Serum levels of S100B protein and neuron-specific enolase are associated with mortality in critically ill patient

  • Izabela Duda Department of Anesthesiology and Intensive Care, School of Medicine, Medical University of Silesia, Poland.
  • Łukasz Krzych Department of Anesthesiology and Intensive Care, School of Medicine, Medical University of Silesia, Poland.
  • Halina Jędrzejowska-Szypułka Department of Physiology, School of Medicine, Medical University of Silesia, Poland.
  • Joanna Lewin-Kowalik
Keywords: S100B, neuron-specific enolase, mortality, critically ill

Abstract

 

Introduction.   Evaluation of the prognostic potential of protein S100B and neuron-specific enolase (NSE) as predictors of mortality in critically ill patients in intensive care units (ICU).

Materials and Methods. The study was conducted on 62 patients. Basic clinical variables and blood samples for S100B and NSE level testing were obtained during the first four days after admission. Mortality was described as the patient's death during hospitalization in the ICU.

Results. 35% of the patients died.  The level of S100B and NSE was significantly higher in non-survivors in comparison with survivors (p=0.007 and p=0.02 respectively). Mortality risk was significantly higher in patients with higher levels of biomarkers than the reference values for S100B (OR 9.00; 95% CI 2.38-33.99; p<0.001) as well as for NSE (OR 5.75; 95%CI 1.31-25,.27; p=0.016). Receiver operating characteristic proved that S100B is a better mortality predictor than NSE (AUC 0.76 for S100B and 0.68 for NSE). From all the other variables, the Apache II score turned out to be the only significant predictor of mortality (AUC 0.88).

Conclusion. There is a significant correlation between mortality in the ICU and increased serum concentration of S100B and NSE. This correlation is stronger for S100B. Testing for serum levels of S100B and NSE may be useful for prediction of treatment outcomes in the ICU patients.

References

References

Anderson RE, Settergren G, Hansson LO. (2001) High Serum S100B levels for trauma patients without head injuries. Neurosurgery 49(6): 1492-1493. https://doi.org/10.1097/00006123-200112000-00056

Barone FC, Clark RK, Price WJ, White RF, Feuerstein GZ, Storer BL, Ohlstein EH. (1993) Neuron-specific enolase increases in cerebral and systemic circulation following focal ischemia. Brain Res 623(1): 77-82.

Cruz D N, de Cal M, Garzotto F, Perazella MA, Lentini P, Corradi V, Ronco C. (2010) Plasma neutrophil gelatinase-associated lipocalin is an early biomarker for acute kidney injury in an adult ICU population. Intensive Care Med 36(3): 444-451. doi: 10.1007/s00134-009-1711-1.

Del Bufalo C, Morelli A, Bassein L, Fasano L, Quarta CC, Pacilli AM, Gunella G. (1995) Severity scores in respiratory intensive care: APACHE II predicted mortality better than SAPS II. Respir Care 40(10):1042-7.

Diez M, Torres A, Ortega L, Maestro M, Hernando F, Gomez A, Picardo A, Granell J, Balibrea JL. (1993) Value of serum neuron-specific enolase in nonsmall cell lung cancer. Oncology 50(2):127-31.

Donato R, Cannon BR, Sorci G, Riuzzi F, Hsu K, Weber DJ, Geczy CL. (2013) Functions of S100 proteins. Curr Mol Med 13(1):24-57.

Ebersoldt M, Sharshar T, Annane D. (2007) Sepsis-associated delirium. Intensive Care Medicine 33(6): 941-950. DOI:10.1007/s00134-007-0622-2

Goyal A, Failla MD, Niyonkuru C, Amin K, Fabio A, Berger RP, Wagner AK. (2013) S100b as a prognostic biomarker in outcome prediction for patients with severe traumatic brain injury. J Neurotrauma 30(11): 946–957. doi: 10.1089/neu.2012.2579

Hamed SA, Hamed EA, Abdella MM. (2009) Septic encephalopathy: relationship to serum and cerebrospinal fluid levels of adhesion molecules, lipid peroxides and S-100B protein. Neuropediatrics 40(2): 66-72. DOI:10.1055/s-0029-1231054

Herrmann M, Curio N, Jost S, Wunderlich MT, Synowitz H, Wallesch CW. (1999) Protein S-100B and neuron specific enolase as early neurobiochemical markers of the severity of traumatic brain injury. Restor Neurol Neurosci 14(2-3): 109-114.

Iacobone E, Bailly-Salin J, Polito A, Friedman D, Stevens RD, Sharshar T. (2009) Sepsis-associated encephalopathy and its differential diagnosis. Crit Care Med 37(10): S331-S336. DOI:10.1097/CCM.0b013e3181b6ed58

Isgrò MA, Bottoni P, Scatena R. (2015) Neuron-specific enolase as a biomarker: biochemical and clinical aspects. Adv Exp Med Biol 867:125-43. DOI:10.1007/978-94-017-7215-0 9

Jensen JU, Heslet L, Jensen T H, Espersen K, Steffensen P, Tvede M. (2006) Procalcitonin increase in early identification of critically ill patients at high risk of mortality. Crit Care Med 34(10): 2596-2602. DOI:10.1097/01.CCM.0000239116.01855.61

Karnak D, Beder S, Kayacan O, Ibiş E, Oflaz G. (2005) Neuron-specific enolase and lung cancer. Am J Clin Oncol 28(6):586-90.

Knaus WA, Zimmerman JE, Wagner DP, Draper EA, Lawrence DE. (1981) APACHE-acute physiology and chronic health evaluation: a physiologically based classification system. Crit Care Med 9(8):591-7.

Korfias S, Stranjalis G, Papadimitriou A, Psachoulia C, Daskalakis G, Antsaklis A, Sakas DE. (2006) Serum S-100B protein as a biochemical marker of brain injury: a review of current concepts. Curr Med Chem 13(30): 3719-3731. DOI: 10.2174/092986706779026129

Korfias S, Stranjalis G, Boviatsis E, Psachoulia C, Jullien G, Gregson B, Mendelow AD, Sakas DE. (2007) Serum S-100B protein monitoring in patients with severe traumatic brain injury. Intensive Care Med 33(2):255-60.

Macedo RC, Tomasi CD, Giombelli VR, Alves SC, Bristot MLU, Locks MFT, Ritter C. (2013) Lack of association of S100β and neuron-specific enolase with mortality in critically ill patients. Rev Bras Psiquiatr 35(3): 267-270.

Marshall JC, Reinhart K. (2009) Biomarkers of sepsis. Crit Care Med 37(7):2290-8. DOI:10.1097/CCM.0b013e3181a02afc

Mercier E, Boutin A, Lauzier F, Fergusson DA, Simard JF, Zarychanski R, Légaré F. (2013) Predictive value of S-100β protein for prognosis in patients with moderate and severe traumatic brain injury: systematic review and meta-analysis. BMJ 346:f1757. doi: 10.1136/bmj.f1757.

Michetti F, Corvino V, Geloso MC, Lattanzi W, Bernardini C, Serpero L, Gazzolo D. (2012) The S100B protein in biological fluids: more than a lifelong biomarker of brain distress. J Neurochem 120(5): 644-659. DOI:10.1111/j.1471-4159.2011.07612.x

Nguyen DN, Spapen H, Su F, Schiettecatte J, Shi L, Hachimi-Idrissi S, Huyghens L. (2006) Elevated serum levels of S-100β protein and neuron-specific enolase are associated with brain injury in patients with severe sepsis and septic shock. Crit Care Med 34(7): 1967-1974. DOI:10.1097/01.CCM.0000217218.51381.49

Nguyen HB, Loomba M, Yang JJ, Jacobsen G, Shah K, Otero RM, Rivers EP. (2010) Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock. J Inflamm 7(6). doi: 10.1186/1476-9255-7-6

Papadopoulos MC, Davies DC, Moss RF, Tighe D, Bennett ED. (2000) Pathophysiology of septic encephalopathy: a review. Crit Care Med 28(8): 3019-3024.

Pfortmueller CA, Drexel C, Krähenmann-Müller S, Leichtle AB, Fiedler GM, Lindner G, Exadaktylos AK. (2016) S-1001B concentrations are a predictor of decreased survival in patients with major trauma, independently of head injury. PLoS One 31;11(3):e0152822. https://doi.org/10.1371/journal.pone.0152822

Rodríguez-Rodríguez A, Egea-Guerrero JJ, León-Justel A, Gordillo-Escobar E, Revuelto-Rey J, Vilches-Arenas Á, Guerrero J M. (2012) Role of S100B protein in urine and serum as an early predictor of mortality after severe traumatic brain injury in adults. Clin Chim Acta 414: 228-233. doi: 10.1016/j.cca.2012.09.025.

Routsi C, Stamataki E, Nanas S, Psachoulia C, Stathopoulos A, Koroneos A, Roussos C. (2006) Increased levels of serum S100B protein in critically ill patients without brain injury. Shock 26(1),: 20-24. DOI:10.1097/01.shk.0000209546.06801.d7

Satoh H., Ishikawa H, Kurishima K, Yamashita YT, Ohtsuka M, Sekizawa K.(2002) Cut-off levels of NSE to differentiate SCLC from NSCLC. Oncology rep 9(3): 581-583.

Siman R, Giovannone N, Toraskar N, Frangos S, Stein SC, Levine JM, Kumar MA. (2011) Evidence that a panel of neurodegeneration biomarkers predicts vasospasm, infarction, and outcome in aneurysmal subarachnoid hemorrhage. PLoS One 6(12): e28938. https://doi.org/10.1371/journal.pone.0028938

Stocchetti N. (2005) Brain and sepsis: functional impairment, structural damage, and markers. Anesth Analg 101(5): 1463-1464. DOI:10.1213/01.ANE.0000181337.03655.0C

Stranjalis G, Korfias S, Papapetrou C, Kouyialis A, Boviatsis E, Psachoulia C, Sakas DE. (2004) Elevated serum S-100B protein as a predictor of failure to short-term return to work or activities after mild head injury. J Neurotrauma 21(8):1070-5. DOI:10.1089/0897715041651088

Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter P M, Sprung C L, Colardyn F, Blecher S. (1998) Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: Results of a multicenter, prospective study. Crit Care Med 26(11):1793-1800

Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, Moreno R, Lipman J, Gomersall C, Sakr Y, Reinhart K. (2009) International study of the prevalence and outcomes of infection in intensive care units. Jama 302(21): 2323-2329. doi:10.1001/jama.2009.1754

Weigand MA, Volkmann M, Schmidt H, Martin E, Böhrer H, Bardenheuer HJ. (2000) Neuron-specific enolase as a marker of fatal outcome in patients with severe sepsis or septic shock. Anesthesiology 92(3): 905-905.

Yao B, Zhang LN, Ai YH. (2014) Serum S100β is a better biomarker than neuron-specific enolase for sepsis-associated encephalopathy and determining its prognosis: a prospective and observational study. Neurochem Res 39(7):1263-1269. doi: 10.1007/s11064-014-1308-0.

Zimmerman JE, Kramer AA, Knaus WA. (2013) Changes in hospital mortality for United States intensive care unit admissions from 1988 to 2012. Crit Care 17:R81. doi: 10.1186/cc12695.

Zongo D, Ribéreau-Gayon R, Masson F, Laborey M, Contrand B, Salmi LR, Montaudon D, Beaudeux JL, Meurin A, Dousset V, Loiseau H, Lagarde E. (2012) S100-B protein as a screening tool for the early assessment of minor head injury. Ann Emerg Med 59(3):209-18. DOI:10.1016/j.annemergmed.2011.07.027

Published
2017-12-31
Section
Articles