A New Proposed Approach to Categorize Sepsis Sub-phenotypes Based on Combined Trajectories of Perfusion Index and Central Venous Oxygen Saturation.

Journal: Shock (Augusta, Ga.)
Published Date: Dec 26, 2025

Abstract

BACKGROUND: Circulatory disturbances in sepsis are heterogeneous but may manifest as a mismatch between peripheral perfusion and tissue oxygenation. Peripheral perfusion index (PI) and central venous oxygen saturation (ScvO 2 ) have been independently validated as prognostic markers in sepsis; however, their combined utility remains unexplored. METHODS: This retrospective cohort study included patients admitted to three intensive care units between January 1, 2015, and December 31, 2021. A novel index, PISO = (PI - 1.1) × ScvO 2 , was calculated every 6 hours during the first 72 hours following sepsis onset. Dynamic time warping and hierarchical agglomerative clustering were applied to PISO trajectories to identify sub-phenotypes, with internal validation and sensitivity analysis. Machine learning algorithms were used to predict the sub-phenotypes using clinical features. Survival was assessed using Kaplan-Meier analysis, with particular focus on the association with 12-hour cumulative fluid balance. RESULTS: Among 12,975 patients, 5,205 (40.1%) developed sepsis; 720 patients with complete PI and ScvO 2 data were included. Three distinct PISO sub-phenotypes were identified. Phenotype 3 (n = 190, 33.0%), characterized by a persistently declining trajectory from negative, was associated with the poorest clinical outcomes. Random forest classifier demonstrated the best performance and identified key early clinical features differentiating each sub-phenotype. Kaplan-Meier analysis revealed that a 12-hour cumulative fluid balance ≤0 mL was significantly associated with improved 28-day survival in phenotype 1 ( P = 0.038) and phenotype 2 ( P = 0.033). CONCLUSIONS: A persistently negative and declining PISO index within the first 72 hours of sepsis onset identifies a high-risk sub-phenotype. A nonpositive 12-hour cumulative fluid balance is associated with improved survival in select sub-phenotypic groups.

Authors

  • Xinchen Wang
    Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, China.
  • Xiaoting Wang
    He University, Shenyang, 110000, China.
  • Yan Kang
    Sino-Dutch Biomedical and Information Engineering School, Northeastern University, Shenyang, Liaoning, People's Republic of China.
  • Xiang Zhou
    Department of Sociology, Harvard University, Cambridge, Massachusetts, USA.
  • Wei Du
    Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Yun Long
    Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

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