Inhaled Sevoflurane Compared to Intravenous Sedation Post Coronary Artery Bypass Grafting

This study has been completed.
Sponsor:
Information provided by:
Karolinska Institutet
ClinicalTrials.gov Identifier:
NCT00484575
First received: June 8, 2007
Last updated: May 19, 2010
Last verified: June 2007
  Purpose

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).


Condition Intervention Phase
Myocardial Reperfusion Injury
Atrial Fibrillation
Drug: Sevoflurane
Drug: propofol
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Inhaled Sevoflurane Compared to Intravenous Sedation Post Coronary Artery Bypass Grafting

Resource links provided by NLM:


Further study details as provided by Karolinska Institutet:

Primary Outcome Measures:
  • Troponin levels [ Time Frame: 2 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • renal function [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]
  • ambient sevoflurane levels [ Time Frame: 2 days ] [ Designated as safety issue: Yes ]
  • cognitive function/memory panorama post ICU [ Time Frame: 1 week ] [ Designated as safety issue: No ]
  • attenuation of inflammatory response [ Time Frame: 2 days ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: June 2007
Study Completion Date: December 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: propofol
propofol for sedation minimum 2 hours in CTICU after CABG
Drug: propofol
propofol given intravenously for sedation in control group
Other Name: Propofol
Experimental: sevoflurane
Sevoflurane via AnaConDa for minimum 2 hours in CTICU after CABG
Drug: Sevoflurane
given by infusion via AnaConDa for sedation with target MAAS 2-3
Other Name: Sevorane

  Hide Detailed Description

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Planned coronary artery bypass grafting

Exclusion Criteria:

  • Combined heart valve surgery
  • Malignant Hyperthermia
  • Postoperative need for mechanical circulation support
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00484575

Locations
Sweden
Karolinska University Hospital Solna, Cardiothoracic Intensive Care Unit
Stockholm, Sweden, 171 76
Sponsors and Collaborators
Karolinska Institutet
Investigators
Principal Investigator: Peter V Sackey, MD, PhD Karolinska Institutet, Institution of Physiology and Pharmacology, Section for Anesthesia and Intensive Care Medicine
Principal Investigator: Jan-Olof Hellström, MD Karolinska Institutet, Institution of Physiology and Phrmacology, Section for Anesthesia and Intensive Care
Principal Investigator: Anders Öwall, MD, PhD Karolinska University Solna, Department of Cardiothoracic Anesthesia and Intensive Care
  More Information

No publications provided

Responsible Party: Peter Sackey, MD, PhD, Dept of Physiology and Pharmacology, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT00484575     History of Changes
Other Study ID Numbers: 2007-000293-23
Study First Received: June 8, 2007
Last Updated: May 19, 2010
Health Authority: Sweden: Medical Products Agency

Keywords provided by Karolinska Institutet:
Sevoflurane
CABG
cardioprotection
AnaConDa

Additional relevant MeSH terms:
Atrial Fibrillation
Myocardial Reperfusion Injury
Reperfusion Injury
Arrhythmias, Cardiac
Cardiomyopathies
Cardiovascular Diseases
Heart Diseases
Myocardial Ischemia
Pathologic Processes
Postoperative Complications
Vascular Diseases
Propofol
Sevoflurane
Anesthetics
Anesthetics, General
Anesthetics, Inhalation
Anesthetics, Intravenous
Central Nervous System Agents
Central Nervous System Depressants
Hematologic Agents
Hypnotics and Sedatives
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014