Survival Analysis By Inflammatory Biomarkers In Severely Injured Patients Undergoing Damage Control Resuscitation
*Taylor E Wallen1, *Dennis Hanseman1, *Charles C Caldwell1, *Yao-Wei W Wang2, *Charles E Wade2, *John B Holcomb3, Timothy A Pritts1, Michael D Goodman1
1University of Cincinnati, Cincinnati, OH;2The University of Texas Health Science Center at Houston, Houston, TX;3University of Alabama Birmingham, Birmingham, AL
OBJECTIVE(S): Advances in early balanced blood product resuscitation have improved mortality after injury. However, many patients continue to succumb to complications with prolonged hospitalizations. Previous work on the posttraumatic host response to injury examined the inflammatory response prior to the current standard of damage control resuscitation. Thus, the effect of damage control resuscitation on inflammatory biomarkers is unknown. Our goal was to identify specific inflammatory mediators that are associated with death following severe trauma and hemorrhagic shock when patients are resuscitated primarily with blood products. METHODS: A retrospective analysis of inflammatory markers obtained from the PROPPR study was performed. Twenty-seven markers were measured at 8 timepoints in the first 72 hours of care. Serum levels were compared between survivors and non-survivors at each timepoint. Biomarkers with significant differences were further analyzed by adjudicated cause of mortality at 30 days (all cause, hemorrhage, multisystem organ failure (MOF), traumatic brain injury (TBI)) to perform a time-based survival analysis. RESULTS: Biomarkers from 680 patients were analyzed. Seven key inflammatory markers (IL-1ra, IL-6, IL-8, IL-10, Eotaxin, IP-10, and MCP-1) were chosen based on serum level linear graphs demonstrating consistent significant differences between the survivors and non-survivors. IL-1ra, IL-6, IL-8, IL-10, Eotaxin, IP-10, and MCP-1 were noted to have the highest hazard ratios of death. Stepwise selection was utilized for multivariate analysis of survival by timepoint (Odds Ratios, all p<0.05): at 2 hours MCP-1 (2.2), at 12 hours Eotaxin (1.7) and IP-10 (1.2), at 24 hours Eotaxin (3.9), and at 72 hours IP-10 (1.3) were associated with death by any cause. Additionally, IL-6 (1.2) at 24 hours and IL-10 (2.0) at 72 hours were associated with death from hemorrhage. CONCLUSIONS: Systemic inflammatory markers including IL-1ra, IL-6, IL-8, IL-10, Eotaxin, IP-10, and MCP-1 are associated with increased risk of mortality after injury in the setting of balanced blood product resuscitation. Future studies should utilize these biomarkers to prospectively calculate risks of morbidity and potential causes of mortality for all trauma patients.
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