Effect of Etomidate on Hemodynamics and Adrenocortical Function After Cardiac Surgery

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of a single dose of etomidate for patients undergoing cardiac surgery with the use of cardiopulmonary bypass (CPB) on post-CPB adrenocortical responsiveness, on requirements of hemodynamic support, and on use of intensive care resources.

Official Title
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Effect of an Anesthetic Induction Dose of Etomidate on Hemodynamics and Adrenocortical Function After Cardiac Surgery

Conditions
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Coronary Artery Disease, Mitral Valve Regurgitation

Intervention / Treatment
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* Drug: Etomidate
* Drug: Propofol
* Drug: Hydrocortisone
* Drug: NaCl 0.9%
* Other: Tetracosactin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients undergoing elective coronary artery bypass graft (primary or re-operation) mitral valve reconstruction/replacement for mitral valve regurgitation Age between 18 and 80 years (extremes included) Subject itself has signed the informed consent No clinically relevant deviation from the laboratory's reference range of biochemistry, hematology, or urinalysis testing Exclusion Criteria: Participation in another ongoing interventional trial Known adrenocortical insufficiency Use of etomidate or propofol within 1 week preoperatively Use of glucocorticoids within 6 month preoperatively Known sensitivity to etomidate, propofol, or emulgator Severe hepatic dysfunction (bilirubin > 3mg/dl) Severe renal dysfunction (plasma creatinine > 180mikromol/l) Sepsis, endocarditis or other chronic inflammatory disease Manifest insulin-dependent diabetes mellitus Positive HIV serology Hemodynamically significant carotid stenosis requiring treatment Serious illnesses: endocrine, neurological, psychiatric, metabolic disturbances Pregnancy or breast-feeding female; females will be subject to pregnancy testing Requirement of rapid sequence induction Emergency surgery History of asthma

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Etomidate as a single induction dose | Drug: Etomidate<br>* Single induction dose of etomidate 0.2%; total dose 0.15 mg/kg<br>|
| Active Comparator: 2<br>Propofol as a single induction dose | Drug: Propofol<br>* Single induction dose of propofol 2%; total dose 1.5 mg/kg<br>|
| Other: 3<br>Hydrocortisone substitution or placebo (50-50%) in etomidate-group | Drug: Hydrocortisone<br>* Hydrocortisone 100 mg/2 ml: day of operation 3x, POD 1 2x, POD 2 1x<br>Drug: NaCl 0.9%<br>* NaCl 0.9% 2 ml; day of operation 3x, POD 1 2x, POD 2 1x<br>Other: Tetracosactin<br>* Diagnostic test, Tetracosactin 250 microg iv<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of absolute and relative adrenal insufficiency |  | Preoperative day to postoperative day (POD) 4 | 
| Cumulative requirements of vasoactive drugs during surgery and in the intensive care unit (ICU) |  | Induction of anesthesia to POD 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of failure to wean off cardiopulmonary bypass on first intention |  | intraoperatively | 
| Serum lactate |  | Induction of anesthesia to discharge ICU | 
| Time to extubation |  | Induction of anesthesia to extubation | 
| Length of stay (LOS) in the intensive care unit (ICU), intermediate care unit (IMC), and hospital |  | Admission to discharge: ICU, IMC, and hospital | 
| Association of results with preoperative risk, stress-dose hydrocortisone replacement, type of surgery |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Etomidate, Propofol, Adrenocortical Insufficiency, Hemodynamic Process, Vasoactive Agonists, Coronary Artery Bypass, Ischemic Coronary Heart Disease, Mitral valve reconstruction/replacement, Mitral valve regurgitation, Heart Valve Prosthesis, Cardiopulmonary Bypass