Using time-course as an essential factor to accurately predict sepsis-associated mortality among patients with suspected sepsis

Biomarker dynamics in different time-courses might be the primary reason why a static measurement of a single biomarker cannot accurately predict sepsis outcomes. Therefore, we conducted this prospective hospital-based cohort study to simultaneously evaluate the performance of several conventional and novel biomarkers of sepsis in predicting sepsis-associated mortality on different days of illness among patients with suspected sepsis. We evaluated the performance of 15 novel biomarkers including angiopoietin-2, pentraxin 3, sTREM-1, ICAM-1, VCAM-1, sCD14 and 163, E-selectin, P-selectin, TNF-alpha, interferon-gamma, CD64, IL-6, 8, and 10, along with few conventional markers for predicting sepsis-associated mortality. Patients were grouped into quartiles according to the number of days since symptom onset. Receiver operating characteristic curve (ROC) analysis was used to evaluate the biomarker performance. From 2014 to 2017, 1483 patients were enrolled, of which 78% fulfilled the systemic inflammatory response syndrome criteria, 62% fulfilled the sepsis-3 criteria, 32% had septic shock, and 3.3% developed sepsis-associated mortality. IL-6, pentraxin 3, sCD163, and the blood gas profile demonstrated better performance in the early days of illness, both before and after adjusting for potential confounders (adjusted area under ROC curve [AUROC]:0.81–0.88). Notably, the Sequential Organ Failure Assessment (SOFA) score was relatively consistent throughout the course of illness (adjusted AUROC:0.70–0.91). IL-6, pentraxin 3, sCD163, and the blood gas profile showed excellent predictive accuracy in the early days of illness. The SOFA score was consistently predictive of sepsis-associated mortality throughout the course of illness, with an acceptable performance.