Anaphylaxis Pharmacotherapy

• Anaphylaxis is a life-threatening, IgE-mediated allergic reaction most commonly triggered by medications, foods, and stinging

insects.

• Symptoms occur rapidly, within minutes up to as late as 1 hour, and can involve urticaria, angioedema, dyspnea, hypotension,

nausea/vomiting, and abdominal pain among many other reactions.

• Some patients experience biphasic anaphylaxis, which is recurrent anaphylaxis that occurs an average of 10 hours (1 to 72 hours)

after the resolution of the initial episode. Mechanisms of biphasic anaphylaxis are poorly understood.

Epinephrine

Role in Therapy

First-line therapy for uniphasic and biphasic anaphylaxis

Mechanism

Non-selective α- and β-adrenergic agonist

α1 receptor: vasoconstriction that alleviates hypotension, erythema, urticaria, angioedema, and upper

airway mucosal edema

β2 receptor: bronchodilation and suppression of further mediator release from mast cells and basophils

β1 receptor: increases heart rate and contractility

Intramuscular

Administration

Dose

• 3 to 0.5 mg OR 0.01 mg/kg (max 0.5 mg in adolescents & adults; max 0.3 mg in children) IM every 5 to 15

minutes

Use 1 mg/mL epinephrine concentration

Route

Administer intramuscularly into the anterolateral aspect of the thigh [refer to literature section]

o

IM absorption > subcutaneous (SQ) absorption

o

Thigh absorption > deltoid administration

Intravenous

Epinephrine

Indications

Inadequate response to multiple IM epinephrine injections

Hypotension unresponsive to fluids

Cardiac or respiratory arrest

Dose

Hemodynamically Stable

Initial: 1 mcg/min IV continuous infusion titrated by 0.5 mcg/min every 10 to 15 min to desired response

Administration:

Evidence details are preserved from the source document in the clinical sections and references.

• Epinephrine is the cornerstone of therapy in anaphylaxis, and delayed use of epinephrine has been associated with an increased

rate of mortality.

• Do not delay the administration of epinephrine for the administration of histamine receptor antagonists or glucocorticoids.
• Continuous epinephrine intravenous infusions may be started in patients that do not respond to multiple doses of IM

epinephrine, have persistent hypotension, and cardiac and/or respiratory arrest.

• Histamine receptor antagonists and glucocorticoids do not prevent biphasic anaphylaxis, and patients should be counseled on

this recurrent reaction.

Literature

Author, year

Design

Purpose

Outcomes

Route of Epinephrine Administration

Simons et al.

1998

RCT

(N=17)

Evaluate epinephrine absorption

between IM and SQ routes in children

• IM injection of epinephrine led to a faster peak

• Shaker MS et al. Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations,

Assessment, Development and Evaluation (GRADE) analysis. J Allergy Clin Immunol. 2020 Apr; 145:1082.

• Lieberman P et al. Anaphylaxis - a practice parameter update 2015. Ann Allergy Asthma Immunol. 2015;115:341-384.
• Russell WS, Farrar JR, Nowak R, et al. Evaluating the management of anaphylaxis in US emergency departments: Guidelines vs.

practice. World J Emerg Med. 2013;4(2):98-106.

• Campbell RL, Li JT, Nicklas RA, Sadosty AT; Members of the Joint Task Force; Practice Parameter Workgroup. Emergency

department diagnosis and treatment of anaphylaxis: a practice parameter. Ann Allergy Asthma Immunol. 2014 Dec;113(6):599-

• Simons FE, Roberts JR, Gu X, Simons KJ. Epinephrine absorption in children with a history of anaphylaxis. J Allergy Clin Immunol.

1998 Jan;101(1 Pt 1):33-7.

• Simons FE, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection. J Allergy Clin

Immunol. 2001 Nov;108(5):871-3.

• Brown SG, Blackman KE, Stenlake V, Heddle RJ. Insect sting anaphylaxis; prospective evaluation of treatment with intravenous

adrenaline and volume resuscitation. Emerg Med J. 2004 Mar;21(2):149-54.

• Grunau BE, Wiens MO, Rowe BH, McKay R, Li J, Yi TW, Stenstrom R, Schellenberg RR, Grafstein E, Scheuermeyer FX. Emergency

Department Corticosteroid Use for Allergy or Anaphylaxis Is Not Associated With Decreased Relapses. Ann Emerg Med. 2015

Oct;66(4):381-9.

• Ko BS, Kim WY, Ryoo SM, Ahn S, Sohn CH, Seo DW, Lee YS, Lim KS, Kim TB. Biphasic reactions in patients with anaphylaxis treated

with corticosteroids. Ann Allergy Asthma Immunol. 2015 Oct;115(4):312-6.