Ketamine Versus Etomidate for Rapid Sequence Intubation

• Sponsor: Hennepin Healthcare Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01823328
• Collaborator: (none)
• Enrollment: 143
• Location: 1
• Arms: 2
• Duration (Months): 25
• Patients Per Site Per Month: 5.7

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effectiveness and safety of ketamine and etomidate during rapid sequence intubation (RSI).

Condition or Disease	Intervention/Treatment	Phase
Airway Control; Anesthesia; Intubation; Complication	Drug: Ketamine; Drug: Etomidate	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 143 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Ketamine Versus Etomidate for Sedation of Emergency Department Patients During Rapid Sequence Intubation
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ketamine Subjects in the ketamine arm will receive ketamine for sedation prior to rapid sequence intubation (RSI).	Drug: Ketamine; Subjects will receive ketamine for sedation prior to rapid sequence intubation.; Other Names: Ketanest Ketaset Ketalar
Active Comparator: Etomidate Subjects in the etomidate arm will receive etomidate for sedation prior to rapid sequence intubation (RSI).	Drug: Etomidate; Subjects will receive etomidate for sedation prior to rapid sequence intubation.; Other Names: Amidate

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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: Temperature >38C or <36C Respiratory Rate >20 or PaCO2 <32 mmHg Heart Rate >90 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

2. 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.

3. 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.

4. 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.

5. 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

6. 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.

7. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415

Sponsors and Collaborators

• Hennepin Healthcare Research Institute

Investigators

• Principal Investigator: Brian E Driver, MD, Hennepin County Medical Canter

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hennepin Healthcare Research Institute
• ClinicalTrials.gov Identifier: NCT01823328
• Other Study ID Numbers: HSR 13-3601
• First Posted: Apr 4, 2013
• Last Update Posted: May 24, 2019
• Last Verified: May 1, 2019

• Keywords provided by Hennepin Healthcare Research Institute: Intubation; Airway; Emergent intubation; Rapid sequence intubation; Rapid sequence induction; RSI; Ketamine; Etomidate; Sepsis; Sedative; Sedation
• Additional relevant MeSH terms: Ketamine; Etomidate

Study Results

Participant Flow

Pre-assignment Detail	14 patients withdrew consent.

Arm/Group Title	Ketamine	Etomidate
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	70	73
COMPLETED	62	67
NOT COMPLETED	8	6

Baseline Characteristics

Arm/Group Title	Ketamine	Etomidate	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	62	67	129
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49 (20)	49 (19)	49 (19)
Sex: Female, Male (Count of Participants)
Female	25 40.3%	23 34.3%	48 37.2%
Male	37 59.7%	44 65.7%	81 62.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	6 9.7%	3 4.5%	9 7%
Asian	0 0%	2 3%	2 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	18 29%	18 26.9%	36 27.9%
White	38 61.3%	37 55.2%	75 58.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	7 10.4%	7 5.4%

Outcome Measures

1. Primary Outcome

Title	SOFA Score
Description	*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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine	Etomidate
Arm/Group Description	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.	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.
Measure Participants	62	67
Median (Inter-Quartile Range) [units on a scale]	6.5	7

2. Secondary Outcome

Title	Mortality in Sepsis and Septic Shock
Description	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: Temperature >38C or <36C Respiratory Rate >20 or PaCO2 <32 mmHg Heart Rate >90 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

Outcome Measure Data

Analysis Population Description

Subgroup of those with sepsis

Arm/Group Title	Ketamine	Etomidate
Arm/Group Description	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.	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.
Measure Participants	9	16
Count of Participants [Participants]	1 1.6%	4 6%

3. Secondary Outcome

Title	Number of Patients With First-pass Success
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine	Etomidate
Arm/Group Description	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.	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.
Measure Participants	62	67
Count of Participants [Participants]	59 95.2%	60 89.6%

4. Secondary Outcome

Title	Doses of Post-intubation Sedation
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine	Etomidate
Arm/Group Description	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.	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.
Measure Participants	62	67
Median (Inter-Quartile Range) [bolus doses of sedation]	1	1

5. Secondary Outcome

Title	Number of Patients With Post-intubation Hypoxemia
Description	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

Outcome Measure Data

Analysis Population Description

Those with oxygen saturation data

Arm/Group Title	Ketamine	Etomidate
Arm/Group Description	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.	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.
Measure Participants	59	66
Peri-intubation hypoxemia	8 12.9%	13 19.4%
Hypoxemia within 2 h of ICU admission	1 1.6%	5 7.5%

6. Secondary Outcome

Title	Number of Patients With Hypotension
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine	Etomidate
Arm/Group Description	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.	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.
Measure Participants	62	67
Hypotension in the first 6 hours of hospitalizatio	24 38.7%	30 44.8%
Hypotension in the ED	16 25.8%	17 25.4%

7. Secondary Outcome

Title	Peak and Plateau Pressure
Description	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)

Outcome Measure Data

Analysis Population Description

Those with peak and plateau pressure available

Arm/Group Title	Ketamine	Etomidate
Arm/Group Description	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.	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.
Measure Participants	60	65
Peak pressure	25	26
Plateau Pressure	16	17

8. Secondary Outcome

Title	Mortality
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine	Etomidate
Arm/Group Description	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.	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.
Measure Participants	62	67
Count of Participants [Participants]	8 12.9%	15 22.4%

Adverse Events

Arm/Group Title	Ketamine		Etomidate
Arm/Group Description	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.		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.
All Cause Mortality
	Ketamine		Etomidate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ketamine		Etomidate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/62 (1.6%)		0/67 (0%)
Cardiac disorders
Severe hypertension	1/62 (1.6%)	1	0/67 (0%)	0
Other (Not Including Serious) Adverse Events
	Ketamine		Etomidate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/67 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.