Early prediction of brain death (BD) after the return of spontaneous circulation (ROSC) in patients with cardiac arrest would be useful for the proper distribution of good quality transplantable organs and medical resources. We aimed to early identify independent risk factors of BD and their predictive performance in out-of-hospital cardiac arrest (OHCA) survivors.

This retrospective observational study included adult OHCA survivors from May 2018 to February 2021. Independent risk factors for progression to BD were identified by performing multivariate logistic regression analysis, including clinical, laboratory, biological parameters and prognostic factors, obtained within 6 h after ROSC. Neuron-specific enolase (NSE) level were categorized into quartile. The primary outcome was BD occurrence.

Overall, 108 patients were included in this analysis, 31 (29%) of whom had BD. In multivariate logistic regression analysis, initial serum NSE levels in the fourth quartile compared to the first quartile (odds ratio [OR], 88.5; 95% confidence interval [CI]: 7.0–1113.6) and absence of pupil light reflex (PLR) (OR, 40.3; 95% CI: 3.8–430.3) were independently associated with BD. According to the receiver operating characteristic curve analysis, initial serum NSE levels and PLR showed good-to-excellent and fair-to-good prognostic performance, respectively (area under the curve [AUC], 0.90; 95% CI: 0.83–0.95 vs. 0.81; 95% CI: 0.72–0.88). Additionally, the combination of both the risk factors (AUC, 0.96; 95% CI: 0.90–0.99) showed significantly higher predictive performance for BD than when using them individually (P = 0.04 and P < 0.01, respectively).

High levels of initial serum NSE and PLR obtained within 6 h after ROSC may help early predict progression to BD in OHCA survivors. A large prospective multicenter study should be conducted to confirm these results.