Ketamine Versus Etomidate for Rapid Sequence Intubation in Critically Ill Adults: A Comprehensive Systematic Review and Meta-Analysis

Emergency endotracheal intubation in critically ill patients requires rapid induction while minimizing hemodynamic instability. Etomidate has traditionally been favored for its cardiovascular stability, whereas ketamine is increasingly used due to its sympathomimetic properties and presumed hemodynamic advantages; however, comparative data on survival and clinically meaningful outcomes remain inconsistent. We conducted a systematic review and meta-analysis to compare the effectiveness and safety of ketamine versus etomidate for emergency intubation in critically ill adults. A comprehensive search of major databases was performed from inception through the most recent available date, including randomized and observational studies directly comparing the two agents. The primary outcome was 30-day survival, and secondary outcomes included first-pass intubation success, post-intubation hypotension, Sequential Organ Failure Assessment (SOFA) score, vasopressor-free days, and ventilator-free days. Pooled estimates were calculated using random-effects models, and heterogeneity was assessed with the I² statistic. A total of 25 comparative studies met the inclusion criteria. There was no significant difference in 30-day survival between ketamine and etomidate (OR: 1.0, 95% CI: 0.83-1.21). First-pass success rates were similar (OR: 0.95, 95% CI: 0.86-1.05). Ketamine was associated with a significantly higher risk of post-intubation hypotension compared with etomidate (OR: 1.32, 95% CI: 1.03-1.69). No significant differences were observed in post-intubation SOFA scores (MD: -0.11, 95% CI: -0.30 to 0.07), vasopressor-free days (MD: -0.03 days, 95% CI: -0.37 to 0.31), or ventilator-free days (MD: -0.07 days, 95% CI: -0.28 to 0.15). Overall, ketamine and etomidate demonstrated comparable short-term survival and procedural success, although ketamine use was associated with increased post-intubation hypotension, supporting individualized induction agent selection based on patient hemodynamic profile and clinical context.