Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial

Richard P Whitlock; P J Devereaux; Kevin H Teoh; Andre Lamy; Jessica Vincent; Janice Pogue; Domenico Paparella; Daniel I Sessler; Ganesan Karthikeyan; Juan Carlos Villar; Yunxia Zuo; Álvaro Avezum; Mackenzie Quantz; Georgios I Tagarakis; Pallav J Shah; Seyed Hesameddin Abbasi; Hong Zheng; Shirley Pettit; Susan Chrolavicius; Salim Yusuf; SIRS Investigators

doi:10.1016/S0140-6736(15)00273-1

Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial

Lancet. 2015 Sep 26;386(10000):1243-1253. doi: 10.1016/S0140-6736(15)00273-1.

Authors

Richard P Whitlock¹, P J Devereaux², Kevin H Teoh³, Andre Lamy⁴, Jessica Vincent⁵, Janice Pogue⁵, Domenico Paparella⁶, Daniel I Sessler⁷, Ganesan Karthikeyan⁸, Juan Carlos Villar⁹, Yunxia Zuo¹⁰, Álvaro Avezum¹¹, Mackenzie Quantz¹², Georgios I Tagarakis¹³, Pallav J Shah¹⁴, Seyed Hesameddin Abbasi¹⁵, Hong Zheng¹⁶, Shirley Pettit⁵, Susan Chrolavicius⁵, Salim Yusuf¹⁷; SIRS Investigators

Affiliations

¹ 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: [email protected].
² 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.
³ Department of Surgery, Southlake Regional Health Centre, Newmarket, ON, Canada.
⁴ 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.
⁵ Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
⁶ University of Bari Aldo Moro, Bari, Italy.
⁷ Department of Outcomes Research, Cleveland Clinic, Cleveland, OH, USA.
⁸ All India Institute of Medical Sciences, New Delhi, India.
⁹ Fundación Cardio Infantil-Instituto de Cardiología, Bogotá, Colombia.
¹⁰ Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
¹¹ Divisão de Pesquisa, Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil.
¹² London Health Sciences Centre, London, ON, Canada.
¹³ Department of Cardiovascular and Thoracic Surgery, University of Thessaly, Larissa, Greece.
¹⁴ Princess Alexandra Hospital, Woolloongabba, Brisbane, QLD, Australia.
¹⁵ Tehran Heart Centre, Tehran University of Medical Sciences, Tehran, Iran.
¹⁶ First Teaching Hospital of Xinjiang Medical University, Urumqi, China.
¹⁷ Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada.

PMID: 26460660
DOI: 10.1016/S0140-6736(15)00273-1

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.

Findings: 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%]).

Interpretation: 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.

Funding: Canadian Institutes of Health Research.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Anti-Inflammatory Agents / therapeutic use*
Cardiopulmonary Bypass / adverse effects
Cardiopulmonary Bypass / methods*
Cardiopulmonary Bypass / mortality
Double-Blind Method
Female
Humans
Male
Methylprednisolone / therapeutic use*
Middle Aged
Systemic Inflammatory Response Syndrome / etiology
Systemic Inflammatory Response Syndrome / prevention & control*

Substances

Anti-Inflammatory Agents
Methylprednisolone

Associated data

ClinicalTrials.gov/NCT00427388

Grants and funding

Canadian Institutes of Health Research/Canada