Randomized Isoflurane and Sevoflurane Comparison in Cardiac Surgery (RISCCS)

Randomized Isoflurane and Sevoflurane Comparison in Cardiac Surgery: A Prospective Randomized Clinical Trial.

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Valvular Heart Disease
• Intervention / Treatment: Drug: Volatile anesthetic

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.

• Study Type: Interventional
• Enrollment (Actual): 464
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A5A5
      • University Hospital - London Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: 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.
Experimental: 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.	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite of: prolonged ICU stay (>= 48 hours) OR death within 30 days of operation	30 days of operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative cardiac troponin T	Troponin T sampled at 6 hours after admission to the ICU. The time of sampling will be recorded. The sample will be taken from an indwelling venous or arterial cannula (if one exists) or by venipuncture.	6 hours after admission to ICU
Length of stay in the ICU (criteria)	The time from admission in ICU (time 0) until the patient's transfer orders to the floor are enacted.	Participants will be followed for the duration of ICU stay, an expected average of 1 day
30-day all-cause mortality	A participant who has died for any reason before the end of 30th day after the operation. Day 1 is the first calendar day after first being admitted to the ICU.	30 days after operation
Duration of tracheal intubation	The time from being admitted to the ICU (time 0) until the patient's tracheal tube is removed for the first time.	Participants will be followed for the duration of ICU stay, an expected average of 1 day
Inotrope or vasopressor usage in the ICU	A participant who is treated at any time after the first hour of their ICU stay with an inotropic or vasopressor by infusion.	Participants will be followed for the duration of ICU stay, an expected average of 1 day
Prolonged inotrope or vasopressor usage in the ICU	Any patient requiring 12 or more continuous hours of any combination of inotropic or vasopressor agent (including the first hour) in the ICU.	Participants will be followed for the duration of ICU stay, an expected average of 1 day
Peak postoperative serum creatinine	Peak postoperative creatinine as recorded in the hospital chart.	Participants will be followed for the duration of hospital stay, an expected average of 1 week
New-onset dialysis	Any patient, not previously on dialysis, requiring postoperative dialysis (hemodialysis or peritoneal dialysis).	Participants will be followed for the duration of hospital stay, an expected average of 1 week
Incidence of new-onset atrial fibrillation	We will capture the proportion of patients who have clinically significant new atrial fibrillation at any time from ICU admission until the end of POD 4. The adjudication of atrial fibrillation will be recorded by the blinded research nurse.	Until end of post-operative day 4
Incidence of intra-aortic balloon pump usage	The proportion of patients having an intra-aortic balloon pump inserted (either in the operating room or in the ICU).	Participants will be followed for the duration of ICU stay, an expected average of 1 day
Length of stay in the ICU (actual)	The time from admission in ICU (time 0) until the patient is discharged from the ICU.	Participants will be followed for the duration of ICU stay, an expected average of 1 day
Length of stay in the hospital (actual)	The time from admission to the ICU until the patient is discharged home from the hospital.	Participants will be followed for the duration of hospital stay, an expected average of 1 week
Readmission to ICU	Readmission to the ICU for any reason.	Participants will be followed for the duration of hospital stay, an expected average of 1 week
Perioperative stroke	A new neurological abnormality persisting > 24 hours with documentation by formal neurological examination and evidence of new brain lesions on a brain imaging study.	Participants will be followed for the duration of hospital stay, an expected average of 1 week
1-year all-cause mortality	A participant who has died for any reason within the first year after the operation. For example, if the operation takes place on June 20 2011, then mortality up to and including June 19 2012 will be counted.	One year after operation

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Investigators: Principal Investigator: Philip M Jones, MD MSc, Lawson Health Research Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: November 16, 2011
• First Submitted That Met QC Criteria: November 18, 2011
• First Posted (Estimate): November 22, 2011

Study Record Updates

• Last Update Posted (Estimate): June 8, 2015
• Last Update Submitted That Met QC Criteria: June 3, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: cardiac surgery; anesthesia; sevoflurane; cardiac anesthesia; preconditioning; troponin; cardioprotection; isoflurane
• Additional Relevant MeSH Terms: Myocardial Ischemia; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Diseases; Coronary Artery Disease; Heart Valve Diseases; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: 16497