Frontiers in medicine · 2026
Derivation of a novel clinical phenotype of sepsis in critically ill patients: a secondary analysis of a multicentre, prospective, observational study.
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Zha YuTao, Cui LiangWen, Nie ZhuSheng, Huang Rui, Zhang Cheng, Zhou Liang, Fang Ming, Peng XiaoChun, Zhang Jie, Wang Heng, Yu Chao, Liu Nian, Shao Min
Аннотация
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.
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.