Anaphylactic Reactions in Anesthesia and Intensive Care

167 Pages·1986·3.55 MB·English

by  Jerrold H. Levy (Auth.)

ANAPHYLACTIC
REACTIONS IN
ANESTHESIA AND
INTENSIVE CARE
Jerrold H. Levy, M.D.
Assistant Professor of Anesthesiology
Emory University School of Medicine
Division of Cardiothoracic Anesthesia
Emory Clinic
Associate Director
Cardiothoracic Intensive Care Unit
Emory University Hospital
Atlanta, Georgia
Butterworths
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Copyright © 1986 by Butterworth Publishers.
All rights reserved.
No part of this publication may be reproduced, stored in a retrieval
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prior written permission of the publisher.
Every effort has been made to ensure that the drug dosage sched-
ules within this text are accurate and conform to standards
accepted at time of publication. However, as treatment recom-
mendations vary in the light of continuing research and clinical
experience, the reader is advised to verify drug dosage schedules
herein with information found on product information sheets.
This is especially true in cases of new or infrequently used drugs.
Library of Congress Cataloging-in-Publication Data
Levy, Jerrold H.
Anaphylactic reactions in anesthesia and intensive
care.
Bibliography: p.
Includes index.
1. Anaphylaxis. 2. Anesthesia—Complications and
sequelae. 3. Surgery—Complications and sequelae.
4. Critical care medicine. I. Title. [DNLM:
1. Anaphylaxis—chemically induced. 2. Anesthesia—
adverse effects. 3. Critical Care. QW 900 L668a]
RD82.7.A48L48 1986 616.97'5 86-6883
ISBN 0-409-95193-5
Butterworth Publishers
80 Montvale Avenue
Stoneham, MA 02180
10 9 8 7 6 5 4 3 21
Printed in the United States of America
PREFACE
Anaphylaxis, often unpredictable and sudden in onset, represents
one of the most serious, potentially lethal emergencies in medical
practice. The allergist sees a patient with an anaphylactic reaction
to insect venom, penicillin, or food, usually to determine the agent
responsible. For anesthesiologists, however, the occurrence of ana-
phylaxis, although rare, is an ever-present threat to a patient's well-
being. Anesthesiologists regularly administer foreign substances in-
cluding anesthetic agents, antibiotics, and blood products, and they
monitor patients during injections of contrast dye or chymopapain.
All these substances can produce anaphylaxis, and anesthesiologists
as well as other clinicians must be able to manage the acute cardio-
vascular and pulmonary dysfunction that might occur.
This book provides anesthesiologists, surgeons, and other in-
terested physicians and health care professionals with a practical
approach to the recognition, understanding, and management of these
life-threatening reactions. The book opens with background chapters
on immunology and the immunologie principles underlying ana-
phylaxis. The various pathophysiologic mechanisms and agents pro-
ducing the clinical syndrome of anaphylaxis are discussed, including
evaluation and management of the patient at risk. General preop-
erative considerations and particular concerns in patients with known
allergies are reviewed. The remaining chapters are devoted to the
diagnosis, treatment, and prevention of anaphylaxis. Lessons learned
from the management of acute cardiopulmonary dysfunction during
cardiovascular surgery and in the intensive care unit, including the
value of epinephrine administration, have proved invaluable in deal-
ing with anaphylaxis arising during or after operation. A detailed
plan is presented. Illustrative cases exemplify the intraoperative and
postoperative diagnosis and management of anaphylactic reactions,
with particular attention to respiratory support. A brief concluding
chapter addresses prevention of future anaphylactic reactions. The
bibliography serves as a comprehensive guide to the English-
and French-language literature on anaphylaxis.
This book encompasses my experiences with individuals in
allergy and immunology, cardiac anesthesiology, physiology, res-
vii
viii Anaphylactic Reactions in Anesthesia and intensive Care
piratory physiology and critical care medicine, and biochemistry. I
would like to thank Doctors Phillip R. Glade, Edward Lowenstein,
Henning Pontoppidan, and I.A. Bernstein, who have had profound
influences on me and who have helped to make this book possible.
I also thank Doctor Carol A. Hirshman for her guidance and support
of my work, and Gilbert and Vivian, for all their support through
the years.
J.H.L.
CHAPTER 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 following a second sublethal injection of a sea
anemone toxin (Actinia sulcata).300 The term anaphylaxis was pro-
posed from the Greek terms ana, "against," and phylaxis, "protec-
tion," 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, prior exposure to an an-
tigen or substance of similar structure is necessary to achieve a sen-
sitization state.411
Anaphylaxis, defined 80 years after the first report, is a life-
threatening immediate hypersensitivity reaction characterized by the
presence of an immediate generalized response, including symptoms
of upper airway obstruction, dyspnea with or without wheezing,
syncope, or hypotension.15199'355·388 The complex of sudden physio-
logic changes involving the cardiovascular, respiratory, and cuta-
neous systems is produced by an allergic reaction. A reaction is
considered allergic when it is produced by immunologie mecha-
nisms; therefore pharmacologie idiosyncracy, direct toxicity, drug
over dosage, drug interactions, or reactions that mimic allergy are not
considered allergic reactions.283·285 Immunologie reactions have two
major characteristics: (1) they involve the interaction of both antigens
with antibodies and/or specific effector cells, and (2) they are repro-
ducible when rechallenged with specific antigens (the amnestic re-
sponse).416 Anaphylactic reactions represent only some of many
different immunologie reactions in humans. The terms anaphylaxis
and immediate hypersensitivity reaction, used in the text inter-
changeably, describe a specific clinical syndrome. However, not all
immediate hypersensitivity reactions are anaphylactic.416 Therefore,
a review of antigens, antibodies, and concepts of immunologie re-
3
4 Mechanisms of AnaphyJaxis
actions will provide a framework for understanding anaphy-
laxis.129'319·416
PROPERTIES OF AN ANTIGEN
Molecules capable of stimulating an immune response when injected
(i.e., immunospecific antibody production or lymphocyte activation)
are called antigens. Antibodies are large protein molecules capable
of binding to antigens. The specificity of the immunologie 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 immuno-
genicity. Specificity and immunogenicity characteristics include mo-
lecular size and degree of foreignness to the recipient. Antigens can
also be low-molecular-weight substances that bind to host proteins
in a hapten mechanism (e.g., drugs), or larger molecules that stim-
ulate an immune response by themselves (e.g., proteins).49 Foreign
polypeptides (e.g., chymopapain) readily elicit an immune response
by themselves. This response is in contrast to that of lower-molec-
ular-weight substances (e.g., penicillin), which cannot stimulate the
immune system unless coupled with proteins to form haptens. The
offending antigen, whether hapten or not, may be the parent com-
pound, a nonenzymatically generated product or a metabolic product
formed in the patient.49
The foreignness of a molecule is important in determining its
ability to stimulate an immune response. Normally, people do not
show an immune response to their own proteins, but proteins of
phylogenetically different species are immunogenic and produce
lymphocyte activation and perhaps antibody formation. Although
we administer blood products that contain a variety of foreign cel-
lular and protein antigens, the incidence of acute allergic reactions
following additional transfusions is low. This response may reflect
structural similarities of proteins. However, prior administration of
horse sera for tetanus or antithymocyte globulin often produces pro-
found acute allergic reactions if a second dose is required. This
immediate hypersensitivity response may reflect a human immu-
nosurveillance system requiring immediate rejection of foreign an-
tigens such as bacteria or parasites.
ANTIBODIES
Antibodies are protein macromolecules with the unique ability to
combine with the antigen that stimulated their production. Immu-
Anaphylaxis, Allergy, and immunology 5
noglobulins 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 comple-
ment activation. 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 bac-
teria to produce clumping, complement activation, or recruitment of
other immunosurveillance systems.
Synthesis
After antigenic exposure and transformation of specific B-cell-
derived lymphocytes in a complex process, antibodies are synthe-
sized in plasma cells and lymphocytes are generated 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, saliva,
and other secretory systems to function as antibodies. Antibodies
such as immunoglobulin E remain primarily bound to mast cells or
basophils, while antibodies such as immunoglobulin A are released
in the saliva and other secretions.
Antigen Figure 1.1 Simplified basic structural
Βο!ί!ί«9 \ configuration of antibody molecule rep-
Sites
resenting human immunoglobulin G. Im-
7 munoglobulins are composed of two heavy
chains and two light chains bound by di-
Fab sulfide linkages (represented by cross bars).
Papain cleaves the molecule into two Fab
.. . ^ _ _ , fragments and one Fc fragment. Antigen
Chain | | | binding occurs on the Fab segments while
the Fc segment is responsible for mem-
brane or complement activation.
Jl J
Heavy
Chain
6 Mechanisms of Anaphylaxis
Immunoglobulin Classes
Differences in the Fc region (constant region) of immunoglobulins
determine the biologic behavior of each molecule. The differences
among the classes of immunoglobulins are summarized in Table 1.1.
Functioning as serum antibodies, they may (1) recognize and neu-
tralize antigens in the circulation (i.e., immunoglobulin G or M), (2)
bind to cells both intravascularly or in tissues to produce immediate
hypersensitivity responses following antigen exposure, or (3) act as
specific cell receptor molecules interacting with antigens causing
lymphocyte proliferation and differentiation into antibody-secreting
cells (i.e., immunoglobulin D).
Immunoglobulin G (TgG)
This antibody comprises approximately 70 percent of the serum im-
munoglobulins. The IgG molecule has a molecular weight of 150,000
and represents 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
t
and IgG readily activate complement but also are bound by phag-
3
ocytic cells. IgG is less active in complement binding, while IgG
2 4
does not bind complement but may bind to mast cells.
Immunoglobulin D (IgDJ
IgD appears to function as a receptor, acting as the principal mem-
brane receptor for lymphocytes. It is present at very low levels in
the serum.
Immunoglobulin E (IgE)
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 two 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.
or s
te
pt
ey
D 000 rechoc 1
Ig 184, brane lymp <0.
mn
eo
M
y
d
o
IgA 170,000 body in bcretions 1-3
ntise
A
s
p
IgM 900,000 - + ntibody to blood grou 0.5-1.5
A
munoglobulins IgG 160,000 a a + Major antibody involved in host defense; crosses placenta 6-14 o mast cells
aracteristics of Im IgE 188,000 + — Sensitize mast cell basophils for anaphyiaxis 3 <0.001X10 mplement but binds t
h o
Table 1.1 Biologie C Characteristic Molecular weight Mast cell binding Complement activation Function Serum concentration (g/L) aIgG does not activate c4
8 Mechanisms of Anaphylaxis
Immunoglobulin M (IgM)
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
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 isohemaggJutinins. Anti-
bodies of this class are synthesized against blood groups not occur-
ring on their own red blood cells. Apparently, antibody production
occurs through antigenic stimulation by carbohydrate allergens in
plants. IgM does not cross the placenta.
Immunoglobulin A (IgA)
IgA, a secretory antibody found in saliva and gastrointestinal and
respiratory secretions, represents an immunologie paint coating the
mucosal surface to provide host protection against pathogenic or-
ganisms.392 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 of the general population even in the absence of apparent
immunologie deficiencies.8·207
CLASSIFICATION OF IMMUNOLOGIC
REACTIONS
Immunologie reactions can be classified into four types based on the
antibody involved, the type of cell modulating the reaction, the na-
ture 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 auto-
regulation. For example, one drug such as penicillin may produce
Type I, II, or III immunologie reactions in different patients. The
different reactions have also been referred to as hypersensitivity re-
actions because the exaggerated responses lead to destruction or
injury of the host's tissues.416 Nonetheless, the classification of Gell
and Coombs still provides a basic understanding of the pathophys-
iology and spectrum of immunologie reactions that the practicing
physician sees clinically.129 A summary of type I through IV im-
munologie reactions is included in Table 1.2.