Etomidate Is Associated with Higher 30-Day Mortality than Ketamine for Emergency Intubation of COVID-19 Patients: A Propensity-Matched Cohort Study

Background: COVID-19 causes adrenal injury that may amplify etomidate-induced adrenal suppression. We compared 30-day mortality between etomidate and ketamine for emergency intubation. Methods: We conducted a TriNetX-based propensity-matched cohort study of adult COVID-19 patients undergoing emergency intubation with etomidate or ketamine (January 2020–June 2025). The primary outcome was 30-day mortality. Three independent propensity-matched cohorts were created using different vasopressor inclusion criteria: primary (no vasopressor on day −1), hemodynamically stable (no vasopressor on day −1 or day 0), and critically ill (vasopressor on both day −1 and day 0). Sensitivity and negative control analyses addressed confounding. Results: Among 9462 primary-cohort pairs, etomidate was associated with higher 30-day mortality (34.43% vs. 31.57%; HR 1.11, 95% CI 1.06–1.17, p < 0.001; NNH 35). The association persisted in stable patients (HR 1.16, p = 0.013) and in critically ill patients (HR 1.15, p < 0.001). Mortality hazard ratios rose progressively with longer follow-up (day 0–7: HR 1.05; day 0–30: HR 1.11), indicating a delayed effect. In stable patients, etomidate was associated with higher vasopressor initiation (HR 1.15, p = 0.005); the between-group difference appeared early (4.41% by day 1) and narrowed thereafter, while the mortality difference emerged later and widened through day 30. Conclusions: Etomidate was consistently associated with higher 30-day mortality in COVID-19 patients (HR 1.11–1.16), unlike the results seen in general critical illness. The temporal pattern of early vasopressor divergence and late mortality divergence, together with consistency across hemodynamic strata, supports disease-specific adrenal vulnerability rather than acute peri-intubation harm. Ketamine may be the preferred induction agent in COVID-19 patients without contraindications.