Etomidate as an induction agent in septic patients: red flags or false alarms?

Despite its widespread use in North America and many other parts of the world, the safety of etomidate as an induction agent for rapid sequence intubation in septic patients is still debated. In this article, we evaluate the current literature on etomidate, review its clinical history, and discuss the controversy regarding its use, especially in sepsis. We address eight questions: (i) When did concern over the safety of etomidate first arise? (ii) What is the mechanism by which etomidate is thought to affect the adrenal axis? (iii) How has adrenal insufficiency in relation to etomidate use been defined or identified in the literature? (iv) What is the evidence that single dose etomidate is associated with subsequent adrenal-cortisol dysfunction? (v) What is the clinical significance of adrenal insufficiency or dysfunction associated with single dose etomidate, and where are the data that support or refute the contention that single-dose etomidate is associated with increased mortality or important post emergency department (ED) clinical outcomes? (vi) How should etomidate's effects in septic patients best be measured? (vii) What are alternative induction agents and what are the advantages and disadvantages of these agents relative to etomidate? (viii) What future work is needed to further clarify the characteristics of etomidate as it is currently used in patients with sepsis? We conclude that the observational nature of almost all available data suggesting adverse outcomes from etomidate does not support abandoning its use for rapid sequence induction. However, because we see a need to balance theoretical harms and benefits in the presence of data supporting the non-inferiority of alternative agents without similar theoretical risks associated with them, we suggest that the burden of proof to support continued widespread use may rest with the proponents of etomidate. We further suggest that practitioners become familiar with the use of more than one agent while awaiting further definitive data.