eMedicine Specialties > Emergency Medicine > Allergy & Immunology

Anaphylaxis: Treatment & Medication

Author: Richard S Krause, MD, Senior Faculty, Department of Emergency Medicine, State University of New York at Buffalo School of Medicine
Contributor Information and Disclosures

Updated: Sep 2, 2009

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.
  • Wheezing or stridor indicates bronchospasm or mucosal edema. Treatment with epinephrine and inhaled beta-agonists is effective for these indications.
  • 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.
  • 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.
  • 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.
  • 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.

Diagnosis and management guidelines are available from the American Academy of Allergy, Asthma, and Immunology; American College of Allergy, Asthma, and Immunology; and Joint Council of Allergy, Asthma, and Immunology.⁷

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.

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.

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.

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.

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.

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.

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