The Feasibility of Studying Metabolites in PICU Multi-Organ Dysfunction Syndrome Patients over an 8-Day Course Using an Untargeted Approach

Mara Leimanis-Laurens; Danny Gil; Andrew Kampfschulte; Claire Krohn; Elizabeth Prentice; Dominic Sanfilippo; Jeremy W Prokop; Todd A Lydic; Surender Rajasekaran

doi:10.3390/children8020151

The Feasibility of Studying Metabolites in PICU Multi-Organ Dysfunction Syndrome Patients over an 8-Day Course Using an Untargeted Approach

Children (Basel). 2021 Feb 18;8(2):151. doi: 10.3390/children8020151.

Authors

Mara Leimanis-Laurens^{1

2}, Danny Gil^{1

2}, Andrew Kampfschulte³, Claire Krohn⁴, Elizabeth Prentice^{1

2}, Dominic Sanfilippo^{1

2}, Jeremy W Prokop^{2

5}, Todd A Lydic⁶, Surender Rajasekaran^{1

2

3}

Affiliations

¹ Pediatric Critical Care Unit, Helen DeVos Children's Hospital, 100 Michigan Street NE, Grand Rapids, MI 49503, USA.
² Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Life Sciences Building, 1355 Bogue Street, East Lansing, MI 48824, USA.
³ Spectrum Health, 100 Michigan Street NE, Grand Rapids, MI 49503, USA.
⁴ College of Human Medicine, Michigan State University, 15 Michigan Street NE, Grand Rapids, MI 49503, USA.
⁵ Department of Pharmacology and Toxicology, Michigan State University, 1355 Bogue Street, East Lansing, MI 48824, USA.
⁶ Department of Physiology, Collaborative Mass Spectrometry Core, Michigan State University, 578 S. Shaw Ln. Chemistry Building, East Lansing, MI 48824, USA.

Abstract

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 the criteria for MODS were screened for eligibility and consented (n = 24), and blood samples were collected at baseline, 72 h, and 8 days; control patients (n = 4) presented for routine sedation in an outpatient setting. A subset 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 liquid chromatography-mass spectrometry (LC-MS) analysis. Chromatographic peak alignment, identification, relative quantitation, and statistical and bioinformatics evaluation were performed using MAVEN and MetaboAnalyst 4.0. Metabolite analysis revealed 115 peaks per sample. From the partial least squares-discriminant analysis (PLS-DA) with variance of importance (VIP) scores above ≥2.0, 7 dynamic metabolites emerged over the three time points: tauro-chenodeoxycholic acid (TCDCA), hexose, p-hydroxybenzoate, hydroxyphenylacetic acid (HPLA), 2_3-dihydroxybenzoic acid, 2-keto-isovalerate, and deoxyribose phosphate. After Bonferroni adjustment for repeated measures, hexose and p-hydroxybenzoate were significant at one time point or more. Kendall's tau-b test was used for internal validation of creatinine. Metabolites may be benign or significant in describing a patient's pathophysiology and require operator interpretation.

Keywords: blood plasma; extracorporeal membrane oxygenation; liquid chromatography–mass spectrometry; metabolites; multiple organ dysfunction syndrome; pediatric intensive care unit.