Phenotyping Sepsis at Emergency Department Presentation Using Early Clinical Data: A Multicenter Cohort Study
Junhyuk Seo, Namkee Oh, Gee Young Suh, Chae-Man Lim, Won Chul Cha, Ryoung-Eun KoBackground:
Sepsis is heterogeneous, and early emergency department (ED) management is constrained by limited information and dynamic clinical trajectories.
Methods:
Using the nationwide Korean Sepsis Alliance (KSA) registry, we applied k-means clustering to nine routine ED variables (demographics, vital signs, Clinical Frailty Scale, mental status, lactate). The model was developed in KSA 3 (2019–2021) and tested for temporal reproducibility in the independent KSA 5 cohort (2022–2023). Phenotypes were compared on 7-day mortality, early sepsis-bundle compliance, and SOFA trajectories; stability was assessed by bootstrap resampling and alternative clustering. One-hour vasopressor non-compliance was decomposed into criterion-not-met versus delivered-with-delay.
Results:
Six phenotypes were identified in 9,430 patients and reproduced in 7,184 (mortality-rank ρ = 1.00; calibration drift, O/E 0.83–1.32). Seven-day mortality ranged 6.7%–31.8%. Extreme-severity phenotypes (A, F, E) were bootstrap-robust (Jaccard 0.65–0.91), whereas intermediate phenotypes (B, D) were less stable (0.21–0.47), consistent with a continuous severity spectrum. Non-compliance composition separated phenotypes that severity scores rank together: predominantly criterion-not-met (appropriate withholding) in low-acuity phenotype C versus delivered-with-delay in high-acuity phenotype E. Phenotypes B and F, matched on presenting physiology and mortality but differing in frailty and mental status, still differed in composition (criterion-not-met 49.6% vs 28.3%; p < 0.001). SOFA trajectories were highest in phenotype E.
Conclusions:
ED-presentation phenotyping using routine variables identifies six cross-sectional signatures along the sepsis severity spectrum rather than definitive subtypes. Decomposing bundle non-compliance shows that it combines appropriate withholding and urgency-associated delay in phenotype-dependent proportions, a distinction one-dimensional severity scores cannot make, relevant to phenotype-stratified resuscitation warranting prospective evaluation.