Etomidate is still a controversial choice for hypnosis induction to facilitate intubation of the trachea in septic, critically ill patients

Numerous studies suggest that in septic children and adults, etomidate is an independent risk factor for mortality, but more recent data is equivocal.

Etomidate's reliable ability to suppress cortisol production by 11-beta hydroxylase suppression has long been known. In the 1980s, excess mortality was seen when this drug was used for continuous sedation of trauma ICU patients. [1] Although definitions vary, relative adrenal insufficiency of ICU patients has also long been associated with worse outcomes. [2] Although the CORTICUS study failed to show outcome differences in septic adults treated with hydrocortisone (whether they responded appropriately to corticotrophin or not), a subset analysis of 96 patients who received etomidate prior to intubation found etomidate use to be an independent risk factor for mortality - whether or not the patients received steroids (OR 1.75, 95% CI 1.06 - 2.90). [3] Furthermore, two systematic reviews also found etomidate to be an independent risk factor for mortality in septic patients. [4,5]

However, more recently, several studies have failed to show this association. For example, Alway et al., in a propensity-matched analysis of over 400 patients from two centers over a 5 year period, showed no mortality difference among patients intubated with etomidate and those who did not receive etomidate. [6] McPhee et al., accessing a large electronic database (> 2000 patients), also found no increased risk of mortality in patients who received etomidate. [7] Finally, a third systematic review in 2015 failed to show an increased risk of death associated with etomidate use, in part, perhaps, due to exclusion of trials the early meta-analyses included. [8]

In summary, the use of etomidate for facilitation of intubation in septic patients has been and is likely to remain controversial. With other agents available, one is left to wonder which set of studies is right, and which is wrong, and whether etomidate is worth the risk.

References

[1] Ledingham IM, Watt I. Influence of sedation on mortality in critically ill multiple trauma patients [letter]. Lancet 1983; 1:1270

[2] Malerba G et al. Risk factors of relative adrenocortical deficiency in intensive care patients needing mechanical ventilation. Int Care Med 2005; 31:388-392.

[3] Cuthbertson BH et al. The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock. Int Care Med 2009; 35:1868-1876.

[4] Albert SG et al. The effect of etomidate on adrenal function in critical illness: a systematic review. Int Care Med 2011; 37:901-910.

[5] Chan CM et al. Etomidate is associated with mortality and adrenal insufficiency in sepsis: A meta-analysis. Crit Care Med 2012; 40:2945-2953.

[6] Alday NJ et al. Effects of etomidate on vasopressor use in patients with sepsis or severe sepsis: A propensity-matched analysis. J Crit Care 2014; 29:517-522.

[7] McPhee LC et al. Single-dose etomidate is not associated with increased mortality in ICU patients with sepsis: Analysis of a large electronic ICU database. Crit Care Med 2013; 42:774-783.

[8] Gu W-J et al. Single-dose etomidate does not increase mortality in patients with sepsis: A systematic review and meta-analysis of randomized controlled trials and observational studies. Chest 2015; 147(2):335-346.