S-100B and neuron-specific enolase as predictors of neurological outcome in patients after cardiac arrest and return of spontaneous circulation: a systematic review

Koichiro Shinozaki, Shigeto Oda, Tomohito Sadahiro, Masataka Nakamura, Yo Hirayama, Ryuzo Abe, Yoshihisa Tateishi, Noriyuki Hattori, Tadanaga Shimada, Hiroyuki Hirasawa, Koichiro Shinozaki, Shigeto Oda, Tomohito Sadahiro, Masataka Nakamura, Yo Hirayama, Ryuzo Abe, Yoshihisa Tateishi, Noriyuki Hattori, Tadanaga Shimada, Hiroyuki Hirasawa

Abstract

Introduction: Neurological prognostic factors after cardiopulmonary resuscitation (CPR) in patients with cardiac arrest (CA) as early and accurately as possible are urgently needed to determine therapeutic strategies after successful CPR. In particular, serum levels of protein neuron-specific enolase (NSE) and S-100B are considered promising candidates for neurological predictors, and many investigations on the clinical usefulness of these markers have been published. However, the design adopted varied from study to study, making a systematic literature review extremely difficult. The present review focuses on the following three respects for the study design: definitions of outcome, value of specificity and time points of blood sampling.

Methods: A Medline search of literature published before August 2008 was performed using the following search terms: "NSE vs CA or CPR", "S100 vs CA or CPR". Publications examining the clinical usefulness of NSE or S-100B as a prognostic predictor in two outcome groups were reviewed. All publications met with inclusion criteria were classified into three groups with respect to the definitions of outcome; "dead or alive", "regained consciousness or remained comatose", and "return to independent daily life or not". The significance of differences between two outcome groups, cutoff values and predictive accuracy on each time points of blood sampling were investigated.

Results: A total of 54 papers were retrieved by the initial text search, and 24 were finally selected. In the three classified groups, most of the studies showed the significance of differences and concluded these biomarkers were useful for neurological predictor. However, in view of blood sampling points, the significance was not always detected. Nevertheless, only five studies involved uniform application of a blood sampling schedule with sampling intervals specified based on a set starting point. Specificity was not always set to 100%, therefore it is difficult to indiscriminately assess the cut-off values and its predictive accuracy of these biomarkers in this meta analysis.

Conclusions: In such circumstances, the findings of the present study should aid future investigators in examining the clinical usefulness of these markers and determination of cut-off values.

References

    1. 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;67:203–210. doi: 10.1212/.
    1. Puttgen HA, Geocadin R. Predicting neurological outcome following cardiac arrest. J Neurol Sci. 2007;261:108–117. doi: 10.1016/j.jns.2007.04.041.
    1. Cummins RO, Chamberlain D, Hazinski MF, Nadkarni V, Kloeck W, Kramer E, Becker L, Robertson C, Koster R, Zaritsky A, Bossaert L, Ornato JP, Callanan V, Allen M, Steen P, Connolly B, Sanders A, Idris A, Cobbe S. Recommended guidelines for reviewing, reporting, and conducting research on in-hospital resuscitation: the in-hospital 'Utstein style'. A statement for healthcare professionals from the American Heart Association, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, the Australian Resuscitation Council, and the Resuscitation Councils of Southern Africa. Resuscitation. 1997;34:151–183. doi: 10.1016/S0300-9572(97)01112-X.
    1. Cummins RO, Chamberlain DA, Abramson NS, Allen M, Baskett PJ, Becker L, Bossaert L, Delooz HH, Dick WF, Eisenberg MS, Evans TR, Holmberg S, Kerber R, Mullie A, Ornato JP, Sandoe E, Skulberg A, Tunstall-Pedoe H, Swanson R, Thies WH. Recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest: the Utstein Style. A statement for health professionals from a task force of the American Heart Association, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, and the Australian Resuscitation Council. Circulation. 1991;84:960–975.
    1. Jacobs I, Nadkarni V, Bahr J, Berg RA, Billi JE, Bossaert L, Cassan P, Coovadia A, D'Este K, Finn J, Halperin H, Handley A, Herlitz J, Hickey R, Idris A, Kloeck W, Larkin GL, Mancini ME, Mason P, Mears G, Monsieurs K, Montgomery W, Morley P, Nichol G, Nolan J, Okada K, Perlman J, Shuster M, Steen PA, Sterz F, Tibballs J, Timerman S, Truitt T, Zideman D. Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries: a statement for healthcare professionals from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Councils of Southern Africa) Circulation. 2004;110:3385–3397. doi: 10.1161/01.CIR.0000147236.85306.15.
    1. Becker LB, Han BH, Meyer PM, Wright FA, Rhodes KV, Smith DW, Barrett J. Racial differences in the incidence of cardiac arrest and subsequent survival. The CPR Chicago Project. N Engl J Med. 1993;329:600–606. doi: 10.1056/NEJM199308263290902.
    1. Kellermann AL, Hackman BB, Somes G. Predicting the outcome of unsuccessful prehospital advanced cardiac life support. JAMA. 1993;270:1433–1436. doi: 10.1001/jama.270.12.1433.
    1. Langhelle A, Nolan J, Herlitz J, Castren M, Wenzel V, Soreide E, Engdahl J, Steen PA. Recommended guidelines for reviewing, reporting, and conducting research on post-resuscitation care: the Utstein style. Resuscitation. 2005;66:271–283. doi: 10.1016/j.resuscitation.2005.06.005.
    1. Zandbergen EG, de Haan RJ, Hijdra A. Systematic review of prediction of poor outcome in anoxic-ischaemic coma with biochemical markers of brain damage. Intensive Care Med. 2001;27:1661–1667. doi: 10.1007/s001340101076.
    1. Ekmektzoglou KA, Xanthos T, Papadimitriou L. Biochemical markers (NSE, S-100, IL-8) as predictors of neurological outcome in patients after cardiac arrest and return of spontaneous circulation. Resuscitation. 2007;75:219–228. doi: 10.1016/j.resuscitation.2007.03.016.
    1. A randomized clinical study of cardiopulmonary-cerebral resuscitation: design, methods, and patient characteristics. Brain Resuscitation Clinical Trial I Study Group. Am J Emerg Med. 1986;4:72–86. doi: 10.1016/0735-6757(86)90255-X.
    1. Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet. 1975;1:480–484. doi: 10.1016/S0140-6736(75)92830-5.
    1. Jennett B, Snoek J, Bond MR, Brooks N. Disability after severe head injury: observations on the use of the Glasgow Outcome Scale. J Neurol Neurosurg Psychiatry. 1981;44:285–293. doi: 10.1136/jnnp.44.4.285.
    1. Grubb NR, Simpson C, Sherwood RA, Abraha HD, Cobbe SM, O'Carroll RE, Deary I, Fox KA. Prediction of cognitive dysfunction after resuscitation from out-of-hospital cardiac arrest using serum neuron-specific enolase and protein S-100. Heart. 2007;93:1268–1273. doi: 10.1136/hrt.2006.091314.
    1. Hachimi-Idrissi S, Zizi M, Nguyen DN, Schiettecate J, Ebinger G, Michotte Y, Huyghens L. The evolution of serum astroglial S-100 beta protein in patients with cardiac arrest treated with mild hypothermia. Resuscitation. 2005;64:187–192. doi: 10.1016/j.resuscitation.2004.08.008.
    1. Hachimi-Idrissi S, Auwera M Van der, Schiettecatte J, Ebinger G, Michotte Y, Huyghens L. S-100 protein as early predictor of regaining consciousness after out of hospital cardiac arrest. Resuscitation. 2002;53:251–257. doi: 10.1016/S0300-9572(02)00027-8.
    1. Mussack T, Biberthaler P, Kanz KG, Wiedemann E, Gippner-Steppert C, Mutschler W, Jochum M. Serum S-100B and interleukin-8 as predictive markers for comparative neurologic outcome analysis of patients after cardiac arrest and severe traumatic brain injury. Crit Care Med. 2002;30:2669–2674. doi: 10.1097/00003246-200212000-00010.
    1. Bottiger BW, Mobes S, Glatzer R, Bauer H, Gries A, Bartsch P, Motsch J, Martin E. Astroglial protein S-100 is an early and sensitive marker of hypoxic brain damage and outcome after cardiac arrest in humans. Circulation. 2001;103:2694–2698.
    1. Mussack T, Biberthaler P, Kanz KG, Wiedemann E, Gippner-Steppert C, Jochum M. S-100b, sE-selectin, and sP-selectin for evaluation of hypoxic brain damage in patients after cardiopulmonary resuscitation: pilot study. World J Surg. 2001;25:539–543. doi: 10.1007/s002680020082.
    1. Rosen H, Rosengren L, Herlitz J, Blomstrand C. Increased serum levels of the S-100 protein are associated with hypoxic brain damage after cardiac arrest. Stroke. 1998;29:473–477.
    1. Reisinger J, Hollinger K, Lang W, Steiner C, Winter T, Zeindlhofer E, Mori M, Schiller A, Lindorfer A, Wiesinger K, Siostrzonek P. Prediction of neurological outcome after cardiopulmonary resuscitation by serial determination of serum neuron-specific enolase. Eur Heart J. 2007;28:52–58. doi: 10.1093/eurheartj/ehl316.
    1. 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;66:62–68. doi: 10.1212/01.wnl.0000191308.22233.88.
    1. Rech TH, Vieira SR, Nagel F, Brauner JS, Scalco R. Serum neuron-specific enolase as early predictor of outcome after in-hospital cardiac arrest: a cohort study. Crit Care. 2006;10:R133. doi: 10.1186/cc5046.
    1. Auer J, Berent R, Weber T, Porodko M, Lamm G, Lassnig E, Maurer E, Mayr H, Punzengruber C, Eber B. Ability of neuron-specific enolase to predict survival to hospital discharge after successful cardiopulmonary resuscitation. CJEM. 2006;8:13–18.
    1. Pfeifer R, Borner A, Krack A, Sigusch HH, Surber R, Figulla HR. Outcome after cardiac arrest: predictive values and limitations of the neuroproteins neuron-specific enolase and protein S-100 and the Glasgow Coma Scale. Resuscitation. 2005;65:49–55. doi: 10.1016/j.resuscitation.2004.10.011.
    1. 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;34:2881–2886. doi: 10.1161/01.STR.0000103320.90706.35.
    1. Meynaar IA, Straaten HM, Wetering J van der, Verlooy P, Slaats EH, Bosman RJ, Spoel JI van der, Zandstra DF. Serum neuron-specific enolase predicts outcome in post-anoxic coma: a prospective cohort study. Intensive Care Med. 2003;29:189–195.
    1. Zingler VC, Krumm B, Bertsch T, Fassbender K, Pohlmann Eden B. Early prediction of neurological outcome after cardiopulmonary resuscitation: a multimodal approach combining neurobiochemical and electrophysiological investigations may provide high prognostic certainty in patients after cardiac arrest. Eur Neurol. 2003;49:79–84. doi: 10.1159/000068503.
    1. Rosen H, Sunnerhagen KS, Herlitz J, Blomstrand C, Rosengren L. Serum levels of the brain-derived proteins S-100 and NSE predict long-term outcome after cardiac arrest. Resuscitation. 2001;49:183–191. doi: 10.1016/S0300-9572(00)00348-8.
    1. Schoerkhuber W, Kittler H, Sterz F, Behringer W, Holzer M, Frossard M, Spitzauer S, Laggner AN. Time course of serum neuron-specific enolase. A predictor of neurological outcome in patients resuscitated from cardiac arrest. Stroke. 1999;30:1598–1603.
    1. Martens P, Raabe A, Johnsson P. Serum S-100 and neuron-specific enolase for prediction of regaining consciousness after global cerebral ischemia. Stroke. 1998;29:2363–2366.
    1. Fogel W, Krieger D, Veith M, Adams HP, Hund E, Storch Hagenlocher B, Buggle F, Mathias D, Hacke W. Serum neuron-specific enolase as early predictor of outcome after cardiac arrest. Crit Care Med. 1997;25:1133–1138. doi: 10.1097/00003246-199707000-00012.
    1. Bassetti C, Bomio F, Mathis J, Hess CW. Early prognosis in coma after cardiac arrest: a prospective clinical, electrophysiological, and biochemical study of 60 patients. J Neurol Neurosurg Psychiatry. 1996;61:610–615. doi: 10.1136/jnnp.61.6.610.
    1. Martens P. Serum neuron-specific enolase as a prognostic marker for irreversible brain damage in comatose cardiac arrest survivors. Acad Emerg Med. 1996;3:126–131. doi: 10.1111/j.1553-2712.1996.tb03399.x.
    1. Stelzl T, von Bose MJ, Hogl B, Fuchs HH, Flugel KA. A comparison of the prognostic value of neuron-specific enolase serum levels and somatosensory evoked potentials in 13 reanimated patients. Eur J Emerg Med. 1995;2:24–27. doi: 10.1097/00063110-199503000-00006.
    1. Karkela J, Bock E, Kaukinen S. CSF and serum brain-specific creatine kinase isoenzyme (CK-BB), neuron-specific enolase (NSE) and neural cell adhesion molecule (NCAM) as prognostic markers for hypoxic brain injury after cardiac arrest in man. J Neurol Sci. 1993;116:100–109. doi: 10.1016/0022-510X(93)90095-G.
    1. Dauberschmidt R, Zinsmeyer J, Mrochen H, Meyer M. Changes of neuron-specific enolase concentration in plasma after cardiac arrest and resuscitation. Mol Chem Neuropathol. 1991;14:237–245.
    1. Roine RO, Somer H, Kaste M, Viinikka L, Karonen SL. Neurological outcome after out-of-hospital cardiac arrest. Prediction by cerebrospinal fluid enzyme analysis. Arch Neurol. 1989;46:753–756.
    1. Prohl J, Rother J, Kluge S, de Heer G, Liepert J, Bodenburg S, Pawlik K, Kreymann G. Prediction of short-term and long-term outcomes after cardiac arrest: a prospective multivariate approach combining biochemical, clinical, electrophysiological, and neuropsychological investigations. Crit Care Med. 2007;35:1230–1237. doi: 10.1097/01.CCM.0000261892.10559.85.
    1. Snyder-Ramos SA, Bottiger BW. Molecular markers of brain damage – clinical and ethical implications with particular focus on cardiac arrest. Restor Neurol Neurosci. 2003;21:123–139.
    1. Schmechel D, Marangos PJ, Brightman M. Neurone-specific enolase is a molecular marker for peripheral and central neuroendocrine cells. Nature. 1978;276:834–836. doi: 10.1038/276834a0.
    1. Pahlman S, Esscher T, Bergvall P, Odelstad L. Purification and characterization of human neuron-specific enolase: radioimmunoassay development. Tumour Biol. 1984;5:127–139.
    1. Schafer BW, Heizmann CW. The S100 family of EF-hand calcium-binding proteins: functions and pathology. Trends Biochem Sci. 1996;21:134–140.
    1. Bianchi R, Adami C, Giambanco I, Donato R. S100B binding to RAGE in microglia stimulates COX-2 expression. J Leukoc Biol. 2007;81:108–118. doi: 10.1189/jlb.0306198.
    1. Van Eldik LJ, Wainwright MS. The Janus face of glial-derived S100B: beneficial and detrimental functions in the brain. Restor Neurol Neurosci. 2003;21:97–108.
    1. Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol. 2007;81:1–5. doi: 10.1189/jlb.0306164.
    1. Marangos PJ, Schmechel DE. Neuron specific enolase, a clinically useful marker for neurons and neuroendocrine cells. Annu Rev Neurosci. 1987;10:269–295. doi: 10.1146/annurev.ne.10.030187.001413.
    1. Usui A, Kato K, Murase M, Hotta T, Tanaka M, Takeuchi E, Abe T. Neural tissue-related proteins (NSE, G0 alpha, 28-kDa calbindin-D, S100b and CK-BB) in serum and cerebrospinal fluid after cardiac arrest. J Neurol Sci. 1994;123:134–139. doi: 10.1016/0022-510X(94)90215-1.
    1. Reade MC, Delaney A, Bailey MJ, Angus DC. Bench-to-bedside review: Avoiding pitfalls in critical care meta-analysis – funnel plots, risk estimates, types of heterogeneity, baseline risk and the ecologic fallacy. Crit Care. 2008;12:220. doi: 10.1186/cc6941.
    1. Smit LH, Korse CM, Bonfrer JM. Comparison of four different assays for determination of serum S-100B. Int J Biol Markers. 2005;20:34–42.
    1. Heizmann CW. S100B protein in clinical diagnostics: assay specificity. Clin Chem. 2004;50:249–251. doi: 10.1373/clinchem.2003.027367.
    1. Donato R, Sorci G, Riuzzi F, Arcuri C, Bianchi R, Brozzi F, Tubaro C, Giambanco I. S100B's double life: Intracellular regulator and extracellular signal. Biochim Biophys Acta. 2009;1793:1008–1022. doi: 10.1016/j.bbamcr.2008.11.009.

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