Randomized Isoflurane and Sevoflurane Comparison in Cardiac Surgery

NCT ID: NCT01477151

Last Updated: 2015-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 464 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2015-03-31

Brief Summary

Anesthesia practice in the 21st century is increasingly outcomes-oriented and evidence-based, but there remain significant gaps in our knowledge, even for commonly-encountered clinical situations. Currently, the two most commonly used drugs used for maintenance of anesthesia in cardiac surgical patients are isoflurane and sevoflurane. There is a belief among many cardiac anesthesiologists that sevoflurane is a better cardiac anesthetic than isoflurane, but there is very little data to support this notion. In fact, very little is known about their comparative effects on important patient outcomes because there has not been a large head-to-head prospective randomized clinical trial. This project will supply the data necessary to critically compare the two anesthetics.

Detailed Description

Current evidence supports the superiority of sevoflurane for myocardial protection during cardiac surgery when compared to total intravenous anesthesia with propofol. However, there is no evidence to suggest that sevoflurane is superior to isoflurane for myocardial protection during cardiac surgery. Sevoflurane may potentially reduce the rate of post-cardiac surgery atrial fibrillation and the time to tracheal extubation compared to isoflurane, but the literature is equivocal on these two important outcomes. Anesthesiologists still frequently use isoflurane for maintenance of cardiac anesthesia, and this is likely because there is substantial uncertainty about whether or not sevoflurane is superior to isoflurane, given the lack of head-to-head RCTs. A large, prospective, pragmatic RCT can ultimately assist clinicians by providing evidence of the non-inferiority (or, possibly the superiority) of one anesthetic compared to the other on important patient outcomes such as ICU length of stay, mortality, renal dysfunction, time to tracheal extubation after cardiac surgery, rates of clinically-important atrial fibrillation, and myocardial damage.

Conditions

Coronary Artery Disease; Valvular Heart Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

sevoflurane

These patients will receive sevoflurane as the volatile anesthetic pre-, during-, and post-cardiopulmonary bypass at a targeted dose of 0.5-2.0 MAC.

Group Type: ACTIVE_COMPARATOR

Volatile anesthetic

Intervention Type: DRUG

The intervention in this trial is randomization to either maintenance of anesthesia with sevoflurane or maintenance of anesthesia with isoflurane. The designated volatile anesthetic will be given at a strict minimal amount throughout the entire cardiac surgery (including cardiopulmonary bypass). This regimen (administration throughout the entire operation) has proved to have the greatest efficacy. Apart from this intervention, the anesthetic for patients participating in this trial will not be substantially different from normal practice, as the intention is to allow normal practice (with the exception of the choice of volatile anesthetic agent) to maximize the applicability and external validity of the trial. The management of anticoagulation, cardiac surgical techniques, and other aspects of the procedure will be managed in an unaltered fashion.

No IV drug infusions will be permitted until after protamine administration.

isoflurane

These patients will receive isoflurane as the volatile anesthetic pre-, during-, and post-cardiopulmonary bypass at a targeted dose of 0.5-2.0 MAC.

Group Type: EXPERIMENTAL

Volatile anesthetic

Intervention Type: DRUG

The intervention in this trial is randomization to either maintenance of anesthesia with sevoflurane or maintenance of anesthesia with isoflurane. The designated volatile anesthetic will be given at a strict minimal amount throughout the entire cardiac surgery (including cardiopulmonary bypass). This regimen (administration throughout the entire operation) has proved to have the greatest efficacy. Apart from this intervention, the anesthetic for patients participating in this trial will not be substantially different from normal practice, as the intention is to allow normal practice (with the exception of the choice of volatile anesthetic agent) to maximize the applicability and external validity of the trial. The management of anticoagulation, cardiac surgical techniques, and other aspects of the procedure will be managed in an unaltered fashion.

No IV drug infusions will be permitted until after protamine administration.

Interventions

Volatile anesthetic

The intervention in this trial is randomization to either maintenance of anesthesia with sevoflurane or maintenance of anesthesia with isoflurane. The designated volatile anesthetic will be given at a strict minimal amount throughout the entire cardiac surgery (including cardiopulmonary bypass). This regimen (administration throughout the entire operation) has proved to have the greatest efficacy. Apart from this intervention, the anesthetic for patients participating in this trial will not be substantially different from normal practice, as the intention is to allow normal practice (with the exception of the choice of volatile anesthetic agent) to maximize the applicability and external validity of the trial. The management of anticoagulation, cardiac surgical techniques, and other aspects of the procedure will be managed in an unaltered fashion.

No IV drug infusions will be permitted until after protamine administration.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients must be 18 years or over (There is no upper age limit to enrollment)
• Eligible procedures are: CABG on-pump or off-pump, single valve repair/replacement, or CABG/single valve combined procedures

Exclusion Criteria

• Cardiac surgeries that are not one of the included cases
• Planned extubation in the operating room
• Patients refusing blood products (vis à vis blood sampling)
• Pregnant patients
• Malignant hyperthermia or documented/stated allergy to potent volatile anesthetic agents

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

OTHER

Sponsor Role: lead

Responsible Party

Philip Jones

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Philip M Jones, MD MSc

Role: PRINCIPAL_INVESTIGATOR

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Locations

University Hospital - London Health Sciences Centre

London, Ontario, Canada

Countries

Canada

References

Jones PM, Bainbridge D, Chu MWA, Fernandes PS, Fox SA, Iglesias I, Kiaii B, Lavi R, Murkin JM. Comparison of isoflurane and sevoflurane in cardiac surgery: a randomized non-inferiority comparative effectiveness trial. Can J Anaesth. 2016 Oct;63(10):1128-1139. doi: 10.1007/s12630-016-0706-y. Epub 2016 Jul 27.

Reference Type: DERIVED

PMID: 27465213 (View on PubMed)

Other Identifiers

16497

Identifier Type: -

Identifier Source: org_study_id