(737) Potential for a Metabolomics-Based Precision Medical Approach for Traumatic Brain Injury Patients

Introduction: Traumatic brain injury (TBI) is marked by early metabolic and inflammatory responses leading to organ failure and death. Currently, the adequacy of resuscitation is assessed using vital signs, noninvasive methods, and basic laboratory indices. This study aimed to characterize the plasma metabolome of pediatric patients with severe traumatic brain injury (TBI) compared to healthy controls to design a precision medical approach.

Methods: After IRB approval and informed consent, 17 pediatric ICU patients (≥1 year to ≤18 years) with severe TBI (GCS ≤ 8) along with healthy controls (n =10) were enrolled. Blood samples for sTBI patients were collected at three timepoints after initial injury: 24±12 hours of injury, 48±12 hours, and on hospital day 9±12 hours. Clinical data including demographics, injury characteristics, and clinical course were collected. We employed liquid chromatography-mass spectrometry (LC-MS/MS) and 1H NMR to biochemically profile the blood plasma. All data were combined using a variety of machine learning modalities.

Results: Significant perturbations in serum metabolites related to energy metabolism were found in patients with severe TBI compared to healthy controls. At admission, TBI patients had 22 high-confidence transcripts elevated that returned to control levels by day 8. We found that plasma betaine, malonate, valine and lysine were downregulated, while plasma 2-hydroxy-butryic acid, pyruvate, glutamate and lactic acid were upregulated (P-value < 0.05). These metabolites are readily available and are shown to relate to the metabolic activity of the brain. The top 20 metabolites (AUC O.8, P-Value < 0.05) were consistently different between controls and all time points of injury in TBI patients. We propose that these metabolites could be used to chart the impact of therapies initiated in the care of severe head trauma such a maintaining proper cerebral perfusion in the early stages of head injury.

Conclusions: This study establishes that significant plasma metabolomic differences exist between sTBI pediatric patients compared to healthy matched controls, with most compelling variations in energetics. Further validation and exploration of these biomarkers and metabolomic profiles in larger cohorts are necessary to assess their clinical utility.