Abstract
Background
To determine neurologic outcome in patients with out-of-hospital cardiac arrest (OHCA) and treatment with mild therapeutic hypothermia (MTH).
Methods
Seventy-three consecutive OHCA patients treated with MTH were retrospectively analyzed. Serum neuron-specific enolase (NSE) was measured 24, 48, and 72 h after admission. In patients with no motor response 48 h after termination of analgosedation (n = 40), clinical neurological examination and evoked potentials (EPs) were determined. Neurological outcome was assessed after 2 months based on the cerebral performance categories (CPC), and categorized as good (CPC 1–3) or poor (CPC 4 and 5).
Results
Forty-three patients had a CPC score of 1–3 and 30 patients had a CPC 4–5. The best predictive value for poor neurologic outcome was an increase of NSE by ≥4.3 ng/mL between day 1 and day 2 (sensitivity 80 %, specificity 100 %, positive predictive value (PPV) 100 %, negative predictive value 86 %). Absolute NSE values were less reliable in the prediction of poor outcome with the highest sensitivity (88 %) and specificity (95 %) if values reached ≥36.3 ng/mL on day 3. Somatosensory EPs (SSEPs) showed a specificity of 100 % and PPV of 100 %; however, sensitivity for evoked potentials was low (29 %). Intriguingly, two initially comatose patients with excessive NSE values (24 h NSE: 101 and 256 ng/mL, and 48 h NSE: 93 and 110 ng/mL, respectively) had physiological SSEPs and regained a CPC score of 1.
Conclusion
In patients treated with MTH after OHCA changes in NSE are more suitable than its absolute serum levels for the prediction of poor neurologic outcome. Since unequivocal prediction of poor neurologic outcome is of utmost importance in these patients the decision to limit therapy must be based on several prediction tools with the highest PPV and specificity including SSEPs.
Similar content being viewed by others
References
Field JM, Hazinski MF, Sayre MR, Chameides L, Schexnayder SM, Hemphill R, Samson RA, Kattwinkel J, Berg RA, Bhanji F, Cave DM, Jauch EC, Kudenchuk PJ, Neumar RW, Peberdy MA, Perlman JM, Sinz E, Travers AH, Berg MD, Billi JE, Eigel B, Hickey RW, Kleinman ME, Link MS, Morrison LJ, O’Connor RE, Shuster M, Callaway CW, Cucchiara B, Ferguson JD, Rea TD, Vanden Hoek TL. Part 1: Executive summary: 2010 american heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010;122(18 Suppl 3):S640–56.
Nolan JP, Soar J, Zideman DA, Biarent D, Bossaert LL, Deakin C, Koster RW, Wyllie J, Bottiger B. European resuscitation council guidelines for resuscitation 2010 section 1. Executive summary. Resuscitation. 2010;81(10):1219–76.
Bradley SM, Gabriel EE, Aufderheide TP, Barnes R, Christenson J, Davis DP, Stiell IG, Nichol G. Survival increases with CPR by emergency medical services before defibrillation of out-of-hospital ventricular fibrillation or ventricular tachycardia: Observations from the resuscitation outcomes consortium. Resuscitation. 2010;81(2):155–62.
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.
Lippert FK, Raffay V, Georgiou M, Steen PA, Bossaert L. European resuscitation council guidelines for resuscitation 2010 section 10. The ethics of resuscitation and end-of-life decisions. Resuscitation. 2010;81(10):1445–51.
The Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549–56.
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.
Daubin C, Quentin C, Allouche S, Etard O, Gaillard C, Seguin A, Valette X, Parienti JJ, Prevost F, Ramakers M, Terzi N, Charbonneau P, du Cheyron D. Serum neuron-specific enolase as predictor of outcome in comatose cardiac-arrest survivors: A prospective cohort study. BMC Cardiovasc Disord. 2011;11:48.
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.
Shinozaki K, Oda S, Sadahiro T, Nakamura M, Abe R, Nakada TA, Nomura F, Nakanishi K, Kitamura N, Hirasawa H. Serum s-100b is superior to neuron-specific enolase as an early prognostic biomarker for neurological outcome following cardiopulmonary resuscitation. Resuscitation. 2009;80(8):870–5.
Oksanen T, Tiainen M, Skrifvars MB, Varpula T, Kuitunen A, Castren M, Pettila V. Predictive power of serum nse and ohca score regarding 6 months neurologic outcome after out-of-hospital ventricular fibrillation and therapeutic hypothermia. Resuscitation. 2009;80(2):165–70.
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.
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.
Rundgren M, Karlsson T, Nielsen N, Cronberg T, Johnsson P, Friberg H. Neuron specific enolase and s-100b as predictors of outcome after cardiac arrest and induced hypothermia. Resuscitation. 2009;80(7):784–9.
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.
Fugate JE, Wijdicks EF, Mandrekar J, Claassen DO, Manno EM, White RD, Bell MR, Rabinstein AA. Predictors of neurologic outcome in hypothermia after cardiac arrest. Ann Neurol. 2010;68(6):907–14.
Zimmerman JE, Kramer AA, McNair DS, Malila FM. Acute physiology and chronic health evaluation (apache) IV: Hospital mortality assessment for today’s critically ill patients. Crit Care Med. 2006;34(5):1297–310.
Cummins RO, Chamberlain DA, Abramson NS, Allen M, Baskett P, Becker L, Bossaert L, Delooz H, Dick W, Eisenberg M, et al. Recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest: The utstein style. Task force of the american heart association, the european resuscitation council, the heart and stroke foundation of canada, and the australian resuscitation council. Ann Emerg Med. 1991;20(8):861–74.
Zandbergen EG, de Haan RJ, Stoutenbeek CP, Koelman JH, Hijdra A. Systematic review of early prediction of poor outcome in anoxic-ischaemic coma. Lancet. 1998;352(9143):1808–12.
Chiappa KH, Ropper AH. Evoked potentials in clinical medicine (second of two parts). N Engl J Med. 1982;306(20):1205–11.
Chiappa KH, Ropper AH. Evoked potentials in clinical medicine (first of two parts). N Engl J Med. 1982;306(19):1140–50.
Bouwes A, Binnekade JM, Zandstra DF, Koelman JH, van Schaik IN, Hijdra A, Horn J. Somatosensory evoked potentials during mild hypothermia after cardiopulmonary resuscitation. Neurology. 2009;73(18):1457–61.
Leithner C, Ploner CJ, Hasper D, Storm C. Does hypothermia influence the predictive value of bilateral absent n20 after cardiac arrest? Neurology. 2010;74(12):965–9.
Rossetti AO, Oddo M, Logroscino G, Kaplan PW. Prognostication after cardiac arrest and hypothermia: A prospective study. Ann Neurol. 2010;67(3):301–7.
Bouwes A, Binnekade JM, Kuiper MA, Bosch FH, Zandstra DF, Toornvliet AC, Biemond HS, Kors BM, Koelman JH, Verbeek MM, Weinstein HC, Hijdra A, Horn J. Prognosis of coma after therapeutic hypothermia: A prospective cohort study. Ann Neurol. 2012;71(2):206–12.
Webb AC, Samuels OB. Reversible brain death after cardiopulmonary arrest and induced hypothermia. Crit Care Med. 2011;39(6):1538–42.
Mader TJ, Nathanson BH, Millay S, Coute RA, Clapp M, McNally B. Out-of-hospital cardiac arrest outcomes stratified by rhythm analysis. Resuscitation. 2012;83(11):1358–62.
Kim YM, Yim HW, Jeong SH, Klem ML, Callaway CW. Does therapeutic hypothermia benefit adult cardiac arrest patients presenting with non-shockable initial rhythms?: A systematic review and meta-analysis of randomized and non-randomized studies. Resuscitation. 2012;83(2):188–96.
Peberdy MA, Callaway CW, Neumar RW, Geocadin RG, Zimmerman JL, Donnino M, Gabrielli A, Silvers SM, Zaritsky AL, Merchant R, Vanden Hoek TL, Kronick SL. Part 9: Post-cardiac arrest care: 2010 american heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010;122(18 Suppl 3):S768–86.
Arrich J, Holzer M, Herkner H, Mullner M (2009) Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation. Cochrane Database Syst Rev (4):CD004128.
Testori C, Sterz F, Behringer W, Haugk M, Uray T, Zeiner A, Janata A, Arrich J, Holzer M, Losert H. Mild therapeutic hypothermia is associated with favourable outcome in patients after cardiac arrest with non-shockable rhythms. Resuscitation. 2011;82(9):1162–7.
Acknowledgments
We thank the staff of the intensive care unit at the Heart Center of the University of Cologne for their great support in the present study.
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Huntgeburth, M., Adler, C., Rosenkranz, S. et al. 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, 358–366 (2014). https://doi.org/10.1007/s12028-013-9848-8
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12028-013-9848-8