• Christopher W Seymour, Sachin Yende, Melanie J Scott, John Pribis, Robert P Mohney, Lauren N Bell, Yi-Fan Chen, Brian S Zuckerbraun, William L Bigbee, Donald M Yealy, Lisa Weissfeld, John A Kellum, and Derek C Angus.
• Department of Critical Care Medicine and Emergency Medicine, University of Pittsburgh School of Medicine, 3550 Terrace St, Scaife Hall, #639, Pittsburgh, PA 15261, USA. seymourcw@upmc.edu
• Intensive Care Med. 2013 Aug 1; 39 (8): 142314341423-34.

PurposeTo determine the global metabolomic profile as measured in circulating plasma from surviving and non-surviving patients with community-acquired pneumonia (CAP) and sepsis.MethodsRandom, outcome-stratified case-control sample from a prospective study of 1,895 patients hospitalized with CAP and sepsis. Cases (n = 15) were adults who died before 90 days, and controls (n = 15) were adults who survived, matched on demographics, infection type, and procalcitonin. We determined the global metabolomic profile in the first emergency department blood sample using non-targeted mass-spectrometry. We derived metabolite-based prognostic models for 90-day mortality. We determined if metabolites stimulated cytokine production by differentiated Thp1 monocytes in vitro, and validated metabolite profiles in mouse liver and kidney homogenates at 8 h in cecal ligation and puncture (CLP) sepsis.ResultsWe identified 423 small molecules, of which the relative levels of 70 (17 %) were different between survivors and non-survivors (p ≤ 0.05). Broad differences were present in pathways of oxidative stress, bile acid metabolism, and stress response. Metabolite-based prognostic models for 90-day survival performed modestly (AUC = 0.67, 95 % CI 0.48, 0.81). Five nucleic acid metabolites were greater in non-survivors (p ≤ 0.05). Of these, pseudouridine increased monocyte expression of TNFα and IL1β versus control (p < 0.05). Pseudouridine was also increased in liver and kidney homogenates from CLP mice versus sham (p < 0.05 for both).ConclusionsAlthough replication is required, we show the global metabolomic profile in plasma broadly differs between survivors and non-survivors of CAP and sepsis. Metabolite-based prognostic models had modest performance, though metabolites of oxidative stress may act as putative damage-associated molecular patterns.

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