Original Article1H-NMR-Based Metabolic Signatures of Clinical Outcomes in Trauma Patients—Beyond Lactate and Base DeficitCohen, Mitchell J. MD; Serkova, Natalie J. PhD; Wiener-Kronish, Jeanine MD; Pittet, Jean-Francois MD; Niemann, Claus U. MDAuthor Information From the Department of Surgery (M.J.C., C.U.N.), University of California, San Francisco, California; Department of Anesthesiology (N.J.S.), Cancer Center Small Animal Imaging Core, University of Colorado Health Sciences Center, Aurora, Colorado; Department of Anesthesia (J.W-K.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; and Department of Anesthesia and Perioperative Care (J.F.P., C.U.N.), University of California, San Francisco, California. Submitted for publication January 4, 2010. Accepted for publication March 29, 2010. Presented at the 68th Annual Meeting of the American Association for the Surgery of Trauma, October 1–3, 2009, Pittsburgh, Pennsylvania. Supported in part by grants from the Foundation of Anesthesia Research and Education, Rochester, MN (to C.U.N.), the International Anesthesia Research Society, Cleveland, OH (to C.U.N.), US Department of Human Health and Human Services grant R 380T10586 (to C.U.N.), NIH K08 GM-085689 (to M.J.C.), and the American Association for the Surgery of Trauma Scholarship (to M.J.C.). Address for reprints: Mitchell Jay Cohen, MD, FACS, Department of Surgery, Ward 3A, San Francisco General Hospital, San Francisco, CA 94110; e-mail: [email protected]. The Journal of Trauma: Injury, Infection, and Critical Care: July 2010 - Volume 69 - Issue 1 - p 31-40 doi: 10.1097/TA.0b013e3181e043fe Buy Metrics Abstract The determination of reliable biomarkers capable to predict clinical outcome of a trauma patient remains essential toward better therapeutic management of the patient in the intensive care unit. Assessment of global metabolic profiling using quantitative nuclear magnetic resonance (NMR)-based metabolomics offers an attractive modern methodology for fast and comprehensive determination of multiple circulating metabolites and for establishing metabolic phenotype of survivors versus nonsurvivors. Multivariate data analysis on 43 quantitative metabolic parameters identified three lipid metabolites, triacylglycerol, glycerol heads of phospholipids, and monounsaturated fatty acids, as being the most discriminative markers to separate survivors versus nonsurvivors at the time of admission. Glucose and glutamate were intermediate predictors, followed by lactate and hydroxybutyrate as two low-weight predictors. Ultimately, cellular and subcellular failure in nonsurviving trauma patients results in multiple systemic biochemical effects and in changes in circulating metabolites in the blood that are characteristic for decreased lipid synthesis and urea cycle activity in the liver, and for increased hyperglycemia, lactic, and ketoacidosis. © 2010 Lippincott Williams & Wilkins, Inc.