Derivation of a novel clinical phenotype of sepsis in critically ill patients: a secondary analysis of a multicentre, prospective, observational study.

Authors

YuTao Zha, LiangWen Cui, ZhuSheng Nie, Rui Huang, Cheng Zhang, Liang Zhou, Ming Fang, XiaoChun Peng, Jie Zhang, Heng Wang, Chao Yu, Nian Liu, Min Shao

Published in

Frontiers in medicine. Volume 13. Pages 1910023. Epub Sep 16, 2026.

Abstract

Sepsis is a highly heterogeneous syndrome. Providing personalized treatment for the various clinical phenotypes of sepsis has been a major challenge for critical care physicians.
This study was a secondary analysis of data derived from a multicenter, prospective, observational study of sepsis patients. Based on relevance to sepsis onset or outcome, 25 parameters were selected by the derived cohort to derive sepsis phenotypes. Clustered phenotypes were derived via k-means clustering and examined in a sensitivity analysis using divisive hierarchical clustering. Then, the relationship between fluid resuscitation therapy and survival outcomes was assessed for each clustered phenotype using generalized estimating equations.
Patients with sepsis were categorized into Cluster A, B and C. Kaplan-Meier analysis showed Cluster A patients had the highest 28-day mortality (P = 0.029 by Log-rank test). In Cluster A, septic patients who received fluid resuscitation had a association than those who did not, with an adjusted RD for 28-day mortality of 16.2% (95% CI, 1.4 to 31.0%, P = 0.032). Sensitivity analyses adjusted for APACHE II and infection site confirmed these findings, with an adjusted RD for 28-day mortality of 6.3% (95% CI, 0.3 to 12.3%, P = 0.040). Hierarchical clustering methods yielded consistent conclusions.
The association between fluid resuscitation and clinical outcomes varied across sepsis phenotypes, suggesting potential heterogeneity in treatment response that requires further prospective validation.Trial registration: The primary study was registered in the China Clinical Registry on February 1, 2022, with the registration number ChiCTR2200056179.

PMID:
42819483
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

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