This observational cohort study (n=1756) aims to collect long-term outcomes from the RSI trial (NCT05277896). It was conducted by Vanderbilt University Medical Center and led by Jonathan Casey, MD, MSc.
The study investigates the potential of ketamine and etomidate in preventing symptoms of post-traumatic stress disorder (PTSD) in critically ill adults undergoing emergency tracheal intubation.
PTSD is a common psychiatric disorder triggered by traumatic events, including medical procedures such as intubation. The study seeks to assess whether ketamine, by blocking pathways in the brain’s glutaminergic system responsible for traumatic memories, can prevent or reduce PTSD symptoms. Previous research has shown that a single dose of ketamine can alleviate PTSD symptoms for up to two weeks in outpatients with chronic PTSD. The study aims to enroll 1,756 participants and is estimated to be completed by March 2028.
This study will include participants in the RSI trial who meet the eligibility criteria for long-term outcomes assessment. Participants must be adults enrolled in the RSI trial and able to follow commands prior to tracheal intubation. Exclusions include aphasic or nonverbal individuals prior to intubation, non-English speakers, and the deaf.
The study design involves two cohorts: one receiving intravenous ketamine and the other receiving intravenous etomidate as sedatives for induction of anesthesia during emergency tracheal intubation. Primary outcome measures include PTSD symptoms at 12 months, assessed using the Checklist for Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Secondary measures include vital status, awareness of paralysis, ICU memories, threat perception, anxiety, depression, quality of life, global cognition, executive function, loss of employment, and physical disability.
Data-sharing plans include making individual patient data available to researchers with approved protocols and proposals. The study started on April 6, 2022, and is estimated to conclude by January 2027. Recruitment is ongoing in Nashville, Tennessee, United States, with Jonathan D Casey as the primary contact.
Trial Details
The RSI-LTO study collects long-term outcomes from the RSI trial (NCT05277896). One-third of adults who are intubated in the ED or ICU experience symptoms of posttraumatic stress disorder (PTSD). PTSD is a psychiatric disorder triggered by a "shocking, scary, or dangerous event." Critical illness, tracheal intubation, and mechanical ventilation can be traumatic and distressing events. Patients may recall the intubation procedure, the feeling of the breathing tube in their throat, or being unable to move ("paralyzed"). While on the breathing machine, patients may experience delirium, frightening hallucinations, and delusions. Patients with PTSD after critical illness can be hypervigilant, anxious, and troubled by intrusive thoughts, nightmares, and flashbacks that last months to years after critical illness and that PTSD negatively impacts patients' marriages, work, and quality of life and increases patients' risk of depression, anxiety, substance use disorder, and suicide. Ketamine may prevent PTSD symptoms by blocking the pathways in the brain's glutaminergic system that are responsible for the formation of traumatic memories In outpatients with chronic PTSD, a single dose of ketamine has been shown to reduce PTSD symptoms for up to 2 weeks. Even a modest reduction in PTSD would translate into tens of thousands of fewer cases of PTSD each year, more cases of PTSD each year than any other medical intervention evaluated to date.NCT Number NCT06179485