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

Abstract

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 °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 °C. The highest associations of NSE with outcomes were observed on day 4 and day 3 after cardiac arrest.

Keywords: Cardiac arrest; Mild hypothermia; Neuron-specific enolase; Prognosis.

Fig. 1

Study flow diagram. ECPR extracorporeal cardiopulmonary resuscitation, NSE neuron-specific enolase

Fig. 2

Neuron-specific enolase (NSE) levels measured on individual days. The NSE levels were significantly lower in the CPC 1–2 group in comparison with the CPC 3–5 group at each time point (P < 0.05). CPC Cerebral Performance Category

Fig. 3

Association of neuron-specific enolase (NSE) with poor neurological outcomes (CPC 3–5). Receiver operating characteristic (ROC) curve for NSE values at Day 1 is schown on Panel a; ROC curve for NSE values at Day 2 is schown on Panel b; ROC curve for NSE values at Day 3 is schown on Panel c; ROC curve for NSE values at Day 4 is schown on Panel d; ROC curve for maximal NSE values is schown on Panel e. AUC area under the curve, CPC Cerebral Performance Category, MAX maximum

Fig. 4

Association of neuron-specific enolase (NSE) with 1-year mortality. Receiver operating characteristic (ROC) curve for NSE values at Day 1 is schown on Panel a; ROC curve for NSE values at Day 2 is schown on Panel b; ROC curve for NSE values at Day 3 is schown on Panel c; ROC curve for NSE values at Day 4 is schown on Panel d; ROC curve for maximal NSE values is schown on Panel e.  AUC area under the curve, MAX maximum