ArticleShock (Augusta, Ga.)2026
A New Proposed Approach to Categorize Sepsis Sub-phenotypes Based on Combined Trajectories of Perfusion Index and Central Venous Oxygen Saturation.
Article in Shock (Augusta, Ga.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
backgroundCirculatory 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.
methodsThis 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.
resultsAmong 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).
conclusionsA 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.
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