Airway Control, Anesthesia, Complication, Intubation
Conditions
Keywords
Intubation, Airway, Emergent intubation, Rapid sequence intubation, Rapid sequence induction, RSI, Ketamine, Etomidate, Sepsis, Sedative, Sedation
Brief summary
The purpose of this study is to compare the effectiveness and safety of ketamine and etomidate during rapid sequence intubation (RSI).
Detailed description
This study is a randomized controlled trial of etomidate versus ketamine during rapid sequence intubation (RSI). RSI refers to the process by which patients who require emergency airway management undergo sedation and paralysis prior to insertion of an endotracheal tube(airway tube). Patients who require intubation will be randomized to have intubation performed with either ketamine or etomidate. All other care will be at the discretion of the treating physicians. The purpose of this study is to compare the efficacy and safety of ketamine and etomidate during rapid sequence intubation.
Interventions
DRUGKetamine
Subjects will receive ketamine for sedation prior to rapid sequence intubation.
DRUGEtomidate
Subjects will receive etomidate for sedation prior to rapid sequence intubation.
Sponsors
Hennepin Healthcare Research Institute
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
* 18 years of age * Undergoing rapid sequence intubation (RSI) in the Emergency Department
Exclusion criteria
* Known contraindication to ketamine or etomidate * Patient has a condition in which an increase in heart rate or blood pressure would be hazardous, as judged by the treating physician * Patient is known or suspected of having increased intracranial pressure, based on the history and physical examination performed by the treating physician. * Females of child-bearing age, defined as 18-50 years, who do not have a documented pregnancy test in this institution confirming that they are not pregnant or who do not have a confirmed surgical procedure preventing pregnancy, i.e., tubal ligation, hysterectomy. The timing of the pregnancy test at which the investigative team will consider a subject to be non-pregnant is a documented negative test during current hospitalization or upon direct transfer from outside institution during current illness. * Patient declines participation in the trial by wearing a bracelet marked KvE declined * Prisoner
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SOFA Score | up to 3 days | \*Maximum SOFA score within three hospital days: all patients. SOFA score is the Sequential Organ Failure Assessment. The minimum score is 0, the maximum score is 24, with higher scores indicating higher likelihood of worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With First-pass Success | up to 5 minutes (average time frame) | The rate of first pass success, defined as successful tracheal intubation on the first attempt. An attempt is defined as the insertion and subsequent removal of the laryngoscopic device from the patient's mouth, regardless of whether an endotracheal tube was inserted. |
| Doses of Post-intubation Sedation | up to 6 hours | The number of bolus doses of sedative administered post-intubation will be compared up to 6 hours (including morphine, dexmedetomidine, propofol , etomidate, ketamine, lorazepam (Ativan), midazolam (Versed), diazepam (Valium), fentanyl, hydromorphone (Dilaudid)). Infusions of these medications will be recorded separately but will not be part of this outcome. |
| Number of Patients With Post-intubation Hypoxemia | up to 2 hours | The following will be compared between the two groups: * Hypoxemia and severe hypoxemia in the peri-intubation period. Peri-intubation hypoxemia was defined as during after the 5 minutes immediately after intubation. * Hypoxemia within the first 2 hours intubation Hypoxemia is defined as SpO2 less than 90%. Severe hypoxemia is defined as SpO2 less than 90% for 60 seconds or more. |
| Mortality in Sepsis and Septic Shock | 30 Days | Evaluate mortality for the sub-group diagnosed with sepsis and septic shock, defined as: \- Suspected infection, and at least 2 of 4 systemic inflammatory response syndrome (SIRS) criteria: 1. Temperature \>38C or \<36C 2. Respiratory Rate \>20 or PaCO2 \<32 mmHg 3. Heart Rate \>90 4. White blood cell count \>12,000 or \<4,000, or \> 10% bands Septic shock: defined as sepsis plus either: 1) Systolic blood pressure \<90 after 1L of intravenous fluid or 2) lactate \>=4mmol/L |
| Peak and Plateau Pressure | up to 30 minutes (average time frame) | The Peak and plateau pressures will be compared between the two groups, with a pre-defined subgroup analysis of patients who are being intubated for severe asthma and chronic obstructive pulmonary disease (COPD). The ventilator was used to measure these values. |
| Mortality | 30 Days or Discharge | Mortality will be assessed at 30 days or at discharge from the hospital, whichever occurs first. This study is not powered to detect a significant difference in mortality, however; this will primarily be a safety study comparing the use ketamine versus etomidate as sedative agents for rapid sequence intubation (RSI) in the Emergency Department (ED). |
| Number of Patients With Hypotension | up to 6 hours | The following will be compared between the two groups: * Hypotension in the ED post-intubation * Hypotension within the first 6 hours of the hospital stay, including time spent in the ED Hypotension is defined as a systolic blood pressure less than 90 mm Hg |
Countries
United States
Participant flow
Pre-assignment details
14 patients withdrew consent.
Participants by arm
| Arm | Count |
|---|---|
| Ketamine Subjects in the ketamine arm will receive ketamine for sedation prior to rapid sequence intubation (RSI).
Ketamine: Subjects will receive ketamine for sedation prior to rapid sequence intubation. | 62 |
| Etomidate Subjects in the etomidate arm will receive etomidate for sedation prior to rapid sequence intubation (RSI).
Etomidate: Subjects will receive etomidate for sedation prior to rapid sequence intubation. | 67 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 8 | 6 |
Baseline characteristics
| Characteristic | Etomidate | Total | Ketamine |
|---|---|---|---|
| Age, Continuous | 49 years STANDARD_DEVIATION 19 | 49 years STANDARD_DEVIATION 19 | 49 years STANDARD_DEVIATION 20 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 9 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 36 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 7 Participants | 0 Participants |
| Race (NIH/OMB) White | 37 Participants | 75 Participants | 38 Participants |
| Sex: Female, Male Female | 23 Participants | 48 Participants | 25 Participants |
| Sex: Female, Male Male | 44 Participants | 81 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 62 | 0 / 67 |
| serious Total, serious adverse events | 1 / 62 | 0 / 67 |
Outcome results
Primary
SOFA Score
\*Maximum SOFA score within three hospital days: all patients. SOFA score is the Sequential Organ Failure Assessment. The minimum score is 0, the maximum score is 24, with higher scores indicating higher likelihood of worse outcome.
Time frame: up to 3 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ketamine | SOFA Score | 6.5 units on a scale |
| Etomidate | SOFA Score | 7 units on a scale |
Secondary
Doses of Post-intubation Sedation
The number of bolus doses of sedative administered post-intubation will be compared up to 6 hours (including morphine, dexmedetomidine, propofol , etomidate, ketamine, lorazepam (Ativan), midazolam (Versed), diazepam (Valium), fentanyl, hydromorphone (Dilaudid)). Infusions of these medications will be recorded separately but will not be part of this outcome.
Time frame: up to 6 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ketamine | Doses of Post-intubation Sedation | 1 bolus doses of sedation |
| Etomidate | Doses of Post-intubation Sedation | 1 bolus doses of sedation |
Secondary
Mortality
Mortality will be assessed at 30 days or at discharge from the hospital, whichever occurs first. This study is not powered to detect a significant difference in mortality, however; this will primarily be a safety study comparing the use ketamine versus etomidate as sedative agents for rapid sequence intubation (RSI) in the Emergency Department (ED).
Time frame: 30 Days or Discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ketamine | Mortality | 8 Participants |
| Etomidate | Mortality | 15 Participants |
Secondary
Mortality in Sepsis and Septic Shock
Evaluate mortality for the sub-group diagnosed with sepsis and septic shock, defined as: \- Suspected infection, and at least 2 of 4 systemic inflammatory response syndrome (SIRS) criteria: 1. Temperature \>38C or \<36C 2. Respiratory Rate \>20 or PaCO2 \<32 mmHg 3. Heart Rate \>90 4. White blood cell count \>12,000 or \<4,000, or \> 10% bands Septic shock: defined as sepsis plus either: 1) Systolic blood pressure \<90 after 1L of intravenous fluid or 2) lactate \>=4mmol/L
Time frame: 30 Days
Population: Subgroup of those with sepsis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ketamine | Mortality in Sepsis and Septic Shock | 1 Participants |
| Etomidate | Mortality in Sepsis and Septic Shock | 4 Participants |
Secondary
Number of Patients With First-pass Success
The rate of first pass success, defined as successful tracheal intubation on the first attempt. An attempt is defined as the insertion and subsequent removal of the laryngoscopic device from the patient's mouth, regardless of whether an endotracheal tube was inserted.
Time frame: up to 5 minutes (average time frame)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ketamine | Number of Patients With First-pass Success | 59 Participants |
| Etomidate | Number of Patients With First-pass Success | 60 Participants |
Secondary
Number of Patients With Hypotension
The following will be compared between the two groups: * Hypotension in the ED post-intubation * Hypotension within the first 6 hours of the hospital stay, including time spent in the ED Hypotension is defined as a systolic blood pressure less than 90 mm Hg
Time frame: up to 6 hours
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ketamine | Number of Patients With Hypotension | Hypotension in the first 6 hours of hospitalizatio | 24 Participants |
| Ketamine | Number of Patients With Hypotension | Hypotension in the ED | 16 Participants |
| Etomidate | Number of Patients With Hypotension | Hypotension in the first 6 hours of hospitalizatio | 30 Participants |
| Etomidate | Number of Patients With Hypotension | Hypotension in the ED | 17 Participants |
Secondary
Number of Patients With Post-intubation Hypoxemia
The following will be compared between the two groups: * Hypoxemia and severe hypoxemia in the peri-intubation period. Peri-intubation hypoxemia was defined as during after the 5 minutes immediately after intubation. * Hypoxemia within the first 2 hours intubation Hypoxemia is defined as SpO2 less than 90%. Severe hypoxemia is defined as SpO2 less than 90% for 60 seconds or more.
Time frame: up to 2 hours
Population: Those with oxygen saturation data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ketamine | Number of Patients With Post-intubation Hypoxemia | Peri-intubation hypoxemia | 8 Participants |
| Ketamine | Number of Patients With Post-intubation Hypoxemia | Hypoxemia within 2 h of ICU admission | 1 Participants |
| Etomidate | Number of Patients With Post-intubation Hypoxemia | Peri-intubation hypoxemia | 13 Participants |
| Etomidate | Number of Patients With Post-intubation Hypoxemia | Hypoxemia within 2 h of ICU admission | 5 Participants |
Secondary
Peak and Plateau Pressure
The Peak and plateau pressures will be compared between the two groups, with a pre-defined subgroup analysis of patients who are being intubated for severe asthma and chronic obstructive pulmonary disease (COPD). The ventilator was used to measure these values.
Time frame: up to 30 minutes (average time frame)
Population: Those with peak and plateau pressure available
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ketamine | Peak and Plateau Pressure | Peak pressure | 25 cm water |
| Ketamine | Peak and Plateau Pressure | Plateau Pressure | 16 cm water |
| Etomidate | Peak and Plateau Pressure | Peak pressure | 26 cm water |
| Etomidate | Peak and Plateau Pressure | Plateau Pressure | 17 cm water |