Bottom Line Up Top: Based on the available evidence, we should strongly consider ketamine over etomidate as our default induction agent in critically ill patients.

Clinical Scenario: A 48 year old man presents with fever, hypotension, hypoperfusion and hypoxemia. Workup reveals multifocal pneumonia and oxygenation only marginally improves with non-invasive ventilation. You decide to intubate the patient after resuscitation. You are handed a vial of etomidate but consider whether you should use ketamine instead.

What Your Gut Says: It probably doesn’t make any difference. Just give whichever agent you’ve got.

What The Evidence Says: Etomidate has long been the favored induction agent for ED RSI in the US. The drug has a number of reported advantages including rapid onset and a favorable hemodynamic profile (etomidate itself does not cause vasodilation or cardiac depression). However, it is well-established that even a single dose of etomidate can cause adrenal suppression (Albert 2011). Proponents of its use often dismissed this effect of the drug as there had never been any evidence it impacted clinical outcomes. Additionally, better alternative induction agents were not available (midazolam and propofol both have intrinsic hemodynamic properties making them less than ideal).

More recently, ketamine has offered an alternative approach to induction. Much like etomidate, it doesn’t have intrinsic hemodynamic effects. Ketamine can lead to increases in blood pressure due to release of endogenous catecholamines. This effect is unlikely to be significant in those with severe or critical injury as they are likely to be catecholamine depleted. Unlike etomidate, ketamine offers the advantage of having no effect on the adrenal glands. Opponents of ketamine often point to the risks of spiking intracranial pressure but this concern has been widely debunked (Cohen 2015).

In the past, the literature has offered inconsistent conclusions on which drug is preferred. However, two recent publications have started to shift the scales towards ketamine.

In 2023, a meta-analysis of randomized trials demonstrated a 3% increased mortality associated with etomidate giving a number needed to harm of 31 (for every 31 patients given etomidate for RSI, there will be one additional death) (Kotani 2023). In 2024, a Bayesian meta-analysis was performed looking at randomized controlled trials comparing ketamine to etomidate in critically ill patients. This study reported that there was “moderate probability that induction with ketamine is associated with a reduced risk of mortality,” (Koroki 2024). The available evidence isn’t completely convincing and it would be disingenuous to completely remove etomidate as an induction agent based on these findings, however, there does appear to be consistency of the findings favoring ketamine over etomidate with no recent data favoring etomidate over ketamine.

Bottom Line: Based on the available data, it would be reasonable to favor ketamine over etomidate as an induction agent in critically ill patients. However, the evidence isn’t adequate to call for a wholesale change and etomidate should not be discarded as a useful alternative agent.

References

Albert SG, Ariyan S, Rather A. The effect of etomidate on adrenal function in critical illness: a systematic review. Intensive Care Med. 2011;37(6):901-910. PMID: 21373823

Cohen L et al. The Effect of Ketamine on Intracranial and Cerebral Perfusion Pressure and Health Outcomes: A Systematic Review. Ann Emerg Med 2015; 65(1): 43-51. PMID: 25064742

Kotani Y et al.Etomidate as an induction agent for endotracheal intubation in critically ill patients: a meta-analysis of randomized trials. J Crit Care 2023;77:. PMID: 37127020

Koroki T, Kotani Y, Yaguchi T, et al. Ketamine versus etomidate as an induction agent for tracheal intubation in critically ill adults: a Bayesian meta-analysis. Crit Care. 2024;28(1):PMID: 38368326

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