Incremental Value of Adding S100B to NSE for High-Specificity Rule-in of Poor Neurological Outcome After Out-of-Hospital Cardiac Arrest

Background: We evaluated whether adding S100B to NSE improved discrimination or high-specificity rule-in of poor neurological outcome after out-of-hospital cardiac arrest (OHCA). Methods: In this single-center retrospective cohort study, comatose adult OHCA survivors treated with targeted temperature management had NSE and S100B measured at 0, 24, 48, and 72 h after return of spontaneous circulation. At each time point, we assessed NSE alone, S100B alone, and a logistic model combining both biomarkers in paired complete cases. Discrimination was assessed using the area under the receiver operating characteristic curve (AUC). Rule-in performance was evaluated using a timepoint-specific threshold that achieved 100% specificity in our cohort. Poor neurological outcome was defined as cerebral performance category 3–5 at 6 months. Results: Among 124 patients, 66 (53.2%) had poor outcomes. AUCs were similar between NSE alone and the combination across all time points (all p > 0.3). At 48 h, the combination ruled in 46/65 (70.8%) patients with poor outcome versus 36/65 (55.4%) with NSE alone, identifying 10 additional patients and a 15.4-percentage-point difference (95% confidence interval, −5.6 to 23.6). Conclusions: Adding S100B to NSE did not improve overall discrimination. The higher 48 h rule-in yield was estimated imprecisely and should be interpreted cautiously. Our findings require external validation before they can be translated to clinical settings.