Identifying a target group for selenium supplementation in high-risk cardiac surgery: a secondary analysis of the SUSTAIN CSX trial

Quirin Notz; Daren K Heyland; Zheng-Yii Lee; Johannes Menger; Johannes Herrmann; Thilo S Chillon; Stephen Fremes; Siamak Mohammadi; Gunnar Elke; C David Mazer; Aileen Hill; Markus Velten; Sascha Ott; Maren Kleine-Brueggeney; Patrick Meybohm; Lutz Schomburg; Christian Stoppe

doi:10.1186/s40635-023-00574-8

Identifying a target group for selenium supplementation in high-risk cardiac surgery: a secondary analysis of the SUSTAIN CSX trial

Intensive Care Med Exp. 2023 Dec 8;11(1):89. doi: 10.1186/s40635-023-00574-8.

Authors

Quirin Notz¹, Daren K Heyland^{2

3}, Zheng-Yii Lee^{4

5}, Johannes Menger⁶, Johannes Herrmann⁶, Thilo S Chillon⁷, Stephen Fremes⁸, Siamak Mohammadi⁹, Gunnar Elke¹⁰, C David Mazer^{11

12}, Aileen Hill¹³, Markus Velten¹⁴, Sascha Ott^{5

15

16}, Maren Kleine-Brueggeney^{5

17}, Patrick Meybohm⁶, Lutz Schomburg^#⁷, Christian Stoppe^#^{18

19}

Affiliations

¹ Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany. [email protected].
² Clinical Evaluation Research Unit, Kingston General Hospital, 76 Stuart St, Kingston, ON, K7L 2V7, Canada.
³ Department of Critical Care Medicine, Queen's University, 99 University Ave, Kingston, ON, K7L 3N6, Canada.
⁴ Department of Anaesthesiology, University of Malaya, Lingkungan Budi, 50603, Kuala Lumpur, Malaysia.
⁵ Department of Cardiac Anaesthesiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Augustenburger Platz 1, 13353, Berlin, Germany.
⁶ Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany.
⁷ Charité Berlin, Institute for Experimental Endocrinology, Hessische Str. 4, 10115, Berlin, Germany.
⁸ University of Toronto, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada.
⁹ Laval University, Quebec Heart and Lung Institute, 2725 Ch Ste-Foy, Quebec City, QC, G1V 4G5, Canada.
¹⁰ Department of Anaesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3, 24105, Kiel, Germany.
¹¹ St. Michael's Hospital, Li Ka Shing Knowledge Institute, 38 Shuter St, Toronto, ON, M5B 1A6, Canada.
¹² Departments of Anesthesiology and Pain Medicine, Physiology and Pharmacology, University of Toronto, 123 Edward Street, Toronto, ON, M5G 1E2, Canada.
¹³ Department of Anaesthesiology and Operative Intensive Care Medicine, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.
¹⁴ Department of Anaesthesiology and Operative Intensive Care Medicine, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
¹⁵ Department of Outcomes Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
¹⁶ German Center for Cardiovascular Research, Partner Site Berlin, Potsdamer Str. 58, 10785, Berlin, Germany.
¹⁷ Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
¹⁸ Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany. [email protected].
¹⁹ Department of Critical Care Medicine, Queen's University, 99 University Ave, Kingston, ON, K7L 3N6, Canada. [email protected].

^# Contributed equally.

Abstract

Background: Recent data from the randomized SUSTAIN CSX trial could not confirm clinical benefits from perioperative selenium treatment in high-risk cardiac surgery patients. Underlying reasons may involve inadequate biosynthesis of glutathione peroxidase (GPx3), which is a key mediator of selenium's antioxidant effects. This secondary analysis aimed to identify patients with an increase in GPx3 activity following selenium treatment. We hypothesize that these responders might benefit from perioperative selenium treatment.

Methods: Patients were selected based on the availability of selenium biomarker information. Four subgroups were defined according to the patient's baseline status, including those with normal kidney function, reduced kidney function, selenium deficiency, and submaximal GPx3 activity.

Results: Two hundred and forty-four patients were included in this analysis. Overall, higher serum concentrations of selenium, selenoprotein P (SELENOP) and GPx3 were correlated with less organ injury. GPx3 activity at baseline was predictive of 6-month survival (AUC 0.73; p = 0.03). While selenium treatment elevated serum selenium and SELENOP concentrations but not GPx3 activity in the full patient cohort, subgroup analyses revealed that GPx3 activity increased in patients with reduced kidney function, selenium deficiency and low to moderate GPx3 activity. Clinical outcomes did not vary between selenium treatment and placebo in any of these subgroups, though the study was not powered to conclusively detect differences in outcomes.

Conclusions: The identification of GPx3 responders encourages further refined investigations into the treatment effects of selenium in high-risk cardiac surgery patients.

Keywords: Cardiac surgery; Critical care; Glutathione peroxidase; Oxidative stress; SUSTAIN CSX; Selenium.