Debating the Early Use of Epinephrine

In a presentation about anaphylaxis titled “Early Use of Epinephrine: What’s the Evidence?” speaker Jay A. Lieberman, MD, of the University of Tennessee Health Science Center and Le Bonheur Children’s Hospital in Memphis, took a devil’s advocate approach to the question.

There is currently an absence of any placebo-controlled experimental trials in humans to show epinephrine’s efficacy in anaphylaxis, he said. Therefore, clinicians must review and apply other applicable data, as well as consider the goals: to decrease costs, morbidity, and mortality.

Animal studies have had “fascinating results,” he said. In a rabbit model, epinephrine resulted in an increased mean arterial pressure (MAP) compared with thyrotropin-releasing hormone (TRH) and normal saline one minute after treatment. However, TRH showed increased MAP over epinephrine at four minutes, and there were no differences in MAP among the three groups beyond four minutes. Furthermore, the study found no difference in survival between treated and control animals.

In a canine study of anaphylactic shock, researchers compared three methods of epinephrine administration versus respective placebos given once hypotension started. The study found that earlier administration of intravenous epinephrine (before maximal hypotension) may produce a more beneficial effect. Another canine model study Lieberman reviewed found that bolus treatment of epinephrine by three methods, when administered at the initiation of allergen challenge, led to limited hemodynamic improvement.

The closest in vivo study in humans, he said, found that standard therapy with epinephrine and fluids, did not immediately reverse the hemodynamic or respiratory abnormalities in the two subjects who had the most severe anaphylactic shock.

“So why do we continually recommend early epinephrine?” Lieberman asked. He noted that case series of fatalities due to anaphylaxis suggest that fatal cases do not receive epinephrine or receive it late. Additionally, studies have shown that administration of epinephrine before arrival in the emergency department is independently associated with a decreased likelihood of requiring multiple doses of epinephrine, decreased hospitalization, and decreased admission to the intensive care unit.

Regardless, the literature shows that some reactions will be fatal whether epinephrine is administered early or not. Lieberman stressed that although epinephrine may be crucial in managing reactions to stings, research has found that inhaled beta agonists may be more important in anaphylaxis cases that are due to food allergy.

“There’s a lot of noise out there,” he added, but conceded that the limited supportive data and the lack of a downside leads him to choose to administer it and to do so early.