Serum Neuron-Specific-Enolase Thresholds for Predicting Postcardiac Arrest Outcome: A Systematic Review and Meta-analysis.

Abstract

OBJECTIVE\nTo determine thresholds of serum neuron-specific-enolase (NSE) for prediction of poor outcome after cardiac arrest with > 95% specificity using a unique method of multiple thresholds meta-analysis.\n\n\nMETHODS\nData from a systematic review by the European Resuscitation Council (ERC 2014) were updated with literature searches from PubMed, Cochrane, and Scopus until August 2020. Search terms included the MeSH terms heart arrest and biological markers ; and the text words cardiac arrest , neuron specific enolase , coma and prognosis . Cohort studies with comatose cardiac arrest survivors aged > 16 years, undergoing targeted temperature management (TTM) and NSE levels within 96 h of resuscitation, were included. Poor outcome was defined as cerebral performance category 3-5 at hospital discharge or later. Studies without extractable contingency tables were excluded. A multiple thresholds meta-analysis model was used to generate summary ROC curves for various time-points. NSE thresholds [and 95% prediction intervals] for > 95% specificity were calculated. Evidence appraisal was performed using a method adapted from the American Academy of Neurology grading criteria.\n\n\nRESULTS\nData from 11 studies (n = 1982) at 0-24 h, 21 studies (n =2815) at 24-48 h, and 13 studies (n =2557) at 48-72 h was analyzed. AUCs for prediction of poor outcomes were significantly larger at 24-48 h and 48-72 h compared to 0-24 h (0.82 and 0.83 vs 0.64). Quality of evidence was very low for most studies because of the risk of incorporation bias-knowledge of NSE levels potentially influenced life support withdrawal decisions. To minimize falsely pessimistic predictions, NSE thresholds at the upper 95% limit of prediction intervals are reported. For prediction of poor outcome with specificity > 95%, upper limits of the prediction interval for NSE were 70.4 ng/mL at 24-48 h, and 58.6 ng/mL at 48-72 h. Sensitivity analyses excluding studies with inconsistent TTM use or different outcome criteria did not substantially alter the results.\n\n\nCONCLUSIONS\nNSE thresholds for highly specific prediction of poor outcome are much higher than generally used. Future studies must minimize bias by masking treatment teams to the results of potential predictors and by pre-specifying criteria for withdrawal of life support.