Derivation of a novel clinical phenotype of sepsis in critically ill patients: a secondary analysis of a multicentre, prospective, observational study
In brief
Three sepsis phenotypes showed different mortality and fluid-treatment associations
In this observational analysis, researchers grouped patients with sepsis into three clinical phenotypes; Cluster A had the highest 28-day mortality. In that group, fluid resuscitation was associated with a 16.2-percentage-point difference in adjusted 28-day mortality, though the abstract does not specify its direction. The findings suggest treatment responses may vary, but need prospective validation.
- Journal
- Frontiers in medicine (Q1)
- Published
- 16 September 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- YuTao Zha, LiangWen Cui, ZhuSheng Nie, Rui Huang, Cheng Zhang, Liang Zhou, et al.
- PMID
- 42819483
- DOI
- 10.3389/fmed.2026.1910023
Why clinicians should know about it
- Picked for Critical Care and Intensive Care Medicine (paper of the day, 4 October 2026): Sepsis phenotypes affect fluid response
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.