Johnson 2004

Download as pdf or txt
Download as pdf or txt
You are on page 1of 9

Anaphylactic Shock: Pathophysiology,

Recognition, and Treatment


Roger F. Johnson, M.D.1 and R. Stokes Peebles Jr., M.D.1

ABSTRACT

Anaphylaxis is a systemic, type I hypersensitivity reaction that often has fatal


consequences. Anaphylaxis has a variety of causes including foods, latex, drugs, and
hymenoptera venom. Epinephrine given early is the most important intervention. Ad-

Downloaded by: New York Medical College. Copyrighted material.


junctive treatments include fluid therapy, H1 and H2 histamine receptor antagonists,
corticosteroids, and bronchodilators; however these do not substitute for epinephrine.
Patients with a history of anaphylaxis should be educated about their condition, especially
with respect to trigger avoidance and in the correct use of epinephrine autoinjector kits.
Such kits should be available to the sensitized patient at all times.

KEYWORDS: Anaphylaxis, epinephrine, shock, allergy

Objectives: After reading this article, the reader should be able to: (1) discuss the pathophysiology of anaphylactic shock; (2) recognize
anaphylactic reactions; and (3) summarize the essential steps in treatment of anaphylactic shock.
Accreditation: The University of Michigan is accredited by the Accreditation Council for Continuing Medical Education to sponsor
continuing medical education for physicians.
Credits: The University of Michigan designates this educational activity for a maximum of 1 category 1 credit toward the AMA
Physician’s Recognition Award.

A naphylaxis is a systemic, type I hypersensitivity Anaphylaxis occurs in persons of all ages and has
reaction that occurs in sensitized individuals resulting in many diverse causes, the most common of which are
mucocutaneous, cardiovascular, and respiratory manifes- foods, drugs, latex, hymenoptera stings, and reactions to
tations and can often be life threatening. Anaphylaxis immunotherapy. Of note, a cause cannot be determined
was first described in 1902 by Portier and Richet when in up to one third of cases.2–4 Anaphylactoid reactions
they were attempting to produce tolerance in dogs to sea are identical to anaphylaxis in every way except the
anemone venom. Richet coined the term aphylaxis (from former are not mediated by immunoglobulin E (IgE).
the Greek a, against, –phylaxis protection) to differenti- Common causes of anaphylactoid reactions include
ate it from the expected ‘‘prophylaxis’’ they hoped to radiocontrast media, narcotic analgesics, and nonsteroi-
achieve. The term aphylaxis was replaced with the term dal antiinflammatory drugs.
anaphylaxis shortly thereafter. Richet won the Signs and symptoms can be divided into
Nobel Prize in medicine or physiology in 1913 for his four categories: mucocutaneous, respiratory, cardiovas-
pioneering work.1 cular, and gastrointestinal. Reactions that surpass

Management of Shock; Editor in Chief, Joseph P. Lynch, III, M.D.; Guest Editors, Arthur P. Wheeler, M.D., Gordon R. Bernard, M.D. Seminars
in Respiratory and Critical Care Medicine, volume 25, number 6, 2004. Address for correspondence and reprint requests: Roger F. Johnson, M.D.,
Center for Lung Research, T-1217 MCN, Vanderbilt University Medical Center, 1161 21st Ave. South, Nashville, TN 37232-2650. E-mail:
roger.johnson@vanderbilt.edu. 1Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University
School of Medicine, Nashville, Tennessee. Copyright # 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001,
USA. Tel: +1(212) 584-4662. 1069-3424,p;2004,25,06,695,703,ftx,en;srm00340x.
695
696 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 25, NUMBER 6 2004

mucocutaneous signs and symptoms are considered to be 53% of those experiencing anaphylaxis and an allergy
severe, and, unfortunately, mucocutaneous manifesta- consultation was obtained in 52%. The hospitalization
tions do not always occur prior to more serious mani- rate was 7% and the case fatality rate was 0.91% (one
festations. Mucocutaneous symptoms commonly consist patient out of 133 expired).3 When projected to the
of urticaria, angioedema, pruritis, and flushing. Com- entire U.S. population on an annual basis these numbers
mon respiratory manifestations are dyspnea, throat are significant.
tightness, stridor, wheezing, rhinorrhea, hoarseness, Neugut et al sought to improve understanding of
and cough. Cardiovascular signs and symptoms include the epidemiology of anaphylaxis by surveying the med-
hypotension, tachycardia, and syncope. Gastrointestinal ical literature.2 They estimated that between 3.3 and 43
manifestations include nausea, vomiting, abdominal million people in the United States (based in 1999
cramps, and diarrhea.2,3,5,6 population estimates of 272 million) are at risk for
First-line treatment of anaphylactic shock is epi- anaphylaxis. In addition, they estimated that between
nephrine. Other adjuvant treatments are often also used; 1453 and 1503 people die each year from anaphylactic or
however, there is no substitute for prompt administra- anaphylactoid reactions (due to food 100, penicillin 400,
tion of epinephrine. radiocontrast media 900, latex 3, stings 40–100). Lim-
A century has passed since the discovery of itations of this study include underreporting, misdiag-
anaphylaxis, and much knowledge has been added to nosis, and failure to recognize cases of anaphylaxis by
our understanding of this syndrome. This article reviews health care providers.2 Regardless, these numbers show
the pathophysiology, recognition, and treatment of ana- that anaphylaxis is a serious health problem in the

Downloaded by: New York Medical College. Copyrighted material.


phylactic shock. United States.

SCOPE OF THE PROBLEM PATHOPHYSIOLOGY


For several reasons the incidence and prevalence of Anaphylactic and anaphylactoid reactions result from
anaphylaxis are unknown. Notably, because anaphylaxis systemic release of mediators from mast cells and baso-
is not a reportable event, no national registry exists to phils. Again, anaphylactoid reactions are chemically and
maintain statistics concerning anaphylactic reactions. In clinically indistinguishable from anaphylactic reactions
addition, the lack of a standard definition and misdiag- except that they are not IgE mediated. These mediators
nosis by health care personnel hampers efforts to de- consist of preformed substances stored in the granules of
scribe the frequency and severity of anaphylaxis. mast cells and basophils (e.g., histamine, tryptase, he-
Furthermore, many people that suffer mild reactions parin, chymase, and cytokines), as well as newly synthe-
never seek medical treatment. Finally, attempting to sized molecules that are principally derived from the
extrapolate data from small, nonstandard patient popu- metabolism of arachadonic acid (e.g., prostaglandins and
lations to a national scale is fraught with problems.2,3 leukotrienes).4
The Rochester Epidemiology Study provides the Anaphylaxis occurs in an individual after reexpo-
best characterization of anaphylaxis in the United sure to an antigen to which that person has produced a
States.3 This computerized, indexed database contains specific IgE antibody. The antigen to which one pro-
medical records from residents of Olmsted County, duces an IgE antibody response that leads to an allergic
Minnesota. Because of this registry, the residents of reaction is called an allergen. The IgE antibodies pro-
Olmsted County have been the subjects of multiple duced may recognize various epitopes of the allergen.
epidemiological studies that are believed to most accu- These IgE antibodies then bind to the high-affinity IgE
rately depict the situation nationally. Important points to receptor (FceRI) on the surface of mast cells and
note, however, are that Olmsted County is 95% white basophils. Upon reexposure to the sensitized allergen,
and has a higher representation of health care workers the allergen may cross-link the mast cell or basophil
than the general population. The Rochester Epidemio- surface-bound allergen-specific IgE resulting in cellular
logic study yielded 154 separate anaphylactic reactions in degranulation as well as de novo synthesis of mediators.7
133 residents between 1983 and 1987. This translated Histamine is thought to be the primary mediator of
into a 30/100,000 person-year occurrence rate and a 21/ anaphylactic shock. Many of the signs and symptoms of
100,000 person-year incidence rate of anaphylaxis. The anaphylaxis are attributable to binding of histamine to its
most common symptoms and signs were cutaneous receptors; binding to H1 receptors mediates pruritis,
(100%), respiratory (69%), oral and gastrointestinal rhinorrhea, tachycardia, and bronchospasm. On the
(24%), and cardiovascular (41%). Anaphylaxis was other hand, both H1 and H2 receptors participate in
more common in the summer months (July–September) producing headache, flushing, and hypotension.4
and episodes were equal among males and females. In addition to histamine release, other important
Episodes were temporally related to suspected triggers mediators and pathways play a role in the pathophysiol-
between a few minutes to 2 hours. Atopy was present in ogy of anaphylaxis. Metabolites of arachadonic acid,
ANAPHYLACTIC SHOCK/JOHNSON, PEEBLES 697

including prostaglandins, principally prostaglandin D2 system development, which leads to less stimulation of
(PGD2) and leukotrienes, principally leukotriene C4 the Th1 pathway.
(LTC4), are elaborated by mast cells and to a lesser
extent basophils during anaphylaxis and, in addition to
histamine, are also thought to be pathophysiologically DIAGNOSIS
important.8,9 PGD2 mediates bronchospasm and vascu- Diagnosis of anaphylaxis in the acute setting is a clinical
lar dilatation, principle manifestations of anaphylaxis. one and starts with a brief, directed history because
LTC4 is converted into LTD4 and LTE4, mediators of treatment must be rendered quickly. This history should
hypotension, bronchospasm, and mucous secretion dur- include questions regarding a previous history of atopy or
ing anaphylaxis in addition to acting as chemotactic anaphylaxis, and exposure to new foods, medications,
signals for eosinophils and neutrophils.8,9 Other path- and insect bites or stings. Due to the varied presentation
ways active during anaphylaxis are the complement of anaphylaxis, it is often not recognized or misdiag-
system, the kallikrein–kinin system, the clotting cascade, nosed. Other conditions that mimic anaphylaxis include
and the fibrinolytic system.8 vasovagal events, mastocytosis, pheochromocytoma, car-
Specific lymphocyte subtypes (CD4þ Th2 T- diac arrhythmias, scromboid poisoning, panic attacks,
cells) are central in the induction of the IgE response. and seizures.5,12,13 Evaluation should focus on manifes-
CD4þ T-cells are segregated into either T-helper 1 tations that are likely to be life threatening. This includes
(Th1) or Th2 types, defined by the cytokine profile evaluation of the respiratory and cardiovascular systems
produced by the individual T cell. Th1 cells are impor- with particular attention to signs and symptoms of

Downloaded by: New York Medical College. Copyrighted material.


tant in cellular immunity and make interferon gamma. airway compromise and impending cardiovascular col-
Th2 responses are important in humoral immunity and lapse.5 See Table 1 for common manifestations and their
critical for the allergic response. Cytokines produced be frequency.
Th2 cells include interleukin (IL)-4, IL-5, IL-9, and IL- After or while the patient is being stabilized, a
13.10 Of great importance, IL-4 is the isotype switch complete history should be obtained. Exposure history
factor for B cells to begin producing IgE.10 The IgE prior to the reaction is paramount and must include
response is thought to be an overly robust immune foods, drugs, stings, or other agents. The time course of
response in certain predisposed (atopic) individuals.10 events is also important because anaphylactic episodes
Multiple factors influence whether one produces a Th2 usually occur shortly after exposure to a trigger; however,
versus a Th1 response including genetic variables, en- manifestations may be delayed by minutes to hours.3,5 In
vironmental factors, and triggers. The hygiene hypoth- anaphylaxis induced by foods, this delay is presumably
esis suggests that exposure to microbes in infancy leads attributable to the time between ingestion and absorption
to ‘‘immune deviation’’ from a Th2 response, which of the offending allergen.8 In general, it has been ob-
predominates in utero, to a predominantly Th1 response. served that the faster the onset of manifestations, the
Lack of this ‘‘immune deviation’’ leads to further perpe- more severe the reaction.2,5 Although history is essential,
tuation of the Th2 response to allergens. Stimuli (mi- it is important to note, however, that anaphylaxis may be
crobes) that lead to a Th1 response cause IL-12 to be the presenting manifestation of hypersensitivity; there-
produced by antigen-presenting cells. IL-12 not only fore, lack of previous history of allergy does not rule out
perpetuates the Th1 response but inhibits IgE produc- anaphylaxis. Atopic persons, as one might imagine, are
tion. Furthermore, cytokines such as interferon gamma predisposed to develop anaphylaxis. Asthma, although a
(produced by Th1 cells) and IL-18 (produced by macro- predictor for more severe reactions, is not recognized to
phages) suppress production of IgE. Thus the Th1 be a predisposing factor.2,6 Two laboratory studies, serum
response is considered to be inhibitory to allergy.10 tryptase and urinary N-methylhistamine, are useful in
The incidence of allergic diseases is on the rise in confirming anaphylaxis. These tests must be obtained in
the United States.2,10 There are several potential reasons fairly close proximity to the reaction to be useful. For
for this observation. Diet may play a role because new example, tryptase levels peak 1 hour after anaphylaxis to
allergens are increasingly being introduced into the bee stings and have a half-life in the serum of 2 hours.14
American diet. For example, the United States is the Similarly, urinary N-methylhistamine peaks 1 hour after
third largest consumer of peanuts in the world, 40% of IV infusion of histamine and returns to baseline levels
consumption is accounted for by peanut butter.11 after 2 hours.14 Tryptase level does seem to correlate with
Furthermore, the dramatic increase in the use of latex severity of the reaction.4 Furthermore, in cases of
products, particularly gloves, in the past 20 years has also suspected fatal anaphylaxis, massively elevated (> 50U/
been implicated. Finally, some invoke the ‘‘hygiene’’ L) postmortem serum tryptase has been shown to be a
hypothesis for the increase in the prevalence of allergic specific indicator of anaphylaxis.15
disease.10 The basis of this hypothesis is that inhabitants Causes of anaphylaxis are varied and are listed in
of Westernized countries are exposed to fewer (or Table 2. The discussion of each and every cause of
different) immunologic challenges during immune anaphylaxis is beyond the scope of this report; however,
698 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 25, NUMBER 6 2004

Table 1 Symptoms and Signs, the Number Out of 133 new information regarding a new method to prophylax
Patients with Anaphylaxis Who Experienced Them against peanut allergy and recognition that gelatin is a
Patients (N ¼ 133) significant cause of anaphylaxis are summarized in the
next sections. Also, latex allergy has been recognized as
Symptom or Sign N %
an important cause of anaphylaxis in the past 20 years,
Cutaneous and we will review some aspects of latex allergy as well.
Urticaria 73 55
Angioedema 74 56
Pruritus 73 55 PEANUT ALLERGY
Flushing 48 36 It is estimated that 1.5 million people in the United
Conjunctivitis or chemosis 30 23 States suffer from peanut and other nut allergies. Nut
Respiratory allergies account for a majority of life-threatening and
Dyspnea 57 43 fatal anaphylactic reactions involving food in the United
Throat tightness 37 28 States.2,11,16 Peanut allergic patients typically live a life
Wheezing 34 26 of careful avoidance. Avoidance, however, is not always
Rhinitis 22 17 enough because inadvertent exposure still occurs in
Laryngeal edema 9 7 sensitized patients every 3 to 5 years.17
Hoarseness 9 7 Currently, management options for patients who
Oral and gastrointestinal suffer from peanut allergy are limited. Prevention by

Downloaded by: New York Medical College. Copyrighted material.


Intraoral angioedema 20 15 exposure avoidance is the first line of management, and
Emesis 12 9 treatment of reactions caused by accidental exposures
Nausea 12 9 constitutes the next tier. Desensitization has an unfavor-
Abdominal cramps 11 8 able risk:benefit ratio and is therefore rarely performed.16
Dysphagia 7 5 Recently Leung et al reported the effect of anti-IgE
Oral pruritus 5 4 therapy in patients with a history of peanut allergy.16 In
Diarrhea 1 1 this randomized, double-blind trial, patients were ran-
Cardiovascular domized to four monthly subcutaneous doses of placebo
Tachycardia 36 27 or three dosage levels (150 mg, 300 mg, 450 mg) of a
Presyncope 20 15 humanized monoclonal antibody to IgE. Tolerance to
Hypotension 15 11 peanuts increased significantly in the higher-dose group
Syncope 4 3 (450 mg), and there was a trend toward increased
Shock 7 5 tolerance in the other two groups. The mechanism of
Chest pain 4 3 protection afforded by this treatment is to block binding
Bradycardia 2 2 of IgE to the FceRI receptors but also leads to down-
Orthostasis 2 2 regulation of the FceRI receptors on basophils. The
Reproduced with permission from Yocum et al.3 increase in tolerance in patients treated with the 450
mg dose translates into an increase in tolerence from 1 to
 9 peanuts. Obviously patients so treated will not have
a normal tolerance to peanuts, but this treatment should
afford protection against unintended ingestions, which
typically are no more than one or two peanuts.16
Table 2 Some Causes of Anaphylactic and
Anaphylactoid Reactions
Anti-IgE therapy has also been used effectively to
treat allergic asthma.18 Final approval for anti-IgE ther-
MEDICATIONS apy to treat patients 12 and over with moderate to severe
Nonsteroidal antiinflammatory drugs, aspirin, antibiotics, opioid allergic asthma is anticipated to occur in June 2003.
analgesics, insulin, protamine, general anesthetics, streptoki-
nase, blood products, progesterone, radiocontrast media,
biologic agents, immunotherapy GELATIN
FOODS In 1993, Kelso et al described an anaphylactic reaction to
Peanuts, tree nuts, fish, shellfish, milk, eggs, bisulfites the measles, mumps, rubella (MMR) vaccine in a child,
HYMENOPTERA VENOM which they ultimately proved was caused by gelatin,
Yellow jackets, hornets, wasps, honeybees, fire ants included as a stabilizer.19 The measles and mumps com-
MISCELLANEOUS ponents of the vaccine are produced in cultures of chick
Latex, exercise, gelatin, menstruation, seminal fluid, dialysis fibroblasts and contain minute amounts of egg pro-
membranes teins.20 Allergic reactions to vaccines, particularly MMR
Adapted from Rusznak and Peebles.41 or components thereof, were previously attributed to
ANAPHYLACTIC SHOCK/JOHNSON, PEEBLES 699

hypersensitivity to eggs. In the minds of Dr. Kelso and decades. The advent of the human immunodeficiency
his colleagues, this made little sense because many virus (HIV) epidemic in the early 1980s and the institu-
children with egg hypersensitivities were uneventfully tion of the universal precautions policy in the late 1980s
administered MMR vaccines whereas only two of 28 are commonly cited contributors to latex hypersensitiv-
reports of anaphylactic reactions to vaccines occurred in ity.26 Furthermore, changes in the manufacturing pro-
egg-allergic children.21 The astute observations of these cess of latex gloves driven by increased demand may have
investigators, coupled with serendipity (their patient led to production of latex products with increased
reported that the reaction to the vaccine was ‘‘kind of allergenicity. The first reported case of anaphylaxis
like what happens when I eat Jell-O’’)21 led these attributed to latex was published in 1984, and by the
investigators to a paradigm-shifting discovery. end of the decade, reports of anaphylaxis to latex were
Following the lead of Kelso et al, investigators in commonplace.26
Japan characterized anaphylactic reactions to vaccines as Risk groups for latex hypersensitivity include
also mediated by anti-gelatin IgE.22 In addition, they patients with spina bifida, patients who have had multi-
uncovered a link to hypersensitivity reactions to orally ple catheterizations of the genitourinary system such as
ingested gelatin, which, interestingly, developed after patients with congenital genitourinary abnormalities,
the vaccine-related reaction in five of seven children. patients who have undergone multiple surgical proce-
The same investigators also traced gelatin as the cause of dures, people working in the manufacture of latex
anaphylaxis in erythropoietin administered intravenously or latex products, atopic individuals, and health care
to hemodialysis patients.23 workers.27,28 Although controversial, a recent study has

Downloaded by: New York Medical College. Copyrighted material.


Gelatin is not only a food product but a compo- suggested that health care workers are not clearly at
nent of both enteral and parenteral medications. Sensi- increased risk for latex sensitization and type I hyper-
tization to gelatin appears to occur via oral intake or sensitivity compared with the general population.28–31
previous vaccination.21 It is also interesting to note that Contact with latex is common; it is estimated that
despite the use of gelatin in the formulations of many as many as 40,000 household products contain latex27
oral drugs, particularly capsule forms, there are scant (Table 3). In addition, it appears that certain fruits and
reports in the literature of hypersensitivity to gelatin vegetables cross-react with latex, and patients that have
administered enterally.21 Therefore, parenterally admi- an allergy to a particular fruit have subsequently devel-
nistered gelatin is more likely to produce hypersensitivity oped an allergy to latex, and conversely, patients with a
than enterally administered gelatin.21 latex allergy have subsequently developed an allergy to
The story for vaccines procured from chick em- particular fruits. This has been termed the latex–fruit
bryos (influenza and yellow fever), which contain sig- syndrome or the latex–food allergy syndrome.27,32 It has
nificantly more egg protein than MMR, is still unclear. been noted that 30 to 80% of people who have latex
There is a paucity of evidence concerning administration allergy also suffer from food allergy.27 Commonly
of influenza vaccine in egg allergic individuals, although implicated foods include banana, kiwi, avocado, and
James et al uneventfully administered influenza vaccine chestnuts; however, others have been implicated as
to egg allergic children using a two-dose regimen in well. It appears that proteins from these natural food
which one tenth of the recommended dose was given products have epitopes that cross react with latex epi-
followed by nine tenths of the recommended dose topes.27,32 This, of course, begs the question as to
30 minutes later.24 The formulation of vaccine contained whether sensitization to latex is attributable to the latex
between 0.02 and 1.2 m g/mL of egg protein. itself, the foods just listed, or a combination of both.
In the American Academy of Pediatrics Red Book,
skin testing prior to administration of yellow fever
vaccine to egg hypersensitive individuals is advocated;
and administration of influenza vaccine to individuals Table 3 Items Containing Latex
with severe anaphylactic reactions to eggs is not
recommended.20,25 HOME
Bandages, balloons, condoms, diaphragms, elastic bands
in clothing, rubber balls, pacifiers, hand grips, shoes, hot
LATEX water bottles, shower curtains, toys, waterproofing paints
Latex was used as early as 1600 BC, and use of latex (not all latex paints)
surgical gloves began to proliferate in the early part of HOSPITAL
the 20th century. Natural rubber latex is derived from Catheters of various types (Foley, nasogastric, intravenous,
the sap of the rubber tree (Hevea brasiliensis). Although etc.), gloves, endotracheal tubes, masks, shoe covers and
hypersensitivity attributed to latex was first reported in caps, oxygen masks, Ambu1-bags, reflex hammer,
the late 1920s, latex has become an increasingly impor- stethoscope, syringes
tant cause of allergy and anaphylaxis over the last 2 Adapted from Condemi27 and Nettis et al.32
700 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 25, NUMBER 6 2004

Downloaded by: New York Medical College. Copyrighted material.

Figure 1 Acute management of anaphylaxis. Reproduced with permission from Joint Task Force on Practice Parameters.5

TREATMENT istration of epinephrine.5 It should be noted that patients


Once the diagnosis of anaphylaxis is believed likely, can progress from being relatively stable to a state of
immediate administration of epinephrine should occur. extremis in a very short time. Biphasic or late phase
A management algorithm is shown in Fig. 1 and an reactions, in which patients have a recrudescence of
explanation of the medications used in the treatment of anaphylactic signs and symptoms several hours after
anaphylaxis is shown in Table 4. Diphenhydramine and the anaphylactic episode, have been described in up to
corticosteroids as well as H2 blockers are also advocated 20% of cases.5,11,12 Patients should therefore be observed
as adjunctive treatments in the management of anaphy- for at least 4 hours because 90% of biphasic reactions
laxis; however, they are no substitute for prompt admin- occur within this time period.11 Observation for as long
ANAPHYLACTIC SHOCK/JOHNSON, PEEBLES 701

Table 4 Treatment of Anaphylaxis


Therapy Indication Dosage Goals

AIRWAY OR
CUTANEOUS REACTIONS
Epinephrine Bronchospasm, laryngeal 0.3–0.5 mL of 1:1,000 Maintain airway patency,
edema, hypotension, solution IM, every reduce fluid extravasation
urticaria, angioedema 10 minutes as needed
Oxygen Hypoxemia Up to 100% Maintain SaO2 > 90%
Albuterol Bronchospasm 0.5 mL of 0.5% solution in 2.5 mL Maintain airway patency
of isotonic saline by nebulizer, or
two puffs by metered-dose inhaler
every 15 minutes, up to three doses
Diphenhydramine Urticaria 1 to 2 mg/kg or 25–50 mg Reduce pruritis and
parenterally antagonize histamine
effects
Methylprednisolone Bronchospasm 125 mg IV every 6 hours Reduce late-phase
reactions
CARDIOVASCULAR

Downloaded by: New York Medical College. Copyrighted material.


REACTIONS
Epinephrine Hypotension 1:10,000 solution given IV at 1 mg/min Maintain systolic blood
initially, then 2–10 mg/min pressure > 90 mm Hg
Intravenous fluids Hypotension 1 L of isotonic saline (0.9% normal Maintain systolic blood
saline) every 20–30 minutes pressure > 90 mm Hg
as needed
Ranitidine4,12 Hypotension 50 mg in 20 mL D5W infused over Can be used in addition to
10–15 minutes epinephrine and IV fluids
to maintain systolic
blood pressure
> 90 mm Hg
Secondary Therapy
Norepinephrine Hypotension 4 mg in 1 L D5W at 2–12 mg/min Maintain systolic blood
pressure > 90 mm Hg
Glucagon Refractory 1 mg in 1 L D5W at 5–15 mg/min Increase heart rate and
hypotension cardiac output
IM, intramuscular; SaO2, oxygen saturation; D5W, 5% dextrose in water.
Adapted from Rusznak and Peebles.41

as 24 hours has been advocated12; however, we advocate similar to biphasic anaphylaxis, is impossible to antici-
monitoring for no more than 10 hours after severe, life- pate based on initial patient presentation.12
threatening episodes of anaphylaxis. Biphasic reactions There are no absolute contraindications to using
can be treacherous because they often occur after symp- epinephrine in the context of anaphylactic shock, and
toms of anaphylaxis have completely resolved. Biphasic failure to do so promptly can lead to adverse outcomes.4
reactions are poorly understood; however, some data This is illustrated by a study in dogs in which treatment
suggest that they tend to occur in cases of more severe with epinephrine at maximal hypotension produced no
initial presentations and in instances when treatment benefit in hemodynamic recovery in a canine model of
with epinephrine has been delayed.11 Others, however, anaphylaxis.33 It is also important to point out that
suggest that it is not possible to predict the occurrence of proper dose and route of administration are essential
biphasic reactions based on initial presentation.4,12 because both over- and underdosage may be life threa-
Furthermore, biphasic reactions can be more difficult tening.13,34 The proper dose of epinephrine in adults is
to treat than the initial episode, often requiring intuba- 0.3 to 0.5 mL of a 1:1000 solution given intramuscularly.
tion.11 Persistent anaphylaxis, anaphylaxis that continues Some authors advocate 0.1 mL of 1:1000 epinephrine IV
for a protracted period of time, has also been described in for the treatment of hypotensive patients or those
the literature.4,8,12 Some authors have observed rates as refractory to IM dosing; however, intravenous dosing
high as 28%, whereas data from others suggest that may be associated with more side effects. Repeat dosing
persistent anaphylaxis is rare.4,12 Persistent anaphylaxis, may be necessary to reverse anaphylaxis. Many health
702 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 25, NUMBER 6 2004

care providers do not recognize the difference between selves are unsure of how to properly use the device.38,39
epinephrine given for treatment of anaphylaxis and Patients with a history of anaphylaxis should be advised
epinephrine given for resuscitation with respect to to carry the autoinjector kit on their person at all times.
dose, route, and rapidity of infusion.13 It has also been Patients should be instructed to seek medical attention,
reported that some proportion of patients die regardless especially if they have had a reaction serious enough to
of treatment with epinephrine.11,13 require use of an epinephrine autoinjector. Ideally,
Recent data have come to light regarding the EpiPen1 or EpiPen Jr1 should be used before its
preferred method of administering epinephrine. Simons expiration date, and this is recommended because epi-
et al performed a study in children in which they nephrine from outdated autoinjectors has considerably
reported that IM injection of epinephrine is superior reduced bioavailability.40 If, however, a patient is sud-
to subcutaneous administration.35 This conclusion was denly in need of epinephrine, it has been shown that
based in delayed epinephrine absorption with subcuta- outdated epinephrine autoinjectors have a percent of
neous compared with IM administration. The difference labeled epinephrine content inversely proportional to
was hypothesized to be due to the cutaneous vasocon- months past expiration date. The authors of this study
strictive properties of epinephrine. They extended their concluded that outdated EpiPen1 and EpiPen Jr1 can
findings to adults and further defined that IM injection be used if no discoloration or precipitate is present. The
into the thigh (vastus lateralis) is preferred to IM basis of their conclusion is that if a life-threatening
injection into the deltoid.36 This conclusion is based anaphylactic episode occurs, the potential benefits of
on the superior serum levels of epinephrine achieved by using outdated autoinjectors outweigh potential risks.40

Downloaded by: New York Medical College. Copyrighted material.


this method in comparison to subcutaneous injection as In patients who are taking beta-blockers and who suffer
well as IM injection into the deltoid. Superiority of anaphylaxis, some case reports suggest glucagen may be
blood flow to the vastus lateralis is hypothesized to effective in those patients who fail to respond to other
account for this difference.36 therapies listed in Table 4.41
It has been suggested that patients taking beta
blockers may be at increased risk for severe reactions
during anaphylaxis.4,5 Beta blockers administered orally CONCLUSION
and even topically may interfere with epinephrine treat- Anaphylaxis is a systemic, type I allergic reaction that
ment by antagonizing its effects at the beta adrenergic often has fatal consequences. Anaphylaxis has a variety of
receptor.4,12 In experimental models, an 80-fold increase causes including foods, latex, drugs, and hymenoptera
in dose of isoproterenol was required to overcome the venom. Epinephrine given early is the most important
effects of beta blockade.4,12 Similarly, angiotensin con- intervention in the treatment of anaphylaxis. Other
verting enzyme (ACE) inhibitors may also be proble- adjunctive treatments include H1 and H2 receptor an-
matic during anaphylaxis.12,37 During anaphylaxis, fluid tagonists, corticosteroids, and bronchodilators; however
shifts occur such that up to 50% of the plasma volume these do not substitute for epinephrine. Patients with a
may be lost from the circulation in as little as history of anaphylaxis should be educated about their
10 minutes.4,37 To compensate for this, angiotensin, a condition, especially with respect to trigger avoidance.
potent vasoconstrictor, is released by the action of the These patients should also be instructed on the correct
renin–angiotensin–aldosterone system. Blockade of use of epinephrine autoinjector kits and be counseled to
ACE prevents this compensatory response from taking keep these kits on their person at all times.
place.4,12,37
An important aspect of treatment is prevention of
further events. This includes, of course, avoidance of the FUNDING
allergen and education of the patient regarding strategies This work was supported by T32 HL07123, the Amer-
for allergen avoidance. It is also important for patients to ican Academy of Allergy, Asthma, and Immunology
be aware of potential cross-reacting allergens, particu- ERT Award, RO1 HL 069949, RO1 AI 054660,
larly drugs and nuts.13 Education of teachers and staff at RO1 AI 45512.
schools and other child care venues is also important.6
Patients prone to anaphylaxis should also be advised to
wear MedicAlert1 bracelets.
In addition, patients prone to anaphylaxis should REFERENCES
be provided with one or more autoinjector kits (Epi-
1. Cohen SG, Zelaya-Quesada M. Portier, Richet, and the
Pen1 or EpiPen Jr1) and should be instructed on their
discovery of anaphylaxis: a centennial. J Allergy Clin Immunol
use. This should take place with an EpiPen1 demon- 2002;110:331–336
strator in the physician’s office. It has been reported that 2. Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the
physicians are deficient in teaching patients to use United States: an investigation into its epidemiology. Arch
autoinjectors, and in some cases, the physicians them- Intern Med 2001;161:15–21
ANAPHYLACTIC SHOCK/JOHNSON, PEEBLES 703

3. Yocum MW, Butterfield JH, Klein JS, et al. Epidemiology an 23. Sakaguchi M, Kaneda H, Inouye S. A case of anaphylaxis to
anaphylaxis in Olmsted County: a population-based study. gelatin included in erythropoietin products. J Allergy Clin
J Allergy Clin Immunol 1999;104:452–456 Immunol 1999;103:349–350
4. Kemp SF, Lockey RF. Anaphylaxis: a review of causes 24. James JM, Zeiger RS, Lester MR, et al. Safe administration of
and mechanisms. J Allergy Clin Immunol 2002;110:341– influenza vaccine to patients with egg allergy. J Pediatr 1998;
348 133:624–628
5. Joint Task Force on Practice Parameters. The diagnosis and 25. American Academy of Pediatrics. Summaries of infectious
management of anaphylaxis. J Allergy Clin Immunol 1998; diseases. In Pickering LK, ed. 2000 Red Book: Report of the
101:S465–S527 Committee on Infectious Diseases. 25th ed. Elk Grove Village,
6. AAAAI Board of Directors. Anaphylaxis in schools and other IL: American Academy of Pediatrics; 2000;175:357–358
child-care settings. J Allergy Clin Immunol 1998;102:173– 26. Ownby DR. A history of latex allergy. J Allergy Clin
176 Immunol 2002;110:S27–S32
7. Long A. The nuts and bolts of peanut allergy. N Engl J Med 27. Condemi JJ. Allergic reactions to natural rubber latex at home,
2002;346:1320–1322 to rubber products, and to cross-reacting foods. J Allergy Clin
8. Dykewicz MS. Anaphylaxis and inflammation. Clin Allergy Immunol 2002;110:S107–S110
Immunol 2002;16:401–409 28. Turjanmaa K, Alenius H, Reunala T, Palosuo T. Recent
9. Daffern PJ, Schwartz LB. Allergic response. In Dale DC, ed. developments in latex allergy. Curr Opin Allergy Clin
WebMD Scientific American Medicine. New York: WebMD Immunol 2002;2:407–412
Reference Group; 2003 29. Garabrant DH, Schweitzer S. Epidemiology of latex
10. Kay AB. Allergy and allergic diseases: first of two parts. N sensitization and allergies in health care workers. J Allergy
Engl J Med 2001;344:30–37 Clin Immunol 2002;110:S82–S95

Downloaded by: New York Medical College. Copyrighted material.


11. Sampson HA. Peanut allergy. N Engl J Med 2002;346:1294– 30. Bauer X. Epidemiology of latex sensitization. J Allergy Clin
1299 Immunol 2003;111:652
12. Kemp SF. Current concepts in pathophysiology, diagnosis, 31. Garabrant DH, Schweitzer S. Reply. J Allergy Clin Immunol
and management of anaphylaxis. Immunol Allergy Clin 2003;111:652
North Am 2001;21:611–634 32. Nettis E, Colanardi MC, Ferrannini A, Tursi A. Latex
13. Pumphrey RSH. Lessons for management of anaphylaxis hypersensitivity: personal data and review of the literature.
from a study of fatal reactions. Clin Exp Allergy Immunopharmacol Immunotoxicol 2002;24:315–334
2000;30:1144–1150 33. Bautista E, Simons FER, Simons KJ, et al. Epinephrine fails
14. Hogan AD, Schwartz LB. Markers of mast cell degranula- to hasten hemodynamic recovery in fully developed canine
tion. Methods 1997;13:43–52 anaphylactic shock. Int Arch Allergy Immunol 2002;128:
15. Brockow K, Vieluf D, Püschel K, et al. Increased postmortem 151–164
serum mast cell tryptase in a fatal anaphylactoid reaction to 34. Johnston SL, Unsworth J, Gompels MM. Adrenaline given
nonionic radiocontrast medium. J Allergy Clin Immunol outside the context of life threatening allergic reactions. BMJ
1999;104:237–238 2003;326:589–590
16. Leung DYM, Sampson HA, Yunginger JW, et al. Effect of 35. Simons FER, Roberts JR, Gu X, Simons KJ. Epinephrine
anti-IgE therapy in patients with peanut allergy. N Engl J absorption in children with a history of anaphylaxis. J Allergy
Med 2003;348:986–993 Clin Immunol 1998;101:33–37
17. Merz B. Studying peanut anaphylaxis. N Engl J Med 36. Simons FER, Gu X, Simons KJ. Epinephrine absorption in
2003;348:975–976 adults: intramuscular versus subcutaneous injection. J Allergy
18. Berger WE. Monoclonal anti-IgE antibody: a novel therapy Clin Immunol 2001;108:871–873
for allergic airways disease. Ann Allergy Asthma Immunol 37. Yocum MW, Khan DA. Assessment of patients who have
2002;88:152–161 experienced anaphylaxis: a 3-year survey. Mayo Clin Proc
19. Kelso JM, Jones RT, Yunginger JW. Anaphylaxis to measles, 1994;69:16–23
mumps, and rubella vaccine mediated by IgE to gelatin. 38. Huang S. A survey of Epi-PEN use in patients with a history
J Allergy Clin Immunol 1993;91:867–872 of anaphylaxis. J Allergy Clin Immunol 1998;102:525–526
20. Crockett RE, Lockey RF. Vaccine hypersensitivity. Immunol 39. Grouhi M, Alshehri M, Hummel D, Roifman CM.
Allergy Clin North Am 2001;21:707–743 Anaphylaxis and epinephrine auto-injector training: who will
21. Kelso JM. The gelatin story. J Allergy Clin Immunol teach the teachers? J Allergy Clin Immunol 1999;104:190–193
1999;103:200–202 40. Simons FER, Gu X, Simons KJ. Outdated EpiPen and
22. Sakaguchi M, Nakayama T, Inouye S. Food allergy to gelatin EpiPen Jr autoinjectors: past their prime? J Allergy Clin
in children with systemic immediate-type reactions, including Immunol 2000;105:1025–1030
anaphylaxis, to vaccines. J Allergy Clin Immunol 1996;98: 41. Rusznak C, Peebles RS. Anaphylaxis. Postgrad Med
1058–1061 2002;111:101–114

You might also like