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

To evaluate the evidence base for the pharmacologic treatment of anaphylaxis.

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.

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.