Effect of Ketamine and Etomidate During RSI on Long Term Outcomes

Study Overview
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Brief Summary
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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.

Official Title
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Effect of Ketamine and Etomidate During Rapid Sequence Intubation on Long- Term Outcomes (Long-Term Outcomes of the RSI Trial)

Conditions
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Post-Traumatic Stress Disorder, Acute Respiratory Failure

Intervention / Treatment
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* Drug: Ketamine
* Drug: Etomidate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Enrolled in RSI trial (NCT05277896) Exclusion Criteria: Aphasic or non-verbal prior to tracheal intubation Cannot follow commands prior to tracheal intubation Non-English speaking Deaf

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Comparator: Ketamine Group<br>Intravenous ketamine as the sedative for induction of anesthesia during emergency tracheal intubation. | Drug: Ketamine<br>* The RSI-LTO study collects long-term outcomes from the RSI trial (NCT05277896). In the RSI trial, patients in the ketamine group will be assigned to receive intravenous ketamine for induction of anesthesia during tracheal intubation. A dose of 2 mg/kg will be recommended, and the group assignment sheet will contain a nomogram providing the recommended dose for a range of patient weights (in pounds and kg). Treating clinicians will be able elect to give a lesser or greater dose of ketamine than recommended if felt to be required for optimal patient care.<br>|
| Comparator: Etomidate Group<br>Intravenous etomidate as the sedative for induction of anesthesia during emergency tracheal intubation. | Drug: Etomidate<br>* The RSI-LTO study collects long-term outcomes from the RSI trial (NCT05277896). In the RSI trial, patients in the etomidate group will be assigned to receive intravenous etomidate for induction of anesthesia during tracheal intubation. A dose of 0.3 mg/kg will be recommended, and the group assignment sheet will contain a nomogram providing the recommended dose for a range of patient weights (in pounds and kg). Treating clinicians will be able elect to give a lesser or greater dose of etomidate than recommended if felt to be required for optimal patient care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PTSD Symptoms at 12 months | The investigators will measure PTSD symptoms at 3 and 12 months using the Checklist for Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (PCL-5). The PCL-5 is a widely used 5-10 minute patient survey validated to characterize severity of symptoms of PTSD. Patients rate 20 items corresponding to the DSM-5 criteria for PTSD on a 5-point Likert scale ranging from 0 (not bothersome) to 4 (extremely bothersome). Total scores range from 0 to 80, with higher scores indicating more severe symptoms of PTSD. Because a value for the PCL-5 score will not exist for patients who die prior to assessment, the main analysis will use a composite endpoint approach where patients whose PCL-5 could not be assessed because they died will be assigned a value of 81 (higher than the worst value on the PTSD symptom scale). | 12 months |