(P06-15-26) Integrated Metabolomics Reveals Time-Dependent Metabolic Pathways Associated With Mortality and Infection in Surgical ICU Patients

Objectives: Surgical intensive care unit (SICU) patients experience high rates of hospital-acquired infection and mortality. However, the metabolic pathways underlying these associations remain unclear. We aimed to identify pathways associated with mortality and hospital-acquired infections in adults with postoperative critical illness using targeted and untargeted metabolomics.

Methods: This secondary analysis of a published clinical trial of glutamine-supplemented parenteral nutrition in SICU patients included non-survivors at 28 days after study entry (n=22), sex and age matched to 28-day survivors after entry (n=22). Plasma concentrations of a 19-amino acid (AA) plasma panel were quantified at baseline, Day 3, and Day 7 after study entry by AA analyzer. Plasma high-resolution metabolomics (HRM) was performed at the same time points using dual-column LC/MS (HILIC+ and C18- electrospray modes). Mortality and adjudicated infections were monitored through day 28. Data integration and network analysis were performed using xMWAS, followed by metabolic pathway enrichment analysis using mummichug.

Results: A total of 8,320 (HILIC+) and 8,898 (C18-) metabolic features, together with the 19-AA panel, were integrated for pathway enrichment analysis. Mortality was associated with arachidonic acid and vitamin A metabolism at baseline; aspartate, alanine, and tryptophan metabolism at Day 3; and glycerophospholipid metabolism, fatty acid activation, the carnitine shuttle, the urea cycle, and glutathione metabolism at Day 7. Hospital-acquired infections were associated with enrichment of the TCA cycle at all time points, with additional involvement of prostaglandin metabolism at baseline; vitamin C and E metabolism at Day 3; and AA, fatty acid biosynthesis, glycerophospholipid metabolism, and prostaglandin formation at Day 7.

Conclusions: Pathway enrichment analysis revealed time-dependent metabolic signatures associated with mortality and hospital-acquired infections. Alterations in lipid, AA, urea, and redox metabolism were associated with mortality. In contrast, infections were associated with energy metabolism pathways, antioxidant vitamins, AA, and lipid metabolism. Plasma HRM may provide insight into nutrition-related pathophysiology and inform future precision nutrition research in SICU patients.

Funding Sources: NIH funded