Pharmacotherapy in refractory anaphylaxis: when intramuscular epinephrine fails

This review aims to provide an evidence-based overview of several pharmacotherapeutic options available for refractory anaphylaxis when intramuscular epinephrine, the drug of choice, fails to provide resolution of signs and symptoms.

The evidence base for the therapy of anaphylaxis is comparatively weak and is largely based on consensus expert recommendations and case reports. There is an increasing recognition that this is problematic. The level of evidence for epinephrine use in anaphylaxis is higher than for other agents. Recent systematic reviews have confirmed the lack of high-grade evidence to support use of antihistamines and corticosteroids in anaphylaxis, both of which statistically continue to be used more frequently than epinephrine. Newer pharmacotherapeutic agents have been proffered, but none has been evaluated with scientific rigor.

Some anaphylactic reactions are so severe that treatment is unsuccessful despite rapid recognition and treatment. Improving the evidence base for the various treatment modalities may further help minimize fatalities once anaphylaxis is recognized. Consensus expert recommendations and case reports suggest a number of pharmacotherapeutic agents that are worthy of high-quality scrutiny through randomized controlled studies in which both treatment and placebo arms receive intramuscular epinephrine injections.