Evaluation of Etomidate on Adrenal Function in Trauma Patients

• Sponsor: University of Tennessee (Other)
• Overall Status: Completed
• CT.gov ID: NCT00462644
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 7
• Patients Per Site Per Month: 4.3

Study Details

Study Description

Brief Summary

Trauma patients are at increased risk for adrenal function insufficiency. A commonly used agent for rapid sequence intubation (RSI) is known to decrease adrenal function. We want to determine the incidence of adrenocortical insufficiency and its significance during the first 24 hours of resuscitation following RSI in trauma patients.

Condition or Disease	Intervention/Treatment	Phase
Adrenal Insufficiency	Drug: RSI sedation with etomidate/succinylcholine; Drug: RSI sedation with fentanyl/midazolam/succinylcholine	N/A

Detailed Description

The study will have two arms. Patients on one arm will be assigned to receive etomidate (0.3 mg/kg) and succinylcholine (1mg/kg) for RSI. Patients on the other arm will receive standard therapy at this institution which consists of Versed (generic name midazolam) (5 mg) plus fentanyl (100 mcgs) as well as succinylcholine for RSI. Both drug regimens have a rapid onset, short duration and short half-life.

Patients will be randomly assigned to one arm of the study. The trauma nurse emergency room responders, intensive care unit staff, or helicopter crew will pull a study envelope which will contain a randomization to either the etomidate arm or standard therapy arm. The numbers will correspond to a log, delineating which medication is given. The nurse will document the medication as RSI Study Drug - etomidate or RSI Study Drug - standard and the randomization packet number (ie, RSI Study Drug, etomidate, #1, RSI Study Drug, standard, #2, etc.) and will document the patient's name and medical record number on the study log in either the helicopter or the ER Resuscitation Bay.

Baseline cortisol level will be drawn prior to RSI. An additional cortisol level will be drawn 4-6 hours later. Following this level, a cortrosyn stimulation test will be performed by giving 0.25 mg cortrosyn IV and rechecking a cortisol level in 60 minutes. Adrenal insufficiency will be defined as a baseline cortisol level of <15 or an increase in cortisol of <9 after cortrosyn administration. Patients will be monitored for 24 hours for hemodynamics, IV fluid administration , and use of vasopressors. Patient will be resuscitated to adequate mean arterial blood pressure and urine output. Any patient found to be adrenal insufficient will be treated with hydrocortisone 50 mg IV every 6 hours.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Single Dose of Etomidate During Rapid Sequence Induction in Trauma Patients Causes Significant Adrenocortical Insufficiency: A Prospective Randomized Study
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Aug 1, 2006
• Actual Study Completion Date: Sep 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Etomidate Etomidate Group patients were randomized to receive etomidate 0.3mg/kg IV plus succinylcholine 1mg/kg IV for RSI medications	Drug: RSI sedation with etomidate/succinylcholine; etomidate 0.3 mg/kg IV plus succinylcholine 1 mg/kg IV
Active Comparator: Fentanyl-Midazolam Fentanyl-Midazolam Group patients were randomized to receive 100ug fentanyl IV, plus 5 mg midazolam IV, plus 1mg/kg succinylcholine IV for RSI medications.	Drug: RSI sedation with fentanyl/midazolam/succinylcholine; 100 micrograms fentanyl IV, plus 5 mg midazolam IV, plus 1 mg/kg succinylcholine IV

Outcome Measures

Primary Outcome Measures

1. Cortisol Levels Pre and Post Rapid Sequence Induction and Cortisol Stimulation Test [pre RSI, 4-6 hours post RSI, and again 60 mins later following ACTH stimulation test]

2. Postintubation Cortisol (Baseline Cortisol Level) [postintubation (baseline cortisol level)]

   cortisol level after randomization and rapid sequence induction

3. Change in Baseline Cortisol [4-6hr after RSI]

   change from baseline cortisol (drawn prior to RSI) to 2nd cortisol level (4-6hrs after RSI, but before stim test)

4. Cortisol Level 60 Minutes After Cortisol Stimulating Test (CST) [60 minutes after administration of cotrosyn]

Secondary Outcome Measures

1. Hospital Length of Stay [time to hospital discharge in days]

   days from admission to hospital discharge

2. Intensive Care Unit (ICU) Length of Stay [time from hospital admission to transfer out of ICU to floor bed]

   ICU length of stay in days

3. Ventilator Days [time from intubation to extubation]

4. Number of Deaths [death in hospital]

   deaths

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Trauma mechanism of injury

• Patient requires rapid sequence induction for ventilatory support

Exclusion Criteria:

• <18 years old

• Prisoners

• Pregnant women

• Patients with a history of adrenal insufficiency

• Patients with adrenal trauma documented by CT scan

• Patients receiving corticosteroids in the previous year

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Erlanger Medical Center	Chattanooga	Tennessee	United States	37403

Sponsors and Collaborators

• University of Tennessee

Investigators

• Principal Investigator: Vicente A Mejia, MD, University of Tennessee

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00462644
• Other Study ID Numbers: 05-050
• First Posted: Apr 19, 2007
• Last Update Posted: Feb 23, 2010
• Last Verified: Feb 1, 2010

• Keywords provided by , ,: adrenal insufficiency; etomidate; rapid sequence induction
• Additional relevant MeSH terms: Adrenal Insufficiency; Fentanyl; Midazolam; Etomidate; Succinylcholine

Study Results

Participant Flow

Recruitment Details	Adult trauma patients admitted to Erlanger Health System's Level I trauma center requiring rapid sequence induction were randomized to one of two approved drug treatment regimens.
Pre-assignment Detail	72 hour waiver of consent granted by the Institutional Review Board (IRB)

Arm/Group Title	Etomidate	Fentanyl-Midazolam
Arm/Group Description	Etomidate Group patients were randomized to receive etomidate 0.3mg/kg IV plus succinylcholine 1mg/kg IV for RSI medications	Fentanyl-Midazolam Group patients were randomized to receive 100ug fentanyl IV, plus 5 mg midazolam IV, plus 1mg/kg succinylcholine IV for RSI medications.
Period Title: Overall Study
STARTED	18	12
COMPLETED	18	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Etomidate	Fentanyl-Midazolam	Total
Arm/Group Description	Etomidate Group patients were randomized to receive etomidate 0.3mg/kg IV plus succinylcholine 1mg/kg IV for RSI medications	Fentanyl-Midazolam Group patients were randomized to receive 100ug fentanyl IV, plus 5 mg midazolam IV, plus 1mg/kg succinylcholine IV for RSI medications.	Total of all reporting groups
Overall Participants	18	12	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0.0 0%
Between 18 and 65 years	14 77.8%	10 83.3%	24.0 80%
>=65 years	4 22.2%	2 16.7%	6.0 20%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.8 (24.5)	43.9 (19.5)	42.6 (22.3)
Sex: Female, Male (Count of Participants)
Female	8 44.4%	3 25%	11.0 36.7%
Male	10 55.6%	9 75%	19.0 63.3%
Region of Enrollment (participants) [Number]
United States	18 100%	12 100%	30.0 100%

Outcome Measures

1. Primary Outcome

Title	Cortisol Levels Pre and Post Rapid Sequence Induction and Cortisol Stimulation Test
Time Frame	pre RSI, 4-6 hours post RSI, and again 60 mins later following ACTH stimulation test

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

2. Secondary Outcome

Title	Hospital Length of Stay
Description	days from admission to hospital discharge
Time Frame	time to hospital discharge in days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etomidate	Fentanyl-Midazolam
Arm/Group Description	Etomidate Group patients were randomized to receive etomidate 0.3mg/kg IV plus succinylcholine 1mg/kg IV for RSI medications	Fentanyl-Midazolam Group patients were randomized to receive 100ug fentanyl IV, plus 5 mg midazolam IV, plus 1mg/kg succinylcholine IV for RSI medications.
Measure Participants	18	12
Mean (Standard Deviation) [days]	13.9 (9.5)	6.4 (4.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etomidate, Fentanyl-Midazolam
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Intensive Care Unit (ICU) Length of Stay
Description	ICU length of stay in days
Time Frame	time from hospital admission to transfer out of ICU to floor bed

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etomidate	Fentanyl-Midazolam
Arm/Group Description	Etomidate Group patients were randomized to receive etomidate 0.3mg/kg IV plus succinylcholine 1mg/kg IV for RSI medications	Fentanyl-Midazolam Group patients were randomized to receive 100ug fentanyl IV, plus 5 mg midazolam IV, plus 1mg/kg succinylcholine IV for RSI medications.
Measure Participants	18	12
Mean (Standard Deviation) [days]	8.1 (7.2)	3.0 (2.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etomidate, Fentanyl-Midazolam
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Ventilator Days
Time Frame	time from intubation to extubation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etomidate	Fentanyl-Midazolam
Arm/Group Description	Etomidate Group patients were randomized to receive etomidate 0.3mg/kg IV plus succinylcholine 1mg/kg IV for RSI medications	Fentanyl-Midazolam Group patients were randomized to receive 100ug fentanyl IV, plus 5 mg midazolam IV, plus 1mg/kg succinylcholine IV for RSI medications.
Measure Participants	18	12
Mean (Standard Deviation) [days]	6.3 (6.5)	1.5 (0.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etomidate, Fentanyl-Midazolam
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	t-test, 2 sided
	Comments

5. Primary Outcome

Title	Postintubation Cortisol (Baseline Cortisol Level)
Description	cortisol level after randomization and rapid sequence induction
Time Frame	postintubation (baseline cortisol level)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etomidate	Fentanyl-Midazolam
Arm/Group Description	Etomidate Group patients were randomized to receive etomidate 0.3mg/kg IV plus succinylcholine 1mg/kg IV for RSI medications	Fentanyl-Midazolam Group patients were randomized to receive 100ug fentanyl IV, plus 5 mg midazolam IV, plus 1mg/kg succinylcholine IV for RSI medications.
Measure Participants	18	12
Mean (Standard Deviation) [micrograms/dL]	18.2 (8.4)	27.9 (13.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etomidate, Fentanyl-Midazolam
	Comments	Normality was tested using the Kolmogorow-Smirnov test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.022
	Comments
	Method	t-test, 2 sided
	Comments

6. Primary Outcome

Title	Change in Baseline Cortisol
Description	change from baseline cortisol (drawn prior to RSI) to 2nd cortisol level (4-6hrs after RSI, but before stim test)
Time Frame	4-6hr after RSI

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etomidate	Fentanyl-Midazolam
Arm/Group Description	Etomidate Group patients were randomized to receive etomidate 0.3mg/kg IV plus succinylcholine 1mg/kg IV for RSI medications	Fentanyl-Midazolam Group patients were randomized to receive 100ug fentanyl IV, plus 5 mg midazolam IV, plus 1mg/kg succinylcholine IV for RSI medications.
Measure Participants	18	12
Mean (Standard Deviation) [micrograms/dL]	-12.8 (9.6)	1.1 (7.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etomidate, Fentanyl-Midazolam
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	t-test, 2 sided
	Comments

7. Primary Outcome

Title	Cortisol Level 60 Minutes After Cortisol Stimulating Test (CST)
Time Frame	60 minutes after administration of cotrosyn

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etomidate	Fentanyl-Midazolam
Arm/Group Description	Etomidate Group patients were randomized to receive etomidate 0.3mg/kg IV plus succinylcholine 1mg/kg IV for RSI medications	Fentanyl-Midazolam Group patients were randomized to receive 100ug fentanyl IV, plus 5 mg midazolam IV, plus 1mg/kg succinylcholine IV for RSI medications.
Measure Participants	18	12
Mean (Standard Deviation) [micrograms/dL]	22.91 (10.4)	39.09 (10.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Etomidate, Fentanyl-Midazolam
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 2 sided
	Comments

8. Secondary Outcome

Title	Number of Deaths
Description	deaths
Time Frame	death in hospital

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Etomidate	Fentanyl-Midazolam
Arm/Group Description	Etomidate Group patients were randomized to receive etomidate 0.3mg/kg IV plus succinylcholine 1mg/kg IV for RSI medications	Fentanyl-Midazolam Group patients were randomized to receive 100ug fentanyl IV, plus 5 mg midazolam IV, plus 1mg/kg succinylcholine IV for RSI medications.
Measure Participants	18	12
Number [participants]	2 11.1%	0 0%

Adverse Events

Time Frame	from intubation until hospital discharge
Adverse Event Reporting Description	Two deaths occurred during hospitalization, but were not due to any study procedures. Deaths were due to trauma injuries sustained in conjunction with pre-existing conditions.
Arm/Group Title	Etomidate		Fentanyl-Midazolam
Arm/Group Description	Etomidate Group patients were randomized to receive etomidate 0.3mg/kg IV plus succinylcholine 1mg/kg IV for RSI medications		Fentanyl-Midazolam Group patients were randomized to receive 100ug fentanyl IV, plus 5 mg midazolam IV, plus 1mg/kg succinylcholine IV for RSI medications.
All Cause Mortality
	Etomidate		Fentanyl-Midazolam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Etomidate		Fentanyl-Midazolam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/18 (11.1%)		0/12 (0%)
Cardiac disorders
death	2/18 (11.1%)	2	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	Etomidate		Fentanyl-Midazolam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/12 (0%)

Limitations/Caveats

Small trial most likely underpowered; large number of exclusions; other limitations discussed in published paper (PMID: 18784570).

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.