Cytokine Biomarker Phenotype for Early Prediction and Triage of Sepsis in Blunt Trauma Patients.

Abstract

BACKGROUND Altered levels of inflammatory markers secondary to severe trauma present a major problem to physicians and are prone to interfering with the clinical identification of sepsis events. This study aimed to establish the profiles of cytokines in trauma patients to characterize the nature of immune responses to sepsis, which might enable early prediction and individualized treatments to be developed for targeted intervention. METHODS A 15-plex human cytokine magnetic bead assay system was used to measure analytes in citrated plasma samples. Analysis of the kinetics of these cytokines was performed in 40 patients with severe blunt trauma admitted to our trauma center between March 2016 and February 2017, with an Injury Severity Score (ISS) greater than 20 with regard to sepsis (Sepsis-3) over a 14-d time course. RESULTS In total, the levels of six cytokines were altered in trauma patients across the 1-, 3-, 5-, 7-, and 14-d time points. Additionally, IL-6, IL-10, IL-15, macrophage derived chemokine (MDC), GRO, sCD40 L, granulocyte colony-stimulating factor (G-CSF), and fibroblast growth factor (FGF)-2 levels could be used to provide a significant discrimination between sepsis and nonsepsis patients at day 3 and afterward, with an area under the curve (AUC) of up to 0.90 through a combined analysis of the eight biomarkers (P < 0.001). Event-related analysis demonstrated 1.5- to 4-fold serum level changes for these cytokines within 72 h before clinically apparent sepsis. CONCLUSIONS Cytokine profiles demonstrate a high discriminatory ability enabling the timely identification of evolving sepsis in trauma patients. These abrupt changes enable sepsis to be detected up to 72 h before clinically overt deterioration. Defining cytokine release patterns that distinguish sepsis risk from trauma patients might enable physicians to initiate timely treatment and reduce mortality. Large prospective studies are needed to validate and operationalize the findings. TRIAL REGISTRATION Clinicaltrials, NCT01713205. Registered October 22, 2012, https://register. CLINICALTRIALS gov/NCT01713205.