TEAM-Project: Trial on the Effect of Anesthetics on Morbidity and Mortality

Study Overview
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Brief Summary
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Volatile anesthetics may provide some protection from myocardial ischemia, an effect called anesthetic preconditioning. In patients undergoing coronary artery bypass surgery, this preconditioning effect resulted in better cardiac performance, faster recovery and lower morbidity and mortality. The investigators will perform a prospective randomized multi-center study to compare volatile with total intravenous anesthesia in patients at a high cardiac risk who undergo major non-cardiac surgery.

Detailed Description
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Basic research and animal studies have detected that volatile anesthetics provide some protection from myocardial ischemia, an effect called anesthetic preconditioning. Recent clinical studies have found that this preconditioning effect is of clinical relevance in patients undergoing coronary artery bypass surgery, resulting in better cardiac function and faster recovery after surgery, and in lower one-year morbidity. In patients undergoing non cardiac surgery, cardiac complications also are the major cause of perioperative morbidity and mortality. Myocardial ischemia frequently occurs during and immediately after non cardiac surgery in patients with coronary artery disease, and is a strong predictor of subsequent cardiac complications and death. Whether or not volatile anesthetics also provide clinically relevant protection from perioperative ischemia and subsequent cardiac complications in patients undergoing non cardiac surgery is unknown. Therefore, we will perform a prospective, randomized multi-center study to compare volatile with total intravenous anesthesia in patients at high cardiac risk who undergo major non cardiac surgery. We hypothesize that the use of a volatile anesthetic will reduce the incidence of perioperative ischaemia and myocardial injury, as indicated primarily by less ST-segment changes in the Holter ECG and, if there will be an effect, secondarily by lower incidences of elevated troponin T and NT-pro-BNP levels. And we hypothesize that the use of a volatile anesthetic will reduce the one-year incidence of cardiac complications and all cause mortality after surgery. The results of this study may apply to a huge percentage of surgical patients because coronary artery disease is the clinically most relevant co-morbidity, and its prevalence is expected to increase with the steadily increasing number of surgical patients aged 65 yr and older.

Official Title
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Multi-Center Trial on the Effect of Anesthetics on Morbidity and Mortality in Patients Undergoing Major Non-cardiac Surgery

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Inhalational anesthetic
* Drug: Intravenous anesthetic, propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients scheduled for a non-cardiac surgical procedure of high or intermediate cardiac risk are eligible if they have documented coronary artery disease (CAD) or are at high risk of CAD. Exclusion Criteria: Ongoing medication with sulfonylurea derivatives (unless stopped ≥ 2 days before surgery) or theophylline Emergency surgery Unstable angina pectoris Preoperative hemodynamic instability Severe hepatic disease Renal insufficiency (creatinine clearance < 30 ml/min) Severe chronic obstructive pulmonary disease (forced expiratory volume in 1 second [FEV1] < 1 litre) Absence of written patient consent

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Inhalational anesthetic<br>Sevoflurane will be used as the main anesthetic in this arm, and no propofol will be administered | Drug: Inhalational anesthetic<br>* Sevoflurane, dosage according to the physician in charge<br>* Other names: Sevorane;|
| Active Comparator: Intravenous anesthetic, propofol<br>Propofol will be used as the main anesthetic in this arm, and no inhalational anesthetic will be administered | Drug: Intravenous anesthetic, propofol<br>* Propofol, dosage according to the physician in charge<br>* Other names: Diprovan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ischemia (Holter-electrocardiogram [ECG], troponin T, ECG) |  | 7 days postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Congestive heart failure (N-terminal B-type natriuretic peptide [NT-pro-BNP]) |  | 2 days postoperatively | 
| influence of genetic polymorphism on cardiac morbidity and mortality |  | 7 days, 6 and 12 months | 
| cardiac morbidity and mortality |  | 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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preconditioning, cardiac protection, morbidity, mortality, major non-cardiac surgery, cardiac mortality and morbidity, high cardiac perioperative risk