In 2020, the American Academy of Allergy, Asthma, & Immunology (AAAAI) updated its anaphylaxis guidelines, specifically advising against the use of first-generation antihistamines such as Benadryl during the acute phase of anaphylaxis or for the prevention of biphasic reactions.
Instead of antihistamines, the AAAAI guidelines advocate for epinephrine as the primary treatment for anaphylaxis, relegating antihistamines to a secondary role only after a patient’s condition has stabilized.
Despite evolving medical guidelines, emergency departments (EDs) in the United States continue to use diphenhydramine, the active ingredient in Benadryl, for treating anaphylaxis.
The medical community’s perception of diphenhydramine has shifted, largely due to its significant side effects and the proven effectiveness of second-generation antihistamines. Unlike their first-generation counterparts, which readily cross the blood-brain barrier and cause drowsiness, second-generation antihistamines are less sedating and have fewer drug interactions. This advancement has led to a reevaluation of treatment protocols, with updated guidelines emphasizing safer and equally efficacious alternatives.
Anaphylactic reactions are on the rise, with a 2.3-fold increase in prevalence observed in emergency departments between 2008 and 2016. Diphenhydramine continues to be the most commonly administered antihistamine in these settings, despite the risks of serious adverse events associated with its intravenous administration, including sedation, cognitive impairment, dizziness, and even fatalities related to overdose.
Recognizing the need for a deeper understanding of current practices, a research team led by Dr Jazeb Ifikhar from the University of Oklahoma School of Community Medicine conducted a cross-sectional analysis. Their objective was to assess the prevalence of diphenhydramine use in US emergency departments for anaphylaxis and urticaria between 2019 and 2021, and to evaluate the potential influence of the 2020 AAAAI guidelines on its usage. Utilizing data from the Centers for Disease Control and Prevention’s National Hospital Ambulatory Medical Care Survey (2019–2021), the team analyzed emergency department records of patients diagnosed with anaphylaxis or urticaria who received at least one medication.
The study’s findings revealed a persistent reliance on diphenhydramine. Among 450 patients—295 with anaphylaxis and 131 with urticaria—a substantial 61.99% received a diphenhydramine prescription. Specifically, diphenhydramine was administered in 57.99% of anaphylaxis cases, 69.45% of urticaria cases, and 73.4% of cases where both conditions were present.
Crucially, the analysis observed no significant change in diphenhydramine use from 2019 to 2021, despite the updated guidelines. Investigators concluded:
Our study indicates stagnant [emergency department] practices regarding diphenhydramine despite evolving guidelines. Bridging the gap between evidence and practice is crucial for patient care for urticaria and anaphylaxis. Future research should identify barriers hindering guideline adoption in US [emergency departments].
