Neuron-Specific Enolase as a Predictor of Death or Poor Neurological Outcome After Out-of-Hospital Cardiac Arrest and Targeted Temperature Management at 33°C and 36°C

J Am Coll Cardiol. 2015 May 19;65(19):2104-14. doi: 10.1016/j.jacc.2015.03.538.


Background: Neuron-specific enolase (NSE) is a widely-used biomarker for prognostication of neurological outcome after cardiac arrest, but the relevance of recommended cutoff values has been questioned due to the lack of a standardized methodology and uncertainties over the influence of temperature management.

Objectives: This study investigated the role of NSE as a prognostic marker of outcome after out-of-hospital cardiac arrest (OHCA) in a contemporary setting.

Methods: A total of 686 patients hospitalized after OHCA were randomized to targeted temperature management at either 33°C or 36°C. NSE levels were assessed in blood samples obtained 24, 48, and 72 h after return of spontaneous circulation. The primary outcome was neurological outcome at 6 months using the cerebral performance category score.

Results: NSE was a robust predictor of neurological outcome in a baseline variable-adjusted model, and target temperature did not significantly affect NSE values. Median NSE values were 18 ng/ml versus 35 ng/ml, 15 ng/ml versus 61 ng/ml, and 12 ng/ml versus 54 ng/ml for good versus poor outcome at 24, 48, and 72 h, respectively (p < 0.001). At 48 and 72 h, NSE predicted neurological outcome with areas under the receiver-operating curve of 0.85 and 0.86, respectively. High NSE cutoff values with false positive rates ≤5% and tight 95% confidence intervals were able to reliably predict outcome.

Conclusions: High, serial NSE values are strong predictors of poor outcome after OHCA. Targeted temperature management at 33°C or 36°C does not significantly affect NSE levels. (Target Temperature Management After Cardiac Arrest [TTM]; NCT01020916).

Keywords: biomarker; cerebral performance; neuroprognostication; prognosis.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Brain Ischemia / enzymology*
  • Brain Ischemia / epidemiology
  • Brain Ischemia / etiology
  • Europe / epidemiology
  • Female
  • Follow-Up Studies
  • Humans
  • Hypothermia, Induced / methods*
  • Incidence
  • Male
  • Middle Aged
  • Out-of-Hospital Cardiac Arrest / complications
  • Out-of-Hospital Cardiac Arrest / enzymology*
  • Out-of-Hospital Cardiac Arrest / mortality
  • Phosphopyruvate Hydratase / blood*
  • Prognosis
  • Prospective Studies
  • Temperature*
  • Treatment Outcome


  • Biomarkers
  • Phosphopyruvate Hydratase

Associated data