Sepsis Endotypes Defined By Cytokine Trajectory Analysis

Methods The Protocol-based Care in Early Septic Shock (ProCESS) trial prospectively enrolled 1341 patients with sepsis having a 19.3% 60-day mortality (Yealy et al., 2014). Biomarker levels were obtained soon after enrollment (t = 0) and at 6, 24 and 72 hours in a convenience cohort of 638 patients having 17.1% mortality. We used trajectory analysis to cluster IL-6, IL-10, and joined IL-6 and IL-10 trajectories in the 638 patients having at least one measurement of IL-6 or IL-10, in patients with markers rising between 0 and 6 hours (presumably earlier in the course of sepsis), and in patients with monotonically decreasing biomarker levels (presumably later in the course of sepsis). Trajectories were described as increasing from t = 0 to 6 hours, decreasing or flat. 60-day mortality was compared between clusters to determine the association between cytokine trajectory and mortality.