Pharmacologic treatment of anaphylaxis: can the evidence base be strengthened?

PURPOSE OF REVIEW: To evaluate the evidence base for the pharmacologic treatment of anaphylaxis. RECENT
FINDINGS: In this review, we focus on four classes of medications (the alpha/beta-agonist epinephrine (adrenaline), H1-antihistamines, H2-antihistamines, and glucocorticoids) that are used in healthcare settings for the initial treatment of anaphylaxis. Epinephrine and many H1-antihistamines and glucocorticoids were introduced before the era of randomized controlled trials and before the era of evidence-based medicine. In anaphylaxis, no randomized controlled trials that are free from methodological problems and meet current standards have been performed with these medications, or with H2-antihistamines. The evidence base for epinephrine injection is stronger than the evidence base for use of other medications in anaphylaxis. Guidelines unanimously recommend prompt injection of epinephrine as the life-saving first-line medication in anaphylaxis; however, they differ in their recommendations for H1-antihistamines, H2-antihistamines, and glucocorticoids. Epinephrine is the only medication that is universally available for anaphylaxis treatment in healthcare settings worldwide. Paradoxically, it is underused in anaphylaxis treatment.
SUMMARY: For ethical reasons, there should never be a placebo-controlled trial of epinephrine in anaphylaxis. We discuss why the possibility of conducting randomized placebo-controlled trials with H1-antihistamines, H2-antihistamines, and particularly with glucocorticoids in anaphylaxis should be considered in order to improve the evidence base for treatment and guide clinical decision-making. We also describe the precautions that will be needed if randomized controlled trials are conducted in anaphylaxis.