The Randomized trial of Sedative choice for Intubation (RSI) trial is a parallel-group, pragmatic, randomized clinical trial comparing the effectiveness of ketamine versus etomidate for sedation during tracheal intubation of critically ill adults. At 5 geographically diverse centers (Vanderbilt, Hennepin, University of Alabama Birmingham, University of Colorado, and Wake Forest), 2,364 critically ill adults undergoing tracheal intubation with sedation in the ED or ICU will be enrolled. Patients will be excluded if they are less than 18 years old, pregnant, incarcerated, diagnosed with traumatic injury, or allergic to ketamine or etomidate, or if the treating clinician determines that either ketamine or etomidate are required or contraindicated.

Enrolled patients will be randomly assigned in a 1:1 ratio to receive either ketamine (1,182 patients) or etomidate (1,182 patients) as sedation for tracheal intubation. Patients will be followed for 12 months after enrollment. Outcome assessors will be blinded to treatment group assignment. The primary outcome will be mortality by 1 month. The secondary outcome will be PTSD symptoms at 12 months.

Exploratory outcomes will include mortality by 3 and 12 months, PTSD symptoms at 3 months, PTSD diagnosis at 3 and 12 months, quality of life, depression, anxiety, cognition, ventilator-free days, vasopressor-free days, ICU-free days, organ dysfunction, delirium and coma, awareness with paralysis, cardiovascular collapse, cardiac arrest, lowest oxygen saturation during and after intubation, highest and lowest blood pressure during and after intubation, number of intubation attempts, and duration of intubation. Aim 3 will use analyses of heterogeneity of treatment effect to predict whether ketamine or etomidate will result in better outcomes for a patient, based on his or her individual characteristics.

Our partnerships with patient, clinician, and health system stakeholders, patient advocacy groups, national organizations for anesthesiology, critical care, and emergency medicine clinicians, and an established critical care evidence dissemination platform will facilitate dissemination and implementation of the trial’s findings, to achieve our goal improving survival and mental health for critically ill adults.