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

## TL;DR

This study reanalyzed a large trial to see if high-dose selenium helps sepsis patients differently based on their sepsis type, but found no significant benefit.

## Contribution

The paper introduces a novel secondary analysis of sepsis trial data using established sepsis phenotypes to assess selenium treatment effects.

## Key findings

- No robust effect of selenium on mortality was found in any sepsis phenotype.
- Phenotype frequencies in the study cohort differed significantly from previous reports.
- 28-day mortality was lowest for α- and β-phenotypes but differences were not significant.

## Abstract

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.

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.

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%).

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.

The online version contains supplementary material available at 10.1186/s40560-025-00790-2.