Effect of Ketamine and Etomidate During RSI on Long Term Outcomes (RSI-LTO)

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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Post-Traumatic Stress Disorder; Acute Respiratory Failure
• Intervention / Treatment: Drug: Ketamine; Drug: Etomidate

• Study Type: Observational
• Enrollment (Estimated): 1756

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
    • Denver, Colorado, United States, 80204
      • Denver Health Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Critically ill adults undergoing emergency tracheal intubation who were enrolled in the RSI trial (NCT05277896) and meet eligibility criteria for long-term outcomes assessment.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Comparator: Ketamine Group; Intravenous ketamine as the sedative for induction of anesthesia during emergency tracheal intubation.	Drug: Ketamine; 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.
Comparator: Etomidate Group; Intravenous etomidate as the sedative for induction of anesthesia during emergency tracheal intubation.	Drug: Etomidate; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vital status	Date and location of death will be assessed from enrollment until 12 months after enrollment by trial personnel using review of electronic health records, phone calls with families, and national death indices.	12 months
Awareness of paralysis	This will be determined by the modified Brice questionnaire and ICU Memory Tool (15-20 minutes). These semi-structured interviews ask subjects about their recollection of the ICU experience, including of being paralyzed. Possible awareness with paralysis event (Present/Absent) will be defined as: (1)reporting memories of the period between losing consciousness and waking up and (2) a sensation/feeling of wakeful paralysis.	3 months
ICU Memories	This will be determined by the ICU Memory Tool (15-20 minutes). These semi-structured interviews ask subjects about their recollection of the ICU experience, including emotions, memories, and the worst thing experienced during mechanical ventilation. Patients will be classified as having (1) factual memories, (2) delusional memories, (3) memories of feelings. These choices are not mutually exclusive as they may have more than one or none of these memories.	3 months
Threat perception	This 7-item questionnaire assesses the patient's perception of feeling threatened during the intubation experience. Scores range from 0 (none at all) to 21 (extremely threatened).	3 months
Anxiety	Anxiety symptoms will be characterized using the General Anxiety Disorder-7 (GAD-7) which is a 7-item questionnaire that ranges from 0 (no anxiety) to 21 (severe anxiety).	12 months
Depression	Depression symptoms will be characterized using the Patient Health Questionnaire-9 (PHQ-9) which is a 9-item questionnaire that ranges from 0 (no depression) to 27 (severe depression).	12 months
Quality of life (EQ-5D-5L)	Quality of life will be characterized using the EuroQol 5-Dimension, 5 level version (EQ-5D-5L) is a 5-question instrument that captures impairments in mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. EQ-5D-5L scores will be summarized using the index value validated for the US population. Index scores range range from -0.573 (quality of life worse than death) to 1.000 (perfect quality of life).	12 months
Global Cognition	Global cognition will be characterized using the Montreal Cognitive Assessment - Blind (MoCA-Blind). The MoCA-Blind assesses memory, attention, language, abstraction, delayed recall, and orientation. Scores range from 0 (severe cognitive impairment) to 22 (no cognitive impairment).	12 months
Executive Function	Oral Trailmaking Test - Patient counts from 1 to 25 and then alternates between numbers and letters (i.e., 1-A-2-B-3-C, etc.,)	12 months
Loss of Employment	Patients are asked what their employment status is prior to the acute illness and at 12-months. Patients will be considered to be have loss of employment if they go from: (1) full to partial employment, (2) full to no employment, or (3) partial to no employment.	12 months
Physical disability	Duke Activity Status Index (DASI) - An 11-item survey that assesses the patient's current ability to perform various physical activities. Scores range from 0 (poor physical function) to 58.2 (excellent physical function).	12 months

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: Patient-Centered Outcomes Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: December 8, 2023
• First Submitted That Met QC Criteria: December 19, 2023
• First Posted (Actual): December 22, 2023

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Imidazoles; Ketamine; Etomidate
• Other Study ID Numbers: 210500-2; BPS-2022C3-30021 (Other Grant/Funding Number: Patient-Centered Outcomes Research Institute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Following publication, individual patient data will be made available for sharing to researchers with 1) a signed data access agreement, 2) research testing a hypothesis, 3) a protocol that has been approved by an institutional review board, and 4) a proposal that has received approval from the principal investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No