Anaesthesia
Conditions
Keywords
Xenon in Anaesthesia
Brief summary
The purpose of this study is to evaluate the quantity of propofol administered with Xenon in two inspiratory concentrations, to maintain comparable depth of anaesthesia during the maintenance period of general anaesthesia.
Detailed description
The inert or noble gas Xenon has anaesthetic properties that have been recognized 50 years ago. Several preclinical studies and investigations using xenon as an inhalational anaesthetic in humans were performed and reported that this gas has many properties of the ideal anaesthetic agent. Moreover, it is known that when xenon is combined with volatile anaesthetics or opioids, the required doses of those substances are reduced, resulting in a lower incidence of side effects. Patients could benefit from the administration of xenon if this inspired concentration would result in reduced doses of co-administered drugs. This trial should allow evaluating the propofol consumption required in combination with xenon administered in inspiratory concentrations of 50% and 70% to maintain comparable depth of general anaesthesia as total i.v. anaesthesia, in ASA III patients presenting increased risk of perioperative cardiac complications and undergoing laparotomy or orthopaedic surgery.
Interventions
DRUGXenon
Maintenance of anaesthesia obtained with Xenon 50% and propofol infusion adjusted to depth of anaesthesia.
DRUGMedical Air in Oxygen
Maintenance of anaesthesia obtained with propofol infusion adjusted to depth of anaesthesia.
Sponsors
Air Liquide SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient ≥ 50 years old * ASA (American Society of Anaesthesiologists) Physical Status III * Patient with increased risk of perioperative cardiac complications (Revised Cardiac Risk Index\>=2) * Surgical operation: laparotomy or orthopaedic surgery or laparoscopy * Planned duration of general anaesthesia in the range of 2-6 hours * Patient willing and able to complete the requirements of this study including the signature of the written informed consent
Exclusion criteria
* Patient with severe impairment of cardiac function (Left Ventricular Ejection Fraction \< 35%) * Patient with drug-eluting stent placed within 12 months prior to selection * Woman of child-bearing potential not implementing adequate contraceptive methods * Pregnant or lactating woman * Surgical procedure in emergency * Chronic opioids pain therapy * Serious illness or medical conditions which are possible contra indication for elective general anaesthesia or administration of intra operative treatments, or which are interfering with the monitoring devices, such as: * Myocardial infarction within 6 months prior to selection * Any significant history of allergy/hypersensitivity to any drugs used during the study, to silicone or to latex * Severely impaired hearing * Known severe neurological disorders * Any medical condition which does not justify the trial participation in the investigator's judgement * General anaesthesia within 7 days prior to selection * Laparotomy within 3 months prior to selection, only for patients undergoing laparotomy * History of drug abuse or psychiatric disorders which would impair the understanding of the necessary information or render medically or legally not able to give written informed consent * Concurrent treatment with any other experimental drugs * Participation in any other clinical trial within 4 weeks prior to selection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose of Propofol (mg) Administered During Maintenance Adjusted to Patient Body Surface Area (BSA in m²) and Maintenance Duration (Min) | Maintenance period (1 Day) | Dose of propofol administered with a Target Controlled Infusion (TCI) device, cerebral concentration equal to 5 µg/mL at the end of induction, and then concentration adjusted to the level of depth of anaesthesia during maintenance. Depth of anaesthesia continuously assessed by signals derived from electroencephalographic recording. Analgesia during induction and maintenance obtained with remifentanil administered with a second TCI device at the stable cerebral concentration of 7 ng/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Awakening Time | 1 Postoperative Day | Time interval between the end of maintenance period and time of Aldrete score ≥ 9. |
| Stay in the Operating Room | 1 Postoperative Day | Time interval between admission in the operating room and discharge from the operating room. |
| Stay in the Recovery Room | 1 Postoperative Day | Time interval between admission in the recovery room and discharge from the recovery room. |
| Haematology - Leucocytes (Giga/L) | 1 Postoperative Day | Leucocytes (Giga/L) obtained from blood samples collected at baseline and in the morning following surgery. |
| Haematology - Erythrocytes (Tera/L) | 1 Postoperative Day. | Erythrocytes (Tera/L) obtained from blood samples collected at baseline and in the morning following surgery. |
| Anaesthesia Recovery Time | 1 Postoperative Day | Time interval between the end of maintenance period and time of tracheal tube removal. |
| Serum Chemistry - AST (GOT) (IU/L) | 1 Postoperative Day | AST (GOT) (IU/L) obtained from blood samples collected at baseline and in Morning following surgery. |
| Serum Chemistry - ALT (GPT) (IU/L) | 1 Postoperative Day | ALT (GPT) (IU/L) obtained from blood samples collected at baseline and in Morning following surgery |
| Serum Chemistry - Gamma GT (IU/L) | 1 Postoperative Day | Gamma GT (IU/L) obtained from blood samples collected at baseline and in Morning following surgery |
| Serum Chemistry - Creatinine (Mcmol/L) | 1 Postoperative Day | Creatinine (mcmol/L) obtained from blood samples collected at baseline and in Morning following surgery |
| Serum Chemistry - Urea (mmol/L) | 1 Postoperative Day | Urea (mmol/L) obtained from blood samples collected at baseline and in Morning following surgery |
| Haematology - Platelets (Giga/L) | 1 Postoperative Day | Platelets (Giga/L) obtained from blood samples collected at baseline and in the morning following surgery |
Countries
France, Germany, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A Xenon 50% (45%-55%) in Oxygen (45%-55%) | 32 |
| Group B Xenon 70% (65%-75%) in Oxygen (25%-35%) | 37 |
| Group C Medical Air in Oxygen (45%-55%) | 33 |
| Total | 102 |
Baseline characteristics
| Characteristic | Total | Group A | Group B | Group C |
|---|---|---|---|---|
| Age, Continuous | 70.3 years STANDARD_DEVIATION 8.3 | 69.8 years STANDARD_DEVIATION 8.2 | 70.0 years STANDARD_DEVIATION 9.7 | 71.1 years STANDARD_DEVIATION 6.9 |
| Body Mass Index | 28.51 Kg/m2 STANDARD_DEVIATION 6.05 | 28.71 Kg/m2 STANDARD_DEVIATION 6.26 | 28.43 Kg/m2 STANDARD_DEVIATION 6.09 | 28.39 Kg/m2 STANDARD_DEVIATION 5.98 |
| Body Surface Area | 1.935 m2 STANDARD_DEVIATION 0.235 | 1.938 m2 STANDARD_DEVIATION 0.228 | 1.926 m2 STANDARD_DEVIATION 0.251 | 1.943 m2 STANDARD_DEVIATION 0.228 |
| Height | 168.5 cm STANDARD_DEVIATION 9.1 | 168.4 cm STANDARD_DEVIATION 8.8 | 168.0 cm STANDARD_DEVIATION 8.9 | 169.2 cm STANDARD_DEVIATION 9.8 |
| History of Cerebrovascular Disease No | 75 participants | 27 participants | 27 participants | 21 participants |
| History of Cerebrovascular Disease Yes | 27 participants | 5 participants | 10 participants | 12 participants |
| History of Congestive Heart Failure No | 73 participants | 23 participants | 28 participants | 22 participants |
| History of Congestive Heart Failure Yes | 29 participants | 9 participants | 9 participants | 11 participants |
| History of Ischemic Heart Disease No | 34 participants | 9 participants | 14 participants | 11 participants |
| History of Ischemic Heart Disease Yes | 68 participants | 23 participants | 23 participants | 22 participants |
| Planned High-Risk Surgical Procedures No | 12 participants | 4 participants | 4 participants | 4 participants |
| Planned High-Risk Surgical Procedures Yes | 90 participants | 28 participants | 33 participants | 29 participants |
| Pre-Operative Serum Creatinine >2.0 mg/dL No | 90 participants | 29 participants | 33 participants | 28 participants |
| Pre-Operative Serum Creatinine >2.0 mg/dL Yes | 12 participants | 3 participants | 4 participants | 5 participants |
| Pre-Operative Treatment With Insulin or Antidiabetics No | 69 participants | 20 participants | 24 participants | 25 participants |
| Pre-Operative Treatment With Insulin or Antidiabetics Yes | 33 participants | 12 participants | 13 participants | 8 participants |
| Sex: Female, Male Female | 34 Participants | 10 Participants | 12 Participants | 12 Participants |
| Sex: Female, Male Male | 68 Participants | 22 Participants | 25 Participants | 21 Participants |
| Weight | 80.88 kg STANDARD_DEVIATION 17.85 | 81.18 kg STANDARD_DEVIATION 17.39 | 80.41 kg STANDARD_DEVIATION 19.61 | 81.12 kg STANDARD_DEVIATION 16.74 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 31 / 32 | 30 / 37 | 32 / 33 |
| serious Total, serious adverse events | 4 / 32 | 7 / 37 | 5 / 33 |
Outcome results
Primary
Dose of Propofol (mg) Administered During Maintenance Adjusted to Patient Body Surface Area (BSA in m²) and Maintenance Duration (Min)
Dose of propofol administered with a Target Controlled Infusion (TCI) device, cerebral concentration equal to 5 µg/mL at the end of induction, and then concentration adjusted to the level of depth of anaesthesia during maintenance. Depth of anaesthesia continuously assessed by signals derived from electroencephalographic recording. Analgesia during induction and maintenance obtained with remifentanil administered with a second TCI device at the stable cerebral concentration of 7 ng/mL.
Time frame: Maintenance period (1 Day)
Population: The main analysis was done in the ITT Data Set (Randomised Patients).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Dose of Propofol (mg) Administered During Maintenance Adjusted to Patient Body Surface Area (BSA in m²) and Maintenance Duration (Min) | 1.683 mg adjusted | Standard Deviation 0.834 |
| Group B | Dose of Propofol (mg) Administered During Maintenance Adjusted to Patient Body Surface Area (BSA in m²) and Maintenance Duration (Min) | 1.005 mg adjusted | Standard Deviation 1.121 |
| Group C | Dose of Propofol (mg) Administered During Maintenance Adjusted to Patient Body Surface Area (BSA in m²) and Maintenance Duration (Min) | 3.987 mg adjusted | Standard Deviation 1.431 |
Comparison: The dose of propofol adjusted to BSA and maintenance duration was expected to be 4.0 mg/m².min in the control group, 2.8 mg/m².min in one xenon group and 3.0 mg/m².min in the other xenon group. With an expected common standard deviation of 2.0 mg/m².min, a type I error of 0.05 (two-sided) and a power of 0.80, the sample size required to show a statistically significant difference between the three groups was estimated to be 48 patients per group, resulting in a total of 144 randomised patients.p-value: <0.0001ANCOVA
p-value: <0.000195% CI: [2.328, 3.724]ANCOVA
p-value: <0.000195% CI: [1.57, 3.011]ANCOVA
p-value: 0.036595% CI: [0.038, 1.432]ANCOVA
Secondary
Anaesthesia Recovery Time
Time interval between the end of maintenance period and time of tracheal tube removal.
Time frame: 1 Postoperative Day
Population: The analysis was done in the ITT Data Set (Randomised Patients).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Anaesthesia Recovery Time | 9.3 minutes | Standard Deviation 15.8 |
| Group B | Anaesthesia Recovery Time | 22.2 minutes | Standard Deviation 62.6 |
| Group C | Anaesthesia Recovery Time | 43.3 minutes | Standard Deviation 180.6 |
Secondary
Awakening Time
Time interval between the end of maintenance period and time of Aldrete score ≥ 9.
Time frame: 1 Postoperative Day
Population: The analysis was done in the ITT Data Set (Randomised Patients).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Awakening Time | 53.9 minutes | Standard Deviation 37.6 |
| Group B | Awakening Time | 70.7 minutes | Standard Deviation 74.2 |
| Group C | Awakening Time | 62.6 minutes | Standard Deviation 34.3 |
Secondary
Haematology - Erythrocytes (Tera/L)
Erythrocytes (Tera/L) obtained from blood samples collected at baseline and in the morning following surgery.
Time frame: 1 Postoperative Day.
Population: The analysis was done in the ITT Data Set (Randomised Patients).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Haematology - Erythrocytes (Tera/L) | Before Anaesthesia | 4.373 Tera/L | Standard Deviation 0.553 |
| Group A | Haematology - Erythrocytes (Tera/L) | Morning Following Surgery | 3.690 Tera/L | Standard Deviation 0.529 |
| Group B | Haematology - Erythrocytes (Tera/L) | Before Anaesthesia | 4.219 Tera/L | Standard Deviation 0.798 |
| Group B | Haematology - Erythrocytes (Tera/L) | Morning Following Surgery | 3.763 Tera/L | Standard Deviation 0.524 |
| Group C | Haematology - Erythrocytes (Tera/L) | Before Anaesthesia | 4.135 Tera/L | Standard Deviation 0.45 |
| Group C | Haematology - Erythrocytes (Tera/L) | Morning Following Surgery | 3.675 Tera/L | Standard Deviation 0.564 |
Secondary
Haematology - Leucocytes (Giga/L)
Leucocytes (Giga/L) obtained from blood samples collected at baseline and in the morning following surgery.
Time frame: 1 Postoperative Day
Population: The analysis was done in the ITT Data Set (Randomised Patients).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Haematology - Leucocytes (Giga/L) | Before Anaesthesia | 8.118 Giga/L | Standard Deviation 2.289 |
| Group A | Haematology - Leucocytes (Giga/L) | Morning Following Surgery | 11.429 Giga/L | Standard Deviation 2.737 |
| Group B | Haematology - Leucocytes (Giga/L) | Before Anaesthesia | 8.301 Giga/L | Standard Deviation 2.98 |
| Group B | Haematology - Leucocytes (Giga/L) | Morning Following Surgery | 11.574 Giga/L | Standard Deviation 4.438 |
| Group C | Haematology - Leucocytes (Giga/L) | Before Anaesthesia | 7.432 Giga/L | Standard Deviation 1.641 |
| Group C | Haematology - Leucocytes (Giga/L) | Morning Following Surgery | 11.280 Giga/L | Standard Deviation 2.818 |
Secondary
Haematology - Platelets (Giga/L)
Platelets (Giga/L) obtained from blood samples collected at baseline and in the morning following surgery
Time frame: 1 Postoperative Day
Population: The analysis was done in the ITT Data Set (Randomised Patients).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Haematology - Platelets (Giga/L) | Before Anaesthesia | 225.036 Giga/L | Standard Deviation 89.556 |
| Group A | Haematology - Platelets (Giga/L) | Morning Following Surgery | 188.036 Giga/L | Standard Deviation 79.083 |
| Group B | Haematology - Platelets (Giga/L) | Before Anaesthesia | 244.656 Giga/L | Standard Deviation 71.724 |
| Group B | Haematology - Platelets (Giga/L) | Morning Following Surgery | 212.594 Giga/L | Standard Deviation 79.424 |
| Group C | Haematology - Platelets (Giga/L) | Before Anaesthesia | 244.214 Giga/L | Standard Deviation 80.484 |
| Group C | Haematology - Platelets (Giga/L) | Morning Following Surgery | 196.250 Giga/L | Standard Deviation 86.871 |
Secondary
Serum Chemistry - ALT (GPT) (IU/L)
ALT (GPT) (IU/L) obtained from blood samples collected at baseline and in Morning following surgery
Time frame: 1 Postoperative Day
Population: The analysis was done in the ITT Data Set (Randomised Patients).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Serum Chemistry - ALT (GPT) (IU/L) | Before Anaesthesia | 28.498 IU/L | Standard Deviation 31.981 |
| Group A | Serum Chemistry - ALT (GPT) (IU/L) | Morning Following Surgery | 50.634 IU/L | Standard Deviation 111.748 |
| Group B | Serum Chemistry - ALT (GPT) (IU/L) | Before Anaesthesia | 24.400 IU/L | Standard Deviation 13.176 |
| Group B | Serum Chemistry - ALT (GPT) (IU/L) | Morning Following Surgery | 81.747 IU/L | Standard Deviation 197.209 |
| Group C | Serum Chemistry - ALT (GPT) (IU/L) | Before Anaesthesia | 28.655 IU/L | Standard Deviation 27.587 |
| Group C | Serum Chemistry - ALT (GPT) (IU/L) | Morning Following Surgery | 48.115 IU/L | Standard Deviation 57.414 |
Secondary
Serum Chemistry - AST (GOT) (IU/L)
AST (GOT) (IU/L) obtained from blood samples collected at baseline and in Morning following surgery.
Time frame: 1 Postoperative Day
Population: The analysis was done in the ITT Data Set (Randomised Patients).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Serum Chemistry - AST (GOT) (IU/L) | Before Anaesthesia | 28.641 IU/L | Standard Deviation 32.661 |
| Group A | Serum Chemistry - AST (GOT) (IU/L) | Morning Following Surgery | 44.723 IU/L | Standard Deviation 66.482 |
| Group B | Serum Chemistry - AST (GOT) (IU/L) | Before Anaesthesia | 31.926 IU/L | Standard Deviation 25.495 |
| Group B | Serum Chemistry - AST (GOT) (IU/L) | Morning Following Surgery | 139.163 IU/L | Standard Deviation 420.704 |
| Group C | Serum Chemistry - AST (GOT) (IU/L) | Before Anaesthesia | 30.544 IU/L | Standard Deviation 27.369 |
| Group C | Serum Chemistry - AST (GOT) (IU/L) | Morning Following Surgery | 62.348 IU/L | Standard Deviation 65.231 |
Secondary
Serum Chemistry - Creatinine (Mcmol/L)
Creatinine (mcmol/L) obtained from blood samples collected at baseline and in Morning following surgery
Time frame: 1 Postoperative Day
Population: The analysis was done in the ITT Data Set (Randomised Patients).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Serum Chemistry - Creatinine (Mcmol/L) | Before Anaesthesia | 94.625 mcmol/L | Standard Deviation 66.513 |
| Group A | Serum Chemistry - Creatinine (Mcmol/L) | Morning Following Surgery | 115.007 mcmol/L | Standard Deviation 144.682 |
| Group B | Serum Chemistry - Creatinine (Mcmol/L) | Before Anaesthesia | 106.825 mcmol/L | Standard Deviation 68.814 |
| Group B | Serum Chemistry - Creatinine (Mcmol/L) | Morning Following Surgery | 102.071 mcmol/L | Standard Deviation 61.185 |
| Group C | Serum Chemistry - Creatinine (Mcmol/L) | Before Anaesthesia | 98.830 mcmol/L | Standard Deviation 40.639 |
| Group C | Serum Chemistry - Creatinine (Mcmol/L) | Morning Following Surgery | 96.273 mcmol/L | Standard Deviation 38.996 |
Secondary
Serum Chemistry - Gamma GT (IU/L)
Gamma GT (IU/L) obtained from blood samples collected at baseline and in Morning following surgery
Time frame: 1 Postoperative Day
Population: The analysis was done in the ITT Data Set (Randomised Patients)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Serum Chemistry - Gamma GT (IU/L) | Morning Following Surgery | 106.234 IU/L | Standard Deviation 198.074 |
| Group A | Serum Chemistry - Gamma GT (IU/L) | Before Anaesthesia | 122.689 IU/L | Standard Deviation 335.374 |
| Group B | Serum Chemistry - Gamma GT (IU/L) | Morning Following Surgery | 73.021 IU/L | Standard Deviation 86.695 |
| Group B | Serum Chemistry - Gamma GT (IU/L) | Before Anaesthesia | 77.012 IU/L | Standard Deviation 80.051 |
| Group C | Serum Chemistry - Gamma GT (IU/L) | Before Anaesthesia | 136.785 IU/L | Standard Deviation 370.826 |
| Group C | Serum Chemistry - Gamma GT (IU/L) | Morning Following Surgery | 90.345 IU/L | Standard Deviation 189.828 |
Secondary
Serum Chemistry - Urea (mmol/L)
Urea (mmol/L) obtained from blood samples collected at baseline and in Morning following surgery
Time frame: 1 Postoperative Day
Population: The analysis was done in the ITT Data Set (Randomised Patients).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Serum Chemistry - Urea (mmol/L) | Before Anaesthesia | 7.453 mmol/L | Standard Deviation 4.623 |
| Group A | Serum Chemistry - Urea (mmol/L) | Morning Following Surgery | 7.317 mmol/L | Standard Deviation 5.458 |
| Group B | Serum Chemistry - Urea (mmol/L) | Before Anaesthesia | 8.680 mmol/L | Standard Deviation 5.882 |
| Group B | Serum Chemistry - Urea (mmol/L) | Morning Following Surgery | 7.964 mmol/L | Standard Deviation 4.404 |
| Group C | Serum Chemistry - Urea (mmol/L) | Before Anaesthesia | 7.886 mmol/L | Standard Deviation 3.087 |
| Group C | Serum Chemistry - Urea (mmol/L) | Morning Following Surgery | 7.609 mmol/L | Standard Deviation 2.876 |
Secondary
Stay in the Operating Room
Time interval between admission in the operating room and discharge from the operating room.
Time frame: 1 Postoperative Day
Population: The analysis was done in the ITT Data Set (Randomised Patients).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Stay in the Operating Room | 273.1 minutes | Standard Deviation 115.5 |
| Group B | Stay in the Operating Room | 288.2 minutes | Standard Deviation 119.1 |
| Group C | Stay in the Operating Room | 315.0 minutes | Standard Deviation 141.5 |
Secondary
Stay in the Recovery Room
Time interval between admission in the recovery room and discharge from the recovery room.
Time frame: 1 Postoperative Day
Population: The analysis was done in the ITT Data Set (Randomised Patients).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A | Stay in the Recovery Room | 187.5 minutes | Standard Deviation 156.3 |
| Group B | Stay in the Recovery Room | 180.7 minutes | Standard Deviation 132 |
| Group C | Stay in the Recovery Room | 218.0 minutes | Standard Deviation 243.7 |