title: Comparison of isoflurane and sevoflurane in cardiac surgery: a randomized non-inferiority comparative effectiveness trial.
abstract: OBJECTIVE
  Volatile anesthetics possess cardioprotective properties, but it is unknown if the cardioprotective effects extend equally to all members of the class. Although sevoflurane is a relatively newer anesthetic than isoflurane, its introduction into practice was not preceded by a head-to-head comparison with isoflurane in a trial focusing on clinically important outcomes. Our objective was to determine whether sevoflurane was non-inferior to isoflurane on a clinically important primary outcome in a heterogeneous group of adults undergoing cardiac surgery.
  
  
  METHODS
  This was a pragmatic randomized non-inferiority comparative effectiveness clinical trial in 464 adults having coronary artery bypass graft and/or single valve surgery during November 2011 to March 2014. The intervention was maintenance of anesthesia with sevoflurane (n = 231) or isoflurane (n = 233) administered at a dose of 0.5-2.0 MAC throughout the entire operation. All caregivers were blinded except for the anesthesiologist and perfusionist. The primary outcome was a composite of intensive care unit (ICU) length of stay ≥ 48 hr and all-cause 30-day mortality. We hypothesized that sevoflurane would be non-inferior to isoflurane (non-inferiority margin < 10% based on an expected event rate of 25%). Secondary outcomes included prolonged ICU stay, 30- and 365-day all-cause mortality, inotrope or vasopressor usage, new-onset hemodialysis or atrial fibrillation, stroke, and readmission to the ICU.
  
  
  RESULTS
  No losses to follow-up occurred. The primary outcome occurred in 25% of sevoflurane patients and 30% of isoflurane patients (absolute difference, -5.4%; one-sided 95% confidence interval, 1.4), thus non-inferiority was declared. Sevoflurane was not superior to isoflurane for the primary outcome (P = 0.21) or for any secondary outcomes.
  
  
  CONCLUSIONS
  Sevoflurane is non-inferior to isoflurane on a composite outcome of prolonged ICU stay and all-cause 30-day mortality. Sevoflurane is not superior to isoflurane on any other of the clinically important outcomes. This trial was registered at clinicaltrials.gov; NCT01477151.
authors.affiliation: Department of Anesthesia & Perioperative Medicine, University of Western Ontario, London, ON, Canada. philip.jones@lhsc.on.ca.|Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada. philip.jones@lhsc.on.ca.|Program in Critical Care, Department of Medicine, The University of Western Ontario, London, ON, Canada. philip.jones@lhsc.on.ca.|Department of Epidemiology & Biostatistics, University of Western Ontario, London, ON, Canada. philip.jones@lhsc.on.ca.|University Hospital - London Health Sciences Centre, Room C3-110, 339 Windermere Rd, London, ON, N6A 5A5, Canada. philip.jones@lhsc.on.ca.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Jones
authors.affiliation: Department of Anesthesia & Perioperative Medicine, University of Western Ontario, London, ON, Canada.|Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.|Program in Critical Care, Department of Medicine, The University of Western Ontario, London, ON, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bainbridge
authors.affiliation: Division of Cardiac Surgery, Department of Surgery, The University of Western Ontario, London, ON, Canada.
authors.forename: Michael W A
authors.initials: MWA
authors.lastname: Chu
authors.affiliation: Clinical Perfusion Services, Cardiac Care, London Health Sciences Centre, London, ON, Canada.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Fernandes
authors.affiliation: Division of Cardiac Surgery, Department of Surgery, The University of Western Ontario, London, ON, Canada.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Fox
authors.affiliation: Department of Anesthesia & Perioperative Medicine, University of Western Ontario, London, ON, Canada.|Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.
authors.forename: Ivan
authors.initials: I
authors.lastname: Iglesias
authors.affiliation: Division of Cardiac Surgery, Department of Surgery, The University of Western Ontario, London, ON, Canada.
authors.forename: Bob
authors.initials: B
authors.lastname: Kiaii
authors.affiliation: Department of Anesthesia & Perioperative Medicine, University of Western Ontario, London, ON, Canada.|Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.
authors.forename: Ronit
authors.initials: R
authors.lastname: Lavi
authors.affiliation: Department of Anesthesia & Perioperative Medicine, University of Western Ontario, London, ON, Canada.|Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.
authors.forename: John M
authors.initials: JM
authors.lastname: Murkin
mesh_terms: D000328:Adult; D000368:Aged; D018685:Anesthetics, Inhalation; D006348:Cardiac Surgical Procedures / Q000379:methods* / Q000401:mortality; D002316:Cardiotonic Agents / Q000627:therapeutic use; D057186:Comparative Effectiveness Research; D001026:Coronary Artery Bypass / Q000379:methods; D003422:Critical Care / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007530:Isoflurane / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007902:Length of Stay; D008297:Male; D008738:Methyl Ethers / Q000627:therapeutic use*; D008875:Middle Aged; D010359:Patient Readmission; D006435:Renal Dialysis; D000077149:Sevoflurane; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
chemical_list: D018685:Anesthetics, Inhalation; D002316:Cardiotonic Agents; D008738:Methyl Ethers; D014662:Vasoconstrictor Agents; D000077149:Sevoflurane; D007530:Isoflurane