The Feasibility of Studying Metabolites in PICU Multi-Organ Dysfunction Syndrome Patients Over an 8-day Course Using An Untargeted Approach

Leimanis-Laurens, M. L.; Gil, D.; Kampfschulte, A.; Krohn, C.; Prentice, E.; Sanfilippo, D.; Prokop, J. W.; Lydic, T.; Rajasekaran, S.

Metabolites are generated from critical biological functions and metabolism. This pediatric study reviewed plasma metabolites in patients suffering from multi-organ dysfunction syndrome (MODS) in the pediatric intensive care unit (PICU) using an untargeted metabolomics approach. Patients meeting criteria for MODS were screened for eligibility and consented (n=24), and blood samples were collected at baseline, 72 hours, and 8 days; control patients (n=4), were presenting for routine sedation in an outpatient setting. A sub-set of MODS patients (n=8) required additional support with veno-atrial extracorporeal membrane oxygenation (VA-ECMO) therapy. Metabolites from thawed blood plasma were determined from ion pairing reversed-phase LC-MS analysis. Chromatographic peak alignment, identification, relative quantitation, statistical and bioinformatics evaluation were performed using MAVEN and MetaboAnalyst 4.0. Metabolite analysis revealed 115 peaks per sample. From the PLS-DA with VIP scores above 2.0, 7 dynamic metabolites emerged over the 3 time points: tauro-chenodeoxycholic acid (TCDCA), hexose, p-hydroxybenzoate, hydroxyphenylacetic acid (HPLA), 2_3-dihydroxybenzoic acid, 2-keto-isovalerate, and deoxyribose phosphate. After Bonferonni adjustment for repeated measures hexose and p-hydroxybenzoate were significant at one time point, or more. Kendalls tau-b test was used for internal validation of creatinine. Metabolites may be benign or significant in describing a patients pathophysiology and require operator interpretation.