Upload
indeenike
View
1.477
Download
2
Embed Size (px)
Citation preview
AnaphylaxisIntroduction
Background
Anaphylaxis is a severe allergic reaction that is rapid in onset and may cause death. There are usually
prominent dermal and systemic signs and symptoms. The full-blown syndrome includes urticaria (hives) and/or
angioedema with hypotension and bronchospasm. The classic form, described in 1902, involves prior
sensitization to an allergen with later re-exposure, producing symptoms via an immunologic mechanism. An
anaphylactoid reaction produces a very similar clinical syndrome but is not immune-mediated. Treatment for
both conditions is similar, and this article uses the term anaphylaxis to refer to both conditions unless otherwise
specified. A recent consensus report reviewed the definition and management of anaphylaxis.1
For a CME/CE activity, see Anaphylaxis. Also see Medscape's Allergy & Immunology Resource Center.
Pathophysiology
Rapid onset of increased secretion from mucous membranes, increased bronchial smooth muscle tone,
decreased vascular smooth muscle tone, and increased capillary permeability occur after exposure to an
inciting substance. These effects are produced by the release of mediators, which include histamine,
leukotriene C4, prostaglandin D2, and tryptase.
In the classic form, mediator release occurs when the antigen (allergen) binds to antigen-specific
immunoglobulin E (IgE) attached to previously sensitized basophils and mast cells. The mediators are released
almost immediately when the antigen binds. In an anaphylactoid reaction, exposure to an inciting substance
causes direct release of mediators, a process that is not mediated by IgE. Increased mucous secretion and
increased bronchial smooth muscle tone, as well as airway edema, contribute to the respiratory symptoms
observed in anaphylaxis. Cardiovascular effects result from decreased vascular tone and capillary leakage.
Histamine release in skin causes urticarial skin lesions.
The most common inciting agents in anaphylaxis are parenteral antibiotics (especially penicillins), IV contrast
materials, Hymenoptera stings, and certain foods (most notably, peanuts). Oral medications and many other
types of exposures also have been implicated. Anaphylaxis also may be idiopathic.
Frequency
United States
The true incidence of anaphylaxis is unknown, partly because of the lack of a precise definition of the
syndrome. Some clinicians reserve the term for the full-blown syndrome, while others use it to describe milder
cases. Fatal anaphylaxis is relatively rare; milder forms occur much more frequently. The frequency of
anaphylaxis is increasing, and this has been attributed to the increased number of potential allergens to which
people are exposed. Up to 500-1,000 fatal cases of anaphylaxis per year are estimated to occur in the United
States. A recent review concluded that the lifetime prevalence of anaphylaxis is 1-2% of the population as a
whole.2
International
Reactions to insects and other venomous plants and animals are more prevalent in tropical areas because of
the greater biodiversity in these areas.
Mortality/Morbidity
Approximately 1 in 5000 exposures to a parenteral dose of a penicillin or cephalosporin antibiotic causes
anaphylaxis. More than 100 deaths per year are reported in the United States. Fewer than 100 fatal reactions
to Hymenoptera stings are reported each year in the United States but this is considered to be an
underestimate. One to 2% of people receiving IV radiocontrast experience some sort of reaction. The majority
of these reactions are minor, and fatalities are rare. Low molecular weight contrast causes fewer and less
severe reactions.
Race
Well-described racial differences in the incidence or severity of anaphylaxis do not exist. Cultural and
socioeconomic differences may influence exposure rates.
Sex
Differences have been reported in the incidence and prevalence of anaphylactic reactions between men and
women. Overall, women have a higher incidence of anaphylaxis than men, but, in some series of children,
males predominate.2
Age
Anaphylaxis occurs in all age groups. Food allergies are more common in the young, whereas more drug
reactions occur in adults, possibly due to greater exposure. Although prior exposure is essential for the
development of true anaphylaxis, reactions occur even when no documented prior exposure exists. Thus,
patients may react to a first exposure to an antibiotic or insect sting. Elderly persons have the greatest risk of
mortality from anaphylaxis due to the presence of preexisting disease.
Clinical
History
Anaphylactic reactions almost always involve the skin or mucous membranes. More than 90% of
patients have some combination of urticaria, erythema, pruritus, or angioedema.
The upper respiratory tract commonly is involved, with complaints of nasal congestion, sneezing, or
coryza. Cough, hoarseness, or a sensation of tightness in the throat may presage significant airway
obstruction.
Eyes may itch and tearing may be noted. Conjunctival injection may occur.
Dyspnea is present when patients have bronchospasm or upper airway edema. Hypoxia and
hypotension may cause weakness, dizziness, or syncope. Chest pain may occur due to bronchospasm
or myocardial ischemia (secondary to hypotension and hypoxia).
GI symptoms of cramplike abdominal pain with nausea, vomiting, or diarrhea also occur but are less
common, except in the case of food allergy.
In a classic case of anaphylaxis, the patient or a bystander provides a history of possible exposures
that may have caused the rapid onset of skin and other manifestations. This history often is partial;
exposure may not be recalled, or it may not be considered significant by the patient or health care
provider. For example, when queried about medications, a patient may not mention over-the-counter
(OTC) products. The clinician may not realize that, while reactions are usually rapid in onset, they also
may be delayed.
For reasons that are not well understood, a lack of dermal findings is more common in children than
in adults.
Physical
General o Physical examination of patients with anaphylaxis depends on affected organ systems and
severity of attack. Vital signs may be normal or significantly disordered with tachypnea,
tachycardia, and/or hypotension. o Place emphasis on determining the patient's respiratory and cardiovascular status.
o Frank cardiovascular collapse or respiratory arrest may occur in severe cases. Anxiety is
common unless hypotension or hypoxia causes obtundation. Shock may occur without
prominent skin manifestations or history of exposure; therefore, anaphylaxis is part of the
differential diagnosis for patients who present with shock and no obvious cause. o General appearance and vital signs vary according to severity of attack and affected organ
system(s). Patients commonly are restless due to severe pruritus from urticaria. Anxiety,
tremor, and a sensation of cold may result from compensatory endogenous catecholamine
release. Severe air hunger may occur when the respiratory tract is involved. If hypoperfusion
or hypoxia occurs, the patient may exhibit a depressed level of consciousness or may be
agitated and/or combative. Tachycardia usually is present, but bradycardia may occur in very
severe reactions.
Skin o The classic skin manifestation is urticaria (ie, hives). Lesions are red and raised, and they
sometimes have central blanching. Intense pruritus occurs with the lesions. Lesion borders
usually are irregular and sizes vary markedly. Only a few small or large lesions may become
confluent, forming giant urticaria. At times, the entire dermis is involved with diffuse erythema
and edema. Hives can occur anywhere on the skin. o In a local reaction, lesions occur near the site of a cutaneous exposure (eg, insect bite). The
involved area is erythematous, edematous, and pruritic. If only local skin reaction (as opposed
to generalized urticaria) is present, systemic manifestations (eg, respiratory distress) are less
likely. Local reactions, even if severe, are not predictive of systemic anaphylaxis on
reexposure. o Lesions typical of angioedema also may manifest in anaphylaxis. The lesions involve mucosal
surfaces and deeper skin layers. Angioedema usually is nonpruritic and associated lesions
are nonpitting. Lesions most often appear on the lips, palms, soles, and genitalia.
Pulmonary o Upper airway compromise may occur when the tongue or oropharynx is involved. When the
upper airway is involved, stridor may be noted. The patient may have a hoarse or quiet voice
and may lose speaking ability as the edema progresses. Complete airway obstruction is the
most common cause of death in anaphylaxis. o Wheezing is common when patients have lower airway compromise due to bronchospasm or
mucosal edema. o In angioedema, due to ACE inhibitors, marked edema of the tongue and lips may obstruct the
airway.
Cardiovascular o Cardiovascular examination is normal in mild cases. In more severe cases, compensatory
tachycardia occurs due to loss of vascular tone.
o Intravascular volume depletion may take place as a consequence of capillary leakage. These
mechanisms also lead to development of hypotension. o Relative bradycardia has been reported.
Causes
A wide variety of substances can cause anaphylaxis. Drugs and foods are the most common causes.
Peanuts, tree nuts, and shellfish are the most commonly implicated foods, while antibiotics (especially
penicillins) and nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common drugs.
Anaphylaxis also may be idiopathic.
In the classic form of anaphylaxis, a foreign protein is the inciting agent (eg, antigen). On initial
exposure, the antigen elicits generation of an IgE antibody. The antibody residue binds to mast cells
and basophils. On reexposure, the antigen binds to the antibody, and the receptors are activated.
Clinical manifestations result from release of immune response mediators such as histamine,
leukotrienes, tryptase, and prostaglandins. The same mechanism occurs when a nonimmunogenic
foreign substance binds as a so-called hapten to a native carrier protein, creating an immunogenic
molecule. Factors influencing severity of a reaction include degree of host sensitivity and dose, route,
and rate of administration of the offending agent.
Parenteral exposures tend to result in faster and more severe reactions. Most severe reactions occur
soon after exposure. The faster a reaction develops, the more severe it is likely to be. While most
reactions occur within hours, symptoms may not occur for as long as 3-4 days after exposure.
Drugs
Penicillin and cephalosporin antibiotics are the most commonly reported medical agents in
anaphylaxis. This prevalence is a function of the immunogenicity and frequent use of these agents.
Because of their molecular and immunologic similarity, cross-sensitivity may exist. o Reports based on skin testing indicate that about 10% of patients allergic to a penicillin
antibiotic are allergic to cephalosporins.
One report suggested that the actual incidence of clinical cross-reactivity is lower
(perhaps 1%), with most reactions considered mild.3 Another paper indicated that
patients with a history of allergy to penicillin seem to have a higher risk (by a factor of
about 3) of subsequent reaction to any drug and that the risk of an allergic reaction to
cephalosporins in patients with a history of penicillin allergy may be up to 8 times as
high as the risk in those with no history of penicillin allergy (ie, at least part of the
observed "cross reactivity" may represent a general state of immune
hyperresponsiveness, rather than true "cross-reactivity").4
One retrospective study evaluated 606 hospitalized patients with a history of penicillin
allergy who were given a cephalosporin. Only one patient (0.17%) had a reaction,
and it was minor.5
o Patients with a history of positive skin tests for penicillin allergy are at high risk of subsequent
reactions. However, approximately 85% of patients with a history of penicillin allergy have
negative skin tests and a low risk of reactions.
When a drug in either class is the drug of choice for a patient with a life-threatening
emergency, a number of options exist. When the history is indefinite, the drug may be
administered under close observation; however, when possible, obtain the patient's
informed consent. Immediate treatment measures for anaphylaxis should be
available. Alternatively, when the history is more convincing, a desensitization or
prophylactic pretreatment protocol may be instituted or another agent selected.
Reactions to medications tend to be more severe and rapid in onset when the antibiotic is
administered parenterally.
A drug reaction may occur in a patient with no prior history of drug exposure.
Aspirin and NSAIDs commonly are implicated in allergic reactions and anaphylaxis. Bronchospasm is
common in patients with reactive airway disease and nasal polyps. Cross-reactivity often occurs
between the various NSAIDs.
ACE inhibitors, widely used in the treatment of hypertension, are associated with angioedema in 0.5-
1.0% of patients who take them. Systemic anaphylaxis is rarely associated with these agents. The
reaction is thought to be medicated by bradykinin and is more common in African Americans.
Intravenous radiocontrast media
IV administered radiocontrast media causes an anaphylactoid reaction that is clinically similar to true
anaphylaxis and is treated in the same way. The reaction is not related to prior exposure. Shellfish or
"iodine allergy" is not a contraindication to use of IV contrast and does not mandate a pretreatment
regimen. As with any "allergic" patient, give consideration to use of low molecular weight (LMW)
contrast.
The term iodine allergy is a misnomer. Iodine is an essential trace element present throughout the
body. No one is allergic to iodine. Patients who report iodine allergy usually have had either a prior
contrast reaction, a shellfish allergy, or a contact reaction to povidone-iodine (Betadine). Manage
these patients as indicated earlier.
Approximately 1-3% of patients who receive hyperosmolar IV contrast experience a reaction. Use of
LMW contrast decreases incidence of reactions to approximately 0.5%. Personnel, medications, and
equipment needed for treatment of allergic reactions always should be available when these agents
are administered. Obtain consent before administration.
Reactions to radiocontrast usually are mild (most commonly urticarial), with only rare fatalities
reported. Risk of a fatal reaction has been estimated at 0.9 cases per 100,000 exposures.
Mucosal exposure (eg, GI, genitourinary [GU]) to radiocontrast agents has not been reported to cause
anaphylaxis; therefore, a history of prior reaction is not a contraindication to GI or GU use of these
agents.
Pretreatment with antihistamines or corticosteroids and use of LMW agents lead to lower rates of
anaphylactoid reactions to IV contrast. Consider these measures for patients who have prior history of
reaction, since rate of recurrence is estimated at 17-60%. Some institutions use only LMW agents.
Patients who are atopic and/or asthmatic also are at increased risk of reaction. In addition, allergic
reaction is more difficult to treat in those taking beta-blockers.
Hymenoptera stings
Hymenoptera stings are a common cause of allergic reaction and anaphylaxis. An uncertain but
enormous number of exposures occur; accurate reaction rates are therefore difficult to estimate. In the
United States, Hymenoptera envenomations result in fewer than 100 reported deaths per year.
Local reaction and urticaria without other manifestations of anaphylaxis are much more common than
full-blown anaphylaxis. Generalized urticaria is a risk factor for subsequent anaphylaxis; but a local
reaction, even if severe, is not a risk factor for anaphylaxis.
Caution patients treated and released from the ED after an episode of anaphylaxis or generalized
urticaria from Hymenoptera envenomation to avoid future exposure when possible. Consider referral to
an allergist for desensitization, particularly when further exposure is likely. Additionally, consider
prescribing a treatment kit with an epinephrine auto-injector and oral antihistamine. Both are effective
measures in preventing or ameliorating future reactions.
Food and environmental allergies
Food allergy is common. Symptoms usually are mild and limited to the GI tract, but full-blown
anaphylaxis can occur. Fatalities are rare compared to number of exposures; however, the number of
exposures is so high that foods may be the commonest cause of anaphylaxis. Anaphylaxis due to
foods may be an underrecognized cause of sudden death and an unappreciated cause of diagnosed
anaphylaxis. Commonly implicated foods include peanuts, tree nuts, legumes, fish and shellfish, milk,
and eggs. Reports of severe allergic reactions to peanuts are increasing.
Latex allergy is an increasingly recognized problem in medical settings, where use of gloves and other
latex products is ubiquitous. Most reactions are cutaneous or involve the mucous membranes.
Anaphylactic reactions occur and have been reported with seemingly benign procedures (eg, Foley
catheter insertion, intraperitoneal exposure to gloves during surgery).
Differential Diagnoses
Angioedema Myocardial Infarction
Anxiety Pulmonary Embolism
Asthma Toxicity, Scombroid
Conversion Disorder Urticaria
Epiglottitis, Adult
Foreign Bodies, Trachea
Other Problems to Be Considered
Globus hystericus
Hereditary angioedema
Monosodium glutamate poisoning (ie, Chinese restaurant syndrome)
Workup
Laboratory Studies
The diagnosis of anaphylaxis is clinical and does not rely on laboratory testing. When typical
symptoms are noted in association with a likely exposure, diagnosis is virtually certain. Ancillary testing
may help assess severity of reaction, although this is primarily a clinical judgment. When unclear,
ancillary testing may help establish the diagnosis.
The only potentially useful test at the time of reaction is measurement of serum mast cell tryptase.
Tryptase is released from mast cells in both anaphylactic and anaphylactoid reactions. Levels are
usually raised in severe reactions. Mast cell tryptase is raised transiently with blood levels reaching a
peak approximately an hour after reaction onset. o Tryptase levels may aid in later diagnosis and treatment.
o Consider the test in cases for which diagnosis of anaphylaxis is uncertain.
o The utility of this test awaits full evaluation.
Cardiac monitoring in patients with severe reactions and in those with underlying cardiovascular
disease is important, particularly when adrenergic agonists are used in treatment. Pulse oximetry also
is useful.
Imaging Studies
Imaging studies are not generally useful in the diagnosis and management of anaphylaxis, although
they may be used as diagnostic aids when diagnosis is unclear.
Other Tests
Sensitivity testing o Testing for sensitivity to penicillin antibiotics may be useful when a penicillin or cephalosporin
antibiotic is the drug of choice for a serious infection in a patient who has a history of severe
allergic reaction. Obtain informed consent, and ensure that resuscitative equipment is
immediately available. Protocols for acute testing for allergy to penicillin or cephalosporin
antibiotics involve administration of increasing IV doses of the chosen antibiotic, while
observing the patient for pruritus, flushing, urticaria, dyspnea, hypotension, or other
manifestations of anaphylaxis. If no manifestations are observed, a full dose of the antibiotic
may be administered safely. o A suggested protocol for IV testing begins with 0.001 mg of the chosen drug. At 10-min
intervals, incrementally increase the dose (eg, 0.001 mg, 0.005 mg, 0.01 mg, 0.05 mg, 0.1 g,
0.5 mg, 1 mg, 10 mg, 50 mg, 100 mg, full dose), while observing the patient. Many other
protocols exist. In most circumstances, perform desensitization on an inpatient basis. If the
necessary resources are available, desensitization may be performed in the ED.
Procedures
Intravenous contrast reaction prevention o Patients with a history of severe reactions to IV contrast material may require use of contrast
in an urgent or emergency situation. Alternatives (eg, noncontrast spiral CT scan for ureteral
stone, Doppler ultrasonography for deep venous thrombosis [DVT], nuclear scans for
pulmonary embolism) should be considered but are not always feasible. In these
circumstances, a prophylactic regimen of corticosteroids and antihistamines may be used.
The precise efficacy of these regimens is difficult to evaluate, but they generally are
considered effective. One author states that the recurrence rate for patients with a previous
reaction was reduced from 17-60% to 9% when conventional contrast material was used; the
rate was reduced to less than 1% when low osmolality material was employed after a
pretreatment regimen. o The use of H2 blockers has not been shown to decrease the risk of reaction to IV contrast.
One study suggests H2 blockers actually appear to increase the risk. o A widely quoted protocol for prevention of reactions to IV contrast suggests the following:
Use low osmolality contrast.
Administer hydrocortisone (200 mg IV); wait 2 hours if clinically appropriate.
Administer diphenhydramine (50 mg IM) immediately before the procedure.
Desensitization regimens
o Desensitization regimens for penicillin and cephalosporin antibiotic allergy have been shown
effective. Because these regimens are lengthy (approximately 6 h), they have limited
applicability to the ED. When patients wait for long periods in the ED or in an observation unit,
consider desensitization regimens. o A typical desensitization regimen involves administering the antibiotic of choice in an initial
dose of 0.01 mg. While observing the patient, double the dose every 10-15 minutes until a full
dose has been administered. o Desensitization regimens do not protect against non-IgE-mediated reactions that may be
severe or even life threatening (eg, Stevens-Johnson syndrome). o While theoretically attractive, premedication regimens have not been clinically shown to
decrease incidence or severity of IgE-mediated allergic reactions to antibiotics.
Treatment
Prehospital Care
Prehospital patients with symptoms of severe anaphylaxis should first receive standard interventions.
Interventions include high-flow oxygen, cardiac monitoring, and IV access. These measures are
appropriate for an asymptomatic patient who has a history of serious reaction and has been re-
exposed to the inciting agent. Additional treatment depends upon the condition of the patient and the
severity of the reaction. Measures beyond basic life support (BLS) are not necessary for patients with
purely local reactions.
Immediately assess airway patency due to the potential for compromise secondary to edema or
bronchospasm. Active airway intervention may be difficult due to laryngeal or oropharyngeal edema. In
this circumstance, it may be preferable to defer intubation attempts, and instead ventilate with a
bag/valve/mask apparatus while awaiting medications to take effect. In extreme circumstances,
cricothyrotomy or catheter jet ventilation may be lifesaving. Inhaled beta-agonists are used to
counteract bronchospasm and should be administered to patients who are wheezing.
The IV line should be of large caliber due to the potential requirement for large-volume IV fluid
resuscitation. Isotonic crystalloid solutions (ie, normal saline, Ringer lactate) are preferred. A keep vein
open (KVO) rate is appropriate for patients with stable vital signs and only cutaneous manifestations. If
hypotension or tachycardia is present, administer a fluid bolus of 20 mg/kg for children and 1 L for
adults. Further fluid therapy depends on patient response. Large volumes may be required in the
profoundly hypotensive patient.
Administer epinephrine to patients with systemic manifestations of anaphylaxis. With mild cutaneous
reactions, an antihistamine alone may be sufficient, thus the potential adverse effects of epinephrine
can be avoided. Patients on beta-blocker medications may not respond to epinephrine. In these cases,
glucagon may be useful. The Medication section describes dosage, routes of administration, and
contraindications for medications discussed in this section. Antihistamines (eg, H1 blockers), such as
diphenhydramine (Benadryl) are important and should be administered for all patients with anaphylaxis
or generalized urticaria.
Corticosteroids are used in anaphylaxis primarily to decrease the incidence and severity of delayed or
biphasic reactions. Corticosteroids may not influence the acute course of the disease; therefore, they
have a lower priority than epinephrine and antihistamines.
Emergency Department Care
ED care begins with standard monitoring and treatment, including oxygen, cardiac monitoring, and a
large-bore IV with isotonic crystalloid solution. Further intervention depends on severity of reaction and
affected organ system(s).
Rapidly assess airway patency in patients with systemic signs or symptoms. If required, intubation may
be difficult to achieve because of upper airway or facial edema. Standard rapid sequence induction
(RSI) techniques can be used but may cause loss of the airway in a patient whose airway anatomy is
altered by edema. Epinephrine may rapidly reverse airway compromise, and bag/valve/mask
ventilation may be effective in the interim when intubation is not possible. Surgical airway intervention
using standard cricothyrotomy is an option when orotracheal intubation or bag/valve/mask ventilation is
not effective. o Wheezing or stridor indicates bronchospasm or mucosal edema. Treatment with epinephrine
and inhaled beta-agonists is effective for these indications. o Recommendations to treat refractory bronchospasm with corticosteroids have been made
because of their effectiveness in reactive airway disease. As in asthma therapy, onset of
action is delayed for several hours. Aminophylline also has been recommended for
bronchospasm in anaphylaxis and may be more rapidly effective than corticosteroids.
Hypotension in anaphylaxis usually is due to vasodilatation and capillary fluid leakage. Epinephrine is
the primary pharmacologic treatment for these findings. H1-blocking antihistamines also may have a
role in reversing hypotension. Some authors also recommend H2-blocking agents. Large volume fluid
resuscitation with isotonic crystalloid often is needed to support the circulation in patients with
cardiovascular manifestations of anaphylaxis. o Refractory hypotension first should be treated with large volumes of crystalloid and repeated
doses of epinephrine or a continuous epinephrine infusion. If this is not effective, other
pressors with alpha-adrenergic activity, such as levarterenol (Levophed) or dopamine, may be
considered. Cases of effective use of military antishock trousers (MAST) for refractory
hypotension have been reported. o Mediators of anaphylaxis are not considered to have direct myocardial toxicity. In patients with
preexisting heart disease, ischemic myocardial dysfunction may occur due to hypotension and
hypoxia. Epinephrine still may be necessary in patients with severe anaphylaxis, but
remember the potential for exacerbating ischemia. If pulmonary congestion or evidence of
cardiac ischemia is present, fluid resuscitation should be approached more cautiously. o Patients taking beta-blockers may be resistant to the effects of epinephrine. Larger than usual
doses may be needed. Glucagon may be effective in this circumstance, because it increases
intracellular cyclic adenosine monophosphate (cAMP) levels by a mechanism that does not
depend upon beta-receptors.
Cutaneous effects of anaphylaxis are uncomfortable but not life threatening. Patients often respond
promptly to epinephrine and H1 antihistamines. Some authors state that corticosteroids help prevent
recurrence of symptoms (both cutaneous and systemic) that may occur 6-8 hours after successful
treatment (so-called biphasic reaction). H2 blockers may have an added effect.
GI symptoms in anaphylaxis respond to H1 antihistamines and epinephrine.
Disposition: Disposition of patients with anaphylaxis depends upon the severity of the initial reaction
and the response to treatment. Patients with non – life-threatening symptoms may be observed for 4-6
hours after successful treatment and then discharged. Patients who have refractory or very
severe anaphylaxis (with cardiovascular and/or severe respiratory symptoms) should be admitted or
treated and observed for a longer period in the ED or an observation area.
After discharge care: Patients with cardiovascular and/or respiratory symptoms who have an
environmental trigger likely to be encountered after discharge should carry self-injectable epinephrine
after discharge. Referral to an allergist should be considered.
Consultations
Acute manifestations of anaphylaxis usually respond to ED treatment. In refractory cases, consult with
an allergist, cardiologist, pulmonologist, or other intensivist.
Consultation with an allergist (when available) is appropriate when desensitization to an antibiotic is
contemplated.
When a patient at high risk for contrast reaction is under consideration for a contrast study,
consultation with the radiologist regarding pretreatment and choice of contrast agent is appropriate.
Refer patients who are treated and released from the ED after an episode of anaphylaxis or
generalized urticaria to their primary care provider or to an allergist for follow-up. At that time,
consideration can be given to skin testing and possible desensitization.
Medication
The primary drug treatments for acute anaphylactic reactions are epinephrine and H1 antihistamines.
Epinephrine is the drug of choice for life-threatening reactions. When the intravenous route is not indicated, the
intramuscular route is preferable to the subcutaneous route due to more rapid and reliable absorption. The
anterolateral thigh is the preferred site, especially in children.
Epinephrine is clearly effective for the most serious effects and H1-blockers are also effective; do not delay or
defer their use in favor of other treatments. Inhaled beta-agonists lack some of the adverse effects of
epinephrine and are useful for cases of bronchospasm, but they may not have additional effects when optimal
doses of epinephrine are used. Corticosteroids are potentially effective in preventing biphasic (ie, recurrent)
reactions. Due to their delayed effect, corticosteroids are not first-line treatments. H2-blocking antihistamines
theoretically are attractive agents for dermal and GI manifestations, but evidence supporting their clinical
effectiveness is less than that for H1-blocking agents. Some evidence suggests that combining H1 and H2
blockers may be more effective than H1 blockers alone. Glucagon may be useful in treating refractory
cardiovascular effects in patients taking beta-blockers.
Parenteral adrenergic agents
Reverse cardiovascular, cutaneous, GI, and pulmonary manifestations of anaphylaxis.
Epinephrine (EpiPen, Adrenalin)
DOC for shock, angioedema, airway obstruction, bronchospasm, and urticaria in severe anaphylactic reactions.
Administer IM (preferred) or SC, except for patients in extremis for whom it is administered IV. May be
administered SL or via ET when no IV access available. Continuous infusion may be administered in cases of
refractory shock.
Dosing
Interactions
Contraindications
Precautions
Adult
0.3-0.5 mL 1:1000 soln SC or IM q15min
0.5-1 mL 1:10,000 soln IV; slow administration; repeat prn
0.3-0.5 mL 1:1000 soln SL q15min
1 mL 1:1000 soln ET in approximately 10 mL NS
IV infusion: 0.1-1 mcg/kg/min
Pediatric
0.01 mL/kg (minimum 0.1 mL) 1:1000 soln IM (preferred) or SC q15min
0.1 mL/kg 1:10,000 soln IV prn slow administration; repeat prn
0.01 mL/kg (minimum 0.1 mL) 1:1000 soln SL q15min
0.01 mL/kg (minimum 0.1 mL) 1:1000 soln ET in approximately 1-3 mL NS
IV infusion: 0.1-1 mcg/kg/min
Dosin
g Interactions Contraindications Precaution
sDosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Inhaled beta-agonists
Used to treat bronchospasm. Doses are identical to those used in the treatment of asthma.
Albuterol (Proventil, Ventolin)
Numerous inhaled beta-agonists are used for treatment of bronchospasm; albuterol is the most commonly used
preparation.
Dosing
Interactions
Contraindications
Precautions
Adult
0.5 mL 0.5% soln in 2.5 cc NS nebulized q15min
Pediatric
0.03-0.05 mL/kg 0.5% soln in 2.5 cc of NS via nebulizer q15min
Dosin
g Interactions Contraindications Precaution
sDosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions H1-receptor blockers (Antihistamines)
Primarily effective against cutaneous effects of anaphylaxis. Also may help antagonize cardiac and respiratory
effects; should be used routinely in most cases of anaphylaxis. IV administration is preferable when a rapid
effect is desired. IM dosing also is effective but has a slower onset than IV and may cause local tissue irritation.
PO doses must be larger than parenteral doses because of 50% first-pass metabolism in the liver. Most
recommendations for use of antihistamines state that they should be continued for 2-3 days after treatment of
the acute anaphylactic event.
Diphenhydramine (Benadryl)
Many effective H1 blockers exist; diphenhydramine is effective and widely available.
Dosing
Interactions
Contraindications
Precautions
Adult
25-50 mg IV/IM q4-6h
50 mg PO q4-6h
Pediatric
1-2 mg/kg IV/IM q4-6h
2 mg/kg PO q4-6h
Dosin
g Interactions Contraindications Precaution
sDosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions H2-receptor blockers (Antihistamines)
H2 blockers are used commonly by clinicians in treatment of allergic reactions and urticaria. Evidence of
additive effect with H1-blocker anaphylaxis exists, but they should not be considered first-line therapy.
Cimetidine (Tagamet)
Many H2 blockers are available. Cimetidine is the prototype drug; other agents have much less evidence of
effectiveness in anaphylaxis.
Dosing
Interactions
Contraindications
Precautions
Adult
300 mg PO/IV/IM q6h
Pediatric
5-10 mg/kg PO/IV/IM q6h
Dosin
g Interactions Contraindications Precaution
sDosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Corticosteroids
These agents have a role in reversing bronchospasm and cutaneous effects of anaphylaxis. Corticosteroids
have a delayed onset of action and do not reverse the cardiovascular effects of anaphylaxis. These agents
should be used in severe reactions, but the use of epinephrine and H1 antihistamines has a higher priority.
Some authors state that corticosteroids help prevent or ameliorate recurrent (biphasic) anaphylaxis, but the
true incidence of this condition has not been determined, and recurrences are usually less severe than the
initial attack.
While corticosteroids usually are administered IV in patients with anaphylaxis for presumed rapidity of effect,
PO and IV corticosteroids are equally efficacious in asthma therapy. When administered acutely,
corticosteroids commonly are continued for 2-3 days. In asthma treatment, large parenteral doses customarily
are administered acutely, followed by lower PO dosing for varying periods. Long-acting parenteral preparations
may be administered as an alternative and have been shown effective in asthma therapy. Optimal dosage
range for corticosteroids has not been established; thus, a range of dosages is provided based on published
recommendations.
Methylprednisolone (Solu-Medrol, Adlone, Medrol, Depo-Medrol)
A multitude of corticosteroid preparations are available. Methylprednisolone is widely available in the ED
because of other uses (ie, acute asthma, spinal cord injury). Supplied in both parenteral and oral formulations.
Discussed here as typical drug of this class.
Dosing
Interactions
Contraindications
Precautions
Adult
40-250 mg IV/IM q6h
2-60 mg PO qd
Pediatric
1-2 mg/kg IV/IM q6h
1 mg/kg PO qd
Dosin
g Interactions Contraindications Precaution
sDosing Interactions Contraindications Precautions Dosing Interactions Contraindications Precautions Antidote, Hypoglycemia
Glucagon appears to benefit by stimulating the release of endogenous catecholamines.
Glucagon
Has inotropic, chronotropic, and vasoactive effects that are independent of beta-receptors. Glucagon also
causes endogenous catecholamine release. Patients taking beta-blocking agents may be resistant to effects of
epinephrine or other adrenergic agents used to treat the cardiovascular effects of anaphylaxis. Glucagon may
be effective in these patients. Should be used in addition to epinephrine, not as a substitute. Reports of
effectiveness of glucagon in anaphylaxis are anecdotal; therefore, it is difficult to specify a dose. Smaller doses
are effective in elevating blood sugar in patients with hypoglycemia, but larger doses have been recommended
in beta-blocker overdose. Given parenterally. IV route is preferable.
Dosing
Interactions
Contraindications
Precautions
Adult
1-10 mg IV/IM/SC; typically 1-2 mg q5min to effect
Pediatric
Not established; adult dose is approximately equivalent to 0.02 mg/kg
Follow-up
Further Inpatient Care
Most patients with anaphylaxis may be treated successfully in the ED and then discharged. Treatment
success operationally may be defined as complete resolution of symptoms followed by a short period
of observation. The purpose of observation is to monitor for recurrence of symptoms (ie, biphasic
anaphylaxis).
Hospital admission is required for patients who (1) fail to respond fully, (2) have a recurrent reaction or
a secondary complication (eg, myocardial ischemia), (3) experience a significant injury from syncope,
or (4) need intubation. As with many other conditions, consider a lower admission threshold when
patients are at age extremes or when they have significant comorbid illness.
The presenting manifestation(s) of anaphylaxis dictate inpatient care. Essentially, this care consists of
continuing the care initiated in the ED.
Consider ICU admission for patients with persistent hypotension. The primary means of support are
adrenergic agents (eg, epinephrine, dopamine) and fluid resuscitation. Persistent hypotension in the
face of pressors and fluid resuscitation is an indication for invasive hemodynamic monitoring with
evaluation of cardiac function and peripheral vascular resistance. Use of these parameters provides
the basis for objective decisions regarding the use of fluids and pressors.
Inpatient management of airway compromise consists of continuation of parenteral and inhaled
adrenergic agents and corticosteroids that were initiated in the ED.
Cutaneous manifestations of anaphylaxis are treated with repeated doses of antihistamines.
Further Outpatient Care
Discharged patients who have been successfully treated for anaphylaxis usually should continue
antihistamines for 2-5 days to prevent recurrence. When corticosteroids have been used as part of the
initial treatment, common practice continues that treatment for a short period.
Inpatient & Outpatient Medications
Inpatient medications are identical to those listed for ED care (see Medication).
Outpatient medications o Outpatient medications primarily consist of oral forms of the medications used in ED
treatment. Adrenergic medications are not listed in this chapter, as it is assumed that patients
who require these on an on-going basis will be admitted. o Consider patients who experience severe reactions to bites, stings, food, or other possibly
unavoidable causes, as candidates for an epinephrine auto-injector prescription. These
injectors may be packaged as kits that also contain an oral antihistamine. o The following regimens are used commonly by clinicians, though very little hard data
concerning the natural history of anaphylaxis treated in the ED exists. In light of this, do not
construe the following as an unqualified recommendation or as a standard of care. Evidence
for efficacy of H2-blocker antihistamines is particularly sparse. The newer nonsedating
antihistamines have not been studied in the context of treatment for anaphylaxis.
o H1-blocker antihistamines
Diphenhydramine (Benadryl) - Adults: 25 mg PO q6h for 2-5 d; Children: 1 mg/kg PO
q6h for 2-5 d
Hydroxyzine (Atarax) - Adults: 25 mg PO q8h for 2-5 d; Children: 1 mg/kg PO q8h for
2-5 do Corticosteroids
Prednisone - Adults: 20-80 mg PO qd for 2-5 d; Children: 1-2 mg/kg PO qd for 2-5 d
Many other glucocorticoid preparations may be used.o H2-blocker antihistamines
Cimetidine - 300 mg PO qid for 2-5 d; Children: Not recommended
Epinephrine auto-injectors prefilled syringes: A number of forms are available.
Instructions for self-administration are included.
Ana-Kit (Bayer): This product is a syringe with 0.3 mL 1:1000 epinephrine solution
packaged with four 2-mg chewable chlorpheniramine tablets. The syringe has 0.1 mL
gradations, allowing the injection of smaller doses for pediatric patients.
EpiPen and EpiPen Jr. Auto-Injector (Center): This product is an auto-injecting
syringe containing 0.3 mL 1:1000 epinephrine solution (EpiPen) or 0.3 mL 1:2000
solution (EpiPen Jr).
Transfer
Requirements for treating a patient with anaphylaxis are likely to exist in most hospitals within the
United States and Canada; therefore, transfer of patients with anaphylaxis would be a very unusual
occurrence in these locations.
Deterrence/Prevention
Preventive therapy for anaphylaxis depends on identification of the inciting agent. When the agent has
been identified, the key to prevention is avoidance. Certain prophylactic or preventative therapies may
be employed when re-exposure cannot be avoided. When the inciting agent is not obviously known
from the history, allergy testing may help identify it. When the allergen is a therapeutic agent for which
subsequent usage is medically necessary, desensitization or pretreatment protocols may be
employed. o Desensitization therapy for reactions to Hymenoptera venom is partially effective in preventing
or ameliorating subsequent severe reactions. o At minimum, patients discharged from the ED after a severe reaction to Hymenoptera venom
should be informed of the availability of this treatment. Referral to the patient's primary care
source or directly to an allergist also may be appropriate.
Complications
Complications from anaphylaxis are rare, and most patients completely recover. Myocardial ischemia
may result from hypotension and hypoxia, particularly when underlying coronary artery disease exists.
Ischemia or arrhythmias may result from treatment with pressors. Prolonged hypoxia also may cause
brain injury. At times, a fall or other injury may occur when anaphylaxis leads to syncope.
Prognosis
Anaphylaxis may occur following re-exposure to the inciting agent. Rates of recurrence vary with the
nature of the inciting agent and host factors. Other than the possibility of recurrence or the occurrence
of complications, anaphylaxis carries no long-term effects.
Patient Education
As described above, caution patients who are discharged after an episode of anaphylaxis to avoid
exposure to an inciting agent. When no inciting agent has been identified, consider referral to an
allergist to identify the cause of anaphylaxis.
Inform patients who react to Hymenoptera venom of the availability of desensitization therapy, and
consider a self-administered epinephrine prescription.
Sting avoidance is important for hypersensitive persons. Patients must be educated concerning steps
they can take to reduce the risk of insect stings. o Caution patients to avoid use of perfumes or hygiene products that include perfumes,
particularly floral scents, as these attract flying Hymenoptera. o Brightly colored clothing attracts bees and other pollinating insects.
o Avoid locations of known hives or nests, and avoid using equipment that disturbs the hive.
o Persons who are sensitive to Hymenoptera and who must be outdoors should carry a sting kit.
On discharge, warn patients of the possibility of recurrent symptoms, and instruct them to seek further
care if this occurs.
For excellent patient education resources, visit eMedicine's Allergy Center and Allergic Reaction and
Anaphylactic Shock Center. Also, see eMedicine's patient education article Severe Allergic Reaction
(Anaphylactic Shock).
Miscellaneous
Medicolegal Pitfalls
Claims of medical negligence related to the emergency treatment of anaphylaxis are not common.
Potential pitfalls are as follows: o Failure to consider the diagnosis in patients with unexplained syncope or shock
o Failure to warn the patient of avoidance or preventive measures
o Prescription or administration of a drug to which the patient is known allergic
o Failure to appreciate the potentially serious nature of symptoms, such as syncope or throat
tightness, in a patient with an allergic reaction o Complications of epinephrine administration in patients without clear indication