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Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival

A Planned Subanalysis of the ENIGMA-II Trial

Beattie, W. Scott, MD, PhD, FRCPC*,†,‡; Wijeysundera, Duminda N., MD, PhD, FRCPC†,§,‖; Chan, Matthew T. V., MBBS, PhD, FANZCA, FHKCA, FHKAM; Peyton, Philip J., MBBS, MD, PhD, FANZCA#,**; Leslie, Kate, MBBS, MD, MEpid, MHlthServMt, FANZCA, FAHMS††,‡‡,§§,‖‖; Paech, Michael J., MBBS, DM, DRCOG, FRCA, FANZCA, FFPMANZCA, FRANZCOG (Hons)¶¶,##; Sessler, Daniel I., MD***; Wallace, Sophie, MPH‖‖,†††; Myles, Paul S., MBBS, MD, MPH, DSc, FANZCA, FCAI, FRCA, FAHMS‖‖,†††,‡‡‡; Galagher, W.; Farrington, C.; Ditoro, A.; Baulch, S.; Sidiropoulos, S.; Bulach, R.; Bryant, D.; O’Loughlin, E.; Mitteregger, V.; Bolsin, S.; Osborne, C.; McRae, R.; Backstrom, M.; Cotter, R.; March, S.; Silbert, B.; Said, S.; Halliwell, R.; Cope, J.; Fahlbusch, D.; Crump, D.; Thompson, G.; Jefferies, A.; Reeves, M.; Buckley, N.; Tidy, T.; Schricker, T.; Lattermann, R.; Iannuzzi, D.; Carroll, J.; Jacka, M.; Bryden, C.; Badner, N.; Tsang, M. W. Y.; Cheng, B. C. P.; Fong, A. C. M.; Chu, L. C. Y.; Koo, E. G. Y.; Mohd, N.; Ming, L. E.; Campbell, D.; McAllister, D.; Walker, S.; Olliff, S.; Kennedy, R.; Eldawlatly, A.; Alzahrani, T.; Chua, N.; Sneyd, R.; McMillan, H.; Parkinson, I.; Brennan, A.; Balaji, P.; Nightingale, J.; Kunst, G.; Dickinson, M.; Subramaniam, B.; Banner-Godspeed, V.; Liu, J.; Kurz, A.; Hesler, B.; Fu, A. Y.; Egan, C.; Fiffick, A. N.; Hutcherson, M. T.; Turan, A.; Naylor, A.; Obal, D.; Cooke, E. on behalf of the ANZCA Clinical Trials Network for the ENIGMA-II Investigators

doi: 10.1213/ANE.0000000000003310
Cardiovascular and Thoracic Anesthesiology: Original Clinical Research Report
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BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery.

METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs).

RESULTS: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55–4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26–3.92]). Patients who suffered a MAPE with troponin elevation but without MI had the highest risk of death (n = 116) (aHR, 4.29 [95% CI, 2.89–6.36]). These 4 types of adverse events similarly affected 1-year disability-free survival.

CONCLUSIONS: MACEs and MAPEs occur at similar frequencies and affect survival to a similar degree. All 3 types of postoperative troponin elevation in this analysis were associated, to varying degrees, with increased risk of death and disability.

From the *Department of Anesthesia and Pain Management, University Health Network, University of Toronto, Toronto, Ontario, Canada

Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada

Departments of Anesthesia

§Anesthesia and Pain Management, Toronto General Hospital, Toronto, Ontario, Canada

Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, Ontario, Canada

Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

#Department of Anaesthesia, Austin Hospital, Melbourne, Victoria, Australia

**Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia

††Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Melbourne, Victoria, Australia

‡‡Department of Anaesthesia, Perioperative and Pain Medicine Unit, Melbourne Medical School, Parkville, Victoria, Australia

§§Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, Victoria, Australia

‖‖Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia

¶¶Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, Perth, Western Australia, Australia

##School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia

***Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio

†††Department of Anaesthesia and Perioperative Medicine, The Alfred Hospital, Melbourne, Victoria, Australia

‡‡‡Department of Anaesthesia and Perioperative Medicine, Monash University, Melbourne, Victoria, Australia.

Alfred

Alfred

Alfred

Austin

Austin

Dandenong

Dandenong

Fremantle

Fremantle

Geelong Hospital

Geelong Hospital

Monash Medical Centre

Monash Medical Centre

Royal Melbourne Hospital

Royal Perth Hospital

St Vincent’s Hospital

St Vincent’s Hospital

Westmead Hospital

Westmead Hospital

Calvary Wakefield

Calvary Wakefield

Peter MacCallum Cancer Centre

Western Hospital

North West Regional Hospital

Canada: McMaster University

Canada: McMaster University

Royal Victoria Hospital

Royal Victoria Hospital

Royal Victoria Hospital

Toronto General Hospital

University of Alberta Hospital

University of Alberta Hospital

London Health Sciences

Hong Kong: Prince of Wales

Tuen Mun Hospital

Tuen Mun Hospital

Pamela Youde Nethersole Eastern Hospital

Pamela Youde Nethersole Eastern Hospital

Malaysia: Hospital Kuala Lumpur

Malaysia: Hospital Kuala Lumpur

Auckland Hospital

Auckland Hospital

Middlemore Hospital

Middlemore Hospital

Christchurch Hospital

Saudi Arabia: King Saud University Hospital

Singapore: Tan Tock Seng Hospital

United Kingdom: Plymouth NHS Trust

United Kingdom: Plymouth NHS Trust

Royal Lancaster Infirmary

Bradford Teaching Hospital

Hull Royal Infirmary

Portsmouth Hospital

King’s College Hospital

Royal Surrey County Hospital

United States: Beth Israel Deaconess Medical Center

United States: Beth Israel Deaconess Medical Center

Cleveland Clinic

Cleveland Clinic

Cleveland Clinic

Cleveland Clinic

Cleveland Clinic

Cleveland Clinic

Cleveland Clinic

Cleveland Clinic

Cleveland Clinic

Louisville Medical Centre

Louisville Medical Centre

Published ahead of print March 12, 2018.

Accepted for publication December 22, 2017.

Funding: This study was supported by the Australian National Health and Medical Research Council; Australian and New Zealand College of Anaesthetists; Heart and Stroke Foundation of Quebec; Heart and Stroke Foundation of Ontario, Canada; and General Research Fund of the Research Grant Council, Hong Kong Special Administrative Region, China.

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Trial Registration: ClinicalTrials.gov (NCT00430989).

ANZCA Clinical Trials Network for the ENIGMA-II investigators is listed in Appendix.

Reprints will not be available from the authors.

Address correspondence to W. Scott Beattie, MD, PhD, FRCPC, Department of Anesthesia and Pain Management, University Health Network, Toronto, Ontario, Canada; and Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada, 200 Elizabeth St, Eaton 3-402, Toronto, Ontario M5G 2C4. Address e-mail to scott.beattie@uhn.ca.

© 2018 International Anesthesia Research Society
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