title: Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Cardiopulmonary bypass initiates a systemic inflammatory response syndrome that is associated with postoperative morbidity and mortality. Steroids suppress inflammatory responses and might improve outcomes in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. We aimed to assess the effects of steroids in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass.
  
  
  METHODS
  The Steroids In caRdiac Surgery (SIRS) study is a double-blind, randomised, controlled trial. We used a central computerised phone or interactive web system to randomly assign (1:1) patients at high risk of morbidity and mortality from 80 hospital or cardiac surgery centres in 18 countries undergoing cardiac surgery with the use of cardiopulmonary bypass to receive either methylprednisolone (250 mg at anaesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients were assigned with block randomisation with random block sizes of 2, 4, or 6 and stratified by centre. Patients aged 18 years or older were eligible if they had a European System for Cardiac Operative Risk Evaluation of at least 6. Patients were excluded if they were taking or expected to receive systemic steroids in the immediate postoperative period or had a history of bacterial or fungal infection in the preceding 30 days. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcomes were 30-day mortality and a composite of death and major morbidity (ie, myocardial injury, stroke, renal failure, or respiratory failure) within 30 days, both analysed by intention to treat. Safety outcomes were also analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00427388.
  
  
  RESULTS
  Patients were recruited between June 21, 2007, and Dec 19, 2013. Complete 30-day data was available for all 7507 patients randomly assigned to methylprednisolone (n=3755) and to placebo (n=3752). Methylprednisolone, compared with placebo, did not reduce the risk of death at 30 days (154 [4%] vs 177 [5%] patients; relative risk [RR] 0·87, 95% CI 0·70-1·07, p=0·19) or the risk of death or major morbidity (909 [24%] vs 885 [24%]; RR 1·03, 95% CI 0·95-1·11, p=0·52). The most common safety outcomes in the methylprednisolone and placebo group were infection (465 [12%] vs 493 [13%]), surgical site infection (151 [4%] vs 151 [4%]), and delirium (295 [8%] vs 289 [8%]).
  
  
  CONCLUSIONS
  Methylprednisolone did not have a significant effect on mortality or major morbidity after cardiac surgery with cardiopulmonary bypass. The SIRS trial does not support the routine use of methylprednisolone for patients undergoing cardiopulmonary bypass.
  
  
  BACKGROUND
  Canadian Institutes of Health Research.
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Department of Surgery, McMaster University, Hamilton, ON, Canada; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. Electronic address: richard.whitlock@phri.ca.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Whitlock
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: P J
authors.initials: PJ
authors.lastname: Devereaux
authors.affiliation: Department of Surgery, Southlake Regional Health Centre, Newmarket, ON, Canada.
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Teoh
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Department of Surgery, McMaster University, Hamilton, ON, Canada; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Andre
authors.initials: A
authors.lastname: Lamy
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Vincent
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
authors.forename: Janice
authors.initials: J
authors.lastname: Pogue
authors.affiliation: University of Bari Aldo Moro, Bari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Paparella
authors.affiliation: Department of Outcomes Research, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Sessler
authors.affiliation: All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ganesan
authors.initials: G
authors.lastname: Karthikeyan
authors.affiliation: Fundación Cardio Infantil-Instituto de Cardiología, Bogotá, Colombia.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Villar
authors.affiliation: Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Divisão de Pesquisa, Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Avezum
authors.affiliation: London Health Sciences Centre, London, ON, Canada.
authors.forename: Mackenzie
authors.initials: M
authors.lastname: Quantz
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, University of Thessaly, Larissa, Greece.
authors.forename: Georgios I
authors.initials: GI
authors.lastname: Tagarakis
authors.affiliation: Princess Alexandra Hospital, Woolloongabba, Brisbane, QLD, Australia.
authors.forename: Pallav J
authors.initials: PJ
authors.lastname: Shah
authors.affiliation: Tehran Heart Centre, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Hesameddin
authors.initials: SH
authors.lastname: Abbasi
authors.affiliation: First Teaching Hospital of Xinjiang Medical University, Urumqi, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
authors.forename: Shirley
authors.initials: S
authors.lastname: Pettit
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Chrolavicius
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000893:Anti-Inflammatory Agents; D008775:Methylprednisolone