Coronary Artery Bypass Graft Surgery, Coronary Artery Disease, General Anesthetic Drug Allergy
Conditions
Keywords
Xenon, Sevoflurane, Propofol, Total intravenous anaesthesia, Anaesthesia, Coronary artery disease, Coronary artery bypass graft
Brief summary
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.
Detailed description
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).
Interventions
DRUGXenon
Inhaled xenon, maximal inspired concentration of 65%.
DRUGSevoflurane
Inhaled sevoflurane, maximal inspired concentration of 1.8%.
DRUGPropofol
Hourly dose of 2-4 mg/kg
Sponsors
Air Liquide Santé International
Orion Corporation, Orion Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood Level of Troponin I | Sampling performed 24 hours after the end of the surgical procedure | Blood level of troponin I measured by a central laboratory |
| Log-transformed Blood Level of Troponin I | Sampling performed 24 hours after the end of the surgical procedure | Blood level of troponin I measured by a central laboratory |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depth of Anaesthesia | 4 hours | On-line monitoring of depth of anaesthesia from bi-spectral electroencephalogram analysis (BIS monitor) |
| Arterial Oxygen Saturation | 4 hours | Arterial blood gases |
| Haemodynamic Profile | 4 hours | Monitoring of heart rate, arterial blood pressure, central venous pressure. |
| Presence or Absence of Postoperative Delirium | 7 days | Confusion Assessment Method |
| Clinical Laboratory Tests | 7 days | — |
| ECG Abnormalities | 7 days | — |
| Vital Signs | 7 days | — |
| Presence of Absence of Adverse Events, Including Myocardial Infarction | 7 days | — |
Countries
France, Germany, Italy, Netherlands
Contacts
PRINCIPAL_INVESTIGATORJan HOFLAND, MD, PhD
Thorax Centre Erasmus MC, Rotterdam, the Netherlands
Participant flow
Recruitment details
A total of 542 patients were enrolled (509 met the inclusion criteria) from 17 centres in 4 countries; 8 sites in France, 6 sites in Germany, 1 site in Italy and 2 sites in The Netherlands. Date of first enrolment: 20 April 2011 Date of last completed: 05 April 2014
Participants by arm
| Arm | Count |
|---|---|
| Xenon Anesthetic agent before and after CPB: xenon | 161 |
| Sevoflurane Anesthetic agent before and after CPB: sevoflurane | 165 |
| TIVA Anesthetic agent before and after CPB: propofol | 166 |
| Total | 492 |
Baseline characteristics
| Characteristic | Xenon | Sevoflurane | TIVA | Total |
|---|---|---|---|---|
| Age, Continuous | 64.66 years STANDARD_DEVIATION 9.12 | 63.86 years STANDARD_DEVIATION 8.66 | 63.89 years STANDARD_DEVIATION 9.4 | 64.14 years STANDARD_DEVIATION 9.06 |
| BMI | 27.65 kg/m² STANDARD_DEVIATION 3.64 | 27.21 kg/m² STANDARD_DEVIATION 3.68 | 27.78 kg/m² STANDARD_DEVIATION 4 | 27.55 kg/m² STANDARD_DEVIATION 3.78 |
| Region of Enrollment France | 89 participants | 93 participants | 93 participants | 275 participants |
| Region of Enrollment Germany | 57 participants | 57 participants | 58 participants | 172 participants |
| Region of Enrollment Italy | 3 participants | 4 participants | 4 participants | 11 participants |
| Region of Enrollment Netherlands | 12 participants | 11 participants | 11 participants | 34 participants |
| Sex: Female, Male Female | 19 Participants | 25 Participants | 20 Participants | 64 Participants |
| Sex: Female, Male Male | 142 Participants | 140 Participants | 146 Participants | 428 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| other Total, other adverse events | 154 / 178 | 139 / 165 | 143 / 166 |
| serious Total, serious adverse events | 30 / 178 | 24 / 165 | 26 / 166 |
Outcome results
Primary
Blood Level of Troponin I
Blood level of troponin I measured by a central laboratory
Time frame: Sampling performed 24 hours after the end of the surgical procedure
Population: The primary analysis was a non-inferiority comparison between Xenon and Sevoflurane and was performed on the Per Protocol (PP) Set composed of all randomised and treated patients with no major protocol deviations during the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Xenon | Blood Level of Troponin I | 2.16 ng/mL |
| Sevoflurane | Blood Level of Troponin I | 2.57 ng/mL |
p-value: 0.0295% CI: [-1.27, 0.47]ANCOVA
Primary
Log-transformed Blood Level of Troponin I
Blood level of troponin I measured by a central laboratory
Time frame: Sampling performed 24 hours after the end of the surgical procedure
Population: The non-inferiority comparison between Xenon and Sevoflurane was repeated using log-transformed blood troponin levels on the PP Set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Xenon | Log-transformed Blood Level of Troponin I | 0.30 ng/mL |
| Sevoflurane | Log-transformed Blood Level of Troponin I | 0.39 ng/mL |
Comparison: As the residuals from the primary ANCOVA model were non-normal and skewed, the non-inferiority analysis was repeated using log-transformed blood troponin levels.p-value: 0.018695% CI: [-0.3, 0.11]ANCOVA
Secondary
Arterial Oxygen Saturation
Arterial blood gases
Time frame: 4 hours
Secondary
Clinical Laboratory Tests
Time frame: 7 days
Secondary
Depth of Anaesthesia
On-line monitoring of depth of anaesthesia from bi-spectral electroencephalogram analysis (BIS monitor)
Time frame: 4 hours
Secondary
ECG Abnormalities
Time frame: 7 days
Secondary
Haemodynamic Profile
Monitoring of heart rate, arterial blood pressure, central venous pressure.
Time frame: 4 hours
Secondary
Presence of Absence of Adverse Events, Including Myocardial Infarction
Time frame: 7 days
Secondary
Presence or Absence of Postoperative Delirium
Confusion Assessment Method
Time frame: 7 days
Secondary
Vital Signs
Time frame: 7 days