Association of neuron-specific enolase values with outcomes in cardiac arrest survivors is dependent on the time of sample collection

Background: Despite marked advances in intensive cardiology care, current options for outcome prediction in cardiac arrest survivors remain significantly limited. The aim of our study was, therefore, to compare the day-specific association of neuron-specific enolase (NSE) with outcomes in out-of-hospital cardiac arrest (OHCA) survivors treated with hypothermia. Methods: Eligible patients were OHCA survivors treated with targeted temperature management at 33 degrees C for 24 h using an endovascular device. Blood samples for NSE levels measurement were drawn on days 1, 2, 3, and 4 after hospital admission. Thirty-day neurological outcomes according to the Cerebral Performance Category (CPC) scale and 12-month mortality were evaluated as clinical end points. Results: A total of 153 cardiac arrest survivors (mean age 64.2 years) were enrolled in the present study. Using ROC analysis, optimal cutoff values of NSE for prediction of CPC 3-5 score on specific days were determined as: day 1 > 20.4 mcg/L (sensitivity 63.3%; specificity 82.1%; P = 0.002); day 2 > 29.0 mcg/L (72.5%; 94.4%; P < 0.001); and day 3 > 20.7 mcg/L (94.4%; 86.7%; P < 0.001). The highest predictive value, however, was observed on day 4 > 19.4 mcg/L (93.5%; 91.0%; P < 0.001); NSE value > 50.2 mcg/L at day 4 was associated with poor outcome with 100% specificity and 42% sensitivity. Moreover, NSE levels measured on all individual days also predicted 12-month mortality (P < 0.001); the highest predictive value for death was observed on day 3 > 18.1 mcg/L (85.3%; 72.0%; P < 0.001). Significant association with prognosis was found also for changes in NSE at different time points. An NSE level on day 4 > 20.0 mcg/L, together with a change > 0.0 mcg/L from day 3 to day 4, predicted poor outcome (CPC 3-5) with 100% specificity and 73% sensitivity. Conclusions: Our results suggest that NSE levels are a useful tool for predicting 30-day neurological outcome and long-term mortality in OHCA survivors treated with targeted temperature management at 33 degrees C. The highest associations of NSE with outcomes were observed on day 4 and day 3 after cardiac arrest.