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Glial fibrillary acidic protein in children with congenital heart disease undergoing cardiopulmonary bypass

Published online by Cambridge University Press:  11 July 2013

Marissa A. Brunetti ,
Jacky M. Jennings ,
R. Blaine Easley ,
Melania Bembea ,
Anna Brown ,
Eugenie Heitmiller ,
Jamie M. Schwartz ,
Ken M. Brady ,
Luca A. Vricella  and
Allen D. Everett
Marissa A. Brunetti*
Affiliation:
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
Jacky M. Jennings
Affiliation:
Departments of Pediatrics and Biostatistics, Johns Hopkins School of Medicine and Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
R. Blaine Easley
Affiliation:
Department of Anesthesiology and Critical Care Medicine, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas, United States of America
Melania Bembea
Affiliation:
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
Anna Brown
Affiliation:
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
Eugenie Heitmiller
Affiliation:
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
Jamie M. Schwartz
Affiliation:
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
Ken M. Brady
Affiliation:
Department of Anesthesiology and Critical Care Medicine, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas, United States of America
Luca A. Vricella
Affiliation:
Department of Cardiac Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
Allen D. Everett
Affiliation:
Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America
*
Correspondence to: M. A. Brunetti, MD, Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th and Civic Center Blvd. 7 South Tower 7C26, Philadelphia, PA 19104, United States of America. Tel: +215-590-2365; Fax: +215-590-4620; E-mail: brunettim@email.chop.edu
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Abstract

Objective: To determine whether blood levels of the brain-specific biomarker glial fibrillary acidic protein rise during cardiopulmonary bypass for repair of congenital heart disease. Methods: This is a prospective observational pilot study to characterise the blood levels of glial fibrillary acidic protein during bypass. Children <21 years of age undergoing bypass for congenital heart disease at Johns Hopkins Hospital and Texas Children's Hospital were enrolled. Blood samples were collected during four phases: pre-bypass, cooling, re-warming, and post-bypass. Results: A total of 85 patients were enrolled between October, 2010 and May, 2011. The median age was 0.73 years (range 0.01–17). The median weight was 7.14 kilograms (range 2.2–86.5). Single ventricle anatomy was present in 18 patients (22%). Median glial fibrillary acidic protein values by phase were: pre-bypass: 0 ng/ml (range 0–0.35); cooling: 0.039 (0–0.68); re-warming: 0.165 (0–2.29); and post-bypass: 0.112 (0–0.97). There were significant elevations from pre-bypass to all subsequent stages, with the greatest increase during re-warming (p = 0.0001). Maximal levels were significantly related to younger age (p = 0.03), bypass time (p = 0.03), cross-clamp time (p = 0.047), and temperature nadir (0.04). Peak levels did not vary significantly in those with single ventricle anatomy versus two ventricle repairs. Conclusion: There are significant increases in glial fibrillary acidic protein levels in children undergoing cardiopulmonary bypass for repair of congenital heart disease. The highest values were seen during the re-warming phase. Elevations are significantly associated with younger age, bypass and cross-clamp times, and temperature nadir. Owing to the fact that glial fibrillary acidic protein is the most brain-specific biomarker identified to date, it may act as a rapid diagnostic marker of brain injury during cardiac surgery.

Keywords

Brain biomarkerglial fibrillary acidic proteincardiopulmonary bypass
Type
Original Articles
Information
Cardiology in the Young , Volume 24 , Issue 4 , August 2014 , pp. 623 - 631
Copyright
Copyright © Cambridge University Press 2013 

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References

1. McKenzie, ED, Andropoulos, DB, DiBardino, D, Fraser, CD. Congenital heart surgery 2005: the brain: it's the heart of the matter. Am J Surg 2005; 190: 289–294.Google Scholar
2. Mahle, WT, Tavani, F, Zimmerman, RA, et al. An MRI study of neurological injury before and after congenital heart surgery. Circulation 2002; 106: I109–I114.CrossRefGoogle ScholarPubMed
3. Sarajuuri, A, Jokinen, E, Puosi, R, et al. Neurodevelopmental and neuroradiologic outcomes in patients with univentricular heart aged 5 to 7 years: related risk factor analysis. J Thorac Cardiovasc Surg 2007; 133: 1524–1532.Google Scholar
4. Lee, JK, Easley, RB, Brady, KM. Neurocognitive monitoring and care during pediatric cardiopulmonary bypass-current and future directions. Curr Cardiol Rev 2008; 4: 123–139.Google Scholar
5. McQuillen, PS, Barkovich, AJ, Hamrick, SE, et al. Temporal and anatomic risk profile of brain injury with neonatal repair of congenital heart defects. Stroke 2007; 38: 736–741.CrossRefGoogle ScholarPubMed
6. Shillingford, AJ, Glanzman, MM, Ittenbach, RF, et al. Inattention, hyperactivity, and school performance in a population of school-age children with complex congenital heart disease. Pediatrics 2008; 121: e759–e767.Google Scholar
7. Hovels-Gurich, HH, Seghaye, MC, Sigler, M, et al. Neurodevelopmental outcome related to cerebral risk factors in children after neonatal arterial switch operation. Ann Thorac Surg 2001; 71: 881–888.Google Scholar
8. Schmitt, B, Bauersfeld, U, Schmid, ER, et al. Serum and CSF levels of neuron-specific enolase in cardiac surgery with cardiopulmonary bypass: a marker of brain injury? Brain Dev 1998; 20: 536–539.Google Scholar
9. Rasmussen, LS, Sztuk, F, Christiansen, M, Elliot, MJ. Normothermic versus hypothermic cardiopulmonary bypass during repair of congenital heart disease. J Cardiothorac Vasc Anesth 2001; 15: 563–566.Google Scholar
10. Anderson, RE, Hansson, LO, Nilsson, O, et al. Increase in serum S100A1-B and S100BB during cardiac surgery arises from extracerebral sources. Ann Thorac Surg 2001; 71: 1512–1517.Google Scholar
11. Lardner, D, Davidson, A, McKenzie, I, Cochrane, A. Delayed rises in S100β levels and adverse neurological outcome in infants and children undergoing cardiopulmonary bypass. Paediatr Anaesth 2004; 14: 495–500.Google Scholar
12. Erb, MA, Heinemann, MK, Wendel, HP, et al. S-100 after correction of congenital heart defects in neonates: is it a reliable marker for cerebral damage? Ann Thorac Surg 200; 69: 1515–1519.Google Scholar
13. Mondello, S, Papa, L, Buki, A, et al. Neuronal and glial markers are differently associated with computed tomography findings and outcome in patients with severe traumatic brain injury: a case control study. Crit Care 2011; 15: R156.Google Scholar
14. Pelinka, LE, Kroepfl, A, Schmidhammer, R, et al. Glial fibrillary acidic protein in serum after traumatic brain injury and multiple trauma. J of Trauma 2004; 57: 1006–1012.Google Scholar
15. Nylen, K, Ost, M, Csajbok, LZ, et al. Increased serum-GFAP in patients with severe traumatic brain injury is related to outcome. J of Neuro Sci 2006; 240: 85–91.CrossRefGoogle ScholarPubMed
16. Kaneko, T, Kasaoka, S, Miyauchi, T, et al. Serum glial fibrillary acidic protein as a predictive biomarker of neurological outcome after cardiac arrest. Resus 2009; 80: 790–794.Google Scholar
17. Dvorak, F, Haberer, I, Sitzer, M, Foerch, C. Characterization of the diagnostic window of serum glial fibrillary acidic protein for the differentiation of intracerebral haemorrhage and ischaemic stroke. Cerebrovasc Dis 2009; 27: 37–41.Google Scholar
18. Panickar, KS, Norenberg, MD. Astrocytes in cerebral ischemic injury: morphological and general considerations. Glia 2005; 50: 287–298.CrossRefGoogle ScholarPubMed
19. Bembea, M, Savage, WJ, Strouse, JJ, et al. Glial fibrillary acidic protein as a brain injury biomarker in children undergoing extracorporeal membrane oxygenation. Pediatr Crit Care Med 2011; 12: 572–579.CrossRefGoogle ScholarPubMed
20. Ennen, CS, Huisman, TA, Savage, WJ, et al. Glial fibrillary acidic protein as a biomarker for neonatal hypoxic-ischemic encephalopathy treated with whole body cooling. Am J Obstet Gynecol 2011; 205: 251e1–251e7.Google Scholar
21. Stewart, A, Tekes, A, Huisman, TA, et al. Glial fibrillary acidic protein as a biomarker for periventricular white matter injury. Am J Obstet Gynecol 2013, March Epub ahead of print.CrossRefGoogle ScholarPubMed
22. Savage, WJ, Barron-Casella, E, Fu, Z, et al. Plasma glial fibrillary acidic protein levels in children with sickle cell disease. Am J of Hematology 2011; 86: 427–429.CrossRefGoogle ScholarPubMed
23. Gaies, MG, Gurney, JG, Yen, AH, et al. Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatr Crit Care Med 2010; 11: 234–238.Google Scholar
24. Wunderlich, MT, Wallesch, CW, Goertler, M. Release of glial fibrillary acidic protein is related to the neurovascular status in acute ischemic stroke. Euro J Neurol 2006; 13: 1118–1123.Google Scholar
25. Herrmann, M, Vos, P, Wunderlich, MT, et al. Release of glial tissue-specific proteins after acute stroke: a comparative analysis of serum concentrations of protein S-100B and glial fibrillary acidic protein. Stroke 2000; 31: 2670–2677.Google Scholar
26. McHarg, J, Ringel, R, Coulson, J, et al. Biomarker assessment of brain injury in the cardiac catheterization laboratory. J Am Coll Cardiol 2011; 57: E417.Google Scholar
27. Missler, U, Orlowski, N, Notzold, A, et al. Early elevation of S-100B protein in blood after cardiac surgery is not a predictor of ischemic cerebral injury. Clin Chim Acta 2002; 321: 29–33.CrossRefGoogle Scholar
28. Missler, U, Wiesmann, M, Wittmann, G, et al. Measurement of glial fibrillary acidic protein in human blood: analytical method and preliminary clinical results. Clinical Chemistry 1999; 45: 138–141.Google Scholar
29. McQuillen, PS, Barkovich, AJ, Hamrick, SE, et al. Temporal and anatomic risk profile of brain injury with neonatal repair of congenital heart defects. Stroke 2007; 38: 736–741.CrossRefGoogle ScholarPubMed
30. Miller, SP, McQuillen, PS, Hamrick, S, et al. Abnormal brain development in newborns with congenital heart disease. N Engl J Med 2007; 357: 1928–1938.Google Scholar