Xenon Compared to Sevoflurane and Total Intravenous Anaesthesia for Coronary Artery Bypass Graft Surgery

• Blood Level of Troponin I [ Time Frame: Sampling performed 24 hours after the end of the surgical procedure ] [ Designated as safety issue: No ]
  Blood level of troponin I measured by a central laboratory
• Log-transformed Blood Level of Troponin I [ Time Frame: Sampling performed 24 hours after the end of the surgical procedure ] [ Designated as safety issue: No ]
  Blood level of troponin I measured by a central laboratory

• Depth of Anaesthesia [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
  On-line monitoring of depth of anaesthesia from bi-spectral electroencephalogram analysis (BIS monitor)
• Arterial Oxygen Saturation [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
  Arterial blood gases
• Haemodynamic Profile [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
  Monitoring of heart rate, arterial blood pressure, central venous pressure.
• Presence or Absence of Postoperative Delirium [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  Confusion Assessment Method
• Clinical Laboratory Tests [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
• ECG Abnormalities [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
• Vital Signs [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
• Presence of Absence of Adverse Events, Including Myocardial Infarction [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]

Xenon is a gaseous anaesthetic agent registered in several European countries. It has been administered safely during cardiac surgery in pilot studies. In animal studies, xenon decreases the size of experimental myocardial infarction.

This 3-arm study will compare xenon, sevoflurane and a propofol-based total intravenous anaesthesia for maintenance of anaesthesia during coronary artery bypass graft surgery conducted with extra-corporeal circulation. Xenon and sevoflurane will be administered before and after extracorporeal circulation. Propofol will be administered during extracorporeal circulation in the three groups of patients.

The study will compare the postoperative myocardial damage observed 24 hours after surgery from blood levels of troponin I, a largely accepted biomarker of myocardial necrosis. The main hypothesis is that the myocardial damage observed after xenon administration will not be superior to the damage observed after sevoflurane administration (non-inferiority). The second hypothesis is that the myocardial damage observed after xenon administration will be inferior to the damage observed after total intravenous anaesthesia.

• Coronary Artery Disease
• General Anesthetic Drug Allergy
• Coronary Artery Bypass Graft Surgery

• Drug: Xenon
  Inhaled xenon, maximal inspired concentration of 65%.
• Drug: Sevoflurane
  Inhaled sevoflurane, maximal inspired concentration of 1.8%.
• Drug: Propofol
  Hourly dose of 2-4 mg/kg

• Experimental: Xenon
  Intervention: Drug: Xenon
• Active Comparator: Sevoflurane
  Intervention: Drug: Sevoflurane
• Active Comparator: Total intravenous anaesthesia
  Intervention: Drug: Propofol

Inclusion Criteria:

• coronary artery disease
• elective surgery, planned coronary artery bypass graft
• moderate hypothermia or normothermia
• cardiac arrest cold and warm cardioplegia
• normal of moderately impaired left ventricular systolic function
• written informed consent

Exclusion Criteria:

• pregnancy or child bearing potential
• ongoing treatment with nicorandil or sulfonylurea medication
• severe renal or hepatic dysfunction
• ongoing myocardial infarction or unstable angina