Original Investigation
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

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Abstract

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)

Key Words

biomarker
cerebral performance
neuroprognostication
prognosis

Abbreviations and Acronyms

CPC
cerebral performance category
FPR
false positive rate
ICU
intensive care unit
IDI
integrated discrimination improvement
NRI
net reclassification index
NSE
neuron-specific enolase
OHCA
out-of-hospital cardiac arrest
ROSC
return of spontaneous circulation

Cited by (0)

The TTM-Trial was funded by independent research grants from the Swedish Heart Lung Foundation; Arbetsmarknadens Försäkringsaktiebolag Insurance Foundation; Swedish Research Council; regional research support, Region Skåne; governmental funding of clinical research within the Swedish National Health Services; Thelma Zoega Foundation; Krapperup Foundation; Thure Carlsson Foundation; Hans-Gabriel and Alice Trolle-Wachtmeister Foundation for Medical Research; Skåne University Hospital, Sweden; TrygFonden, Denmark; the European Clinical Research Infrastructures Network; and the European Critical Care Research Network. There was no commercial funding. Funding organizations neither had any access to the data nor had any influence on the analysis or interpretation. Drs. Collignon and Devaux have received support from the Ministry of Higher Education and Research of Luxembourg and National Research Fund. Dr. Wise has served on the advisory board of Bard Medical. Dr. Erlinge has received speakers fees from ZOLL and Philips. Drs. Nielsen and Pellis have received speaker fees from Bard Medical. Dr. Erlinge has received speaker fees from Zoll and Philips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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