Adrenal Insufficiency
Conditions
Keywords
adrenal insufficiency, etomidate, rapid sequence induction
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.
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.
Interventions
DRUGRSI sedation with etomidate/succinylcholine
etomidate 0.3 mg/kg IV plus succinylcholine 1 mg/kg IV
DRUGRSI sedation with fentanyl/midazolam/succinylcholine
100 micrograms fentanyl IV, plus 5 mg midazolam IV, plus 1 mg/kg succinylcholine IV
Sponsors
University of Tennessee
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cortisol Level 60 Minutes After Cortisol Stimulating Test (CST) | 60 minutes after administration of cotrosyn | — |
| 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 | — |
| Postintubation Cortisol (Baseline Cortisol Level) | postintubation (baseline cortisol level) | cortisol level after randomization and rapid sequence induction |
| 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital Length of Stay | time to hospital discharge in days | days from admission to hospital discharge |
| 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 |
| Ventilator Days | time from intubation to extubation | — |
| Number of Deaths | death in hospital | deaths |
Countries
United States
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 details
72 hour waiver of consent granted by the Institutional Review Board (IRB)
Participants by arm
| Arm | Count |
|---|---|
| Etomidate Etomidate Group patients were randomized to receive etomidate 0.3mg/kg IV plus succinylcholine 1mg/kg IV for RSI medications | 18 |
| 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. | 12 |
| Total | 30 |
Baseline characteristics
| Characteristic | Fentanyl-Midazolam | Etomidate | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0.0 Participants |
| Age, Categorical >=65 years | 2 Participants | 4 Participants | 6.0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 14 Participants | 24.0 Participants |
| Age Continuous | 43.9 years STANDARD_DEVIATION 19.5 | 41.8 years STANDARD_DEVIATION 24.5 | 42.6 years STANDARD_DEVIATION 22.3 |
| Region of Enrollment United States | 12 participants | 18 participants | 30.0 participants |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 11.0 Participants |
| Sex: Female, Male Male | 9 Participants | 10 Participants | 19.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 18 | 0 / 12 |
| serious Total, serious adverse events | 2 / 18 | 0 / 12 |
Outcome results
Primary
Change in Baseline Cortisol
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etomidate | Change in Baseline Cortisol | -12.8 micrograms/dL | Standard Deviation 9.6 |
| Fentanyl-Midazolam | Change in Baseline Cortisol | 1.1 micrograms/dL | Standard Deviation 7.6 |
p-value: 0.003t-test, 2 sided
Primary
Cortisol Level 60 Minutes After Cortisol Stimulating Test (CST)
Time frame: 60 minutes after administration of cotrosyn
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etomidate | Cortisol Level 60 Minutes After Cortisol Stimulating Test (CST) | 22.91 micrograms/dL | Standard Deviation 10.4 |
| Fentanyl-Midazolam | Cortisol Level 60 Minutes After Cortisol Stimulating Test (CST) | 39.09 micrograms/dL | Standard Deviation 10.8 |
p-value: <0.001t-test, 2 sided
Primary
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
Primary
Postintubation Cortisol (Baseline Cortisol Level)
cortisol level after randomization and rapid sequence induction
Time frame: postintubation (baseline cortisol level)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etomidate | Postintubation Cortisol (Baseline Cortisol Level) | 18.2 micrograms/dL | Standard Deviation 8.4 |
| Fentanyl-Midazolam | Postintubation Cortisol (Baseline Cortisol Level) | 27.9 micrograms/dL | Standard Deviation 13.4 |
Comparison: Normality was tested using the Kolmogorow-Smirnov test.p-value: 0.022t-test, 2 sided
Secondary
Hospital Length of Stay
days from admission to hospital discharge
Time frame: time to hospital discharge in days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etomidate | Hospital Length of Stay | 13.9 days | Standard Deviation 9.5 |
| Fentanyl-Midazolam | Hospital Length of Stay | 6.4 days | Standard Deviation 4.4 |
p-value: 0.007t-test, 2 sided
Secondary
Intensive Care Unit (ICU) Length of Stay
ICU length of stay in days
Time frame: time from hospital admission to transfer out of ICU to floor bed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etomidate | Intensive Care Unit (ICU) Length of Stay | 8.1 days | Standard Deviation 7.2 |
| Fentanyl-Midazolam | Intensive Care Unit (ICU) Length of Stay | 3.0 days | Standard Deviation 2.4 |
p-value: 0.011t-test, 2 sided
Secondary
Number of Deaths
deaths
Time frame: death in hospital
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etomidate | Number of Deaths | 2 participants |
| Fentanyl-Midazolam | Number of Deaths | 0 participants |
Secondary
Ventilator Days
Time frame: time from intubation to extubation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etomidate | Ventilator Days | 6.3 days | Standard Deviation 6.5 |
| Fentanyl-Midazolam | Ventilator Days | 1.5 days | Standard Deviation 0.8 |
p-value: 0.007t-test, 2 sided