 5. Acute
e. Acidosis 6. Partial
f. Alkalosis 7. pH
g. Alkalosis 8. Partially
h. Normal pH 9. Increased
i. Alkalosis 10. a. Respiratory acidosis
b. Respiratory acidosis
EXERCISE 2-2 Respiratory c. Respiratory alkalosis
Acid-Base Status d. Metabolic alkalosis
1. Carbonic e. Metabolic acidosis
2. PaCO2
3. Hypercarbia EXERCISE 2-5 Acid-Base
4. a. Respiratory alkalosis Classification
b. Normal PaCO2 Set A
c. Normal PaCO2 1. Uncompensated respiratory acidosis
d. Respiratory alkalosis 2. Uncompensated metabolic alkalosis
e. Respiratory acidosis 3. Mixed (combined) respiratory and meta-
5. a. Decrease bolic alkalosis
b. Decrease 4. Mixed (combined) respiratory and meta-
c. Increase bolic acidosis
d. Decrease 5. Uncompensated respiratory
e. Increase alkalosis
6. Uncompensated metabolic alkalosis
EXERCISE 2-3 Metabolic 7. Mixed (combined) respiratory and meta-
Acid-Base Status bolic alkalosis
1. Metabolic 8. Uncompensated metabolic acidosis
2. Nonrespiratory 9. Uncompensated metabolic acidosis
3. Actual 10. Uncompensated respiratory
4. 24 2 mEq/L acidosis
464 Answers
Set B 3. Moderate hypoxemia

1. Compensated respiratory acidosis 4. Severe hypoxemia
2. Partially compensated respiratory acidosis 5. Moderate hypoxemia
3. Partially compensated respiratory alkalosis 6. Hyperoxemia
4. Normal acid-base status 7. Mild hypoxemia
5. Partially compensated metabolic acidosis 8. Hyperoxemia
6. Uncompensated metabolic acidosis 9. Normoxemia
7. Partially compensated respiratory alkalosis 10. Normoxemia
8. Uncompensated metabolic alkalosis (PaCO2
is still in the normal range) EXERCISE 2-9 Complete Blood Gas
9. Partially compensated metabolic alkalosis Classification
10. Mixed (combined) respiratory and meta- 1. Partially compensated respiratory alkalo-
bolic acidosis sis with mild hypoxemia
2. Compensated metabolic alkalosis with
EXERCISE 2-6 Alternative severe hypoxemia
Terminology 3. Uncompensated respiratory acidosis with
1. Failure moderate hypoxemia
2. Temporal 4. Compensated respiratory alkalosis with
3. Acute hyperoxemia
4. Respiratory 5. Mixed (combined) alkalosis with moder-
5. a. Chronic respiratory acidosis or chronic ate hypoxemia
ventilatory failure 6. Partially compensated metabolic alkalosis
b. Acute respiratory acidosis or acute ven- with mild hypoxemia
tilatory failure 7. Normal acid-base status with hyperoxemia
c. Acute respiratory alkalosis 8. Uncompensated metabolic alkalosis with
d. Uncompensated metabolic acidosis moderate hypoxemia
(remember that temporal adjectives are 9. Uncompensated metabolic alkalosis with
inappropriate for primary metabolic normoxemia
problems) 10. Normal acid-base status with normoxemia
e. Acute respiratory alkalosis
f. Uncompensated metabolic alkalosis EXERCISE 2-10 Complete Blood Gas
Classification Using [BE] as the
EXERCISE 2-7 Oxygenation Metabolic Index
Assessment 1. Partially compensated metabolic acidosis
1. PaO2 with moderate hypoxemia
2. 80 to 100 mm Hg 2. Mixed (combined) respiratory and meta-
3. Normoxemia bolic alkalosis with severe hypoxemia
4. Hypoxemia 3. Uncompensated metabolic acidosis with
5. Partial pressure hyperoxemia
6. Hyperoxemia 4. Respiratory alkalosis and metabolic aci-
7. Lower dosis with normoxemia (perhaps this is
8. Is not complete compensation, but given only
9. 90% this information, one cannot be sure of
10. Cardiovascular the precise primary problem)
11. Should 5. Mixed acidosis with mild hypoxemia
12. 45 6. Uncompensated respiratory acidosis with
normoxemia
EXERCISE 2-8 PaO2 Classification 7. Uncompensated respiratory alkalosis with
Adults mild hypoxemia
1. Hyperoxemia 8. Partially compensated metabolic acidosis
2. Severe hypoxemia with severe hypoxemia
Answers 465
9. Compensated respiratory acidosis with 2. C) Compensation for severe metabolic

moderate hypoxemia acidosis. The basic primary acid-base distur-
10. Normal acid-base status with bance is metabolic and not respiratory. The
hyperoxemia respiratory hyperventilation is compensatory
or a secondary acid-base disturbance. This sit-
EXERCISE 2-11 Complete Blood uation is compatible with diabetic ketoacido-
Gas Classification: Additional Examples sis and the deep breathing pattern (Kussmauls
Set A breathing) that accompanies it. Therapy
1. Mixed acidosis with moderate hypoxemia must be directed at the primary disturbance
2. Uncompensated respiratory alkalosis with and not the bodys compensatory mechanisms.
severe hypoxemia 3. E) COPD. This is a classic blood gas for
3. Normal acid-base status with hyperoxemia compensated respiratory acidosis or
4. Partially compensated metabolic acidosis chronic ventilatory failure. COPD is like-
with normoxemia wise the classic cause of chronic ventilatory
5. Uncompensated respiratory acidosis with failure. The elevated bicarbonate and rela-
mild hypoxemia tively normal pH are essential clues to this
6. Partially compensated respiratory acidosis determination.
with normoxemia 4. C) Oxygen mask. The most critical
7. Mixed alkalosis with severe hypoxemia problem with this blood gas is the severe
8. Compensated metabolic acidosis with hypoxemia. Remember, it is wise to assume
severe hypoxemia severe hypoxemia will result in hypoxia.
9. Compensated metabolic alkalosis with Hypoxia is life-threatening and must be
normoxemia treated immediately and aggressively. An
10. Compensated respiratory acidosis with oxygen mask will deliver more oxygen faster
hyperoxemia than a nasal cannula; therefore, it is the
treatment of choice. The uncompensated
Set B respiratory alkalosis is a normal response
1. Uncompensated respiratory alkalosis with of the body to severe hypoxemia and will
normoxemia be corrected if PaO2 returns to normal.
2. Partially compensated respiratory acidosis 5. C) Primary respiratory acidosis and pri-
with severe hypoxemia mary metabolic acidosis (mixed acidosis)
3. Mixed acidosis with moderate hypoxemia and likely hypoxia secondary to severe
4. Uncompensated respiratory alkalosis with hypoxemia. The tissue hypoxia appears to
hyperoxemia be causing lactic (metabolic) acidosis.
5. Partially compensated metabolic acidosis
with moderate hypoxemia
6. Mixed acidosis with mild hypoxemia CHAPTER 3
7. Normal acid-base status with hyperoxemia
8. Uncompensated metabolic alkalosis with ON-CALL CASE 3-1 ABGs and Critical
moderate hypoxemia Thinking
9. Mixed alkalosis with normoxemia Assessment
10. Partially compensated respiratory acidosis Abnormalities:
with normoxemia pH
PaCO2
PaO2
NBRC Challenge 2
It is noteworthy that the sample contained froth.
1. A) Mechanical ventilation. Patient has
uncompensated respiratory acidosis, which Explanation:
is also known as acute ventilatory failure. A PaO2 of 153 mm Hg on room air indicates a
Treatment for ventilatory failure is to technical error. Samples with froth should be
re-establish adequate ventilation. discarded because they obviously contain a
466 Answers
substantial amount of air. The most pro- 4. Barometer

nounced effect of air contamination in a blood 5. 760 mm Hg
gas sample is a change in PaO2. The maximum 6. Decreased
PaO2 attainable with room air and hyperventi- 7. Daltons law states that the sum of the
lation is only approximately 130 mm Hg. The partial pressures in a mixture of gases is
decrease in PaCO2 and increase in pH could equal to the total pressure.
also be attributable to air contamination 8. Kinetic
because the PCO2 in room air is near zero and a 9. Will not
low PaCO2 would increase pH. A repeat blood 10. Will not
gas sample is necessary to provide information 11. Fractional concentration of inspired oxy-
about this patients oxygenation and acid-base gen in a dry gas phase
status. Treatment and intervention cannot be 12. a. 150 mm Hg
based on this obviously erroneous data. b. 137 mm Hg
c. 340 mm Hg
ON-CALL CASE 3-2 ABGs and Critical d. 232 mm Hg
Thinking e. 483 mm Hg
Assessment 13. Gay-Lussacs law states that if volume and
Abnormalities: mass remain fixed, the pressure exerted by
SaO2 B/P a gas varies directly with the absolute tem-
pH RR perature of the gas.
PaCO2 HR 14. Body temperature and pressure saturated
PaO2 Fever (37 C, 760 mm Hg, 47 mm Hg water
Normal [HCO3] SpO2 vapor)
15. 150 mm Hg
Explanation: 16. Henrys law states that when a gas is
It is noteworthy that an experienced clinician exposed to a liquid, the partial pressure of
observed a flash of blood and auto-filling a gas in a liquid phase equilibrates with
of the syringe. Although the PaO2 is the same the partial pressure of a gas in a gaseous
as normal mixed venous PO2, other clinical phase.
information tends to confirm that this is an 17. Charles law: Pressure is constant (remem-
arterial sample. For example, the pulse oxime- ber that Charles law is always the same
ter also indicates hypoxemia and the presence pressure [acronym CLASP]).98
of cyanosis suggests a problem with oxygena- Boyles law: Temperature is constant
tion. Cardiopulmonary stress is also apparent (remember that Boyles law is always the
from the elevated vital signs and hypocarbia, same temperature [acronym BLAST]).
which again is suggestive of an oxygenation Gay-Lussacs law: Volume is constant.98
disturbance. A venous sample cannot be 18. a (lowercase)
identified or confirmed by blood gas values 19. Humidification and external respiration
alone. Sick patients may indeed have arterial 20. Absolute, potential
values that resemble normal venous values.
Looking at the entire situation, data, and EXERCISE 3-2 Air in Blood Gas Samples
patient description, it appears that this is an 1. Are not
arterial sample from a severely hypoxemic 2. (c) Change in PaO2
patient. 3. Is not
4. Duration of exposure
5. Greater than
EXERCISES 6. a. Increased
b. Increased
EXERCISE 3-1 Basic Physics of Gases c. Decreased
1. Brownian movement d. Increased
2. Pressure is defined as force per unit area. e. Decreased
3. Water vapor pressure 7. Is not
Answers 467
8. 2 EXERCISE 3-6 Temperature Effects on

9. Decrease Blood Gases
10. Increase 1. High
2. 5
EXERCISE 3-3 Venous Sampling or 3. 0.03 (see Table 3-8)
Admixture 4. 10%
1. Will 5. Not be
2. Discarded
3. Short EXERCISE 3-7 Summary of Potential
4. Does not necessarily mean Sampling Errors
5. Is not Air in the blood sample
6. Pulmonary artery Venous sampling or admixture
7. Pv-O2 = 40 mm Hg Excessive or improper anticoagulant
Pv-CO2 = 48 mm Hg Rate of metabolism
Sv-O2 = 75% Temperature disparities between patient and
8. Femoral machine (see Box 3-1)
EXERCISE 3-4 Blood Gas EXERCISE 3-8 Blood Gas / Electrolyte

Anticoagulation Specimens
1. Lithium heparin 1. Will
Sodium 2. Balanced
2. 1000 U/mL 3. Mixing
3. Decreased PCO2 4. PPACK
4. Is not 5. Elevate
5. Dilution
6. Low (because of the dilution effect)
NBRC Challenge 3
7. 2 mL
8. 1% 1. A) PaO2. Because the increased leukocytes
9. a. New syringe designs will consume oxygen from the sample more
b. Use of dry, crystalline heparin quickly than normal.
2. D) I & II only. The partial pressures of
EXERCISE 3-5 Blood Gas Error Due gases have the greatest effect with pH of the
to Metabolism heparin also having some effect.
1. Does 3. B) II & III. A bluish sample suggests possi-
2. PaO2 decreases ble venous blood as does failure of the
PaCO2 increases syringe to auto-fill.
pH decreases 4. C) III only. Temperature correction is easily
3. 5 mm Hg accomplished but generally not recom-
0.05 mended for clinical application.
4. High 5. D) Electrolytes. Icing samples leads to
5. Half hemolysis and elevated potassium and
6. 10% decreased ionized calcium.
7. 30
8. 30
9. Is not CHAPTER 4
10. Leukocytes (white blood cells)
Reticulocytes (immature red blood cells) ON-CALL CASE 4-1 ABGs and Critical
Platelets Thinking
11. Leukocyte larceny Assessment
12. 2 Abnormalities:
13. Leukocytosis SaO2
14. More PaO2
468 Answers
Patient is known to have thrombocytosis. At BTPS, the PaO2 would actually be 48 mm Hg.
Pulse oximeter reading is inconsistent with Therefore, this patient is quite hypoxemic.
ABG saturation. Furthermore, the high temperature would lead
to increased metabolism and oxygen need.
Explanation: Thus, the patient is in dire need of oxygen.
The PaO2 on the blood gas report may be sur- This fact is somewhat obscured because blood
prisingly low due to the presence of thrombo- gases are temperature-corrected and provides
cytosis. Remember, very high white blood cell an example as to why temperature correction
counts, platelet counts, or reticulocyte counts, is not advocated and may be misleading.
could lead to excessive oxygen consumption
from within the blood gas sample due to the Intervention
high metabolism of these cells. This is the same Importance:
phenomenon that occurs with leukemia and Clearly, oxygen therapy is in dire need.
leukocyte larceny and could explain the low
PaO2 seen despite a very good pulse oximeter Objective:
reading. The saturation on the blood gas Get (BTPS) PaO2 to an acceptable level
report, which is a calculated value, is also low (e.g., 80100 mm Hg) as a first priority.
because it is calculated based on PaO2. Secondary issues include bronchial hygiene
needs, chest radiography, possibly sputum cul-
Evaluation: ture, and identification of the type of pneumonia
Additional useful information would be vital present.
signs to determine if there are any other phys-
iologic indications of hypoxemia. If an addi- Action:
tional blood gas is drawn, it should be Place the patient on an oxygen mask.
acquired in an iced, glass syringe and analyzed Interpret all future blood gases at BTPS. If
as quickly as possible after acquisition to min- blood gas values are reported at a temperature
imize error due to continued metabolism. other than BTPS, BTPS values should be
Analysis of saturation via CO-oximetry would recorded along with temperature-corrected
also be useful to determine precise saturation. values.
ON-CALL CASE 4-2 ABGs and Critical

Thinking EXERCISES
Assessment
Abnormalities: EXERCISE 4-1 Basic Electrical
PaO2 Principles
SaO2 1. Electricity
pH 2. Cathode, anode
Patient is severely febrile (41 C). 3. Electromotive
Blood gases have been temperature corrected. 4. Volt
5. Potentiometer
Explanation: 6. Ampere
The patient seems only mildly hypoxemic; 7. Ohm
however, the blood gases have been temperature- 8. Voltage = amp ohm
corrected and normal values are not known 9. Watts
for this temperature. Blood gases should be 10. Conductor
interpreted at BTPS where normal values are
known. EXERCISE 4-2 Electrodes and
Terminology
Evaluation: 1. Electrochemical cell systems
Additional useful information would be blood 2. An entire measuring system for one of the
gas values at normal body temperature. blood gases
Answers 469
3. Electrode terminal EXERCISE 4-7 Quality Control and

4. Metal, glass Statistics
5. Half-cell 1. Quality control
6. Working half-cells 2. Proficiency testing
Reference half-cells 3. Mean
7. Working (or measuring) 4. Standard deviation
5. 68%
EXERCISE 4-3 The PO2 Electrode 6. 95%
1. Ammeter 7. PaO2 = 5 mm Hg standard deviation
2. Platinum PaCO2 = 2.5 mm Hg standard
3. Silver chloride deviation
4. Consumes 8. Less
5. Polarographic 9. Coefficient of variation (CV)
6. Clark 10. Percent (%)
7. Polypropylene
8. Cuvette EXERCISE 4-8 Quality Control Charts1
9. Anode 1. Controls, or control samples
10. Voltage 2. 2 levels, 8 hours
3. Performance records
EXERCISE 4-4 The pH Electrode Quality control charts
1. Glass 4. Levey-Jennings
2. Working 5. Systematic error
3. Is not 6. Trending
4. Potentiometric 7. Shifting
5. Nernst equation 8. Random error
6. Silver chloride 9. Dispersion
7. Calomel 10. In control
8. Mercury/mercurous chloride
9. Liquid junction EXERCISE 4-9 Quality Control Charts2
10. Calomel 1. Accuracy
2. Precision
EXERCISE 4-5 The PCO2 Electrode 3. Precision
1. Does not 4. Accuracy
2. Teflon or silicone rubber 5. Aging of the electrode or battery
3. Bicarbonate Protein contamination
4. 2 6. 0.02 pH units
5. Is not 7. Alkaline
6. Hydrolysis 8. 1% to 2%
7. Severinghaus 9. Results
8. Voltage 10. Two
9. 1
10. PO2 EXERCISE 4-10 Types of
Controls
EXERCISE 4-6 Quality 1. Do not
Assurance/Preventive 2. Do not
Maintenance 3. Tonometer
1. Clinical 4. Time
2. Quality assurance 5. An infectious risk
3. Analytical 6. Emulsions
4. 0.1 7. Emulsions
5. 1 to 3 min 8. Commercially
470 Answers
9. PO2 Explanation:
10. Fluorocarbon The acid-base data cannot be explained
because they are not internally consistent.
EXERCISE 4-11 Continuous Blood
Gas Monitoring Evaluation:
1. Measurement The clinician should call the lab to double-
2. Do not check the laboratory results.
3. In vivo
4. Clark Intervention
5. Must Importance:
6. Oxygen or carbon dioxide If internally consistent results are not avail-
7. Cardiac output able, a repeat sample is necessary. Therapeutic
8. Gas Stat system intervention should not occur until we are sure
9. Wall we have reliable data. The administration
10. Ex vivo (on demand) of bicarbonate (although commonplace years
ago during cardiac arrest) is inappropriate for
two reasons. First, and most important, one
NBRC Challenge 4
should never administer bicarbonate to a patient
1. A) The cathode should be cleaned and the with a pH of 7.52. The pH should be the
membrane should be changed. primary focus of acid-base treatment and not
2. B) II and IV only. This is proficiency simply the [BE], [HCO3], or PaCO2. Second,
testing for external quality control and helps one should never initiate treatment when acid-
evaluate accuracy not precision. base data are not internally consistent. Upon
3. B) Trending is a form of systematic error calling the laboratory, it was found that the
that may result from these conditions. [BE] was actually + 11 mEq/L and there was an
4. D) Precision error in the telephone report. Administration
5. C) CIABG. Measurement of tissue wall PO2 of bicarbonate to this patient was totally
may occur with these devices. inappropriate and could be life-threatening.
Recognition of lack of internal consistency
could have been life-saving.
CHAPTER 5
ON-CALL CASE 5-1 ABGs and Critical Thinking
Thinking Assessment
Assessment Abnormalities:
Abnormalities: SaO2
SaO2 pH
pH PaCO2
PaCO2 [HCO3]
[BE] [BE]
PaO2 PaO2
ABG classification: The blood gas cannot be ABG classification: Uncompensated respiratory
classified because it is not internally consistent. acidosis (acute ventilatory failure) with moder-
It is not possible to have a high pH (alkalemia) ate hypoxemia. (Note this blood gas would
when both a respiratory acidosis (increased have been classified as a partially compensated
PaCO2) and metabolic acidosis (decreased respiratory acidosis using the rules described in
[BE]) are present. There must be an error in the Chapter 2. See discussion, which follows under
data reported. It is noteworthy that this was a explanation.) Plasma bicarbonate is elevated
telephone report, which could have resulted in whereas the base excess of the blood (another
a miscommunication of data. metabolic index) is decreased.
Answers 471
Explanation: 7. Acidosis
The data are consistent with a drug overdose 8. Alkalosis
and acute respiratory acidosis. The hypoxemia 9. Normal
is likely a result of simple hypoventilation. The 10. Can
apparently conflicting messages regarding meta-
bolic status provided by the bicarbonate and EXERCISE 5-3 Calculation of
base excess simply represents flaws in these Expected pH
indices associated with hypercapnia. Again, the
bicarbonate level is elevated due to hydrolysis in In Hypocarbia: Expected pH = 7.40 + (40 mm
hypercapnia and the base excess of the blood is Hg PaCO2)0.01
decreased due to in vitroin vivo discrepancies. In Hypercarbia: Expected pH = 7.40 (PaCO2
These values are normal for acute respiratory aci- 40 mm Hg)0.006
dosis and do not represent renal compensation. 1. Expected pH = 7.40 (50 mm Hg
40 mm Hg)0.006
Evaluation: Expected pH = 7.40 0.06
A drug screen and history and physical exami- Expected pH = 7.34
nation are indicated. 2. Expected pH = 7.40 (60 mm Hg
40 mm Hg)0.006
Intervention Expected pH = 7.28
Importance: 3. Expected pH = 7.40 + (40 mm Hg
Immediate intervention might include a nar- PaCO2)0.01
cotic antagonist. If this was not effective, intu- Expected pH = 7.40 + (40 mm Hg
bation to ensure a patent and protected airway 25 mm Hg)0.01
and mechanical ventilation to restore normal Expected pH = 7.40 + 0.15
ventilation and acid-base balance would be Expected pH = 7.55
indicated. 4. Expected pH = 7.25
5. Expected pH = 7.60
EXERCISES 7. Expected pH = 7.22
EXERCISE 5-1 Gross Inconsistency 9. Expected pH = 7.58
1. I 10. Expected pH = 7.37
2. C
3. I EXERCISE 5-4 Indirect Metabolic
4. I Assessment
5. I Actual pH Expected pH Indirect Metabolic
6. C Relationship Status
7. C Actual pH = expected Normal metabolic
8. C pH 0.03 status
9. I Actual pH > expected Metabolic alkalosis
10. C pH + 0.03
Actual pH < expected Metabolic acidosis
EXERCISE 5-2 Principles of Indirect pH 0.03
Metabolic Assessment
Actual Expected Indirect
1. Can pH pH Metabolic
2. 0.10 Status
3. 0.06 1. 7.34 = 7.34 Normal metabolic
4. 7.60 status
5. 7.22 2. 7.30 = 7.28 + 0.02 Normal metabolic
6. Normal status
472 Answers
3. 7.52 = 7.55 0.03 Normal metabolic EXERCISE 5-7 pH [H+] Conversion

status pH
4. 7.15 < 7.25 Metabolic acidosis 1. 7.35
5. 7.62 = 7.60 + 0.02 Normal metabolic 2. 7.24
status 3. 7.48
6. 7.56 > 7.50 Metabolic alkalosis 4. 7.50
7. 7.38 > 7.22 Metabolic alkalosis 5. 7.32
(probably 6. Linear relationship does not hold true outside
compensatory) the range of 7.20 to 7.50 (3060 nEq/L)
(probably 9. 7.52 (Again, remember that the linear
compensatory) relationship begins to deteriorate beyond
10. 7.34 = 7.37 0.03 Normal metabolic 7.50; nevertheless, this is a reasonable
status estimate.)
10. 7.29
EXERCISE 5-5 Accuracy Check
by Comparing Direct and Indirect EXERCISE 5-8 Application of Modified
Metabolic Status Hendersons Equation
Indirect Direct Consistency
Status Status pH [H+] PaCO2 [HCO3]
1. Normal Normal Consistent (nEq/L) (mm Hg) (mEq/L)
2. Normal Alkalosis Inconsistent 1. 7.32 48
3. Normal Acidosis Inconsistent 2. 7.43 37
4. Acidosis Normal Inconsistent 3. 7.47 33
5. Normal Normal Consistent 4. 60 20
6. Alkalosis Alkalosis Consistent 5. 7.40 40
7. Alkalosis Normal Inconsistent 6. 50 50
8. Acidosis Acidosis Consistent 7. 7.50 30
9. Acidosis Normal Inconsistent 8. 7.20 45
10. Normal Alkalosis Inconsistent 9. 7.40 18
10. 52 18
EXERCISE 5-6 The Rule of Eights in EXERCISE 5-9 Calculation of [HCO3]

Accuracy Check From Total CO2
(Factor PaCO2) = predicted bicarbonate 1. 36.2 mEq/L
2. 24.8 mEq/L
pH Factor
3. 16.5 mEq/L
7.60 8/8
7.50 6/8 4. 19.2 mEq/L
7.40 5/8 5. 20.0 mEq/L
7.30 4/8
7.20 2.5/8 EXERCISE 5-10 Metabolic Indices
7.10 2/8 1. CO2 combining power
Total CO2
Predicted Actual Consistency 2. Does not
1. 30 28 C 3. Does
2. 42 40 C 4. 10 mm Hg
3. 22.5 29 I
5. 5 mm Hg
4. 9 20 I
6. Standard bicarbonate
5. 15 25 I
6. 40 39 C 7. Low
7. 10 9 C 8. T40 standard bicarbonate
8. 50 30 I 9. Whole blood buffer base ([BB])
9. 19 19 C 10. Base excess ([BE]) or [BE] blood
10. 17.5 10 I 11. Low
Answers 473
12. In vitro Explanation:

13. [BE]ecf Given postoperative leg surgery in an elderly
14. [Hb] 5 g% individual, there should be a high index of
15. 0.10 units suspicion for pulmonary emboli. The high
minute ventilation PaCO2 disparity and the
abrupt onset of shortness of breath are also
NBRC Challenge 5
typical of pulmonary embolus. Hemoptysis,
1. C) The blood gas should be checked and/ chest pain, and hypoxemia are also frequent
or run again. It is impossible to have a findings. Elevation in vital signs (increased
respiratory and metabolic acidosis and a HR/BP) is most likely secondary to moderate
high pH. hypoxemia.
2. E) Increased plasma bicarbonate due to
hydrolysis. The bicarbonate will go up Evaluation:
roughly 1 mEq/L for each 10 mm Hg Pulmonary angiography confirms the diagnosis.
acute increase in PaCO2. Therefore, this A lung perfusion scan is inconclusive because
blood gas represents a simple acute res- perfusion will tend to match ventilation in pri-
piratory acidosis with a bicarbonate mary ventilatory disturbances.
elevation secondary to hydrolysis, not
compensation. Intervention
3. D) The blood gas and pulse oximeter Importance:
readings are incongruent. Saturation is very First priority is to get oxygenation at an
different from partial pressure. When acceptable level.
SpO2 is 90%, PaO2 is typically about Anticoagulant or thrombolytic drug therapy
60 mm Hg. should also be initiated.
4. D) 7.55. The acute PaCO2pH relationship
would apply. For every 1 mm Hg drop in ON-CALL CASE 6-2 ABGs and Critical
PaCO2, pH will acutely increase approxi- Thinking
mately 0.01 units. Assessment
5. D) The change in [BE] and [HCO3] is due Abnormalities:
to hypercapnia. This blood gas shows how SaO2 B/P
acute hypercapnia will affect bicarbonate pH HR
and base excess of the blood in opposing PaCO2 Temperature
directions. PaO2 RR
Normal [HCO3]
ABG classification: Uncompensated respiratory
CHAPTER 6 alkalosis with moderate hypoxemia.
ON-CALL CASE 6-1 ABGs and Critical Explanation:
Thinking Given postoperative abdominal status,
Assessment patients may avoid deep breathing due to pain
Abnormalities: and anesthesia that may lead to atelectasis
SaO2 B/P (collapsed alveoli) and pneumonia (lung infec-
Normal pH HR tion). Elevated temperature (fever) and hypox-
Normal PaCO2 Normal temperature emia suggest pulmonary shunting, and we
PaO2 RR. need to be concerned about progressive shunt
Normal [HCO3] V producing disease (e.g., pneumonia/atelectasis)
ABG classification: Normal acid-base status following surgery. Elevation in vital signs
with moderate hypoxemia. Large minute ven- (increased HR/BP) and hyperventilation (low
tilation PaCO2 disparity suggests deadspace PaCO2) are most likely secondary to moderate
disease. In normal lungs, tripling the minute hypoxemia. Remember, when there is a prob-
ventilation should result in a PaCO2 of lem with low blood oxygenation (hypoxemia),
approximately 25 mm Hg. the circulatory system attempts to compensate
474 Answers
(increased HR/BP) and assure tissue oxygena- 7. More

tion. Hyperventilation also ensues. 8. Secondary polycythemia
9. Blood
Evaluation: 10. Hypoxia
Additional data: Chest radiograph, [WBC], 11. May be
sputum cultureto identify potential microbes, 12. May be
would all help to facilitate definitive diagnosis.
White-out on chest radiograph and/or increased EXERCISE 6-2 External Respiration
white blood cells (leukocytosis) confirms bacte- and Normal Pulmonary
rial pneumonia. Perfusion
1. a. Adequate ventilation
Intervention b. Adequate ventilation-perfusion
Importance: match
First priority is to get oxygenation to an c. Adequate diffusion
acceptable level. 2. PaCO2
If pneumonia and secretions are present, 3. Partial pressure of O2 (PO2)
antibiotics and bronchial hygiene (secretion 4. 60 mm Hg
removal) are indicated. Most abnormal labo- 5. Most
ratory data will normalize if the root problem 6. Absent
is corrected. 7. Is not
8. 2
Objective: 9. 3
The first goal is to get the PaO2 and/or SpO2 10. 1
in an acceptable adult range.
EXERCISE 6-3 Normal Distribution
Action: of Ventilation
Place the patient on a moderately high FIO2 1. Compliance
(e.g., 50% aerosol mask would also provide Resistance
humidity to loosen secretions). Monitor with 2. Apices
pulse oximetry to ensure saturation moves to 3. More
an acceptable range. Encourage deep breathing 4. (+2 cm H2O) (8 cm H2O) =
with incentive spirometry. (+2 cm H2O + 8 cm H2O) = 10 cm H2O
5. Larger
6. Compressive
EXERCISES 7. Higher
8. Bases
EXERCISE 6-1 Introduction to 9. Tidal volume
Oxygenation 10. More
1. Cardiopulmonary
2. The exchange of O2 and CO2 between the EXERCISE 6-4 Abnormal Pulmonary
alveoli and the pulmonary capillaries Perfusion
3. The quantitative movement of a sufficient 1. Compensatory
volume of O2 from the pulmonary capillar- 2. Generalized
ies to its cellular destination 3. Higher
4. The exchange of O2 and CO2 between the 4. a. Heart failure (decreased cardiac output)
systemic capillaries and the body cells or b. Positive pressure ventilation
tissue 5. The perfusion zones may shift downward
5. Quantitative if an increased pulmonary vascular resist-
6. O2 loading ance is associated with a weak or damaged
O2 transport heart that could not increase the force of
O2 unloading contraction.
Answers 475
6. a. Acidemia EXERCISE 6-8 Physiologic Shunting

b. Hypoxemia 1. Lower
7. Pulmonary fibrosis or COPD 2. Silent
8. PAO2 3. Anatomic and capillary
4. 2%
EXERCISE 6-5 Abnormal Distribution 5. Bronchial
of Ventilation Pleural
1. Will Thebesian
2. Secretions 6. True (absolute)
3. Airway resistance Relative
4. Airway resistance 7. Absolute
5. Gravity 8. (Any 2)
6. Decrease Pneumonia
7. Obese Pulmonary edema
8. Smokers Atelectasis
9. Supine 9. Approximately 1%
10. 44 years of age 10. Hypoxemia
11. PACO2
EXERCISE 6-9 Diffusion
EXERCISE 6-6 Ventilation-Perfusion 1. Equilibration time, adequate surface
Matching area
1. Cardiac minute output 2. Pulmonary capillary transit
2. Alveolar minute ventilation 3. 0.75 sec
3. 1/1 4. 0.25 sec
4. More 5. Smaller
5. 0.8 6. Faster
6. 3 7. Grahams law
7. 0.6 8. 1
8. 130 mm Hg 9. Decreased
9. True capillary shunt 10. 70 m2
10. True alveolar deadspace
EXERCISE 6-7 Physiologic NBRC Challenge 6

Deadspace 1. D) Physiologic deadspace measurement will
1. No be increased in the presence of deadspace
2. Higher disease (e.g., decreased cardiac output, pul-
3. 200 mL monary embolus) or application of mechan-
4. Low ical ventilation.
5. Physiologic 2. E) To calculate physiologic deadspace, mean
6. 0.5 exhaled gas must be collected in a Douglas
7. Mean bag and the average PCO2 measured.
8. 0.2 to 0.4 3. D) The Acute Respiratory Distress Syndrome
9. Less than 0.6 and congenital heart defects (shunt-producing
10. Mechanical deadspace diseases) may lead to elevated pulmonary
11. Wasted shunt fractions. Although a slight increase in
12. Increase the shunt may accompany pulmonary embo-
13. Will not lus, it is primarily a deadspace producing
14. 30 mm Hg disease.
15. Increased physiologic deadspace 4. A) Tuberculosis is most often seen in the
16. Normal deadspace upper lung zones due to the high PO2
17. Carbon dioxide (CO2) levels in this area.
476 Answers
5. C) A decrease in PaO2 during exercise sug- [HCO3] B/P

gests a problem with lung diffusion such as PaO2
pulmonary fibrosis. ABG classification: Uncompensated metabolic
acidosis with mild hypoxemia. The patient
appears to be in cardiopulmonary distress and
CHAPTER 7 shows signs and symptoms of shock (cold and
clammy). The B/P is very low.
Thinking Explanation:
Assessment The data are consistent with shock and circu-
Abnormalities: latory hypoxia. Again, despite the fact that
pH HR oxygenation appears acceptable according to
Normal PaCO2 B/P the blood gases, the patient has substantial
[HCO3] [Hb] circulatory hypoxia, which needs to be cor-
Normoxemia RR rected immediately. The concurrent metabolic
ABG classification: Uncompensated metabolic acidosis suggests lactic acidosis secondary to
acidosis with normoxemia. hypoxia.
The PaO2 is only 94 mm Hg on FIO2 of
0.60. Oxygenation ration 1.3. The [Hb] is one, Evaluation:
third of normal. The source of the hypotension must be sought.
It could be due to cardiac pump failure, hypo-
Explanation: volemia, or systemic vasodilation.
The data are consistent with severe anemia and
a substantial decrease in arterial oxygen con- Intervention
tent; probably secondary to bleeding following Importance:
surgery. Despite the fact that oxygenation Intervention depends on the nature of the
appears acceptable via the blood gases, the cardiovascular disturbance but should aim
patient has severe anemic hypoxia, which to improve cardiovascular status and blood
needs to be corrected immediately. The con- pressure.
current metabolic acidosis suggests lactic
acidosis secondary to hypoxia.
EXERCISES
Evaluation:
Although the heart rate and blood pressure are EXERCISE 7-1 Oxygen Transport
slightly elevated, the patient should be evalu- 1. Dissolved oxygen
ated for hypovolemia and bleeding. Auscultation Combined oxygen
and a chest radiograph would be indicated to 2. 0.003 mL O2/100 mL blood/mm Hg
evaluate the poor oxygenation ratio. 3. Vol%
4. Decrease
Intervention 5. Linear
Importance: 6. Hemoglobin
Immediate intervention would include a trans- 7. Iron (Fe)
fusion to ensure sufficient hemoglobin for Porphyrin
carrying oxygen. 8. 4
9. SaO2
ON-CALL CASE 7-2 ABGs and Critical 10. Combined
Thinking
Assessment EXERCISE 7-2 Oxyhemoglobin
Abnormalities: Dissociation Curve
pH HR 1. PaO2
PaCO2 RR 2. Nonlinear
Answers 477
3. 26 mm Hg 4. 12.81 vol%
60 mm Hg 18.60 vol%
250 mm Hg 9.34 vol%
4. Large 5. 20 vol%
5. Small 6. 40 mm Hg
6. Association 75%
7. End 7. 5.0 vol%
8. 97%98% 8. Fick
9. 90% 9. Increases
10. Upper 10. 250 mL/min
Lower
EXERCISE 7-6 Cyanosis
EXERCISE 7-3 Oxyhemoglobin 1. Cyanosis
Affinity 2. Peripheral
1. P50 3. Mucous membranes
2. 26 mm Hg 4. 20% desaturated
3. PCO2 5. Average 5 g% desaturated Hb in
pH capillaries
Temperature 6. 2 g%
DPG 7. Anemia
4. Right 8. Polycythemia
Decreased 9. (100% 80% = 20% Hb desat in arterial
5. Bohr blood)
6. Detrimental (100% 60% = 40% Hb desat in venous
7. Unloading blood)
8. Decrease (20 g% 0.2) + (20 g% 0.4)/2
Increase (4 g%) + (8 g%)/2 = 6 g% Hb desat in
9. 7.40 capillaries
40 mm Hg Because the average amount of Hb desat
10. Men in the capillaries of this patient is more
than 5 g%, this patient appears cyanotic.
EXERCISE 7-4 2,3-Diphosphoglycerate 10. (100% 80% = 20% Hb desat in arterial
1. Decreases blood)
2. Abundant (100% 60% = 40% Hb desat in venous
3. Unloading blood)
4. Increase (10 g% 0.2) + (10 g% 0.4)/2
5. Infusion of stored blood (2 g%) + (4 g%)/2 = 3 g% Hb desat in
6. Possible capillaries
7. 24 hours Because the average amount of Hb desat
8. Decreased in the capillaries of this patient is less than
9. Sustained 5 g%, this patient does not appear cyanotic.
10. Acid-citrate dextrose
EXERCISE 7-7 O2 Transport/
EXERCISE 7-5 Oxygen Content HbCO/HbF
1. CaO2 1. 15 mL O2/min
2. 0.3 vol% 2. 1000 mL O2/min
0.18 vol% 3. 750.18 mL O2/min
1.2 vol% 499.95 mL O2/min
3. 19.095 vol% 418.02 mL O2/min
14.472 vol% 4. 245 times
10.72 vol% 5. Carboxyhemoglobin
478 Answers
6. HbCO is incapable of carrying O2. 4. B) A low cardiac output is the classic cause
HbCO shifts the oxyhemoglobin curve of an increased arteriovenous difference.
to the left. 5. E) Lipogenesis secondary to a high car-
7. 20 mm Hg bohydrate intake can result in an RQ as high
8. Greater as 1.3.
9. CO-oximeter
10. 80%
CHAPTER 8
EXERCISE 7-8 Methemoglobinemia and
Sickle Cell Disease ON-CALL CASE 8-1 ABGs and Critical
1. Methemoglobin Thinking
2. Methemoglobinemia Assessment
3. Methemoglobinemia Abnormalities:
4. Methylene blue pH
5. Cyanosis PaCO2
6. HbF [HCO3]
7. Chest pain PaO2
Fever SaO2
Leukocytosis ABG classification: Mixed respiratory acido-
8. 85% sis and metabolic acidosis with moderate
9. metHb hypoxemia.
10. 10%
Explanation:
EXERCISE 7-9 Internal Respiration Regarding acid-base, the metabolic acidosis is
1. Decreased O2, decreased pH, increased likely due to the renal failure described. The
temperature, increased CO2 recent respiratory acidosis is most likely due to
2. 11 vol% in the heart the administration of bicarbonate to a patient
1 vol% in the skin with controlled ventilation. Bicarbonate will
3. Mitochondria produce CO2 via the hydrolysis reaction that is
4. 10% normally excreted; however, this patient can-
5. 0.8 not increase alveolar ventilation; therefore,
6. 1.0 PaCO2 rises. The worsening hypoxemia is
7. 10 probably secondary to the acute hypercapnia
8. Krebs cycle superimposed on the pulmonary shunting from
9. Lactic acid the acute respiratory distress syndrome (ARDS).
10. Central No additional data are needed to confirm
11. 1.3 the interpretation.
Intervention
NBRC Challenge 7
Importance:
1. D) CO-oximetry. It is likely the patient An increase in alveolar ventilation would nor-
has methemoglobinemia because it may malize the PaCO2. This would improve acid-
be observed following administration of base balance as well as oxygenation. This is
topical anesthetics and appears as abrupt probably best done by increasing the respira-
cyanosis. tory rate while avoiding dangerous lung pres-
2. B) Methylene blue I.V. sures in ARDS. If this could not be done
3. E) II, III, and IV only. Hypercapnia and without increasing lung pressures significantly,
acidemia could cause this due to a right shift an alternative would be permissive hypercap-
of the oxyhemoglobin curve. Alternatively, nia. However, in this case, FIO2 or positive
some forms of abnormal Hb species may end-expiratory pressure (PEEP) would have to
also have decreased affinity for oxygen. be used to increase oxygenation and more
Answers 479
bicarbonate may need to be administered if 10. Acid

one wanted to keep the pH > 7.30. 11. Lungs
12. Volatile
ON-CALL CASE 8-2 ABGs and Critical 13. Carbonic acid (H2CO3)
Thinking 14. Kidneys
Assessment 15. Bicarbonate (HCO3)
Abnormalities:
pH EXERCISE 8-2 Underlying Chemistry of
PaCO2 H2CO3 Regulation
Normal [HCO3] 1. Does not
Normal oxygenation 2. Closed
ABG classification: Uncompensated respira- 3. Left
tory alkalosis with normoxemia while breath- 4. Law of mass action
ing FIO2 0.4. 5. Left

6. H 2O + CO 2 H 2CO 3 HCO 3 +

Explanation: H+
Regarding acid-base balance, the mechanical 7. Direct, linear
deadspace did not increase PaCO2 as intended 8. PaCO2
but, in fact, PaCO2 decreased. Mechanical 9. Increase
deadspace is ineffective in the patient who sim- 10. Acidic
ply increases alveolar ventilation on their own
by either increasing rate or tidal volume. EXERCISE 8-3 CO2 Homeostasis
1. Metabolic
. rate
Intervention 2. VCO2
Importance: 3. Alveolar
. ventilation
The patient should have alveolar ventilation 4. VA
reduced. 5. Massive burns, sepsis
6. Sodium bicarbonate (NaHCO3)
Objective: 7. Decreased
It would be desirable to get the pH below 7.50 8. Tidal volume.
and the PaCO2 above 30 mm Hg. 9. VT RR = V
10. Is not
Action: 11. PaCO
. 2
The patients tidal volume and/or rate should 12. VA = (VT VD) RR
be reduced in order to decrease alveolar venti- 13. Inversely
lation. Another alternative might be to sedate 14. Increase
the patient. 15. Decreases
EXERCISE 8-4 CO2 Transport

EXERCISES 1. Dissolved CO2
Carbonic acid
EXERCISE 8-1 Hydrogen Ions and pH Bicarbonate
1. Is not Carbamino compounds
2. Negative log of the free [H+] 2. Higher
3. 7.35 to 7.45 3. 0.03 mEq/L/mm Hg
4. Inverse, logarithmic 4. 80 mm Hg 0.03 mEq/L/mm Hg
5. 0.3 = 2.4 mEq/L
6. Acid 5. Is
7. Base 6. Slow
8. Homeostasis 7. Bicarbonate
9. Lungs, kidneys 8. Faster
480 Answers
9. Carbonic anhydrase 8. Bicarbonate

10. Hemoglobin Inorganic phosphates
11. Chloride (Cl) Proteins
12. Hamburger 9. Quantity of the buffer
13. Erythrocytes pK of the weak acid in the buffer system
14. Carbamino compound Open versus closed buffer system
15. Carbamino-hemoglobin 10. 50%
16. Does not 11. Open
17. Less 12. 1
18. Haldane 13. Bicarbonate
19. 10% 14. Hemoglobin
20. 2% 15. Isohydric principle
EXERCISE 8-5 The Kidney and EXERCISE 8-8 Henderson-Hasselbalch

Acid-Base Balance Equation
1. Excretion of fixed acids 1. Hendersons equation
Regulation of blood [HCO3] 2. p
2. Cannot 3. pH = pKc + log [HCO3]/[H2CO3]
3. Protein 4. 6.1
4. Lipid 5. 24 mEq/L
5. Ketoacids 6. 40 mm Hg 0.03 mEq/L/mm Hg =
6. Lactic acid 1.2 mEq/L
7. 50 to 60 7. 20:1
8. Hydrochloric acid (HCl) 8. 1.3
9. Excrete and produce 9. pH [HCO3]/PaCO2
10. [HCO3] 10. Denominator
11. Ratio between the numerator and
EXERCISE 8-6 Basic Chemistry Related denominator
to Buffers 12. Compensation
1. Base 13. 24 mEq/L/40 mm Hg
2. Conjugate acid-base pair
3. HCO3, Hb EXERCISE 8-9 Acid-Base Physiology
4. Different and Terminology
5. High 1. Renal
6. Greater 2. Alkalosis
7. Weaker 3. Acidosis
8. Deoxygenated 4. Metabolic
9. Strong 5. 48 to 72 hours
10. Acid or a base 6. Rarely
Amphoteric 7. a. Metabolic acidosis
b. Respiratory acidosis
EXERCISE 8-7 Blood Buffer Systems c. Respiratory alkalosis
1. Do not d. Metabolic alkalosis
2. Weaker acids 8. Primary
3. Weak acid 9. Laboratory or secondary
Salt of the conjugate base of the weak acid 10. Hypobasemia
4. Salt
5. Carbonic acid (H2CO3)
NBRC Challenge 8
Sodium bicarbonate (NaHCO3)
6. Carbonic acid (H2CO3) and sodium chlo- 1. C) I and II only. The patient appears to
ride (NaCl) have COPD and chronic renal bicarbonate
7. NaHCO3 + H2O retention for compensation.
Answers 481
2. E) These results are consistent and Intervention

expected. Venous bicarbonate should be Importance:
higher due to CO2 transport. First priority would be to get oxygenation and
3. E) The pulmonary changes (hypoventila- cardiac output to an acceptable level. It would
tion and mild hypoxemia) suggest compen- probably be wise to increase FIO2 to maintain
sation for a metabolic alkalosis. an SpO2 of at least 90%. The next priority
4. A) Increased CO2 production is a common would be to evaluate cardiac output more
cause of CO2 retention in burn patients. specifically and maintain B/P through appro-
5. C) Blood buffers respond immediately to priate use of cardiotonics and fluids.
protect the pH.
Thinking
CHAPTER 9 Assessment
Abnormalities:
ON-CALL CASE 9-1 ABGs and Critical SaO2
Thinking pH
Assessment PaCO2
Abnormalities: PaO2
SaO2 [HCO3]
pH ABG classification: Mixed respiratory and
PaCO2 metabolic acidosis with mild hypoxemia.
PaO2
[HCO3] Explanation:
ABG classification: Partially compensated The hypoxemia is due at least in part to hypo-
metabolic acidosis with moderate hypoxemia. ventilation. The hypoventilation is secondary
to the drug overdose and depression of venti-
Explanation: latory drive with subsequent decrease in alveolar
The respiratory alkalosis appears to be second- oxygen. Calculation of the P(Aa)O2 on room
ary to the acute hypoxemia. The patient had a air yields a value of 28 mm Hg. Because the
substantial shunt earlier at 10:00 AM as evi- normal P(Aa)O2 is less than 20 mm Hg, this
denced by the P(Aa)O2 and FIO2/PaO2 ratio. value suggests another factor contributing to
Because it was stated that the patient had pneu- the hypoxemia, specifically an increased phys-
monia, this is the likely cause of the pulmonary iologic shunt. The increased shunt could be
shunt and hypoxemia. The acute onset of a consequence of aspiration. Therefore, the
hypoxemia appears to be due to a decreased likelihood of aspiration and additional gas
cardiac output as evidenced by the hypoten- exchange impairment is likely.
sion, arrhythmias, chest pain, and shortness of
breath. In healthy individuals, a decrease in Evaluation:
cardiac output would only have a minimal Additional data: A chest radiograph would
effect on PaO2 because of the small percentage provide additional evidence of aspiration.
of shunted blood. In this individual, however,
the decrease in cardiac output could have a Intervention
substantial impact on PaO2 because of the high Importance:
shunt fraction, which was pre-existing. The first priority is to establish an airway and
maintain sufficient alveolar ventilation.
Evaluation: Therefore, if the hypoventilation could not be
Additional data: Measurement of cardiac out- quickly reversed, the patient should be intu-
put and shunt fraction would be ideal if the bated and ventilated. Also, the patient should
patient had a Swan-Ganz catheter in place. be observed for worsening hypoxemia and
Pulmonary wedge pressure and central venous shunting as a result of the likely aspiration.
pressure would also help guide fluid and drug Bronchial clearance maneuvers should be initi-
therapy. ated as necessary.
482 Answers
EXERCISES 3. Mixed venous blood

4. Pulmonary artery catheter
EXERCISE 9-1 Hypoxemia and the Role 5. - )O2
C(av
of Cardiac Output . .
6. Qsp/QT
1. Adequacy 7. P(Aa)O2
Efficiency 8. P(Aa)O2
2. Hypoventilation 9. PaO2/FIO2 or the oxygenation ratio
Absolute shunting (PaO2/%FIO2)
Relative shunting 10. 20%
Diffusion defects
(Note that these four common causes EXERCISE 9-5 Differential Diagnosis of
form the acronym HARD.) Hypoxemia and Effects of Altitude on
3. Relative shunting Hypoxemia
4. Always 1. Multiple mechanisms
5. Minimal 2. Hypoventilation
6. Lower 3. Poor
7. Fall 4. White-out
8. A large percentage of venous blood enter- 5. Edema
ing the arteries 6. Decreased cardiac output
9. Cannot 7. Hyperventilation
10. Increased Excessive oxygen therapy
EXERCISE 9-2 Alveolar-Arterial O2 8. Relative
Gradients 9. 130 mm Hg
10. Bronchodilators
1. P(Aa)O2
Nitrides
2. 10 mm Hg
11. Hemodialysis
20 mm Hg
12. Liver
3. Ventilation-perfusion mismatch
13. Increase
4. Mean
14. 5000
5. PAO2 = PIO2 1.2(PaCO2)
15. 4
6. PIO2 = (PB PH2O) FIO2
7. 50 EXERCISE 9-6 The P(Aa)O2 in
8. Absorption atelectasis Differential Diagnosis
9. Increases
PAO2 = PIO2 1.2(PaCO2)
10. PAO2 = PIO2 PaCO2
P(Aa)O2 Diagnosis
EXERCISE 9-3 Oxygenation Ratios (mm Hg)
1. More 1. 38 Hypoventilation with
2. 0.75 increased physiologic
3. 0.3 to 1.0 shunting
4. 100 mm Hg 2. 28 Hypoventilation with
5. 400 increased physiologic
shunting
6. Oxygenation
3. 10 Simple hypoventilation
7. 2.0 4. 14 Simple hypoventilation
8. Does not 5. 25 Hypoventilation with
9. PaO2/PAO2 increased physiologic
10. Do shunting
6. Absolute shunting
EXERCISE 9-4 Indices of Physiologic 7. Relative shunting
Shunting 8. Absolute shunting
1. Corrects 9. Relative shunting
2. Classic 10. Absolute shunting
Answers 483
NBRC Challenge 9 Intervention

1. B) Pneumonia. The P(Aa)O2 of 35 mm Hg Importance:
on room air suggests increased physiologi- The patient needs to be oxygenated first to
cal shunting. Pneumonia is the only shunt preclude hypoxia. Bronchial hygiene with
producing disease listed. bronchodilators would be useful. Appropriate
2. A) Hypoventilation. A normal P(Aa)O2 antibiotics would also be useful.
indicates the patient has simple hypoventi-
lation without shunting disease. Objective:
3. D) PaO2. In the presence of a substantial The goal in oxygen therapy is to keep PaO2 at
shunt (e.g., 30%), a drop in cardiac output 60 mm Hg and SaO2 at 90% in acute exacer-
will decrease mixed venous PO2 and will bation of COPD.
cause hypoxemia.
4. E) Decrease very slightly or not at all. Since Action:
the normal shunt fraction is so small, a Mechanical ventilation should be avoided
decrease in cardiac output tends to have if at all possible in COPD because these
only very minimal effect on PaO2. patients are prone to other problems and are
5. A) Increase, increase. Since the PaO2/PAO2 difficult to wean. Low concentration FIO2
is inversely proportional to shunting, both should be initiated at approximately FIO2
indices of shunting will increase when the 0.28. This FIO2 is most likely to result in an
ratio decreases. increase in PaO2 of about 18 mm Hg, which
is the appropriate target. This can be admin-
istered with 2 LPM nasal cannula or Venti-
CHAPTER 10 mask. The patient should be watched for signs
of further deterioration (decreasing pH,
ON-CALL CASE 10-1 ABGs and Critical increasing PaCO2, or progressive loss of
Thinking consciousness) and/or deterioration of vital
Assessment signs. Arterial blood gases should be drawn at
Abnormalities: least 30 minutes after initiation of therapy.
SaO2 ON-CALL CASE 10-2 ABGs and Critical
pH Thinking
PaCO2 Assessment
PaO2
Abnormalities:
[HCO3]
ABG classification: Partially compen- SaO2
sated respiratory acidosis with severe hypo- pH
xemia. PaCO2
PaO2
Explanation: [HCO3]
The patient appears to be in acute exacerba- ABG classification: Mixed respiratory and
tion of COPD that is most likely secondary to metabolic acidosis with moderate hypoxemia.
the recent acute infection.
Explanation:
Evaluation: The patient appears to be in severe acute respi-
Additional data: Chest radiography, vital ratory distress syndrome. The chest radiograph
signs, and blood work would help to evaluate and pulmonary wedge pressure are consistent
for possible pneumonia. Elevated temperature with this. The history of hypotension and sep-
and [WBC] and white-out on chest radiograph sis also makes this patient a good candidate for
confirms bacterial infection. Sputum culture acute respiratory distress syndrome. Finally,
may be beneficial to determine the type of the oxygenation ratio less than 1 indicates
microbe involved. severe pulmonary shunting. If the oxygenation
484 Answers
ratio were greater than 2, the diagnosis would EXERCISE 10-2 Hazards and
be acute lung injury. Guidelines in Oxygen Therapy
1. 55
Evaluation: 2. 7.20
Additional data: Measurement of cardiac out- 3. 60
put and shunt fraction would reinforce the 4. FIO2
diagnosis because the patient apparently has a PaO2
Swan-Ganz catheter in place. Duration of exposure
5. 150 mm Hg
Intervention 6. Pulse oximetry
Importance: 7. Correction of hypoxia
The patient needs oxygen to prevent tissue 8. COPD
hypoxia, positive end-expiratory pressure to 9. 3
address the true shunting (1020 cm H2O), 10. CO2 narcosis
and, finally, the ventilatory failure would ide-
ally be corrected. EXERCISE 10-3 General Treatment
and Positioning in Oxygen-Loading
Objective: Problems
Ideally, we can restore this patient to a normal 1. Maintain an adequate PaO2
PaCO2 and ventilation. We can also ensure Minimize cardiopulmonary work
that oxygenation is adequate with a PaO2 of at Prevent or alleviate hypoxia
least 60 mm Hg, and SaO2 greater than 90%. 2. Oxygen therapy
It would also be desirable to normalize the Body positioning
pulmonary shunt, though we do not want to PEEP/CPAP
exacerbate VILI or MODS. Mechanical ventilation
Alveolar recruitment maneuvers
Action: Nitric oxide
The patient should be intubated and placed on 3. Cardiac output may change
mechanical ventilation using the ARDS/Net Effects of airway closure
approach. This would include using a tidal vol- Ventilation-perfusion relationships
ume goal of no more than 6 mL/kg ideal body 4. Supine
weight, a maximal alveolar pressure of 30 cm 5. Sitting
H2O, using permissive hypercapnia, if neces- 6. Sitting
sary, while maintaining a pH at least greater 7. Up
than 7.20. (Refer to the section in the chapter 8. Down
regarding ARDS/Net.) 9. Is not
10. Prone
EXERCISES EXERCISE 10-4 Oxygen Toxicity/

ALI/ARDS
EXERCISE 10-1 Oxygen Therapy 1. Bleomycin
1. Oxygen therapy 2. Amiodarone
2. Severe 3. Paraquat
3. PaO2 < 60 mm Hg 4. 50 mm Hg
SaO2 < 90% 5. Acute Lung Injury and Acute Respiratory
4. Alveolar oxygen supply Distress Syndrome
5. Relative 6. Less
6. High-flow 7. Heterogeneous
7. FIO2 0.24 8. 30 cm H2O
8. Higher 9. Volume induced lung injury
9. Low-flow 10. Multiple organ dysfunction syndrome
10. 0.400.70 11. ARDS/Net
Answers 485
12. 6 2. C) I and II only. A tidal volume 6 mL/kg

13. Permissive hypercapnia ideal body weight and a maximum alveolar
14. Decreased pressure of 30 cm H2O are consistent with
15. 7.20 ARDS/Net. PEEP is usually set between 10
and 20 cm H2O.
EXERCISE 10-5 PEEP/CPAP 3. A) PEEP. PEEP therapy is effective in car-
1. ARDS diogenic pulmonary edema because it
2. CPAP decreases preload and improves cardiac
3. PEEP function.
4. EPAP 4. D) II and III only. Prone positioning and
5. Threshold nitric oxide
. . therapy have been shown to
6. Continuous improve V/Q in ARDS.
7. 1020 5. C) Decrease PEEP to 5 cm H2O. Current
8. Is thinking (reference 305) is that once FIO2
9. Improves is decreased to 0.50, PEEP should be reduced
10. Beneficial to 5 cm H2O. Decreasing FIO2 to 0.40 and
then extubation should then follow this
EXERCISE 10-6 Complications of PEEP action.
1. Decreased cardiac output
Pulmonary barotrauma
2. Hypovolemic CHAPTER 11
3. High
4. Above ON-CALL CASE 11-1 ABGs and Critical
5. Mean Thinking
6. Unilateral Assessment
7. Threshold Abnormalities:
8. Decreased venous return Normal acid-base status (pH, PaCO2, and
9. Increase [HCO3])
10. Differential PaO2
Oxygenation ratio (PaO2/FIO2)
EXERCISE 10-7 Auto-PEEP Pv-O2
1. Auto-PEEP ABG classification: Normal acid-base status
2. COPD with mild hypoxemia
3. High
4. Increases Explanation:
5. Is not The patients pulmonary shunt seems slightly
6. Expiratory improved as evidenced by the PaO2 increase
7. Increasing with the increased PEEP on the same FIO2.
8. High Nevertheless, the substantial decrease in Pv-O2
9. Decrease indicates that tissue oxygenation has deterio-
10. Should not rated. This is most likely due to a decrease in
cardiac output associated with the PEEP. PEEP
is usually beneficial in cardiogenic pulmonary
NBRC Challenge 10
edema, however, it appears that 15 cm H2O is
1. D) Nasal cannula 1 LPM. Because it is a too much in this patient.
patient with COPD, we administer low
FIO2. Because the target PaO2 in COPD Evaluation:
exacerbation is 60 mm Hg, and as a guide- Evaluation of hemodynamic data (if a Swan-
line, PaO2 increases approximately 3 torr Ganz catheter or central venous pressure line is
per 1% increase in FIO2, a nasal cannula at in place) would be useful. Perhaps the patient
1 LPM should deliver FIO2 of 0.24 and has become hypovolemic secondary to drug
increase PaO2 approximately 9 mm Hg. therapy such as Lasix.
486 Answers
Intervention EXERCISES
Importance:
The most important priority is tissue oxygena- EXERCISE 11-1 Hypoxic Assessment
tion. 1. Arterial oxygenation
Blood Hemoglobin Concentration
Objective: Circulatory Status
The Pv-O2 must be returned to the normal 2. Hypoxia
range of 35 to 45 mm Hg. 3. Is not
4. Arterial oxygenation status
Action: 5. Usually
PEEP should be restored to the previous 6. Is not
level. 7. 60
8. Does not ensure
ON-CALL CASE 11-2 ABGs and Critical 9. 55
Thinking 10. Cardiovascular system
Assessment
Abnormalities: EXERCISE 11-2 SaO2
pH 1. Is not
Normal PaCO2 2. Do not
[HCO3] 3. Functional
PaO2 4. Is not
SaO2 5. Fractional
Pv-O2 6. Fractional
Lactate 7. Functional
ABG classification: Uncompensated metabolic 8. Trending of
acidosis with mild hypoxemia. 9. Are not
10. 2
Explanation:
The patient appears to be hypoxic as indicated EXERCISE 11-3 Laboratory Diagnosis
by the lactic acidosis. Other indices of oxy- of Anemia
genation (PaO2, SaO2, Pv-O2) all look accept- 1. Normal [RBC] 5 million/mm3 ( 700,000)
able, but sepsis is often characterized by a in men
problem with internal respiration and systemic Normal [RBC] 4.5 million/mm3 ( 500,000)
arterial-venous shunting or failure of the cells in women
to accept oxygen. Normal [Hb] is 15 g% in men
Normal [Hb] is 13 to 14 g% in women
Intervention 2. Anemia
Importance: 3. Hematocrit
The immediate concern is to minimize the 4. Anisocytosis
apparent hypoxia and decrease the lactic 5. Macrocytosis
acidosis. 6. MCV
7. Poikilocytosis
Objective: 8. Reticulocytes
Because this patient may be suffering from 9. 34 2%
pathologic oxygen supply dependency (see 10. Hypochromia
section on Covert Hypoxia), it would prob-
ably be wise to increase oxygen transport EXERCISE 11-4 Types of Anemia and
to see if this would improve the patients Treatment
overall oxygenation status (i.e., decrease 1. Aplastic
lactate). 2. Iron deficiency
Answers 487
3. Thalassemia EXERCISE 11-8 Cardiovascular

4. Erythropoietin, folic acid, vitamin B12 Treatment
5. Pernicious anemia 1. Sitting
6. Folic acid deficiency 2. Feet up
7. Increased cardiac output, increased DPG 3. Detrimental, beneficial
8. 30%45% 4. Chronotropic
9. Hemolytic
10. Thalassemia EXERCISE 11-9 Lactate
EXERCISE 11-5 Cardiovascular 1. Lactic
System/Shock 2. Lactate
3. 0.91.9 mM/L
1. Cardiac minute
. output
4. 9
2. C.O. or Q
5. Correlates
3. Cardiac index (C.I.)
6. Liver, quickly
4. Thermodilution, Fick equation
7. Is not
5. Is
8. 10:1
6. Urine output, neurological status, blood
9. Increased
pressure, pulse, capillary refill, cyanosis,
10. Is not
warmth of extremities
7. Heart, blood volume, blood vessels
EXERCISE 11-10 Mixed Venous
8. Shock
Oxygenation Indices
9. Vasoconstriction
10. Restlessness, anxiety, alteration of level of 1. Swan-Ganz catheter (pulmonary artery
consciousness, cyanosis, decreased urine catheter)
output, lactic acidosis, respiratory alkalo- 2. 75%
sis, cold clammy extremities 3. Sv-O2
4. 35 mm Hg
EXERCISE 11-6 Types of Shock 5. Both pulmonary and cardiovascular
1. C.O. = heart rate stroke volume changes
2. Decreases 6. Increased
3. Increases, decreases 7. Decreased
4. Cardiogenic shock 8. Normal PaO2, low Pv-O2
5. Hypovolemia 9. High
6. Low 10. Usually
7. Congestive heart failure
8. Hypovolemic shock EXERCISE 11-11 Oxygen
9. Septic Uptake/Utilization
10. Anaphylactic 1. Is not
2. Critical oxygen delivery point
EXERCISE 11-7 Hemodynamic 3. 8 to 10
Monitoring 4. Unnecessary because the additional oxy-
1. Right atrium gen is not used
2. 2 to 10 5. May be increased
3. Heart failure 6. Covert
4. Swan-Ganz catheter 7. Poor
5. 25/10 8. Multiple organ dysfunction
6. 5 to 12 syndrome
7. Left-sided heart failure 9. Prostacyclin
8. ARDS 10. Unchanged, may be increased
9. Diastolic 11. Pathologic
488 Answers
NBRC Challenge 11 Objective:

The goal is to restore potassium and the other
1. C) Hypovolemic shock. The low hemody-
electrolytes to the normal range.
namic pressures throughout (especially
CVP) suggest low blood volume in the ON-CALL CASE 12-2 ABGs and Critical
cardiopulmonary system. Thinking
2. C) Gastric tonometry. Gastric tonometry is Assessment
a relatively new technique for evaluation of
Abnormalities:
mucosal acidosis reflective of poor perfusion.
pH
3. A) Cardiogenic shock. The high CVP and
PaCO2
especially the high PWP is diagnostic of
[HCO3]
LHF.
4. A) Sitting. The sitting position is likely to
CO2 10 mEq/L
minimize venous return, which is optimal
K 5.2 mEq/L
in the failing heart.
Albumin 3.2 g/dL
5. E) III and IV only. An increased C(av-)O2
and a decreased SvO2 both are suggestive
metabolic acidosis with normoxemia.
of a decreased cardiac output.
Explanation:
The patient appears to have a primary
CHAPTER 12 metabolic acidosis. The first step in evaluat-
ing a metabolic acidosis is to calculate the
ON-CALL CASE 12-1 ABGs and Critical anion gap. The anion gap equals 16 mEq/L,
Thinking which is near the upper limits of normal;
Assessment however, the anion gap reads falsely low
Abnormalities: when hypoalbuminemia is present. Therefore,
pH CO2 the anion gap should be higher by approxi-
PaCO2 K mately 3 mEq/L. This anion gap is beyond the
[HCO3] Na normal range for that level of albumin and
Cl indicates an increased fixed acid in the blood.
metabolic alkalosis with normoxemia. Evaluation:
Evaluate the patient to see if he or she ingested
Explanation: a toxin. Measurement of blood glucose helps
The history of thiazide diuretics should alert to rule out diabetic ketoacidosis, and assessment
one to the possibility of hyponatremia, fluid of blood urea nitrogen and creatinine levels
depletion, and hypokalemia. Symptoms associ- helps to rule out renal failure. Oxygenation
ated with hypokalemia are present; namely, should be suspected because of the history
weakness, lethargy, and muscle cramps, and of anemia. The [Hb] should be checked.
electrocardiography (ECG) demonstrates an Furthermore, cardiovascular assessment and
inverted T wave and a prominent U wave. It lactate measurement would help determine if
appears to be a classic case of hypokalemia lactic acidosis is present.
associated with chronic diuretic therapy.
Intervention
Intervention Importance:
Importance: The most important priority is to determine
To prevent dangerous arrhythmias, correct the the cause of the metabolic acidosis. If the pH
potassium level as soon as possible. Administer falls below 7.20 (or hyperkalemia worsens),
potassium slowly to allow for movement into administration of sodium bicarbonate may be
the intracellular space. The patient also indicated. If serious anemia is present, blood
appears to need some sodium and chloride. transfusion may be indicated.
Answers 489
EXERCISES EXERCISE 12-4 Chemical

Mechanisms of Sodium
EXERCISE 12-1 Regulation of
Reabsorption and the
Ventilation
Renin-Angiotensin System
1. Medulla
1. NaCl mechanism and the NaHCO3
2. CSF
mechanism
3. Gases, ions
2. Chloride (Cl)
4. Cheyne-Stokes respiration
3. Hydrogen (H+) or potassium (K+) ion
5. Carotid, aortic
4. Is
6. May stimulate the peripheral
5. Hydrolysis
chemoreceptors:
6. In alkalemia, K+ is secreted and H+ is
b) Hypoxemia
retained
c) Cyanide poisoning
7. Juxtaglomerular
d) Hypercarbia (PaCO2 70 mm Hg)
8. Renin
e) Cardiogenic shock
9. Aldosterone
7. Peripheral
10. NaHCO3
8. 60
9. Central EXERCISE 12-5 Total Sodium
10. Depressed Reabsorption and Diuretics
11. Greater
1. Proximal tubule
12. Hypoxemia
2. 80%
13. Hypercarbia
3. NaHCO3
14. Hypercarbia
4. Reclaimed
15. J-receptor
5. Proximal
EXERCISE 12-2 Renal Function 6. NaCl
1. Cortex, medulla 7. Loop
2. Ureters 8. Alkalosis, hypokalemia
3. Nephron 9. Is
4. Glomerulus 10. Acetazolamide
5. Afferent
6. Proximal convoluted tubule EXERCISE 12-6 Hyperaldosteronism,
7. Cannot Urinary Buffers, and Potassium
8. Oliguria 1. Alkalosis
9. Secretion 2. Increased H+ excretion
10. Glomerular filtrate Hypokalemia
3. Secondary
EXERCISE 12-3 Body Fluids and 4. Mineralocorticoid
Electrolytes 5. Primary
1. Intracellular 6. Glucocorticoids
2. Intravascular 7. pH of 4.50
3. Serum 8. Bicarbonate
4. Interstitial Ammonia
5. Non-electrolyte Phosphate
6. Cations 9. Increases
7. Potassium 10. Intracellular
8. Sodium 142 mEq/L
Potassium 4 mEq/L EXERCISE 12-7 Law of
Calcium 5 mEq/L Electroneutrality, Anion Gap, and
Magnesium 2 mEq/L Stewarts Strong Ion Difference
9. Sodium 1. Hypochloremia
10. Na+ 2. Acidosis
490 Answers
3. Na (TCO2 + Cl) = A Explanation:

4. 12 to 14 The blood gas and laboratory data are consis-
5. Hyperchloremic metabolic acidosis tent with acute salicylate intoxication. The high
6. Increases anion gap suggests a metabolic acidosis, but the
7. A 28 mEq/L; increased fixed acids blood gas also appears to indicate a primary
8. A 22 mEq/L; increased fixed acids respiratory alkalosis. This is the classic picture
9. A 10 mEq/L; decreased base of an adult with salicylate toxicity.
10. A 15 mEq/L; decreased base
11. Decrease Evaluation:
12. Dependent Serial blood gas and salicylate levels should
13. PCO2, (SID), [ATOT] be measured because the patient may get pro-
gressively worse, especially if the aspirin was
enteric coated. The enteric coating may slow
NBRC Challenge 12
absorption and delay serious symptoms. In
1. C) Serum electrolytes. The recommended a reported case, a patient was shown to have
first step in the diagnosis of primary a salicylate level greater than 125 mg/dL
metabolic acidosis is to calculate the 24 hours after presentation.513
anion gap from the serum electrolyte
report. Intervention
2. D) Holding the administration of KCl. The Importance:
patient currently has a normal plasma Carefully monitor the patient for any signs of
potassium concentration. worsening toxicity. Initiate hemodialysis quickly
3. B) Serum potassium. The ECG, especially following any signs of deterioration.
in a patient with chronic renal failure, sug-
gests hyperkalemia. ON-CALL CASE 13-2 ABGs and Critical
4. A) Albumin. Hypoalbuminemia will lower Thinking
the anion gap and hyperalbuminemia will Assessment
increase it. Hypoalbuminemia is a common Abnormalities:
condition in the critically ill. PaO2
5. C) Had lactic acidosis. Hypoxia is the PaCO2
most common cause of high anion gap [HCO3] and Total CO2
lactic acidosis. The normalization of Na
the anion gap following oxygen therapy K
is highly suggestive of hypoxic lactic Cl
acidosis. ABG classification: Partially compensated
metabolic alkalosis with moderate hypoxemia.
CHAPTER 13 Explanation:
The blood gas and electrolytes are consistent
ON-CALL CASE 13-1 ABGs and with severe dehydration secondary to vomiting.
Critical Thinking
Assessment Intervention
Abnormalities: Importance:
PaO2 Salicylate level The patient needs I.V. therapy, including
PaCO2 Anion gap (23 mEq/L) sodium chloride to restore fluids. Potassium
[HCO3] [K] should likewise be administered slowly because
ABG classification: Compensated respiratory abrupt increases to dangerous levels could pre-
alkalosis with hyperoxemia. However, it is cipitate arrhythmias. Oxygen therapy would be
more likely that this represents mixed respira- useful because the patient is hypoventilating at
tory alkalosis and metabolic acidosis with substantial levels to compensate for the meta-
hyperoxemia. bolic alkalosis. If the pH does not respond to
Answers 491
fluid and potassium replacement, dilute HCl EXERCISE 13-3 High Anion Gap
might be indicated for treatment of severe Metabolic Acidosis: Toxins and
alkalemia. Azotemic Renal Failure
1. Increase in fixed acids
2. Salicylate
EXERCISES 3. Methanol (wood alcohol)
4. Ethylene glycol
EXERCISE 13-1 Respiratory Acidosis 5. Toluene
1. Accumulation 6. Azotemic renal failure
2. COPD 7. BUN and creatinine
3. COPD 8. Prerenal
4. Should not 9. Uremia
5. Are 10. 4 mg/dL
6. Status asthmaticus
7. Vital capacity EXERCISE 13-4 High Anion Gap
8. Hypokalemia Metabolic Acidosis: Lactic Acidosis
9. Less and Ketoacidosis
10. Increases 1. Common
11. Quantity 2. Hepatic
12. An increased 3. Acetoacetic acid
13. Pickwickian Beta-hydroxybutyric acid
14. Ondines 4. Acetone
15. COPD 5. Ketone
O2 excess in COPD 6. Starvation
Drugs Alcoholic ketoacidosis
Extreme ventilation-perfusion mismatch Diabetes mellitus
Exhaustion 7. Acetest
Neuromuscular disorders 8. Mellitus, hyperglycemia
Iatrogenic respiratory acidosis 9. Insulin
Neurologic disorders 10. Hyperglycemia
Excessive CO2 production 11. Dehydration
(The acronym code nine may help when 12. 500 mg/dL
recalling these major causes.) 13. Kussmauls breathing
14. Glycosuria
EXERCISE 13-2 Respiratory Alkalosis 15. Toxins
1. Depleting Azotemic renal failure
2. Hypoxemia Lactic acidosis
3. Hering-Breuer Ketoacidosis
4. J-receptor (The acronym talk may help when recall-
5. Stimulate ing these major causes.)
6. Acidosis
7. Decreased EXERCISE 13-5 Normal Anion Gap
8. Respiratory alkalosis Metabolic Acidosis
9. Acidosis 1. Hyperchloremic
10. Hypoxemia (moderate to severe) 2. Kidneys
Overzealous mechanical ventilation Intestines
Restrictive lung disorders 3. Renal tubular acidosis (RTA)
Neurologic origin 4. High
Shock/Decreased cardiac output 5. Enteric
(The acronym horns may help when 6. Diarrhea
recalling these major causes.) 7. Acetazolamide
492 Answers
8. Children 4. E) Discontinue the narcotic. Narcotics are

9. High known to depress ventilation in COPD and
10. Renal tubular acidosis should be avoided.
Enteric drainage tubes 5. D) I. I, II and III only. Blood glucose, BUN,
Diarrhea and lactate all provide clues as to possible
Urinary diversion causes of high anion gap acidosis.
Carbonic anhydrase inhibitors
Early renal disease
Dilution acidosis CHAPTER 14
Biliary or pancreatic fistulas
Acidifying salts ON-CALL CASE 14-1 ABGs and Critical
Sulfur, hydrogen sulfide, and drugs Thinking
Eucapnic ventilation post-hypocapnia Assessment
(The acronym reduced base may help Abnormalities:
when recalling these major causes.) PaO2 and SaO2
PaCO2
EXERCISE 13-6 Metabolic Alkalosis [HCO3]
1. Cannot K
2. Intracellular Cl
3. Gastric fluid loss Anion gap
4. (HCO3) anion ABG classification: On first impression, it
5. Bartters appears to be a compensated metabolic alkalo-
6. Acidosis, alkalosis sis; however, the degree of compensation seems
7. Primary hyperaldosteronism excessive and the history suggests primary respi-
8. Glucocorticoids ratory acidosis. The best classification would be
9. Alkalosis a mixed respiratory acidosis and metabolic alka-
10. Hypokalemia losis. Plotting the data on an acid-base map is
Ingestion of large amounts of alkali or licorice also consistent with a mixed acid-base disorder.
Gastric fluid loss
Hyperaldosteronism secondary to non- Explanation:
adrenal factors The long-standing COPD has probably caused
Bicarbonate administration the respiratory acidosis. Diuretics and steroids
Adrenocortical hypersecretion often cause primary metabolic alkalosis and
Steroids this may be the reason for this. Hypokalemia is
Eucapnic ventilation post-hypercapnia also consistent with the effects of these drugs.
(The acronym high base may help when The high anion gap suggests that lactic acido-
recalling these major causes.) sis is also present but is masqueraded by the
other acid-base disorders. This may actually be
termed a triple acid-base disorder.
NBRC Challenge 13
1. C) Diamox. A carbonic anhydrase inhibitor Evaluation:
would tend to lower pH. A lactate measurement may confirm the pres-
2. C) Tissues are likely acidotic. It has been ence of lactic acid accumulation.
shown that tissue pH and PCO2 are most
often acidotic and hypercapnic despite Intervention
arterial hypocapnia during profound circu- Importance:
latory shock. The patient probably requires careful rehydra-
3. A) [Hb]. The high lactate and anion gap tion and potassium replacement. Both should be
suggest hypoxia. Anemia is a potential approached slowly to avoid hyperkalemia and
cause of tissue hypoxia. fluid overload especially considering the CHF.
Answers 493
If plasma lactic acidosis appears to be present, serum potassium. If hyperkalemia persists or

the patient should also receive oxygen therapy. worsens, dialysis will likely be necessary.

Thinking EXERCISES
Assessment
Abnormalities: EXERCISE 14-1 Factors Complicating
PaO2 and SaO2 (mild) Acid-Base Disturbances
pH 1. Respiratory system
PaCO2 Renal system
[HCO3] 2. PaCO2 increased
[K] [HCO3] increased
Anion gap [BE] increased
ABG classification: Partially compensated 3. Compensation for previous hypercapnia
metabolic acidosis with mild hypoxemia. 4. Lactic acidosis
5. pH
Explanation: 6. COPD
It appears that the patient has metabolic aci- 7. Low-flow O2 therapy
dosis secondary to renal failure. The high 8. Compensation
anion gap is consistent with this diagnosis. The 9. More
hyperkalemia, although common in metabolic 10. Acidosis
acidosis, is also consistent with this. The
hyperkalemia is also a matter of some concern EXERCISE 14-2 Mixed Acid-Base
because it may lead to serious complications. Disturbances
1. Mixed
Evaluation: 2. 95%
Measurement of blood urea nitrogen [BUN] 3. Does not
and creatinine would facilitate the diagnosis of 4. pH 7.31 after maximal compensation
azotemic renal failure. These values are likely (50% return)
substantially elevated. 5. pH 7.50 after maximal compensation
(50% return)
Intervention 6. 18 mm Hg
Importance: 30 mm Hg
The foremost concern is to decrease the 22 mm Hg
serum potassium to a safe level. A second- 7. Hypochloremia
ary goal might be to correct the metabolic 8. Hyperchloremia
acidosis. 9. Day
10. Absence of compensation
Objective: Long-standing renal or pulmonary disease
It is best to decrease the potassium below 6.0, Excessive compensation
preferably lower. Respiratory assistance
Temporal inconsistencies
Action: Settings conducive to mixed disturbances
Sodium bicarbonate is useful in metabolic aci- (Note that the acronym alerts may help
dosis accompanied with hyperkalemia because when recalling these situations.)
alkalinization of the extracellular fluid would
facilitate the movement of potassium back into EXERCISE 14-3 Respiratory Acid-Base
the intracellular space. Despite the fact that the Treatment
pH is above 7.10, sodium bicarbonate intra- 1. Supportive (palliative) treatment
venously may be indicated to help lower the Corrective treatment
494 Answers
2. pH The kidney cannot correct metabolic alka-

3. Respiratory acidosis (acidemia) losis in the absence of sufficient potassium.
4. pH 2. E) Leave the patient on the current settings.
5. 7.25 This is classic permissive hypercapnia.
6. Low FIO2 (0.24 to 0.40) or noninvasive The key in ARDS is to minimize alveolar
positive-pressure ventilation pressures whereas mild-to-moderate hyper-
7. Respiratory rate capnia is secondary and generally of minimal
Tidal volume consequence.
Mechanical deadspace 3. B) Noninvasive positive-pressure ventilation
8. Gradually is effective in the management of COPD
and helps to avoid mechanical ventilation
EXERCISE 14-4 Treatment of Metabolic and intubation.
Acidosis 4. C) Most likely acidotic. Typically during
1. Is not cardiac arrest, there is a venous para-
2. Liver dox and tissue pH remains acidotic despite
3. Sodium bicarbonate (NaHCO3) arterial blood gases that manifest respira-
4. pH < 7.10 tory alkalosis.
5. Hypokalemia 5. D) Dilute HCl acid I.V. This is the treat-
6. Intracranial ment of choice for severe sustained meta-
7. Hypercapnia (respiratory acidosis) bolic alkalosis; however, an experienced
8. Has intensivist should administer it carefully.
9. THAM or Carbicarb
10. [BE] 0.3 weight in kg/2 =
HCO3 dose CHAPTER 15
11. Is
12. Is not ON-CALL CASE 15-1 ABGs and Critical
13. Much Thinking
14. Venous paradox Assessment
15. Fall Abnormalities:
16. [20] 0.3 80 kg/2 = HCO3 dose Normal PaO2 and SaO2
480/2 = HCO3 dose = 240 mEq pH
PaCO2
EXERCISE 14-5 Treatment of Normal [HCO3]
Metabolic Alkalosis PetCO2 followed by an abrupt increase
1. Potassium, chloride, fluid volume ABG classification: Uncompensated respiratory
replacement alkalosis with normoxemia.
2. Cimetidine or ranitidine
3. 3.5 mEq/L Explanation:
4. Slowly The patient is being intentionally hyperventi-
5. Acetazolamide (Diamox) lated to minimize intracranial pressure due to
6. 7.55 her head surgery. The original PaCO2PetCO2
7. Dilute hydrochloric acid gradient is appropriately about 6 mm Hg, which
8. Central is normal. This gradient is expected in a healthy
9. 100 mEq/L young female with otherwise normal lungs.
10. Common
Evaluation:
Although we need to be skeptical about
NBRC Challenge 14
PetCO2 changes reflecting PaCO2 changes in
1. D) KCl I.V. Therapy for mild-to-moderate all patients, there is usually a good correlation
metabolic alkalosis typically includes KCl I.V., between changes in PetCO2 and PaCO2 in this
especially in the patient with hypokalemia. type of patient. Therefore, we should carefully
Answers 495
evaluate the ventilator circuit and obtain an Evaluation:

arterial blood gas. If intracranial pressure is The increased gradient may suggest the develop-
being monitored, it should also be checked to ment of increased deadspace such as a pul-
ensure it is not increasing. monary embolus but the results are inconclusive.
Intervention Intervention
Importance: Importance:
The foremost concern is to decrease the carbon The foremost concern is to restore arterial
dioxide to a safe level. PaCO2 to an acceptable level.
Objective: Objective:
Restore PaCO2 levels back to 25 to Restore PaCO2 levels back to 35 to 45 mm Hg.
30 mm Hg.
Action:
Action: Ensure ventilator circuit is intact and make
Ensure ventilator circuit is intact and necessary changes to restore ventilation.
make necessary changes to restore hyper-
ventilation. EXERCISES
ON-CALL CASE 15-2 ABGs and EXERCISE 15-1 Basic Principles of
Critical Thinking Oximetry
Assessment
1. Arterial blood gas analysis
Abnormalities: 2. Measurement
PaO2 (mild hypoxemia) 3. Qualitative
Normal pH 4. Photoelectric effect
Normal PaCO2 5. Lambert-Beer
Normal [HCO3] 6. Optical density
PetCO2 7. Oximeter
ABG classification: Normal acid-base status 8. Spectrophotometer
with mild hypoxemia. 9. Isobestic
10. Same
Explanation: 11. Hemolyzed
The patient is being appropriately ventilated 12. Are not
via mechanical ventilation. The PaCO2 to 13. Oxyhemoglobin
PetCO2 gradient is slightly elevated (10 mm Hg). Desaturated hemoglobin
This could. be. due to a variety of reasons Carboxyhemoglobin
including V/Q mismatch or increased dead- Methemoglobin
space. The increase in arterial PaCO2 without 14. Fractional
a concurrent rise in PetCO2 is not uncommon 15. Hewlett-Packard
in mechanically ventilated patients. This could
reflect an increase in deadspace or a variety of EXERCISE 15-2 Pulse Oximetry
other things. Most importantly, the clinician 1. Pulse oximetry
must recognize that PetCO2, although stable 2. Plethysmograph
in this patient, does not adequately reflect 3. Pulse
PaCO2 in most mechanically ventilated 4. Diastole
patients and should not be relied on as an indi- 5. Accurate
cator of PaCO2. Assuming that PaCO2 was 6. 2
unchanged in this patient would have left 7. Red and infrared
the hypercarbic problem unidentified. When 8. Optical shunting
in doubt, an arterial blood gas measurement 9. Does not
should be obtained. 10. Dual oximetry
496 Answers
EXERCISE 15-3 Transcutaneous 3. Sidestream

PO2/PCO2 4. Slow
1. PtcO2 5. Is not
2. More 6. Elevated
3. Less 7. Fall
4. Stratum corneum 8. Falls
Epidermis 9. Rise
Dermis 10. Obstructive
5. High, no 11. Carbon dioxide production
6. 43.5 C 12. Cardiac output
7. Less
8. Higher NBRC Challenge 15
9. Wetting
10. Do 1. B) Decreased PetCO2. Decreased perfusion
11. Burn of the lungs results in decreased carbon
12. 2 to 6 dioxide in the exhaled gas.
13. Infants 2. D) The patient has increased deadspace.
14. PtcO2 Although the PaCO2 to PetCO2 is less
15. SpO2 than foolproof, an increasing gradient is
consistent with increased alveolar dead-
EXERCISE 15-4 Capnometry space such as might occur with a pul-
Technique monary embolus.
1. Capnography 3. A) PtcO2. The patient needs to be carefully
2. Mass spectrometers monitored for progression into hyperox-
Infrared absorption capnometers emia. Transcutaneous measurement is best
3. Mass spectrometers suited for this monitoring because it is most
4. Infrared sensitive.
5. Choppers 4. E) CO-oximetry. The most likely explanation
6. Sidestream is that methemoglobinemia has developed,
Mainstream which can be detected with CO-oximetry.
7. Sidestream 5. D) II, III, I. The best monitors for identify-
8. Artificial airways ing patient mishaps are shown to be in rank
9. Slower order: pulse oximetry, capnography, and
10. Mainstream ECG.
EXERCISE 15-5 Capnograms

1. Almost zero
2. Alveolar
Illustration Credits
Chapter 1 Figure 4-9, From Siggaard-Andersen, O.: The Acid-Base

Figure 1-1, Modified from Croxton, F. E.: Elementary Status of the Blood, 4th ed. Baltimore, Lippincott
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Dover Publications, 1953; Siggaard-Andersen, Copenhagen, Denmark;
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Anatomy and Physiology, 5th ed. St. Louis, Mosby, From Principles to Practice. Washington D.C., AACC
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Pegington, J., and Abrahams, P.H.: Color Atlas of N. R., and Bakow, E. D. (eds): Comprehensive
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Structure and Function in Man, 5th ed. Philadelphia, Blood Gases, 5th ed. St. Louis, Mosby, 1994;
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the Human Body, 29th ed. Philadelphia, Lea & Gases, 5th ed. St. Louis, Mosby, 1994.
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Chapter 3 FL, Grune & Stratton, 1971;
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Physiology, 9th ed. Philadelphia, W.B. Saunders, A.: Distribution of blood flow in isolated lung; relation
1996; to vascular and alveolar pressures. J. Appl. Physiol.
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Williams and Wilkins, 1974, Copyright 1963 by O. Gas Exchange, 3rd ed. Oxford, London, Blackwell
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497
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Instructors Resource Manual for the AACCN Core and Zaccari, J.: Effects of methemoglobinemia on pulse
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Physiology. Philadelphia, W.B. Saunders, 1983; ing caused by sickle cell disease. N. Engl. J. Med.
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Chapter 7 2000;
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Textbook of Surgery, 16th ed. Philadelphia, W.B. acute inflammatory-postinfectious polyneuropathy. In
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Instructors Resource Manual for the AACCN Core Philadelphia, W.B. Saunders, 1982.
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Essentials of Medicine, 5th ed. Philadelphia, W.B. Figure 15-5, From Neuman, M. R.: Pulse Oximetry:
Saunders, 2001; Physical Principles, Technical Realization and Present
Figure 12-7, From Guyton, A. C.: Textbook of Medical Limitations. New York, Plenum Press, 1986;
Physiology, 10th ed. Philadelphia, W.B. Saunders, 2000; Figure 15-6, From Oxygen Transport Physiology
Figure 12-8, From McCance, K. L., and Heuther, S. E.: Slide Series. Hayward, CA, Nellcor Incorporated,
Pathophysiology: The Biologic Basis for Disease in 1987;
Adults and Children, 2nd ed. St. Louis, Mosby, 1994; Figure 15-7, From Brown, M., and Vender, J. S.:
Figure 12-9, Modified from Guyton, A. C.: Basic Human Noninvasive oxygen monitoring. In Vender, J. S. (ed):
Physiology, 2nd ed. Philadelphia, W.B. Saunders, 1977; Critical Care Clinics: Intensive Care Monitoring, vol. 4.
Figure 12-10, Modified from Guyton, A. C.: Basic Human Philadelphia, W.B. Saunders, 1988, p 495;
Physiology. 2nd ed. Philadelphia, W.B. Saunders, 1977; Figure 15-8, From Ramage, J. E. Hemodynamic and gas
Figure 12-11, Modified from Guyton, A. C.: Basic Human exchange monitoring. In Hess, D. R., et al. (eds):
Physiology, 2nd ed. Philadelphia, W.B. Saunders. Respiratory Care: Principles and Practice. Philadelphia,
1977; W.B. Saunders, 2002;
500 Illustration Credits
Figure 15-9, Modified from materials courtesy Figure 15-17, From Scanlan, C. L.: Analysis and
Novametrix Medical Systems, Wallingford, CT; monitoring of gas exchange. In Scanlan, C. L., Wilkins,
Figure 15-10, From Oxygen Transport Physiology Slide R. L., and Stoller, J. K. (eds): Egans Fundamentals of
Series. Hayward, CA, Nellcor Incorporated, 1987; Respiratory Care, 7th ed. St. Louis, Mosby, 1999;
Figure 15-11, From Brown, M., and Vender, J. S.: Figure 15-18, From Capnography: A Quick Reference.
Noninvasive oxygen monitoring. In Vender, J. S. (ed): Hayward, CA, Nellcor Incorporated, 1988;
Critical Care Clinics: Intensive Care Monitoring, vol. 4. Figure 15-19, From Snyder, J. V., Elliot, J. L., and
Philadelphia, W.B. Saunders, 1988; Grenvik, A.: Capnography. In Spence, A. A.: Clinics in
Figure 15-12, From Oxygen Transport Physiology Critical Care Medicine: Respiratory Monitoring in
Slide Series. Hayward, CA, Nellcor Incorporated, Intensive Care. Edinburgh, Churchill Livingstone, 1982;
1987; Figure 15-20, From Nuzzo, P. E., and Anton, W. R.:
Figure 15-13, From Masimo Corporation product litera- Practical applications of capnography. Respir. Ther.
ture, Irvine, CA; Nov/Dec:1217, 1986;
Figure 15-14, From, Brown, M., and Vender, J. S.: Figure 15-21, From Hess, D.: Capnometry and capnogra-
Noninvasive oxygen monitoring. In Vender, J. S. (ed): phy: Technical aspects, physiological aspects, and clin-
Intensive Care Monitoring, vol. 4. Philadelphia, W.B. ical applications. Respir. Care 35(6):563, June 1990;
Saunders. 1988; Figure 15-22, From Hess, D.: Capnometry and capnogra-
Figure 15-15, From Scanlon, C. L.: Analysis and monitor- phy: Technical aspects, physiological aspects, and clinical
ing of gas exchange. In Scanlan, C. L., Wilkins, R. L., applications. Respir. Care 35(6):564, June 1990;
and Stoller, J. K. (eds): Egans Fundamentals of Figure 15-23, From Ramage, J. E.: Hemodynamic and gas
Respiratory Care, 7th ed. St. Louis, Mosby, 1999; exchange monitoring. In Hess, D. R., et al. (eds):
Figure 15-16, From Hicks, G. H.: Blood gas and acid-base Respiratory Care: Principles and Practice. Philadelphia,
measurement. In Dantzker, D. R., MacIntyre, N. R., W.B. Saunders, 2002;
and Bakow, E. D. (eds): Comprehensive Respiratory Figure 15-24, From Single Breath Carbon Dioxide (product
Care. Philadelphia, W.B. Saunders, 1995; literature). Novametrix Medical Systems, Inc.
Index
Note: Page numbers followed by f indicate figures; those followed by t indicate tables; and those followed by b indicate
boxed material.
A Acetoacetate, 347 CO2 transport in, 203205, 204f,

A. See Anion gap (A). Acetoacetic acid, 347 205t
AARC. See American Association Acetone, 347 Henderson-Hasselbalch
for Respiratory Care (AARC). Acid(s) equation in, 210218
ABGs. See Arterial blood gas(es) defined, 197 hydrogen ions and pH in,
(ABGs). excretion of, 197 196198
Absorbance optodes, 104, 104f fixed kidneys in, 205206, 205t
Absorption atelectasis, 255 defined, 198 lungs and regulation of volatile
Absorption optodes, 104, 104f excretion of, 206, 322323, acid in, 198205
Absorption spectrum, 389, 389f 322f, 323f Acid-base map, 118, 365367, 365f,
AC block, 158159 metabolism of, 205206, 205t 366f
AC (alveolar-capillary) membrane origin of, 205206 Acid-base pairs, conjugate, 207
diffusion across, 156159, 157f, regulation of, 205 Acid-base status, 3646, 37f, 37t
158f strong vs. weak, 207208, 207f, base excess [BE] assessment in, 42
thickening of, 158159 208t basic (primary) acid-base distur-
AC (alveolar-capillary) unit volatile bance in, 3842, 38t, 40t, 41f
ideal, 148, 149, 149t, 150f defined, 198 classification vs. interpretation
silent, 149t, 153, 153f regulation of, 198205, 308313 of, 46
ventilation-perfusion ratio Acid groups, 198 compensation assessment in,
in, 147148 Acid hemoglobin (HHb), 209, 210f 4246, 44f, 45f, 45t
Accreditation, 107 Acid homeostasis, 197198 metabolic, 3940, 40t
Accuracy Acid-base balance, 197 pH assessment in, 37, 37f, 37t
of blood gas electrodes, 8990, 89t indicators of, 45 respiratory, 3839, 38t
vs. precision, 9596, 95f, 96f kidneys in, 205206, 205t Acid-base terminology, 217218
of pulse oximetry, 397398, pulse oximetry and, 403 Acid-base treatment, 369379
402403 Acid-base compensation corrective, 370
Accuracy checks, 114120 defined, 213 for metabolic acidosis, 374377
acid-base map in, 118 Henderson-Hasselbalch equation for metabolic alkalosis, 377379
acute PaCO2-pH relationship in, with, 213214, 214f217f overview of, 369370
116, 116t lungs and kidneys in, 213 for respiratory acidosis, 371373
bicarbonate calculation in, 119120 Acid-base conditions, primary vs. for respiratory alkalosis, 373374
external congruity in, 118120 secondary, 217218 supportive (palliative), 370371
FIO2-PaO2 incongruity in, 120 Acid-base data, factors that may Acidemia
indirect metabolic assessment in, complicate, 362364 acute respiratory, case study on,
116117, 116b, 116t, 117t Acid-base diagnosis 422, 434
internal consistency in, 115118, vs. classification, 333 unexplained, case study on, 420,
116b, 116t118t general vs. definitive, 333 432433
laboratory to laboratory support information for, 333 Acidifying agents, for severe
congruity in, 119120 Acid-base disturbance metabolic alkalemia,
modified Henderson equation in, basic (primary), 3842, 38t, 378379
117118, 118t 40t, 41f Acidifying salts, metabolic acidosis
patient-laboratory congruity chronic renal failure and, 364 due to, 350
in, 120 completely compensated, 4446, Acidosis
pH in 44f, 45f, 45t of cerebrospinal fluid, 342343
expected, 116, 116b, 116t mixed (combined). See Mixed due to sodium bicarbonate
[H+] and, 118, 118t acid-base disturbance(s). therapy, 375
rule of eights in, 117, 118t partially compensated, 4344, 45t compensatory, 217218
SaO2-SpO2 incongruity in, 120 respiratory pathology and, defined, 37
total CO2 in, 119 362364 dilution, 316, 349
Acetazolamide (Diamox) due to therapeutic intervention, high anion gap, 325, 325f,
interference with NaHCO3 364 344347, 344f, 345b
reabsorption by, 321 uncompensated, 4243 laboratory, 213
metabolic acidosis due to, 349 Acid-base homeostasis, 196218 lactic, 346347
for severe metabolic alkalemia, 379 buffer systems in, 206210 in COPD, 363364
501
502 Index
Acidosis (Continued) drug-induced, 336 Air, 62

metabolic due to electrolyte composition of atmospheric and
due to acidifying salts, 350 deficiencies, 338 alveolar, 6364, 63t, 64t
alkalinizing agents for, 374377 due to excessive CO2 humidification of, 64, 64t
anion gap and, 324325, 325f production, 339340 saturated, 64
high, 344347, 344f, 345b due to exhaustion, 337 Air bubble, in blood sample, 6667,
normal, 348350, 348f, 348t iatrogenic, 338339 67f, 75t
due to azotemic renal identification of, 41f Air contamination, sampling error
failure, 346 low-flow O2 therapy for, due to, 6667, 67f, 75t
due to biliary or pancreatic 371372 Air travel
fistulas, 349350 with mechanical ventilation, by COPD patients, 267
Carbicarb for, 376 338339, 371, 372373 hypoxemia and, 238239
due to carbonic anhydrase due to neurologic disorders, 339 Air-entrainment mask, 248, 248f
inhibitors, 349 due to neuromuscular disease, Airway closure
causes of, 343350, 344f 337338, 337f, 338f abnormal distribution of ventila-
compensation for, 213214, noninvasive pressure support tion due to, 146147, 146f
216f, 367368, 367t ventilation for, 372 body position effect on, 264265
complete, 45f permissive hypercapnia for, 372 Airway resistance, increased, abnor-
partial, 4142, 43 physiologic response to, 334 mal distribution of ventila-
defined, 3941, 40t during spontaneous breathing, tion due to, 145146, 145f
due to diarrhea, 349 371372 Alcohol, for arterial blood
due to dilution acidosis, 349 treatment for, 371373 collection, 16
due to diuretics, 321 uncompensated, 42 Alcoholic ketoacidosis, 347
due to early renal disease, 349 due to ventilation-perfusion Aldactone (spironolactone), interfer-
due to enteric drainage mismatch, 336 ence with NaHCO3 reabsorp-
tubes, 349 terminology for, 217218 tion by, 321
due to eucapnic ventilation Acquired immunodeficiency Aldosterone, 320, 320f
posthypocapnia, 350 syndrome (AIDS), transmis- Aldosteronoma, 354
hyperchloremic, 325, 325f, sion via blood contact of, 9 ALI. See Acute lung injury (ALI).
348350, 348b, 348f Active transport, 317 Alkalemia
identification of, 41f, 42 Acute chest syndrome, 185186 and hypokalemia, 319
due to ketoacidosis, 347 Acute lung injury (ALI) severe metabolic, 378379
due to lactic acidosis, 346347 body positioning for, 266 unexplained, case study on,
with mechanical ventilation, 364 mechanical ventilation for, 423, 434
overcorrection of, 354 256258 Alkali loading, metabolic alkalosis
physiologic response to, 343 nitric oxide for, 266 due to, 352
due to renal tubular PEEP for, 260 Alkalinizing agents, for metabolic
acidosis, 348349 Acute respiratory distress syndrome acidosis, 374377
sodium bicarbonate for, 374376 (ARDS) Alkalosis
during spontaneous body positioning for, 266 bicarbonate overcorrection, 375
breathing, 364 mechanical ventilation for, compensatory, 217218
due to sulfur, hydrogen 256258, 256b defined, 37
sulfide, or drugs, 350 nitric oxide for, 266 laboratory, 212213
due to toxins, 344345 PEEP for, 260 metabolic
treatment for, 374377 Acute respiratory distress syndrome acetazolamide for, 379
tris-hydroxymethyl-amino- (ARDS)/Net technique, 257 acidifying agents for, 378
methane (THAM) for, 376 Acute respiratory problem, 49, 49t due to adrenocortical
uncompensated, 43 Acute tubular necrosis, 346 hypersecretion, 354
due to urinary diversion, 349 Adrenocortical hypersecretion, due to alkali loading, 352
mixed (combined), 40, 41 metabolic alkalosis due to, due to Bartters syndrome,
renal tubular, 348349 354 353354
respiratory Aerobic metabolism, via oxidative due to bicarbonate
causes of, 334340, 335b, 335f phosphorylation, 188, 189f administration, 354
CO2 retention in, 371373 Afferent arteriole, 313, 313f due to blood transfusions, 354
compensation for, 213, 214f, Afterload, 287 causes of, 351355, 351b, 351f
367, 367t Aging chloride for, 378
complete, 44, 44f, 45f PaO2 with, 47 cimetidine or ranitidine for, 377
partial, 43 P(Aa)O2 with, 233 compensation for, 214, 217f,
due to COPD, 335336 AIDS (acquired immunodeficiency 218, 367t, 368

decreasing VCO2 for, 372 syndrome), transmission via complete, 4445, 44f, 45f
defined, 38, 38t blood contact of, 9 partial, 43, 44
Index 503
Alkalosis (Continued) Alveolar deadspace, 150f Anatomic shunting, 150f, 154,

defined, 40, 40t relative, 150, 150f, 152 155, 155t
due to diuretics, 321, 354 true, 149150, 150f, 152 hypoxemia due to, 237
due to eucapnic ventilation Alveolar hypoventilation, hypox- Anemia, 276281
posthypercapnia, 355 emia due to, 236237, 239t aplastic, 278

fluid volume replacement Alveolar minute ventilation (VA), blood transfusions for, 280281
for, 378 147, 200 Cooleys, 279
due to gastric fluid loss, Alveolar oxygen tension, ideal criteria for, 276
353, 353f or mean, 233 defined, 169, 276
due to glucocorticoids, 322 Alveolar plateau, 409, 409f etiology of, 278280, 279f
hydrochloric acid for, 378 Alveolar pressure (PAlv), 141, 143f hemolytic, 280
due to hyperaldosteronism, 321 Alveolar recruitment maneuver and hypoxia, 280
hypochloremic, 324 (ARM), 258 iron deficiency, 277f, 278279
due to hypokalemia, 352, 377 Alveolar size, and transpulmonary laboratory diagnosis of, 276278,
identification of, 41f, 42 pressure, 141142 277f, 278f, 278t, 279t
due to inadequate renal Alveolar ventilation, 139, 201 macrocytic, 277
perfusion, 354 breathing pattern and, 202, 202f megaloblastic, 277f
due to licorice, 322, 352353 effective, 151 microcytic, 277
with mechanical ventilation, 379 minute vs., 201203, 201t, 202f PaO2 and PvO2 in, 293, 293f
mild-to-moderate, 377378 Alveolar-arterial oxygen tension pernicious, 279
physiologic response to, 351 gradient. See P(Aa)O2. sickle cell, 184186, 185f, 280
potassium for, 377378 Alveolar-capillary (AC) membrane types of, 278280, 279b
due to secondary hyper- diffusion across, 156159, Anesthetics, topical, methemoglo-
aldosteronism, 353354 157f, 158f binemia due to, 183184
severe, 378379 thickening of, 158159 Angiotensin I, 319, 320f
due to steroids, 355 Alveolar-capillary (AC) unit Angiotensin II, 319320, 320f
treatment for, 377379 ideal, 148, 149, 149t, 150f Anion(s), 315
uncompensated, 43 silent, 149t, 153, 153f Anion gap (A), 324326, 325f
mixed (combined), 40, 41 ventilation-perfusion ratio in, hypoalbuminemia and, 326,
uncompensated, 43 147148 326t
respiratory Alveoli, 63, 136 in metabolic acidosis, 344
causes of, 341343, 341b, Ambient light, with pulse high, 344347, 344f, 345b
341f oximetry, 399 normal, 348350, 348f, 348t
compensation for, 213, 215f, American Association for Anisocytes, 279t
367, 367t Respiratory Care (AARC) Anisocytosis, 277, 277f
complete, 45f on guidelines for arterial and Anode, 83
partial, 43 capillary blood sampling, Anticoagulant
defined, 3839, 38t 30, 30t for arterial blood collection,
identification of, 41, 41f on guidelines for capnography/ 1315, 24
with mechanical ventilation, capnometry, 415b arterial blood collection with, 9
342, 373374 on guidelines for oxygen blood gas sampling error due to,
physiologic response to, 340341 therapy, 250, 251b, 252b 6971, 70f, 70t, 75t
of pregnancy, 342 on guidelines for transcutaneous electrolyte sampling error due
rebreathing for, 373 blood gas monitoring, 406b to, 75
during spontaneous on indications for arterial blood Antifreeze, metabolic acidosis due
breathing, 373 gas sampling, 4 to, 345
treatment for, 373374 Ammeter, 84, 85f Aortic bodies, 309310
terminology for, 217218 Ammonia, as urinary buffer, Aoyagi, Takuo, 394
Allen test, modified, 2021, 21f 322323, 322f Aplastic anemia, 278
Altitude Ammonium chloride, for severe Apneustic center, in regulation of
and barometric pressure, metabolic alkalemia, 378 ventilation, 308
66, 66t Ampere (amp), 83 Aqueous buffers, as quality control
hypoxemia and, 238239 Ampholyte, 208 materials, 102
and PO2, 66, 66t Amphoteric substance, 208 Arcuate vein, 313f
Alveolar air Amyl nitrate, methemoglobinemia ARDS. See Acute respiratory distress
composition of, 63t, 64 due to, 183 syndrome (ARDS).
water vapor pressure of, 64 Anaerobic glycolysis, 188 Arginine monohydrochloride, for
Alveolar collapse, hypoxemia Anaerobic metabolism, 290 severe metabolic alkalemia,
due to, 237 Analytical error, 9192 378
Alveolar consolidation, hypoxemia Anaphylactic shock, 284285 Argon, in atmospheric and alveolar
due to, 237 Anatomic deadspace, 150f, 151 air, 63t
504 Index
ARM (alveolar recruitment Arterial carbon dioxide tension. Atelectasis

maneuver), 258 See PaCO2. abnormal distribution of
Arterial blood Arterial end-tidal PCO2 difference ventilation due to, 146f
as mixture of oxygenated and [P(aet)CO2], 152 absorption, 255
shunted blood, 229, 229f Arterial line(s) capillary shunting due to, 152153
pulsatile, 396 cost of, 2829 Atmosphere, 62
venous vs., 78, 8f, 24 insertion of, 2527 Atmospheric air
Arterial blood collection, 825 Arterial line sampling, 2728, composition of, 6364, 63t, 64t
AARC guidelines for, 30, 30t 27f, 28f water vapor pressure of, 64
alcohol, gauze, and tape for, Arterial line systems, Atmospheric pressure, 62
1516 blood-conserving, 28 Auto-filling, during arterial blood
anticoagulant for, 1315, 24 Arterial monitoring system, collection, 24
with anticoagulants, 9 pressurized, 26, 26f Autopositive end-expiratory
aseptic technique for, 1516 Arterial oxygen content (CaO2), pressure (auto-PEEP),
with bleeding disorders, 9 154, 176, 176b, 177b, 177f 263264, 264f
in children or neonates, 12 Arterial oxygen saturation. See SaO2. Average, 93
with chronic airway Arterial oxygen tension. See PaO2. Axillary artery, blood collection
obstruction, 11 Arterial oxygenation, indicators of, from, 17f
complications of, 8, 1718, 22b, 4, 273276 Azotemia, 346
25b, 30t Arterial pH prerenal, 346
documentation of, 1112 as acid-base index, 4 Azotemic renal failure, metabolic
with exercise, 11 normal values for, 4t, 6, 37t acidosis due to, 346
explanation to patient of, 16 units of measurement for, 6
infection control with, 910 Arterial puncture B
local anesthetic for, 16, 18 axillary, 17f Backscatter oximetry, 391392, 392f
materials for, 1216, 13f, 14f, 15b brachial, 17f, 2122, 22f, 2425 Barach, Alvan, 258
with mechanical ventilation, 12 choice of hand/arm for, 19 Barbiturates, respiratory acidosis
with oxygen therapy, 1112 complications of, 8, 1718, 22b, due to, 336
patient identification and 25b, 30t Barometer, 62
assessment for, 1012, 12b dorsalis pedis, 17f Barometric pressure, altitude
patient status and, 912 femoral, 17f, 22, 23f and, 66, 66t
preparation for, 916 legal issues involving, 22b Barotrauma, pulmonary, due to
puncture technique for, 1624 materials for, 1216, 13f, 14f, 15b PEEP, 262
sample handling in, 2425 pain of, 11, 16 Bartters syndrome, metabolic
standard precautions for, 10 radial, 17f21f, 1821, 2224, 23f alkalosis due to, 353354
in steady state, 1011 site selection for, 1617, 16b, Base(s), defined, 197
syringe for, 1213, 13f, 14f 17f, 18f Base excess of blood. See [BE].
Arterial blood gas(es) (ABGs), 330 superficial temporal, 17f Base excess of extracellular fluid
in cardiopulmonary technique for, 1624 ([BE]ecf), 125126, 126t
resuscitation, 375 ulnar, 17f Base homeostasis, 198
in COPD, 362 umbilical, 17 Baseline absorption, 396
indices in, 45, 4t venous puncture during, 22, 2324 [BB], 124
normal ranges for, 4t, 56, 5f Arterialized capillary blood, [BE], 124125
units of measurement for, sampling of, 2930, 30t as acid-base index, 45
67, 7t Arteriolar constriction/dilation, assessment of, 42
Arterial blood gas analysis and cellular oxygen supply, normal values for, 4t, 6
AARC guidelines for, 30, 30t 187188 units of measurement for, 6
cost of, 34, 2829 Arteriospasm, due to arterial Beddoes, Thomas, 250
importance of, 34, 2829 puncture, 18 [BE]ecf, 125126, 126t
indications for, 34, 2829 Arteriovenous oxygen content Beta-hydroxybutyrate, 347
pulse oximetry vs., 34 difference [C(av)O2], 178, Beta-hydroxybutyric acid, 347
Arterial blood pressure, 285286 178b, 179b, 288t Between-subject biologic
Arterial blood sample. See also in estimated shunt equations, variation, 92
Arterial blood collection. 232233 Bicarbonate. See HCO3
anticoagulant for, 1315, 24 Aseptic technique, for arterial blood (bicarbonate).
documentation of, 1112 collection, 1516 Biliary fistulas, metabolic acidosis
handling of, 2425 Aspirin due to, 349350
icing of, 15 metabolic acidosis due to, 344345 Biochemical respiration,
transport of, 15 respiratory alkalosis due to, 342 188189, 189f
Arterial cannulation, 2528, Assayed liquids, 103 Biologic variation, inherent, 92
26f28f Asthma, oxygen therapy for, 253, 254 Bladder, 313f
Index 505
Bleeding disorders, arterial blood structure and function of, 8489, Blood pressure, arterial, 285286
collection with, 9 85f89f Blood transfusion(s)
Bleomycin terminology for, 8384, 84f for anemia, 280281
mechanical ventilation with, 258 Blood gas index(ices), 122126 metabolic alkalosis due to, 354
oxygen therapy with, 255 base excess of blood as, 124125 Blood urea nitrogen (BUN), 346
Blood base excess of extracellular fluid Blood volume, 283284, 284f, 315
base excess of. See [BE]. as, 125126, 126t Blood-brain barrier, 309
oxygen loading into. buffer base as, 124 Blood-gas factor, 92, 101
See External respiration. plasma bicarbonate as, 122, 122b Body fluids, 314315, 314f, 315f
Blood buffers, 209210, 209b, 210f standard bicarbonate as, Body positioning, for hypoxemia
Blood conserving arterial line 122124, 123f and shunting, 264266
systems, 28 T40 standard bicarbonate as, 124 Body temperature and pressure
Blood gas classification, 3550 Blood gas interpretation, 3536 saturated (BTPS), blood gases
acid-base status in, 3646, Blood gas machine, sampling errors measured at, 65, 65f, 73, 74
37f, 37t due to temperature control Bohr effect, 174
metabolic, 3940, 40t in, 74 Bohr equation, Enghoff
respiratory, 3839, 38t Blood gas monitoring modification of, 151
alternative terminology for, 4850 continuous, 103106, 104f, 105f Bone marrow failure, anemia due
base excess [BE] assessment in, 42 vs. measurement techniques, to, 278
basic (primary) acid-base distur- 103106, 388 Bowmans capsule, 313, 313f
bance in, 3842, 38t, 40t, 41f noninvasive, 387415 Boyles law, 65
case studies on, 49b, 50b with capnometry, 406414, Brachial artery, blood collection
compensation assessment in, 407f412f, 412b, 415b from, 17f, 2122, 22f, 2425
4246, 44f, 45f, 45t invasive vs., 388 Bradycardia, 282
complete, 48 with oximetry, 388393, Breathing
efficiency of oxygen uptake 389f392f Cheyne-Stokes, 309, 309f
in, 48, 48t backscatter, 391392, 392f Kussmauls, 347

oxygenation status in, 4647, 46f, CO , 392 spontaneous
46t, 47f ear, 392393 respiratory acidosis with,
pH assessment in, 37, 37f, 37t pulse, 393403, 395f397f, 371372
systematic approach to, 36, 36b 400b, 401f respiratory alkalosis with, 373
temporal adjectives in, 4950, 49t transmission, 390391, 391f, Breathing pattern
ventilatory failure in, 4849 392f and alveolar ventilation, 202,
Blood gas electrodes, 8290 of transcutaneous PO2/PCO2, 202f
accuracy of, 8990, 89t 403406, 404f, 406b and deadspace, 151
basic principles of, 8283 Blood gas sampling errors, 6675, Bronchospasm, abnormal distribution
calibration of, 92 66b, 75t of ventilation due to, 146f
Clark, 8586, 86f due to air contamination, 6667, Brownian movement, 61
vs. continuous monitoring, 67f, 75t BTPS (body temperature and pressure
103106, 104f, 105f due to anticoagulant effects, saturated), blood gases
PCO2, 8889, 88f, 89f 6971, 70f, 70t, 75t measured at, 65, 65f,
pH, 8688, 87f due to dilution effects, 7071, 70f 73, 74
PO2, 8486, 85f, 86f due to icing, 7172 Buffer(s)
preventive maintenance for, 92 due to leukocyte larceny, 7273 blood, 209210, 209b, 210f
quality control for, 92103 due to metabolism effects, 7173, extracellular fluid, 209, 209b,
accuracy vs. precision in, 71t, 75t 210
9596, 95f, 96f due to plastic vs. glass syringes, interactions of, 210
control limits in, 94, 94f 7172 intracellular fluid, 209, 209b, 210
control materials in, 96103 due to temperature alterations, quantity of, 209
control samples in, 94 7374, 73f, 74t urinary, 322323, 322f, 323f
electrode drift in, 96 due to venous sampling or admix- Buffer base [BB], 124
error patterns in, 95, 95f ture, 6769, 68t, 69t, 75t Buffer solutions, 208
external, 9293 Blood gas values, target, 74 Buffer system(s), 206210
internal, 92 Blood loss, anemia due to, 280 effectiveness of, 209, 210f
Levey-Jennings control charts Blood oxygen compartment(s), open vs. closed, 209210, 210f
in, 9495, 94f, 96, 96f 165179 pK of, 209, 210f
statistics for, 93 combined oxygen as, 167176, Buffering reactions, 208
trouble-shooting in, 96, 97t101t 168f172f, 174b176b, 174f, BUN (blood urea nitrogen), 346
Westgard rules in, 96, 101t, 102f 176f Burns
Sanz, 88 dissolved oxygen as, 165167, case study on, 427429, 437
Severinghaus, 89, 89f 166f, 167f respiratory acidosis due to, 340
506 Index
C in arterial blood. See PaCO2. heart rate and, 282

Calcium (Ca2+), 315f, 316t, 317 in venous blood, 7, 292t increased, 144, 144f
Calibration, 92, 405 production of, 200201 with increased shunt,
Calomel electrode terminal, 88 excessive, 339340 230231, 230f
Calorimeter, indirect, 189 respiratory quotient and, 339 as index of tissue oxygenation, 281
CAO (chronic airflow obstruction). thermic effect and, 339340 measurement of, 281
See Chronic obstructive total, 119, 121122 with pulmonary artery
pulmonary disease (COPD). transport of, 203205, 204f, 205t catheter, 288
CaO2, 154, 176, 176b, 177b, 177f Carbon dioxide (CO2) analyzers, normal, 281, 288t
Capillary, distance from, and cellular 407408, 407f, 408f with increased shunt,
oxygen supply, 187, 187f Carbon dioxide (CO2) capacity, 121 229230, 230f
Capillary PO2 (Pc/O 2), 154 Carbon dioxide (CO2) combining Cardiogenic pulmonary edema,
Capillary sampling, 2930, 29b, power, 121 287288, 289f, 289t
29f, 30t Carbon dioxide (CO2) PEEP for, 260
Capillary shunting, 150f homeostasis, 200203 Cardiogenic shock, 282283, 283f,
hypoxemia due to, 237 Carbon dioxide (CO2) narcosis, 254 287, 288t
relative, 153, 155, 155t Carbon dioxide (CO2) retention, in Cardiopulmonary interaction, in
true, 149, 150f, 152153, 153f, respiratory acidosis, 371373 tissue oxygenation, 136138
155, 155t Carbon dioxide (CO2) tension. Cardiopulmonary resuscitation (CPR)
Capnograms, 408410 See PCO2. arterial blood gases in, 375
abnormal, 409410, 411f arterial. See PaCO2. PetCO2 during, 413414
normal, 408409, 409f, 410f venous, 7, 292t sodium bicarbonate during,
volumetric, 410, 411f, 412f Carbon monoxide (CO), 181182 374375
Capnography Carbonic acid (H2CO3), 198 Cardiopulmonary system,
AARC guidelines for, 415b chemical equilibrium of, 198 135136, 136f
defined, 406407 in CO2 transport, 203 Cardiovascular compensatory
Capnometers, infrared absorption, concentration of CO2 and, changes, 136137
407408, 407f 199200 Cardiovascular disorders, treatment
Capnometry, 406414 excretion of, 199200, 200f of, 289290
AARC guidelines for, 415b in hydrolysis reaction, 199 Cardiovascular drugs, 290
defined, 406 and law of mass action, 198199 Cardiovascular response, to respira-
measurement techniques in, levels of, 38 tory alkalosis, 340341
407408, 407f, 408f measurement of, 211 Carotid bodies, 309310
Carbamino compounds, in CO2 pK of, 209, 210f Catheter, for arterial cannulation, 27
transport, 204205 production of, 199, 199f Cathode, 83
Carbamino-hemoglobin, in CO2 Carbonic anhydrase, in CO2 Cations, 315
transport, 204205 transport, 204 plasma, 316317, 316t
Carbicarb, for metabolic acidosis, 376 Carbonic anhydrase inhibitors, 321 C(av)O2, 178, 178b, 179b, 288t
Carbohydrate metabolism, fixed metabolic acidosis due to, 349 in estimated shunt equations,
acids from, 205, 205t Carboxyhemoglobin (HbCO), 232233
Carbon dioxide (CO2) 181182, 182f Cc/O
2, 154
in atmospheric and alveolar air, 63t pulse oximetry with, 398, 402 Cellular oxygen supply, 186188,
complete equilibration of, 157 SaO2 and, 275276, 392 187f
dissolved, 203, 211 smoke inhalation and, 291 Cellular oxygen utilization,
ratio of bicarbonate to, Cardiac arrest, and sodium bicar- 188189, 188t, 189f
211, 212f bonate therapy, 374375 Cellular oxygenation, 135
end-tidal partial pressure of, 152, Cardiac index (CI), 281, 288t cardiopulmonary interaction in,

407, 409 Cardiac minute output (Q, CO), 136138
during cardiopulmonary 147, 281 steps in, 136, 137f
resuscitation, 413414 Cardiac output Central sleep apnea, respiratory
causes of decreased, 412b body position effect on, 264 acidosis due to, 339
causes of increased, 412b clinical assessment of, 281 Central venous pressure (CVP),
as indicator of PaCO2, decreased, 144, 144f 286, 287, 288t
410412, 412b with increased shunt, 230, 230f Cerebral cortex, in regulation of
usefulness of, 413414 with normal shunt, 229, 229f ventilation, 308
for verification of PaO2 and PvO2 in, 293, 293f Cerebrospinal fluid (CSF)
intubation, 413 due to PEEP, 260262, 261f acidosis of, 342343
excretion of, 201203 respiratory alkalosis due to, 343 due to sodium bicarbonate
and H2CO3, 199200, 199f, 200f defined, 136 therapy, 375
in hydrolysis reaction, 199 effect on PaO2 of, 228231, 229f, PCO2 in, 309
partial pressure of. See PCO2. 230f Charles law, 65
Index 507
Chemical equilibrium, 198 Cimetidine, for metabolic of oxygen therapy, 251b, 252b
Chemical reaction, reversible, 198 alkalosis, 377 of PEEP, 260263, 261f263f
Chemical stimuli, respiratory Circulatory shock, PaO2 and PvO2 of pulse oximetry, 400, 400b
alkalosis due to, 342 in, 293, 293f Compressive force, 142
Chemical system, closed, 198 Circulatory status, 281290 Conductor, 83
Chemoreceptors, in regulation of cardiac output in, 281 Congestive heart failure (CHF)
ventilation, 308312, 308f, hemodynamic monitoring of, body position effect on, 265
309f, 311t 285289, 286f, 288t, and COPD, case study on,
central, 308309, 309f 289f, 289t 429430, 438
interactions of, 310312, 311t shock in, 281285, 283f285f hemodynamic changes in, 287,
peripheral, 309310 Citrate, in blood gas sample, 69, 70t 289f
Cheyne-Stokes ventilation, 309, 309f Cl. See Chloride (Cl). pump effectiveness in, 282
CHF. See Congestive heart Clark electrode, structure and Congruity
failure (CHF). function of, 8586, 86f external, 118120
Children Clinical alveolar air equation, 233 laboratory to laboratory, 119120
arterial blood collection in, 12 Clinical Laboratory Improvement patient-laboratory, 120
capillary sampling in, 2930, 29b, Amendments (CLIA), 107 Conjugate acid-base pairs, 207
29f, 30t Closed chemical system, 198 Consistency, internal, 115118,
Chloride (Cl) Closing volume study, 147 116b, 116t118t
distribution of, 315f, 316t CO (carbon monoxide), 181182 Contact bridge, 88
in metabolic alkalosis, 378 CO (cardiac minute output), 147, 281 Continuous intra-arterial blood gases
Chloride replacement, 353 CO2. See Carbon dioxide (CO2). (CIABG), 104106, 104f, 105f
Chloride shift, in CO2 transport, Coagulation disorders, arterial Continuous monitoring, of blood
204, 204f blood collection with, 9 gases, 103106, 104f, 105f
Chronic airflow obstruction (CAO). Coefficient of variation (CV), 93 Continuous positive airway pressure
See Chronic obstructive COLD (chronic obstructive lung dis- (CPAP), 259, 259f, 260f
pulmonary disease (COPD). ease). See Chronic obstructive Control(s), 94
Chronic obstructive lung disease pulmonary disease (COPD). commercially prepared, 103
(COLD). See Chronic Collecting duct, 314 types of, 96103
obstructive pulmonary Collecting tubule, 313f Control charts, 9495, 94f, 96, 96f
disease (COPD). Colorimetric CO2 analysis, 408 Control limits, 94, 94f
Chronic obstructive pulmonary Colorimetry, 389 Control samples, 94
disease (COPD) Coma, due to sodium bicarbonate Controlled mechanical ventilation,
acid-base disturbance in, 362364 therapy, 375 259, 259f
acute exacerbation of, case study Combined acid-base disturbances. Conversion factors, for pressure
on, 425426, 435436 See Mixed acid-base units, 7, 7t
acute hypercapnia in, 363 disturbance(s). Cooleys anemia, 279
with lactic acidosis, 363364 Combined oxygen, 4, 167176 CO-oximetry, 4, 392
air travel with, 267 2,3-diphosphoglycerate in, for calculation of SaO2, 274
arterial blood collection with, 11 175176, 175b, 176b COPD. See Chronic obstructive
arterial blood gases in, 362 hemoglobin in, 167170, pulmonary disease (COPD).
body position and airway 168f, 169f Corrective treatment, 370
closure in, 265266 normal volume of, 176, 177b, 177f Coumadin (warfarin), arterial blood
and congestive heart failure, case oxyhemoglobin dissociation curve collection with, 9
study on, 429430, 438 for, 170175, 171f, 172f, Covert hypoxia, 295296, 295f
oxygen therapy for, 253254, 312 174b, 174f CPAP (continuous positive airway
long-term, 267 saturation of, 170, 170f pressure), 259, 259f, 260f
respiratory acidosis due to, 336 transport of, 180, 180b CPR. See Cardiopulmonary
oxyhemoglobin dissociation curve Compensation resuscitation (CPR).
in, 173 absence of, 368 Creatine kinase reaction, 291
relative hyperventilation in, 362 assessment of, 4246, 44f, 45f, 45t Creatinine, 346
with lactic acidosis, 362363 defined, 36, 42 Critical oxygen delivery point,
respiratory acidosis due to, excessive, 369 294295, 295f
335336 patterns of, 367368, 367t CSF. See Cerebrospinal fluid (CSF).
ventilation in, 311312, 311t terminology for, 217218 Curare cleft, 410, 411f
Chronic respiratory problem, therapeutic, 371 Current, 83
49, 49t Compliance, with PEEP, 261, 262 Cuvette oximeter, 392
CI (cardiac index), 281, 288t Complications CV (coefficient of variation), 93
CIABG (continuous intra-arterial of arterial cannulation, 2526 CvO2, 154, 292t
blood gases), 104106, 104f, of arterial puncture, 6, 1718, CVP (central venous pressure),
105f 24b, 25b, 30t 286, 287, 288t
508 Index
Cyanide in anemia, 280 basic components of, 84, 84f

hypoxia due to, 188189 decreased, 175176, 176b basic principles of, 8283
in smoke inhalation, 291 increased, 175, 175b calibration of, 92, 405
Cyanide poisoning, PvO2 in, 294 and oxyhemoglobin dissociation Clark, 8586, 86f
Cyanosis, 178179, 179b curve, 174, 174b, 174f, 175 defined, 83
peripheral vs. central, 178 in tissue oxygenation, 138 miniature, 104
Dipyridamole, arterial blood PCO2, 8889, 88f, 89f
D collection with, 9 pH, 8688, 87f
Daltons law, 62 Dispersion, 95, 95f, 102f PO2, 8486, 85f, 86f
Deadspace, 149152 Dissociation preventive maintenance for, 92
absolute, 149t electromechanical, 375 quality control for, 92103
alveolar, 150f of hydrogen ions, 207208, 207f, accuracy vs. precision in,
relative, 150, 150f, 152 208t 9596, 95f, 96f
true, 149150, 150f, 152 Dissociation constant, 211 control limits in, 94, 94f
anatomic, 150f, 151 Dissolved oxygen, 165167, control materials in, 96103
breathing pattern and, 151 166f, 167f control samples in, 94
defined, 149 normal volume of, 176, 176b, 177f electrode drift in, 96
disorders of, 152, 152t transport of, 179180, 180b error patterns in, 95, 95f
mechanical, 151 Distal (convoluted) tubule, 313f, 314 external, 9293
physiologic, 150f, 151152 Distending force, 142 internal, 92
relative, 149t, 150f Diuresis, hyperosmolar, 347 Levey-Jennings control charts
Deflation reflex, 312 Diuretics, 314, 321 in, 9495, 94f, 96, 96f
Deoxyhemoglobin, 170 metabolic alkalosis due to, 354 statistics for, 93
Dependent lung regions, airway Dorsalis pedis artery, blood trouble-shooting in, 96, 97t101t
closure and ventilation of, collection from, 17f Westgard rules in, 96, 101t, 102f
146147 Downs, John B., 255 response time of, 405
Depressant drugs, respiratory DPG. See 2,3-Diphosphoglycerate Sanz, 88
acidosis due to, 336 (DPG). Severinghaus, 89, 89f
Dermis, 403, 404f D-phenylalanyl-L-prolyl-L-arginine structure and function of, 8489,
Diabetes mellitus chloromethyl ketone 85f89f
case study on, 424425, 435 (PPACK), 75 terminology for, 8384, 84f
ketoacidosis in, 347 Driving pressure, 157, 293, 293f Electrode drift, 96, 405
Diamox. See Acetazolamide decreased, 158 Electrode terminal(s), 8384
(Diamox). Drug effect, on transcutaneous calomel, 88
Diarrhea, metabolic acidosis PO2, 405 Electrolytes, 315317
due to, 349 Drug-induced metabolic acidosis, 350 defined, 315
Diffuse lung disease, body Drug-induced respiratory distribution of, 315316, 315f
positioning for, 266 acidosis, 336 plasma, 316317, 316t
Diffuse retinopathy of Dyes, pulse oximetry with, 398399 sampling errors for, 7576
prematurity, 255 Dynamic equilibrium, 198 Electromechanical dissociation,
Diffusion, 156159 Dyshemoglobin species, 392 375
available time for, 156 Electromotive force, 83
defined, 317 E Electroneutrality, law of, 324326,
driving pressure in, 157 Ear oximetry, 392393 325f, 326t
equilibration and, 156159, Edecrin (ethacrynic acid), 321 Emotional stimuli, respiratory
157f, 158f Edema, pulmonary alkalosis due to, 343
in external respiration, 138f, 139 capillary shunting due to, 152, 153f Emulsions, as quality control
Grahams law for, 156 cardiogenic, 287288, 289f, 289t materials, 102103
molecular size in, 156 PEEP for, 260 End-tidal partial pressure of CO2
requirements for, 156 case study on, 430432, 438439 (PetCO2). See PetCO2.
solubility coefficient in, 156 noncardiogenic, 288, 289f, 289t Enghoff modification, of
speed of, 156157 Efferent arteriole, 313f Bohr equation, 151
surface area and, 159 Electrical resistance, 83 Enteric drainage tubes, metabolic
Diffusion barriers, 158, 158f Electricity, 8283 acidosis due to, 349
Diffusion defect(s), 158159 Electrochemical cell, 83 EPAP (expiratory positive airway
hypoxemia due to, 238 Electrochemical cell systems, 83 pressure), 259
oxygen therapy for, 248 Electrochemical oxygen probe, 104 Epidermis, 403, 404f
Dilution acidosis, 316, 349 Electrochemical reaction, in PO2 Epoetin (recombinant human
Dilution error, 7071, 70f electrode, 84, 85f erythropoietin), 169170
2,3-Diphosphoglycerate (DPG), Electrode(s), 8290 Equilibration
175176 accuracy of, 8990, 89t complete, 157
Index 509
Equilibration (Continued) gravity dependence of, 139, 139f origin of, 205206
and diffusion, 156159, 157f, 158f normal distribution of, regulation of, 205
incomplete, 158 139141, 139f141f, 144f Fixed performance systems, for
Error(s) Wests zone model of, 139141, oxygen therapy, 248, 249f
analytical, 9192 140f, 141f Flashing pulsation, during arterial
nonanalytical, 91 with positive-pressure blood collection, 24
postanalytical, 91 ventilation, 146 Flow resistors, 259260
preanalytical, 91 shunting in, 150f, 152155, 153f, Fluid compartments, 314315,
random, 95, 102f 154f, 155t 314f, 315f
sampling. See Sampling errors. tidal volume in, 142, 143f Fluid overload, due to sodium
systematic, 95, 102f ventilation in, 138f, 139 bicarbonate therapy,
Error patterns, 95, 95f abnormal distribution of, 375376
ERV (expiratory reserve volume), 145147, 146f Fluid volume replacement, for
142f normal distribution of, metabolic alkalosis, 378
Erythrocytes. See Red blood cell(s) 141143, 142f, 143f Fluid-gas difference, 92
(RBCs). ventilation-perfusion matching in, Fluorescence optodes, 104105, 105f
Erythropoietin, 169170 138f, 139, 147149, Folic acid deficiency, 279280
Ethacrynic acid (Edecrin), 321 148f150f, 149t Formed elements, 276
Ethylene glycol, metabolic acidosis Extracellular fluid, 314f, 315, 315f Fraction of inspired oxygen.
due to, 345 base excess of, 125126, 126t See FIO2 .
Eucapnia, defined, 350 Extracellular fluid buffers, 209, Fractional concentration (F), 62, 62f
Eucapnic ventilation 209b, 210 Fractional SaO2, 274, 275, 392, 402
posthypercapnia, metabolic Extracellular volume contraction, 316 Froth, in blood gas sample, 67
alkalosis due to, 355 Extravascular fluid, 315 Functional residual capacity (FRC)
posthypocapnia, metabolic Extrinsic factor, 279 abnormal
acidosis due to, 350 abnormal distribution of
Ex vivo blood gas systems, 106 F ventilation due to, 146,
Exercise, arterial blood collection F (fractional concentration), 62, 62f 146f, 147
with, 11 Femoral artery, blood collection and airway closure, 147

Exhaled minute ventilation (VE), from, 17f, 22, 23f defined, 141, 142f
152, 201 Femoral nerve, 23f gas distribution at, 141142,
Exhaustion, respiratory acidosis Femoral vein, 23f 142f, 143f
due to, 337 Fetal hemoglobin (HbF, FHb), 183 with PEEP, 262
Expiratory positive airway pressure pulse oximetry with, 398 regional variation in, 141
(EPAP), 259 in sickle cell disease, 280 Functional saturation, 274, 392, 402
Expiratory reserve volume Fever, respiratory acidosis due to, 340
(ERV), 142f Fick equation, 178, 179b G

Expired ventilation (VE), 152, 201 FIO2, 63 Gas(es)
External congruity, 118120 for carbon monoxide altitude effect on, 66, 66t
External quality assessment poisoning, 182 basic physics of, 6166
scheme, 93 normal, 63 fractional concentration of, 62, 62f
External quality control, 9293 in oxygen therapy in liquids, 6566, 66f
External respiration, 138159, 166f for COPD, 253 molecular behavior of, 6162
with airway closure, 146147 high, 251b, 255 pressure of, 61
and alveolar and atmospheric PO2 in low-flow system, partial, 6263, 63f
and PCO2, 64 249250, 250t as quality control materials, 101
in cellular oxygenation, 136, 137f and PaO2 symbols for, 63
with compensatory incongruity of, 120 temperature, pressure, and
disturbances, 147 normal relationship of, 48, 48t volume of, 65, 65f
criteria for, 138139, 138f in shunting, 155, 234, 235 Gas distribution, at function
deadspace in, 149152, 150f, 152t and P(Aa)O2, 234 residual capacity, 141142,
defined, 136 in shunting, 155, 232, 234, 235 142f, 143f
diffusion in, 138f, 139, 156159, Fistula(s) Gas laws, 65, 65f
157f, 158f biliary or pancreatic, metabolic Gas Stat instrument, 105
functional residual capacity in acidosis due to, 349350 Gas transport, 136
abnormal, 146 defined, 349 Gastric fluid loss, metabolic
gas distribution at, 141142, Fixed acids alkalosis due to, 353, 353f
142f, 143f defined, 198 Gastric tonometry, 297
perfusion in excretion of, 206, 322323, 322f, Gastrointestinal disturbance, case
abnormal distribution of, 323f study on, 420, 433
143145, 144f, 145f metabolism of, 205206, 205t Gaussian distribution, 56, 5f
510 Index
Gauze, for arterial blood ratio to dissolved CO2 of, carbamino-, 204205
collection, 16 211, 212f carboxy- (HbCO), 181182, 182f
Gay-Lussacs law, 65, 65f regulation of, 206, 321 pulse oximetry with, 398, 402
Globin, 167, 168, 168f units of measurement for, 6 SaO2 and, 275276, 392

Glomerular filtrate, 313 HCO3 (bicarbonate) smoke inhalation and, 291
Glomerular filtration, 314 actual, 39, 122 desaturated, 170, 178179, 179b
Glomerulus, 313, 313f distribution of, 315f, 316t and erythrocytes, 168170, 169f
Glucocorticoids, metabolic alkalosis for metabolic acidosis, 374376 fetal (HbF, FHb), 183
due to, 322, 355 alternatives to, 376377 pulse oximetry with, 398
Glycolysis, 290 metabolic alkalosis due to, 354 in sickle cell disease, 280
anaerobic, 188 plasma concentration of. inadequate synthesis of, 278279
Glycosuria, 347 See [HCO3]. met- (metHb), 183184, 184f
Glycyrrhizic acid, metabolic alkalosis standard, 122124, 123f functional saturation with, 392
due to, 352353 T40, 124 maintenance of adequate SaO2

Grahams law, 156 HCO3 (bicarbonate) buffer system, with, 276
Gravity, and hypoxemia, 265266 210, 210f pulse oximetry with, 398, 402

Gravity dependence HCO3 (bicarbonate) overcorrection oxy- (Hb-O2).
of perfusion, 139, 139f alkalosis, 375 See Oxyhemoglobin.
of ventilation, 146147 Hct. See Hematocrit (Hct). oxygen carrying capacity of, 176
Guillain-Barr syndrome, respiratory Heart attack, pump effectiveness reduced, 170
acidosis due to, 337, 337f in, 282 saturated, 170, 170f
Heart failure, congestive. See structure of, 167168, 168f, 169f
H Congestive heart failure sulf-, 184, 392
[H+], 196197 (CHF). variant forms of, 182186, 183f
clinical significance of, 196 Heart rate pulse oximetry with, 398
description of, 196197 and cardiac output, 282 Hemoglobin A (HbA), 167, 182,
dissociation of, 207208, normal, 282 183f
207f, 208t Hematocrit (Hct) Hemoglobin buffer system, 209, 210f
and oxyhemoglobin affinity, 174, defined, 276 Hemoglobin H (HbH), 183
174b, 174f ideal, 281 Hemoglobin (Hb) Kansas, 183, 183f
pH and, 118, 118t, 197 normal, 276 Hemoglobin M (HbM), 184
H+ excretion, 322323, 322f, 323f and oxygen transport, 180f, 181, Hemoglobin (Hb) Rainier, 183, 183f
sodium reabsorption via, 276, 276f Hemoglobin S (HbS), 184186, 185f
318319, 318f Hematoma, due to arterial Hemoglobin (Hb) Seattle, 183f
Haldane effect, 174, 205, 312 puncture, 18 Hemolysis
Half-cells, 8384, 84f Hematuria, 314 anemia due to, 280
reference, 84, 84f Heme group, 167, 168, 168f, 169f in oximetry, 391
working (measuring), 84, 84f Hemodialysis, hypoventilation Hemolytic anemia, 280
Hamburger phenomenon, 204, 204f due to, 237 Hemophilia, arterial blood
Handwashing, 10 Hemodynamic monitoring, 285289 collection with, 9
Hb. See Hemoglobin (Hb). of arterial blood pressure, Hemorrhage, due to arterial
[Hb] (blood hemoglobin 285286 puncture, 18
concentration), 276281, of central venous pressure, 286 Hemorrhagic shock, 283284, 284f,
276f278f, 278t, 279b, 279t of pulmonary artery pressure, 287, 288t
Hb-O2. See Oxyhemoglobin. 286287, 286f Hemoximetry, AARC guidelines
HCl (hydrochloric acid) of pulmonary wedge pressure, 287 on, 30t
production of, 353, 353f using pulmonary artery catheter, Henderson equation, 211
for severe metabolic alkalemia, 287289, 288t, 289f, 289t modified, 117118, 118t, 211
378 Hemodynamics Henderson-Hasselbalch equation,
H2CO3. See Carbonic acid (H2CO3). defined, 285 210214
[HCO3] (plasma concentration of effects on pulse amplitude of, clinical applications of, 212214,
bicarbonate) 396, 396f 214f217f
as acid-base index, 45, 122 Hemoglobin (Hb), 167170 development of, 210211
calculated, 119 abnormalities of, 181186 numeric calculations with,
classification of, 3940, 40t SpO2 and, 275 211212, 212f
in CO2 transport, 203 absorption spectrum of, 389, Henrys law, 6566, 66f
normal values for, 4t, 6, 211 389f, 391, 391f Heparin
PCO2 and, 122124, 122b, 123f, acid (HHb), 209, 210f for arterial blood collection,
212 and [BB], 124 9, 1315
pH and, 40, 40t blood concentration of, 276281, with arterial cannulation, 26, 26f
prediction of, 117, 118t 276f278f, 278t, 279b, 279t dry balanced, 75
Index 511
Heparin (Continued) Hyperchloremic metabolic acidosis, chronic, peripheral

sampling errors due to 325, 325f, 348350, 348b, chemoreceptors in, 311
blood gas, 6971, 70f, 70t 348f clinical appearance of, 239, 240b
for electrolytes, 75 Hyperchromia, 278 defined, 46, 138, 228
Hepatitis, transmission via blood Hyperdynamic shock, 284, 285f, differential diagnosis of, 236239,
contact of, 10 288t 239t
Hering-Breuer reflex, 312, 342 PaO2 and PvO2 in, 293294, 294f due to diffusion defects, 238, 239t
Hewlett-Packard ear oximeter, 393 Hyperglycemia, 347 oxygen therapy for, 248
HHb (acid hemoglobin), 209, 210f Hyperkalemia, 316, 317f effects of altitude and air
High anion gap acidosis, 325, 325f plasma, 323324, 324f travel in, 238239
High-flow systems, for oxygen Hyperlactatemia, 290 due to hypoventilation,
therapy, 248, 249f primary, 291 236237, 239t
Histotoxic hypoxia, 188189 secondary, 291, 347 oxygen therapy for, 248
Homeostasis, defined, 197 Hyperosmolar diuresis, 347 and hypoxia, 47, 47f, 138
HPO4, 316t Hyperoxemia, 46, 46f, 46t, mechanisms of, 228, 228b, 228f
Human immunodeficiency virus 239240, 255 mild, 46t, 47, 47f, 247
(HIV), transmission via blood Hypertension, as compensatory moderate, 46t, 47, 47f, 138, 247
contact of, 9 response, 137 PaCO2 in, 311
Humidification, of air, 64, 64t Hyperthermia, malignant, respira- PaO2 and PvO2 in, 293, 293f
Humidity tory acidosis due to, 339340 peripheral chemoreceptors in,
absolute, 64 Hyperventilation 310311
potential, 64 in COPD, 362363 permissive, 258
relative, 64 hyperoxemia due to, 46, 46f pseudo-, 72
and water vapor pressure, 64 to lower intracranial pressure, 373 respiratory alkalosis due to,
Hydrochloric acid (HCl) Hyperventilation syndrome, 343 341342
production of, 353, 353f Hypoalbuminemia, and anion gap, severe, 46t, 47, 47f, 138, 247
for severe metabolic alkalemia, 378 326, 326t due to shunting
Hydrogen ion concentration. See [H+]. Hypocapnia, 38, 340341 absolute, 237, 239t
Hydrogen sulfide, metabolic acidosis Hypocarbia, 38 oxygen therapy for, 248
due to, 350 effect on [HCO3] of, 122b relative, 238, 239t
Hydrolysis effect, 122 eucapnic ventilation post-, oxygen therapy for, 247, 248f
Hydrolysis reaction, 89, 122, 199 metabolic acidosis due to, 350 treatment of, 246267
Hydronium ions, 196197 Hypochloremic metabolic acute vs. chronic, 247
Hydroxyurea, for sickle cell alkalosis, 324 body positioning for, 264266
disease, 186 Hypochromia, 278, 279t mechanical ventilation for,
Hyperaldosteronism, 321322 Hypodermis, 404f 256258, 256b
primary, 354 Hypokalemia, 316317 nitric oxide for, 266
secondary to nonadrenal alkalemia and, 319 objectives in, 246
factors, 353354 cardiovascular effects of, options for, 247, 247b
Hyperbaric oxygen, for carbon 316317, 317f oxygen therapy for, 247255
monoxide poisoning, 182 due to diuretics, 321 AARC clinical practice guide-
Hyperbilirubinemia, pulse oximetry metabolic alkalosis due to, lines for, 250, 251b, 252b
with, 398399 353, 377 administration devices for,
Hypercapnia, 38 plasma, 324, 324f 248250, 248f, 249f, 250t
clinical appearance of, 239, respiratory acidosis due to, 338 clinical approach to,
240b, 334 due to sodium bicarbonate 250254, 251b, 252b
in COPD, 363364 therapy, 375 excessive, 254255
effect on [HCO3] of, 123f Hypoventilation FIO2 levels in
eucapnic ventilation post-, due to hemodialysis, 237 in COPD, 253
metabolic alkalosis due hypoxemia due to, 236237, 239t high, 255
to, 355 oxygen therapy for, 248 in low-flow system, 253
oxygen therapy for, 253254 with increased shunting, 236237 goals in, 250
permissive, 257, 338339 Hypovolemia, 283 high PaO2 levels in, 255
neuromuscular blocking agents Hypovolemic shock, 283284, 284f, high-flow (fixed performance)
for, 336 287, 288t systems for, 248, 248f
for respiratory acidosis, 372 Hypoxemia, 4647 long-term, 267
due to sodium bicarbonate therapy acute, 247 low-flow (variable
arterial, 376 peripheral chemoreceptors in, performance) systems for,
intracellular, 375 310311 249250, 249f, 250t
Hypercarbia, 38 aging effect on, 47 mechanisms of effectiveness
effect on [HCO3] of, 122b, 123f assessment of, 228 of, 247248, 248f
512 Index
Hypoxemia (Continued) hypoxemic, prevention of, 273274 Intracellular fluid, 314, 314f, 315f
in nonoxygen-sensitive local vs. diffuse, 138 Intracellular fluid buffers,
patients, 250253 in septic shock, 293294, 294f 209, 209b, 210
in oxygen-sensitive tissue, 138 Intracranial pressure (ICP),
patients, 253 Hypoxic potential, 47, 47f hyperventilation to
in preterms and lower, 373
neonates, 252b I Intra-individual variation, 92
with progressive IC (inspiratory capacity), 142f Intrapleural pressure (Ppl), 141, 143f
hypercapnia, 253254 Icing Intravascular fluid, 315
in spontaneously breathing of arterial blood sample, 15 Intrinsic factor, 279
patient, 250254 sampling error due to, 7172 Intubation, verification of, PetCO2
palliative, 246247, 247b effect on electrolyte for, 413
PEEP for, 258264 measurements of, 76 IRDS (idiopathic respiratory distress
auto, 263264, 264f ICP (intracranial pressure), hyper- syndrome), PEEP for, 260
clinical approach to, 263 ventilation to lower, 373 Iron deficiency anemia, 277f,
complications of, 260263, Ideal unit, 148, 149, 149t, 150f 278279
261f263f Idiopathic respiratory distress IRV (inspiratory reserve volume),
definition and waveforms of, syndrome (IRDS), PEEP for, 142f
258259, 259f 260 Isobestic point, 391, 391f
equipment systems for, in control, 94, 94f
259260, 260f Incongruity J
indications for, 260 FIO2-PaO2, 120 Jakob-Creutzfeldt disease,
mechanism of effectiveness SaO2-SpO2, 120 transmission via blood
of, 260, 261f Indirect calorimeter, 189 contact of, 10
overview of, 258 Indirect metabolic assessment, Juxtapulmonary capillary receptors
Hypoxemic hypoxia, prevention of, 116117, 116b, 116t, 117t (J receptors), 312313, 342
273274 Infants
Hypoxia arterial blood collection in, K
anemia and, 280 12, 17, 17f K+. See Potassium (K+).
assessment of, 272297 capillary sampling in, 2930, 29b, [K+], plasma, 323324, 324f
key indicator(s) in, 273, 273b, 29f, 30t KCl (potassium chloride), for
290297 methemoglobinemia in, 184 metabolic alkalosis, 377
gastric tonometry as, 297 Infection(s) Ketoacid(s), 205t, 347
lactate as, 290291, 346347 due to arterial blood collection, Ketoacidosis, 347
mixed venous oxygenation 910 alcoholic, 347
indices as, 291294, due to arterial cannulation, 26 diabetic, 347
292f294f, 292t respiratory alkalosis due to, 342 Ketone bodies, 347
oxygen uptake and utilization Inflation reflex, 312 Ketosis, 347
as, 294296, 295f Infrared absorption capnometers, Kidney(s)
vital organ function as, 297 407408, 407f acid excretion by, 197, 198
oxygen supply variable(s) in, Inspiratory capacity (IC), 142f in acid-base balance,
272, 273290, 273b Inspiratory reserve volume 205206, 205t
arterial oxygenation as, (IRV), 142f in acid-base compensation, 213
273276 Inspired oxygen, fraction of. sodium regulation in, 317322,
blood hemoglobin See FIO2. 318f320f, 320t
concentration as, 276281, Intercapillary distance, and cellular Kidney function, 313314, 313f
276f278f, 278t, 279b, oxygen supply, 187, 187f Kilopascal (kPa), 7, 7t
279t Inter-individual biologic variation, 92 Kilowatt (kW), 83
cardiac output as, 281 Internal consistency, 115118, 116b, Kinetic energy, of gas molecules, 61
circulatory status as, 281290 116t118t Kussmauls breathing, 347
hemodynamic monitoring Internal quality control, 92
as, 285289, 286f, 288t, Internal respiration, 136, 137f, L
289f, 289t 166f, 186189, 187f Laboratory accreditation, 107
PaO2 as, 273 International Conference on Laboratory acidosis, 213
SaO2 as, 274276 Acid-Base Terminology, Laboratory alkalosis, 212213
shock as, 281285, 83f285f 217218 Laboratory to laboratory congruity,
causes of, 188189 International System of Units (SI), 7 119120
covert (occult), 295296, 295f Interstitial fluid, 315, 315f Lactate, as indicator of hypoxia,
defined, 47, 138 Interstitial volume, 314f 290291, 346347
histotoxic, 188189 Intra-arterial blood gases, continuous, Lactate/pyruvate (L/P) ratio, 291
hypoxemia and, 47, 47t, 138 104106, 104f, 105f Lactic acid, 290
Index 513
Lactic acidosis, 346347 Mafenide acetate (Sulfamylon standard bicarbonate as,

in COPD, 363364 acetate cream), metabolic 122124, 123f
Lambert-Beer law, 390, 395 acidosis due to, 349 T40 standard bicarbonate as, 124
Law of mass action, 198199 Magnesium (Mg2+), 315f, 316t, 317 total CO2 as, 121122
Left atrial pressure, 288289 Mainstream analyzers, 408, 408f, Metabolic acid-base status,
Left ventricular end-diastolic 409, 410f 3940, 40t
pressure (LVEDP), 287 Malignant hyperthermia (MH), Metabolic acidosis
Left-sided heart failure, 282 respiratory acidosis due to, due to acidifying salts, 350
Leukocyte larceny, 7273 339340 alkalinizing agents for, 374377
Levey-Jennings control charts, Manometer, 62 anion gap and, 324325, 325f
9495, 94f, 96, 96f Mass action, law of, 198199 high, 344347, 344f, 345b
Licorice, metabolic alkalosis due to, Mass spectrometry, 407 normal, 348350, 348f, 348t
322, 352353 Mean, 93 due to azotemic renal failure, 346
Light transmission, thickness of Mean airway pressure, with due to biliary or pancreatic
solution and, 394f, 395 PEEP, 262 fistulas, 349350
Light wavelengths, used in pulse Mean corpuscular hemoglobin Carbicarb for, 376
oximetry, 396397, 397f concentration (MCHC), 278, due to carbonic anhydrase
Lipid metabolism, fixed acids from, 278t inhibitors, 349
205, 205t Mean corpuscular volume (MCV), causes of, 343350, 344f
Liquid(s) 277, 277f, 278t compensation for, 213214, 216f,
assayed, 103 Mean expired gas samples 367368, 367t

gases in, 6566, 66f (PECO2), 151 complete, 45f
tonometered, as quality control Measurement techniques, vs. partial, 4142, 43
materials, 102 monitoring techniques, defined, 3941, 40t
Liquid junction, 88 103106, 388 due to diarrhea, 349
Lithium heparin Mechanical deadspace, 151 due to dilution acidosis, 349
for arterial blood collection, 1315 Mechanical ventilation due to diuretics, 321
sampling errors due to abnormal distribution of due to early renal disease, 349
blood gas, 69 ventilation due to, 146, 146f due to enteric drainage tubes, 349
for electrolytes, 75 arterial blood collection with, 12 due to eucapnic ventilation
Local anesthetic, for arterial blood for hypercapnia, metabolic posthypocapnia, 350
collection, 16, 18 alkalosis due to, 355 hyperchloremic, 325, 325f,
Loop diuretics, 321 for hypocarbia, metabolic 348350, 348b, 348f
Loop of Henle, 313f, 314 acidosis due to, 350 identification of, 41f, 42
Low noise optical probe, 401, 401f for hypoxemia and shunting, due to ketoacidosis, 347
Low-flow systems, for oxygen 256258, 256b due to lactic acidosis, 346347
therapy, 249250, 249f, metabolic acidosis with, 350, 364 with mechanical ventilation, 364
250t metabolic alkalosis with, 355, 379 overcorrection of, 354
for respiratory acidosis, mixed acid-base disturbance with, physiologic response to, 343
371372 369 due to renal tubular acidosis,
L/P (lactate/pyruvate) ratio, 291 respiratory acidosis with, 348349
Lung(s) 338339, 371, 372373 sodium bicarbonate for, 374376
acid excretion by, 197, 198 respiratory alkalosis with, during spontaneous breathing, 364
in acid-base compensation, 213 342, 373374 due to sulfur, hydrogen sulfide, or
chloride shift in, 204, 204f Median nerve, 20f, 21 drugs, 350
and regulation of volatile acids, Mediterranean disease, 279 due to toxins, 344345
198205 Medullary center, in regulation of treatment for, 374377
Lung capacities, 142f ventilation, 308 tris-hydroxymethyl-aminomethane
Lung compliance, with PEEP, 261, Megaloblast(s), 277, 277f, 279t (THAM) for, 376
262 Megaloblastic anemia, 277f uncompensated, 43
Lung function, PaO2 /PAO2 for Metabolic acid-base condition, 213 due to urinary diversion, 349
evaluation of, 234 Metabolic acid-base index(ices), Metabolic alkalemia, severe,
Lung injury, acute. See Acute lung 120126 378379
injury (ALI). base excess of blood as, 124125 Metabolic alkalosis
Lung volumes, 142f base excess of extracellular fluid acetazolamide for, 379
LVEDP (left ventricular end-diastolic as, 125126, 126t acidifying agents for, 378
pressure), 287 blood gas, 122126 due to adrenocortical
buffer base as, 124 hypersecretion, 354
M CO2 combining power as, 121 due to alkali loading, 352
Macrocytes, 279t plasma bicarbonate as, 122, 122b due to Bartters syndrome,
Macrocytosis, 277, 277f preblood gas, 121122 353354
514 Index
Metabolic alkalosis (Continued) Methylene blue, for methemoglo- Multiple organ dysfunction
due to bicarbonate binemia, 184 syndrome (MODS), 257, 296
administration, 354 Mg+ (magnesium), 315f, 316t, 317 Myasthenia gravis, respiratory
due to blood transfusions, 354 MH (malignant hyperthermia), acidosis due to, 338, 338f
causes of, 351355, 351b, 351f respiratory acidosis due to, Myocardial infarction, pump
chloride for, 378 339340 effectiveness in, 282
cimetidine or ranitidine for, 377 Microcytes, 279t
compensation for, 214, 217f, 218, Microcytosis, 277, 277f N
367t, 368 Milk-alkali syndrome, 352 Na+. See Sodium (Na+).
complete, 4445, 44f, 45f Mineralocorticoid excess, 322 NaCl. See Sodium chloride (NaCl).
partial, 43, 44 Miniature electrode systems, 104 NaHCO3. See Sodium bicarbonate
defined, 40, 40t Minute ventilation, 201 (NaHCO3).
due to diuretics, 321, 354 alveolar vs., 201203, 201t, 202f Nail polish, pulse oximetry with, 398
due to eucapnic ventilation exhaled, 201 Narcotic(s), respiratory acidosis
posthypercapnia, 355 Mitral valve replacement, case study due to, 336
fluid volume replacement for, 378 on, 426427, 436 Narcotic overdose, case study on,
due to gastric fluid loss, 353, 353f Mixed acid-base disturbance(s), 419420, 432
due to glucocorticoids, 322 364369 Nasal cannulas, 249250, 249f,
hydrochloric acid for, 378 alerts to, 368369, 368b 250t, 251b, 252b
due to hyperaldosteronism, 321 common settings of, 369, 369b Nasogastric suction, case study on,
hypochloremic, 324 due to compensatory patterns, 422423, 434
due to hypokalemia, 352, 377 367368, 367t National Institute of Standards
identification of, 41f, 42 defined, 40, 364365 and Technology (NIST)
due to inadequate renal example of, 41 certification, 92
perfusion, 354 with excessive compensation, Needle(s)
due to licorice, 322, 352353 369 for arterial blood collection, 12,
with mechanical ventilation, 379 in long-standing pulmonary or 13f, 14f
mild-to-moderate, 377378 renal disease, 368369 safety with, 10, 13, 14f, 15b, 24
physiologic response to, 351 partially compensated, 43 Neon, in atmospheric and alveolar
potassium for, 377378 recognition of, 365369, air, 63t
due to secondary hyper- 365f, 366f Neonates
aldosteronism, 353354 with respiratory assistance, 369 arterial blood collection in,
severe, 378379 temporal inconsistencies in, 369 12, 17, 17f
due to steroids, 355 uncompensated, 43, 368 capillary sampling in, 2930, 29b,
treatment for, 377379 Mixed venous blood, 6869, 69t, 29f, 30t
uncompensated, 43 291292, 292t dilution effect of heparin in, 71
Metabolic alkalosishypokalemia Mixed venous carbon dioxide idiopathic respiratory distress
syndrome, 353 partial pressure (Pv CO2), 7, syndrome in, PEEP for, 260
Metabolic assessment, indirect, 292t oxygen therapy in, 252b
116117, 116b, 116t, 117t Mixed venous gases, continuous Nephron, 313314, 313f
Metabolic cart, 189 monitoring of, 106 Neurogenic shock, 284, 288t
Metabolic disturbance(s), 39 Mixed venous oxygen content, 154, Neurologic disorders
Henderson-Hasselbalch equation 176178, 178b respiratory acidosis due to, 339
with, 212213, 216f, 217f Mixed venous oxygen partial respiratory alkalosis due to,
Metabolic indices, 45, 4t pressure. See PvO2. 342343
Metabolism Mixed venous oxygen saturation Neurologic response, to respiratory
blood gas sampling errors (Sv O2), 292, 292f, 292t alkalosis, 340
due to, 7173, 71t, 75t Mixed venous oxygenation indices, Neuromuscular blocking agents,
qualitative effects of, 71 291294, 292f294f, 292t respiratory acidosis due to,
quantitative effects of, 71, 71t mm Hg, 67, 7t 336
Methanol, metabolic acidosis due MODS (multiple organ dysfunction Neuromuscular disease, respiratory
to, 345 syndrome), 257, 296 acidosis due to, 337338,
Methemoglobin (metHb), 183184 Molar extinction coefficient, 390 337f, 338f
functional saturation with, 392 Molecular size, and speed of Neuromuscular junction, in
maintenance of adequate SaO2 diffusion, 156 myasthenia gravis, 338, 338f
with, 276 Monitoring, blood gas. See Blood Newborns. See Neonates.
pulse oximetry with, 184, 184f, gas monitoring. NIST (National Institute of
398, 402 Morphine, respiratory acidosis due Standards and Technology)
Methemoglobinemia, 183184, 398 to, 336 certification, 92
Methyl salicylate, metabolic acidosis Motion artifact, in pulse oximetry, Nitric oxide, for hypoxemia and
due to, 344 399400 shunting, 266
Index 515
Nitrogen, in atmospheric and alveolar Optical probe, low noise, 401, 401f two wavelength methodology
air, 63t Optical shunting, with pulse for, 396397, 397f
Nitroglycerin, methemoglobinemia oximetry, 399 usefulness of, 401402
due to, 183 Optodes, 104105, 104f, 105f and ventilation, 403
Nocturnal Oxygen Therapy Trial Oxalate, in blood gas sample, 69, 70t transmission, 390391, 391f, 392f
(NOTT), 267 Oxidative phosphorylation, aerobic Oxygen (O2)
Nomogram, for calculation of metabolism via, 188, 189f in atmospheric and alveolar air, 63t
SaO2 , 274 Oximeter(s), 388, 390 combined, 4, 167176
Nonanalytical error, 91 Oximetry, 388393, 389f392f 2,3-diphosphoglycerate in,
Non-electrolytes, 315 backscatter (reflection), 391392, 175176, 175b, 176b
Noninvasive blood gas monitoring, 392f hemoglobin in, 167170, 168f,
387415 for calculation of SaO2, 274275 169f

with capnometry, 406414, CO , 4, 392 normal volume of, 176, 177b,
407f412f, 412b, 415b for calculation of SaO2, 274 177f
invasive vs., 388 defined, 390 oxyhemoglobin dissociation
with oximetry, 388393, 389f392f ear, 392393 curve for, 170175, 171f,
backscatter, 391392, 392f historical development of, 388 172f, 174b, 174f

CO , 392 pulse, 393403 saturation of, 170, 170f
ear, 392393 accuracy of, 397398, 402403 transport of, 180, 180b
pulse, 393403, 395f397f, and acid-base balance, 403 complete equilibration of, 157
400b, 401f advances in technology for, dissolved, 4, 165167, 166f, 167f
transmission, 390391, 391f, 401, 401f normal volume of, 176, 176b,
392f advantages of, 393 177f
of transcutaneous PO2 /PCO2, ambient light with, 399 transport of, 179180, 180b
403406, 404f, 406b vs. arterial blood gas distribution in blood of, 176, 177f
Noninvasive pressure support sampling, 34 fraction of inspired. See FIO2.
ventilation, for respiratory for calculation of SaO2, hyperbaric, for carbon
acidosis, 372 274275 monoxide poisoning, 182
Non-rebreathing mask, 249, 249f, conventional underlying partial pressure of. See PO2.
251b technologies of, 394 in alveoli, 155, 234235
Non-respiratory indices, 45, 4t as cross-check of arterial vs. in arterial blood. See PaO2.
Normal distribution, 56, 5f venous sample, 68 inhaled. See PIO2.
Normal range, 93 with decreased perfusion, 399 in venous blood. See PvO2.
Normoblasts, 278, 279t, 280 with dyes and pigments, Oxygen administration devices,
Normochromia, 278 398399 248250, 248f, 249f, 250t
Normoxemia, 46, 46t false alarms in, 400 Oxygen carrying capacity, of
NOTT (Nocturnal Oxygen general application of, 401403 hemoglobin, 176
Therapy Trial), 267 hazards and complications of, Oxygen content, 176179
Nutrition, total parenteral, respira- 400, 400b of arterial blood, 154, 176, 176b,
tory acidosis due to, 339, with hemoglobin variants, 398 177b, 177f
340 historical development of, 394 of ideal capillary blood, 154
with hyperbilirubinemia, of mixed venous blood, 154,
O 398399 176178, 178b
O2 . See Oxygen (O2). indications for, 400b Oxygen content difference,
Obese patients, body position and with methemoglobinemia, 184, arteriovenous, 178, 178b,
airway closure in, 265 184f 179b
Ohm, 83 for monitoring, 393394 Oxygen delivery. See Oxygen
Ohms law, 83 motion artifact in, 399400 transport.
Oil of wintergreen, metabolic with nail polish, 398 Oxygen delivery point, critical,
acidosis due to, 344 optical interference with, 399 294295, 295f
Oliguria, 314 overview of, 393394 Oxygen extraction, variable, 188,
On-demand blood gas systems, 106 and oxygen saturation, 120, 188t
Ondines curse, respiratory acidosis 396, 397, 397f Oxygen free radicals, 255
due to, 339 photoelectric plethysmography Oxygen hoods, 252b
100% O2 test, 237 in, 394397, 394f397f Oxygen loading, into blood.
Open lung approach, 257 sites for, 395, 395f See External respiration.
Optical cross talk, with pulse technical limitations of, Oxygen masks, 249, 249f, 250t,
oximetry, 399 397400, 400b 251b, 252b
Optical density, 390 temperature effect on, 400 Oxygen saturation. See SaO2.
Optical interference, with pulse transcutaneous PO2 vs., Oxygen supply, cellular, 186188,
oximetry, 399 405406 187f
516 Index
Oxygen supply dependency hematocrit and, 180f, 181, 276, normal values for, 233
pathological, 295296 276f and physiologic shunt, 233234
physiologic, 294 oxyhemoglobin curve and, PaCO2
Oxygen tension. See PO2. 174175, 175f classification of, 3839, 38t
arterial. See PaO2. quantitative, 179181, 180b, 180f in COPD, 253254, 311312, 311t
venous. See PvO2. total, 180, 180b effect of increasing shunting on,
Oxygen therapy Oxygen unloading, 137f 154f, 155
AARC clinical practice guidelines Oxygen uptake effect of metabolism on, 71, 71t
for, 250, 251b, 252b in covert hypoxia, 295296, 295f and [HCO3], 123124, 123f, 212
administration devices for, efficiency of, 48, 48t heparin effect on, 70, 70f
248250, 248f, 249f, 250t, in multiple organ dysfunction in hypoxemia, 311
251b, 252b syndrome, 296 in iced samples, 72
arterial blood collection with, normal, 294295 normal values for, 4t, 6
1112 vasodilator effects on, 296 and oxygenation ratio, 235
clinical approach to, 250254, Oxygen utilization, cellular, PetCO2 as indicator of, 410412,
251b, 252b 188189, 188t, 189f 412b
complications of, 251b, 252b Oxygenation pH and, 39, 40t
for COPD, 253254, 312 arterial, indicators of, 4, 273276 acute relationship of, 116, 116t
FIO2 levels in, 253 cellular (tissue), 135 as pulmonary shunting index, 231
long-term, 267 cardiopulmonary interaction in, units of measurement for, 67
respiratory acidosis due to, 136138 and ventilation, 310, 311
336 steps in, 136, 137f total expired, 152
excessive, 254255 indicators of, 4 as ventilation index, 4, 203
FIO2 levels in normal values for, 4t, 6 in ventilatory failure, 4849
in COPD, 253 Oxygenation disturbance, case study P(aet)CO2, 152
high, 251b, 255 on, 423424, 434 Pagophagia, 279
in low-flow system, 249250, Oxygenation ratio, 48, 48t, 235 Pain, of arterial puncture, 11, 16
250t Oxygenation status, 4647, 46f, Palliative therapy
goals in, 250, 251b, 252b 46t, 47f for acid-base disturbances, 370371
high PaO2 levels in, 255 Oxyhemoglobin, 167, 170 for hypoxemia and shunting,
high-flow (fixed performance) Oxyhemoglobin affinity, 173174, 246247, 247b
systems for, 248, 248f 174b, 174f PAlv, 141, 143f
hyperoxemia due to, 46, 46f factors that alter, 174, 174b, 174f Pancreatic fistulas, metabolic
for hypoxemia and shunting, Oxyhemoglobin dissociation curve, acidosis due to, 349350
247255 170175, 171f PAO2, 155, 234235
indications for, 251b, 252b association/dissociation PaO2
long-term, 267 portions of, 173 aging effect on, 6, 47
low-flow (variable performance) as bar graph, 170172, 172f air contamination effect on,
systems for, 249250, 249f, in chronic obstructive pulmonary 6667, 67f
250t disease, 173 altitude effect on, 6
for respiratory acidosis, 371372 2,3-diphosphoglycerate and, 174, body position effect on, 265
mechanisms of effectiveness of, 174b, 174f, 175 cardiac output and, 228231,
247248, 248f key landmarks on, 170, 171f 229f, 230f
monitoring of, 251b and SAO2SpO2 incongruity, 120 classification of, 4647, 46f, 46t
in nonoxygen-sensitive patients, shifts of, 174, 174b, 174f continuous monitoring of, 106
250253 with carboxyhemoglobin, in COPD, 253, 311312, 311t
in oxygen-sensitive patients, 253 181182, 182f FIO2 and
PaO2/PAO2 as guide to, 234 clinical effects of, 174175, 175f incongruity of, 120
in preterms and neonates, 252b significance of PO2 changes on, normal relationship of, 48, 48t
with progressive hypercapnia, 172173, 172f in shunting, 155, 234, 235
253254 as two straight lines, 170, 171f heparin effect on, 70
for respiratory acidosis, high, 255
371372 P in iced samples, 72
in spontaneously breathing P. See Partial pressure (P). as indicator of hypoxia, 273274
patient, 250254 P50, 171f, 173174 leukocyte count and, 7273
Oxygen toxicity, 255 Pa (pascal), 7 low, 253
Oxygen transfer, percentage of P(Aa)O2, 155 with mechanical ventilation, 258
successful, 234 with aging, 233 metabolism effect on, 71, 71t
Oxygen transport, 137f, 166f calculation of, 233 normal values for, 4t, 6
combined, 180, 180b FIO2 and, 234 with oxygen therapy, 250, 255
dissolved, 179180, 180b limitations of, 234 long-term, 267
Index 517
PaO2 (Continued) transcutaneous monitoring of, in azotemia, 346

as oxygenation index, 4 403, 405, 406b and [BE]ecf, 125126, 126t
paradoxical effect of PEEP on, 262 P(ae)CO2, 412413 classification of, 37, 37t
percentage oxygen effect on, 6 PCO2 electrodes clinical significance of, 37
and perfusion, 145, 145f accuracy of, 89, 89t in compensation, 45, 45f, 45t
with plastic vs. glass syringe, 13 structure and function of, 8889, defined, 197
PtcO2 and, 404405 88f, 89f expected, 116, 116b, 116t, 117,
and SaO2, 170, 173 troubleshooting guide for, 98t99t 117t
shunting and, 154f, 155 Peachtree syringe, 14f fluorescence systems for

significance of, 167 PECO2, 151 measurement of, 105
spontaneous variability of, 11 PEEP. See Positive end-expiratory and [H+], 118, 118t, 197
in supine vs. sitting position, 6 pressure (PEEP). [HCO3] and, 40, 40t
units of measurement for, 67 Performance characteristics, 90 metabolism effect on, 71, 71t
venous admixture and, 68, 68t Performance record, 94 of mixed venous blood, 292t
and ventilation, 145, 145f, 310 Performance standards, 93 normal, 4t, 6, 37, 37t, 211
PaO2 /%FIO2, 48, 48t Perfusion and oxyhemoglobin affinity, 174,
PaO2 /FIO2, 155, 235 abnormal distribution of, 174b, 174f
PaO2 /PAO2, 155, 234235 143145, 144f, 145f PaCO2 and, 39, 40t, 116, 116t
PAP (pulmonary artery pressure), compensatory disturbances in, plasma, 323324, 324f
286287, 286f, 288t 143, 145, 145f temperature effect on, 74t
diastolic, 288, 288t generalized decrease in, 144145, of urine, 348
Paraldehyde (Paral), metabolic 144f venous, 78
acidosis due to, 345 generalized increase in, 144, 144f and ventilation, 310
Parenteral nutrition, total, respiratory gravity dependence of, 139, 139f pH assessment, 37, 37f, 37t
acidosis due to, 339, 340 local changes and, 145, 145f pH electrodes
Partial pressure (P), 6263, 63f macroscopic changes and, 145 accuracy of, 89, 89t
of atmospheric and alveolar air, normal distribution of, 139141, structure and function of, 8688,
6364, 63t 139f141f, 144f 87f
of carbon dioxide. See PCO2. in normal lung, 148, 148f troubleshooting guide for,
in arterial blood. See PaCO2. primary disturbances in, 97t98t
in venous blood, 7, 292t 143145 pH homeostasis, 197
and fractional concentration, pulse oximetry with decreased, 399 Phosphate(s)
6263, 62f, 63f and transcutaneous PO2, 405 distribution of, 315f, 316
of oxygen. See PO2. Wests zone model of, 139141, as urinary buffer, 323, 323f
in alveoli, 155, 234235 140f, 141f Phosphorus, serum (HPO4), 316t
in arterial blood. See PaO2. Peripheral venous blood, 69 Photodetector, 389
inhaled. See PIO2. Peritubular capillaries, 313f Photoelectric effect, 389390, 390f
in venous blood. See PvO2. Permissive hypercapnia, 257, Photoelectric plethysmography,
Partial rebreathing masks, 249, 338339 394397, 394f397f
249f, 250t, 251b neuromuscular blocking agents Physiologic deadspace (VD), 150f,
Pascal (Pa), 7 for, 336 151152
Pathological oxygen supply for respiratory acidosis, 372 as percentage of tidal volume
dependency, 295296 Pernicious anemia, 279 (VD/VT), 151152
Patient identification, 10 PetCO2, 152, 407, 409 Physiologic oxygen supply
Patient-laboratory congruity, 120 during cardiopulmonary dependency, 294
Pc/O
2, 154 resuscitation, 413414 Physiologic shunting, 154155
PCO2 causes of decreased, 412b assessment of, 155, 232236
air contamination effect on, 67 causes of increased, 412b classic shunt equation for, 154, 232
alveolar vs. atmospheric, 64 as indicator of PaCO2, 410412, clinical significance of, 154155,
arterialized capillary, 29 412b 154f
during cardiopulmonary usefulness of, 413414 components of, 150f
resuscitation, 375 for verification of intubation, 413 defined, 154, 232
in cerebrospinal fluid, 309 pH estimated shunt equations for,
fluorescence systems for abnormal, 37 232233
measurement of, 105 clinical manifestations of, indices of, 232236, 232b
and [HCO3], 122124, 122b, 123f 37, 37f measurement of, 154
normal values for, 6 arterial normal values for, 154
and oxyhemoglobin affinity, 174, as acid-base index, 4 Pica, 279
174b, 174f normal values for, 4t, 6, 37t Pickwickian syndrome, respiratory
temperature effect on, 7374, units of measurement for, 6 acidosis due to, 339
73f, 74t arterialized capillary, 29 Pierson, David, 258
518 Index
Pigments, pulse oximetry with, Positioning, for hypoxemia and Pressure

398399 shunting, 264266 of gas, 61
PIO2 Positive end-expiratory pressure partial. See Partial pressure (P).
calculation of, 233 (PEEP), 258264 Pressure bandages, after arterial
low, 228 auto (covert, inadvertent, blood collection, 16, 24
normal, 63 occult), 263264, 264f Pressure unit conversion factors,
pK clinical approach to, 263 7, 7t
of buffer system, 209, 210f complications of, 260263, Pressurized arterial monitoring
of carbonic acid, 209, 210f 261f263f system, 26, 26f
pKc, normal, 211 continuous mechanical Preterm infants
PL (transpulmonary pressure), ventilation with, 259, 259f oxygen therapy in, 252b
141142, 143f definition and waveforms of, SpO2 targets for, 402
Plasma, 276, 315, 315f 258259, 259f Preventive maintenance, 92
Plasma electrolytes, 316317, 316t differential lung, 262, 263f Proficiency testing, 9293
Plasma volume, 314f equipment systems for, 259260, Prostacyclin, effect on oxygen
Plethysmogram, 395396, 396f 260f uptake of, 296
Plethysmograph, defined, 394 indications for, 260 Protein catabolism, fixed acids from,
Plethysmography, photoelectric, mechanism of effectiveness of, 205, 205t
394397, 394f397f 260, 261f Proteinuria, 314
Pneumonia, capillary shunting due overview of, 258 Proximal (convoluted) tubule,
to, 152 with spontaneous breathing, 259 313314, 313f
Pneumotaxic center, in regulation of withdrawal from, 263 Pseudohypoxemia, 72
ventilation, 308 Positive-pressure ventilation, Psychogenic shock, 284
PO2, 4, 6 abnormal distribution of PtcCO2, 403, 405, 406b
altitude and, 66, 66t ventilation due to, 146, 146f PtcO2, 403406, 404f, 406b
alveolar Postanalytical error, 91 Pulmonary artery catheter, 286, 286f
vs. atmospheric, 64 Potassium (K+) hemodynamic monitoring using,
ideal or mean, 233 imbalance of, 316317, 317f 287289, 288t, 289f, 289t
arterial. See PaO2. in intracellular and extracellular insertion of, 286287, 286f
capillary, 154 fluid, 315, 315f Pulmonary artery diastolic pressure,
arterialized, 29 in metabolic alkalosis, 377378 288, 288t
fluorescence systems for plasma concentration of, 316, 316t Pulmonary artery pressure (PAP),
measurement of, 105, 105f serum concentration of, 352 286287, 286f, 288t
linear relationship of dissolved sodium reabsorption via diastolic, 288, 288t
oxygen with, 167, 167f excretion of, 319, 319f Pulmonary barotrauma, due to
and SO2, 170173, 171f, 172f, 275 Potassium chloride (KCl), for PEEP, 262
temperature effect on, 73, 73f, metabolic alkalosis, 377 Pulmonary capillary transit time,
74, 74t Potassium deficit, in metabolic 156, 157f, 158
transcutaneous monitoring of, alkalosis, 377 Pulmonary circulation, 8f
403406, 404f, 406b Potassium loss, in metabolic Pulmonary disease, and acid-base
venous. See PvO2. alkalosis, 377 disturbance, 362364
PO2 electrodes Potential, 83 mixed, 368369
accuracy of, 8990, 89t Potentiometer, 83 Pulmonary edema
calibration of, 92 Potentiometric method, 86 capillary shunting due to, 152,
structure and function of, 8486, PPACK (D-phenylalanyl-L- 153f
85f, 86f prolyl-L-arginine cardiogenic, 287288, 289f, 289t
troubleshooting guide for, chloromethyl ketone), 75 PEEP for, 260
99t101t Ppl (intrapleural pressure), 141, 143f case study on, 430432, 438439
Poikilocytes, 279t Preanalytical error, 91 noncardiogenic, 288, 289f, 289t
Poikilocytosis, 277 Preblood gas indices, 121122 Pulmonary gas trapping, with PEEP,
Point-of-care (POC) testing, Precaution samples, 10 263264, 264f
106107 Precision, accuracy vs., 9596, Pulmonary perfusion. See Perfusion.
Poisons, metabolic acidosis due 95f, 96f Pulmonary secretions, increased,
to, 345 Pregnancy, respiratory alkalosis abnormal distribution of
Polarographic technique, 85 of, 342 ventilation due to, 146, 146f
Polarography, for PO2 electrode, Preload, 287 Pulmonary vascular resistance (PVR)
8485, 85f Premature infants increased, 144f, 145
Polycythemia, secondary, 138 oxygen therapy in, 252b normal, 288t
Polypeptide chains, in hemoglobin, SpO2 targets for, 402 Pulmonary wedge pressure (PWP),
168, 168f, 169f Prematurity, diffuse retinopathy 287288, 288t
Polyuria, 314 of, 255 increased, 287
Index 519
Pulsatile arterial blood, 396 Q size of, 169

Pulse amplitude, effects of Q (cardiac minute output), 147, 281 abnormal, 277, 277f

hemodynamics on, 396, Qsp, 154 structure of, 169, 169f

396f Qsp/QT. See Physiologic shunting. Red blood cell concentration

Pulse oximetry, 393403 Qs/QT, 154 (RBC), normal, 276

accuracy of, 397398, 402403 QT, 154 Red cell volume, 314f
and acid-base balance, 403 Quality assurance, 9192 Reference solution, for pH
advances in technology for, Quality control, 92103 electrode, 86, 87f
401, 401f accuracy vs. precision in, 9596, Reflection oximetry, 391392,
advantages of, 393 95f, 96f 392f
ambient light with, 399 control limits in, 94, 94f Reflex(es)
vs. arterial blood gas sampling, control materials in, 96103 Hering-Breuer (stretch), 312, 342
34 control samples in, 94 J receptor, 312313, 342
for calculation of SaO2, 274275 electrode drift in, 96 in regulation of ventilation, 308,
conventional underlying error patterns in, 95, 95f 308f, 312313
technologies of, 394 external, 9293 Regional gas exchanges, in normal
as cross-check of arterial vs. internal, 92 lung, 149, 149f
venous sample, 68 Levey-Jennings control charts in, Regulations, 107
with decreased perfusion, 399 9495, 94f, 96, 96f Relative humidity (RH), 64
with dyes and pigments, 398399 statistics for, 93 Renal artery, 313f
false alarms in, 400 trouble-shooting in, 96, Renal disease
general application of, 401403 97t101t early, metabolic acidosis
hazards and complications of, Westgard rules in, 96, 101t, 102f due to, 349
400, 400b Quality management, 9091, 90f long-standing, mixed acid-base
with hemoglobin variants, 398 Quality specifications, 90, 90f disturbance with, 368369
historical development of, 394 Renal failure
with hyperbilirubinemia, 398399 R anemia due to, 279
indications for, 400b Radial artery azotemic, metabolic acidosis due
with methemoglobinemia, blood collection from, 1821, to, 346
184, 184f 2224 chronic, and acid-base
for monitoring, 393394 cannulation of, 25 disturbance, 364
motion artifact in, 399400 location of, 17f19f Renal function, 313314, 313f
with nail polish, 398 occlusion of, 26 Renal perfusion, metabolic alkalosis
optical interference with, 399 pulsations from, 1920, 19f due to inadequate, 354
overview of, 393394 puncture of, 2224, 23f Renal tubular acidosis (RTA),
and oxygen saturation, 120, 396, and ulnar collateral circulation, metabolic acidosis due to,
397, 397f 2021, 21f 348349
photoelectric plethysmography in, Radial nerve, 19f, 20, 20f Renal vein, 313f
394397, 394f397f Random error, 95, 102f Renin-angiotensin system,
sites for, 395, 395f Ranitidine, for metabolic 319320, 320f
technical limitations of, 397400, alkalosis, 377 Reservoir bags, 249, 249f
400b RAP (right atrial pressure), 286 Residual volume (RV), 142f
temperature effect on, 400 RBCs. See Red blood cell(s) (RBCs). airway closure and, 147
transcutaneous PO2 vs., 405406 Reabsorption, of sodium, 317322, Respiration
two wavelength methodology for, 318f320f, 320t biochemical, 188189, 189f
396397, 397f Real-time information, 103106, external, 138159, 166f
usefulness of, 401402 388, 398 with airway closure, 146147
and ventilation, 403 Rebreathing and alveolar and atmospheric
PvCO2, 7, 292t capnography of, 409, 411f PO2 and PCO2, 64
PvO2, 7 for respiratory alkalosis, 373 in cellular oxygenation,
in clinical disturbances, 293294, Recombinant human erythropoietin 136, 137f
293f, 294f (Epoetin), 169170 with compensatory
measurement with pulmonary Red blood cell(s) (RBCs), 168169 disturbances, 147
artery catheter of, 288 hemoglobin in, 168169 criteria for, 138139, 138f
mechanisms of decreased, 231 immature, 277278, 278f deadspace in, 149152,
PVR (pulmonary vascular resistance) loss of, anemia due to, 280 150f, 152t
increased, 144f, 145 mature, 277, 277f defined, 136
normal, 288t normal, 277, 277f diffusion in, 138f, 139,
PWP (pulmonary wedge pressure), production of, 169 156159, 157f, 158f
287288, 288t inadequate, 279280 functional residual capacity in
increased, 287 shape of, 277, 277f abnormal, 146
520 Index
Respiration (Continued) during spontaneous breathing, RV (residual volume), 142f

gas distribution at, 141142, 371372 airway closure and, 147
142f, 143f treatment for, 371373
perfusion in uncompensated, 42 S
abnormal distribution of, due to ventilation-perfusion Salicylates
143145, 144f, 145f mismatch, 336 metabolic acidosis due to,
gravity dependence of, Respiratory alkalosis 344345
139, 139f causes of, 341343, 341b.341f respiratory alkalosis due to, 342
normal distribution of, compensation for, 213, 215f, Salt bridge, 88
139141, 139f141f, 144f 367, 367t Sample handling, for arterial blood
Wests zone model of, complete, 45f collection, 2425
139141, 140f, 141f partial, 43 Sampling errors
with positive-pressure defined, 3839, 38t blood gas, 6675, 66b, 75t
ventilation, 146 identification of, 41, 41f due to air contamination,
shunting in, 150f, 152155, with mechanical ventilation, 342, 6667, 67f, 75t
153f, 154f, 155t 373374 due to anticoagulant effects,
tidal volume in, 142, 143f physiologic response to, 340341 6971, 70f, 70t, 75t
ventilation in, 138f, 139 of pregnancy, 342 case studies on, 69b, 73b
abnormal distribution of, rebreathing for, 373 due to dilution effects, 7071,
145147, 146f during spontaneous breathing, 373 70f
normal distribution of, treatment for, 373374 due to icing, 7172
141143, 142f, 143f Respiratory disease, and acid-base due to leukocyte larceny, 7273
ventilation-perfusion matching disturbance, 362364 due to metabolism, 7173, 71t,
in, 138f, 139, 147149, mixed, 368369 75t
148f150f, 149t Respiratory distress syndrome due to plastic vs. glass syringes,
internal, 136, 137f, 166f, acute 7172
186189, 187f body positioning for, 266 due to temperature alterations,
Respiratory acid-base condition, 213 mechanical ventilation for, 7374, 73f, 74t
Respiratory acid-base status, 256258, 256b due to venous sampling or
3839, 38t nitric oxide for, 266 admixture, 6769, 68t,
Respiratory acidemia, acute, case PEEP for, 260 69t, 75t
study on, 422, 434 idiopathic, PEEP for, 260 for electrolytes, 7576
Respiratory acidosis Respiratory disturbance(s), 39 Sanz electrode, 88
causes of, 334340, 335b, 335f Henderson-Hasselbalch equation SaO2
CO2 retention in, 371373 with, 212213, 214f, 215f in COPD, 253
compensation for, 213, 214f, 367, Respiratory exchange ratio, 189 defined, 170, 170f, 274
367t Respiratory quotient (RQ), 189 determination of, 274275
complete, 44, 44f, 45f and CO2 production, 339 fractional, 274, 275, 392, 402
partial, 43 total parenteral nutrition and, 339 functional, 274, 302, 402
due to COPD, 335336 Respiratory rate (RR), 201 maintenance of adequate,

decreasing VCO2 for, 372 Restrictive lung disease, respiratory 275276
defined, 38, 38t alkalosis due to, 342 normal values for, 4t, 6
drug-induced, 336 Reticulocyte(s), 277, 278f, 279t and oxygen therapy, 267
due to electrolyte Reticulocyte count, and as oxygenation index, 4, 275
deficiencies, 338 hemolysis, 280 PaO2 and, 170, 173
due to excessive CO2 Reticulocytosis, 277278 pulse oximetry and, 120, 396,
production, 339340 Retinopathy of prematurity, 397, 397f
due to exhaustion, 337 diffuse, 255 SaO2SpO2 incongruity, 120
iatrogenic, 338339 Retrolental fibroplasia, 255 Saturated air, 64
identification of, 41f Reversible chemical reaction, 198 Saturation
low-flow O2 therapy for, RH (relative humidity), 64 fractional, 274, 275, 392, 402
371372 Right atrial pressure (RAP), 286 functional, 274, 392, 402
with mechanical ventilation, Right ventricular pressure, 288t of hemoglobin, 170, 170f.
338339, 371, 372373 RQ (respiratory quotient), 189 See also SaO2.
due to neurologic disorders, 339 and CO2 production, 339 50%, 171f, 173174
due to neuromuscular disease, total parenteral nutrition and, 339 SD (standard deviation), 56, 5f, 93
337338, 337f RR (respiratory rate), 201 Secretions, increased, abnormal
noninvasive pressure support RTA (renal tubular acidosis), distribution of ventilation
ventilation for, 372 metabolic acidosis due to, due to, 146, 146f
permissive hypercapnia for, 372 348349 Sedative-hypnotics, respiratory
physiologic response to, 334 Rule of eights, 117, 118t acidosis due to, 336
Index 521
Septic shock, 284, 285f, 288t mechanisms of, 152 positive end-expiratory pressure
PaO2 and PvO2 in, 293294, 294f normal, with decreased cardiac for, 258264
Septicemia, transmission via blood output, 229, 229f auto, 263264, 264f
contact of, 10 PaO2 as index of, 231 clinical approach to, 263
Serum, 315 physiologic, 154155 complications of, 260263,
SET (signal extraction technology), assessment of, 155, 232236 261f263f
396, 401, 401f classic shunt equation for, definition and waveforms of,
Severinghaus electrode, 89, 89f 154, 232 258259, 259f
Shifting, 95, 95f clinical significance of, equipment systems for,
Shock, 281285 154155, 154f 259260, 260f
anaphylactic, 284285 components of, 150f indications for, 260
due to blood volume, defined, 154, 232 mechanism of effectiveness
283284, 284f estimated shunt equations for, of, 260, 261f
cardiogenic, 282283, 283f, 287, 232233 overview of, 258
288t indices of, 232236, 232b SI (International System of Units), 7
circulatory, PaO2 and PvO2 in, measurement of, 154 Sickle cell(s), 279t
293, 293f normal values for, 154 Sickle cell anemia, 184186,
clinical symptoms of, 282 relative, 149t, 150f 185f, 280
due to congestive heart failure, 282 hypoxemia due to, 238, 239t Sickle cell crisis, 185
defined, 281 oxygen therapy for, 247, 248f Sickle cell trait, 186
etiology of, 282285 treatment of, 246267 SID (strong ion difference), 326327
hypovolemic (hemorrhagic), for acute vs. chronic disease, 247 Sidestream analyzers, 408, 408f,
283284, 284f, 287, 288t body positioning for, 264266 409, 410f
neurogenic, 284, 288t mechanical ventilation for, Signal extraction technology (SET),
pathogenesis of, 281282 256258, 256b 396, 401, 401f
psychogenic, 284 nitric oxide for, 266 Silent unit, 149t, 153, 153f
due to pump effectiveness, objectives in, 246 Skin, anatomy of, 403, 404f
282283, 283f options for, 247, 247b Skin pigmentation, and pulse
respiratory alkalosis due to, 343 oxygen therapy for, 247255 oximetry, 398
septic (hyperdynamic), 284, AARC clinical practice guide- Sleep apnea, central, respiratory
285f, 288t lines for, 250, 251b, 252b acidosis due to, 339
PaO2 and PvO2 in, administration devices for, Smoke inhalation, cyanide in, 291
293294, 294f 248250, 248f, 249f, 250t SO2, PO2 and, 170173, 171f, 172f,
due to vascular tone, clinical approach to, 275
284285, 285f 250254, 251b, 252b SO4, 315f, 316t
Shunt equation(s) excessive, 254255 Sodium (Na+)
classic, 232, 232b FIO2 levels in extracellular vs. intracellular, 315f
estimated, 232233 in COPD, 253 plasma, 316, 316t
Shunting, 152156 high, 255 Sodium bicarbonate (NaHCO3)
absolute, hypoxemia due to, in low-flow system, 253 as buffer solution, 208
237, 239t goals in, 250 for metabolic acidosis, 374376
oxygen therapy for, 248 high PaO2 levels in, 255 alternatives to, 376377
anatomic, 150f, 154, 155, 155t high-flow (fixed performance) respiratory acidosis due to, 340
hypoxemia due to, 237 systems for, 248, 248f Sodium bicarbonate (NaHCO3)
capillary, 150f long-term, 267 mechanism, of sodium
hypoxemia due to, 237 low-flow (variable perform- reabsorption, 318319, 318f,
relative, 150f, 153, 155, 155t ance) systems for, 249250, 319f
true, 149, 150f, 152153, 153f, 249f, 250t diuretics that interfere with, 321
155, 155t mechanisms of effectiveness Sodium bicarbonate (NaHCO3)
defined, 152 of, 247248, 248f overcorrection, metabolic
disorders of, 155, 155t in nonoxygen-sensitive alkalosis due to, 354
hypoxemia due to, 237238, 239t patients, 250253 Sodium chloride (NaCl), for
increased in oxygen-sensitive patients, metabolic alkalosis, 378
with decreased cardiac output, 253 Sodium chloride (NaCl) mechanism,
230, 230f in preterms and neonates, of sodium reabsorption,
hypoventilation with, 236237 252b 317318, 318f
with increased cardiac with progressive hypercapnia, diuretics that interfere with, 321
output, 230231, 230f 253254 Sodium heparin, sampling errors
with normal cardiac output, in spontaneously breathing due to
229230, 230f patient, 250254 blood gas, 6970
indices of, 232236, 232b palliative, 246247, 247b for electrolytes, 75
522 Index
Sodium reabsorption, 317322 Sulfate ion (SO4), 315f, 316t Tidal, defined, 63
NaCl mechanism of, 317318, Sulfhemoglobin, 184, 392 Tidal volume (TV, VT), 142f, 201
318f Sulfur, metabolic acidosis due to, 350 normal distribution of, 142, 143f
NaHCO3 mechanism of, Superficial temporal artery, blood physiologic deadspace as
318319, 318f, 319f collection from, 17f percentage of, 151
renin-angiotensin system in, Supportive treatment, 370371 Tissue(s), chloride shift at, 204, 204f
319320, 320f Surface area, and diffusion, 159 Tissue hypoxia, 138
total, 320321, 320t SvO2, 292, 292f, 292t Tissue oxygenation, 135
Sodium regulation, in kidney, Swan-Ganz pulmonary artery cardiopulmonary interaction in,
317322, 318f320f, 320t catheter, 286, 286f 136138
Solubility coefficient(s), 165167, and differential diagnosis, steps in, 136, 137f
166f 287288 Tissue plasminogen activator,
and speed of diffusion, 156 hemodynamic monitoring using, arterial blood collection with,
Spectrometry, mass, 407 287289, 288t, 289f, 289t 9
Spectrophotometer, 389, 390, insertion of, 286287, 286f TLC (total lung capacity), 142f
390f Symbols, 63 Toluene, metabolic acidosis due
Spectrophotometry, 389390, 389f, Syphilis, transmission via blood to, 345
390f contact of, 10 Tonometered liquids, as quality
Spectroscope, 388 Syringe(s) control materials, 102
Spinal cord injury, respiratory for arterial blood collection, Tonometry, 102
acidosis due to, 339 1213, 13f, 14f gastric, 297
Spironolactone (Aldactone), plastic vs. glass, 13, 7172 Topical anesthetics, methemo-
interference with NaHCO3 redirection of, 2324 globinemia due to, 183184
reabsorption by, 321 vents on, 67 Torr, 7, 62
SpO2, 120, 274275 Systematic error, 95, 102f Total body water, 315f
and abnormal Hb species, 275 Systemic circulation, 7, 8f Total CO2, 119, 121122

in COPD, 253 Total expired ventilation (VE),
incongruity of SaO2 and, 120 T 152, 201
relative insensitivity of, 275 T40 standard bicarbonate, 124 Total lung capacity (TLC), 142f
targets for, 402 Tachycardia, as compensatory Total parental nutrition (TPN),
Spontaneous breathing response, 137 respiratory acidosis due to,
respiratory acidosis with, 371372 Target blood gas values, 74 339, 340
respiratory alkalosis with, 373 Temperature Total quality management, 9091,
Standard(s), 92 and hypoxia, 189 90f
Standard deviation (SD), 56, 5f, 93 and oxyhemoglobin affinity, 174, Toxin(s)
Standard precautions, 10 174b, 174f metabolic acidosis due to,
Starling resistor, 141 sampling errors due to alterations 344345
Starlings curve, 287 in, 7374, 73t, 74t respiratory alkalosis due to,
Starvation, ketosis due to, 347 and water vapor pressure, 64, 64t 342
Statistics, for quality control, 93 Temperature effect Transcutaneous PO2/PCO2 monitor-
Status asthmaticus, case study on, on pulse oximetry, 400 ing, 403406, 404f, 406b
421422, 433434 on transcutaneous PO2, 405 Transcutaneous techniques, for
Steady state, arterial blood Temperature-corrected values, 74 blood gas monitoring, 104
collection in, 1011 Temporal adjectives, in blood gas Transfusion(s)
Steroids, metabolic alkalosis due to, classification, 4950, 49t for anemia, 280281
322, 355 Tension, of gas, 62 metabolic alkalosis due to, 354
Stewart, Peter, 326327 Thalassemia, 279 Transmission optodes, 104, 104f
Stewarts strong ion difference, THAM (tris-hydroxymethyl- Transmission oximetry, 390391,
326327 aminomethane), for meta- 391f, 392f
Stirring effect, 92 bolic acidosis, 376 Transport, of arterial blood
Stopcock, three-way, 2728, 27f, 28f Therapeutic compensation, 371 sample, 15
Stratum corneum, 403, 404f Thermic effect, respiratory acidosis effect on electrolytes of, 76
Streptokinase, arterial blood due to, 339340 Transpulmonary pressure (PL),
collection with, 9 Thiazide diuretics, 321 141142, 143f
Stretch reflex, 312, 342 Threshold resistors, 259260 Trending, 95, 95f
Stroke volume, 282, 288t Thrombolytics, arterial blood Tris-hydroxymethyl-aminomethane
Strong ion difference (SID), collection with, 9 (THAM), for metabolic aci-
326327 Thrombosis dosis, 376
Sulfamylon acetate cream (mafenide due to arterial cannulation, Trouble-shooting, 96, 97t101t
acetate), metabolic acidosis 26, 26f True alveolar deadspace unit, 149
due to, 349 due to arterial puncture, 1718 Tubular reabsorption, 314
Index 523
Tubular secretion, 314 Venous contamination error, 6769, deteriorating, with PEEP,
TV (tidal volume), 142f, 201 68t, 69t, 75t 262, 262f
normal distribution of, 142, 143f Venous oxygen tension. See PvO2. Ventilation-perfusion unit
physiologic deadspace as Venous paradox, 361362, 374375 ideal, 148, 149, 150f
percentage of, 151 Venous puncture, inadvertent, 22, silent, 149t
2324, 6769, 68t, 69t ventilation-perfusion ratio in,
U Venous return, 283 147148
Ulnar artery, blood collection optimization of, 289290 Ventilatory failure, 4849, 371
from, 17f Venous samples, inadvertent, 6769, Venti-masks, 251b
Ulnar collateral circulation, 68t, 69t VILI (volume-induced lung injury),
adequacy of, 2021, 21f Ventilation 257
Ulnar nerve, 20f abnormal distribution of, Vital capacity (VC), 142f
Umbilical artery, blood collection 145147, 146f Vital organ function, 297
from, 17 alveolar, 139, 201 Vitamin B12 deficiency, 279280
Unilateral lung disease, body breathing pattern and, 202, Volatile acid(s)
positioning for, 266 202f defined, 198
Uremia, 346 effective, 151 regulation of, 198205, 308313
Ureter(s), 313f minute vs., 201203, 201t, 202f Voltage, 83
Uretero-enterostomy, metabolic Cheyne-Stokes, 309, 309f Volume deficit, 316
acidosis due to, 349 compensatory disturbances in, Volume-induced lung injury
Uretero-ileostomy, metabolic acido- 145f, 147 (VILI), 257
sis due to, 349 in COPD, 311312, 311t Volumetric capnograms,
Uretero-sigmoidostomy, metabolic defined, 139 410, 411f, 412f
acidosis due to, 349 in external respiration, 138f, 139 Volutrauma, 256257

Urinary bladder, 313f indicators of, 4 V/Q (ventilation-perfusion ratio),
Urinary buffers, 322323, 322f, mechanical. See Mechanical 148149, 148f, 149f, 149t
323f ventilation. deteriorating, with PEEP, 262,
Urinary diversion, metabolic acido- minute, 201 262f
sis due to, 349 alveolar vs., 201203, 201t, 202f VT (tidal volume), 142f, 201
Urine exhaled, 201 normal distribution of, 142, 143f
formation of, 314 noninvasive pressure support, for physiologic deadspace as
pH of, 348 respiratory acidosis, 372 percentage of, 151
normal distribution of, 141143,
V 142f, 143f W
VA, 147, 200 in normal lung, 148, 148f Wall effect, 106
VanishPoint retractable needle PaCO2 and, 310, 311 Warfarin (Coumadin), arterial blood
syringe, 14f PaO2 and, 310 collection with, 9
Variable performance systems, for pH and, 310 Wasted ventilation, 149, 150f, 152
oxygen therapy, 249250, positive-pressure, abnormal Water, total body, 315f
249f, 250t distribution of ventilation Water deficit, 316
Vascular dyes, pulse oximetry with, due to, 146, 146f Water excess, 316
398 primary disturbances in, 145147, Water vapor, in alveolar air, 63t
Vascular tone, 284285, 285f 146f Water vapor pressure, 62
Vasodilator, effect on oxygen uptake pulse oximetry and, 403 of alveolar and atmospheric air, 64
of, 296 regulation of, 308313, 308f effect of temperature and humidity
Vasovagal reaction, due to arterial chemoreceptors in, 308312, on, 64, 64t
puncture, 18 308f, 309f, 311t Waterfall effect, 141
VC (vital capacity), 142f reflexes in, 308, 308f, Watts, 83
VCO2, decreasing, for respiratory 312313 Westgard rules, 96, 101t, 102f
acidosis, 372 total expired, 152 Wests zone model, of perfusion,
VD, 150f, 151152 wasted, 149, 150f, 152 139141, 140f, 141f
VD/VT, 151152 Ventilation-perfusion matching, Whole blood, as quality control
VE, 152, 201 138f, 139, 147149, materials, 102

Venous admixture, 68, 68t 148f150f, 149t Whole blood buffer base (BB), 124
Venous blood Ventilation-perfusion mismatch Within-subject variation, 92
arterial vs., 78, 8f, 24 capnography of, 409, 411f Wood alcohol, metabolic acidosis
mixed, 6869, 69t hypoxemia due to, 238 due to, 345
peripheral, 69 respiratory acidosis due to, 336

Venous carbon dioxide tension, Ventilation-perfusion ratio (V/Q),
7, 292t 148149, 148f, 149f, 149t

Clinical Blood Gases Assessment Intervention

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Clinical

William J. Malley, MS, RRT, CPFT

CLINICAL BLOOD GASES: ASSESSMENT ISBN 0-7216-8422-X

Pharmacology is an ever-changing field. Standard safety precautions must be followed, but as

Previous edition copyrighted 1990.

International Standard Book Number 0-7216-8422-X

Managing Editor: Mindy Hutchinson

Printed in the United States of America

Last digit is the print number: 9 8 7 6 5 4 3 2 1

LINDA K. EVANS, RN, MSN

The Kidneys and Acid-Base Renal Function, 313

Status Asthmaticus, 421 Pulmonary Edema, 430

Introduction to Blood Gases

acid-base indices. Non-respiratory indices are Normal Ranges

blood sample; this is followed by a description therefore, a predisposition to bleeding compli-

ON CALL CASE 1-1 ABGs and Critical Thinking

A 70-year-old female in Denver arrives in the emergency ARTERIAL BLOOD GASES

Hypodermic Syringe Hypodermic Needle

Figure 1-3. Basic components of hypodermic needle and syringe.

Rubber seal insert

Directions: 2. With the syringe at 90, 3. The needle and PeachCapp

Box 1-1 Needle Safety

temporal artery is usually used.14 Alternatively,

gradually with subsequent diminution or ces-

relatively small, is very accessible. The arm is

Figure 1-9. Superficial dissec-

where the artery passes above the radius

circulation may be compromised and that radial

Femoral Artery. The femoral artery can be

Box 1-3 Legal Issues

Figure 1-14. Radial puncture. The wrist is

opposite hand. While maintaining a palpable

values than those actually present in the arterial Sample Handling

ON CALL CASE 1-2 ABGs and Critical Thinking

A 33-year-old male police officer presents to the PaCO2 33 mm Hg

to vascular occlusion is estimated to occur in

appears to be related to the period of cannula-

Although arterial cannulation is not with-

Flush solution Patient

Sample port Sample port

Figure 1-18. Sampling position of three-way

AARC CLINICAL PRACTICE

Anaerobic arterial blood Anaerobic arterial or Free flowing capillary blood

Exercise 1-1 Blood Gas Values

Exercise 1-2 Arterial versus Venous Blood

1. Define the following terms: arteries and veins.

Exercise 1-3 Preparation for Arterial Sampling

Exercise 1-4 Arterial Blood Sampling

Exercise 1-5 Internet Work

pH Assessment low pH (i.e., pH <7.10) is often associated

BASIC (PRIMARY) ACID-BASE

Table 2-3. CLASSIFICATION OF METABOLIC Identification of Primary Acid-Base

Alkalosis demonstrates two primary problems both

Example 2-5 not primarily affected. For example, when an

Example 2-11 7.45

because it is generally accepted that the body

does not overcompensate for a primary

the pH reaches the normal range, compensa- C

tory mechanisms abate. pH 7.40

Table 2-5. DETERMINATION OF THE PRIMARY Table 2-6. CLASSIFICATION OF DEGREE OF