Abstract Body: Introduction: After out-of-hospital cardiac arrest (OHCA) with return of spontaneous circulation (ROSC), hypoxic-ischemic brain injury is the leading cause of severe disability and death, but accurate, early prognostication and selection for neuroprotective therapies remains challenging. Additional early biomarkers could improve post-arrest care. Glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) are proteins associated with glial and neuronal injury. This study aimed to determine whether early blood levels of GFAP and UCH-L1 are associated with neurologic outcome.
Methods: We retrospectively analyzed OHCA patients transported to a single urban academic ED over 15 months. Exclusions included traumatic arrests, prisoners, and pregnant patients. Blood samples were collected within 12 hours of ED arrival, and plasma was analyzed for GFAP and UCH-L1 using Abbott Alinity i system (Abbott Laboratories, Abbott Park, IL). Clinical and outcome data were obtained from the EMR and EMS registry. Neurologic outcome at discharge was assessed using the Cerebral Performance Category (CPC), with CPC 1–2 defined as neurologically intact. Biomarker concentrations were log-2 transformed and grouped using k-medians clustering to categorize data points with greater similarity within than between clusters to improve interpretability. Associations between biomarker clusters and outcomes were evaluated using covariate-adjusted logistic regression.
Results: 171 patients were included. Median age was 53 years (IQR 41–54), and 72% were male. Most arrests were non-shockable (81%) and 47% were witnessed. Overall, 33% survived to discharge, and 28% were neurologically intact. Median time to sample collection was 6 hours (IQR 3–9). GFAP levels ranged from 0.9 to >50,000 pg/ml; UCH-L1 from 95.8 to >25,000 pg/ml. Results from covariate-adjusted analyses suggested dose-dependent associations between higher GFAP and UCH-L1 levels and decreased neurologically intact survival. Effects were most pronounced in the highest GFAP cluster (>895 pg/ml; aOR 0.11, 95% CI = 0.02–0.64) and highest UCH-L1 cluster (>9,947 pg/ml; aOR 0.21, 95% CI = 0.04–1.09).
Conclusion: In this retrospective study, higher concentrations of early GFAP and UCH-L1 levels were associated with poorer neurologic outcomes at discharge. These biomarkers show promise and warrant further study for early prognostication and potential selection for early neuroprotective therapies.