Medication Summary
The primary drug treatments for acute anaphylactic reactions are epinephrine and H1 antihistamines. According to the 2013 World Allergy Association update, [48] 2015 Joint Task Force anaphylaxis update, [47] and 2010 NIAID guidelines, [66] epinephrine is the drug of choice for life-threatening reactions. When the intravenous (IV) route is not indicated, the intramuscular (IM) route is preferable to the subcutaneous (SC) route due to more rapid and reliable absorption. The anterolateral thigh is the preferred site, in children and adults. There is evidence for better absorption at this site as compared to a deltoid IM injection or SC injection. A summary of pharmacological management recommendations is available in the Joint Task Force anaphylaxis update, [47] NIAID report, [66] or WAO report. [48]
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 gastrointestinal (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.
Adrenergic Agonists
Class Summary
These agents help maintain blood pressure, antagonize effects of released mediators, and prevent further release of mediators.
Epinephrine (Adrenaline, EpiPen, EpiPen Jr, Twinject, Adrenaclick)
Epinephrine is the drug of choice for treating anaphylaxis. It has alpha-agonist effects that include increased peripheral vascular resistance and reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Its beta-agonist effects include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.
Antihistamines
Class Summary
Antihistamines are 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)
Diphenhydramine has a long history of efficacy and relative safety. It has an FDA indication for anaphylaxis. IV administration provides faster onset of action.
Hydroxyzine (Vistaril)
Hydroxyzine is an H1 antihistamine. It may suppress histamine activity in the subcortical region of the CNS.
H2 Receptor Antagonists
Class Summary
These agents block effects of released histamine at H2 receptors, thereby treating vasodilation, possibly some cardiac effects, and glandular hypersecretion. H2 blockers with H1 blockers have additive benefit over H1 blockers alone in treating anaphylaxis. Ranitidine (Zantac) probably preferred over cimetidine (Tagamet) in anaphylaxis in light of the risk for hypotension with rapidly infused cimetidine and the multiple, complex drug interactions with cimetidine. Famotidine (Pepcid) IV is another good alternative.
Cimetidine (Tagamet)
Many H2 blockers are available. Cimetidine is the prototype drug; other agents have much less evidence of effectiveness in anaphylaxis.
Ranitidine (Zantac)
Ranitidine is an H2 antagonist, which, when combined with an H1 type, may be useful in treating allergic reactions that do not respond to H1 antagonists alone.
Famotidine (Pepcid)
H2 antagonist that when combined with an H1 type, may be useful in treating allergic reactions that do not respond to H1 antagonists alone.
Bronchodilators
Class Summary
These agents stimulate beta2-adrenergic receptors in bronchial smooth muscle, causing bronchodilation. Inhaled beta-agonists are used to counteract bronchospasm and should be administered to patients who are wheezing.
Albuterol (Proventil HFA, Ventolin HFA, ProAir HFA)
Albuterol is a beta agonist for bronchospasm refractory to epinephrine. It relaxes bronchial smooth muscle by action on beta2-receptors, with little effect on cardiac muscle contractility.
Corticosteroids
Class Summary
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. It is unclear whether corticosteroids administered systemically during the initial phase of anaphylaxis can weaken or prevent late-phase reactions. [77]
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)
Methylprednisolone may help prevent late-phase allergic reactions (biphasic anaphylaxis). It has no immediate effects.
Prednisone
Prednisone is an immunosuppressant for treatment of allergic reactions. It may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Positive Inotropic Agents
Class Summary
These agents help maintain blood pressure independent of adrenergic receptors by increasing intracellular levels of cyclic AMP. In addition, stimulate release of endogenous catecholamines.
Glucagon (GlucaGen)
Glucagon might be beneficial for severe anaphylaxis in patients taking beta-blockers (it should be used in addition to epinephrine, not as a substitute), although data are limited to case reports. Glucagon can also be used to reverse bronchospasm.
Pancreatic alpha cells of the islets of Langerhans produce glucagon, a polypeptide hormone. Glucagon exerts opposite effects of insulin on blood glucose. It elevates blood glucose levels by inhibiting glycogen synthesis and enhancing formation of glucose from noncarbohydrate sources, such as proteins and fats (gluconeogenesis). It increases hydrolysis of glycogen to glucose (glycogenolysis) in liver in addition to accelerating hepatic glycogenolysis and lipolysis in adipose tissue. It also increases force of contraction in the heart and has a relaxant effect on the GI tract.
The dose used for anaphylaxis is higher than the usual dose of 1 mg (1 U) IV/IM/SC used to treat hypoglycemia.
Vasopressors
Class Summary
These agents are useful as adjunctive therapy to IV fluids to treat refractory hypotension from anaphylaxis.
Dopamine (Intropin)
Dopamine often is considered the drug of choice for anaphylaxis-induced refractory hypotension. It stimulates both adrenergic and dopaminergic receptors.
The hemodynamic effect is dependent on dose. Lower doses predominantly stimulate dopaminergic receptors, which, in turn, produce renal and mesenteric vasodilation. Cardiac stimulation and peripheral vasoconstriction are produced by higher doses.
More than 50% of patients are satisfactorily maintained on doses of less than 20 mcg/kg/min.
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- Overview
- Presentation
- DDx
- Workup
- Treatment
- Approach Considerations
- Initial Emergency Department Interventions
- Administration of Epinephrine
- Administration of Antihistamines and Corticosteroids
- Management of Blood Pressure
- Treatment of Gastrointestinal Symptoms
- Short-Term Desensitization Procedures
- Administration of Anti-IgE
- Inpatient Care
- Prevention of Anaphylaxis
- Dietary Measures
- Consultations
- Long-Term Monitoring
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- Medication
- Questions & Answers
- References
