eMedicine Specialties > Emergency Medicine > Pediatric

Pediatrics, Anaphylaxis

Jeffrey F Linzer Sr, MD, MICP, FAAP, FACEP, Associate Professor of Pediatrics and Emergency Medicine, Emory University School of Medicine; Associate Medical Director for Business Affairs and Compliance and EMS/Pre-Hospital Care Coordinator, Department of Pediatrics, Division of Pediatric Emergency Medicine, Emory University School of Medicine; Emergency Pediatric Group, Children's Healthcare of Atlanta at Egleston; Co-Medical Director and Consulting Staff, Children's Sedation Service, Children's Healthcare of Atlanta at Egleston

Updated: Oct 5, 2009

Introduction

Background

Anaphylaxis is an acute, potentially life-threatening syndrome, with multisystemic manifestations resulting from the rapid release of inflammatory mediators.

The term anaphylaxis, derived from Greek for "contrary to protection," was coined by Charles R. Richet and Paul Portier in 1902 after their experiments showed a small, nonlethal dose of toxin caused rapid death in sensitized dogs. While the clinical presentation and management are the same, some authors use the term anaphylaxis for immunoglobulin E (IgE)–mediated reactions and anaphylactoid for non–IgE-mediated reactions. The term anaphylaxis syndrome is best used to describe the clinical event.

In children, foods can be a very significant trigger for IgE-mediated anaphylaxis. Milk, eggs, wheat, and soy (MEWS) as a group are the most common food allergens; however, peanuts and fish are among the most potent. Children can develop anaphylaxis from the fumes of cooking fish or residual peanut in a candy bar.

Other common triggers include preservatives (in food and drugs), medications (antibiotics), insect venom (bee sting), and bioactive substances (eg, blood, blood products). Environmental allergens such as pollens, molds, and dust mites are a less common and infrequent cause of anaphylaxis.

Non-IgE triggers include infection, opiates, radiocontrast dye, and exercise.

Pathophysiology

Both IgE and non-IgE activation of mast cells and basophils ignites a cascade that results in the release and production of several inflammatory and vasoactive substances. These bioactive materials include histamine, tryptase, heparin, prostaglandins (PGD₂, PGF₂), leukotrienes (LTC₄, LTD₄, and LTE₄), cytokines (TNF‑α), and platelet-activating factor (PAF). In anaphylaxis, these substances most commonly involve the skin, respiratory, cardiovascular, and gastrointestinal systems. As a result, urticaria, angioedema, bronchospasm, bronchorrhea, laryngospasm, increased vascular permeability and decreased vascular tone, and bloody diarrhea can develop.
 
The most common cause of mediator release is due to an IgE-mediated reaction. A previously sensitized B lymphocyte produces IgE against a specific antigen. The IgE resides on the mast cells and basophils. When the specific antigen, or one similar to it, binds to the high affinity FcεRI-α receptor of the immunoglobulin, mast cell and basophil degranulation occurs.
 
Non-IgE mediator release can be triggered by several different mechanisms including stimulation of the complement cascade to produce C3a, C4a, and C5a anaphylatoxin, neuropeptide and cytokine activity, and direct contact (kallikrein-kinin system) stimulation by certain agents (eg, opiates, radiocontrast media).
 
Many of the clinical presentations seen in anaphylaxis are due to activation of multiple histamine receptors,^{[1 ]}For example, acute bronchospasm (wheezing, dyspnea) is a result of the interaction between H₁ and H₂ receptor activity; bronchial smooth muscle constriction and increased mucus viscosity from H₁ receptor activity and H₂ activity causes increased mucus production. The combination of H₁ and H₂ receptor stimulation results in increased vascular permeability, flushing, hypotension, tachycardia, and headache. H₁ and H₃ activity results in cutaneous itch and nasal congestion.
 
However, histamine is not the only agent that causes the symptoms in anaphylaxis.^{[2 ]}Prostaglandin, leukotrienes, and PAF all contribute to the bronchoconstriction, vascular changes, and changes in vascular capacitance (increased vascular permeability and vasodilatation). A recent study showed an inverse correlation between PAF acetylhydrolase activity and the severity of anaphylaxis.^{[3 ]}Compared to a placebo group, those patients with anaphylaxis due to peanuts were more likely to have a fatal outcome with low PAF acetylhydrolase activity.

Frequency

United States

Frequency estimates are difficult to determine. Part of the reason may be due to the methodology used by researchers (differing criteria and populations), part likely is due to underreporting, and part is likely due to lack of consistent diagnoses.

In a review of the literature by Neugut et al, the overall occurrence of anaphylaxis in the United States ranges from 1.24-16.8%.^{[4 ]}However, a working group on anaphylaxis from the American College of Allergy, Asthma, and Immunology estimated the lifetime prevalence at 0.5-2%.^{[5 ]}

International

Prevalence is similar to that in the United States.^{[5 ]}

Mortality/Morbidity

Risk of death due to respiratory and cardiovascular complications is significant. Mortality rate estimates vary from 100 to more than 500 cases per year in the United States. The estimated death rate is 0.002%.^{[4 ]}

Race

While asthma is more prevalent and has a higher mortality rate in African American children, race does not appear to affect the frequency of having anaphylaxis.^{[8 ]}

Sex

Anaphylaxis appears to be more common in boys until the age of 15 years when the balance changes and female preponderance continues through adulthood.^{[5,9 ]}

Age

While Bohlke and colleagues estimated the rate of anaphylaxis in children at 10.5 per 100,000 person-years,^{[10 ]}the Rochester Epidemiology Project showed a rate of 75.1 per 100,000 person-years in children aged 9 years and 65.2 per 100,000 person-years in children in the 10- to 19-year-old group.^{[7 ]}

Clinical

History

Anaphylaxis is a range of signs and symptoms from hives with wheezing to cardiovascular collapse and death.^{[11 ]}It can occur with or without shock. More than 80% of the patients will present with cutaneous symptoms (eg, hives, pruritus, facial swelling). Generally, at least 2 organ systems (skin, respiratory, cardiovascular, gastrointestinal systems) are involved; however, anaphylaxis can present with a low systolic blood pressure for age or decrease in systolic blood pressure by more than 30% after known allergen exposure alone.^{[12 ]}

The Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium proposed a diagnostic criteria that would identify at least 95% of the patients with anaphylaxis.^{[12 ]}The primary clinical diagnostic criteria includes the acute onset of skin and/or mucosal symptoms along with either respiratory compromise (eg, bronchospasm, stridor, shortness of breath) and/or reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia, syncope, incontinence).

• Usually, cutaneous symptoms present first.
• Often, a history of exposure to a known trigger is given, (eg, bee sting, peanut ingestion, antibiotic administration). At times, the inciting agent may be unknown or unclear.
• Symptoms may develop slowly and insidiously over several hours or may rapidly progress over several minutes. Parenteral agents generally have a faster onset of symptoms than ingested ones.
• Children may not be able to express the initial symptoms of anaphylaxis. They may initially have apparent discomfort or a generalized irritability. Additionally, the child may not be able to identify the triggering agent (eg, food) even when known to the parent or caretaker.
• Between 5% and 20% of patients may experience a recurrence of anaphylaxis 8-12 hours after the initial presentation.^{[13 ]}Prolonged symptoms can last up to 32 hours despite treatment.^{[11 ]}

Physical

Initial symptoms may include an awareness that "something isn't right"; a tingling sensation in the mouth; itchy, watery nose and eyes; and/or the feeling of being warm and flushed.

• Cutaneous (skin)
  • Urticaria (hives, welts, "whelps")
  • Pruritus (itching)
  • Angioedema (swelling) of the face, extremities, or both
• Ear, nose, mouth
  • Nasal congestion
  • Sneezing
  • Rhinorrhea (runny nose)
  • Metallic taste
  • Laryngeal edema (throat tightness)
• Respiratory
  • Cough
  • Wheezing
  • Hoarseness
  • Chest pain (respiratory symptom in children)
  • Shortness of breath
  • Stridor ("crowing" inspiratory sound)
• Gastrointestinal
  • Nausea/vomiting
  • Abdominal cramps
  • Diarrhea (at times bloody)
• Cardiovascular
  • Tachycardia (rapid heart rate)
  • Arrhythmias (irregular heart beat)
  • Decreased peripheral perfusion
  • Hypotension (low blood pressure - usually a late finding in children)
• Central nervous system
  • Dizziness
  • Syncope (fainting)
  • Altered mental status
  • Coma

Causes

Foods are the most common trigger of anaphylaxis in children, with peanuts being the primary cause.^{[14 ]}

The following is only meant to be illustrative of the more common triggers but should not be considered an exhaustive listing. These triggering agents may cause an IgE- or non–IgE-mediated anaphylaxis.

• Foods (most common cause in children) - Milk, eggs, wheat, soy, fish, shell fish, legumes (peanuts), tree nuts
• Medicinals - Antibiotics (penicillins, cephalosporins), local anesthetics (lidocaine), analgesics (aspirin, nonsteroidal anti-inflammatory drugs [ibuprofen], opiates [codeine, morphine]), dextran, radiocontrast media
• Biologicals - Venoms (bee sting, ant or snake bite), blood and blood products, vaccines, allergen extracts
• Preservatives and additives - Metabisulfite, monosodium glutamate
• Other -Latex, unknown/idiopathic

Differential Diagnoses

Other Problems to Be Considered

Mastocytosis
Physical urticaria
Red man syndrome (vancomycin related)
Vocal cord dysfunction

Workup

Laboratory Studies

Anaphylaxis is essentially a clinical diagnosis. Laboratory tests generally are not useful for the acute diagnosis of this condition.

• Serum histamine level rises quickly with the onset of symptoms but does not remain elevated after 30-60 minutes.
• Serum tryptase level peaks 60-90 minutes after the onset of symptoms and remains elevated for up to 5 hours.
  • β-tryptase is released with degranulation of mast cells, while α-tryptase is secreted constitutively by them.
  • The ratio of total tryptase to β-tryptase can help distinguish systemic mastocytosis from anaphylaxis. A ratio £ 10 implies anaphylaxis, while ³ 20 is consistent with systemic mastocytosis.^{[15 ]}Other tests that may be useful in distinguishing anaphylaxis from other conditions in the differential include C1 inhibitor functional assay (C1INH) (hereditary angioedema) and urine vanillylmandelic acid and serum serotonin levels (carcinoid syndrome).

Imaging Studies

No imaging studies assist in making this diagnosis.

Other Tests

Radioallergosorbent test (RAST) or cutaneous antigen testing (preferably by a specialist) can be used after recovery to try to identify the inciting antigen.

Treatment

Prehospital Care

Prehospital care should be directed at stabilization of the airway, breathing, and circulation.

• Epinephrine is the first drug of choice.
  • The 1:1000 strength should preferentially be administered intramuscularly (IM) in to the thigh. Subcutaneous administration is no longer recommended.^{[16 ]}
  • Intravenous (IV) or intraosseous (IO) administration (1:10,000 strength) should be reserved for patients with marked hypotension.
• High-flow oxygen by nonrebreather mask
  • In the awake child who is having some difficulty maintaining their airway, a nasopharyngeal (NP) airway is better tolerated than an oropharyngeal (OP) airway.
  • Continuous positive airway pressure (CPAP) may be considered prior to using an advanced airway (eg, noninvasive pharyngeal airway, endotracheal intubation) if the child is unable to maintain his or her airway, has decreased oxygen saturation, and/or has decreasing level of consciousness.
  • Nebulized albuterol should be administered for cough and wheezing unresponsive to epinephrine.
• Intravenous (IV) access should be obtained. Intraosseous (IO) access should be considered when intravenous access cannot be quickly obtained in unstable patients.
• Patients with signs of poor profusion should be placed in a modified Trendelenburg position with the legs elevated.
• Crystalloid fluids should be given rapidly if the patient is hypotensive or has other signs of shock.
• Diphenhydramine may be given orally (for mild symptoms) via intramuscular or intravenous administration.

Emergency Department Care

Not all patients will present in shock. Most patients present with skin complaints (eg, urticaria, angioedema) along with respiratory or cardiovascular symptoms. Primary attention is directed at the ABCs. If not already given, epinephrine (which acts as a physiologic antagonist) should be administered as soon as the diagnosis is suspected.

• Epinephrine, 1:1000 intramuscularly (IM), is the initial drug of choice. It may be repeated every 5-15 minutes. Administration in the anterolateral thigh appears to provide superior absorption compared with deltoid and subcutaneous injections.^{[17,18 ]}Subcutaneous injection is not recommended.^{[12,16,19 ]}
• Because of the risk of potentially lethal dysrhythmias, intravenous/intraosseous (IV/IO) epinephrine (1:10,000) is reserved for the patient with uncompensated shock.
• If the patient is hypoxic or with respiratory complaints, high-flow oxygen (warm, humidified preferred) by nonrebreather mask should be given.
  • The use of noninvasive positive pressure (eg, CPAP) may help avoid the need for an advanced airway. In those patients with signs of significant hypoxia, an advanced airway (eg, supraglottic airway device, endotracheal intubation) should be considered. The airway should be secured with an endotracheal tube early in cases of upper airway obstruction.
  • Nebulized albuterol (2.5-5 mg/dose) may be used for bronchospasm not responding to epinephrine.
    • While the addition of ipratropium to albuterol has been shown to be beneficial in severe asthma exacerbations in children, this combination in anaphylaxis has not been studied.
    • Nebulized epinephrine has been used for stridor secondary to laryngeal edema but has not been studied in anaphylaxis.
• An intravenous line should be started in all but the mildest cases. Intraosseous access should be considered when intravenous access cannot be quickly obtained in unstable patients.
• Placing the patient in the modified Trendelenburg position with legs elevated should be used for initial vascular support. Patients with hypotension unresponsive to positioning and epinephrine should receive a rapid crystalloid fluid bolus of (lactated Ringer or isotonic sodium chloride) of 20 mL/kg. Repeat boluses up to 60-80 mL/kg may be necessary for correcting the hypovolemia.
  • Recall that children are more likely to have compensated shock where tachycardia and signs of hypoperfusion (eg, decreased peripheral pulses, cool extremities) are present but the blood pressure is normal.^{[20 ]}A systolic pressure of less than the 5^th percentile for age would indicate uncompensated shock:
    • <70 mm Hg in children aged 1-12 months
    • <70 mm Hg + (2X age in years) in children aged 1-10 years
    • <90 mm Hg in children ≥10 years of age
• Patients unresponsive to fluid resuscitation should receive vasopressors.
  • Epinephrine (0.1-1 mcg/kg/min IV) should be considered as the initial vasopressor in children. Doses at <0.3 mcg/kg/min will tend to have more β-activity, whereas α-action becomes more pronounced at higher doses.
  • Dopamine (2-20 mcg/kg/min IV) may be used in addition to epinephrine. Greater α-activity is seen at higher doses.
  • Norepinephrine (0.1-2 mcg/kg/min IV) is a potent vasopressor. It is usually considered in children unresponsive to epinephrine.
• The combination of H₁ and H₂ antihistamines appears to be more effective, especially for cutaneous symptoms.^{[12,21 ]}Their onset of activity is slower than epinephrine and are considered next-in-line treatment.
  • Diphenhydramine 1 mg/kg (not to exceed 50 mg/dose) may be given IV/IM/PO; oral use should be restricted to mild cases.
  • Second-generation H₁ antihistamines (eg, cetirizine, loratadine) have not been studied in anaphylaxis.
  • Ranitidine 1 mg/kg (not to exceed 50 mg/dose IV or 150 mg/dose PO) has a low side effect profile in children. Oral treatment may be used in mild cases.
• Corticosteroids do not have an immediate effect on the symptoms but may help reduce or prevent a biphasic "late phase" reaction.
  • The choice between of methylprednisolone (IV), prednisone, or prednisolone (PO) 1-2 mg/kg should be based on the patient's presentation and condition. The effect and time of onset are similar. Dose may be repeated at 6-hour intervals as indicated.
  • No published studies compare dexamethasone with other corticosteroids in the treatment of anaphylaxis. However, based on its use in other allergic conditions, a dose of 0.15-0.6 mg/kg IV would be appropriate.
• Glucagon may help with refractory symptoms in the patient taking a beta-blocker. In children, administer 20-30 mcg/kg (not to exceed a cumulative dose of 1 mg) IV over 5 minutes followed by an IV maintenance infusion and titrated to clinical effect at 5-15 mcg/min.
• Observation and hospitalization
  • A delayed or biphasic response may occur in 1-20% of patients.^{[22 ]}The literature is unclear as to which patients are at greatest risk from having this condition. The secondary response may be milder, the same, or more severe than the initial presentation.
  • Even patients with mild symptoms should be observed for a minimum period of time. While the time of observation should be individualized to the patient, a minimum of 4-8 hours appears appropriate.
  • Patients with greater risk of biphasic response should be observed a minimum of 12-24 hours. Severity of symptoms, delay in receiving epinephrine, and ingested antigen have been implicated as risk factors.
  • Children who require fluid resuscitation, multiple doses of epinephrine, or repeated doses of a bronchodilator should be hospitalized.
  • At a minimum, children who require vasopressors or glucagon should be admitted to a tertiary pediatric intensive care center.

Consultations

• ED consultation with a pediatric critical care specialist should be obtained in unstable patients and those unresponsive to treatment.
• Outpatient consultation with an allergist is appropriate for most patients with anaphylaxis, especially those with the following:
  • Significant clinical presentation or those requiring prolonged treatment
  • History of atopic disease
  • Unclear trigger or inciting agent
  • Recurrent episodes of anaphylaxis

Medication

It cannot be stressed enough that the early use of epinephrine is the most important step in managing anaphylaxis.^{[11,16,23 ]}Antihistamines (H₁ and H₂ blockers), corticosteroids, crystalloid fluids, and other adrenergic agonists can also be beneficial in the management of this condition.

Adrenergic Agonist Agents

These agents stimulate different adrenergic receptors. Effectiveness in treating anaphylaxis depends on which receptor types are stimulated and on the concentration of receptors in the target tissues.

Epinephrine (Adrenaline, EpiPen, EpiPen Jr.)

DOC for treating anaphylaxis. Elicits alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Beta-agonist effects of epinephrine include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.
IM administration in the anterolateral thigh appears to provide superior absorption compared with deltoid and subcutaneous injections.

Dosing

Adult

Pediatric

Initial treatment: 0.01 mg/kg/dose (ie, 0.01 mL/kg/dose 1:1000 [1 mg/mL]) IM q5-15min (dose range, 0.1-0.5 mg/dose)
Significant hypoperfusion evident: 0.01 mg/kg/dose IV/IO (ie, 0.1 mL/kg/dose 1:10,000 [0.1 mg/mL])
Auto-injectors for IM administration by patient or caregiver into (clothed or unclothed) anterolateral thigh:
10-20 kg:
EpiPen Jr (1:2000 [0.5 mg/mL]): Delivers 0.15 mg/dose (0.3 mL)
>20 kg:
EpiPen (1:1000; 1 mg/mL): Delivers 0.3 mg/dose (0.3 mL)

Interactions

Increases toxicity of beta-blocking and alpha-blocking agents and of halogenated inhalational anesthetics; TCAs enhance pressor response

Contraindications

Documented hypersensitivity; cardiac arrhythmias or angle-closure glaucoma; local anesthesia in areas such as fingers or toes because vasoconstriction may produce sloughing of tissue; do not use during labor (may delay second stage of labor)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in elderly patients, prostatic hypertrophy, hypertension, cardiovascular disease, diabetes mellitus, hyperthyroidism, and cerebrovascular insufficiency; rapid IV infusions may cause death from cerebrovascular hemorrhage or cardiac arrhythmias

Dopamine (Intropin)

Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effect is dependent on the dose. Lower doses (<5 mcg/kg/min) predominantly stimulate dopaminergic receptors that, in turn, produce renal and mesenteric vasodilation. Cardiac stimulation and renal vasodilation produced by higher doses.

Dosing

Adult

Pediatric

1-20 mcg/kg/min IV; titrate to effect; not to exceed 50 mcg/kg/min

Interactions

MAO inhibitors may prolong effects of dopamine; beta-adrenergic blockers may antagonize peripheral vasoconstriction caused by high doses of dopamine; butyrophenones (eg, haloperidol) and phenothiazines can suppress dopaminergic renal and mesenteric vasodilation induced with low-dose dopamine infusion; concurrent administration of diuretic agents with low-dose dopamine may produce additive effects on urine flow; hypotension and bradycardia may occur with phenytoin; dopamine may decrease effects of phenytoin

Contraindications

Documented hypersensitivity; pheochromocytoma; ventricular fibrillation

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Closely monitor urine flow, cardiac output, pulmonary wedge pressure, and blood pressure during infusion; prior to infusion, correct hypovolemia with either whole blood or plasma, as indicated; monitoring central venous pressure or left ventricular filling pressure may be helpful in detecting and treating hypovolemia

Norepinephrine (Levophed)

For protracted hypotension following adequate fluid-volume replacement. Stimulates beta1- and alpha-adrenergic receptors, which, in turn, increases cardiac muscle contractility and heart rate as well as vasoconstriction. As a result, systemic blood pressure and coronary blood-flow increases.
After obtaining a response, the rate of flow should be adjusted and maintained at a low normal blood pressure, such as 80-100 mm Hg systolic, sufficient to perfuse vital organs.

Dosing

Adult

Pediatric

0.1-2 mcg/kg/min IV, titrate to effect

Interactions

Effects increase when administered concurrently with tricyclic antidepressants, MAO inhibitors, antihistamines, guanethidine, methyldopa, ergot alkaloids; atropine may block reflex tachycardia caused by norepinephrine and enhances pressor response

Contraindications

Documented hypersensitivity; peripheral or mesenteric vascular thrombosis because ischemia may be increased and the area of infarct extended

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Correct blood-volume depletion, if possible, before giving norepinephrine therapy; extravasation may cause severe tissue necrosis and, thus, should be administered into a large vein; caution in occlusive vascular disease

Antihistamines

Antihistamines decrease histamine activity by reversible competitive blockade of the histamine receptor. H ₁ -receptor stimulation can lead to bronchial smooth muscle constriction and capillary leakage. H ₂ -receptor activity increases gastric acid secretion and pacemaker rate. Stimulation of histamine H ₁ and H ₂ receptors may produce vasodilation and dysrhythmias. Therefore, use of H ₁ and H ₂ blockers should be considered.

Diphenhydramine (Benadryl)

Competes with histamine for H ₁ -receptor sites in GI tract, blood vessels, and respiratory tract. Preferred agent when IV antihistamine is required.

Dosing

Adult

Pediatric

1 mg/kg/dose PO/IV/IM q6h prn; not to exceed 300 mg/d

Interactions

Potentiates effect of CNS depressants; because of alcohol content, do not give syrup dosage form to patient taking medications that can cause disulfiramlike reactions

Contraindications

Documented hypersensitivity; use with MAOIs

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause paradoxical excitation; may exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction

Cetirizine (Zyrtec)

Competitive H1-receptor blocker similar to diphenhydramine. Metabolite of hydroxyzine. May be used as part of discharge post-ED or hospital care.
This medication has not been studied in the treatment of acute anaphylaxis.

Dosing

Adult

Pediatric

<2 years: Not established
2-5 years: 2.5 mg once daily
>5 years: 5-10 mg PO qd or divided bid

Interactions

Increases CNS toxicity of depressants

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in hepatic or renal dysfunction; doses higher than 10 mg/d may cause drowsiness

Loratadine (Alavert, Claritin)

Competitive H1-receptor blocker similar in activity to diphenhydramine. May be used as part of discharge post-ED or hospital care.
This medication has not been studied in the treatment of acute anaphylaxis.

Dosing

Adult

10 mg PO qd on empty stomach

Pediatric

<2 years: Not established
2-5 years: 5 mg PO qd
>5 years: Administer as in adults

Interactions

Ketoconazole, erythromycin, procarbazine, and alcohol may increase loratadine levels

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Initiate therapy at lower dose in liver impairment

Ranitidine (Zantac)

H ₂ antagonist (DOC) which, when combined with an H ₁ type, may be useful in treating allergic reactions that do not respond to H ₁ antagonists alone.

Dosing

Adult

Pediatric

IV: 1 mg/kg/dose IV, not to exceed 50 mg/dose; may repeat IV dose q6-8h, not to exceed 200 mg/d
PO: 1 mg/kg/PO, not to exceed 150 mg/dose PO; may repeat PO dose q12h, not to exceed 300 mg/d

Interactions

May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment

Bronchodilators

Bronchodilators provide relief of bronchial smooth muscle contraction.

Albuterol (AccuNeb, Proventil)

DOC that relaxes bronchial smooth muscle and may decrease mediator release from mast cells and basophils. May inhibit airway microvascular leakage. Although not FDA-approved for children younger than 2 years, standard of care data support use in this age group.

Dosing

Adult

Pediatric

<15 kg: 2.5 mg via nebulizer q20-30min
>15 kg: 5 mg via nebulizer q20-30min
As clinically indicated or for convenience, multiple treatments may be given by continuous nebulization
<15 kg: 5-7.5 mg over 1 h via nebulizer
≥15 kg: 10-15 mg over 1 h via nebulizer
Alternatively, 0.5 mg/kg/h via continuous nebulization; not to exceed 2-3 mg/kg/h or 15 mg/h

Interactions

Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hyperthyroidism, diabetes mellitus, hypokalemia, muscle tremors, and cardiovascular disorders

Corticosteroids

Anti-inflammatory activity counters actions caused by histamine and other inflammatory mediators. Also potentiates the effect of beta-agonists.

Prednisolone (Millipred, Prelone)

Decreases inflammatory reactions by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.

Dosing

Adult

Pediatric

Initial dose: 1-2 mg/kg/d PO
Subsequent doses: 1-2 mg/kg/d PO qd or divided bid for 3-7 d; not to exceed 80 mg/d
Note: Children who have used systemic corticosteroid within the previous 60 d may require a longer tapering regimen over 7-21 d
This medication is available both as a liquid and orally disintegrating tablets

Interactions

Decreases effects of salicylates and toxoids (for immunizations); phenytoin, carbamazepine, barbiturates, and rifampin decrease effects of corticosteroids

Contraindications

Documented hypersensitivity; viral, fungal or tubercular skin lesions

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hyperthyroidism, osteoporosis, cirrhosis, nonspecific ulcerative colitis, peptic ulcer, diabetes, and myasthenia gravis

Prednisone (Sterapred, Prednisone Intensol Concentrate)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Blocks the release of inflammatory mediators by inhibition of phospholipase A₂.

Dosing

Adult

Pediatric

Initial dose: 1-2 mg/kg/d PO
Subsequent doses: 1-2 mg/kg/d PO qd or divided bid for 3-7 d; not to exceed 80 mg/d
Note: Children who have used systemic corticosteroid within the previous 60 d may require a longer tapering regimen over 7-21 d

Interactions

Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; viral, fungal, tubercular skin, or connective tissue infections; peptic ulcer disease; hepatic dysfunction; GI bleeding or ulceration

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in varicella, measles, and diabetes mellitus; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Methylprednisolone (Medrol) or methylprednisolone sodium succinate (Solu-Medrol)

Steroids ameliorate delayed effects of anaphylactoid reactions and may limit biphasic anaphylaxis.

Dosing

Adult

Pediatric

1-2 mg/kg/dose PO/IM; may repeat q6h prn

Interactions

Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin, and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics; grapefruit juice increases prednisolone concentrations; methylprednisolone and cyclosporine mutually inhibit one another resulting in increased plasma levels of each drug

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use

Dexamethasone (Decadron)

Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability. Blocks release of inflammatory mediators by inhibition of phospholipase A₂. Administer IM as an alternative to IV. Current liquid products have a high percentage of alcohol and are not very concentrated; therefore, a large volume (ie, 30 mL) is typically required to provide the dose. Additionally, the liquid form is not very palatable. To circumvent this problem, some practitioners have administered the IV solution orally with a flavoring agent (off-label use).

Dosing

Adult

Pediatric

0.15-0.6 mg/kg IV/IM; not to exceed 20 mg
PO administration not ideal but possible in emergency; may administer IV solution by PO route if needed

Interactions

Effects decrease with coadministration of barbiturates, phenytoin, and rifampin; dexamethasone decreases effect of salicylates and vaccines used for immunization

Contraindications

Documented hypersensitivity; active bacterial or fungal infection

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Increases risk of multiple complications, including severe infections; monitor adrenal insufficiency when tapering drug; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications of glucocorticoid use

Adenyl Cyclase Activator

Glucagon has been used to reverse bradycardia and hypotension associated with beta-adrenergic blocker overdose. Proposed mechanism of action is increased cyclic adenosine monophosphate production resulting in positive ionotropic and chronotropic effects.

Glucagon

DOC for severe anaphylaxis in patients taking beta-blockers (should be used in addition to epinephrine, not as a substitute).
Pancreatic alpha cells of the islets of Langerhans produce glucagon, a polypeptide hormone. Exerts opposite effects of insulin on blood glucose. Glucagon elevates blood glucose levels by inhibiting glycogen synthesis and enhancing formation of glucose from noncarbohydrate sources, such as proteins and fats (gluconeogenesis). Increases hydrolysis of glycogen to glucose (glycogenolysis) in liver in addition to accelerating hepatic glycogenolysis and lipolysis in adipose tissue. Glucagon also increases force of contraction in heart and has a relaxant effect on GI tract.
Dose used for anaphylaxis is higher than usual dose of 1 mg (1 U) IV/IM/SC used to treat hypoglycemia.

Dosing

Adult

Pediatric

20-30 mcg/kg IV infused over 5 min; not to exceed 1 mg; followed by 5-15 mcg/min continuous IV infusion

Interactions

Effects of anticoagulants may be enhanced by glucagon (although onset may be delayed); monitor prothrombin activity and for signs of bleeding in patients receiving anticoagulants; adjust dose accordingly

Contraindications

Documented hypersensitivity; pheochromocytoma

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Monitor blood glucose levels in hypoglycemic patients until they are asymptomatic; glucagon is effective in treating hypoglycemia only if sufficient liver glycogen is present; since liver glycogen availability is necessary to treat hypoglycemic patients, glucagon has virtually no effect on patients in states of starvation, adrenal insufficiency, or chronic hypoglycemia

Follow-up

Further Inpatient Care

• Patients with symptoms that require admission should continue to receive supportive care (eg, intravenous fluids, vasopressors, antihistamines, steroids) as indicated.

Further Outpatient Care

• Patients with anaphylaxis should follow up with their pediatrician and be given a referral for allergy evaluation and counseling.

Inpatient & Outpatient Medications

• All patients who had more than mild symptoms and/or required more than 4 hours of observation should be given a prescription for an auto-injector of epinephrine. Patients and families should be advised to call 911 or seek immediate medical attention after epinephrine self-administration.
• Patients should be continued on H ₁ and H ₂ blockers for 3 days after resolution of symptoms. A second generation H ₁ may be used as part of discharge care.
• A 3-day course of oral steroids may be warranted.

Transfer

• Patients who require aggressive or extensive stabilization should be admitted to an intensive care unit at a tertiary pediatric center.

Deterrence/Prevention

• Consider discharging patients with an action plan (such as those from the American Academy of Asthma, Allergy and Immunology or Food Allergy and Anaphylaxis Network).
• Exposure to inciting agent, if known, should be avoided.
• When avoidance is impossible, the patient should receive prophylaxis with H ₁ and H ₂ antihistamines and steroids after exposure. Also, the patient should have an auto-injector of epinephrine readily available for use if severe symptoms develop.

Complications

• Respiratory failure
• Shock
• Multiorgan system failure
• Disseminated intravascular coagulation

Prognosis

• Prognosis is good if treated early.
• Development of shock is a poor prognostic indicator.

Patient Education

• Patients and their caregivers should be educated about exposure risk, early management, and access to medical care.
• For excellent patient education resources, visit eMedicine's Allergy Center and Allergic Reaction and Anaphylactic Shock Center. Also, see eMedicine's patient education articles Severe Allergic Reaction (Anaphylactic Shock), Food Allergy, and Allergy: Insect Sting.
• For more information, see Medscape's Allergy Resource Center.

Miscellaneous

Medicolegal Pitfalls

• Using medications other than epinephrine for initial care
• Failure to identify and treat appropriately
• Failure to prescribe an auto-injector of epinephrine
• Nonreferral to an allergy-immunology specialist

References

1. Simons EFR. Advances in H1-antihistamines. N Engl J Med. Nov 2004;351 (21):2203-17. [Medline].

2. Ogawa Y, Grant JA. Mediators of anaphylaxis. Immunol Allergy Clin North Am. May 2007;27(2):249-60, vii. [Medline].

3. Vadas P, Gold M, Perelman B, Liss GM, Lack G, Blyth T. Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis. N Engl J Med. Jan 3 2008;358(1):28-35. [Medline].

4. Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the United States: an investigation into its epidemiology. Arch Intern Med. Jan 8 2001;161(1):15-21. [Medline]. [Full Text].

5. Lieberman P, Camargo CA Jr, Bohlke K, et al. Epidemiology of anaphylaxis: findings of the American College of Allergy, Asthma and Immunology Epidemiology of Anaphylaxis Working Group. Ann Allergy Asthma Immunol. Nov 2006;97(5):596-602. [Medline].

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10. Bohlke K, Davis RL, DeStefano F, Marcy SM, Braun MM, Thompson RS. Epidemiology of anaphylaxis among children and adolescents enrolled in a health maintenance organization. J Allergy Clin Immunol. Mar 2004;113(3):536-42. [Medline].

11. [Guideline] Joint Task Force on Practice Parameters, American Academy of Allergy, Asthma and Immunology; American College of Allergy,Asthma and Immunology and Joint Council of Allergy, Asthma and Immunology. The diagnosis and management of anaphylaxis: an updated practice parameter. J Allergy Clin Immunol. Mar 2005;115(3 Suppl 2):S483-523. [Medline].

12. Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. Feb 2006;117(2):391-7. [Medline]. [Full Text].

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Keywords

anaphylaxis, anaphylaxis symptoms, anaphylaxis in children, allergic reaction, treating anaphylaxis, anaphylaxis syndrome, bee sting, drug allergy, food allergens, food allergy, latex allergy, peanut anaphylaxis, severe allergic reaction, venomous sting/bite

Contributor Information and Disclosures

Author

Jeffrey F Linzer Sr, MD, MICP, FAAP, FACEP, Associate Professor of Pediatrics and Emergency Medicine, Emory University School of Medicine; Associate Medical Director for Business Affairs and Compliance and EMS/Pre-Hospital Care Coordinator, Department of Pediatrics, Division of Pediatric Emergency Medicine, Emory University School of Medicine; Emergency Pediatric Group, Children's Healthcare of Atlanta at Egleston; Co-Medical Director and Consulting Staff, Children's Sedation Service, Children's Healthcare of Atlanta at Egleston
Jeffrey F Linzer Sr, MD, MICP, FAAP, FACEP is a member of the following medical societies: American Academy of Pediatrics, American College of Allergy, Asthma and Immunology, American College of Emergency Physicians, and Medical Association of Georgia
Disclosure: Nothing to disclose.

Medical Editor

Kirsten A Bechtel, MD, Associate Professor, Department of Pediatrics, Yale University School of Medicine; Attending Physician, Department of Pediatric Emergency Medicine, Yale-New Haven Children's Hospital
Kirsten A Bechtel, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Wayne Wolfram, MD, MPH, 
Wayne Wolfram, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Pediatrics, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Richard G Bachur, MD, Associate Professor of Pediatrics, Harvard Medical School; Associate Chief and Fellowship Director, Attending Physician, Division of Emergency Medicine, Children's Hospital of Boston
Richard G Bachur, MD is a member of the following medical societies: American Academy of Pediatrics, Society for Academic Emergency Medicine, and Society for Pediatric Research
Disclosure: Nothing to disclose.

AAAAI Board of Directors. Position Statement: Anaphylaxis in schools and other child-care settings. American Academy of Allergy Asthma & Immunology. Available at http://www.aaaai.org/media/resources/academy_statements/position_statements/ps34.asp. Accessed August 19, 2007.

AAAAI School Tools: Allergy & Asthma Resources for Professionals. Available at http://www.aaaai.org/professionals/school_tools.stm. Accessed April 30, 2009.

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