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Three Part Question

What is the [risk of a biphasic reaction] in [patients with acute anaphylaxis] who have been [successfully treated with resolution of symptoms].

Clinical Scenario

26-year-old man presents to the emergency department (ED) with concern for recent perioral swelling, wheezing, nausea and urticaria after bee envenomation. He has a known allergy to bees and was able to administer 1 dose of intramuscular epinephrine. He arrived to your ED within thirty minutes and his symptoms of anaphylaxis are largely resolved. You consider how long to monitor the patient in the ED.

Search Strategy

Medline 1966-08/19 using PubMed, Cochrane Library (2019), and Embase.
[(exp anaphylaxis) AND (exp biphasic reaction)]. Limit to English language.

Search Outcome

38 studies were identified; two recent systematic reviews addressed the clinical question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Pourmand A, et al. August 2018 United States	155 studies of patients in ED setting with anaphylaxis	Systematic review	Time to biphasic reaction	Wide range from 1 to 72 hours, with a mean greater than 8 hours; most occurrences happening outside the recommended 4 to 6 hour period	Limited evidence on symptoms related to biphasic reaction, limited evidence for corticosteroid use with no RCT regarding this treatment and biphasic reactions
			Rate of occurrence of biphasic anaphylaxis	Older studies suggested a biphasic reaction can occur in up to 20% of patients. Larger, more recent studies suggest the incidence is more likely about 4%. One study found the incidence to be 2.2% in the pediatric population.
Kim TH, et al. February 2019 Republic of Korea	Adult patients with anaphylaxis and biphasic anaphylactic reactions	Meta-Analysis of 12 studies	Pooled negative predictive value for a biphasic reaction	The pooled NPV for biphasic anaphylactic reaction at 1 hour was 95.0%, and 97.3% at greater than 6 hours.	Limited studies and rarity of disease may lead to selection bias, ambiguous definition of biphasic reaction, features of anaphylaxis not described

Comment(s)

Biphasic anaphylaxis is an anaphylactic episode followed by an asymptomatic period with return of anaphylactic symptoms in the absence of further exposure to the triggering antigen. The traditional recommended ED observation time is 4-6 h after complete resolution of symptoms for every anaphylaxis patient. However, there is limited data to identify predisposing factors to recurrent reactions, and more recent data suggests this clinical entity is rare (4%) and can occur at any time between 10 minutes to 6 days. Consider sending the ED patient home with injectable epinephrine (epi pen) and steroids after a 1-hour observation period.

Clinical Bottom Line

Biphasic anaphylaxis is a rare clinical entity with low morbidity and mortality. A 1-hour observation period has been shown to achieve a 95.0% negative predictive value (NPV), with little added clinical benefit when extending the observation period.

References

1. Pourmand A, Robinson C, Syed W, Mazer-Amirshahi M. Biphasic anaphylaxis: A review of the literature and implications for emergency management. Am J Emerg Med 2018 Aug;36(8):1480-1485
2. Kim TH, Yoon SH, Hong H, Kang HR, Cho SH, Lee SY. Duration of Observation for Detecting a Biphasic Reaction in Anaphylaxis: A Meta-Analysis Int Arch Allergy Immunol 2019;179(1):31-36