title: 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.
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.
  
  
  OBJECTIVE
  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).
authors.affiliation: Department of Anesthesia and Intensive Care, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg. Electronic address: stammet.pascal@chl.lu.
authors.forename: Pascal
authors.initials: P
authors.lastname: Stammet
authors.affiliation: Competence Centre for Methodology and Statistics, Luxembourg Institute of Health, Luxembourg, Luxembourg.
authors.forename: Olivier
authors.initials: O
authors.lastname: Collignon
authors.affiliation: Department of Cardiology B, The Heart Centre, Rigshospitalet University Hospital, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Hassager
authors.affiliation: Department of Intensive Care, University Hospital of Wales, Cardiff, United Kingdom.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Wise
authors.affiliation: Department of Anesthesia and Intensive Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Hovdenes
authors.affiliation: Department of Intensive Care, Liverpool Hospital, Sydney, Australia.
authors.forename: Anders
authors.initials: A
authors.lastname: Åneman
authors.affiliation: Department of Intensive Care, Academic Medical Centrum, Amsterdam, the Netherlands.
authors.forename: Janneke
authors.initials: J
authors.lastname: Horn
authors.affiliation: Laboratory of Cardiovascular Research, Luxembourg Institute of Health, Luxembourg, Luxembourg.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Devaux
authors.affiliation: Department of Cardiology, Skåne University Hospital, Lund, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
authors.affiliation: Department of Cardiology B, The Heart Centre, Rigshospitalet University Hospital, Copenhagen, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Kjaergaard
authors.affiliation: Department of Intensive Care, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Gasche
authors.affiliation: Department of Cardiothoracic Anesthesiology RT, The Heart Centre, Rigshospitalet University Hospital, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Wanscher
authors.affiliation: Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Cronberg
authors.affiliation: Department of Anesthesia and Intensive Care, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Friberg
authors.affiliation: Copenhagen Trial Unit, Centre of Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Wetterslev
authors.affiliation: Department of Intensive Care, Santa Maria degli Angeli, Pordenone, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Pellis
authors.affiliation: Department of Intensive Care, Leeuwarden Medical Centrum, Leeuwarden, the Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Kuiper
authors.affiliation: Department of Clinical Biology, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
authors.forename: Georges
authors.initials: G
authors.lastname: Gilson
authors.affiliation: Department of Anesthesia and Intensive Care, Helsingborg Hospital, Helsingborg, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Nielsen
mesh_terms: D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000201:enzymology* / Q000453:epidemiology / Q000209:etiology; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D058687:Out-of-Hospital Cardiac Arrest / Q000150:complications / Q000201:enzymology* / Q000401:mortality; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D013696:Temperature; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D010751:Phosphopyruvate Hydratase
keywords: biomarker; cerebral performance; neuroprognostication; prognosis