Anaphylactic Reactions in Anesthesia and Intensive Care

261 Pages·1992·5.26 MB·English

by  Jerrold H. Levy (Auth.)

Anaphylactic Reactions
in Anesthesia and
Intensive Care
Second Edition
Jerrold H. Levy, M.D.
Associate Professor of Anesthesiology
Emory University School of Medicine
Division of Cardiothoracic Anesthesiology and Critical Care
Emory Clinic
Associate Director
Cardiothoracic Intensive Care Unit
Emory University Hospital
Atlanta, Georgia
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Library of Congress Cataloging-in-Publication Data
Levy, Jerrold H.
Anaphylactic reactions in anesthesia and intensive care / Jerrold
H. Levy.—2nd ed.
p. cm.
Includes bibliographical references and index.
ISBN 0-7506-9064-X (case bound : alk. paper)
1. Anaphylaxis. 2. Anesthesia—Complications and sequelae.
3. Critical care medicine—Complications and sequelae. I. Title.
[DNLM: 1. Anaphylaxis—chemically induced. 2. Anesthesia—adverse
effects. QW 900 L668a]
RD82.7.A48L48 1992
616.97'5—dc20
DNLM/DLC
for Library of Congress 91-47872
CIP
British Library Cataloguing in Publication Data
Levy, Jerrold H.
Anaphylactic reactions in anesthesia and intensive care—2nd ed
I. Title
616.975
ISBN 0-7506-9064-X
Butterworth-Heinemann
80 Montvale Avenue
Stoneham, MA 02180
10 9 8 7 6 5 4 3 21
Printed in the United States of America
Preface
Anaphylaxis, which is often unpredictable and sudden in onset, represents
one of the most serious, potentially lethal emergencies in medical practice. Anes-
thesiologists routinely administer foreign substances, including anesthetic agents,
antibiotics, blood products, and other drugs, and monitor patients during injec-
tions of contrast media during diagnostic studies. Because all of these substances
can produce anaphylaxis, anesthesiologists and other clinicians must be prepared
to deal with the acute cardiovascular and pulmonary dysfunction that might
occur.
This book provides anesthesiologists, intensivists, and other interested phy-
sicians and health care professionals with a practical approach to the recognition,
understanding, and management of these life-threatening reactions. Lessons
learned from the treatment of acute cardiopulmonary dysfunction during cardio-
vascular surgery and in the intensive care unit, including the importance of
vasoactive drug administration (i.e., epinephrine), have proven invaluable in
dealing with anaphylaxis that occurs perioperatively.
The second edition of Anaphylactic Reactions in Anesthesia and Intensive
Care has been revised and updated. The extensive bibliography serves as a
comprehensive guide to the literature on anaphylaxis. The second edition includes
new information on the mechanisms of action of histamine and other mediators
that produce cardiopulmonary dysfunction, as well as more extensive data on
peptide and lipid mediators. Chapter 4 reviews the importance of complement
activation and its interaction with contact activation, and the plasma proteins
of the coagulation, fibrinolytic and kinin-generating pathways. Chapter 5 dis-
cusses nonimmunologic histamine release by drugs and peptides and the direct
effects of drugs on vascular responses. This edition elaborates on management
of the allergic patient and reviews drug allergy and diagnostic tests. The list of
agents implicated in anaphylaxis has been updated to include latex, newer an-
esthetic drugs, antibiotics, and peptides (i.e., insulin, streptokinase). It includes
more comprehensive data regarding muscle relaxants, protamine, and new drugs
on the horizon. Chapters 9 and 10 update pharmacologic approaches to and
therapeutic plans for anaphylaxis, including experimental therapeutic approaches
to inhibiting complement activation and reversing pulmonary vasoconstriction
and plans for treating bronchospasm and right ventricular failure.
v
vi I PREFACE
I would like to acknowledge the contributions made by other investigators
to the elucidations of, and therapeutic approaches to, anaphylactic reactions in
anesthesia and intensive care around the world, including Drs. Carol Hirshman
and N. Franklin Adkinson, Jr. at Johns Hopkins; Dr. Michael Weiss at the
University of Washington; Dr. Roberto Levi at Cornell; Dr. Jonathan Moss at
the University of Chicago; Drs. Marie-Claire Laxenaire, Denise Moneret-Vautrin,
and Daniel Vervloet in France; Drs. Wilfred Lorenz and Alfred Doenicke in
Germany; Drs. Malcolm Fisher, Brian Baldo, and David Harle in Australia; Dr.
David Sage in New Zealand; and Drs. John Watkins and Richard Clark in the
United Kingdom. I especially thank Dr. Roberto Levi for reviewing Chapters 2
and 3; Drs. Michael Weiss, N. Franklin Adkinson, Jr., Roberto Levi, and Law-
rence Schwartz for their help in developing new ways to investigate perioperative
anaphylaxis; and Kathleen Mainland for her assistance and editorial guidance
for the first and second editions. Finally, I would like to thank Gilbert and Vivian
Levy for all of their support through the years.
JHL
1
Anaphylaxis, Allergy, and
Immunology
Anaphylaxis was first reported by Charles Richet and Paul Portier in 1902
to describe a profound hypersensitivity response—shock and death—in dogs
after a second sublethal injection of a sea anemone toxin {Actinia sulcata) (Portier
and Richet, 1902). The term anaphylaxis was proposed from the Greek terms
ana, meaning against, and phylaxis, meaning protection, to indicate the reverse
of prophylaxis. Previous administration of toxin at sublethal dosages did not
confer protection to subsequent injections as Richet intended but sensitized the
animals to the foreign protein. For anaphylaxis to occur, previous exposure to
an antigen or substance of similar structure is necessary to achieve a sensitization
state.
Anaphylaxis, defined 90 years after the first report, is a life-threatening
immediate hypersensitivity reaction characterized by the presence of an imme-
diate generalized response, including symptoms of upper airway obstruction,
dyspnea with or without wheezing, syncope, or hypotension (Austen, 1974;
Bochner and Lichtenstein, 1991; Kelly and Patterson, 1974; Sheffer, 1985). The
complex of sudden physiologic changes involving the cardiovascular, respiratory,
and cutaneous systems is produced by an allergic reaction. A reaction is consid-
ered allergic when it is produced by immunologic mechanisms; therefore, phar-
macologic idiosyncracy, direct toxicity, drug overdosage, drug interactions, or
reactions that mimic allergy are not considered allergic reactions (Patterson,
1984; Parker, 1975). Immunologic reactions have two major characteristics: 1)
they involve the interaction of both antigens with antibodies, specific effector
cells, or both; and 2) they are reproducible when rechallenged with specific
antigens (the anamnestic response) (DeSwarte, 1986; Watkins et al., 1982). Ana-
phylactic reactions represent only some of many different immunologic reactions
in humans. The terms anaphylaxis and immediate hypersensitivity reaction used
in the text describe a specific clinical syndrome; however, not all immediate
hypersensitivity reactions are anaphylactic. Therefore, a review of antigens,
3
4 I MECHANISMS OF ANAPHYLAXIS
antibodies, and concepts of immunologic reactions provides a framework for
understanding anaphylaxis.
PROPERTIES OF AN ANTIGEN
Molecules capable of stimulating an immune response when injected (i.e.,
immunospecific antibody production or lymphocyte activation) are called anti-
gens. Antibodies are large protein molecules capable of binding to antigens. The
specificity of the immunologic response to produce unique antibodies directed
against a chemical structure represents an important characteristic. A molecule's
ability to act as an antigen to stimulate an immune response is called its immu-
nogenicity. Specificity and immunogenicity characteristics include molecular size
and degree of foreignness to the recipient (Butler and Beiser, 1973). Antigens
can also be low-molecular-weight substances that bind to host proteins in a
hapten mechanism (e.g., drugs), or larger molecules that stimulate an immune
response by themselves (e.g., proteins). Only a few large-molecular-weight drugs
(e.g., streptokinase, chymopapain, and insulin) are complete antigens (Table 1.1).
Smaller-molecular-weight polypeptides, such as protamine (molecular weight
4500 to 5000), are probably also complete antigens; however, most commonly
used drugs are small organic compounds with a low molecular weight of around
1000 daltons. For a small molecule to become immunogenic, it must form a
stable bond with a circulating or tissue macromolecule. When drugs bind to
larger molecules to become antigenic, they are called haptens. Fortunately most
drugs are not sufficiently reactive in the human body to form a stable complex
with larger molecules. Based on the extensive work on penicillin allergy, it is
probable that reactive drug metabolites bind with a carrier protein to become
complete antigens. For most other allergic drug reactions, the formation of
reactive metabolites and their conjugations with macromolecules can only be
inferred.
The foreignness of a molecule is important in determining its ability to
stimulate an immune response. Normally people do not show an immune re-
sponse to their own proteins, but proteins of phylogenetically different species
are immunogenic and produce lymphocyte activation and perhaps antibody
formation. Although healthcare workers administer blood products that contain
Table 1.1 Different Molecules That Function as Antigens to Induce Sensitization and
IgE Production
Complete Antigens Haptens Mirror Molecules
Protamine Penicillin Succinylcholine
Streptokinase Thiobarbiturates Atracurium
Insulin Sulfa drugs Symmetric
biquaternary
Antisera
ammonium compounds
Anaphylaxis, Allergy, and Immunology I 5
a variety of foreign cellular and protein antigens, the incidence of acute allergic
reactions after additional transfusions is low. This response may reflect structural
similarities of proteins. Previous administration of horse sera for tetanus or
antithymocyte globulin often produces profound acute allergic reactions if a
second dose is required, however. This immediate hypersensitivity response may
reflect a human immunosurveillance system requiring immediate rejection of
foreign antigens that are present on bacteria or parasites.
ANTIBODIES
Antibodies are protein macromolecules with the unique ability to combine
with the antigen that stimulated their production. Immunoglobulins represent
proteins of a specific structure that function as antibodies. Although all antibodies
are immunoglobulins, not all immunoglobulins have antibody function. The
structure of the basic antibody unit is Y shaped, as shown in Figure 1.1. The
base of the antibody molecule provides the biologic diversity responsible for
different physiologic functions, such as cellular binding or complement activa-
tion. Proteolytic enzymes cleave the antibody molecule to produce two antibody
fragments known as Fab (antibody binding) and Fc (cell membrane binding)
regions. The two combining sites on the molecules can cross-link two antigen
groups on cells or bacteria to produce clumping, complement activation, or
recruitment of other immunosurveillance systems.
Synthesis
After antigenic exposure and transformation of specific B cell-derived lym-
phocytes in a complex process, antibodies are synthesized in plasma cells and
lymphocytes are activated in the lymph nodes, Peyer's patches of the intestine,
and other reticuloendothelial organs involving regulatory thymus-derived (T cell)
lymphocytes. After synthesis, immunoglobulins are released into the blood,
Antigen
Figure 1.1 Simplified basic structural configuration
of antibody molecule representing human immuno-
globulin G. Immunoglobulins are composed of two
heavy chains and two light chains bound by disulfide
linkages (represented by cross bars). Papain cleaves
the molecule into two Fab fragments and one Fc
fragment. Antigen binding occurs on the Fab seg-
ments whereas the Fc segment is responsible for
Chain membrane or complement activation.
6 I MECHANISMS OF ANAPHYLAXIS
saliva, and other secretory systems to function as antibodies. Antibodies such as
immunoglobulin E remain primarily bound to mast cells or basophils, whereas
antibodies such as immunoglobulin A are released in the saliva and other
secretions.
Immunoglobulin Classes
Differences in the Fc region (constant region) of immunoglobulins deter-
mine the biologic behavior of each molecule. The differences among the classes
of immunoglobulins are summarized in Table 1.2. Functioning as serum anti-
bodies, they may 1) recognize and neutralize antigens in the circulation (i.e.,
immunoglobulin G or M), 2) bind to cells both intravascularly or in tissues to
produce immediate hypersensitivity responses after antigen exposure, or 3) act
as specific cell receptor molecules interacting with antigens to cause lymphocyte
proliferation and differentiation into antibody-secreting cells (i.e., immunoglob-
ulin D [IgD]).
Immunoglobulin G
Immunoglobulin G (IgG) comprises approximately 70% of the serum im-
munoglobulins. The IgG molecule has a molecular weight of 150,000 and rep-
resents the classic antibody structure with two light chains and two heavy chains.
After the Fab regions have combined with a bivalent antigen, conformational
changes occur in the Fc region of the molecule to activate complement. Different
subclasses of IgG molecules exist depending on differences in the gamma chain.
IgG! and IgG3 readily activate complement but also are bound by phagocytic
cells. IgG2 is less active in complement binding, whereas IgG4 does not bind
complement but may bind to mast cells.
Immunoglobulin D
IgD appears to function as a receptor, acting as the principal membrane
receptor for lymphocytes. It is present at very low levels in the serum.
Immunoglobulin E
Immunoglobulin E (IgE), also called reaginic antibody, is the antibody
responsible for anaphylaxis and other type I immediate hypersensitivity reactions
(see following section). This class of immunoglobulins is present in low serum
concentrations, is heat labile, and can be inactivated by heating the serum to
56°C for 2 hours. The epsilon chain has a high carbohydrate content, which
characterizes the Fc region of the molecule. Mast cell and basophil surface
membranes avidly bind the Fc portion of the IgE molecule.
Immunoglobulin M
Immunoglobulin M (IgM), the largest of the immunoglobulins, has the
basic structure of the IgG molecule and appears as a pentameter of IgG. IgM
molecules are the first antibodies formed after immunization. Although certain
Anaphylaxis, Allergy, and Immunology 5
p-o-
eh
0 recmp
IgD 84,00 rane on lys <0.1
1 mbor yte
etc
M
y
d
o
b
IgA 170,000 body in cretions 1-3
ntise
A
s
p
IgM 900,000 + body to ood grou 0.5-1.5
ntibl
A
unoglobulins IgG 160,000 ajor antibody in involvedhost defense; crosses pla-centa 6-14 o mast cells.
mm M ds t
Characteristics of I IgE 188,000 + Sensitize mast cells/basophils for anaphylaxis 3 <0.001 x 10 e complement but bin
c vat
Table 1.2 Biologi Characteristic Molecular weight Mast cell binding Complement activation Function Serum concentra-tion (g/L) 4* IgG does not acti
8 I MECHANISMS OF ANAPHYLAXIS
IgM molecules fix complement, most do not participate in allergic reactions.
Naturally occurring antibodies to the ABO blood groups in humans are IgM
molecules, also called isohemagglutinins. Antibodies of this class are synthesized
against blood groups not occurring on their own red blood cells. Apparently
antibody production occurs through antigenic stimulation by carbohydrate al-
lergens in plants. IgM does not cross the placenta.
Immunoglobulin A
Immunoglobulin A (IgA), a secretory antibody found in saliva and gas-
trointestinal and respiratory secretions, represents an immunologic paint coating
the mucosal surface to provide host protection against pathogenic organisms
(Tomasi, 1968). The basic unit of IgA resembles IgG but is linked to a small
peptide called the J chain. IgA molecules are synthesized in lymphocytes, released
into the lamina propria, and transported across the mucosal cells. A secretory
component of the mucosal cells is attached to the IgA chain. IgA deficiency
occurs in approximately 1 in 850 people even in the absence of apparent im-
munologic deficiencies (Ammann and Hong, 1971; Kolstinen, 1975).
CLASSIFICATION OF IMMUNOLOGIC
REACTIONS
Immunologic reactions can be classified into four types based on the anti-
body involved, the type of cell modulating the reaction, the nature of the antigen,
and the duration of the reaction. Although the different reactions are classified
as functionally distinct, the immune system is highly complex and interacts at
different levels for autoregulation. For example, one drug, such as penicillin,
may produce type I, II, III, or IV immunologic reactions in different patients.
The different reactions have also been referred to as hypersensitivity reactions
because the exaggerated responses lead to destruction or injury of the host's
tissues (DeSwarte, 1986; Watkins et al., 1982). Nonetheless, the classification of
Gell and Coombs still provides a basic understanding of the pathophysiology
and spectrum of immunologic reactions seen clinically (Gell et al., 1975). A
summary of type I through IV immunologic reactions in included in Table 1.3.
Type I
Anaphylactic reactions are examples of type I reactions; they are also called
immediate hypersensitivity reactions. The antibody mediating the response is an
IgE type that attaches to the surface of mast cells and basophils. When an antigen
binds to the IgE antibody on the surface of these cells, cellular activation and
degranulation ensue with the release of a variety of pharmacologically active
substances classically producing anaphylaxis (see Chapter 2). Not all type I
allergic reactions are anaphylactic, however. Other examples of type I allergy
include classic penicillin allergy, bee-sting reactions, extrinsic asthma, and allergic
rhinitis. Allergic reactions are considered type I reactions (Roitt et al., 1989).