Assessment of key plasma metabolites in combat casualties

BACKGROUND: Previous studies have indicated that hemorrhagic shock and injury cause significant early changes in metabolism. Recently, global changes in metabolism have been described using metabolomics in animal models and civilian trauma. We evaluated metabolic changes associated with combat injury to identify early biomarkers and aid in triage. METHODS: Plasma obtained at emergency department presentation and intervals thereafter from patients injured during combat operations in Iraq (n = 78) were compared with healthy control subjects (n = 40). Using proton Nuclear Magnetic Resonance (NMR), water-soluble metabolites were detected and quantified. Resulting metabolic profiles were analyzed with partial least squares discriminant analysis, Receiver Operating Characteristic (ROC), and cluster analyses to identify features of combat injury and mortality. RESULTS: Significant alterations to metabolism resulted from traumatic injury. Metabolic profiles of injured patients differed from those of healthy controls, driven by increased 5-aminolevulinate and hypoxanthine that persisted through 24 hours. Among combat-injured patients, increased succinate and malonate best discriminated between those who survived from those who did not. Higher levels of succinate and hypoxanthine were associated with increased injury severity. ROC analysis showed that these metabolites had equivalent or superior performance to lactate in distinguishing the presence of trauma, injury severity, and mortality. CONCLUSION: Combat injury is associated with several changes at the metabolic level compared with healthy individuals. Novel potential biomarkers of mortality (succinate, malonate), injury severity (succinate, hypoxanthine), and the presence of trauma (hypoxanthine, 5-aminolevulinate) perform as well as or better than the common clinical standard, lactate.