Ian Ward Abdalla Maia, Ian Ward A. Maia, Sérgio Renato da Rosa Decker, Lucas Oliveira J. e Silva, Rafael von Hellmann, Júlio César Garcia de Alencar, Ludhmila Abrahao Hajjar, Julia M. Dorn de Carvalho, Daniel Pedrollo, Caio Gorla Nogueira, Natalia Mansur P. Figueiredo, Carlos Henrique Miranda, Danilo Martins, Thiago D. Baumgratz, Bruno Bergesch, Osmar Colleoni, Juliana Zanettini, Ana Paula Freitas, R. Tambelli, Maria Cristina Costa, Wilsterman Correia, Rafael Garcia de Maria, Ubirajara A. V. Filho, Andre P. Weber, Vinicius da Silva Castro, Carlos Fernando Drumond Dornelles, Barbara S. Tabach, Nicole Pinheiro Moreira, Patrícia Lopes Gaspar, Hélio Penna Guimarães, Gabriela Stanzani, Thiago F. Gava, Aidan F. Mullan, Caitlin S. Brown, Fernanda Bellolio, Molly M. Jeffery, Otavio Ranzani, Bruno A. M. P. Besen, Brazilian Airway Registry Cooperation (BARCO) group, Carolline Alaia Colin, Andrey Caique Jorge da Silva, Andre Dos Santos Cleto, Gabriele Escocia Marinho, Vanessa Giffoni, Hilana K Zenly, G. Navarro, Paola Horanna Rodrigues de Freitas, Hiram Silva, Kaue Teixeira Lima, Gabriela Zanon, Samara Pinheiro De Souza, Larissa Ferreira Alves da Silva Alves da Silva, Cristian Amaral Pereira, Cirio Osvaldo Auler, Bruna Brignoli Bernardino, Bruna Bruna Zagonel, Eduarda Capra Bertolin, Yuri Carlotto Ramires, Sibele Catarina Bernardi Jacob, Vinicius cius Sartor Henrique, Cleiton Cordeiro Prola, Rita de Souza Melo, Andrea de Vargas Tomelero, Eduardo Eduardo Scheffel, Fernando Fernando Morgado, Marjurye Gross Ramos Pereira, Eduardo Henrique Guadagnin, Shanna Habner, H.J. Kilian, Eduardo Jaeger Mensch, Lucas Oliveira Junqueira e Silva Junqueira e Silva, Antonio Carlos Klug Cogo, Natascha Kokay Nepomuceno, Ana Luisa Lanius, Lara Faria Lara Faria, Bruna Lavagnini, Gustavo Lavall Dill Lavall Dill, Paulo Victor Lopes, Luiz Artur Nunes Ribeiro, A Maciel, Mariana Pessini, Carolina Antonia Pietrobon, Lucas Pires Freitas Pires Freitas, Morgana Pizzolatti Marins, Ana Leticia Pizzutti, Cleiton Prola, Lucas Rodrigues De Oliveira, Vinícius Silva Castro, Sabrina Sabrina Favaretto, Alexandre G. M. Schmidt, Luiz Augusto de Carvalho Francisco Soares, Camila Zanco Zanco, Liliane de Oliveira Miranda, Felipe Barbosa Vallt, Anna Cristina Bertoldi Lemos Teodoro, Isabella Busnello Felipe, Beatriz Ceron Pretti, Luis Felipe Fucuta Figueira, Marcelo Guimaraes Coelho, A. Ferreira
Importance: The choice of induction agent during rapid sequence intubation (RSI) of critically ill adults may affect clinical outcomes. Although ketamine and etomidate are frequently used for RSI, their comparative effectiveness remains controversial. Objective: To compare the safety of etomidate vs ketamine for emergency RSI in critically ill adults. Design, Setting, and Participants: This cohort study used a target trial emulation with observational data collected between March 1, 2022, and April 30, 2024, from 18 emergency departments across Brazil, with data from the Brazilian Airway Registry Cooperation. Adults who underwent RSI and received either etomidate or ketamine as a sole hypnotic agent were included; those with preintubation cardiac arrest or immediate postintubation transfer were excluded. Exposure: Administration of etomidate or ketamine as the induction agent for RSI. Main Outcomes and Measures: The primary outcome was 28-day in-hospital mortality. Secondary outcomes included 7-day in-hospital mortality, first-attempt intubation success, and major adverse events (new hemodynamic instability, severe hypoxemia, and cardiac arrest) within 30 minutes after intubation. Inverse probability of treatment weighting was used to adjust for confounding. Risk ratios (RRs) and risk differences (RDs) with 95% CIs were used to compare outcomes between groups. Results: Among 1810 patients (median age, 64 years [IQR, 50-74 years]; 1048 men [57.9%]), 514 received ketamine and 1296 received etomidate. The median shock index was higher in the ketamine group than the etomidate group (0.81 [IQR, 0.65-1.01] vs 0.76 [IQR, 0.59-0.99]), and preintubation vasopressor use was more common in the ketamine group than the etomidate group (191 of 514 [37.2%] vs 391 of 1296 [30.2%]). Weighted 28-day mortality was higher with etomidate than ketamine (60.5% [95% CI, 57.2%-63.8%] vs 54.4% [95% CI, 45.0%-63.9%]; RR, 1.14 [95% CI, 1.03-1.27]; RD, 7.6% [95% CI, 2.0%-13.3%]). Seven-day mortality was also higher with etomidate than ketamine (35.2% [95% CI, 32.0%-38.3%] vs 30.1% [95% CI, 23.5%-36.7%]; RR, 1.19 [95% CI, 1.04-1.35]). New hemodynamic instability within 30 minutes after intubation was more frequent with ketamine (24.2% [95% CI, 20.4%-28.0%] vs 18.9% [95% CI, 16.7%-21.0%]; RR, 0.78 [0.64-0.95]). There were no statistically significant differences in the other secondary outcomes. Conclusions and Relevance: In this cohort study of critically ill adults undergoing RSI, etomidate use was associated with higher in-hospital mortality at 7 and 28 days compared with ketamine. These findings highlight the need for definitive randomized clinical trials to compare both agents.