Pharmacy to Dose: The Critical Care Podcast RSI Trial Deep Dive
Jan 21, 2026
Nicole Acquisto, clinical research pharmacist and emergency medicine professor, and Matthew Semler, physician-researcher leading pragmatic critical care trials, dissect the RSI trial comparing ketamine and etomidate. They review prior evidence, study design and logistics, surprising hemodynamic findings, subgroup signals in sepsis, and implications for practice and future research. Short, clear, and focused discussion.
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Vanderbilt Had A Split Culture For Induction Agents
- At Vanderbilt ICU practice favored etomidate while the ED favored ketamine, creating natural practice variation that motivated the trial.
- Semler described patients intubated on different floors historically getting different induction drugs based on culture.
RSI Trial Took Eight Years To Complete
- The RSI trial took eight years from first protocol draft (2017) to publication (2025), reflecting long funding and regulatory hurdles.
- Matthew Semler highlighted that complex U.S. drug-regulatory requirements and funding delays were key drivers of the duration.
Pragmatic Design Focused On Mortality And Immediate Hemodynamics
- RSI was a pragmatic, unblinded, multicenter U.S. trial randomizing ketamine versus etomidate for induction with clinicians controlling all other care.
- Primary outcome was 28-day in-hospital mortality; secondary was a composite cardiovascular collapse during intubation (BP<65, new/increased vasopressors, or arrest).