Inhaled Sevoflurane Compared to Intravenous Sedation Post Coronary Artery Bypass Grafting
Primary Purpose
Myocardial Reperfusion Injury, Atrial Fibrillation
Status
Completed
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
Sevoflurane
propofol
Sponsored by
About this trial
This is an interventional treatment trial for Myocardial Reperfusion Injury focused on measuring Sevoflurane, CABG, cardioprotection, AnaConDa
Eligibility Criteria
Inclusion Criteria:
- Planned coronary artery bypass grafting
Exclusion Criteria:
- Combined heart valve surgery
- Malignant Hyperthermia
- Postoperative need for mechanical circulation support
Sites / Locations
- Karolinska University Hospital Solna, Cardiothoracic Intensive Care Unit
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
propofol
sevoflurane
Arm Description
propofol for sedation minimum 2 hours in CTICU after CABG
Sevoflurane via AnaConDa for minimum 2 hours in CTICU after CABG
Outcomes
Primary Outcome Measures
Troponin levels
Secondary Outcome Measures
renal function
ambient sevoflurane levels
cognitive function/memory panorama post ICU
attenuation of inflammatory response
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00484575
Brief Title
Inhaled Sevoflurane Compared to Intravenous Sedation Post Coronary Artery Bypass Grafting
Official Title
Inhaled Sevoflurane Compared to Intravenous Sedation Post Coronary Artery Bypass Grafting
Study Type
Interventional
2. Study Status
Record Verification Date
June 2007
Overall Recruitment Status
Completed
Study Start Date
June 2007 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
December 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Karolinska Institutet
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Inhaled sevoflurane during coronary artery bypass grafting (CABG) reduces postoperative Troponin levels and may be associated with improved outcome. A dose-response effect has been demonstrated by de Hert et al, with greatest reductions of Troponin when Sevoflurane was used during the entire operation, as compared to Sevoflurane during parts of the operation.
Sevoflurane, as other inhaled anesthetic agents, is sedative in low doses. Postoperative sedation after CABG is currently achieved with intravenous propofol.
A new simplified method of administration of isoflurane or sevoflurane has been developed and tested by members of the research group. The Anesthetic Conserving Device is a modified heat-moisture exchanger (HME) that permits direct infusion of sevoflurane to the airway, where it is vaporized in an evaporator rod in the device.
The primary aim (and primary hypothesis)of the current trial is to examine if postoperative sedation with sevoflurane after CABG is associated with improved cardiac outcome, measured as reduced levels of Troponin, BNP and reduced incidence of cardiac events, such as atrial fibrillation, need for inotropic drugs and myocardial infarction, compared with conventional propofol sedation.
Other end-points of the trial are potential renal (protective) effects measured with cystatin C levels, need for dialysis but also measurements of inorganic fluorides in serum, as well as environmental aspects of sevoflurane sedation in a Cardiothoracic Intensive Care Unit. Furthermore, potential differences in ICU memories and well-being during stay in the intensive Care Unit will be investigated via patient questionnaires.
Besides routine blood sampling, plasma will be saved for later analysis of inflammatory mediators (biobank).
Detailed Description
Sevoflurane, an inhaled anesthetic is currently recommended for anesthesia during coronary artery bypass grafting (CABG).
Inhaled sevoflurane during CABG reduces postoperative Troponin levels and may be associated with improved outcome. A dose-response effect of Sevoflurane cardioprotection has been demonstrated by de Hert et al, with greatest reductions of Troponin when Sevoflurane was used during the entire operation, as compared to Sevoflurane during parts of the operation or not at all.
Postoperative sedation after CABG is currently achieved with intravenous propofol.
Sevoflurane, as other inhaled anesthetic agents, is sedative in low doses. A new simplified method of administration of isoflurane or sevoflurane has been developed and tested by members of the research group. The Anesthetic Conserving Device (AnaConDa®) is a modified heat-moisture exchanger (HME) that permits direct infusion of sevoflurane to the airway, where it is vaporized in an evaporator rod in the device. Studies of isoflurane sedation with the AnaConDa® have shown good sedation effects and short wake-up times.
The primary aim (and primary hypothesis)of the current trial is to examine if postoperative sedation with sevoflurane after CABG is associated with improved cardiac outcome, measured as reduced levels of Troponin, BNP and reduced incidence of cardiac events, such as atrial fibrillation, need for inotropic drugs and myocardial infarction, compared with conventional propofol sedation.
Other end-points of the trial are potential renal (protective) effects measured with cystatin C levels, need for dialysis but also measurements of inorganic fluorides in serum, as well as environmental aspects of sevoflurane sedation in a Cardiothoracic Intensive Care Unit. Furthermore, potential differences in ICU memories and well-being during stay in the intensive Care Unit will be investigated via patient questionnaires.
Besides routine blood sampling, plasma will be saved for later analysis of inflammatory mediators (biobank).
Methods:
120 patients planned for CABG (without valve surgery) will be enrolled in the trial. Patients with malignant hyperthermia are excluded, as well as patients with need for mechanical circulation support.
Routine anesthesia and CABG will be followed by randomisation to either inhaled sevoflurane or intravenous propofol. Patients will be transferred from the operating room to the Cardiothoracic Intensive Care Unit (CICU)with propofol sedation. Upon arrival to the CICU sedation will according to randomisation will replace propofol.
Thereafter patients will be kept sedated according to the MAAS Scale until vital parameters are stable and extubation criteria are fulfilled or for a maximum of 48 hours. Time from arrival at CICU to extubation, as well as time from termination of sedative to extubation will be measured. Total time in CICU will be recorded as well as time from arrival to discharge criteria are fulfilled.
Troponin, BNP, Creatinine, Cystatin C, CRP will be measured before CABG, and at regular time intervals postoperatively. A blood sample for storage of plasma will be taken 12 hours postoperatively, preliminary for measurement of interleukin activity as this may be attenuated by inhaled anesthetics. Hemodynamics will be recorded during CICU care, as well as need for inotropic drugs, cardioversion, arrythmias or adverse events.
Environment will be monitored with dosimeter measurements and with spectrophotometry.
After extubation patients will be monitored regarding cognitive recovery during the first hour. When discharged from the CICU, patients will receive a questionnaire in order to describe the memory panorama from the ICU stay after 1-2 days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Reperfusion Injury, Atrial Fibrillation
Keywords
Sevoflurane, CABG, cardioprotection, AnaConDa
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
propofol
Arm Type
Active Comparator
Arm Description
propofol for sedation minimum 2 hours in CTICU after CABG
Arm Title
sevoflurane
Arm Type
Experimental
Arm Description
Sevoflurane via AnaConDa for minimum 2 hours in CTICU after CABG
Intervention Type
Drug
Intervention Name(s)
Sevoflurane
Other Intervention Name(s)
Sevorane
Intervention Description
given by infusion via AnaConDa for sedation with target MAAS 2-3
Intervention Type
Drug
Intervention Name(s)
propofol
Intervention Description
propofol given intravenously for sedation in control group
Primary Outcome Measure Information:
Title
Troponin levels
Time Frame
2 days
Secondary Outcome Measure Information:
Title
renal function
Time Frame
1 week
Title
ambient sevoflurane levels
Time Frame
2 days
Title
cognitive function/memory panorama post ICU
Time Frame
1 week
Title
attenuation of inflammatory response
Time Frame
2 days
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Planned coronary artery bypass grafting
Exclusion Criteria:
Combined heart valve surgery
Malignant Hyperthermia
Postoperative need for mechanical circulation support
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter V Sackey, MD, PhD
Organizational Affiliation
Karolinska Institutet, Institution of Physiology and Pharmacology, Section for Anesthesia and Intensive Care Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jan-Olof Hellström, MD
Organizational Affiliation
Karolinska Institutet, Institution of Physiology and Phrmacology, Section for Anesthesia and Intensive Care
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anders Öwall, MD, PhD
Organizational Affiliation
Karolinska University Solna, Department of Cardiothoracic Anesthesia and Intensive Care
Official's Role
Principal Investigator
Facility Information:
Facility Name
Karolinska University Hospital Solna, Cardiothoracic Intensive Care Unit
City
Stockholm
ZIP/Postal Code
171 76
Country
Sweden
12. IPD Sharing Statement
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Inhaled Sevoflurane Compared to Intravenous Sedation Post Coronary Artery Bypass Grafting
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