Multimodal assessment of favorable neurological outcome using NSE levels and kinetics, EEG and SSEP in comatose patients after cardiac arrest

Background Prognostic markers of good neurological outcome after cardiac arrest (CA) remain limited. We aimed to evaluate the prognostic value of neuron-specific enolase (NSE), electroencephalogram (EEG) and somatosensory evoked potentials (SSEP) in predicting good outcome, assessed separately and in combination. Methods A retrospective study was conducted in a tertiary CA center, using a prospective registry. We included all patients comatose after discontinuation of sedation and with one EEG and NSE blood measurement at 24, 48 or/and 72 h after CA. The primary outcome was favorable neurological outcome at three months, a Cerebral Performance Categories (CPC) scale 1-2 defining a good outcome. Results Between January 2017 and April 2024, 215 patients were included. Participants were 63 years old (IQR [52-73]), and 73% were male. At 3 months, 54 patients (25.1%) had a good outcome. Compared to the poor outcome group, NSE blood levels were significantly lower in the good outcome group at 24 h (39 IQR[27-45] vs 54 IQR[37-82]mu g/L, p < 0.001), 48 h (26 [18-43] vs 107 [54-227]<mu>g/L, p < 0.001) and 72 h (20 <mu>g/L IQR [15-30] vs 184 mu g/l IQR [60-300], p < 0,001). Normal NSE (i.e., < 17 mu g/L) at 24 h was highly predictive of good outcome, with a predictive positive value (PPV) of 71% despite a sensitivity (Se) of 9%. The best cut-off values for NSE at 24, 48 and 72 h were below 45.5, 51.5 and 41.5 mu g/L, yielding PPV of 64%, 80% and 83% and sensitivities of 74%, 93% and 90%, respectively. A decreasing trend in NSE levels between 24 and 72 h was also highly predictive of good outcome (PPV 82%, Se 81%). A benign EEG pattern was more frequently observed in the good outcome group (87.1 vs 14.9%, p < 0.001) and predicted a good outcome with a PPV of 72% and a Se of 94%. Regarding SSEPs, a bilateral N20-baseline amplitude > 0.85 mu V was predictive of good outcome (PPV 75%, Se 100%). The combination of NSE < 51.5 <mu>g/l at 48 h, a decreasing NSE trend between 24 and 72 h and a benign EEG showed the best predictive value (PPV 96%, Se 76%). Conclusion In comatose patients after CA, a low NSE levels at 24, 48 h or 72 h, a decreasing trend in NSE over time, a benign EEG and a high N20 amplitude are robust markers of favorable outcome, reducing prognosis uncertainty.