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Clinical controversies: Stop playing games with anaphylaxis: Emergency medicine news


anaphylaxis, epinephrine, biphasic reaction


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

Steroids are an example of controversial treatments, the smoke and mirrors often given for anaphylaxis, where epinephrine is minimized, and other adjunct drugs are mistakenly highlighted.

Glucocorticoids, usually methylprednisolone 1-2 mg / kg, are often given to prevent recurrence of anaphylaxis, but their evidence is lacking. The practice began many years ago and evolved from the management of asthma and croup with the idea that glucocorticoids reduce inflammation and prevent the dreaded biphasic reaction, which consists of an initial episode of anaphylaxis followed by an asymptomatic period of about 12 hours. A return of symptoms then occurs, despite no repeated 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; More recent studies 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.) Deaths are extremely rare.

There are many theories as to why biphasic reactions occur, but the most popular is the inadequate or delayed administration of epinephrine. An interesting prospective study of 430 emergency room visits for anaphylaxis found that five percent of patients had biphasic reactions. The median time from the onset of anaphylaxis to the initial dose of epinephrine was much longer in those with biphasic reactions (78 versus 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 of age (OR 1.55; 95% CI 1.01-2.38). (J Allergy Clin Immunol. 2020; 145[4]: 1082; An update of practice parameters in 2015 by Lieberman et al., Stated that glucocorticoids have no role in the treatment of anaphylaxis given their time to onset and lack of benefit proven. (Ann Allergy Asthma Immunol. 2015; 115[5]: 341.)

Another review of 31 observational studies published in 2017 demonstrated no benefit of glucocorticoids in preventing the serious consequences of anaphylaxis. They also reviewed 22 studies evaluating 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 leave the emergency room. They play a role in patients who are admitted who have angioedema or bronchospasm due to asthma, but this is 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 Pediatrician. 2021; 175[7]: 723;

Look behind the curtain

One of the most common causes of anaphylactic death is the late administration of epinephrine, for good reason. We are guilty of blurring the lines on anaphylaxis when it should be simple. Patients are given add-on drugs like anti-H1 (cetirizine 10 mg or diphenhydramine 25 mg IV) and H2 blockers (famotidine 10 mg IV) countless times, but the epinephrine is delayed, underdosed, or not administered. None of the adjunct drugs reduce mortality or relieve 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 the life-saving epinephrine.

There is no absolute contraindication to the use of epinephrine. It is the only drug that effectively treats anaphylaxis and reduces mortality. It has fewer reported side effects than glucocorticoids when dosed appropriately. Common side effects include mild anxiety, restlessness, palpitations, and headaches. A theoretical risk of more serious side effects exists in people with heart disease, but the risk of anaphylaxis revealing coronary ischemia and worsening target organ perfusion is certainly more pressing.

We need to stop the anaphylaxis games and focus on the one treatment that works. The standard of care is 0.01 mg / kg IM epinephrine for patients of all ages, with a maximum dose of 0.5 mg per single dose. Epinephrine is the only drug that treats all the pathological components of anaphylaxis. We are fooled by a cheap magic trick. Steroids may sound mystical, but they’re just smoke and mirrors when we dig deeper into the evidence

Dr Briggsis an assistant professor of emergency medicine at the University of Southern Alabama in Mobile. He is the Founder, Podcast Co-Host and Editor-in-Chief of EM Board Bombs (, a multiplatform educational tool designed to prepare the board and focus on what you need to know for the practice of emergency medicine. Follow him on twitter@blakebriggsmd.