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The effect of a selenium-based anti-inflammatory strategy on postoperative functional recovery in high-risk cardiac surgery patients - A nested sub-study of the sustain CSX trial

Ott S 1 , Lee ZY 2 , Müller-Wirtz LM 3 , Cangut B 4 , Roessler J 5 , Patterson W 6 Show all authors , Thomas CM 7 , Bekele BM 8 , Windpassinger M 9 , Lobdell K 10 , Grant MC 11 , Arora RC 12 , Engelman DT 13 , Fremes S 14 , Velten M 15 , O'Brien B 16 , Ruetzler K 17 , Heyland DK 18 , Stoppe C 19

Affiliations 

  • 1 Deutsches Herzzentrum der Charité, Department of Cardiac Anaesthesiology and Intensive Care Medicine, Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany; Outcomes Research Consortium, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: Sascha.ott@dhzc-charite.de
  • 2 Deutsches Herzzentrum der Charité, Department of Cardiac Anaesthesiology and Intensive Care Medicine, Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Anaesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 3 Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, 66424 Homburg, Saarland, Germany; Outcomes Research Consortium, Department of Anesthesiology, Cleveland Clinic, OH, USA. Electronic address: lukas@muellerwirtz.de
  • 4 Department of Cardiovascular Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: busra.cangut@mountsinai.org
  • 5 Outcomes Research Consortium, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Institute of Anaesthesiology, University Hospital Zurich, 8091 Zurich, Switzerland
  • 6 Outcomes Research Consortium, Department of Anesthesiology, Cleveland Clinic, OH, USA. Electronic address: patterw@ccf.org
  • 7 Deutsches Herzzentrum der Charité, Department of Cardiac Anaesthesiology and Intensive Care Medicine, Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Infectious Diseases and Respiratory Medicine, Berlin, Germany. Electronic address: christian-michael.thomas@dhzc-charite.de
  • 8 Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum der Charité (DHZC), Augustenburger Platz 1, 13353 Berlin, Germany. Electronic address: biniam.bekele@dhzc-charite.de
  • 9 Department of Anesthesia, Critical Care and Pain Medicine, Division of General Anesthesia and Intensive Care Medicine, Medical University Vienna, Vienna, Austria. Electronic address: Marita.windpassinger@meduniwien.ac.at
  • 10 Department of Thoracic and Cardiovascular Surgery, Sanger Heart and Vascular Institute, Carolinas Medical Center, Charlotte, NC 28203, USA. Electronic address: kevin.lobdell@atriumhealth.org
  • 11 Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD, USA; Armstrong Institute for Patient Safety and Quality, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address: mgrant17@jhmi.edu
  • 12 Division of Cardiac Surgery, Harrington Heart and Vascular Institute, University Hospitals, Cleveland, OH, USA
  • 13 Heart and Vascular Program, Baystate Health and University of Massachusetts Chan Medical School-Baystate, 759 Chestnut Street, Springfield, MA 01199, USA
  • 14 Division of Cardiac Surgery, Schulich Heart Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, M4N 3M5, Department of Surgery, University of Toronto, Toronto, Canada. Electronic address: stephen.fremes@sunnybrook.ca
  • 15 Department of Anesthesiology and Pain Management, Division of Cardiovascular and Thoracic Anesthesiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: Markus.Velten@utsouthwestern.edu
  • 16 Deutsches Herzzentrum der Charité, Department of Cardiac Anaesthesiology and Intensive Care Medicine, Berlin, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany; St Bartholomew's Hospital and Barts Heart Centre, Department of Perioperative Medicine, London EC1A 7BE, UK. Electronic address: Ben.obrien@dhzc-charite.de
  • 17 Outcomes Research Consortium, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Department of General Anesthesia, Anesthesiology Institute, Cleveland Clinic, Cleveland, USA. Electronic address: ruetzlk@ccf.org
  • 18 Clinical Evaluation Research Unit, Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada. Electronic address: dkh2@queensu.ca
  • 19 Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital, Würzburg, Würzburg, Germany; Department of Cardiac Anesthesiology and Intensive Care Medicine, Charité Berlin, Berlin, Germany. Electronic address: Christian.stoppe@gmail.com
Life Sci, 2024 Aug 15;351:122841.
PMID: 38897349 DOI: 10.1016/j.lfs.2024.122841

Abstract

AIM: The cardiac surgery-related ischemia-reperfusion-related oxidative stress triggers the release of cytotoxic reactive oxygen and nitrogen species, contributing to organ failure and ultimately influencing patients' short- and long-term outcomes. Selenium is an essential co-factor for various antioxidant enzymes, thereby contributing to the patients' endogenous antioxidant and anti-inflammatory defense mechanisms. Given these selenium's pleiotropic functions, we investigated the effect of a high-dose selenium-based anti-inflammatory perioperative strategy on functional recovery after cardiac surgery.

MATERIALS AND METHODS: This prospective study constituted a nested sub-study of the SUSTAIN CSX trial, a double-blinded, randomized, placebo-controlled multicenter trial to investigate the impact of high-dose selenium supplementation on high-risk cardiac surgery patients' postoperative recovery. Functional recovery was assessed by 6-min walk distance, Short Form-36 (SF-36) and Barthel Index questionnaires.

KEY FINDINGS: 174 patients were included in this sub-study. The mean age (SD) was 67.3 (8.9) years, and 78.7 % of the patients were male. The mean (SD) predicted 30-day mortality by the European System for Cardiac Operative Risk Evaluation II score was 12.6 % (9.4 %). There was no difference at hospital discharge and after three months in the 6-min walk distance between the selenium and placebo groups (131 m [IQR: not performed - 269] vs. 160 m [IQR: not performed - 252], p = 0.80 and 400 m [IQR: 299-461] vs. 375 m [IQR: 65-441], p = 0.48). The SF-36 and Barthel Index assessments also revealed no clinically meaningful differences between the selenium and placebo groups.

SIGNIFICANCE: A perioperative anti-inflammatory strategy with high-dose selenium supplementation did not improve functional recovery in high-risk cardiac surgery patients.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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