Abstract
Objectives To assess ultra-early neuroprognostic significance of GFAP, NF-L, UCH-L1, tau, and S100B concentrations, change trajectory, and combination profile after Out-of-Hospital Cardiac Arrest (OHCA).
Methods Prospective enrollment of 22 OHCA and 10 control patients at an academic tertiary care center between May 1, 2017 and January 28, 2020. Blood was collected within one hour of return of spontaneous circulation (ROSC) (H0), at hours 6 (H6), 12, 18, 24, and daily or until discharge or death. Biomarker concentrations, multifactor score, and trajectory change were assessed and compared to final neurologic status (good vs poor Cerebral Performance Category; CPC 1–2 vs CPC 3–5, respectively).
Results 10 patients had good and 12 had poor neurologic outcomes. Poor outcome patients had higher biomarker concentrations and combined biomarker scores at early time points. The earliest significant difference between good and poor outcome patients’ serum biomarkers were at H12 for GFAP (good median: 425 pg/mL [IQR:370−630] vs poor: 5954[1712–65,055] pg/mL; p < 0.001), H12 for NF-L (64[41–69] vs 898[348–1990] pg/mL; p < 0.001), H0 for Tau (31[8–51] vs 124[53–238] pg/mL; p = 0.025), H0 for UCH-L1 (898[375–1600] vs 2475[1898–4098] pg/mL; p = 0.008), and H6 for S100B (123[70–290] vs 895[360–1199] pg/mL; p = 0.002). Four biomarker composite scores differed by H12 (78.03[52.03–111.25] vs 749 [198.46–4870.63] pg/mL; p = 0.003). Machine-learning approach also identified that four-marker score trajectory group memberships are in concordance with patient outcome.
Conclusions Ultra-early serial serum concentrations of neuronal and astroglial biomarkers may be of neuroprognostic significance following OHCA.
Conclusion The findings of this exploratory study suggest that ultra-early serial measurement of serum brain-specific proteins after OHCA may provide early, reliable, and objective information useful in neuroprognostication. Clinical utility may be enhanced through simultaneous additive evaluation multiple biomarkers. Future studies are anticipated and will need to include larger multicentered cohorts, undifferentiated patient populations, and longer-duration evaluations in order to validate these findings and account for variations in chronic disease, co-morbid conditions, and other confounding variables.
