Daily Literature Update
Evaluation of Etomidate Use and Association with Mortality Compared with Ketamine among Critically Ill Patients
Wunsch H, Bosch NA, Law AC, Vail EA, Hua M, Shen BH, Lindenauer PK, Juurlink DN, Walkey AJ, Gershengorn HB. Evaluation of Etomidate Use and Association with Mortality Compared with Ketamine among Critically Ill Patients. Am J Respir Crit Care Med. 2024 Nov 15;210(10):1243-1251. doi: 10.1164/rccm.202404-0813OC. PMID: 39173173.
Study Type: Retrospective observational cohort study with propensity score matching
Population: Critically ill adults receiving invasive mechanical ventilation (IMV) in ICUs (n=1,689,945; matched subset n=44,546)
Intervention: Receipt of etomidate on day of IMV initiation versus ketamine
Outcomes: Hospital mortality; effect modification by post-intubation corticosteroid use
Key Findings
- 43.7% of patients receiving IMV received etomidate.
- In matched analysis, etomidate was associated with higher hospital mortality vs ketamine (21.6% vs 18.7%), absolute risk difference 2.8% (95% CI 2.13.6%), adjusted OR 1.28 (95% CI 1.211.34).
- Findings were consistent across subgroups and sensitivity analyses.
- Post-intubation corticosteroid administration did not reduce increased mortality risk associated with etomidate.
Context & Related Research
- Systematic review & meta-analysis, 2025: No 30-day survival difference etomidate vs ketamine; etomidate linked to adrenal insufficiency; ketamine increased vasopressor needs. (PMID: 40239104)
- Meta-analysis of RCTs: Etomidate increased mortality vs other agents; risk ratio 1.16 (95% CI 1.011.33; P=0.03). (PMID: 37127020)
- Bayesian meta-analysis: Ketamine associated with moderate probability (83.2%) of improved survival in critically ill patients. (PMID: 38368326)
- Background source: Adrenal suppression risk with etomidate and hemodynamic stability facts. (Wikipedia)
Strengths & Limitations
| Strengths | Limitations |
|---|---|
| Very large ICU cohort from Premier Healthcare Database (1.7 million patients) | Observational design, cannot prove causality |
| Propensity score matching to balance confounders | Potential unmeasured confounding (e.g., illness severity scores not included) |
| Consistent findings across multiple sensitivity and subgroup analyses | Limited info on timing/doses of corticosteroids and vasopressors |
Clinical Implications & Impact
Pharmacists should weigh risks of etomidate-related adrenal suppression and increased mortality against ketamine9s hemodynamic effects in RSI for critically ill patients. Consideration of alternative induction agents may improve hospital survival outcomes. Post-intubation corticosteroid administration does not mitigate etomidate9s mortality risk. Close monitoring for adrenal insufficiency and hemodynamic instability remains essential.
Conclusion
In a large ICU cohort, use of etomidate on the day of invasive mechanical ventilation was associated with increased hospital mortality compared with ketamine, independent of corticosteroid treatment.
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Citations
- Wunsch H et al. Am J Respir Crit Care Med. 2024;210(10):1243-1251. PMID:39173173
- Systematic review & meta-analysis. 2025. PMID:40239104
- Meta-analysis of RCTs. 2023. PMID:37127020
- Bayesian meta-analysis. 2023. PMID:38368326
- Wikipedia contributors. Etomidate. Accessed 2024.
