(861) Acylcarnitine Species in Children With Acute Brain Injury on ECMO: A Pilot Case-Control Study

Introduction: Acylcarnitines (ACs) play a key role in mitochondrial β-oxidation of fatty acids. Decreased plasma levels indicate altered energy metabolism in patients with traumatic brain injury, with limited data in other types of acute brain injury (ABI). In this study, we aimed to evaluate AC species as markers of altered bioenergetics in high risk children on ECMO.

Methods: We conducted a pilot nested case-control study within a multicenter prospective observational study, BEAM (Biomarkers of Brain Injury in Critically-Ill Children on ECMO). Using tandem mass spectrometry, we measured 34 AC species in plasma collected on the last day on ECMO in children with (n=15) vs without (n=15) ABI while on ECMO. ABI was defined as acute ischemic stroke, intracranial hemorrhage, and/or hypoxic ischemic injury confirmed by neuroimaging. Random Forest with Boruta wrapper was used for feature selection of AC species in order of importance.

Results: Children with vs without ABI were matched by age (median 88 days [IQR 20, 253] vs 76 days [IQR, 23, 497]) and ECMO mode (venoarterial ECMO 14/15 vs 14/15). The four most important AC species were propionylcarnitine (C3), isobutyryl/butyrylcarnitine (C4), 3-hydroxyisovaleryl/2-methyl 3-hydroxybutyrylcarnitine (C5OH), and glutaryl/3-hydroxydecanoylcarnitine (C5-DC/C10-OH), with lower levels in those with vs without ABI confirmed by neuroimaging (median 0.25, IQR, 0.19, 0.34 μmol/L vs 0.50, IQR 0.41, 0.70 μmol/L; median 0.24, IQR, 0.17, 0.34 μmol/L vs 0.58, IQR, 0.32, 0.79 μmol/L; median 0.05, IQR, 0.03, 0.06 μmol/L vs 0.08, IQR, 0.05, 0.12 μmol/L; and median 0.04, IQR, 0.04, 0.07 μmol/L vs 0.07, IQR, 0.05, 0.14 μmol/L, respectively). False discovery rate-adjusted p-values from Wilcoxon rank sum tests for differences between cases and controls in the four AC species were: p=0.026, p=0.042, p=0.078, and p=0.078, respectively.

Conclusions: In this pilot case-control study of children with vs without ABI during ECMO, short-chain AC plasma concentrations were lower in those with ABI, indicating altered bioenergetics. Decreased levels may be related to systemic processes of metabolic dysfunction despite adequate tissue oxygen delivery on ECMO. Potential interventions to reestablish homeostasis could be beneficial to multiple organ support, including the brain.