Neuron-Specific Enolase as a Predictor of Death or Poor Neurological Outcome After Out-of-Hospital Cardiac Arrest and Targeted Temperature Management at 33 degrees C and 36 degrees C.
[en] 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 degrees C or 36 degrees 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 degrees C or 36 degrees C does not significantly affect NSE levels. (Target Temperature Management After Cardiac Arrest [TTM]; NCT01020916).
Neuron-Specific Enolase as a Predictor of Death or Poor Neurological Outcome After Out-of-Hospital Cardiac Arrest and Targeted Temperature Management at 33 degrees C and 36 degrees C.
Publication date :
2015
Journal title :
Journal of the American College of Cardiology
ISSN :
0735-1097
eISSN :
1558-3597
Publisher :
Elsevier, Netherlands
Volume :
65
Issue :
19
Pages :
2104-14
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
V. Lemiale, F. Dumas, and N. Mongardon Intensive care unit mortality after cardiac arrest: the relative contribution of shock and brain injury in a large cohort Intensive Care Med 39 2013 1972 1980
S. Laver, C. Farrow, D. Turner, and J. Nolan Mode of death after admission to an intensive care unit following cardiac arrest Intensive Care Med 30 2004 2126 2128
I. Dragancea, M. Rundgren, E. Englund, H. Friberg, and T. Cronberg The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest Resuscitation 84 2013 337 342
C. Sandroni, F. Cavallaro, and C.W. Callaway Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: a systematic review and meta-analysis. Part 2: patients treated with therapeutic hypothermia Resuscitation 84 2013 1324 1338
C. Sandroni, F. Cavallaro, and C.W. Callaway Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: a systematic review and meta-analysis. Part 1: patients not treated with therapeutic hypothermia Resuscitation 84 2013 1310 1323
E.G. Zandbergen, A. Hijdra, and J.H. Koelman Prediction of poor outcome within the first 3 days of postanoxic coma Neurology 66 2006 62 68
E.F. Wijdicks, A. Hijdra, G.B. Young, C.L. Bassetti, S. Wiebe Quality Standards Subcommittee of the American Academy of Neurology Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology Neurology 67 2006 203 210
M. Rundgren, T. Cronberg, H. Friberg, and A. Isaksson Serum neuron specific enolase-impact of storage and measuring method BMC Res Notes 7 2014 726
C.D. Deakin, L.J. Morrison, and P.T. Morley Part 8: advanced life support: 2010 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations Resuscitation 81 Suppl 1 2010 e93 e174
C. Sandroni, A. Cariou, and F. Cavallaro Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine Intensive Care Med 40 2014 1816 1831
N. Nielsen, J. Wetterslev, and T. Cronberg Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest N Engl J Med 369 2013 2197 2206
N. Nielsen, J. Wetterslev, and N. al-Subaie Target temperature management after out-of-hospital cardiac arrest - a randomized, parallel-group, assessor-blinded clinical trial - rationale and design Am Heart J 163 2012 541 548
N. Nielsen, P. Winkel, and T. Cronberg Detailed statistical analysis plan for the target temperature management after out-of-hospital cardiac arrest trial Trials 14 2013 300
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects JAMA 310 2013 2191 2194
T. Cronberg, J. Horn, M.A. Kuiper, H. Friberg, and N. Nielsen A structured approach to neurologic prognostication in clinical cardiac arrest trials Scand J Trauma Resusc Emerg Med 21 2013 45
B. Jennett, and M. Bond Assessment of outcome after severe brain damage Lancet 1 1975 480 484
F.E. Harrell Regression Modelling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis Chapter 5: Resampling, Validating, and Simplifying the Model 2001 Springer-Verlag New York, Inc. New York, NY 88 103
E.B. Wilson Probable inference, the law of succession, and statistical inference J Am Stat Assoc 22 1927 209 212
M.J. Pencina, R.B. D'Agostino Sr., R.B. D'Agostino Jr., and R.S. Vasan Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond Stat Med 27 2008 157 172 discussion 207-12
M. Tiainen, R.O. Roine, V. Pettila, and O. Takkunen Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia Stroke 34 2003 2881 2886
M. Rundgren, T. Karlsson, N. Nielsen, T. Cronberg, P. Johnsson, and H. Friberg Neuron specific enolase and S-100B as predictors of outcome after cardiac arrest and induced hypothermia Resuscitation 80 2009 784 789
T. Oksanen, M. Tiainen, and M.B. Skrifvars Predictive power of serum NSE and OHCA score regarding 6-month neurologic outcome after out-of-hospital ventricular fibrillation and therapeutic hypothermia Resuscitation 80 2009 165 170
M. Huntgeburth, C. Adler, and S. Rosenkranz Changes in neuron-specific enolase are more suitable than its absolute serum levels for the prediction of neurologic outcome in hypothermia-treated patients with out-of-hospital cardiac arrest Neurocrit Care 20 2014 358 366
J.E. Fugate, E.F. Wijdicks, and J. Mandrekar Predictors of neurologic outcome in hypothermia after cardiac arrest Ann Neurol 68 2010 907 914
C. Daubin, C. Quentin, and S. Allouche Serum neuron-specific enolase as predictor of outcome in comatose cardiac-arrest survivors: a prospective cohort study BMC Cardiovasc Disord 11 2011 48
J. Reisinger, K. Hollinger, and W. Lang Prediction of neurological outcome after cardiopulmonary resuscitation by serial determination of serum neuron-specific enolase Eur Heart J 28 2007 52 58
R. Pfeifer, M. Franz, and H.R. Figulla Hypothermia after cardiac arrest does not affect serum levels of neuron-specific enolase and protein S-100b Acta Anaesthesiol Scand 58 2014 1093 1100
I.G. Steffen, D. Hasper, and C.J. Ploner Mild therapeutic hypothermia alters neuron specific enolase as an outcome predictor after resuscitation: 97 prospective hypothermia patients compared to 133 historical non-hypothermia patients Crit Care 14 2010 R69
M. Oddo, and A.O. Rossetti Early multimodal outcome prediction after cardiac arrest in patients treated with hypothermia Crit Care Med 42 2014 1340 1347
M. Mlynash, M.S. Buckwalter, and A. Okada Serum neuron-specific enolase levels from the same patients differ between laboratories: assessment of a prospective post-cardiac arrest cohort Neurocrit Care 19 2013 161 166
J. Arrich, A. Zeiner, and F. Sterz Factors associated with a change in functional outcome between one month and six months after cardiac arrest: a retrospective cohort study Resuscitation 80 2009 876 880
L.B. Becker, T.P. Aufderheide, and R.G. Geocadin Primary outcomes for resuscitation science studies: a consensus statement from the American Heart Association Circulation 124 2011 2158 2177
T. Zellner, R. Gartner, J. Schopohl, and M. Angstwurm NSE and S-100B are not sufficiently predictive of neurologic outcome after therapeutic hypothermia for cardiac arrest Resuscitation 84 2013 1382 1386
J.C. Rittenberger, and C.W. Callaway Temperature management and modern post-cardiac arrest care N Engl J Med 369 2013 2262 2263
