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. 2025 Apr 14;13(1):21.
doi: 10.1186/s40560-025-00790-2.

Treatment effect of intravenous high-dose selenium in sepsis phenotypes: a retrospective analysis of a large multicenter randomized controlled trial

David I Radke #  1 , Holger Bogatsch #  2   3 , Christoph Engel  3 , Frank Bloos  4 , Patrick Meybohm  5 , Michael Bauer  4 , Anna Lulu Homayr  6 , Christian Stoppe  5   7 , Gunnar Elke  8 , Matthias Lindner  6 ; SepNet Critical Care Trials Group
Collaborators, Affiliations

Treatment effect of intravenous high-dose selenium in sepsis phenotypes: a retrospective analysis of a large multicenter randomized controlled trial

David I Radke et al. J Intensive Care. .

Abstract

Background: Treatment effect of high-dose intravenous selenium remains controversial in patients with sepsis or septic shock. Here, we reanalyzed data from the randomized placebo-controlled trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT) to reveal possible treatment differences according to established sepsis phenotypes.

Methods: In this secondary data analysis of the SISPCT trial all 1089 patients of the original study were included. Patients were assigned to one of the four phenotypes by comparing patient variables with the Sepsis Endotyping in Emergency Care (SENECA) validation cohort. Survival analyses were performed using Kaplan-Meier and log-rank tests.

Results: No robust effect of selenium on mortality and other outcome parameters could be determined in any sepsis phenotype. Phenotype frequencies were markedly different in our study cohort compared to previous reports (α: 2.2%, β: 6.3%, γ: 68.0%, δ: 23.4%). Differences in mortality between the respective phenotypes were not significant overall; however, 28-day mortality showed a lower mortality for the α- (20.8%) and β-phenotype (20.3%), followed by the γ- (27.1%), and δ-phenotype (28.5%).

Conclusions: Application of the four sepsis phenotypes to the SISPCT study cohort showed discrete but non-significant mortality differences within 28 days. However, beneficial treatment effects of high-dose intravenous selenium were still not detectable after categorizing the SISPCT study cohort according to four phenotype criteria.

Keywords: Individualized medicine; Micronutrient; Oxidative stress; Pharmaconutrition; Sepsis; Sepsis phenotypes; Septic shock; Sodium selenite.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study protocol of the SISPCT trial was approved by the ethics board of Jena University Hospital (Internal File No. 2242-03/08). Written informed consent was obtained from all patients or their legal representatives. Consent for publication: Not applicable. No individual participant data is reported that would require consent to publish from the participant. Competing interests: All authors have provided information on potential conflicts of interests directly or indirectly related to the work submitted in the journal’s disclosure forms. FB reported receiving lecture honoraria from biosyn, Gilead, and CSL Behring and public funding for the SISPCT trial to his department by the German Federal Ministry of Education and Research and unrestricted research grants for the SISPCT trial from biosyn and Thermo Fisher Scientific. CS received honorarium as speaker and/or consultant for Fresenius, Baxter and BBRAUN. GE received honorarium as speaker and/or consultant for Fresenius. All other authors declared that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Flowchart of study cohort
Fig. 2
Fig. 2
Survival functions of study population treated with selenium or placebo clustered in phenotypes γ and δ after 90 days. A shows cumulative survival of γ-phenotype, B shows cumulative survival of δ-phenotype. α- and β-phenotype not shown
Fig. 3
Fig. 3
Survival functions according to phenotypes. A shows cumulative survival after 28 days, B shows cumulative survival after 90 days
See this image and copyright information in PMC

References

    1. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet. 2020;395(10219):200–11. - PMC - PubMed
    1. Manzanares W, Dhaliwal R, Jiang X, Murch L, Heyland DK. Antioxidant micronutrients in the critically ill: a systematic review and meta-analysis. Crit Care. 2012;16(2):R66. - PMC - PubMed
    1. Manzanares W, Biestro A, Torre MH, Galusso F, Facchin G, Hardy G. High-dose selenium reduces ventilator-associated pneumonia and illness severity in critically ill patients with systemic inflammation. Intensive Care Med. 2011;37(7):1120–7. - PubMed
    1. Valenta J, Brodska H, Drabek T, Hendl J, Kazda A. High-dose selenium substitution in sepsis: a prospective randomized clinical trial. Intensive Care Med. 2011;37(5):808–15. - PubMed
    1. Steinbrenner H, Sies H. Selenium homeostasis and antioxidant selenoproteins in brain: implications for disorders in the central nervous system. Arch Biochem Biophys. 2013;536(2):152–7. - PubMed

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