Ketamine Versus Etomidate for Rapid Sequence Intubation

• ClinicalTrials.gov Identifier: NCT01823328
• Recruitment Status: Completed
• First Posted: April 4, 2013
• Results First Posted: May 24, 2019
• Last Update Posted: May 24, 2019
• Sponsor: Hennepin Healthcare Research Institute
• Information provided by (Responsible Party): Hennepin Healthcare Research Institute

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Airway Control; Anesthesia; Intubation; Complication
• Interventions: Drug: Ketamine; Drug: Etomidate
• Enrollment: 143

Participant Flow

Recruitment Details
Pre-assignment Details	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 [1]	62	67
Not Completed	8	6
Reason Not Completed
Withdrawal by Subject	8	6
[1] The number of completions is lower than the number started because of withdrawal by patients.

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 Number of Baseline Participants		62	67	129
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	62 participants	67 participants	129 participants
		49 (20)	49 (19)	49 (19)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	62 participants	67 participants	129 participants
	Female	25 40.3%	23 34.3%	48 37.2%
	Male	37 59.7%	44 65.7%	81 62.8%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	62 participants	67 participants	129 participants
	American Indian or Alaska Native	6 9.7%	3 4.5%	9 7.0%
	Asian	0 0.0%	2 3.0%	2 1.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	18 29.0%	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%	0 0.0%
	Unknown or Not Reported	0 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.
Overall Number of Participants Analyzed	62	67
Median (Inter-Quartile Range); Unit of Measure: units on a scale
	6.5; (5 to 9)	7; (5 to 9)

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.
Overall Number of Participants Analyzed	9	16
Measure Type: Count of Participants; Unit of Measure: Participants
	1 11.1%	4 25.0%

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.
Overall Number of Participants Analyzed	62	67
Measure Type: Count of Participants; Unit of Measure: 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.
Overall Number of Participants Analyzed	62	67
Median (Inter-Quartile Range); Unit of Measure: bolus doses of sedation
	1; (0 to 2)	1; (0 to 2)

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.
Overall Number of Participants Analyzed	59	66
Measure Type: Count of Participants; Unit of Measure: Participants
Peri-intubation hypoxemia	8 13.6%	13 19.7%
Hypoxemia within 2 h of ICU admission	1 1.7%	5 7.6%

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.
Overall Number of Participants Analyzed	62	67
Measure Type: Count of Participants; Unit of Measure: Participants
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.
Overall Number of Participants Analyzed	60	65
Median (Inter-Quartile Range); Unit of Measure: cm water
Peak pressure	25; (23 to 30)	26; (22 to 31)
Plateau Pressure	16; (14 to 20)	17; (16 to 20)

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.
Overall Number of Participants Analyzed	62	67
Measure Type: Count of Participants; Unit of Measure: Participants
	8 12.9%	15 22.4%

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting 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.
All-Cause Mortality
	Ketamine		Etomidate
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Ketamine		Etomidate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/62 (1.61%)		0/67 (0.00%)
Cardiac disorders
Severe hypertension † [1]	1/62 (1.61%)	1	0/67 (0.00%)	0
† Indicates events were collected by systematic assessment; [1] After ketamine administration one patient had severely elevated blood pressure > 200/100 mm Hg
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Ketamine		Etomidate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0.00%)		0/67 (0.00%)

Limitations and 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.

Results Point of Contact

• Name/Title: Audrey Hendrickson
• Organization: Hennepin Healthcare
• Phone: 612-873-9528
• EMail: Audrey.Hendrickson@hcmed.org

• Responsible Party: Hennepin Healthcare Research Institute
• ClinicalTrials.gov Identifier: NCT01823328
• Other Study ID Numbers: HSR 13-3601
• First Submitted: March 28, 2013
• First Posted: April 4, 2013
• Results First Submitted: August 29, 2018
• Results First Posted: May 24, 2019
• Last Update Posted: May 24, 2019