Effect of High-Dose Selenium on Postoperative Organ Dysfunction and Mortality in Cardiac Surgery Patients

JAMA Surgery, vol. 158, pp. 235

Abstract

Importance: Selenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery. Objective: To assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients. Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021. Adult cardiac surgery patients with a European System for Cardiac Operative Risk Evaluation II score-predicted mortality of 5% or more or planned combined surgical procedures were randomized. Interventions: Patients were randomly assigned (1:1) by a web-based system to receive either perioperative intravenous high-dose selenium supplementation of 2000 μg/L of sodium selenite prior to cardiopulmonary bypass, 2000 μg/L immediately postoperatively, and 1000 μg/L each day in intensive care for a maximum of 10 days or placebo. Main Outcomes and Measures: The primary end point was a composite of the numbers of days alive and free from organ dysfunction during the first 30 days following cardiac surgery. Results: A total of 1416 adult cardiac surgery patients were analyzed (mean [SD] age, 68.2 [10.4] years; 1043 [74.8%] male). The median (IQR) predicted 30-day mortality by European System for Cardiac Operative Risk Evaluation II score was 8.7% (5.6%-14.9%), and most patients had combined coronary revascularization and valvular procedures. Selenium did not increase the number of persistent organ dysfunction-free and alive days over the first 30 postoperative days (median [IQR], 29 [28-30] vs 29 [28-30]; P = .45). The 30-day mortality rates were 4.2% in the selenium and 5.0% in the placebo group (odds ratio, 0.82; 95% CI, 0.50-1.36; P = .44). Safety outcomes did not differ between the groups. Conclusions and Relevance: In high-risk cardiac surgery patients, perioperative administration of high-dose intravenous sodium selenite did not reduce morbidity or mortality. The present data do not support the routine perioperative use of selenium for patients undergoing cardiac surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT02002247.

Authors 46

1. Christian Stoppe corresponding

   University of Ottawa · Ottawa Heart Institute

   Affiliation as printed

   University of Ottawa Heart Institute, Ottawa, Ontario, Canada

2. Bernard J McDonald

   University of Ottawa · Ottawa Heart Institute

   Affiliation as printed

   University of Ottawa Heart Institute, Ottawa, Ontario, Canada

3. Patrick Meybohm

   Universitätsklinikum Würzburg

   Affiliation as printed

   Department of Anaesthesiology, Intensive Care, Emergency, and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany

4. Kenneth B. Christopher

   Brigham and Women's Hospital

   Affiliation as printed

   Division of Renal Medicine, Brigham and Women’s Hospital, Boston, Massachusetts

   Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts

5. Stephen Edward Fremes

   Sunnybrook Hospital · Sunnybrook Research Institute

   Affiliation as printed

   Sunnybrook Research Institute, Toronto, Ontario, Canada

6. Richard Paul Whitlock

   Hamilton Health Sciences

   Affiliation as printed

   Hamilton Health Sciences, Hamilton, Ontario, Canada

7. Siamak Mohammadi

   Institut universitaire de cardiologie et de pneumologie de Québec · Université Laval

   Affiliation as printed

   Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada

8. Dimitri Kalavrouziotis

   Institut universitaire de cardiologie et de pneumologie de Québec · Université Laval

   Affiliation as printed

   Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada

9. Gunnar Elke

   University Hospital Schleswig-Holstein

   Affiliation as printed

   University Hospital Schleswig-Holstein, Kiel, Germany

10. Rolf Rossaint Aachen

    Universitätsklinikum Aachen

    Affiliation as printed

    University Hospital Aachen, Aachen, Germany

11. Philipp Helmer

    Universitätsklinikum Würzburg

    Affiliation as printed

    Department of Anaesthesiology, Intensive Care, Emergency, and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany

12. Kai D. Zacharowski

    University Hospital Frankfurt

    Affiliation as printed

    University Hospital Frankfurt, Frankfurt, Germany

13. Ulf Guenther

    Carl von Ossietzky Universität Oldenburg

    Affiliation as printed

    Oldenburg Clinic, University of Oldenburg, Oldenburg, Germany

14. Matteo Parotto

    University of Toronto · Toronto General Hospital

    Affiliation as printed

    Department of Anesthesiology and Pain Medicine, Toronto General Hospital, Toronto, Ontario, Canada

    Division of Critical Care Medicine, Department of Anesthesia and Interdepartmental University of Toronto, Toronto, Ontario, Canada

15. Bernd Niemann

    Universitätsklinikum Gießen und Marburg

    Affiliation as printed

    University Hospital of Giessen, Giessen, Germany

16. Andreas Böning

    Universitätsklinikum Gießen und Marburg

    Affiliation as printed

    University Hospital of Giessen, Giessen, Germany

17. C. David Mazer

    St. Michael's Hospital · University of Toronto

    Affiliation as printed

    Department of Anesthesiology and Pain Medicine, Department of Physiology, University of Toronto, Toronto, Ontario, Canada

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

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

18. Philip M. Jones

    London Health Sciences Centre

    Affiliation as printed

    London Health Sciences Centre, London, Ontario, Canada

19. Marion Ferner

    University Medical Center of the Johannes Gutenberg University Mainz

    Affiliation as printed

    University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

20. Yoan Lamarche

    Montreal Heart Institute · Hôpital du Sacré-Cœur de Montréal

    Affiliation as printed

    Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada

    Montreal Heart Institute, Montreal, Quebec, Canada

21. François Lamontagne

    Hôpital Fleurimont

    Affiliation as printed

    Hôpital Fleurimont (CHUS), Sherbrooke, Quebec, Canada

22. Oliver Joannis Liakopoulos

    University Hospital Cologne

    Affiliation as printed

    Department of Cardiothoracic Surgery, Heart Center, University Hospital of Cologne, Cologne, Germany

23. Matthias Müller

    Universitäts-Herzzentrum Freiburg-Bad Krozingen

    Affiliation as printed

    University Heart Center Freiburg Bad Krozingen, Bad Krozingen, Germany

24. Alexander Zarbock

    University Hospital Münster

    Affiliation as printed

    University Hospital Münster, Münster, Germany

25. Mária Wittmann

    University Hospital Bonn

    Affiliation as printed

    University Hospital Bonn, Bonn, Germany

26. Andreas Goetzenich Aachen now with Abiomed Europe GmbH

    Abiomed (Germany) · Universitätsklinikum Aachen

    Affiliation as printed

    University Hospital Aachen, Aachen, Germany

    now with Abiomed Europe GmbH, Aachen, Germany

27. Erich Kilger

    Ludwig-Maximilians-Universität München

    Affiliation as printed

    Ludwig Maximilian University of Munich, Munich, Germany

28. Lutz Schomburg

    Charité - Universitätsmedizin Berlin

    Affiliation as printed

    Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany

29. Andrew G. Day

    Queen's University · Clinical Evaluation Research Unit

    Affiliation as printed

    Clinical Evaluation Research Unit, Queen’s University, Kingston, Ontario, Canada

    Clinical Evaluation Research Unit, Queen's University, Kingston, Ontario, Canada

30. Daren Keith Heyland

    Queen's University · Clinical Evaluation Research Unit

    Affiliation as printed

    Clinical Evaluation Research Unit, Queen’s University, Kingston, Ontario, Canada

    Department of Critical Care Medicine, Queen’s University, Kingston, Ontario, Canada

    Clinical Evaluation Research Unit, Queen's University, Kingston, Ontario, Canada

    Department of Critical Care Medicine, Queen's University, Kingston, Ontario, Canada

31. Gregory M. T. Hare
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators

32. Michael WA Chu
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators

33. Pierre Voisine
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators

34. François Dagenais
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators

35. Éric Dumont
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators

36. Frédérique Jacques
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators

37. Éric Charbonneau
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators

38. Jean Perron
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators

39. Simone Lindau
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators

40. Roupen Hatzakorizan
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators

41. Assad Haneya
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators

42. Georg Trummer
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators

43. Angela Jareth
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators

44. Xuran Jiang
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators

45. Ellen Dresen
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators

46. Aileen Hill
    Affiliation as printed

    for the SUSTAIN CSX Study Collaborators