ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2026
Identification of vital sign trajectory phenotypes and treatment response heterogeneity in critically ill patients with ischemic stroke: A multicenter study with external validation.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 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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Abstract
Critically ill patients with ischemic stroke exhibit heterogeneous hemodynamic patterns, yet previous trajectory-based studies have focused on single vital sign parameters. We conducted a multicenter retrospective cohort study to identify vital sign trajectory phenotypes, evaluate their prognostic value compared with traditional severity scores, and explore treatment response heterogeneity. Using group-based multi-trajectory modeling of six vital signs (systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, respiratory rate, and oxygen saturation) during the first 12 h after intensive care unit admission, we analyzed 3100 patients from MIMIC-IV for development and 3951 patients from eICU and Chinese Critical Care Database for external validation. Three distinct phenotypes were identified: tachycardic-tachypneic (25.6%), hypertensive-stable (37.5%), and low-diastolic quiescent (36.8%), with in-hospital mortality rates of 29.7%, 5.9%, and 14.9%, respectively. After multivariable adjustment, the tachycardic-tachypneic phenotype demonstrated significantly elevated in-hospital mortality risk compared with hypertensive-stable (HR 3.55, 95% CI 2.23-5.64), with consistent associations for 28-day (HR 4.38, 95% CI 2.97-6.46) and one-year mortality (HR 4.50, 95% CI 3.35-6.04). Phenotype-based classification outperformed SOFA, SAPS II, and Charlson index for one-year mortality prediction. Exploratory analysis revealed phenotype-specific dose-mortality associations for normal saline volumes, with tachycardic-tachypneic and hypertensive-stable phenotypes showing lower predicted mortality at higher Day 1 vol (2357-3500 mL and 1929-3500 mL), while low-diastolic quiescent showed lower predicted mortality with restricted Day 2 fluids (0-714 mL). Propofol similarly showed differential dose-mortality associations across phenotypes. These findings support trajectory-based phenotyping for early risk stratification and may inform precision-guided therapeutic approaches in critically ill ischemic stroke patients.
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