Etomidate Versus Ketamine for Emergency Endotracheal Intubation: a Prospective Randomized Clinical Trial

Study Overview
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Brief Summary
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Patients who are having problems breathing sometimes require placement of a breathing tube in their mouth and windpipe. The purpose of this breathing tube is to save the patient's life. It is common to give the patient a medication to sedate him or her before the breathing tube is placed. For patients who are gravely ill two medications are commonly used: etomidate or ketamine. Both medications have risks and benefits. Researchers at UT-Southwestern Medical Center and Parkland Memorial Hospital would like to do a study to figure out which one is better for our patients.

Detailed Description
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Critically ill individuals who require emergency endotracheal intubation (placement of a breathing tube in the patient's mouth) usually require sedation or anesthesia to make this process tolerable. There are several medication choices for anesthesia, including medications like etomidate, ketamine and propofol. Of these, etomidate and ketamine are frequently used for critically ill patients because they have minimal effects on the patient's vital signs (blood pressure and heart rate). Both etomidate and ketamine are standard-of-care medications, locally and nationally, and both are frequently used to sedate a patient for this procedure. Both etomidate and ketamine have potential side effects. One of the potential side effects of etomidate is suppression of adrenal gland function. It is not known if this affects patients' outcomes in significant ways. One of the potential side effects of ketamine is a slight increase in patients' heart rates. It is not known if this affects patients' outcomes in significant ways. The EvK Trial will be conducted at Parkland Memorial Hospital by investigators in the Departments of Anesthesiology, Emergency Medicine, Medicine / Critical Care Medicine, Surgery, and Pharmacy. The study will randomize critically ill patients who require emergency endotracheal intubation to one of two groups: Etomidate or Ketamine. We will observe the patients' outcomes. The only study intervention involves randomizing individual patients to one medication or the other. All study follow-up beyond that point is done by review of medical records. Because of the nature of this study - an emergency procedure on a critically ill patient - the study will require institutional review board permission not to obtain written informed consent from the patient prior to randomization of study drug for administration for endotracheal tube placement. Prior to enrollment of patients the study team will carry out a comprehensive Community Consultation Plan, which is designed to inform the community about the research study. This is in accordance with rules set forth by the U.S. Food and Drug Administration (FDA 21 CFR 50.24).

Official Title
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Etomidate Versus Ketamine for Emergency Endotracheal Intubation: a Prospective Randomized Clinical Trial

Conditions
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Cardiopulmonary Arrest, Respiratory Arrest

Intervention / Treatment
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* Drug: Etomidate
* Drug: Ketamine
* Procedure: Emergency Endotracheal Intubation
* Device: Mechanical Ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patient (male or female) requiring emergency endotracheal intubation. Exclusion Criteria: Children (<18 years old). Women who are known to be pregnant. Any patient who has been previously randomized in the EvK Trial. Patients who require endotracheal intubation without sedative medication. For example, patients in full cardiac arrest. Patients with a known allergy to ketamine or etomidate. Any individual wearing a MedAlert bracelet indicating that he/she has formally opted out of the EvK Trial.

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etomidate<br>Patients randomized to this group will receive etomidate immediately prior to emergency endotracheal intubation. | Drug: Etomidate<br>* Patients randomized to this group will receive etomidate immediately prior to emergency endotracheal intubation.<br>Procedure: Emergency Endotracheal Intubation<br>* Patients enrolled in the study will be endotracheally intubated. (A breathing tube will be placed into the patient's mouth and trachea). This procedure is being done as part of standard emergency care. Standard endotracheal tubes will be used. Our hospital uses primarily Mallinckrodt (TM) brand endotracheal tubes.<br>Device: Mechanical Ventilation<br>* Patients enrolled in the study will be mechanically ventilated, using a standard ventilator used in our hospital. The mechanical ventilator is attached to the patient's endotracheal tube and helps sustain the patient's life. Our hospital uses several brands of mechanical ventilators.<br>|
| Experimental: Ketamine<br>Patients randomized to this group will receive ketamine immediately prior to emergency endotracheal intubation. | Drug: Ketamine<br>* Patients randomized to this group will receive ketamine immediately prior to emergency endotracheal intubation.<br>Procedure: Emergency Endotracheal Intubation<br>* Patients enrolled in the study will be endotracheally intubated. (A breathing tube will be placed into the patient's mouth and trachea). This procedure is being done as part of standard emergency care. Standard endotracheal tubes will be used. Our hospital uses primarily Mallinckrodt (TM) brand endotracheal tubes.<br>Device: Mechanical Ventilation<br>* Patients enrolled in the study will be mechanically ventilated, using a standard ventilator used in our hospital. The mechanical ventilator is attached to the patient's endotracheal tube and helps sustain the patient's life. Our hospital uses several brands of mechanical ventilators.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at Day 7 | Survival is defined as the number of participants survived at day 7 following emergency endotracheal intubation | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at Day 28 | Survival is defined as the number of participants survived at day 28 following emergency endotracheal intubation | Day 28 | 
| Sequential Organ Failure Assessment (SOFA) Scores | Sequential Organ Failure Assessment (SOFA) is a scoring system that assesses the performance of several organ systems. Possible scores range from 0 to 24. Higher score indicates higher degree of organ dysfunction | Day 1, Day 2, Day 3, Day 4 | 
| Duration of Mechanical Ventilation | Duration (in days) from insertion to removal of mechanical ventilation | From time of documented insertion until the time of documented removal, assessed up to 28 days | 
| Duration of Catecholamine Therapy | Time (in days) from start to end of catecholamine therapy | From time of documented start of therapy until the time of documented end of therapy, assessed up to 28 days | 
| Length of Stay in ICU | Length (in days) of ICU stay | Assessed up to 28 days | 
| Number of Participants With New Diagnosis of Adrenal Insufficiency | New diagnosis of adrenal insufficiency will be assessed by the the primary treating medical or surgical team via chart review | Day 28 | 
| Number of Attempts Necessary to Intubate | This referrers to the number of documented intubation attempts necessary to intubate the patient. | Immediate (Day 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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etomidate, ketamine, endotracheal intubation, anesthesia induction medications