Differentiating Late Awakeners from Non-Awakeners in Comatose Cardiac Arrest Survivors: Diagnostic Value of Multimodal Monitoring in Patients with Indeterminate Prognosis

Background: Current guidelines recommend prognostication at 72 h after cardiac arrest, yet a subset of patients (Late Awakeners) recover consciousness after this window. This study investigated diagnostic markers to distinguish Late Awakeners from those with permanent poor outcomes (Non-Awakeners) to prevent premature withdrawal of life-sustaining therapy. Methods: We analyzed adult OHCA patients treated with TTM from 2009 to 2019 who remained comatose (Glasgow Coma Scale Motor score < 6) at 72 h. Patients were categorized as Late Awakeners (obeyed commands > 72 h) or Non-Awakeners. The diagnostic performance of maximal Neuron-Specific Enolase (NSE) levels within 72 h and brainstem reflexes was assessed using receiver operating characteristic (ROC) analysis. Model calibration was evaluated using the Hosmer–Lemeshow test, and internal validation was performed using bootstrap resampling. Results: Of 213 patients comatose at 72 h, 20 (9.4%) were identified as Late Awakeners. The median time to awakening was 4.4 days (IQR 3.4–8.3) from ROSC. Late Awakeners exhibited significantly preserved corneal reflexes (85.0% vs. 20.2%) compared to Non-Awakeners. The optimal NSE cut-off value to predict late awakening was