Skip to main content
Top
Published in: Critical Care 1/2017

Open Access 01-12-2017 | Research

Association of neuron-specific enolase values with outcomes in cardiac arrest survivors is dependent on the time of sample collection

Authors: Dagmar Vondrakova, Andreas Kruger, Marek Janotka, Filip Malek, Vlasta Dudkova, Petr Neuzil, Petr Ostadal

Published in: Critical Care | Issue 1/2017

Login to get access

Abstract

Background

Despite marked advances in intensive cardiology care, current options for outcome prediction in cardiac arrest survivors remain significantly limited. The aim of our study was, therefore, to compare the day-specific association of neuron-specific enolase (NSE) with outcomes in out-of-hospital cardiac arrest (OHCA) survivors treated with hypothermia.

Methods

Eligible patients were OHCA survivors treated with targeted temperature management at 33 °C for 24 h using an endovascular device. Blood samples for NSE levels measurement were drawn on days 1, 2, 3, and 4 after hospital admission. Thirty-day neurological outcomes according to the Cerebral Performance Category (CPC) scale and 12-month mortality were evaluated as clinical end points.

Results

A total of 153 cardiac arrest survivors (mean age 64.2 years) were enrolled in the present study. Using ROC analysis, optimal cutoff values of NSE for prediction of CPC 3–5 score on specific days were determined as: day 1 > 20.4 mcg/L (sensitivity 63.3%; specificity 82.1%; P = 0.002); day 2 > 29.0 mcg/L (72.5%; 94.4%; P < 0.001); and day 3 > 20.7 mcg/L (94.4%; 86.7%; P < 0.001). The highest predictive value, however, was observed on day 4 > 19.4 mcg/L (93.5%; 91.0%; P < 0.001); NSE value >50.2 mcg/L at day 4 was associated with poor outcome with 100% specificity and 42% sensitivity. Moreover, NSE levels measured on all individual days also predicted 12-month mortality (P < 0.001); the highest predictive value for death was observed on day 3 > 18.1 mcg/L (85.3%; 72.0%; P < 0.001). Significant association with prognosis was found also for changes in NSE at different time points. An NSE level on day 4 > 20.0 mcg/L, together with a change > 0.0 mcg/L from day 3 to day 4, predicted poor outcome (CPC 3–5) with 100% specificity and 73% sensitivity.

Conclusions

Our results suggest that NSE levels are a useful tool for predicting 30-day neurological outcome and long-term mortality in OHCA survivors treated with targeted temperature management at 33 °C. The highest associations of NSE with outcomes were observed on day 4 and day 3 after cardiac arrest.
Literature
1.
go back to reference Grasner JT, Lefering R, Koster RW, Masterson S, Bottiger BW, Herlitz J, Wnent J, Tjelmeland IB, Ortiz FR, Maurer H, et al. EuReCa ONE-27 Nations, ONE Europe, ONE Registry: A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe. Resuscitation. 2016;105:188–95.CrossRefPubMed Grasner JT, Lefering R, Koster RW, Masterson S, Bottiger BW, Herlitz J, Wnent J, Tjelmeland IB, Ortiz FR, Maurer H, et al. EuReCa ONE-27 Nations, ONE Europe, ONE Registry: A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe. Resuscitation. 2016;105:188–95.CrossRefPubMed
2.
go back to reference Stub D, Bernard S, Duffy SJ, Kaye DM. Post cardiac arrest syndrome: a review of therapeutic strategies. Circulation. 2011;123(13):1428–35.CrossRefPubMed Stub D, Bernard S, Duffy SJ, Kaye DM. Post cardiac arrest syndrome: a review of therapeutic strategies. Circulation. 2011;123(13):1428–35.CrossRefPubMed
3.
go back to reference Callaway CW, Donnino MW, Fink EL, Geocadin RG, Golan E, Kern KB, Leary M, Meurer WJ, Peberdy MA, Thompson TM, et al. Part 8: Post-Cardiac Arrest Care: 2015 American Heart Association Guidelines Update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132(18 Suppl 2):S465–482.CrossRefPubMedPubMedCentral Callaway CW, Donnino MW, Fink EL, Geocadin RG, Golan E, Kern KB, Leary M, Meurer WJ, Peberdy MA, Thompson TM, et al. Part 8: Post-Cardiac Arrest Care: 2015 American Heart Association Guidelines Update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132(18 Suppl 2):S465–482.CrossRefPubMedPubMedCentral
4.
go back to reference Nolan JP, Neumar RW, Adrie C, Aibiki M, Berg RA, Bottiger BW, Callaway C, Clark RS, Geocadin RG, Jauch EC, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke. Resuscitation. 2008;79(3):350–79.CrossRefPubMed Nolan JP, Neumar RW, Adrie C, Aibiki M, Berg RA, Bottiger BW, Callaway C, Clark RS, Geocadin RG, Jauch EC, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke. Resuscitation. 2008;79(3):350–79.CrossRefPubMed
5.
go back to reference Dragancea I, Rundgren M, Englund E, Friberg H, Cronberg T. The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest. Resuscitation. 2013;84(3):337–42.CrossRefPubMed Dragancea I, Rundgren M, Englund E, Friberg H, Cronberg T. The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest. Resuscitation. 2013;84(3):337–42.CrossRefPubMed
6.
go back to reference Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346(8):557–63.CrossRefPubMed Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346(8):557–63.CrossRefPubMed
7.
go back to reference Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346(8):549–56.CrossRef Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346(8):549–56.CrossRef
8.
go back to reference Nolan JP, Soar J, Cariou A, Cronberg T, Moulaert VR, Deakin CD, Bottiger BW, Friberg H, Sunde K, Sandroni C. European Resuscitation Council and European Society of Intensive Care Medicine Guidelines for Post-resuscitation Care 2015: Section 5 of the European Resuscitation Council Guidelines for Resuscitation 2015. Resuscitation. 2015;2015(95):202–22.CrossRef Nolan JP, Soar J, Cariou A, Cronberg T, Moulaert VR, Deakin CD, Bottiger BW, Friberg H, Sunde K, Sandroni C. European Resuscitation Council and European Society of Intensive Care Medicine Guidelines for Post-resuscitation Care 2015: Section 5 of the European Resuscitation Council Guidelines for Resuscitation 2015. Resuscitation. 2015;2015(95):202–22.CrossRef
9.
go back to reference Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, et al. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med. 2013;369(23):2197–206.CrossRefPubMed Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, et al. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med. 2013;369(23):2197–206.CrossRefPubMed
10.
go back to reference Zandbergen EG, Hijdra A, Koelman JH, Hart AA, Vos PE, Verbeek MM, de Haan RJ. Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology. 2006;66(1):62–8.CrossRefPubMed Zandbergen EG, Hijdra A, Koelman JH, Hart AA, Vos PE, Verbeek MM, de Haan RJ. Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology. 2006;66(1):62–8.CrossRefPubMed
11.
go back to reference Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S. 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. 2006;67(2):203–10.CrossRefPubMed Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S. 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. 2006;67(2):203–10.CrossRefPubMed
12.
go back to reference Stammet P, Collignon O, Hassager C, Wise MP, Hovdenes J, Aneman A, Horn J, Devaux Y, Erlinge D, Kjaergaard J, et al. 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. J Am Coll Cardiol. 2015;65(19):2104–14.CrossRefPubMed Stammet P, Collignon O, Hassager C, Wise MP, Hovdenes J, Aneman A, Horn J, Devaux Y, Erlinge D, Kjaergaard J, et al. 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. J Am Coll Cardiol. 2015;65(19):2104–14.CrossRefPubMed
13.
go back to reference Shinozaki K, Oda S, Sadahiro T, Nakamura M, Hirayama Y, Abe R, Tateishi Y, Hattori N, Shimada T, Hirasawa H. S-100B and neuron-specific enolase as predictors of neurological outcome in patients after cardiac arrest and return of spontaneous circulation: a systematic review. Crit Care. 2009;13(4):R121.CrossRefPubMedPubMedCentral Shinozaki K, Oda S, Sadahiro T, Nakamura M, Hirayama Y, Abe R, Tateishi Y, Hattori N, Shimada T, Hirasawa H. S-100B and neuron-specific enolase as predictors of neurological outcome in patients after cardiac arrest and return of spontaneous circulation: a systematic review. Crit Care. 2009;13(4):R121.CrossRefPubMedPubMedCentral
14.
15.
go back to reference DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44(3):837–45.CrossRefPubMed DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44(3):837–45.CrossRefPubMed
16.
17.
go back to reference Mlynash M, Buckwalter MS, Okada A, Caulfield AF, Venkatasubramanian C, Eyngorn I, Verbeek MM, Wijman CA. Serum neuron-specific enolase levels from the same patients differ between laboratories: assessment of a prospective post-cardiac arrest cohort. Neurocrit Care. 2013;19(2):161–6.CrossRefPubMed Mlynash M, Buckwalter MS, Okada A, Caulfield AF, Venkatasubramanian C, Eyngorn I, Verbeek MM, Wijman CA. Serum neuron-specific enolase levels from the same patients differ between laboratories: assessment of a prospective post-cardiac arrest cohort. Neurocrit Care. 2013;19(2):161–6.CrossRefPubMed
18.
go back to reference Stern P, Bartos V, Uhrova J, Bezdickova D, Vanickova Z, Tichy V, Pelinkova K, Prusa R, Zima T. Performance characteristics of seven neuron-specific enolase assays. Tumour Biol. 2007;28(2):84–92.CrossRefPubMed Stern P, Bartos V, Uhrova J, Bezdickova D, Vanickova Z, Tichy V, Pelinkova K, Prusa R, Zima T. Performance characteristics of seven neuron-specific enolase assays. Tumour Biol. 2007;28(2):84–92.CrossRefPubMed
19.
go back to reference Huntgeburth M, Adler C, Rosenkranz S, Zobel C, Haupt WF, Dohmen C, Reuter H. 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. 2014;20(3):358–66.CrossRefPubMed Huntgeburth M, Adler C, Rosenkranz S, Zobel C, Haupt WF, Dohmen C, Reuter H. 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. 2014;20(3):358–66.CrossRefPubMed
20.
go back to reference Cronberg T, Rundgren M, Westhall E, Englund E, Siemund R, Rosen I, Widner H, Friberg H. Neuron-specific enolase correlates with other prognostic markers after cardiac arrest. Neurology. 2011;77(7):623–30.CrossRefPubMed Cronberg T, Rundgren M, Westhall E, Englund E, Siemund R, Rosen I, Widner H, Friberg H. Neuron-specific enolase correlates with other prognostic markers after cardiac arrest. Neurology. 2011;77(7):623–30.CrossRefPubMed
21.
go back to reference Storm C, Nee J, Jorres A, Leithner C, Hasper D, Ploner CJ. Serial measurement of neuron specific enolase improves prognostication in cardiac arrest patients treated with hypothermia: a prospective study. Scand J Trauma Resusc Emerg Med. 2012;20:6.CrossRefPubMedPubMedCentral Storm C, Nee J, Jorres A, Leithner C, Hasper D, Ploner CJ. Serial measurement of neuron specific enolase improves prognostication in cardiac arrest patients treated with hypothermia: a prospective study. Scand J Trauma Resusc Emerg Med. 2012;20:6.CrossRefPubMedPubMedCentral
22.
go back to reference Daubin C, Quentin C, Allouche S, Etard O, Gaillard C, Seguin A, Valette X, Parienti JJ, Prevost F, Ramakers M, et al. Serum neuron-specific enolase as predictor of outcome in comatose cardiac-arrest survivors: a prospective cohort study. BMC Cardiovasc Disord. 2011;11:48.CrossRefPubMedPubMedCentral Daubin C, Quentin C, Allouche S, Etard O, Gaillard C, Seguin A, Valette X, Parienti JJ, Prevost F, Ramakers M, et al. Serum neuron-specific enolase as predictor of outcome in comatose cardiac-arrest survivors: a prospective cohort study. BMC Cardiovasc Disord. 2011;11:48.CrossRefPubMedPubMedCentral
23.
go back to reference Tiainen M, Roine RO, Pettila V, Takkunen O. Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia. Stroke. 2003;34(12):2881–6.CrossRefPubMed Tiainen M, Roine RO, Pettila V, Takkunen O. Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia. Stroke. 2003;34(12):2881–6.CrossRefPubMed
24.
go back to reference Bouwes A, Binnekade JM, Kuiper MA, Bosch FH, Zandstra DF, Toornvliet AC, Biemond HS, Kors BM, Koelman JH, Verbeek MM, et al. Prognosis of coma after therapeutic hypothermia: a prospective cohort study. Ann Neurol. 2012;71(2):206–12.CrossRefPubMed Bouwes A, Binnekade JM, Kuiper MA, Bosch FH, Zandstra DF, Toornvliet AC, Biemond HS, Kors BM, Koelman JH, Verbeek MM, et al. Prognosis of coma after therapeutic hypothermia: a prospective cohort study. Ann Neurol. 2012;71(2):206–12.CrossRefPubMed
25.
go back to reference Oksanen T, Tiainen M, Skrifvars MB, Varpula T, Kuitunen A, Castren M, Pettila V. Predictive power of serum NSE and OHCA score regarding 6-month neurologic outcome after out-of-hospital ventricular fibrillation and therapeutic hypothermia. Resuscitation. 2009;80(2):165–70.CrossRefPubMed Oksanen T, Tiainen M, Skrifvars MB, Varpula T, Kuitunen A, Castren M, Pettila V. Predictive power of serum NSE and OHCA score regarding 6-month neurologic outcome after out-of-hospital ventricular fibrillation and therapeutic hypothermia. Resuscitation. 2009;80(2):165–70.CrossRefPubMed
26.
go back to reference Mortberg E, Zetterberg H, Nordmark J, Blennow K, Rosengren L, Rubertsson S. S-100B is superior to NSE, BDNF and GFAP in predicting outcome of resuscitation from cardiac arrest with hypothermia treatment. Resuscitation. 2011;82(1):26–31.CrossRefPubMed Mortberg E, Zetterberg H, Nordmark J, Blennow K, Rosengren L, Rubertsson S. S-100B is superior to NSE, BDNF and GFAP in predicting outcome of resuscitation from cardiac arrest with hypothermia treatment. Resuscitation. 2011;82(1):26–31.CrossRefPubMed
27.
go back to reference Steffen IG, Hasper D, Ploner CJ, Schefold JC, Dietz E, Martens F, Nee J, Krueger A, Jorres A, Storm C. 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. 2010;14(2):R69.CrossRefPubMedPubMedCentral Steffen IG, Hasper D, Ploner CJ, Schefold JC, Dietz E, Martens F, Nee J, Krueger A, Jorres A, Storm C. 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. 2010;14(2):R69.CrossRefPubMedPubMedCentral
28.
go back to reference Pfeifer R, Franz M, Figulla HR. Hypothermia after cardiac arrest does not affect serum levels of neuron-specific enolase and protein S-100b. Acta Anaesthesiol Scand. 2014;58(9):1093–100.CrossRefPubMed Pfeifer R, Franz M, Figulla HR. Hypothermia after cardiac arrest does not affect serum levels of neuron-specific enolase and protein S-100b. Acta Anaesthesiol Scand. 2014;58(9):1093–100.CrossRefPubMed
Metadata
Title
Association of neuron-specific enolase values with outcomes in cardiac arrest survivors is dependent on the time of sample collection
Authors
Dagmar Vondrakova
Andreas Kruger
Marek Janotka
Filip Malek
Vlasta Dudkova
Petr Neuzil
Petr Ostadal
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2017
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-017-1766-2

Other articles of this Issue 1/2017

Critical Care 1/2017 Go to the issue