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Clinical Controversies

Clinical Controversies

Stop Playing Games with Anaphylaxis

Briggs, Blake MD

doi: 10.1097/01.EEM.0000815540.84209.3c
    anaphylaxis, epinephrine, biphasic reaction

    We all know anaphylaxis as the sudden, dramatic onset of mast-cell degeneration resulting in life-threatening distributive shock. Prompt diagnosis is essential because death can occur in minutes. Unfortunately, it remains underreported and undertreated, and we still get it wrong despite the treatment being straightforward.

    Steroids are one example of controversial treatments, the smoke and mirrors often given for anaphylaxis, where epinephrine is downplayed, and other adjunctive medications are incorrectly emphasized.

    Glucocorticoids, typically methylprednisolone 1-2 mg/kg, are often given to prevent recurrence of anaphylaxis, yet their evidence is lacking. The practice began many years ago and evolved from managing asthma and croup with the thought that glucocorticoids reduce inflammation and prevent the dreaded biphasic reaction, which consists of the initial episode of anaphylaxis followed by an asymptomatic period of approximately 12 hours. A return of symptoms then occurs, despite no repeat exposure to the offending agent. The reported incidence of biphasic reactions has long been debated. (J Allergy Clin Immunol. 1986;78[1 Pt 1]:76; Studies done more recently in emergency departments report an average rate of five percent, with a median onset of 11 hours. (J Allergy Clin Immunol Pract. 2015;3[3]:408.) Fatalities are exceedingly rare.

    A lot of theories exist about why biphasic reactions occur, but the most popular is inadequate or delayed epinephrine administration. One interesting prospective study of 430 emergency department visits for anaphylaxis found that five percent of the patients had biphasic reactions. The median time from anaphylaxis onset to initial epinephrine dose was much longer in those who had biphasic reactions (78 v. 45 minutes). (J Allergy Clin Immunol Pract. 2020;8[4]:1230.)

    Glucocorticoids do not reduce the incidence of biphasic reactions, according to a 2020 systemic review (OR 0.87; 95% CI 0.74-1.02). They might even increase the risk of biphasic reactions in patients under 18 years old (OR 1.55; 95% CI 1.01-2.38). (J Allergy Clin Immunol. 2020;145[4]:1082; A practice parameter update in 2015 by Lieberman, et al., stated that glucocorticoids have no role in treating anaphylaxis given their time of onset and lack of proven benefit. (Ann Allergy Asthma Immunol. 2015;115[5]:341.)

    Another review of 31 observational studies published in 2017 demonstrated no benefit of glucocorticoids in preventing severe outcomes from anaphylaxis. They also looked at 22 studies that assessed the effect of glucocorticoids on biphasic reactions; only one study showed a possible beneficial effect. (J Allergy Clin Immunol Pract. 2017;5[5]:1194.)

    Glucocorticoids have no role in anaphylactic patients who respond well to epinephrine and are discharged from the ED. They have a role in patients who are being admitted, have angioedema, or have bronchospasm from asthma, but these are a minority of patients. Most anaphylactic patients are discharged. Glucocorticoids are not harmless. Even a short “burst” course has been associated with pneumonia, gastrointestinal bleeding, and sepsis five to 30 days after treatment. (JAMA Pediatr. 2021;175[7]:723;

    Look Behind the Curtain

    One of the most common causes of anaphylactic fatality is delayed epinephrine administration, for good reason. We are guilty of muddying the waters on anaphylaxis when it should be straightforward. Patients are given adjunctive medications like H1 blockers (cetirizine 10 mg or diphenhydramine 25 mg IV) and H2 blockers (famotidine 10 mg IV) countless times, but epinephrine is delayed, underdosed, or not given. None of the adjunctive medications reduces mortality or relieves airway obstruction caused by anaphylaxis. (Ann Allergy Asthma Immunol. 2014;113[6]:599; You can give these medications for symptom management, but never let them take precedence over life-saving epinephrine.

    No absolute contraindications for using epinephrine exist. It is the only medication that effectively treats anaphylaxis and reduces mortality. It has less reported side effects than glucocorticoids when dosed appropriately. Common side effects include mild anxiety, restlessness, palpitations, and headaches. A theoretical risk of worse adverse effects exists in those with cardiac disease, but the risk of anaphylaxis unmasking coronary ischemia and worsening end-organ perfusion is certainly more pressing.

    We need to stop the games when it comes to anaphylaxis and concentrate on the only treatment that works. The standard of care is 0.01 mg/kg IM epinephrine for patients of any age, with a max dose of 0.5 mg per single dose. Epinephrine is the only drug that addresses all the pathologic components of anaphylaxis. We are being fooled by a cheap magic trick. Steroids may seem mystical, but they are just smoke and mirrors when we delve into the evidence

    Dr. Briggsis an assistant professor of emergency medicine at the University of South Alabama in Mobile. He is the founder, podcast co-host, and editor-in-chief of EM Board Bombs (, a multiplatform educational tool designed to provide board prep and focus on what you need to know for the practice of emergency medicine. Follow him on Twitter@blakebriggsmd.

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    • mgmaxwell9:30:49 AMI don't really see any documentation that epinephrine is often or commonly delayed in the treatment of anaphylaxis. I did 40 years in EM and was board certified in 1982, and I can say anaphylaxis is extremely rare and would be skeptical of studies of it if they include the much more common anaphylactoid reaction. Have they changed the definition of anaphylaxis to include a different shade of anaphylactoid symptoms?