Etomidate versus ketamine for in-hospital rapid sequence intubation: a systematic review and meta-analysis

Rapid sequence intubation (RSI) is a critical procedure in emergency and intensive care settings. Etomidate has been favored for its hemodynamic stability; however, concerns about adrenal insufficiency have prompted interest in ketamine as an alternative induction agent. This systematic review and meta-analysis aimed to compare the effects of etomidate vs ketamine on 30-day survival and other clinical outcomes in critically ill patients undergoing in-hospital RSI. A comprehensive literature search was conducted until 1 November 2024, across PubMed, Embase, Web of Science, Cochrane databases, and clinical trial registries. Eligible studies included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) assessing etomidate vs ketamine for RSI. The primary outcome was 30-day survival. Secondary outcomes encompassed intubation difficulty, post-intubation vasopressor use, cardiovascular collapse, Sequential Organ Failure Assessment score, systemic steroid use, organ support-free days, and adrenal insufficiency. Fourteen studies comprising 23 926 patients (19 288 receiving etomidate; 4638 receiving ketamine) met the inclusion criteria. Pooled analyses of RCTs and CCTs revealed no significant difference in 30-day survival between the two agents [RCTs: odds ratio (OR) = 0.92, 95% confidence interval (CI): 0.68-1.24, P  = 0.58; CCTs: OR = 1.16, 95% CI: 0.92-1.45, P  = 0.58]. Ketamine was associated with a higher requirement for post-intubation vasopressor support (OR = 0.71, 95% CI: 0.53-0.96, P  = 0.03) and an increase in ICU-free days. Etomidate use correlated with a significantly higher incidence of adrenal insufficiency (OR = 2.43, 95% CI: 1.67-3.53, P  < 0.001). No significant differences were observed in intubation difficulty, cardiovascular collapse, or systemic steroid use between the groups. Ketamine and etomidate showed no significant difference in 30-day survival among critically ill patients undergoing RSI. However, etomidate was associated with a higher incidence of adrenal insufficiency, while ketamine required more post-intubation vasopressor support. Provenance and peer review: Not commissioned, externally peer-reviewed.