Abstract: We included eight studies in the review and seven in the meta-analysis. Of those seven studies, only two were judged to be at low risk of bias. Overall, no strong evidence exists that etomidate increases mortality in critically ill patients when compared to other bolus dose induction agents (odds ratio (OR) 1.17; 95% confidence interval (CI) 0.86 to 1.60, 6 studies, 772 participants, moderate quality evidence). Due to a large number of participants lost to follow-up, we performed a post hoc sensitivity analysis. This gave a similar result (OR 1.15; 95% CI 0.86 to 1.53). There was evidence that the use of etomidate in critically ill patients was associated with a positive adrenocorticotropic hormone (ACTH) stimulation test, and this difference was more pronounced at between 4 to 6 hours (OR 19.98; 95% CI 3.95 to 101.11) than after 12 hours (OR 2.37; 95% CI 1.61 to 3.47) post-dosing. Etomidate's use in critically ill patients was associated with a small increase in SOFA score, indicating a higher risk of multisystem organ failure (mean difference (MD) 0.70; 95% CI 0.01 to 1.39, 2 studies, 591 participants, high quality evidence), but this difference was not clinically meaningful. Etomidate use did not have an effect on ICU LOS (MD 1.70 days; 95% CI -2.00 to 5.40, 4 studies, 621 participants, moderate quality evidence), hospital LOS (MD 2.41 days; 95% CI -7.08 to 11.91, 3 studies, 152 participants, moderate quality evidence), duration of mechanical ventilation (MD 2.14 days; 95% CI -1.67 to 5.95, 3 studies, 621 participants, moderate quality evidence), or duration of vasopressor use (MD 1.00 day; 95% CI -0.53 to 2.53, 1 study, 469 participants). Although we have not found conclusive evidence that etomidate increases mortality or healthcare resource utilization in critically ill patients, it does seem to increase the risk of adrenal gland dysfunction and multi-organ system dysfunction by a small amount. The clinical significance of this finding is unknown. This evidence is judged to be of moderate quality, owing mainly to significant attrition bias in some of the smaller studies, and new research may influence the outcomes of our review. The applicability of these data may be limited by the fact that 42% of the patients in our review were intubated for "being comatose", a population less likely to benefit from the haemodynamic stability inherent in etomidate use, and less at risk from its potential negative downstream effects of adrenal suppression.

Plain-language summary: We looked at the evidence up to February 2013 and found 1666 studies. We included eight studies in our review and seven studies (involving 772 patients) in our meta-analysis. The studies involved people who were in an unstable condition and critically ill. They were given one dose of etomidate or another sedative agent for endotracheal intubation. We reran the search in August 2014. We will deal with any studies of interest when we update the review. No strong evidence exists to suggest that etomidate, when compared to other bolus dose induction agents, increases mortality in critically ill patients. We must be careful in interpreting this finding because only large studies would be able to show a difference in mortality. So far, no such study has been completed. Etomidate does seem to impair adrenal gland functioning. Functioning is impaired most between four and six hours after etomidate is given. Sequential Organ Failure Assessment (SOFA) scores are used to find out how badly someone’s organs are failing. Using etomidate results in worse SOFA scores but this difference is small and not clinically meaningful. The effects of impaired adrenal gland functioning and higher SOFA scores on people’s health is unknown. Using etomidate does not seem to increase the length of time someone is in hospital (including an intensive care unit), the length of time a person is connected to a mechanical ventilator (a machine to assist with breathing), or the use of vasopressors (medicines to increase blood pressure). Most of the evidence was moderate quality. This is mainly because some small studies we looked at did not check up on people adequately after they were intubated. Most people that were involved in one study were intubated because they were in a coma. These people comprise 42% of those involved in the studies we looked at. People in a coma are unlike other critically ill people because they may not benefit to the same extent from having stable blood pressure during endotracheal intubation, which etomidate provides, nor are they at high risk from impaired adrenal gland function compared to other critically ill patients, for example those with severe infection.