Clinicians May be Underdosing Epinephrine for Anaphylaxis with Current Autoinjectors

By Jeff Craven /alert Contributor
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Although 0.3 mg of epinephrine is the standard dose used in adrenaline autoinjectors (AAIs) for management of anaphylaxis, clinicians may be underdosing children and adults using this dosage. Recent research released as a poster for the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting suggests an epinephrine dose of 0.5 mg results in a better absorption profile and improved cardiac benefits over the 0.3 mg epinephrine dose. 

“A single injection of adrenaline is insufficient to counteract anaphylaxis in around 10% of cases,” Paul J. Turner, MD, PhD, of the National Heart & Lung Institute, at Imperial College London in the United Kingdom (UK), said in an interview with MD /alert. While international guidelines recommend a 0.5 mg dose of epinephrine in older adults and children, current autoinjectors use 0.3 mg doses of epinephrine, which can lead to “an effective underdosing of 30% by body weight,” in a person weighing 40 kg, Dr. Turner said. 

“This has been raised as a concern at inquests in the UK, and also by the UK and European equivalent to the FDA,” he added.

Turner and colleagues performed a randomized, single-blind, cross-over study evaluating absorption of 0.3 mg and 0.5 mg doses of epinephrine using an AAI (Emerade; UK) in 12 participants who were food allergic and at risk of anaphylaxis. Participants consisted of adolescents at a mean age of 15.4 years old, median 61.8 kg, and the cohort was 58% male. 

The epinephrine doses were administered over two hospital visits approximately 1 month apart, and their cardiovascular profile was monitored using a non-invasive monitoring device (Cheetah NICOM; Cheetah Medical, Inc.; Newton Center, MA). Blood was drawn one hour before administration of epinephrine and for 3 hours after injection.

The investigators found there were no significant adverse events regardless of dosage, but the 0.5 mg group experienced a higher peak of plasma injection epinephrine concentration (P = .01) and greater plasma profile (area under the curve, P < .05) compared with the 0.3 mg group. Cardiac output in the 0.5 mg group was greater and more sustained than in the 0.3 mg group, and both doses were well tolerated with regard to cardiac safety.

“Manufacturers of epinephrine auto-injectors must consider producing 0.5 mg devices for use in the community,” Turner said.

Turner noted that the findings are currently under peer review and more data will be available in an upcoming publication.


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