The choice of the drug used to induce sedation during emergency intubation in critically ill patients may have a meaningful impact on in-hospital survival. This is suggested by a recent study analyzing clinical outcomes associated with the use of etomidate and ketamine, two of the most commonly used agents for rapid sequence intubation in emergency departments.
The study, published in JAMA Network Open, is a multicenter investigation based on data from 18 hospitals in Brazil and was led by an international team of specialists in emergency medicine and critical care. The research included participation from the Sant Pau Research Institute (IR Sant Pau), through Dr. Otavio Ranzani, head of the DataHealth Lab at IR Sant Pau and senior coauthor of the article.
The study evaluated 1,810 critically ill adult patients who required emergency intubation and received either etomidate or ketamine as the sole induction agent. Using an advanced observational design that emulates a clinical trial, the investigators compared in-hospital mortality at 7 and 28 days after the procedure, adjusting results for multiple clinical and demographic variables.
The results show that patients who received etomidate had higher in-hospital mortality compared with those treated with ketamine. In the primary analysis, 28-day mortality was higher in the etomidate group, with a clinically meaningful absolute risk difference. This association remained consistent across multiple sensitivity analyses, reinforcing the robustness of the findings.
Regarding secondary outcomes, no significant differences were observed between the two groups in first-attempt intubation success or in most of the adverse events assessed. A higher frequency of early hemodynamic instability was observed in patients who received ketamine, a finding previously described and potentially related to the pharmacological properties of the drug and to patients’ clinical profiles.
Dr. Otavio Ranzani highlights the clinical relevance of the results: “Our data suggest that the choice of induction agent during emergency intubation is not a neutral decision and may influence outcomes as relevant as in-hospital survival. Although this is an observational study, the magnitude and consistency of the observed association justify further investigation into the impact of induction agents on clinical outcomes across different settings.” Dr. Ranzani adds, “This month, one of the largest clinical trials on this topic, the long-anticipated RSI trial, was published in The New England Journal of Medicine, showing neutral results regarding mortality but also raising questions about whether it had sufficient power to assess this outcome or whether its findings are applicable to settings beyond U.S. emergency departments and ICUs, where the trial was conducted.”
The authors emphasize that the study does not allow a definitive causal relationship to be established, but it does provide solid evidence to question the routine use of etomidate in critically ill patients. Particularly in a context in which widely available alternatives such as ketamine exist. In this regard, the work reinforces the need for continued research into how pharmacological decisions made in emergencies can have meaningful consequences for patient outcomes.
The participation of IR Sant Pau in this study reflects its commitment to clinical research aimed at improving the safety and outcomes of critically ill patients, as well as to generating high-impact scientific evidence that helps optimize clinical practice.
Maia IWA, Decker SRR, Oliveira J E Silva L, von Hellmann R, Alencar JCG, Hajjar LA, de Carvalho JMD, Pedrollo DF, Nogueira CG, Figueiredo NMP, Miranda CH, Martins D, Baumgratz TD, Bergesch B, Colleoni O, Zanettini J, Freitas AP, Tambelli R, Costa MC, Correia W, de Maria RG, Filho UAV, Weber AP, da Silva Castro V, Dornelles CFD, Tabach BS, Moreira NP, Gaspar PL, Guimarães HP, Stanzani G, Gava TF, Mullan A, Brown CS, Bellolio F, Jeffery MM, Ranzani OT, Besen BAMP, Brazilian Airway Registry Cooperation (BARCO) group. Ketamine, etomidate, and mortality in emergency department intubations. JAMA Netw Open 2025;8:e2548060. https://doi.org/10.1001/jamanetworkopen.2025.48060
