Pediatric Multi-Organ Dysfunction Syndrome: Analysis by an Untargeted “Shotgun” Lipidomic Approach Reveals Low-abundance Plasma Phospholipids and Dynamic Recovery Over 8-Day Period, a Single-Center Observational Study

Abstract

Lipids are stable molecules involved in metabolism and inflammation. We investigated the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) (n=24) were analyzed at three time points and cross referenced to sedation controls (n = 4) for a total of N=28. Eight of the patients with MODS, needed veno-arterial extracorporeal membrane oxygenation (VA ECMO) support to survive. Blood plasma lipid profiles were quantified by nano-electrospray (nESI), direct infusion high resolution/accurate mass spectrometry (MS), and tandem mass spectrometry (MS/MS) and compared to nutritional profiles and PEdiatric Logistic Organ Dysfunction (PELOD) scores. PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provided stratification between sedation controls and all MODS patients for lysophosphatidylserine (lysoPS) (p-value = 0.004), total phosphatidylserine (PS) (p-value = 0.015), and total ether-linked phosphatidylethanolamine (PE) (p-value = 0.03). Phospholipids in patients needing ECMO were observably closer to sedation controls than other MODS patients. Nutrition intake revealed changes in lipid profiles that corresponded to calorie and protein intake. Lipid measurement in the intensive care environment shows dynamic changes over an 8-day PICU course, suggesting novel indicators for defining critically ill children.

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

“…After IRB approval, a short-term longitudinal design was adopted at Helen DeVos Children's Hospital (2016-062-SH/HDVCH). Samples were collected under the protocol and study design [10][11][12] in a quaternary-care, urban, pediatric hospital in Western, Michigan. In brief, patients who were identified as having MODS were enrolled, 24 in total, with an additional 4 sedation-control patients.…”

“…We have previously described the current cohort of patients for patient whole blood transcriptomics [10,11], and plasma lipidome [12]. This has revealed a complex biology in a heterogenous patient population with a non-uniform patient response to treatments over an 8-day course (stabilization and recovery phases) of illness during a PICU admission.…”

“…This has revealed a complex biology in a heterogenous patient population with a non-uniform patient response to treatments over an 8-day course (stabilization and recovery phases) of illness during a PICU admission. Complimentary to these previously reported analytic modalities from whole blood [10][11][12], the aim of this current report was two-fold: 1) to characterize total blood plasma metabolites (polar, charged) using an untargeted approach, 2) to determine change in metabolites over an 8-day PICU course. There is a gap in our understanding of the complex interaction between pediatric critical illness, specifically multi-organ dysfunction syndrome (MODS) [13] (affecting twenty percent of PICU admissions [14], resulting in ten times the mortality rate [15]), and their respective blood metabolites.…”

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

“…We have previously described the current cohort of patients for patient whole blood transcriptomics [ 10 , 11 ] and plasma lipidome [ 12 ]. This has revealed a complex biology in a heterogenous patient population with a non-uniform patient response to treatments over an 8-day course (stabilization and recovery phases) of illness during pediatric intensive care unit (PICU) admission.…”

“…This has revealed a complex biology in a heterogenous patient population with a non-uniform patient response to treatments over an 8-day course (stabilization and recovery phases) of illness during pediatric intensive care unit (PICU) admission. Complementary to these previously reported analytic modalities from whole blood [ 10 , 11 , 12 ], the aim of this current report was threefold: (1) to determine the feasibility of undertaking blood plasma metabolite work in the PICU setting, (2) characterize total blood plasma metabolites (polar, charged) using an untargeted approach, and (3) to determine change in metabolites over an 8-day PICU course. There is a gap in our understanding of the complex interaction between pediatric critical illness, specifically multi-organ dysfunction syndrome (MODS) [ 13 ] (affecting 20% of PICU admissions [ 14 ], resulting in 10 times the mortality rate [ 15 ]), and their respective blood metabolites.…”