Cardiopulmonary Arrest, Respiratory Arrest
Conditions
Keywords
etomidate, ketamine, endotracheal intubation, anesthesia induction medications
Brief summary
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
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).
Interventions
DRUGEtomidate
Patients randomized to this group will receive etomidate immediately prior to emergency endotracheal intubation.
DRUGKetamine
Patients randomized to this group will receive ketamine immediately prior to emergency endotracheal intubation.
PROCEDUREEmergency Endotracheal Intubation
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.
DEVICEMechanical Ventilation
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.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival at Day 7 | Day 7 | Survival is defined as the number of participants survived at day 7 following emergency endotracheal intubation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sequential Organ Failure Assessment (SOFA) Scores | Day 1, Day 2, Day 3, Day 4 | 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 |
| Duration of Mechanical Ventilation | From time of documented insertion until the time of documented removal, assessed up to 28 days | Duration (in days) from insertion to removal of mechanical ventilation |
| Duration of Catecholamine Therapy | From time of documented start of therapy until the time of documented end of therapy, assessed up to 28 days | Time (in days) from start to end of catecholamine therapy |
| Survival at Day 28 | Day 28 | Survival is defined as the number of participants survived at day 28 following emergency endotracheal intubation |
| Number of Participants With New Diagnosis of Adrenal Insufficiency | Day 28 | New diagnosis of adrenal insufficiency will be assessed by the the primary treating medical or surgical team via chart review |
| Number of Attempts Necessary to Intubate | Immediate (Day 1) | This referrers to the number of documented intubation attempts necessary to intubate the patient. |
| Length of Stay in ICU | Assessed up to 28 days | Length (in days) of ICU stay |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Etomidate Patients randomized to this group will receive etomidate immediately prior to emergency endotracheal intubation.
Etomidate: Patients randomized to this group will receive etomidate immediately prior to emergency endotracheal intubation.
Emergency Endotracheal Intubation: 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.
Mechanical Ventilation: 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. | 396 |
| Ketamine Patients randomized to this group will receive ketamine immediately prior to emergency endotracheal intubation.
Ketamine: Patients randomized to this group will receive ketamine immediately prior to emergency endotracheal intubation.
Emergency Endotracheal Intubation: 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.
Mechanical Ventilation: 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. | 395 |
| Total | 791 |
Baseline characteristics
| Characteristic | Etomidate | Ketamine | Total |
|---|---|---|---|
| Age, Continuous | 55.8 years STANDARD_DEVIATION 15.2 | 55.4 years STANDARD_DEVIATION 16 | 55.6 years STANDARD_DEVIATION 15.6 |
| Race/Ethnicity, Customized Black | 133 Participants | 122 Participants | 255 Participants |
| Race/Ethnicity, Customized Hispanic | 141 Participants | 139 Participants | 280 Participants |
| Race/Ethnicity, Customized Other | 13 Participants | 27 Participants | 40 Participants |
| Race/Ethnicity, Customized White | 250 Participants | 246 Participants | 496 Participants |
| Region of Enrollment United States | 396 participants | 395 participants | 791 participants |
| Sex: Female, Male Female | 153 Participants | 150 Participants | 303 Participants |
| Sex: Female, Male Male | 243 Participants | 245 Participants | 488 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 142 / 396 | 131 / 395 |
| other Total, other adverse events | 0 / 396 | 0 / 395 |
| serious Total, serious adverse events | 10 / 396 | 9 / 395 |
Outcome results
Primary
Survival at Day 7
Survival is defined as the number of participants survived at day 7 following emergency endotracheal intubation
Time frame: Day 7
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Etomidate | Survival at Day 7 | 306 Participants |
| Ketamine | Survival at Day 7 | 336 Participants |
Secondary
Duration of Catecholamine Therapy
Time (in days) from start to end of catecholamine therapy
Time frame: From time of documented start of therapy until the time of documented end of therapy, assessed up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Etomidate | Duration of Catecholamine Therapy | 1 Days |
| Ketamine | Duration of Catecholamine Therapy | 1 Days |
Secondary
Duration of Mechanical Ventilation
Duration (in days) from insertion to removal of mechanical ventilation
Time frame: From time of documented insertion until the time of documented removal, assessed up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Etomidate | Duration of Mechanical Ventilation | 5 Days |
| Ketamine | Duration of Mechanical Ventilation | 5 Days |
Secondary
Length of Stay in ICU
Length (in days) of ICU stay
Time frame: Assessed up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Etomidate | Length of Stay in ICU | 8 Days |
| Ketamine | Length of Stay in ICU | 9 Days |
Secondary
Number of Attempts Necessary to Intubate
This referrers to the number of documented intubation attempts necessary to intubate the patient.
Time frame: Immediate (Day 1)
Population: Clinical information incomplete or missing from 5 patients randomized to Etomidate and 6 patients randomized to Ketamine.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Etomidate | Number of Attempts Necessary to Intubate | 1 Attempt (successfully intubated) | 357 Participants |
| Etomidate | Number of Attempts Necessary to Intubate | 2 Attempts (successfully intubated) | 29 Participants |
| Etomidate | Number of Attempts Necessary to Intubate | 3 or More Attempts (successfully intubated) | 4 Participants |
| Etomidate | Number of Attempts Necessary to Intubate | Surgical Airway | 1 Participants |
| Ketamine | Number of Attempts Necessary to Intubate | Surgical Airway | 3 Participants |
| Ketamine | Number of Attempts Necessary to Intubate | 1 Attempt (successfully intubated) | 355 Participants |
| Ketamine | Number of Attempts Necessary to Intubate | 3 or More Attempts (successfully intubated) | 5 Participants |
| Ketamine | Number of Attempts Necessary to Intubate | 2 Attempts (successfully intubated) | 26 Participants |
Secondary
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
Time frame: Day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Etomidate | Number of Participants With New Diagnosis of Adrenal Insufficiency | 11 Participants |
| Ketamine | Number of Participants With New Diagnosis of Adrenal Insufficiency | 4 Participants |
Secondary
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
Time frame: Day 1, Day 2, Day 3, Day 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Etomidate | Sequential Organ Failure Assessment (SOFA) Scores | Day 1 | 10.7 score on a scale | Standard Deviation 4.6 |
| Etomidate | Sequential Organ Failure Assessment (SOFA) Scores | Day 2 | 9.8 score on a scale | Standard Deviation 5.1 |
| Etomidate | Sequential Organ Failure Assessment (SOFA) Scores | Day 3 | 8.4 score on a scale | Standard Deviation 5.3 |
| Etomidate | Sequential Organ Failure Assessment (SOFA) Scores | Day 4 | 7.4 score on a scale | Standard Deviation 5.2 |
| Ketamine | Sequential Organ Failure Assessment (SOFA) Scores | Day 2 | 9.5 score on a scale | Standard Deviation 4.9 |
| Ketamine | Sequential Organ Failure Assessment (SOFA) Scores | Day 4 | 7.4 score on a scale | Standard Deviation 5.4 |
| Ketamine | Sequential Organ Failure Assessment (SOFA) Scores | Day 1 | 10.9 score on a scale | Standard Deviation 4.5 |
| Ketamine | Sequential Organ Failure Assessment (SOFA) Scores | Day 3 | 8.4 score on a scale | Standard Deviation 5.1 |
Secondary
Survival at Day 28
Survival is defined as the number of participants survived at day 28 following emergency endotracheal intubation
Time frame: Day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Etomidate | Survival at Day 28 | 254 Participants |
| Ketamine | Survival at Day 28 | 264 Participants |