Plasma Phospholipid Fatty Acid Profiles in Septic Shock

et al. 2021

Preprint

Glycero- and sphingo- lipids are important in plasma membrane structure, caloric storage and signaling. An un-targeted lipidomics approach for a cohort of critically ill pediatric intensive care unit (PICU) patients, undergoing multi-organ dysfunction syndrome (MODS) was compared to sedation controls. After IRB approval, patients meeting criteria for MODS were screened, con-sented (n=24), and blood samples were collected from the PICU at HDVCH, Michigan; eight pa-tients needed veno-arterial extracorporeal membrane oxygenation (VA ECMO). Sedation con-trols were presenting for routine sedation (n=4). Plasma lipid profiles were determined by nano-electrospray (nESI) direct infusion high resolution/accurate mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Biostatistics analysis was performed using R v 3.6.0. 61 patient samples over 3 time points revealed a ceramide metabolite, hexosylceramide (Hex-Cer) was high across all time points (mean 1.63% - 3.19%; vs. controls 0.22%). Fourteen species sta-tistically differentiated from sedation controls (P-value ≤0.05); sphingomyelin (SM) [SM(d18:1/23:0), SM(d18:1/22:0), SM(d18:1/23:1), SM(d18:1/21:0), SM(d18:1/24:0)]; and glycer-ophosphotidylcholine (GPC) [GPC(36:01), GPC(18:00), GPC(O:34:02), GPC(18:02), GPC(38:05), GPC(O:34:03), GPC(16:00), GPC(40:05), GPC(O:36:03)]. Hex-Cer has been shown to be involved in viral infection and may be at play during acute illness. GPC(36:01) was elevated in all MODS patients at all time points and is associated with inflammation and brain injury.

Section: Discussionmentioning

confidence: 99%

Hexosylceramides and glycerophosphatidylcholine GPC(36:1) increase in Multi-Organ Dysfunction Syndrome patients with Pediatric Intensive Care Unit Admission over 8-day hospitalization

et al. 2021

Preprint

“…Patients with MODS present with dyslipidemia at first detection of organ pathology based on our lipidomic profiles presented in this report. Patients with MODS are compromised at the time of baseline, undergoing membrane disruption/remodeling, catabolic state, canabalism, and lipid dysregulation [37], resulting in decreased phospholipids as has been previously reported for pneumonia [38] and septic patients [39]. In contrast to the MODS patients, ECMO patients have phospholipid profiles that are observedly different at baseline and throughout the eight-day course.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

Preprint

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.

Hexosylceramides and Glycerophosphatidylcholine GPC(36:1) Increase in Multi-Organ Dysfunction Syndrome Patients with Pediatric Intensive Care Unit Admission over 8-Day Hospitalization

et al. 2021

JPM

Glycero- and sphingo-lipids are important in plasma membrane structure, caloric storage and signaling. An un-targeted lipidomics approach for a cohort of critically ill pediatric intensive care unit (PICU) patients undergoing multi-organ dysfunction syndrome (MODS) was compared to sedation controls. After IRB approval, patients meeting the criteria for MODS were screened, consented (n = 24), and blood samples were collected from the PICU at HDVCH, Michigan; eight patients needed veno-arterial extracorporeal membrane oxygenation (VA ECMO). Sedation controls were presenting for routine sedation (n = 4). Plasma lipid profiles were determined by nano-electrospray (nESI) direct infusion high resolution/accurate mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Biostatistics analysis was performed using R v 3.6.0. Sixty-one patient samples over three time points revealed a ceramide metabolite, hexosylceramide (Hex-Cer) was high across all time points (mean 1.63–3.19%; vs. controls 0.22%). Fourteen species statistically differentiated from sedation controls (p-value ≤ 0.05); sphingomyelin (SM) [SM(d18:1/23:0), SM(d18:1/22:0), SM(d18:1/23:1), SM(d18:1/21:0), SM(d18:1/24:0)]; and glycerophosphotidylcholine (GPC) [GPC(36:01), GPC(18:00), GPC(O:34:02), GPC(18:02), GPC(38:05), GPC(O:34:03), GPC(16:00), GPC(40:05), GPC(O:36:03)]. Hex-Cer has been shown to be involved in viral infection and may be at play during acute illness. GPC(36:01) was elevated in all MODS patients at all time points and is associated with inflammation and brain injury.